World Allergy Organization Journal 2017, 10(Suppl 1):25
DOI 10.1186/s40413-017-0155-2
MEETING ABSTRACTS
Open Access
WAO International Scientific Conference
(WISC 2016) Abstracts
Jerusalem, Israel. 6–9 December 2016
Published: 20 June 2017
A1
A four-loci interaction model: a new predictive tool for asthma in
Chinese children 5 years and younger
Jun Bao, Yi-Hui Wang, Quan-Hua Liu, Yi-Xiao Bao
Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine,
Pediatric Respirology, Shanghai, China
Correspondence: Jun Bao
World Allergy Organization Journal 2017, 10(Suppl 1):A1
Background
Asthma is the most common chronic respiratory disease in childhood. However, it is quite difficult to make a prompt diagnosis of
asthma in a child 5 years and younger, partly due to a lack of objective diagnostic means. Our previous studies on susceptibility gene of
asthma showed that a gene-gene interaction among 4 single nucleotide polymorphisms including IL13 rs20541 and IL4 rs2243250,
ADRB2 rs1042713 and FcER1B rs569108 had a predictable role for
asthma in wheezing children.
Objective
The study was aimed to further investigate the predictive effects of
the four-loci interaction model in Chinese preschool children with
asthma.
Methods
A total of 212 wheezing children aged 6 months to 5 years were
enrolled and followed up for at least one year at Shanghai Xinhua
Hospital between Dec 2014 and Mar 2016. Clinical data and lab findings of atopy were collected. All the children were divided into the
high-risk group and the low-risk group according to genotypes of
the four-loci interaction model. The differences of clinical features
were compared between the two groups. The predictive effects for
asthma were analyzed among asthma predictive index (API), 2015
Canadian Diagnostic Criteria for Asthma in Preschoolers and our
four-loci interaction model.
Results
Of all the enrolled 212 children, 117 (55.2%) were assigned into the
high-risk group and 95 (44.8%) were the low-risk group. Compared
with the low-risk group, the high-risk group had more yearly
episodes of wheeze and a higher level of blood eosinophilia. More
children in the high-risk group presented with afebrile wheeze,
eczema and positive food or aero allergens and had a history of
tobacco exposure. If the asthma-predictive effect of positive API was
considered as 1, the four-loci interaction model had a sensitivity of
77.2%, a specificity of 80.0% and an AUC area of 0.786 with a modest
consistency (P=0.22, Kappa=0.49), while the Canadian criteria had a
sensitivity of 97.8%, a specificity of 53.3% and an AUC area of 0.539
with a low consistency (P<0.01, Kappa=0.265).
Conclusions
The four-loci interaction model is associated with the phenotypes of
wheezing in Chinese preschoolers. It has a consistent predictive
effect with API for asthma and is more specific than the Canadian criteria in the diagnosis of asthma, which indicates that the four-loci
interaction model may be developed as a new objective predictive
tool for asthma in Chinese children 5 years and younger.
A2
Loss of esophageal epithelial SPINK7 unleashes uncontrolled
proteolytic activity, impaired epithelial barrier, defective
differentiation and pro-inflammatory cytokine production
Nurit Azouz1, Julie Caldwell1, Leanne Ray1, Mark Rochman1,
Melissa Mingler1, Matthew Eilerman1, Ting Wen1, Jocelyn Biagini Myers2,
Gurjit Khurana Hershey2, Leah Kottyan3, Lisa Martin 3, Rothenberg Marc1
1
Cincinnati Childrens Hospital Medical Center, Division of Allergy and
Immunology, Cincinnati, OH, United States; 2Cincinnati Childrens
Hospital Medical Center, Division of Asthma Research, Cincinnati, OH,
United States ; 3Cincinnati Childrens Hospital Medical Center, Division of
Human Genetics, Cincinnati, OH, United States
Correspondence: Nurit Azouz
World Allergy Organization Journal 2017, 10(Suppl 1):A2
Background
Epithelial barrier impairment has been implicated in the development of allergic disease. However, the molecular mechanisms by
which impaired epithelial barrier function induces Th2-type immune
responses remain largely unknown. In this study, we examined the
role of the serine peptidase inhibitor kazal type (SPINK)7 on epithelial
barrier function and mucosal Th2-associated immune responses in
the esophagus, with a focus on eosinophilic esophagitis (EoE), a
chronic, antigen-driven, inflammatory allergic disease.
Methods
Primary human esophageal epithelial cells stably transduced with
either control or SPINK7-directed shRNAs were cultured at the airliquid interface (ALI) to induce squamous cell differentiation. The
integrity of the epithelium was examined by functional assays complemented with histological and ultrastructural analyses as well as
quantitation and localization of junctional proteins by immunofluorescence microscopy. The impact of SPINK7 on epithelial protease activity and global transcription was assessed. Furthermore, cytokine
and chemokine secretion were analyzed following SPINK7 silencing.
In vitro assays using recombinant proteins were conducted to identify direct targets of SPINK7. Protease activity of human esophageal
tissue was measured, and receptor expression of esophageal tissuederived eosinophils was quantified. Using a genetic approach, we
assessed whether genetic variants in the SPINK7 gene were associated with EoE susceptibility.
Results
Loss of SPINK7 expression caused a defect in epithelial cell differentiation, reduced expression of barrier proteins including filaggrin, impaired epithelial barrier function, and unleashed the production of a
set of pro-inflammatory mediators including IL-8, GM-CSF and CCL2.
Mechanistically, recombinant SPINK7 directly inhibited urokinase
plasminogen activator (uPA) and kallikrein (KLK)5 and translational
studies revealed increased uPA activity in the esophagus of EoE
© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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World Allergy Organization Journal 2017, 10(Suppl 1):25
patients and a marked decrease in expression of the uPA receptor
by esophageal eosinophils. Genetic studies revealed epistasis
between genetic variants in SPINK7 and PLAU (gene product, uPA)
with atopy risk variants in ST2 and thymic stromal lymphopoietin
(TSLP), respectively.
Conclusions
We propose that SPINK7 deficiency and uncontrolled protease activity serve a causative role in compromising the esophageal barrier.
We suggest that SPINK7 represents a novel checkpoint in regulating
innate immunity, and its deficiency, as occurs in EoE, induces proinflammatory and pro-allergic responses characterized by excessive
cytokine production and epithelial barrier impairment, likely via a
KLK- and uPA-dependent mechanism. Additionally, EoE disease
susceptibility is influenced by genetic interactions between variants
in this pathway (SPINK7 and PLAU) and cardinal atopy pathways (ST2
and TSLP).
A3
Epidemiological transition of viruses associated with wheezing.
The role of new virus
Victor Gonzalez-Uribe1, Jaime Del Rio-Chivardi2, Blanca Del Rio-Navarro2
1
Universidad La Salle Facultad Mexicana de Medicina, Mexico City,
Mexico ; 2Hospital Infantil de Mexico Federico Gomez Pediatric Allergy &
Clinical Immunology, Mexico City, Mexico
Correspondence: Victor Gonzalez-Uribe
World Allergy Organization Journal 2017, 10(Suppl 1):A3
Background
Recurrent episodes of wheezing, coughing and respiratory distress in
early life are associated with viral infections, being a common background in the history of patients with persistent wheezing & subsequent onset of asthma. This study allows to determine the prevalence
of viruses associated with wheezing in preschool patients.
Methods
Analytical cohort study was conducted in preschool children who had
airway infections with wheezing; in them, associated viruses were identified by nasopharyngeal and/or bronchial lavage with DNA extraction/
viral RNA visualization and analysis by microarray. All patients underwent clinical history. Univariate statistical analysis was performed.
Results
A total of 714 patients were included for 1 year 6 months to 6 years
of life, the mean age 3.7 years. In 342 patients (47.9%) a viral agent
was not found, however, in patients with positive results, 38.4%, was
isolated only one virus, 9.8% had coinfection by 2 viruses and 3.9%
coinfection by 3 viruses. The viruses identified in order of frequency
were: Rhinovirus 88 (12.3%), Respiratory Syncytial Virus (RSV) B 46
(6.4%), Parainfluenza3 31 (4.3%), VSRA 31 (4.3%), VSRA + Bocavirus
25 (3.5%), Influenza A H1N1 16 (2.2%), Enterovirus 14 (2%), VSRA +
RSVB 12 (1.7%), Bocavirus 9 (1.3%) and the remaining 14.1% 10 other
viruses.
Conclusions
While traditional viruses such as rhinovirus or RSV had greater
participation, the presence of “nontraditional” viruses or coinfection by 2 or more virus requires asking questions about the participation of early immunological changes that favor the genesis
of the disease.
A4
Aeroallergen sensitizations in patients with allergic rhinitis in
mainland China
Hongfei Lou1, Siyuan Ma1, Yan Zhao2, Feifei Cao3, Fei He2,
Zhongyan Liu2, Chengshuo Wang1, Claus Bachert4, Luo Zhang1
1
Beijing TongRen Hospital, Department of Otolaryngology Head and
Neck Surgery, Beijing, China ; 2Beijing Institute of Otolaryngology, Beijing
Key Laboratory of Nasal Diseases, Beijing, China ; 3Beijing TongRen
Hospital, Department of Allergy, Beijing, China ; 4Ghent University
Hospital, Upper Airways Research Laboratory, Ghent, Belgium
Correspondence: Hongfei Lou
World Allergy Organization Journal 2017, 10(Suppl 1):A4
Page 2 of 39
Background
Sensitization pattern of allergic rhinitis (AR) was not clear within main
land China.
Objective
Our aim was to investigate the pattern of sensitization in AR patients
within mainland China and to define the minimal panel of skin prick
test (SPT) allergens required to identify a patient as sensitized.
Methods
In the current patient-based study, 7148 patients suffering from AR
symptoms in 28 provinces from 4 regions of mainland China underwent standardized SPT with 21 common aeroallergens. Conditional
approach allowed to determine the allergens selection.
Results
Among the 7148 suspected AR patients, 6350 (88.8%) had at least
one positive skin prick reaction. The prevalence of positive skin prick
responses was 47.2% for Der f and 41.4% for Der p, respectively,
which were the two most prevalent aeroallergens in main land
China. The highest standardized sensitization rates for house dust
mites were observed in south China (69.2% for Der f and 61.4% for
Der p, respectively). However, in north-west China with cold arid and
desert/steppe climate, the three most prevalent aeroallergens were
mugwort, ragweed and dandelion (58.2%, 47.1% and 45.3%, respectively). Sensitization rates of outdoor aeroallergens were higher in
moderate/severe AR compared to mild AR. Similar allergen sensitization
pattern was observed in persistent AR compared to intermittent AR.
Skin index of sensitization to outdoor allergens and mold allergens was
found to be significantly correlated with symptom VAS score of AR,
whereas severity of AR was not significantly correlated with skin index
of reactivity of Derp, Der f and Alterneria. Sensitization rates of outdoor
allergens and animal dander was higher in patients with AR and conjunctivitis compared to patients with only AR. Overall, eight allergens
(Der f, mugwort, blatella, hazel, coosefoot, penicillium notatum, animal
dander and Der p) allowed to identified more than 95% of sensitized
subjects. However, differences were observed between regions, 4 allergens being sufficient for south China (Der f, blatella, dandelion and ragweed) as opposed to eight for middle China (same order in mainland
China).
Conclusions
Dust mites were the most prevalent allergens in patients with AR in
mainland China. There were significant differences in patterns of sensitizations in patients from different geographic areas. Eight allergens
allowed the identification of the majority of sensitized subjects.
A5
Oral food challenge outcomes in a tertiary care center
Elissa Abrams, Allan Becker
University of Manitoba Section of Allergy and Immunology, Department
of Paediatrics and Child Health, Winnipeg, Canada
Correspondence: Elissa Abrams
World Allergy Organization Journal 2017, 10(Suppl 1):A5
Background
Open oral food challenges are the usual clinical standard for food tolerance. However, clinicians continually search for better predictive
approaches.
Methods
A retrospective chart review of all food challenges in children between
2008 and 2010 was performed.
Results
Using available predictive approaches 313 challenges were performed (105 peanut, 71 egg, 41 milk, 29 tree nut, 67 other) in children 8 months - 18 years old (median age 5.5 years). There were
104 failures (33%); 82 objective, and 22 subjective. Older children
were more likely to fail an oral challenge than younger children
(p=0.046). Rates of asthma (72% vs 47%) and atopic dermatitis
(74% vs 60%) were significantly higher among those who failed oral
challenges (p=0.0014 and p=0.03 respectively). Rates of food allergy
(48% overall) and aeroallergen sensitization (81% overall) were not
significantly different.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Risk of challenge failure was significantly different between food allergens (p=0.0013) with more failures noted for peanut (43%) than
tree nut (34%), milk (22%), or egg (17%). Skin test size was significantly correlated with challenge failure for peanut only (p<0.0001).
Specific IgE was significantly correlated with challenge failure for
peanut only (p<0.0001). Food dose eliciting a reaction was significantly different (p=0.0177) between milk (3.0 mL), egg (2.0 mg), tree
nut (0.75 mg), and peanut (0.30 mg). There was no significant correlation between initial reaction characteristics and reaction characteristics at oral challenge.
Among challenge failures, 20/104 (19%) met the criteria for anaphylaxis, with significantly more tree nut (70%) and peanut challenges
(20%) causing anaphylaxis than milk (7%) or egg (5%) (p=0.0003).
There were 5/8 (63%) failed cashew challenges, of which 4/5 (80%)
required epinephrine; 3/5 (60%) of whom had no known prior exposure to cashew (skin tested 2°nut allergy). Cashew was significantly
more likely to cause a reaction at oral challenge than the other tree
nuts (24%; p=0.05) and other allergens (17%; p=0.0004).
Conclusions
Most challenge failures were to peanut and most severe reactions
were to peanut and tree nut. Failures to peanut and tree nut occurred at low doses while most egg and milk reactions occurred at
high doses. Those who failed a challenge had more atopic disease
and were older. Cashew challenges commonly caused anaphylaxis
even in children with no known prior exposure to cashew.
A6
Effect of Morin in bleomycin-induced pulmonary fibrosis in rats:
critical role of inflammatory, fibrotic and apoptotic biomarkers
Amit Kandhare1, Subhash Bodhankar1
1
Poona College of Pharmacy, Bharati Vidyapeeth Deemed University,
Department of Pharmacology, Erandwane, Paud Road, Pune 411038,
Maharashtra, India
Correspondence: Amit Kandhare
World Allergy Organization Journal 2017, 10(Suppl 1):A6
Background
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive multifactorial
disease with limited successful treatment. Morin [2-(2,4-dihydroxyphenyl)3,5,7-trihydroxy-4H-1-benzopyran-4-one] is a flavonoid possesses potent
anti-inflammatory and anti-oxidant property.
Objective
To evaluate the effect of morin against bleomycin (BLM) induced pulmonary fibrosis by assessing various behavioral, biochemical, molecular
and ultrastructural changes in the laboratory rats.
Methods
IPF was induced in male Sprague-Dawley rats by single intratracheal
BLM (6 IU/kg) injection followed by Morin (10, 30 and 100 mg/kg,
p.o.) or Methylprednisolone (10 mg/kg, p.o.) treatment for 28 days.
Sham control rats received saline instead of BLM. The lung function
test, biochemical, histopathological and molecular changes were analyzed in lung and bronchoalveolar lavage fluid (BALF).
Results
Treatment with Morin significantly restored the BLM-induced alteration
in body weight, lung index, lung function test and hematology. The altered total and differential cell count in BALF and blood were significantly restored by Morin treatment. The decreased peripheral blood
oxygen content after BLM instillation was significantly increased by
Morin treatment. Morin significantly enhanced the BALF and lung antioxidant status, through modulating the SOD, GSH, MDA, NO level and
Nrf2, HO-1 mRNA expression. Morin treatment significantly restored the
altered mRNA expression of lung inflammatory markers (TNF-α, IL-1β,
IL-6, and IL-8), fibrotic markers (TGF-β, collagen-1, Muc5ac, NF-kB and
Smad-3) and apoptotic markers (Bax, Bcl-2, and Caspase-3). BLMinduced histological inflammatory, fibrotic insult and ultrastructural
changes in the lung was reduced by Morin treatment.
Page 3 of 39
Conclusion
Morin has potential anti-fibrotic efficacy through induction of Nrf2,
which in turn modulated inflammatory, fibrotic and apoptotic molecules to reduce pathogenesis of BLM-induced pulmonary fibrosis.
References:
1. Kandhare AD, Ghosh P, Bodhankar SL. Morin attenuates airway
hyperresponsiveness of allergic asthma via down regulation of immuneinflammatory biomarkers. Paper presented at: In Proceedings of the 15th
International Congress of Immunology (ICI). 22 Aug - 27 Aug, 2013., 2013;
Milan, Italy.
2. Kandhare AD, Bodhankar SL, Mohan V, Thakurdesai PA. Effect of
glycosides based standardized fenugreek seed extract in bleomycininduced pulmonary fibrosis in rats: Decisive role of Bax, Nrf2, NF-kappaB,
Muc5ac, TNF-alpha and IL-1beta. Chem Biol Interact. 2015;237(0):151-165.
A7
Susceptibility to exacerbations in asthma
Nicole Grossman 1, Gheorghe Doros 2, Francine Laden 3, Anne Fuhlbrigge4,
Michael Wechsler 5, Wilson Pace 6, Barbara Yawn 7, Elliot Israel 4
1
Brigham and Women Pulmonary Critical Care, Boston, MA, United
States ; 2Harvard University, Harvard Clinical Research Institute, Boston,
MA, United States ; 3Harvard TH Chan School of Public Health,
Environmental Health, Boston, MA, United States ; 4Brigham and
Women’s Hospital, Pulmonary Critical Care, Boston, MA, United States ;
5
National Jewish Health, Pulmonary Critical Care, Denver, CO, United
States ; 6American Academy of Family Physicians, Family Medicine,
Denver, CO, United States ; 7University of Minnesota, Family and
Community Health, Minneapolis, Minnesota, MN, United States
Correspondence: Nicole Grossman
World Allergy Organization Journal 2017, 10(Suppl 1):A7
Background
Asthma exacerbations requiring hospital admission account for more
than 50% of the estimated 56 billion dollars spent each year on
asthma care in the United States. Fifty percent of asthmatics report a
history of an exacerbation in the prior year even though the majority
of such patients have “mild” disease. The characteristics and determinants of exacerbations are incomplete.
Objective
In a large intervention study, we tested the hypothesis that an exacerbation prone phenotype exists in adult asthma independent of
asthma control.
Methods
We analyzed exacerbations (requirement for corticosteroids) and their
associations in a cohort of 1,070 self-identified adult Black Americans
with asthma eligible for, or on, Step 3 NAEPP asthma therapy who participated in a randomized 6-18 month open-label trial of tiotropium vs.
long acting beta agonist as add-on therapy to inhaled corticosteroids.
Asthma control at entry was assessed by ACQ5. Severity of prior exacerbations was graded as requiring oral corticosteroids or ED visit or
hospitalization. Phenotypic characteristics included age, gender, BMI,
smoking history and environment, environmental allergies, years from
first asthma diagnosis, baseline/study medications, short acting beta
agonist (SABA) usage, spirometric indices, and additional patientreported asthma measures (AQLQ, ASUI).
Results
The likelihood of a future exacerbation did increase with worsening
asthma control. Exacerbations occurred in 21% of subjects with
baseline ACQ≤0.75, 29% of subjects with 0.75<ACQ<1.5, and 39%
of those with ACQ≥1.5 (OR per 1 SD change (1.18 units): 1.811;
P<0.001). The strongest predictor of exacerbations was a history of
exacerbations in the preceding year (OR 3.802; P<0.001). The severity of past exacerbations did not correlate with the likelihood of a
future exacerbation. Lower baseline FEV1/FVC was also associated
with increased exacerbations.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Conclusions
While exacerbations were more likely with worsening ACQ scores,
there appears to be an exacerbation susceptibility phenotype independent of asthma control. This phenotype may need precision
therapeutic targeting.
A8
The macrophage response to respiratory viral infection in normal
and asthmatic conditions: mathematical model
Junehyuk Lee1, Frederick Adler 2, Peter Kim3
1
Soonchynhyang University Respiratory-Allergy, Bucheon, South Korea ;
2
Utah University, Biology, SLC, UT, United States ; 3Sydney University,
Mathematics, Sydney, Australia
Correspondence: Junehyuk Lee
World Allergy Organization Journal 2017, 10(Suppl 1):A8
Background
Respiratory viral infection is an important cause of aggravation and exacerbation of asthma. Despite many studies, it is not well understood
how viral infections cause an exacerbation of asthma and provoke
more severe symptoms in asthmatics than normal people. We constructed a mathematical model and simulate the changes of response
after viral stimulation.
Methods
The mathematical model included two types of macrophages, classically and alternatively activated macrophages, and their related cytokines and enzymes. The normal response model was adjusted the
parameters from published data and three asthma-like conditions were
built with control the production rates of key-cytokines. The changes
over time after viral stimulation were observed.
Results
A higher viral load or longer duration of infection provokes a stronger
immune response from the macrophage system in the model. The
model predicts that asthma-like conditions will respond differently to
respiratory viral infection than normal conditions with an increased
duration and magnitude of inflammatory responses.
Conclusions
This model explain the differences in response to respiratory viral infection in normal and asthmatic subjects, and show how this skews
the system toward a response that generates more severe symptoms
in asthmatic patients.
A9
Nosocomial infections in pediatric cardiovascular surgery: how
should we add anti-biofilm antibiotic?
Yung Feng Huang1, Ying Yao Chen1, Chiun Yen Pan2, Herng Sheng Lee3
1
Kaohsiung Veterans General Hospital, Pediatrics, Kaohsiung, Taiwan ;
2
Kaohsiung Veterans General Hospital, Cardiac Surgery, Kaohsiung,
Taiwan ; 3Kaohsiung Veterans General Hospital, Pathology, Kaohsiung,
Taiwan
Correspondence: Yung Feng Huang
World Allergy Organization Journal 2017, 10(Suppl 1):A9
Background
Ventilator associated pneumonia (VAP) is a frequent cause of nosocomial infection (NI) after cardiac surgery in pediatric patients, and
results in a significantly longer stay in the intensive care unit. Azithromycin has been shown to retard Pseudomonas aeruginosa biofilm
formation. Staphylococcus epidermidis and Staphylococcus aureus
are the most frequent causes of nosocomial infections and infections
on indwelling medical devices, which characteristically involve
biofilms
Objective
This study was to determine whether an anti-biofilm antibiotic (azithromycin) reduced NI and VAP for patients undergoing pediatric
cardiac surgery.
Methods
We enrolled 207 patients (<20 years) who underwent cardiovascular
surgery for congenital heart disease. Data on postoperative courses
were compared between children with and without intravenous
azithromycin treatment. We administered perioperative conventional
Page 4 of 39
antimicrobial prophylaxis (cefazolin and gentamicin) for 3 days, with
(AZI group) and without (previous group) intravenous azithromycin
for 3 days. Furthermore, 78 patients from the medical record retrieval
system of KVGH (Kaohsiung Veterans General Hospital) from 2012 to
2015 were recorded (NOW group).
Results
The previous group had higher rates of VAP infection, longer periods of
ventilator dependence and length of post-operative stay in hospital
than AZI Group. There was a significantly higher rate of NI in the previous group compared to the AZI group (P < 0.05). We also found the
same trend with higher rate of NI in NOW group compared with AZI
group (P < 0.05).
Conclusions
We suggest that patients only receiving conventional antimicrobial
prophylaxis are more likely to have NI than those receiving additional
anti-biofilm azithromycin treatment.
A10
Emergency response community effectiveness: an analysis of
anaphylaxis-related EMS events in the USA
Michael Khalemsky1, David G. Schwartz1
1
Bar-Ilan University, Graduate School of Business Administration, Ramat
Gan, Israel
Correspondence: Michael Khalemsky
World Allergy Organization Journal 2017, 10(Suppl 1):A10
Background
Adherence by chronic patients to medical regimens is dismally low,
with under 30% of patients carrying their Adrenaline Auto Injectors
(AAI) at all times (Song et. al, 2014). Rapid administration of Adrenaline
is the widely accepted initial treatment for anaphylaxis. The Emergency
Response Communities (ERC) approach uses a smartphone-based regulated social network of patients who are required to carry life-saving
medications and can help each other in case of absence of the medication when a sudden attack occurs (Schwartz et. al, 2014). While traditional EMS response is always preferred, ERCs have the potential to
augment emergency response by providing the AAI before EMS arrival.
Objective
To assess the applicability and potential of the ERC approach for anaphylaxis events in the USA.
Methods
We developed a Monte Carlo simulation-based software tool, the Emergency Response Community Effectiveness Modeler, which accepts parameters such as population density, medical condition prevalence,
adherence levels, smartphones penetration, community adoption etc.,
to create a detailed comparison of potential smartphone-initiated
Samaritan/member response to traditional EMS response. We used
EMS data from the U.S. National EMS Information System (NEMSIS) and
analyzed geographies based on urbanicity classifications using RUCA
(Rural-Urban Commuting Area) and ERS urban influence codes. Our
experiments, based on a full year (2013) of NEMSIS data explored
14,366 calls to 911 involving anaphylaxis.
Results
The average probability across all geographies that the ERC will be
faster than EMS varies from about 3% for the worst-case scenario, to
about 13% percent for the most likely scenario and up to 34% for
the most optimistic scenario. There is a strong positive correlation
between the population density and the expected probability that
ERC will be faster than the EMS. Simulations show the ERC to be
most effective in heavily populated metropolitan areas. For example,
in areas with population density above 6,460 people per km2 (e.g.
New York City, San Francisco etc.), the average probability that ERC
will be faster is nearly 59%. The expected time savings vary from
3.72 minutes in metropolitan areas and up to 5.55 minutes in small
towns and rural areas.
Conclusions
Our findings support that ERC is able to provide an effective addition
to traditional EMS response in the USA, especially in metropolitan
areas in which most anaphylaxis-related EMS calls occur (77%). For
anaphylaxis patients these few minutes of faster response can be lifesaving and can improve prognosis.
World Allergy Organization Journal 2017, 10(Suppl 1):25
A11
About 3% of chronic spontaneous urticaria patients have vitiligo
and thyroiditis (autoimmune polyglandular syndrome IIIC)
Pavel Kolkhir1, Dmitry Pogorelov1, Nikolay Kochergin1
1
Sechenov First Moscow State Medical University, Dermatology and
Venereology, Moscow, Russia
Correspondence: Pavel Kolkhir
World Allergy Organization Journal 2017, 10(Suppl 1):A11
Background and objective
Autoimmune polyglandular syndromes (APS) are a group of rare
disorders characterized by autoimmune activity against endocrine
and non-endocrine organs and classified into 4 types. APS type IIIC
includes autoimmune thyroiditis (AIT), vitiligo and/or alopecia and/or
other autoimmune disease such as chronic spontaneous urticaria
(CSU). We report for the first time the prevalence of APSIIIC in CSU
and make an attempt to characterize this subgroup of patients.
Methods
We retrospectively evaluated medical records from 234 adult CSU patients over a 3-year period. Urticaria activity score 7 (UAS7) and Chronic
Urticaria Quality of Life Questionnaire (CU-Q2oL) results were obtained
and autologous serum skin test (ASST) was performed. Vitiligo was diagnosed on clinical grounds, AIT – on anti-thyroid antibody tests. The
thyroid status was determined by measuring TSH, T3, T4 blood levels.
The patients were treated in accordance with EAACI/GA(2)LEN/EDF/
WAO guidelines. Comparison between different groups of patients was
carried out using the chi-square test.
Results
Twenty three percent (55/234) of patients had the combination of
CSU and AIT, 1.3% (3/234) – had CSU and vitiligo and 2.6% (6/234)
were diagnosed with APSIIIC. APSIIIC patients comprised 66.7% (6/9)
of the total number of patients who had CSU and vitiligo. In contrast,
APSIIIC was seen in only 9.8% (6/61) of patients with CSU and AIT
(χ2=17.833, p<0.001, V=0.505). Five APSIIIC patients were female and
1 was male; the age varied from 34 to 67 years. The duration of CSU
was from 6 months to 13 years (mean: 5 years 3 months). All patients
had generalized vitiligo for 5-35 years (mean: 19 years). The duration
of AIT was from 6 months to 21 years (mean: 12 years). ASST was
strongly positive in all cases. APSIIIC patients were ASST positive significantly more often than CSU patients without AIT and/or vitiligo
(100% vs 58.3%, χ2=4.062, p=0.044, V=0.228). The patients were
followed for a period from 1 to 38 months. We observed the efficacy
of cyclosporine A (CsA) in 3 patients with poor response to updosed
antihistamines. In our male patient, adding CsA to high doses of antihistamines led to improvement in CSU symptoms, induction of remission and marked reduction of vitiligo lesions.
Conclusions
We found that APSIIIC occurs in 2.6% of CSU patients. Vitiligo preceded
CSU development in all cases and may be a prognostic factor for
APSIIIC in CSU patients. Genetic and autoimmune mechanisms may explain the presence of different components of APS.
A12
Mast cell degranulation in physical urticaria-dissociation of
histamine and tryptase
Hirsh Komarow1, Michael Young2, Robin Eisch1, Linda Scott1,
Dean Metcalfe1
1
National Institute of Allergy and Infectious Diseases, National Institutes
of Health, Mast Cell Biology Section, Laboratory of Allergic Diseases,
Bethesda, MD, United States ; 2 Leidos Biomedical Research, Inc.,
Frederick National Laboratory for Cancer Research Clinical Research
Directorate/Clinical Monitoring Research Program, Frederick, MD, United
States
Correspondence: Hirsh Komarow
World Allergy Organization Journal 2017, 10(Suppl 1):A12
Background
The urticarial lesions of physical urticaria are thought to be the result
of mast cell activation and degranulation, which is supported by the
finding of increased serum levels of mast cell mediators during some
urticarial flares.
Page 5 of 39
Objective
To determine serum levels of histamine and tryptase, mast cell
markers of degranulation, following challenge testing in patients with
physical urticaria.
Methods
An IV catheter was placed in 10 patients with documented physical
urticaria and 8 control subjects. Serial blood draws were obtained
at baseline and at specific time points during and after urticarial
challenge testing. Challenge testing for cold urticaria consisted of
cold hand water submersion (10° C) to 2 inches above the wrist for
5 minutes; for vibratory urticaria, vortex vibratory stimulation for 4
minutes at 2400 rpm; and for cholinergic urticaria, 15-25 minute
treadmill exercise until there was profuse sweating with continued
exercise for >10 minutes. Samples were assayed in patients and
control subjects for histamine and tryptase to determine the onset,
peak and drop in serum mediator levels.
Results
Evidence for mast cell degranulation was established by examination
of skin biopsies and documentation of a significant increase in serum
histamine level with challenge testing. In subjects with cold urticaria
(n=7) the mean serum peak for histamine was 45.5 nM and occurred
at 5 min post challenge, for patients with vibratory urticaria (n=2) the
peak was 110 nM at 2 min post challenge and for one patient with
cholinergic urticaria after 20 min of exercise, the peak reached 300
nM. There were no significant increases in histamine levels in control
patients. Evidence of mediator release resolved in all patients by 30
minutes except for the one patient with cholinergic urticara where
serum histamine was still elevated 120 minutes after challenge. Corresponding tryptase levels did not change significantly (range 2-10
ng/mL) when assayed through 60-120 minutes in all subjects despite
histochemical evidence of local release of mast cell tryptase.
Conclusions
Challenge testing in patients with cold, vibratory and cholinergic
urticaria induces an early onset and significant peak in serum histamine thus implicating mast cell degranulation in the pathogenesis,
yet increased tryptase was not detectable. The discordant ability of
histamine and tryptase to reach the systemic circulation may reflect
upon the unique characteristics of these mediators and their release
in physical urticaria.
A13
Retrospective review of beta lactam allergy prevalence in a referral
population
Alexander Singer1, Andrew Wakeman, Thomas Gerstner3, Elissa Abrams3
1
University of Manitoba, Family Medicine, Winnipeg, Canada ; 2UCD
Medical School, Dublin, Ireland ; 3University of Manitoba, Paediatric
Allergy, Winnipeg, Canada
Correspondence: Alexander Singer
World Allergy Organization Journal 2017, 10(Suppl 1):A13
Background
Penicillin allergies are over diagnosed. About 90% of those avoiding
penicillin class antibiotics are tolerant when allergy tested. In addition,
most patients with true penicillin allergy will lose their sensitivity over
time. The label ‘penicillin allergic’ is linked with poorer health outcomes
and higher healthcare costs.
Methods
A retrospective chart review was performed for all patients evaluated
for beta lactam allergy from January 2010 to June 2015 in a community allergy clinic. Evaluation was by intradermal testing and/or oral
drug provocation test when deemed appropriate. Final outcomes
were decided by a consensus of consultant investigators based on
reaction history and results of skin and/or oral drug provocation
testing.
Results
Our sample includes 306 referred patients with a recent history of a
reaction to a beta lactam antibiotic. Mean age was 11.6 (SD 17.3);
49.5% of patients were male. Most reactions were to amoxicillin, and
most reactions were reported as mild non-urticarial skin reactions.
There were only 1/106 (0.009%) positive intradermal tests. Only 2/
191 (0.01%) patients reacted with an oral drug provocation test with
World Allergy Organization Journal 2017, 10(Suppl 1):25
symptoms consistent with IgE-mediated hypersensitivity. Six patients
were deemed unfit candidates for testing based on elements in reaction history suggestive of a serious delayed reaction. Four patients
had delayed non-urticarial exanthems after oral drug provocation
testing. Overall, 294 patients (96.1%) of those evaluated were determined not to require future avoidance of any beta lactam antibiotic.
Increased risk of anaphylaxis was ruled out in 99.3% of cases.
Conclusions
Patients with documented beta lactam allergy were rarely allergic
upon evaluation. This supports arguments for strategic widespread
testing and delabelling of ‘penicillin allergic’ outpatient populations,
particularly for pediatric patients.
A14
Diagnostic accuracy of fractional exhaled nitric oxide
measurement for cough variant asthma and eosinophilic
bronchitis in adult patients with chronic cough: a meta-analysis
Woo-Jung Song1, Ji-Su Shim1, Ha-Kyeong Won1, Sung-Yoon Kang1,
Kyoung-Hee Sohn1, Byung-Keun Kim1, Eun-Jung Jo2, Min-Hye Kim3,
Sang-Heon Kim4, Heung-Woo Park1, Sun-Sin Kim1, Yoon-Seok Chang1,
Alyn H Morice5, Byung-Jae Lee6, Sang-Heon Cho1, Kyung-Up Min1
1
Seoul National University, College of Medicine, Department of Internal
Medicine, Seoul, South Korea ; 2Pusan National University, College of
Medicine, Department of Internal Medicine, Busan, South Korea ; 3Ewha
Woman’s University, School of Medicine, Department of Internal
Medicine, Seoul, South Korea ; 4 Hanyang University, College of
Medicine, Department of Internal Medicine, Seoul, South Korea ; 5Hull
York Medical School, Castle Hill Hospital, University of Hull, Cottingham
Centre for Cardiovascular and Metabolic Research, Cottingham, United
Kingdom ; 6Sungkyunkwan University, School of Medicine, Department
of Medicine, Seoul, South Korea
Correspondence: Kyung-Up Min
World Allergy Organization Journal 2017, 10(Suppl 1):A14
Background
Cough variant asthma (CVA) and eosinophilic bronchitis (EB) are two
major conditions presenting as chronic cough; however, conventional methacholine challenge and induced sputum tests are technically demanding and have been restricted to specialized centers.
Fractional exhaled nitric oxide (FeNO) measurement is a simple, rapid
and non-invasive test, and could be a point-of-care alternative to the
conventional diagnostics in chronic cough.
Objective
To obtain summary estimates of diagnostic test accuracy of FeNO in
predicting CVA and/or EB in adult patients with chronic cough
Methods
Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies which
reported the diagnostic accuracy of FeNO for detecting CVA or EB
were included. Risk of bias was assessed with QUADAS-2. Random effects meta-analyses were performed to obtain summary estimates of
the diagnostic accuracy of FeNO.
Results
A total of 15 studies involving 2,187 adult patients with chronic cough
were identified. FeNO had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area
under curve (AUC) to be 0.87 (95% CI 0.83-0.89). Specificity was higher
and more consistent than sensitivity. However, in non-asthmatic
chronic cough population, the diagnostic accuracy to predict EB was
found to be relatively lower (the summary AUC 0.81 [95% CI 0.77-0.84])
and specificity was inconsistent.
Conclusions
The present meta-analyses indicated the diagnostic potential of FeNO
as a ‘rule in’ test for detecting CVA in adult patients with chronic cough.
However, FeNO may not be useful to predict EB in non-asthmatic
chronic cough. These findings warrant further studies to validate the
roles of FeNO in clinical practice of chronic cough patients.
Page 6 of 39
A15
Evaluation of oral desensitization with nickel (Tionickel) in patients
suffering from SNAS
Maria Assunta Boscolo 1, Giulio Brivio 1, Sergio Bosisio 1, Nicoletta
Manzocchi 1, Edoardo Pulixi 1, Giulia Grignani 1, Eloisia D’Andrea 1,
Massimo Ricci 1, Elena Passini 1, Maurizio Italia 1
1
Merate Hospita,l Allergology, Osnago, Italy
Correspondence: Maria Assunta Boscolo
World Allergy Organization Journal 2017, 10(Suppl 1):A15
Background
The SNAS (Systemic Nickel Allergy Syndrome) appears with symptoms in various organs (oculorhinitis, asthma, eczema, urticaria, abdominal pain, diarrhoea, epigastric pain) in a fair percentage of
patients suffering from proven ACD (Allergic Contact Dermatitis),
caused by hypersensivity to nickel.
Objective
The object of the research is the evaluation of the effectiveness of
the desensitization with Tionickel (Lofarma) associated with a lownickel diet, in patients suffering from SNAS, in comparison with the
mere low-nickel diet.
Methods
The research was carried out on 66 patients over a period of 3 years.
62 males and 4 females aged between 18 and 68 (average age 36).
26 patients opted to follow the mere low-nickel diet.
40 patients chose to follow a low-nickel diet + desensitization with
Tionickel.
Results
The 26 patients treated with the mere diet did not suffer from any
symptoms during the period in which they were following the diet.
The symptoms appeared again, much more slightly, with the interruption of the diet. During check challenges, the symptoms showed
up with higher doses of nickel.
Out of 40 patients treated with Tionickel + diet:
7 interrupted the therapy due to considerable side effects.
2 interrupted the treatment due to pregnancy.
10 follow a free diet with no symptoms after the end of therapy.
21 suffer from occasional and slight symptoms when they eat food
containing a quantity of nickel, which is higher than 500 mg/kg
Conclusions
Desensitization with Tionickel associated with a low-nickel diet has
shown a clear effectiveness in terms of reduction of the symptoms,
in comparison with patients following the mere diet.
The course of desensitization with Tionickel could not be completed
on a considerable number of patients (7 over 40), due to serious side
effects.
A16
Is smoking an enabler to experiment with other drugs for
teenagers living in a small city in the South of Brazil?
Marilyn Urrutia-Pereira1, Stefani Fagundes2, Vinicius Jardim Oliano3,
Dirceu Solé 4
1
Federal University of Pampas (Unipampa), Children Pediatric,
Uruguaiana, Brazil ; 2Federal University of Pampas (Unipampa), Pediatrics,
Uruguaiana, Brazil ; 3University of Campanha Region (URCAMP),
Pediatrics, Uruguaiana, Brazil ; 4Federal University of São Paulo Allergy,
Clinical Immunology and Rheumatology, São Paulo, Brazil
Correspondence: Marilyn Urrutia-Pereira
World Allergy Organization Journal 2017, 10(Suppl 1):A16
Background
Despite anti-smoking prevention programs, many teens start smoking at school age.
Objective
Our objectives were to determine the prevalence and risk factors associated with smoking in adolescents living in Uruguaiana, RS, Brazil.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Methods
A thousand public school teenagers living in the city of Uruguaiana
RS, Brazil, participated in this study, answering the modified California Smoking Survey, where questions on use of alcohol and cannabis
were added.
Results
According to the fact of experimenting smoking at least once they
were considered experimenters (Ex; 35,7%) the ones who did not,
non-experimenters (NEx; 64,3%). Both groups were similar as to
vender. Among Ex adolescents 22.7% have chronic respiratory problems, 79.8% reported having ease in getting cigarettes, 39.7% having
been affected by a smoker friend. 13,7% of them referred to use
electronic cigarettes, 39.2% try hookah and 56% live with mother’s
smokers. The frequency of having used an alcoholic beverage and/or
smoked cannabis, were significantly high among Ex in comparison to
NEx. The beginning of smoking coincided with the beginning of
ingestion of alcohol and they were significantly relevant before 12
years of age. The knowledge and the use of other forms of cigarette
(electronic and hookah) were significantly higher among Ex. The
teenagers do not associate them to health hazards.
Conclusions
The prevalence of tobacco experimentation is high, starting early on
life and is associated with the increased use of other drugs: alcohol
and cannabis.
A17
Comprehensive evaluation before thermoplasty treatment: The
University of Cincinnati experience
Sadia Benzaquen1, Alejandro Aragaki1, Ricardo Balestra, Dawn Harden1,
Danielle Caudell-Stamper1
1
University of Cincinnati, Pulmonary, Cincinnati, OH, United States
Correspondence: Sadia Benzaquen
World Allergy Organization Journal 2017, 10(Suppl 1):A17
Bronchial thermoplasty (BT) is a new endoscopic treatment for severe
persistent asthma which applies heat temperature (65 degrees Celsius) to the small airway for 10 seconds causing atrophy of the small
muscle. The treatment is performed as an outpatient procedure on 3
different occasions, each 3 weeks apart. Unfortunately, the cost and
insurance approval remain major issues in the US. In order to obtain
insurance approval, we have created a comprehensive work-up for
people with severe persistent asthma who are referred to the IP
(interventional pulmonology) clinic at the University of Cincinnati.
All of the patients attend an office visit with complete PFTs with and
without BD response. If the PFTs do not show obstruction or BD response, the patients get a methacholine challenge test to rule out
the diagnosis of asthma.
Before consideration for BT, all of the patients get a dynamic bronchoscopy to rule out VCD, laryngopharyngeal reflux disease or EDAC
(excessive dynamic airway collapse). All of the patients get allergy
testing, total IGE and IGG/IGE anti aspergillus. Finally, we order a
HRCT to rule out bronchiectasis. Depending on the findings of the
initial work up, they may need other procedures, such as an extensive work up for GERD.
Between January 2011 and January 2015, we evaluated a total of 50
patients who were referred for thermoplasty. The mean age was 49
years. The sample was 68% female and 32% male. Seventy-four percent of the patients had obesity or morbid obesity. Medication use
was as follows: 80% on oral corticosteroids, 90% on ICS, 95% on a
LABA, 96% on SABA, 2% on short anticholinergic, 18% on long acting
anticholinergic, 56% on antileukotriene receptor antaganoist, 20% on
Xolair, and 4% on amynophiline. The mean FeVi1 1.99 liters. Interestingly, we found that 56% of the patients had another diagnosis in
addition to asthma. Specifically, 30% had excessive dynamic airway
collapse, 8% had VCD, and 18% had LPR. Of all the screened patients,
only 44% completed the thermoplasty treatment. Forty-two percent
were good candidates for thermoplasty, but never got the approval
by their insurance, and 14 percent were not appropriate candidates
for thermoplasty.
In conclusion, we believe that thermoplasty is another tool that may
benefit our patients with severe persistent asthma. It is important to
Page 7 of 39
select the appropriate patients in order to get insurance approval
and have a high treatment success rate.
A18
An oral immunotherapy for treatment of asthma and other allergic
airway diseases by using microRNAs
Gilbert Glady
EBMA clinical research, Colmar, France
World Allergy Organization Journal 2017, 10(Suppl 1):A18
Background
Rhinitis and asthma are highly prevalent chronic diseases prevalent
in both developed and developing countries, where a lot of people
of all ages and ethnic backgrounds are affected. Evidences indicate
that etiology of asthma and allergic diseases is complex and has
strong genetic and environmental components.
Objective
All these data explain the large number of treatments available
today, but not always satisfying related to long term efficacy and
safety. It may therefore be of interest to have a biomimetic treatment
globally recovering the different molecular and cellular mechanisms
involved in these allergic diseases.
Methods
The inflammatory process in the airways displays several common
characteristics in asthma and allergic rhinitis, e.g. IgE-dependent activation of mast cells, infiltration of eosinophils, and an increase in the
number of T4-lymphocytes and Th-2 type cytokine concentrations. In
addition, cytokines associated with regulatory T-cells and Th1 and
Th17 cells have been found to be essential.
microRNAs (miRNAs) are short, single-stranded RNA molecules, that
cause degradation of target mRNAs or inhibit their translation. Each
miRNA can have one or more target transcripts, while each transcript
may be regulated by one or more microRNAs; therefore, miRNAs cumulatively influence the expression of a large proportion of genes.
Current knowledge shows different specific mechanisms by which
miRNAs impact allergic inflammation in tissues: - polarization of Th2
cells, - development and functions of T8-cells and innate immune
cells found in or recruited into the inflamed tissue, - chronic inflammation through effects in epithelial cells.
As miRNAs can be either inhibited or overexpressed, there is an obvious potential for miRNAs as novel target molecules for the development of biological therapeutics.
Results
To avoid any side effects, our team prepare microRNAs on a nanobiological level by using high dilutions of them; it follows a sublingual administration to reach quickly the main immune cells and molecules.
A clinical study with 61 patients showed that this kind of sub-lingual
immunotherapy could allow to reduce a corticotherapy significantly
and improve several clinical respiratory symptoms by a majority of
these asthma patients.
Conclusions
So it becomes possible to regulate chronic allergic diseases like asthma
and rhinitis by using the own regulatory means of the immune system
without penalizing it otherwhere.
A19
New onset soy-related exercise induced anaplylaxis (EIA) in
adolesences with peanut allergy
Mark Holbreich
Allergy Consultants, Indianapolis, IN, United States
World Allergy Organization Journal 2017, 10(Suppl 1):A19
Background
The incidence of peanut allergy in the United States is rising dramatically. We have recognized a number of peanut allergic patients who
have previously tolerated soy who developed soy-related exercise
induced anaphylaxis (EIA) in adolescence.
Objective
We hope to make allergists aware of the risk of soy-related EIA in
their peanut allergic patients as they reach adolescence.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Methods
The charts of 3 patients who presented with soy-related EIA were
reviewed for clinical data related to peanut allergy and soy-related EIA.
Results
Case #1 is a 17 year old male diagnosed with peanut allergy at age
1 year. At age 13 he ingested a soy butter sandwich at school. Then
during physical activity that followed immediately after eating the
meal he developed EIA. He was treated with antihistamines and albuterol and symptoms resolved. His prick skin test (PST) was positive to soy butter. He had previously been tolerating soy. Case #2 is
a 15 year old male diagnosed with peanut allergy at age 1 year. At
age 12 years he developed EIA after eating a lunch patty at school.
The patty contained soy protein concentrate. His PST was positive
to soy as well as to the lunch patty. He has previously tolerated
soy. Case #3 is a 14 year old female diagnosed with peanut allergy
at age 1 year. Following ingestion of a portion of soybean (edamame) she developed EIA during a swim practiced that followed
the meal. She required albuterol and injected epinephrine as well
as an emergency room visit. Her PST was positive to edamame.
Conclusion
We suspect that allergists will be seeing more soy-related EIA as their
young patients with severe peanut allergy approach adolescence.
The mechanism of this is not well understood. Soy is a frequent additive to foods and the diagnosis of soy-related EIA places new burdens on these families and children.
Consent
The author received informed consent from the patients’ parents to
publish.
A20
The role of gene polymorphism of Toll-like receptors 2,4 and Clara
cell protein in the development of asthma in adults
Nataliya Lyakhovska, Igor Kaidashev
Supreme State educational institution of Ukraine “Ukrainian Medical
Stomatological Academy”, Ministry of Health, Poltava, Ukraine
Correspondence: Nataliya Lyakhovska
World Allergy Organization Journal 2017, 10(Suppl 1):A20
Background
Genetic aspects of asthma and atopy have been widely studied.
Candidate genes and loci of chromosomes probably responsible for
the occurrence of bronchial asthma (BA) are defined by a large amount.
Objective
The aim of our work was to study polymorphisms 2258G / A gene
TLR2 (rs5743708) and 896A / G genaTLR4 (rs4986791), Clara cell protein gene (A38G), with a specific weight of 16 kDa (CC16) in the adult
population. We examined 45 patients with asthma in the period
without exacerbation.
Methods
Diagnosis of asthma and severity was approved accordance with the
criteria GINA. To determine the sensitivity to allergens used skin prick
test. Determination of polymorphisms TLR2 gene and gene TLR4, gene
CC16 carried by polymerase chain reaction with special primers.
Results
Patients with BA significantly more common had genotype GA
(11,1%) gene TLR2 (p = 0.04) compared with the control group. In patients who are carriers of a mutant allele of a gene TLR2 A history
pneumonia frequently observed (p = 0.046) and there were signs of
candidiasis (p = 0.034) compared with patients with no polymorphism. In the study of polymorphism of TLR 4 found that genotype AG
statistically more likely (p = 0.04) is found in the BA group (15.6%)
than in the control group. Patients with polymorphism 896A/G TLR4
gene disease begins in childhood (p = 0.03) in the spectrum of
sensitization were dietary factors (p = 0.02) and there were other
manifestations of allergic diseases (p = 0.045). Polymorphic variant
gene 38G CC16 significantly more common in patients with BA than
in the control population (p = 0.019). Clinical manifestations in
patients with BA who are carriers of the gene allele 38G CC16 are
fungal sensitization, atopic dermatitis and history of tuberculosis, the
need for frequent doses of glucocorticoids.
Conclusions
Page 8 of 39
The study of polymorphisms 896A / G gene TLR4 and 2258G/A TLR2
gene, A38G gene CC16 gene demonstrated their direct impact on the
pathogenetic features of bronchial asthma. And is the basis for our next
research of biomarkers of allergic inflammation (IgE, Il-4, Il-10), T-reg cell
in patients who are carriers of polymorphisms of genes studied.
A21
The effect of anti-IgE monoclonal antibody on other allergic
comorbidities of severe asthma patients
Jaromir Bystron, Beata Hutyrova
University Hospital Allergology and Clin. Immunology, Olomouc, Czech
Republic
Correspondence: Jaromir Bystron
World Allergy Organization Journal 2017, 10(Suppl 1):A21
Background
Omalizumab is approved for the treatment of severe persistent allergic asthma and chronic spontaneous urticaria, although a number of
studies confirmed the effectiveness of this therapy also on other IgEmediated diseased.
Objective
The aim of this study was to evaluate the effect of anti-IgE treatment
on other allergic diseases in patients treated with omalizumab for severe allergic asthma enrolled in the CAR (Czech Anti-IgE Registry).
Results
In 209 patients included in the CAR the effect of treatment with
omalizumab on clinical manifestations of allergic rhinitis (n = 185),
atopic dermatitis (n = 63), food allergy (n = 55), and chronic urticaria
(n = 12) after 12 months of therapy was also evaluated. The positive
effect of treatment with omalizumab was observed in 83.3% of patients with allergic rhinitis (improvement in 64.9% of patients,
complete remission of symptoms in 18.4% of patients). Improvement
of chronic urticaria was reported in 41.7% of patients and complete
remission also observed in 41.7% of subjects. In 46.0% of patients
the improvement of atopic dermatitis was observed and 34.9% of patients had no symptoms of skin disease. Food allergy was improved
in 25.5% of patients and in 38.2% of patients the symptoms have
subsided. In food allergies, compared to other monitored diseases,
there was the highest percentage of patients (32.7%) with no change
in symptoms during treatment with omalizumab.
Conclusions
In the CAR registry of patients with severe allergic asthma treated
with omalizumab the positive effect of anti-IgE therapy on other allergic comorbidities was found. Majority of patients with allergic rhinitis, atopic dermatitis, chronic urticaria and food allergies experienced
the improvement or complete remission of the symptoms of particular diseases.
A22
Anaphylaxis caused by chicory might be associated with
sensitization to cannabis
Galina Balakirski1, Luk Vanstreels1, Gerda Wurpts1, Hans F Merk1,
Jens Malte Baron1, Johanna Plange1, Hans-Peter Rihs2, Monika Raulf2,
Stefani Roeseler1
1
University Hospital of RWTH Aachen, Department of Dermatology and
Allergology, Aachen, Germany ; 2Ruhr-University Bochum, Institute for
Prevention and Occupational Medicine of the German Social Accident
Insurance, Bochum, Germany
Correspondence: Galina Balakirski
World Allergy Organization Journal 2017, 10(Suppl 1):A22
Background
A 31 years old female patient developed severe facial angioedema
shortly after a dinner with turkey, potatoes, chicory and a readymade sauce. She also had some Schweppes® together with a pill out
of acetylsalicylic acid, paracetamol and caffeine during the meal due
to headache. In our department she recovered rapidly after intravenous administration of prednisolone, dimetindene and ranitidine.
Objective
In order to explore the cause of the anaphylactic reaction the patient
consumed turkey, potatoes, a ready-made sauce and Schweppes®
World Allergy Organization Journal 2017, 10(Suppl 1):25
once more, however tolerated the meal without any problems. She
also took a pill containing paracetamol and caffeine and experienced
no reaction after this self-experiment.
Anamnestically the patient reported to suffer from signs and symptoms of allergic rhinoconjunctivitis due to the known sensitization to
tree and grass pollen, and to house dust mites. Furthermore she
experienced signs and symptoms of an oral allergy syndrome by
nuts. She also reported to smoke marijuana frequently. During preparation of the joints the patient described symptoms of allergic rhinoconjunctivitis with itchy eyes, sneezing, and runny nose, but not
during marijuana smoking.
Methods
We performed a skin prick test with analgesics including acetylsalicylic acid with a negative result. The prick to prick test with chicory
(>10 mm) and cannabis (7 mm) were positive. Specific (s) IgE was detected with the ImmunoCAP system: sIgE to rPru p 3 (lipid transfer
protein (LTP) of peach) was CAP class 3, sIgE to rCan s 3 (LTP of Cannabis sativa) was CAP class 2.
Results
Only few cases of anaphylactic reactions caused by chicory are reported in the literature. The most common allergen (in over 90% of
cases) is LTP of lettuce Lac s 1, which shows cross-reactivity to Pru p
3. The LTP of marijuana Can s 3 is also described with cross-reactivity
to Pru p 3 (1).
Conclusions
In the literature case reports about patients with symptoms of allergic rhinoconjunctivitis due to marijuana exist, who developed allergic
symptoms including anaphylaxis after consuming tomato or peach
months later [2]. The suggested mechanism is a cross-reaction of LTP
Can s 3 to peach (Pru p 3) and tomato (Lyc e 3) [1,2]. Also in our case
we assumed a primary sensitization to Can s 3 with cross-reaction to
other LTPs (i.e. Pru p 3, Lac s 1, Cor a 8), that could explain an anaphylactic reaction after consuming chicory.
Consent
The authors received informed consent from the patient to publish.
References
1. Armentia A et al.J Allergy Clin Immunol Pract 2014;2(3):351-2
2. Gamboa P et al. J Allergy Clin Immunol 2007;120(6):1459-60
A23
A comprehensive environmental and building pathology
assessment of asthmatic children in Buenos Aires, Argentina
Alberto Tolcachier1, Armando Chamorro, Ruth Otero2
1
Durand Hospital, Allergy, Buenos Aires, Argentina ; 2Soluciones
Ambientales CIH, Buenos Aires, Argentina
Correspondence: Alberto Tolcachier
World Allergy Organization Journal 2017, 10(Suppl 1):A23
Background
Indoor air quality in a child’s dwelling is a matter of concern because
its deterioration often leads to development of allergies and asthma.
Numerous studies justify the application of interventions to reduce
respiratory symptoms associated with environmental burden of allergens, especially in children. Additinally, several meta-analyzes and
guidelines warn about the importance of avoiding the potential environmental pollutants that may trigger or exacerbate respiratory
symptoms, and state recommendations concerning measures of hygiene, temperature control, humidity exposures and maintenance of
building structures.
Objective
Given the lack of accurate environmental investigations in homes of
asthmatic children in Argentina, a pilot study of 10 selected homes
in the City of Buenos Aires and its surroundings, inhabited by asthmatic children was conducted.
Methods
The home environmental evaluation included the potential asthmatriggering contaminants, allergens, airborne particulate characterization,
thermal comfort, Infrared thermography and building envelope moisture levels and air pollutants to which the child might be exposed, utilizing resources from the Centers for Disease Control and Prevention
Page 9 of 39
(CDC), US Environmental Protection Agency (EPA), and various Healthy
Homes Initiatives. Building forensic pathology elements, including
home envelope analysis and cooling and heating units, that may contribute to poor indoor air quality have also been incorporated into the
evaluation.
Results
The results of the study show an overwhelming evidence of building
failure causes coupled with in some cases a significant level of measured allergens in indoor samples that can potentially trigger allergenic and asthma related symptoms to the youth.
Conclusions
This study focuses on finding potential environmental contaminants
that may trigger or exacerbate respiratory challenges within the
youths, in order to provide residents of those homes precise guidelines for building repairs, renovations, remediation and mitigation of
building related failures and allergen control, based on real-life scenario. To date, no study is known to have specifically addressed this
issue in Argentina.
A24
Hypersensitivity pneumonitis in a farmer
Joel Brooks1, Michael Hess2, Jared Benz2, Joseph MacDonald2
1
Yale University, School of Medicine, Allergy and Immunology, New
Haven, CT, United States ; 2Heart of Lancaster Regional Medical Center,
Internal Medicine, Lititz, PA, United States
Correspondence: Joel Brooks
World Allergy Organization Journal 2017, 10(Suppl 1):A24
Background
Hypersensitivity pneumonitis (HP) is a complex syndrome resulting
from repeated exposures to a variety of organic particles. These antigens provoke an immune response in lung parenchyma and small
airways. It presents as an acute, sub-acute, or chronic condition and
occurs in occupational, home, and recreational settings. There are
several proposed diagnostic criteria for HP including exposure to an
offending antigen, respiratory signs and symptoms, radiographic
findings (such as reticular, ground glass, or nodular opacities), altered
spirometry and lung volumes, bronchoalveolar lavage with lymphocytosis, histopathology showing mononuclear cell infiltrate or noncaseating granulomas, or positive inhalation testing to the antigen or
environment.
Objective
Recognize the clinical features of hypersensitivity pneumonitis and
assess and treat patients presenting with this condition.
Methods
A 53 year old male with history of asthma presented to his primary care physician (PCP) after experiencing several days of fevers, wheezing, and shortness of breath. He was working in his
grain silo two days prior with possible mold and pesticide exposures. His PCP prescribed a short course of corticosteroids. There
was no improvement in symptoms and the patient presented to
the emergency department. His initial oxygen saturation was in
the low 80s requiring five liters of oxygen via nasal cannula. On
exam, the patient had extensive crackles and rales diffusely
throughout all lung fields. His labs were unremarkable except for
an elevated CRP. His chest x-ray showed bilateral alveolar infiltrates. His constellation of signs and symptoms were consistent
with hypersensitivity pneumonitis. The patient was placed on
Solumedrol 40 MG IV twice daily for 48 hours and albuterol/ipratropium nebulized treatments with clinical improvement before
transitioning to an oral prednisone taper.
Results
Farmer’s lung affects 0.4%-7% of the farming population and is one
of the most common forms of HP. The prevalence varies by region,
with approximately 9% of famers affected in the humid zones and
2% in drier zones Treatment consists of antigen avoidance and
corticosteroid therapy with the recommended dose of prednisone
0.5-1mg/kg daily for 1-2 weeks, with a 2-4 week taper. Approximately
50% of farmers with this condition develop minor lung functional abnormalities. The recovery process may take years after the antigen
exposure ceases.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Conclusions
Hypersensitivity pneumonitis must be considered in populations
such as farmers who are commonly exposed to inciting antigens.
The mainstay of treatment is atigen avoidance with a corticosteroids
course. Maintenance steroids are not usually necessary and the majority of patients recover with minimal functional lung deficits.
Consent
The authors received informed consent from the patient to publish.
A25
Respiratory distress as the initial manifestation of microscopic
polyangiitis
Joel Brooks1, Jared Benz2, Usma Chatha2, Dale Lent2
1
Yale University, School of Medicine, Allergy and Immunology, New
Haven, CT, United States ; 2Heart of Lancaster Regional Medical Center
Internal Medicine, Lititz, PA, United States
Correspondence: Joel Brooks
World Allergy Organization Journal 2017, 10(Suppl 1):A25
Background
Microscopic polyangiitis (MPA) is a systemic necrotizing vasculitis that
affects small vessels in multiple organs, including the kidneys and
lungs. Initial presentation includes fatigue, fevers, arthralgias, and
weight loss. With progression, patients develop glomerulonephritis. Pulmonary involvement, commonly alveolar hemorrhage, is frequent and
manifests with dyspnea, cough, or hemoptysis. The detection of antineutrophil cytoplasmic antibody (ANCA) and anti-myeloperoxidase
(MPO) antibody are useful serologic markers for diagnosis.
Objective
Recognize the clinical features of MPA and assess and treat patients
presenting with this condition.
Methods
An 87-year-old Caucasian female with history of giant cell arteritis
(GCA) and stage III chronic kidney disease was hospitalized with respiratory failure, fatigue, dry cough, and lower extremity edema. A
CT revealed bilateral infiltrates. Laboratory studies included an ESR
>100, creatinine of 4.7 (baseline: 1.4), hemoglobin of 6.1, proteinuria,
and hematuria with fine granular casts. Concern was raised for vasculitis with alveolar hemorrhage and steroids were initiated. A thorough
rheumatologic workup was performed including ANCA studies. She
declined a renal biopsy. Her condition deteriorated and she was transitioned to comfort measures and expired. Posthumously, her antiMPO antibody returned elevated (605.7), supporting the diagnosis of
MPA.
Results
MPA, granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA) are the small vessel vasculitis that
are known as the ANCA-associated vasculitis. There are shared features between these conditions including renal involvement with
pauci immune focal segmental necrotizing glomerulonephritis. GPA
is most commonly associated with a positive anti-PR3 (c-ANCA),
while EGPA and MPA are more commonly associated with a positive
p-ANCA. The anti-MPO (p-ANCA) is most commonly associated with
MPA, but it can appear positive in any ANCA-associated vasculitis.
Therefore, diagnosis must be made by combing the clinical features
with the diagnostic findings. Therapy includes high dose corticosteroids with immunosuppressive agents. Plasma exchange is beneficial
in severe renal disease and alveolar hemorrhage. A unique feature of
this case was the patient’s history of GCA, which is linked to several
inflammatory conditions.
Conclusions
MPA is diagnosed by combining clinical suspicion with laboratory
findings. A broad differential must be maintained when treating patients with suspected vasculitis. Vasculitic conditions are associated
with poor prognoses without timely treatment with glucocorticoids
and immunosuppressive agents. As there is a variable prognosis,
prompt treatment must be initiated to decrease morbidity and
mortality.
Consent
The authors received informed consent from the patient to publish.
Page 10 of 39
A26
Relationship between nasal polyposis and serum level of vitamin D
Şükran Köse 1, Bengü Gireniz Tatar 2, Gülgün Akkoçlu 2, İbrahim
Çukurova 3, İlker Ödemiş 2, Ayşin Kılınç Toker 2
1
Tepecik Training and Research Hospital, Infectious Diseases and Clinical
Microbiology and Immunology, izmir, Turkey ; 2Tepecik Training and
Research Hospital, Infectious Diseases and Clinical Microbiology, izmir,
Turkey ; 3Tepecik Training and Research Hospital, Department of
Otorhinolaryngology, izmir, Turkey
Correspondence: Şükran Köse
World Allergy Organization Journal 2017, 10(Suppl 1):A26
Background
Nasal polyps are one of the most common mass lesions of the nose.
Nasal Polyposis (NP) is an inflammatory condition of unknown etiology. Treatment of NP is a significant challenge to the physicians.
Also some genetic factors are implicated in the pathogenesis of NP,
but gene expressions required for its development are still unclear.
The understanding of the pathophysiology underlying cause in NP is
necessary to treatment options.
Objective
In this study we aimed to invastigate relationship between nasal
polyposis and serum level of vitamin d has been proven to have immunomodulatory effects.
Methods
A total of 41 NP patients and 40 healthy controls were included in the
study, from January 2013 to December 2015 at the Izmir Tepecik
Training and Research Hospital. The study was performed retrospectively. In study patients and control groups, serum 25-hydroxyvitamin
D[25(OH)D] levels were studied by chemiluminescence immunoassay.
Results
The average age of NP patients is 48,4 and control group is 46,2.
50% of the control group and 44% of NP patients are female gender.
Serum 25(OH)D levels were detected in NP patients and healthy controls below normal range. Serum 25(OH)D level was 13.6 ng/ml in NP
patients and 12.9 ng/ml in the control group. There was no significant statistical difference between groups (p> 0.05). In both groups,
serum 25(OH)D levels were lower in women than men.
Conclusions
The etiology of NP is unclear and it is known to have associations
with allergy, asthma, cystic fibrosis and aspirin sensitivity. This situation shows that systemic rather than local involvement. Treatment
of NP involves a combination of medical therapy and surgery. Different studies have shown that vitamin d have the immunomodulatory
effects. In our study found low serum levels of 25(OH)D in patients
both study and control groups. In comparison with serum levels of
25(OH)D between study and control group, there is no significant
difference. We believe that additional studies have more number of
patients, are useful.
A27
IgE levels among non Ahmadu Bello University staff attending the
sick bay of the University in Samaru, Zaria, Nigeria
Abdullahi Hasssan1, Abdulrazaq Abdullahi Gobir2
1
Federal medical Centre Scientific Research, Keffi, Nasarawa state, Nigeria ;
2
Faculty of Medicine, Ahmadu Bello University Community Medicine, Zaria,
Kaduna State, Nigeria
Correspondence: Abdullahi Hasssan
World Allergy Organization Journal 2017, 10(Suppl 1):A27
Background
IgE is a monomeric unique homocytotropic molecule that protects
individual in Falciparum malaria and Nematodes infection. It is responsible for immune response in hypersensitivity reaction type1
and anaphylaxis.
Objective
The aim of this study is to know the levels of IgE antibody in the
population under reference.
Methodology
The study is a prospective cross sectional studies. IgE serum concentration was determined using double antibody (sandwich) ELISA
World Allergy Organization Journal 2017, 10(Suppl 1):25
Technique. Blood collected at the study Centre from the study population and separated to obtained serum following standard protocol.
The study subjects recruited were General outpatients, Nonsmokers,
non-asthmatic, non-pregnant (if females) and non-staff of the university selected via stratified random sampling technique to obtained
89 clients being the study population.
Results
IgE range in the study was found to be between 21iu/ml to 450iu/
ml, while normal range was between 21iu/ml to 150iu/ml. 35 (39.3%)
of the study population were males of which 20 (57%) have IgE
levels <150iu/ml, while 15 (43%) have IgE levels> 150iu/ml. 54
(60.7%) were females, of these females’ clients, 44 (81.5%) have normal IgE levels, while 10 (18.5%) have IgE levels> 150iu/ml. The occupation of the clients under study, revealed that 20(22.5%) were
employed and 15 (75%) have IgE levels <150iu/ml while 15 (25%)
have IgE levels> 150iu/ml.10(11.2%) were unemployed amongst
them, 4 (40%) have IgE levels <150iu/ml and 6 (60%) have IgE
levels> 150iu/ml. 21 (23.6%) were self-employed from which 7
(33.3%) have IgE levels <150iu/ml and 14 (66.7%) have IgE levels>
150iu/ml. 38 (42.7%) clients were students, 18 (47.3%) of the students
have IgE levels <150iu/ml, while 20 (52.7%) students have IgE levels>
150iu/ml. On clients’ residents, 55 (68.2%) leaves in Samaru where 40
(72.7%) clients amongst them have IgE levels <150iu/ml and 15
(27.3%) have IgE levels> 150iu/ml. 20 (22.5%) clients leave in Palladan where 12 (60%) have IgE levels <150iu/ml while 8 (40%) have
IgE levels > 150iu. 14(15.7%) were Giwa residents and 5 (36%) have
IgE levels <150iu/ml while 9 (64%) have IgE levels > 150iu/ml.
Conclusion
It is being observed that IgE levels has correlation with gender, occupation and place of resident. Knowing IgE levels will help in reducing
morbidity and mortality related to allergies.
A28
Characteristics of serious adverse drug reactions: experience in a
single university hospital
Cheol-Woo Kim1, Young Hwa Choi2, Jeong Hye Lee1, Rae Jeong Cho1
1
Inha University School of Medicine, Incheon, South Korea ; 2Ajou
University School of Medicine, Suwon, South Korea
Correspondence: Cheol-Woo Kim
World Allergy Organization Journal 2017, 10(Suppl 1):A28
Background
The incidence of adverse drug reactions (ADRs) may have been continuously increased as drug use increases. Development of ADRs, especially serious ADRs (SAEs) causes unnecessary patient suffering
and may threaten the patient’s life in severe cases. Therefore, efforts
should be made to prevent the occurrence of SAEs, which require
correct recognition for the characteristics and nature of the SAEs.
Objectives
This study was performed for the characterization of SAEs based on
spontaneously reported pharmacovigilance database in a single university hospital.
Methods
ADRs reported to Inha University Hospital Pharmacovigilance Center
were collected from Jan 2012 to Dec 2015, and cases of SAEs were
selected. Clinical information was collected from electronic medical
records.
Results
A total of 495 SAEs (4.9%) among 10,064 ADRs were identified
through spontaneous reporting system. Among them, 294 (59.4%)
were developed in female patients, and 298 (60.2%) were reported
from patients aged 50 and over. SAEs were reported by doctors
(41.4%), nurses (24.4%), and pharmacists (34.1%). ADR relatedhospitalization or prolongation of existing hospitalization was the
most common cause of SAEs, and other medically important event
was the second cause. Antineoplastic agents (31.7%), anti-infectives
(19.2%), and agents for central nervous system (14.5%) were the drug
class commonly involved, and cephalosporin antibiotics and NSAIDs
were the leading subclass. Thirty-two cases of severe cutaneous adverse reaction such as Stevens-Johnson syndrome and toxic epidermal necrolysis were detected during study period.
Page 11 of 39
Conclusion
Cephalosporin antibiotics and NSAIDs are the most important causative
agents that cause SAEs. Hospitalization or extension of the hospital stay
are the most common cause of SAEs. Patients with previous history of
SAEs or those using high risk drugs need systemic management to control the development of SAEs.
A29
Spirodela polyrhiza L. extract modulates activation of the atopic
dermatitis-related ion channels, Orai1 and TRPV3 and inhibits mast
cell degranulation
Yu Ran Nam, Joo Hyun Nam, Woo Kyung Kim
Dongguk University, Physiology, Goyang-Korea, South Korea
Correspondence: Woo Kyung Kim
World Allergy Organization Journal 2017, 10(Suppl 1):A29
Background
Increased intracellular calcium in response to T cell receptor/IgE receptor stimulation is a key process in many CD4+ T cell and mast cell
functions. In CD4+ T cells, an increase in intracellular Ca2+ concentration ([Ca2+]i) induces Th2 cell differentiation and proliferation and
cytokine production through activation of calcium-dependent transcription factors, such as NFAT, and protein kinases, such as PKC. In
mast cells, IgE receptor-induced increased [Ca2+]i stimulates exocytosis of histamine-containing granules, activates the production and
secretion of leukotriene C4, and increases the synthesis and release
of pro-inflammatory cytokines. Therefore, agents that inhibit the calcium channels Orai1 and TRPV3 have therapeutic potential for alleviating inflammatory diseases, including atopic dermatitis.
Objective
In this study, we investigated the effects of an extract of Spirodela polyrhiza (Spirodelae Herba, SH) on the modulation of calcium ion channels,
Orai-1 and TRPV3 as a potential novel therapeutic for AD and confirmed
the regulatory role of these ion channels in mast cell degranulation.
Methods
A methanol extract of SH was prepared, and HEK293T cells overexpressing human Orai1 AND TRPV3 were treated with the extract. Modulation of the ion channels in RBL-2H3 cells was measured using a
conventional whole-cell patch-clamp technique. IgE-antigen complexstimulated mast cell degranulation was measured using a betahexosaminidase activity assay along with morphological observation.
Results
SH extract (100 μg/mL) significantly inhibited Orai1 activity in Orai1STIM1 co-overexpressing HEK293T cells. In addition, HS extract significantly increased TRPV3 activity compared to that in the presence of 2APB (100 μM), which induces full activation. SH extract (20, 50, and 100
μg/mL) inhibited degranulation in IgE-antigen complex-stimulated RBL2H3 cells as measured by a decrease in β-hexosaminidase activity.
Conclusions
Our results suggest that SH extract has potential for the treatment of
abnormal skin barrier pathologies in atopic dermatitis by modulating
the activities of the calcium ion channels Orai1 and TRPV3 and inhibiting mast cell degranulation. To the best of our knowledge, this is the
first report on an herbal effect on the modulation of ion channels associated with skin barrier disruption in atopic dermatitis pathogenesis.
A30
Allergen specific immunotherapy: effect on immunological
markers and clinical outcomes in asthmatic children - a real life
clinical trial
Ivana Filipovic1, Zorica Zivkovic 2, Djordje Filipovic 3
1
Faculty of Medical Science Kragujevac-Immunology, Kragujevac, Serbia ;
2
Children’s Hospital for Lung Diseases and Tuberculosis- Medical Center
Dr Dragisa Misovic-Pediatric, Belgrade, Serbia ; 3Institution for Emergency
Medical Care Anesthesiology, Belgrade, Serbia
Correspondence: Ivana Filipovic
World Allergy Organization Journal 2017, 10(Suppl 1):A30
Background
Allergen-specific immunotherapy (AIT) holds a great promise in the
management of allergic conditions, as the only with the capability to
World Allergy Organization Journal 2017, 10(Suppl 1):25
change the natural causes of allergic diseases. Most studies evaluated
clinical scores as the main parameters, whereas immunological andor inflammatory factors were studied only occasionally.
The aim of this study was to investigate the efficacy of SLIT on FeNO,
as well as to compare the relationship to asthma symptom and
medication score and parameters of lung function.
Methods
59 asthmatic children were included in the study. 34 patients were
received sublingual allergen specific immunotherapy (SLIT) plus
standard pharmacotherapy while 29 children received only standard
pharmacotherapy according to the GINA guideline. Efficacy was
evaluated using FeNo, asthma and medication symptom score and
lung function tests. The results of the test were compared at baseline, during the first year of follow up period and at the end of the
observational period.
Results
FeNO values decreased significantly in SLIT group (X2=52,220;
p<0,001) compared to baseline during the first and the second year
of follow up period, whereas control group values remained similar.
The SLIT group experienced significant improvement in asthma
symptoms and medication score, whereas the control group did not.
Lung function tests were also changed significantly but only in the
SLIT group.
Conclusions
SLIT improves biological and clinical parameters in asthmatic children
during the first year of follow up period with a sustainable improvement during the second year. This is one of the first studies found
positive correlation between subjective parameters such as asthma
and medication score and objective parameter FeNO and lung
function.
A31
Induction of IL-9-producing Mucosal Mast Cells (MMC9s)
contributes to the comorbidity of allergic diseases
Dana Shik, Andrew Smith, Wang Yui Hsi
CCHMC Allergy and Immunology, Cincinnati, OH, United States
Correspondence: Dana Shik
World Allergy Organization Journal 2017, 10(Suppl 1):A31
Background
Clinical studies reveal that certain individuals with atopic dermatitis
(AD) in early life are prone to develop food allergy and asthma, also
known as atopic march. However, the underlying mechanisms that
contribute to the comorbidity of allergic disorders remain unclear.
Objective
Determine the role of MMC9s in co-morbid allergic diseases and the
effect of IL-33 on MMC9 accumulation and function.
Methods
To establish an experimental atopic march model, mice that develop
AD after vitamin D3 analog treatments were inoculated with ingested
antigens before subjecting to intranasal allergen challenges. The roles
of IL-33/ST2 signals in regulating the progression of allergic diseases
were examined using genetically-modified mice. Duodenal biopsies
from atopic patients who were tested negative (control) or positive for
food allergy (FA) and additional allergic disorders were procured to
compare their IL-9 and IL-13 production after IL-33 in vitro stimulation.
Results
We have recently identified the novel IL-9-producing mucosal mast
cells (MMC9s) which can secrete prodigious amounts of IL-9 and
mast cell (MC) mediators to promote IgE-mediated food allergy.
Epidermal thymic stroma lymphopoietin (TSLP) induction after skin
sensitizations induce atopic dermatitis in mice (AD-like mice).
Repeated intragastric inoculations with ovalbumin (OVA), but not
saline, induced MMC9 accumulation in the gut of AD-like mice which
eventually developed symptoms of experimental food allergy. Notably, intranasal OVA challenge triggered significant leukocyte infiltrations and IL-4 and TARC production in the bronchoalveolar lavage
fluid in AD-like mice inoculated intragastrically with OVA but not saline. Flow cytometric analysis reveals that intranasal OVA challenge
induced an increase of pulmonary MMC9s, but a decrease of intestinal MMC9s in AD-like mice that had developed experimental food
Page 12 of 39
allergy. Interestingly, after skin sensitization, mice deficient of IL-33
receptor (St2) failed to produce intestinal MMC9s, resulting in the
resistance to develop experimental food allergy and airway inflammation after intranasal OVA challenge. In duodenal biopsies from
comorbid allergic disease (CAD) patients, MMC9 occurrence and IL33-stimulated IL-9 and IL-13 production were significantly higher
than in control individuals.
Conclusions
Our results suggest that MMC9 induction in the gut of AD-like mice
may perpetuate the progression of allergic diseases and that IL-33/
ST2 signals may amplify MMC9 function and airway MMC9 accumulation to promote airway inflammation. Thus, MMC9 may serve as a
key cellular checkpoint that bridges epidermal TSLP production to
asthma development and contributes to the co-morbidity and severity of allergic disorders.
A32
Another case of acquired angioedema secondary to a
lymphoproliferative disease successfully treated with Rituximab
Stuart Friedman1, Yonatan Gizaw2, Rima Bakhda2, Kumail Mohammed2
1
Schmidt College of Medicine Florida Atlantic University Clinical
Integrative Medicine, Boca Raton, FL, United States ; 2Boca Raton
Regional Hospital Medicine, Boca Raton, FL, United States
Correspondence: Stuart Friedman
World Allergy Organization Journal 2017, 10(Suppl 1):A32
Background
There are fewer than 150 reported cases of acquired angioedema.
There are only a few cases with documented successful treatment
with rituximab. We have added to the literature another case with
documentation of the clinical presentation as well as documented response to the treatment with rituximab.
Objective
To report the presentation, evaluation and management of an 84
year old female with recurrent severe oropharyngeal angioedema. To
add to the literature that demonstrates that rituximab, by mediating
the lysis of B-cells can be effective as a treatment for lymphoproliferative disorder associated acquired angioedema.
Methods
The patient is cared for by SF. Medical records were reviewed and laboratory tests were obtained at our hospital. Treatment with rituximab was rendered at our hospital’s cancer center.
Results
C1 esterase inhibitor functional and quantitative were reduced as
were C1q and C4. Evaluation revealed an enlarged spleen and
enlarged peri-portal and portcaval lymph nodes. Flow cytometry was
compatible with a low grade splenic mantle cell lymphoma. Treatment
was rendered with rituximab. C1 esterase inhibitor values improved
and there has not been any recurrence of angioedema.
Conclusions
Patients presenting with angioedema accompanied by low/absent
C1 esterase levels should be evaluated for lymphoproliferative autoimmune or disorders. If these types of disorders are found, rituximab
treatment should be considered. We have added to the literature
with an additional case of acquired angioedema responding to treatment with rituximab.
A33
Single practice eight-year experience treating food allergy with
oral immunotherapy
Richard Wasserman1, Angela Hague1, Deanna Pence1, Joanna Rolen1,
Robert Sugerman1, Stacy Silvers1, Qurat Kamili2
1
Medical City Dallas Hospital Pediatrics, Dallas, TX, United States ;
2
Medical City Dallas Hospital Medicine, Dallas, TX, United States
Correspondence: Richard Wasserman
World Allergy Organization Journal 2017, 10(Suppl 1):A33
Background
The prevalence of food allergy, a socially debilitating and potentially
life-threatening disorder, has increased significantly over the past ten
years. Patients and families are avidly seeking treatment but there
World Allergy Organization Journal 2017, 10(Suppl 1):25
are few options. Consequently, interest in FOIT (food oral immunotherapy) in the private practice setting has risen commensurately.
Objective
To assess the experiences and treatment outcomes of 481 FOIT
treated patients, 343 who reached their target dose and 75 who did
not. Partial data on 63 patients who were dose escalating when the
data collection was closed is included as well.
Methods
A retrospective record review of patients initiating FOIT from 6/10/08
to 6/1/16 was approved by the North Texas IRB. Patients received
FOIT doses beginning with <5mcg of nut or 100mcg of other food
protein with target protein doses of 3600mg (egg white) to 8000mg
(wheat) and 10,826mg (four nuts).
Results
Patients were treated with FOIT if they had a clear history of
allergic reaction and supportive skin prick testing or specific IgE.
Most patients with an equivocal history or testing were challenged to prove food allergy. Patients whose specific IgE suggested that food challenge would be inappropriately unsafe were
treated without a prior confirmatory challenge. No patient was
excluded because of a history of a serious reaction or a high specific IgE.
Eighty percent of patients reached their target dose and began maintenance. Egg treated patients were more likely to reach the target
(94%) than milk (78%) or peanut (79%) treated patients. Patients discontinued peanut FOIT primarily because of EoE-like OIT related gastrointestinal syndrome (ELOGS) or systemic reactions; 6.3% and 4.7%
respectively. Among peanut treated patients who reached maintenance, 18 (9.4%) later discontinued treatment, 7 because of taste aversion. Of the milk treated patients who didn’t reach or couldn’t be
confirmed to have reached the target, 8 (44%) were lost to follow up, 3
(17%) discontinued because of reactions and 4 (22%) because of
ELOGS.
Conclusions
Consistently, over the eight-year experience with FOIT, approximately
80% of patients reach their target dose. FOIT can be successfully performed in an appropriately prepared allergy office.
A34
Evaluation of PD-1 expression on T-lymphocytes in allergic rhinitis
Nadezhda Knauer1, Alexandr Zazernyi2, Elena Blinova1, Daria Demina3,
Vladimir Kozlov1
1
Research Institute of Fundamental and Clinical Immunology, Laboratory
of Clinical Immunopathology, Novosibirsk, Russia ; 2 Novosibirsk State
Medical University Pediatric Faculty, Novosibirsk, Russia ; 3 Research
Institute of Fundamental and Clinical Immunology, Allergology
Department of the Clinic of Immunopathology, Novosibirsk, Russia
Correspondence: Nadezhda Knauer
World Allergy Organization Journal 2017, 10(Suppl 1):A34
Background
According to the recent reports, pathogenesis of allergic diseases includes either increasing of the number of the activated effector cells
or decreasing of the number of T-regulatory cells (Tregs) and the reduction of their functional activity.
Objective
The evaluation of the expression of the activation markers on Tlymphocytes, such as PD-1 and CD25, as well as evaluation the number
of Tregs, in healthy volunteers and patients with allergy is important
for understanding some aspects of allergy pathogenesis.
Methods
10 healthy volunteers (age 23±4.8) and 11 patients with allergic rhinitis (AR) with sensitization to birch pollen allergens or house dust allergens (age 28±7.8) were included in the study. The sensitization
was confirmed by skin prick tests. Peripheral blood mononuclear
cells (PBMCs) were extracted from heparinized blood, then stained
by fluorescently labelled monoclonal antibodies. The number of cells
in each population (CD4+CD25+, CD8+CD25+, CD4+CD25high, CD8
+CD25high, CD4+PD-1+, CD8+PD-1+, CD4+CD25highPD-1+, CD8
+CD25highPD-1+) were evaluated by flow cytometry. We defined
CD4+CD25high as Tregs, and cells expressing markers PD-1 or CD25
Page 13 of 39
as activated cells. Statistical analysis was made using Mann-Whitney
criterion, the difference was considered significant if p<0.05.
Results
We have found the significant decreasing of Tregs (CD4+CD25high)
number in patients group. Moreover the density of CD25-expression
on Tregs was significantly lower in this group. The number of CD4
+PD-1+ lymphocytes in volunteers group was significantly lower than
in patients with AR. We have found the same tendency for activated
T-lymphocytes CD8+PD-1+. The significant difference of PD-1expression on Tregs between group of donors and patients group
was not found.
Conclusions
We have found that number of lymphocytes with PD-1, which can
be considered to be the marker of activation, is increased in patients
with AR in comparison with healthy donors – significantly in case of
CD4+-T-lymphocytes and as a tendency in case of CD8+-T-lymphocytes. In the same time, the number of Tregs decreased in patients
group. Moreover, the expression of CD25 on Tregs was lower than in
donors group. These results can confirm the theory that allergic diseases can be associated not only with increasing the number of activated effector cells, especially, T-helpers, but also with the reduction
of Tregs-subpopulation and, probably, their functional dysfunctions.
A35
Per a 10 favours Th2 responses by PAR-2 activation and increased
p-STAT 3 levels
Komal Agrawal, Sagar Kale, Naveen Arora
CSIR-Institute of Genomics and Integrative Biology Allergy and
Immunology section, Delhi, India
Correspondence: Komal Agrawal
World Allergy Organization Journal 2017, 10(Suppl 1):A35
Background
Per a 10, a major serine protease allergen from Periplaneta americana favours Th2 responses by activating dendritic cells to higher IL23 and secrete lower IL-12p70.
Objective
The present study is aimed to elucidate the role of proteases in regulating the balance between members of IL-12 cytokine family.
Methods
Female Balb/c mice were administered Per a 10, heat-inactivated Per
a 10 (Δ Per a 10) or PBS on days 0,2,4,10,12,14 and sacrificed on 15th
day. PAR-2 activation in Per a 10 sensitized mice was blocked by
administering PAR-2 cleavage blocking antibody via intranasal route
30 min before sensitization. Cytokines, total cell count in BALF and
specific IgE and IgG1 levels in sera were analysed. The mRNA levels
of cytokine subunits and p-STAT3 were analysed in lungs by RT PCR
and Western blot. PAR-2 activation on BMDCs was blocked using
antibody and stimulated with Per a 10. p-STAT3 and cytokines level
were measured using flow cytometry and ELISA respectively.
Results
Per a 10 administration leads to higher levels of p-STAT3 in lungs of
mice as compared to proteolytically inactive counterpart. IL-4, IL-17A,
TSLP, specific IgE and IgG1 levels, eosinophil peroxidise activity and
total cell count were lower in SAM-11 administered group as compared to isotype control indicating role of PAR-2 signalling in Th2 responses. IL-12p35 and IL-12p70 levels were higher and IL-23p19 and
IL-23 levels were lower in SAM11 administered group as compared
to isotype control pointing a role of PAR-2 activation in transcriptional regulation of cytokine subunits. There was no change in IL-12/
23p40 transcript levels. p-STAT3 levels were lower in the lungs of
SAM11 administered mice. SAM-11 treated BMDCs lead to lower pSTAT3 levels as compared to isotype treated BMDCs. Further, Per a
10 stimulation in SAM-11 treated BMDCs showed higher IL-12p35
and lower IL-23p19 at transcript level as compared to isotype control.
Cytokine analysis in supernatant revealed higher IL-12p70 and lower
IL-23 levels indicating role of PAR2 mediated signalling in the secretion of IL-23 and IL-12p70 by dendritic cells.
Conclusions
Per a 10 regulates the balance between IL-12p70 and IL-23 by activating PAR-2 and STAT3 in dendritic cells.
World Allergy Organization Journal 2017, 10(Suppl 1):25
A36
Association of C-reactive protein and interleukin-6 with chronic
kidney disease in patients with diabetes type 2
Volha Vasilkova1, Tatiana Mokhort2
1
Gomel State Medical University Endocrinology, Gomel, Belarus ; 2
Belarusian State Medical University Endocrinology, Minsk, Belarus
Correspondence: Volha Vasilkova
World Allergy Organization Journal 2017, 10(Suppl 1):A36
Background
Background: Chronic kidney disease (CKD) is a serious complication
of diabetes associated with increased risk of mortality, cardiovascular
and renal outcomes [1]. Systemic inflammation has been defined as
a marker of cardiovascular risk in patients with CKD [2].
Objective
Aim of our study was to evaluate the association of inflammatory
biomarkers including C-reactive protein (CRP) and interleukin-6 (IL-6)
with CKD in patients with diabetes type 2 (DT2).
Methods
Seventy eight patients both sexes with type 2 diabetes aged 54.69
±11.07 years were studied. Control group included 37 subjects the
same age. CKD was defined as eGFR <60 ml/min/1.73 m2 or the
presence of albuminuria (≥30 mg/24-h) for three or more months.
Multivariate regression analysis was used to examine associations between the inflammatory biomarkers and CKD adjusting for CKD risk
factors.
Results
Patients with CKD and DT2 had a mean eGFR of 46.2 mL/min/1.73
m2 compared to 95.3 mL/min/1.73 m2 among controls without CKD
and DT2. The median serum levels of CRP and IL-6 were significantly
higher in patients with CKD and DT2 compared to controls (p<0.05).
After adjusting for important covariables, the median of IL-6, but not
CRP, remained significantly higher. In multivariate linear regression
analyses, serum level of IL-6 was inversely and significantly associated with eGFR (−4.89; −7.75 to −1.63; p<0.001) and positively related to urinary albumin excretion (0.24; 0.04 to 0.43; p=0.0004).
Conclusions
Our data suggest that IL-6 is associated with the prevalence of CKD
in patients with DT2, independent from established CKD risk factors.
References
1. Levey AS, Coresh J. Chronic kidney disease. Lancet. 2012; 379:165–80.
2. Belinda T. Lee, Faheemuddin A. Ahmed, L. Lee Hamm, Federico J. Teran
et al. Association of C-reactive protein, tumor necrosis factor-alpha, and
interleukin-6 with chronic kidney disease. BMC Nephrology. 2015; 16:77.
A37
Legalized marijuana- medical and recreational- in the USA:
concerns beyond cannabis sativa?
William Silvers
University of Colorado School of Medicine Medicine GWV, Aurora, CO,
United States
World Allergy Organization Journal 2017, 10(Suppl 1):A37
Background
Since the passage of legalized medical marijuana (MJ) in the USA
(now 26 states plus District of Columbia) and recreational marijuana
(now 4 states, initially Colorado in 2014), an increasing number of allergic patients are presenting due to MJ exposure. The majority have
significant exposure in the grow industry or heavy consumers, indicating that cannabis sativa is a mild allergen. Some highly atopic patients have reactions with less exposure. However, the techniques for
growth and extraction are changing, and factors other than the weed
allergen itself may be responsible for adverse reactions.
Objective
Describe a spectrum of reactions.
Case reports
Case 1. A 28 y/o white male presented with rhinitis worsening
around “pot” in 2010. When he began working as a “trimmer” at a
growth house in 2014, symptoms flared and included wheezing and
Page 14 of 39
chronic cough. He improved with nasal steroids and bronchodilator
use.
Case 2. A 30 y/o white male presented with AR, conjunctivitis, contact dermatitis, and asthma symptoms after MJ exposure, having no
previous asthma history. He moved to Colorado to work in the MJ industry, initially as a grower and then retail. He grew his own MJ
plants. FEV1 was 52% predicted with 38% bronchodilator improvement. FeNO was elevated at 89 ppb, skin tests had multiple positives
to pollen, and “puddle” tests were positive to MJ. After treatment, his
FEV1 improved to 80% predicted, FeNO decreased to 30 ppb, and
symptoms improved.
Case 3. A 26 y/o white male was referred by an emergency physician
with suspected anaphylaxis after smoking MJ, and subsequently with
passive exposure. He described using a “concentrator wax” on top of
the MJ flower. Immunocap tests were negative to pollens, but positive to danders, and dust mites. With a negative MJ flower “puddle”
test, consideration was given to other potential triggers, such as pesticides (now outlawed for inhaled and edible MJ production in Colorado), mold, dust mite, psychophysiologic reactions, or other
unknown factors in the waxes. Anecdotes: During a marijuana “bust”
in September, 2015, 2 Drug Enforcement Agency agents presented
with asthma exacerbations to the MJ brought into their offices, despite one being on omalizumab. The other had a history of reactions
to “strain specific” marijuana exposure.
Conclusion
Although cannabis sativa may be a mild allergen for most, increasing
workplace exposure and
Consent
The author received informed consent from the patients to publish.
A38
Management of refractory recurrent pericarditis and Familial
Mediterranean Fever (FMF) related attacks with IVIG and
interleukin 1 inhibition
Rachel Eisenberg, Rushita Mehta, Arye Rubinstein
Montefiore Medical Center Allergy and Immunology, Bronx, New York,
United States
Correspondence: Rachel Eisenberg
World Allergy Organization Journal 2017, 10(Suppl 1):A38
Background
Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by episodes of fever, gastrointestinal (GI) serositis, and other findings including arthritis, pericarditis,
skin lesions, and myalgias. Recommended treatment for both FMF
and recurrent pericarditis is colchicine. We present a 32 year old female with uncontrolled FMF and chronic pericarditis on colchicine
who clinically improved with intravenous gammaglobulin (IVIG)
along with abortive and preventive anti IL1-beta biologicals.
Case report
A 32 year old female presented with nausea, vomiting, abdominal
cramps, and chills since adolescence, generally occurring once every
2-8 weeks. She also had intermittent knee and wrist pain, as well as
brown skin lesions overlying her ankles. During her first pregnancy
her abdominal symptoms worsened leading to her diagnosis of FMF
by genetic testing (V726A mutation). Fat pad biopsy was negative for
amyloidosis. Despite treatment with colchicine she continued to have
nausea and GI serositis 1-3 times monthly. Additionally, the patient
had a 12-year history of refractory recurrent constrictive pericarditis
unresponsive to colchicine and steroids. She required cardiocentesis
yielding 450ml of pericardial fluid. Immunologic workup was notable
for elevated Serum IL-1β levels at 69.6 (normal <3.99 pg/ml) and
hypogammaglobulinemia. High dose IVIG and abortive anakinra therapy was initiated. Over the course of a year on IVIG she reported decreased frequency and severity of recurrences. She had two mild
recurrences of pericarditis and one episode of GI serositis both of
which responded promptly to 3 doses of subcutaneous anakinra. She
then developed a hypersensitivity reaction to anakinra with hives
and pruritus. Skin prick and intradermal testing to anakinra was positive. Anakinra was discontinued with plan to treat recurrences with
abortive rilonacept. She had one episode of GI serositis and chest
World Allergy Organization Journal 2017, 10(Suppl 1):25
pain since then, treated and responsive to one dose of rilonacept.
She was subsequently maintained on rilonacept prophylaxis every
other week, without recurrences of abdominal attacks or chest pain
for the past five months.
Conclusion
Currently, colchicine is the first line therapy and only proven effective
treatment for FMF flares and recurrent pericarditis. We present a case refractory to these drugs, whose symptoms of FMF and pericarditis
responded to high-dose IVIG and to anti IL1 abortive and prophylactic
treatments. The combination of IVIG and IL1-beta receptor inhibition may
be a superior therapy for FMF and associated pericarditis. Whether it will
have a benefit in prevention of amyloidosis has yet to be determined.
Consent
The authors received informed consent from the patient to publish.
A39
Assessing severity of peanut-allergic reactions during research
food challenges
Antony Aston1, Paul Turner1, Monica Ruiz-Garcia1, Robert Boyle1, Simon
Brown2
1
Imperial College London Paediatric Allergy & Immunology, London,
United Kingdom ; 2University of Western Australia Emergency Medicine,
Perth, Australia
Correspondence: Antony Aston
World Allergy Organization Journal 2017, 10(Suppl 1):A39
Background
Determining the severity of allergic reactions with a valid and discriminatory scoring system has important implications for research. Existing
grading systems do not offer sufficient discrimination to facilitate research into the mechanisms of severity, immunotherapy outcomes
where only partial tolerance is induced, and allergen risk management.
Objective
To develop and validate a severity score for food-allergic reactions.
Methods
We developed an in-house scoring system, utilising PRACTALL criteria, with validation against inflammatory mediator measurements
of patients experiencing anaphylaxis in a cohort of patients with anaphylaxis presenting to Emergency Departments in Australia (Brown
et al., JACI 2013;132:1141-1149). We then sought to refine and further
validate the score using symptom data collected prospectively in
two cohorts of peanut-allergic individuals undergoing DBPCFC to
peanut. The severity of reaction was also graded according to several
existing schemata in the literature (Ewan & Clark (2001), Sampson
(2003), Hourihane (2005), Niggemann & Beyer (2016)). Clinicaltrials.gov registration NCT02149719 and NCT02665793; informed consent
was obtained prior to challenge.
Results
One hundred fift gao 105 participants (adults, n=60; children, n=45)
underwent DBPCFC, resulting in anaphylaxis (NIAID criteria) in 29
(27%) cases and less severe symptoms in the remainder. The scoring
system resulted in a normal distribution of reaction severity in the
cohort, by D’Agostino & Pearson normality test, confirming good discrimination between reactions of differing severity compared to
traditional grading systems, and allowing a better assessment of
the relationship between inflammatory mediators such as mast cell
tryptase and reaction severity.
Conclusion
The proposed severity score provides good discrimination and normal distribution of food-allergic reactions for the research setting.
The tool is currently being applied to data from ongoing studies of
anaphylaxis pathophysiology and oral immunotherapy.
A40
Hematopoietic stem cell transplantation in combined
immunodeficiency associated with RelB deficiency
Yael Dinur Schejter, Adi Ovadia, Vy Kim, Brenda Reid, Chaim Roifman
Hospital for Sick Children, Allergy and Immunology, Toronto, Canada
Correspondence: Yael Dinur Schejter
World Allergy Organization Journal 2017, 10(Suppl 1):A40
Page 15 of 39
Background
We report for the first experience with hematopoietic stem cell transplantation (HSCT) for RelB deficiency, a new form of combined immunodeficiency (CID). RelB is a key mediator of the alternative
pathway of the NFĸB family of transcription factors.
Methods
Two patients previously described (Merico et al. 2015; Sharfe et al.
2015) with CID associated with RelB deficiency underwent an HSCT
from a 10/10 matched unrelated donors, using busulfan and cyclophosphamide conditioning regimen, and graft versus host (GVHD)
prophylaxis with methylprednisone and cyclosporin A (CSA). Patient
data was compiled retrospectively from medical records and entered
into the Canadian Centre for Primary Immunodeficiency Registry. Follow up period was 2.5-4 years.
Results
Patient 1 suffered from recurrent otitis media (OM) and pneumoniae,
ecthyma gangrenosum, disseminated HSV infection, adenoviral infection and intermittent bilateral knee swelling. Patient 2, first cousin of
patient 1, suffered from recurrent OM, perinatal pneumothorax,
pneumonia, a urinary tract infection, oral thrush, chronic cough and
failure to thrive. Both patients had a profound B and T cell impairment with low in vitro T cell responses to mitogen stimulation, poor
response to specific antibodies, dysplastic thymus and low T cell excision circles (TREC) values.
Patient 1 underwent HSCT at the age of two years. Engraftment was
rapid and post transplant course was unremarkable except for one
episode of Staphylococcus aureus infection as well as HSV1 skin infections. CSA prophylaxis was switched to mycophenolate mofetil
due to nephrotoxicity, which subsequently resolved. He developed
Grade I skin GVHD on day +13 and was treated with a pulse of methylprednisolone with resolution of symptoms, but subsequently developed chronic skin GVHD 18 months after transplant. He was initially
treated topically but was later on started on methotrexate therapy
due to worsening of his skin GVHD, with good response. He is currently 4 years post transplant and has full donor chimerism, but continues to suffer chronic skin GVHD. Patient 2 was transplanted at the
age of 3 years. Engraftment was rapid and his post transplant course
was uneventful initially, but later on he suffered 1 episode of OM
and pneumonia. He did not develop GVHD. He is currently well 2.5
years post transplant. Chimerism studies show a stable donor T cell
engraftment at 60% of total T cells. T cell mitogen responses are
present and immunoglobulin levels are normal, off intravenous immunoglobulin therapy.
Conclusion
HSCT can reverse combined immune deficiency in RelB deficient
patients.
Consent
The authors received informed consent from the patients’ guardian/
parent to publish.
A41
Dining out: a survey of experiences in Canadians with food
allergies
Lana Rosenfield1, Ernie Avilla2, Laurie Harada3, Marilyn Allen3,
Susan Waserman1
1
McMaster University Division of Clinical Immunology and Allergy,
Hamilton, Canada ; 2McMaster University Department of Medicine,
Hamilton, Canada ; 3Food Allergy Canada, Toronto, Canada
Correspondence: Lana Rosenfield
World Allergy Organization Journal 2017, 10(Suppl 1):A41
Background
Dining out poses a risk for food allergic individuals. Potential explanations include cross contamination with food allergens or inadequate information on ingredients. This risk is increased when individuals do not
carry an Epinephrine Auto-injector (EAI) when dining-out, or fail to use
it when indicated. We evaluated the experience of food allergic individuals in Canada when dining out and their perceptions of risk reduction
strategies such as stock EAI.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Methods
We conducted a cross sectional study to evaluate the dining-out experiences of food allergic individuals. Online surveys were administered to adults (>18 years of age) with food allergy and parents/
caregivers of children (<18 years of age) with food allergy from Food
Allergy Canada’s database in February 2015.
Results
Population: Of 1,580 respondents, we included 1165 fully completed
surveys in the analysis. 23.9% were food allergic, 66.1% had a child
with food allergy and 10% had another family member with food
allergy.
Carriage of EAIs: When dining out, 87.8% of respondents stated that
they ‘always’ carried, 2.3% ‘never’ carried, 4.4% ‘usually’ carried, and
1.5% ‘sometimes’ carried an EAI (4% did not provide an answer to
this question).
Dining out experience: 1096 of 1165 (94%) respondents indicated
that they dine out, while 3% said they do not. 53% who dine out
would check a restaurant website to assess for potential allergens,
46% will call ahead, 95% will speak to restaurant staff. Only 2% will
not tell restaurant staff about their allergies. Of 1096 who dine out,
33% have experienced an allergic reaction while dining-out (43%
adults; 46% children, 11% other family member). Prior to the reaction, 22.3% informed staff of food allergy, 10% spoke to the chef,
4.3% called the restaurant in advance, and 3% presented a list of
allergies.
Perception of stock EAI: Overall, 87.5% respondents would continue
to carry an EAI if there was stock EAI at a restaurant. 44.5% would
have increased comfort dining out if EAI was present on the
premises.
Conclusion
The survey demonstrates a significant rate (1 in 3) of allergic reactions in food allergic individuals while dining out, this is spite of asking about relevant food allergens. It also emphasizes the importance
of always carrying an EAI, not practiced by 12% of respondents.
While the majority would carry EAI even with stock EAI in a restaurant, half would feel more comfortable with it present.
A42
Association of serum triglyceride and cholesterol with asthma in
adults
Ho Joo Yoon 1, Gun Woo Koo1, Suk-Il Chang2, Hye-Ran Yoon 3,
Dong Won Park 1, Tai Sun Park1, Ji Yong Moon 1, Sang-Heon Kim 1,
Tae Hyung Kim 1, Jang Won Sohn 1, Dong Ho Shin 1
1
Hanyang University College of Medicine Department of Internal
Medicine, Seoul, South Korea; 2Sungae General Hospital Department of
Internal Medicine, Seoul, South Korea; 3Duksung Women’s University
College of Pharmacy, Seoul, South Korea
Correspondence: Ho Joo Yoon
World Allergy Organization Journal 2017, 10(Suppl 1):A42
Background
Dyslipidemia is a risk factor for cardiovascular diseases by affecting
immune and inflammatory reactions. Previous studies suggested that
dyslipidemia is closely associated with asthma and atopy, while the
results are not consistent.
Objective
In this study, we aimed to examine the possible association of dyslipidemia with asthma by analyzing data from Korean National Health
and Nutrition Examination Survey (KNHANES) in Korean adults.
Methods
We performed cross-sectional study of adults aged ≥19 from KNHANES
2010. Asthma outcome was obtained by standardized questionnaire
from the participants. Serum levels of triglycerides (TG), total cholesterol (TC), LDL and HDL cholesterols were compared between asthma
and non-asthma. Multivariate logistic regression analysis was performed to explore the association of dyslipidemia and asthma.
Results
Serum level of TG was higher in subjects with asthma than nonasthma, while there were no significant difference between levels of
TC, LDL and HDL cholesterol. In multivariate analysis adjusting for
age, sex, body mass index, education level and household income,
Page 16 of 39
serum level of TG showed significant inverse relationship with asthma
outcomes: asthma ever (adjusted OR 0.76, 95% CI 0.62-0.91, P = 0.004)
and diagnosed asthma (adjusted OR 0.67, 95% CI 0.52-0.86, P = 0.002).
Conclusions
In adult population of Korea, serum TG is inversely related with
asthma. There is no close relationship between serum level of cholesterol (TC, LDL and HDL cholesterol) with asthma.
A43
Complex evaluation of the health status of primary-school aged
children (Adjara region)
Tsici Jorjoliani1, Lia Jorjoliani2, Nino Adamia3, 1
1
D.aghmashenebeli University Pediatric, Tbilisi, Georgia; 2I.Javakhishvili
Tbilisi Steit University Pediatric, Tbilisi, Georgia; 3Tbilisi State Medical
University Pediatric, Tbilisi, Georgia
Correspondence: Tsici Jorjoliani
World Allergy Organization Journal 2017, 10(Suppl 1):A43
Goal of the research was complex evaluation of the health status of
the primary-school aged children residing in various regions (urban,
rural) of Adjaria.
Cross-section, one-stage research was conducted in the City of
Batumi and village Tsikhisdziri. In the process of survey health status
of children of 4 public schools, from 6 to 9 years old was studied.
Observations covered up to 800 school children in total. Screening
included consultations of the multidisciplinary group of specialists,
additional laboratory and instrumental studies intended for the purpose of accurate diagnostics.
Performed studied showed that 28.3% of the studied population was
actually healthy, 55% had functional disorders and 16.7% - chronic
diseases. In both, urban and rural areas the share of the digestion
system, blood and blood-generating organs, nervous system, ophthalmological pathologies and locomotion system diseases prevailed.
A44
Study on hand washing practices and occurrence of Microbes on
the hands of food handlers.
Deepika Ramachandra
BMCRI Immunology, Bangalore, India
World Allergy Organization Journal 2017, 10(Suppl 1):A44
Background
Food safety has emerged as an important global issue with international trade and public health implications. Studies revealed that
food borne diseases are a serious health hazard and an important
cause of morbidity and mortality in developing countries. Food can
transmit a wide range of diseases in a condition termed food infection where food serves as a vehicle for transfer of pathogens to the
consumer in whom the pathogen grow and cause disease. Data on
risk factors for food borne diseases indicate that the majority of outbreaks result from inappropriate food handling practices. Food handlers with poor hygiene, working in food serving establishments
could be potential source of infections of many enteric pathogenic
bacteria. There is evidence from the food industry showing that
microorganism are transferred to the hands in the process of handling food and through poor personal hygiene, resulting in the hands
being heavily contaminated with enteric pathogens. Hand washing, a
simple and effective way to cut down on cross contamination is all
too often forgotten. In addition, if individuals do not wash their
hands before putting on the gloves, both the interior and exterior
gets contaminated and microorganisms on the hand could multiply
rapidly in the moist and warm environment
Objective
1. To isolate and identify the organism from hands of food handlers
in hospital and private eateries before and after the hand wash
2.To demonstrate appropriate hand washing technique to the food
handlers.
3.To evaluate the effect of hand washing technique which is a simple
and cost effective method of disinfection.
4.To study and compare any difference in the isolated microbes from
the two groups
World Allergy Organization Journal 2017, 10(Suppl 1):25
of food handlers i.e. hospital and private eateries.
Methods
Sample size: n1-50; staff working in hospital kitchen, hostel kitchen
and canteen: n2-50; staff working in private eateries around the hospital. Informed consent shall be obtained from each subject included
in the study, samples will be taken from the palm of the food handlers from index fingers and thumb of both right and left hands
using a sterile swab wetted with normal saline. A simple 13 seconds
hand wash whereby the hands were soaped lathered and during
lathering rinsed underneath a faucet of flowing water. Aerobic cultures will be done on Mac Conkey’s Agar and Blood Agar, and shall
be incubated at 370C, for 18 hours. If there is growth, the total viable
count shall be determined. Antibiotic sensitivity testing will be done
using Standard Kirby Bauer’s method. The results obtained will be
statistically analyzed and evaluated.
A45
Food Allergy
Liana Jorjoliani, Rusudan Karseladze, Lali Saginadze, Nino Adamia, Natalia
Chkuaseli
Tbilisi State Medical University, Department of Pediatrics, Tbilisi, Georgia
Correspondence: Liana Jorjoliani
World Allergy Organization Journal 2017, 10(Suppl 1):A45
Objective
To investigate the prevalence of food allergies in the population of
preschool children from the city of Batumi and to identify the most
common causes of the allergies in the study population
Methods
The study was conducted in children population, in Batumi, according to the random and representative sample, by the cross section
method of epidemiological survey. On the first stage of the survey
840 children aged from 6 months to 7 years, (50.6% girls and 49.4% boys) were questioned by random selection. Analyzed using SPSS
Statistical Package for Windows, version 13.0
Results
According to study results, for last 12 months 6.1% of the studied
children had signs of allergies. According to clinical-allergic study, allergic rash – in kind of dermatitis and urticaria (76%) was significantly
(p<0.05) higher than manifestation rate of gastrointestinal symptoms
(24%). The most common causes of food allergies in the study population were eggs (22.3%), fish (22.6%), milk (18.6%), honey (13.7%;),
nut (4.3%) and different food additives.
Conclusions
Therefore, in childhood allergic skin manifestation of food allergy
is high. According to the obtained data risk factor control could
provide basis for the purposeful and effective preventive measures in future. There is a need to work on educating of parents
and caregivers.
A46
Micro-array component-resolved study of Felis domestica major
allergen molecules in cat allergic patients in Moscow region,
Russia
Anna Dolgova1, Olga Stukolova1, Anna Sudina1, Anna Cherkashina1,
German Shipulin 1
1
Central Research Institute for Epidemiology, Federal Service on
Consumers’ Rights Protection and Human Well-Being Surveillance
Molecular Diagnostics and Epidemiology, Moscow, Russia
Correspondence: Anna Dolgova
World Allergy Organization Journal 2017, 10(Suppl 1):A46
Background
In Russia, 37% of households have cats and cat allergy frequently occurs. However there is still no information about IgE reactivity to individual cat allergens in this region.
Page 17 of 39
Objective
We aimed to determine the profile of IgE reactivity to three major
cat allergens Fel d1, Fel d 2 and Fel d 4 in cat allergic patients in
Moscow region, Russia.
Methods
The study was conducted using sera from 230 anonymous subjects:
174 patients with ≥ 0.35 IU/mL serum levels of IgE to cat dander extract (e1, ImmunoCAP) and 56 negative controls. Allergens were
expressed as recombinant proteins in Escherichia coli (Fel d 1 and
Fel d 4) or purified from cat serum (Fel d 2). IgE levels were measured using microarray method.
Results
Fel d 1 was found to bind IgE from 91.4%, Fel d 2 from 33.3% and
Fel d 4 from 49.4% of the patients’ sera tested. Mean IgE reactivity to
Fel d 1 was significantly higher than to Fel d 2 and Fel d 4. We found
a moderate positive correlation between total IgE and specific IgE to
Fel d 1 and low positive correlation between total IgE and Fel d 2
and Fel d 4 specific IgE. Only one sample classified by ImmunoCAP
as negative, showed slight positive signal to Fel d 4. About 98% of
the patients could be diagnosed as cat allergic using the combination of these three allergens (correlation coefficient to ImmunoCAP
is 0.94 with PPV=1 and NPV=0.93).
Conclusions
Sensitization to cat individual allergens in Russia is comparable to
previous studies in other regions. Three investigated proteins
together (Fel d 1, Fel d 2 and Fel d 4) are suitable for use as a
sensitization markers equally as well as cat dander extract in in vitro
molecular (serological) diagnostics. Moreover, component resolved
approach provides an opportunity to predict course and outcome of
disease, helps to prescribe adequate AIT treatment and may also be
used for the monitoring of patients undergoing immunotherapy.
A47
Topical nasal bacterial therapy associated with pre-seasonal
allergoid SCIT in patients with grass allergy
Giulio Brivio, Maria Assunta Boscolo
Ospedale Civile San Leopoldo Mandic Allergology Merate, Lecco, Italy
Correspondence: Giulio Brivio
World Allergy Organization Journal 2017, 10(Suppl 1):A47
Background
Pre-seasonal allergoid vaccine, associated with preventive bacterial
nasal therapy, may be more effective in treating allergic symptoms.
Objective
The purpose of the study was to evaluate the effectiveness and possible side effects of preventive topical nasal therapy with a suspension
of inactivated bacteria followed by a pre-seasonal allergoid subcutaneous immunotherapy (SCIT) in patients with grass allergy, compared
with a group of patients treated only with an allergoid SCIT.
Methods
The two groups, consisting of 15 patients each, are consistent in age
and sex and both monosensitised to grasses. To each patient was
assigned a score card of symptoms and a possible anti-allergic drug
therapy. Patients in group A were treated with a bacterial topical
nasal therapy (from Anallergo SpA, Florence, Italy) during months of
November and December followed by a pre-seasonal allergoid SCIT
(Anallergo) during the months of February and March. The group B
was treated only with the allergoid SCIT (Anallergo) during the
months of February and March.
Results
Conjunctivitis Gr. A 993 vs Gr. B 1211, Nasal Blockage Gr.A 1315 vs
Gr. B, Sneezing Gr. A 1436 vs Gr. B 1724, Rhinorrhea Gr. A 1163 vs Gr.
B 1419, Cough Gr. A 798 vs Gr. B 843, Dyspnea Gr. A 611 vs Gr. B
717, Drugs Gr. A 576 vs Gr. B 759.
Conclusions
The results show that the total symptoms were significantly lower
during and after the SCIT in patients who had taken advantage of
World Allergy Organization Journal 2017, 10(Suppl 1):25
the preventive therapy with the bacterial suspension (group A), compared to those treated only with the pre-seasonal allergoid SCIT (group
B). Likewise, the use of symptomatic drugs in group A was lower than
those in group B, confirming the efficacy of the protocol under study.
A48
Simplified method for Eucapnic Voluntary Hyperventilation (EVH)
challenge to diagnose Exercise Induced Bronchospasm (EIB)
Richard Rosenthal1, 2, Harvey Howe3, Paul Knause4
1
Johns Hopkins School of Medicine Medicine, Baltimore, Maryland,
United States; 2Inova Fairfax Hospital, Fairfax, VA, United States; 3Self,
Vienna, VA, United States; 4Self, Arlington, VA, United States
Correspondence: Richard Rosenthal
World Allergy Organization Journal 2017, 10(Suppl 1):A48
Background
A vastly simplified method for the conduct of EVH challenges is
presented.
Objective
The long established “gold standard” method for EVH challenge (Phillips Y.Y.et al, 1985) need have been simplified using more readily acquired and assembled equipment. This lends itself to greater ease of
use, precision, reproducibility and interpretive value.
Methods
A compressed gas mixture of 5% CO2, 21% O2 and 74% N2 is required to maintain eucapnea when patients voluntarily (without exercise) hyperventilate in order to simulate the hyperpnea of exercise.
The resultant dehydration of airway surface liquid is considered to
osmotically cause the release of mediators to which bronchial
smooth muscle responds in patients who have EIB. (Anderson, S.D.,
2000). Originally, in order to reduce the gas tank pressure to ambient
and regulate the volume of gas delivered, the gas was manually
valved into an unwieldy weather balloon which patients had to keep
at constant inflation. There was no data collection, written record or
report. The simplified method, described here, employs a patient demand valve which reduces the tank pressure to ambient and a pressure gage fitted in parallel to the gas tank. The volume of gas
delivered to the patient is computed from the decrease in the tank
pressure after 6 minutes of voluntary hyperventilation. Using a computer loaded with the correct algorithms, patients are coached to
ventilate a target volume or the volume delivered determined afterwards by reading the pressure drop from the gage. A program computes the percent of estimated Maximum Voluntary Ventilation and
a record and interpretation is produced after serial pulmonary functions are compared to pre-challenge values.
Results
This simplified method has been successfully used to screen patients
for the presence of EIB. Numerous applications include determination
of suitability for military duty, respiratory health certification for
SCUBA diving, evaluation of dyspnea of unknown origin, workup of
asthma for more individualized treatment, evaluation of disability,
evaluation of cold weather athletes, therapeutic use exemptions for
otherwise prohibited drugs in IOC and other sanctioned athletic
events and pharmaceutical studies of drugs designed to treat the EIB
component of asthma.
Conclusions
The universally accepted, well documented EVH challenge for EIB
was unwieldy, not generally available and therefore too rarely used.
The easily conducted simplified method described here makes the
established technique more available and will expand the applications so that patients with dyspnea will have their illnesses better
characterized and therefore better treated.
A49
An EDA-ID patient with autoimmune C3 Nephritic Factor managed
with Rituximab
Rony Greemberg, Jean Jacques De Bruycker, Isabel Fernandez, Françoise
Le Deist, Elie Haddad
CHU Sainte-Justine, Allergy & Clinical Immunology, Montreal, Canada
Correspondence: Rony Greemberg
World Allergy Organization Journal 2017, 10(Suppl 1):A49
Page 18 of 39
Background
Hypomorphic IKBKG/NEMO mutations in males lead to hypohidrotic
ectodermal dysplasia with immunodeficiency (EDA-ID) as well as immunodeficiency without EDA. IKBKG mutations may also present with
autoimmune manifestations, including inflammatory bowel disease,
arthritis and autoimmune hemolytic anemia.
We report a NEMO patient with autoimmune underlying process.
Specifically, the presence of Nephritic Factor, C3Nef, an autoantibody
that binds to the alternative complement pathway C3 convertase,
C3bBb, preventing its decay, and leading to the consumption of C3
complement.
Case Report
A 5 years old male presented with multiple pyogenic bacterial infections, recurrent febrile episodes, sparse hair, hypodontia and conical
shaped teeth. Genetic Testing identified a deletion of 6 nucleotides
in exon 4, 487_492delGCCACT, in the IKBKG gene, resulting in the
frame deletion of 2 amino acids. Subsequently, the patient was diagnosed with EDA-ID.
While on Immunoglobulin replacement therapy, he developed sepsis
with Streptococcus Pneumoniae bacteremia. The patient also had a
chronic EBV infection. Further investigative workup was significant
for severe decrease of both CH50 and complement C3, and for the
presence C3 Nephritic Factor- C3Nef. Interestingly, the patient had
no hematuria, no proteinuria and renal function was normal.
Rituximab, was chosen as a therapy option, with the purpose to eliminate both the B cell reservoir of EBV and the production source for
the autoantibody C3Nef.
Rituximab treatment induced a transient and moderate increase of
CH50 levels and reduced EBV viremia.
Conclusions
To our knowledge, this is the first NEMO patient described with autoantibody C3Nef.
We encourage to investigate NEMO patients with low complement
C3 and CH50 for the presence of the possibly overlooked autoantibody C3Nef. One could hypothesize that this low complement level
could be the reason for increased susceptibility to multiple pyogenic
infections in this patient. Our case also describes Rituximab as a safe
therapeutic option although the level of CH50 were not normalized.
Consent
The authors received informed consent from the patient’s guardian/
parent to publish.
A50
Sociodemographic and socioeconomic risk factors for adolescent
atopic dermatitis in South Korea
Yeong Ho Rha1, Kyung Suk Lee2, Sun Hee Choi1
1
Kyung Hee University School of Medicine Pediatrics, Seoul, South Korea;
2
CHA Unitersity Scool of Medicine Pediatircs, Bungdang, South Korea
Correspondence: Yeong Ho Rha
World Allergy Organization Journal 2017, 10(Suppl 1):A50
Background
There have been many suggestions for medical, socioeconomic and
sociodemographic risk factors for atopic dermatitis (AD) from the
studies in an attempt to prevent and treat AD.
Objective
We conducted this study specifically focusing on the relationship between various socioeconomic and demographic variables, and AD in
Korean adolescents.
Methods
We used data of Korea Youth Risk Behavior Web-Based Survey
(KYRBWS) which includes 79,202 Korean adolescents aged 12 to 18
years. Data was collected by the self-answering surveying method in
2010. Dependent variable was atopic dermatitis; independent variables
were gender, parents’ education level, family affluence scale (FAS), low
subjective family economic status, and obesity. Multivariate analysis
was conducted in order to analyze the relationship between socioeconomic and sociodemographic risk factors and AD.
Results
The prevalence of AD based on KYRBWS 2010 in Korean adolescents was
23.1%. In univariate analysis, female, urban, high parental education level,
World Allergy Organization Journal 2017, 10(Suppl 1):25
FAS was strongly correlated with AD. In multivariate analysis, female,
urban, college or higher parental education level, obesity, high FAS, low
subjective family economic status were correlated with AD.
Conclusions
We found that Korean adolescents’ AD was strongly correlated with
socioeconomic and sociodemographic risk factors. Thus, it is important to modulate the socioeconomic and sociodemographic risk
factors to control AD systematically in adolescent in Korea.
A51
Prescription patterns of epinephrine auto-injectors for treatment
of anaphylaxis in Manitoba children
Herman Tam, Estelle Simons, Elinor Simons
Department of Pediatrics and Child Health, University of Manitoba,
Winnipeg, Canada
Correspondence: Herman Tam
World Allergy Organization Journal 2017, 10(Suppl 1):A51
Background
Epinephrine is the first-line medication for treatment of anaphylaxis.
Recent data pertaining to dispensing patterns of epinephrine autoinjectors (EAIs) are limited.
Methods
Using the Drug Programs Information Network (DPIN) Manitoba administrative pharmaceutical claims database, we analyzed dispensing
data for EAIs among 0- to 16-year-olds from January 1, 2011 to
March 31, 2015. We identified the number and percentage of children and teenagers for whom at least one EAI was dispensed. We
evaluated the appropriateness of the EAI dose (0.15 mg or 0.3 mg)
for the child’s age. We also conducted adjusted multivariable logistic
regression to determine if concomitant prescription of an asthma
medication, family income quintile, and rural versus urban region of
residence affected the odds of dispensing a higher-than-expected or
lower-than-expected dose.
Results
EAIs were dispensed 25,562 times for 8,998 children (2.5% of the
pediatric population). EpiPen and Allerject were the two most common EAIs dispensed (98.2%); 53.6% of doses were 0.15 mg and
46.4% were 0.3 mg. Three percent of prescriptions may have been
inappropriately dosed based on age (1.62% of children at or below
age 5 years were dispensed a 0.3 mg EAI, 95% CI: 1.36%-1.94% and
1.44% of children at or above age 12 years were dispensed a 0.15
mg EAI, 95% CI: 1.13%-1.83%). Children at or below age 5 years with
a higher-than-expected dose had higher odds of concomitant
asthma medication prescription (odds ratio [OR] 1.36, 95% CI: 1.081.72), family income in the lowest 20% (OR 2.90, 95% CI: 2.02-4.14),
and rural residence (OR 1.43, 95% CI: 1.12-1.82). Children at or above
age 12 years with a lower-than-expected dose had higher odds of
having family income in the lowest 20% (OR 2.36, 95% CI: 1.33-4.20)
but not of concomitant asthma medication prescription (OR 0.72,
95% CI: 0.49-1.05) or rural residence (OR 1.39, 95% CI: 0.94-2.04).
Conclusions
Most EAIs were dosed appropriately based on the age of the
child. Anaphylaxis comorbidity and barriers to accessing emergency anaphylaxis treatment were associated with unexpectedly
high EAI doses prescribed for younger children. Older children
prescribed the lower dose may have had poor access to healthcare for prescription updates. Factors accounting for dosing preferences may be important for improving the proportion of
children for whom the correct dose of EAI prescription is
dispensed.
A52
The complexity of immune diagnosis child’s with recurrent
inflammation of the respiratory tract, suspected food allergy and
impaired immunity – case report
Maria Golebiowska-Wawrzyniak, Katarzyna Markiewicz
Institute of Mother and Child, Clinical Immunology, Warszawa, Poland
Correspondence: Maria Golebiowska-Wawrzyniak
World Allergy Organization Journal 2017, 10(Suppl 1):A52
Page 19 of 39
Background
5-year-old girl referred to the Clinic Immune Department due to recurrent pharyngitis, bronchitis and pneumonia running with plenty
of mucous secretions, was examined. Symptoms above were accompanied by recurrent abdominal pain and abnormal abundant stools constipation or diarrhea. Written informed consent in accordance
with the Declaration of Helsinki was obtained from the parents of
the child before the examination, and the parents and the child were
informed about the objective of the study, as well as the course of
the examination and tests.
Objective
The purpose of the study is to diagnose the reasons of recurrent inflammation of the respiratory tract.
Methods
For evaluation of child’s immune status the immunological profile
was prepared : concentration of IgG, IgA, IgM made by nephelometry; lymphocyte blastic transformation test (LBTT) of peripheral blood
with phytohemagglutinin, milk antigens, flour antigens and autotransformation as a control – morphological method; spontaneous
reduction of Nitrotetrazolium Blue Test (NBT) by neutrophils, and
phagocytosis assay. For allergy evaluation the allergology profile was
made: total IgE concentration; IgE specific for inhaled and food allergens (Euroimmun panels and Phadia ImmunoCAP – ELFA method)
also manual LBTT test with milk and flour antigens and testing for
celiac disease were made.
Results
IgG, IgA, IgM concentrations were not elevated. Impairment of T-cell
function. Food allergy IgE-independent - increased LBTT with milk
and flour antigens. Stimulation index for flour in the normal range,
but the percentage value is increased (35%). Autotransformation
(LBTT) increased (32%; norm -15%) which affects the value of the
index, suggesting the correct result. Allergy IgE-dependent, the
presence of sIgE for d1 and t3 (0.38 KU/L; 0.55 KU/L; ImmunoCAP).
Confirmed intolerance to gluten (tTG - IgA 394.4 ELIA U/ml; tTG - IgG
33.0 ELIA U/ml, norm <7 ELIA U/ml).
Conclusions
Recurrent inflammation of the respiratory tract in children require
performance of the enhanced diagnostics covering testing of the immunological and allergological profile. Frequently, gastrological diagnostics is added.
A53
The role of skin prick test and oral challenge in the diagnosis of
amoxicillin and amoxicillin/clavulanate allergy in children
Yoram Faitelson1, Miguel Stein1, Avigdor Mandelberg2, Ilan Dalal1
1
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Allergy
and Immunology Unit, Wolfson Medical Center, Holon, Israel; 2Sackler
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel The Pulmonary
Unit, Department of Pediatrics, Wolfson Medical Center, Holon, Israel
Correspondence: Yoram Faitelson
World Allergy Organization Journal 2017, 10(Suppl 1):A53
Background
Suspected adverse reactions to amoxicillin in children are common
but only rarely these reactions are truly allergic. There is no standardized test that establishes the diagnosis of amoxicillin or amoxicillin/
clavulanate allergy in children and current methods that are used
such as skin prick test (SPT) are painful and time consuming.
Objective
We assessed the utility of SPT followed by oral graded challenge in
the diagnosis of amoxicillin and amoxicillin/clavulanate allergies in
children.
Methods
Children with a history of immediate or non-immediate reactions to
amoxicillin or amoxicillin/clavulanate, were tested by SPT with amoxicillin and penicillin G, followed by oral graded challenge with amoxicillin or amoxicillin/clavulanate, respectively. Those who had negative
challenge were instructed to continue the oral challenge for 2 consecutive days at home. Data were collected on clinical characteristics
of the adverse reaction, personal and relatives’ drug allergies, and
history of personal and relatives’ atopy.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Results
One hundred and thirty three children were enrolled to this study.
Median age at time of study - 4.1 years (range, 0.7-18 years); 70
(52%) were male. One hundred and twenty six children (95%) had
suspected allergic reaction (mainly rash) to amoxicillin and 7 (5%)
had suspected reaction to amoxicillin/clavulanate. One hundred and
twenty eight children (96%) were tested by SPT with amoxicillin and
penicillin G and none had a positive reaction. All the children underwent an oral graded challenge with amoxicillin or amoxicillin/clavulanate. There were 3 children (2%) who had mild immediate reaction
and 7 children (5%) who had mild non-immediate reaction to amoxicillin. Statistical analysis revealed that family history of drug allergy
(adjusted odds ratio = 7.9; 95% CI, 1.9-32.6) was associated with failure of the oral challenge. History of a reaction occurring after 3 days
of exposure was associated with successful challenge (adjusted odds
ratio = 6.8; 95% CI, 0.8-56.3). Age, gender and a history of atopy were
not statistically significant different between those who passed and
those who failed the oral challenge.
Conclusion
In our cohort, the true incidence of allergy was only 7%. Oral graded
challenge was safe and SPT with amoxicillin and penicillin G did not
contribute to the diagnosis of allergy. History of a reaction occurring
after 3 days of exposure predicted successful challenge while family
history of drug allergy was associated with challenge’s failure. Further
studies with larger population are needed to confirm the usefulness
of SPT in the diagnosis of allergic reactions to amoxicillin or amoxicillin/clavulanate in children.
A54
Socio-economic status influences the prevalence of food
sensitisation and food allergy in urban Cape Town children
Michael Levin1, Lelani Hobane2, Wisdom Basera2, Maresa Botha1,
Claudia Gray1, Heather Zar3
1
University of Cape Town, Paediatric Allergology, Cape Town, South
Africa; 2University of Cape Town, Public health, Cape Town, South Africa;
3
University of Cape Town, Paediatrics, Cape Town, South Africa
Correspondence: Michael Levin
World Allergy Organization Journal 2017, 10(Suppl 1):A54
Background
Health outcomes are known to be influenced by socio-economic status
(SES), however, there is limited data exploring the relationship between
SES and food sensitisation (FS) or food allergy (FA) in children.
Objective
To describe prevalence and explore associations of FS and FA to SES
(measured using household size, parental education, household income and employment status) in urban Cape Town children.
Methods
Prevalence of FS and FA was assessed in the South African Food sensitisation and Food Allergy study in 739 of 764 eligible 1-3 year old
children (96.7% participation rate) attending randomly selected
crèches in the Cape Town metropole. Skin prick testing (SPT) was
done to 7 commonly allergenic foods (egg, milk, peanut, wheat, soy,
fish and hazelnut) and food allergy confirmed by open food challenge. Associations between SES and FS/FA were assessed using the
Z-test, Chi-square/Fisher’s exact and Wilcoxon Ranksum tests.
Results
In 739 participants, 91 were sensitised at any degree of reactivity to 1
or more foods and 648 negative for all foods (87.7%). FS prevalence at
SPT≥1mm to any food was 12.3%, at SPT≥3mm 9.6% and at SPT≥7mm
4.5%. Challenge proven IgE-mediated FA was 2.4%.
Statistically significantly higher prevalence of FS was seen in children
with employed (or student) parents rather than unemployed parents
(none unemployed 13.5%, one unemployed 8.2%, both unemployed
0%; p=0.03). Parents of children with sensitisation had significantly
higher total monthly household income. The disparity in household income in those with and without sensitisation increased with increasing
cut-off levels of sensitisation from R2000/month at SPT≥1mm to any
food (p=0.06), to R3500/month at SPT≥3mm (p=0.02) and R6000/month
at SPT≥7mm (p=0.02).
Page 20 of 39
A higher prevalence of sensitisation was apparent in children with
parents who attained tertiary education compared to parents who
attained primary/secondary education however these results did not
achieve statistical significance.
Total cumulative skin tests did not show any significant associations
with any SES measure. Differences in FA patterns were evident but
low numbers preclude meaningful assessment of significance. Household size showed no association with FS and FA. No significant differences in sensitisation patterns were noted between ethnic groups.
Conclusions
Certain markers of SES are associated with food sensitisation in
young children in Cape Town. Enlargement of the cohort may allow
the effect of SES on food allergy to be assessed.
A55
Different therapeutic response in smoking and non-smoking
asthmatics to inhaled corticosteroids
Biserka Jovkovska Kjaeva1, Zoran Arsovski2
1
Clinic of Pulmonology and Allergy, Skopje, Macedonia; 2Clinic of
Pulmonology and Allergy Functional Diagnostic, Skopje, Macedonia
Correspondence: Biserka Jovkovska Kjaeva
World Allergy Organization Journal 2017, 10(Suppl 1):A55
Background
Evidence suggest that smoking asthmatics have impared responce to
asthma therapy compared to nonsmoking asthmatics.
Objective
The aim of the study was to determine if there is a difference in
therapeutic response to the therapeutic dose of inhaled Fluticasone
propionate in patients smokers and nonsmokers with mild asthma.
Methods
Thirty eight patients with mild asthma, between 18-50 years old, were
included in a randomized parallel study. They were divided into two
groups: smokers (16) and nonsmokers (22). They have received inhaled
Fluticasone propionate 250 μg bid as a regular dose for 6 weeks. As a
rescue medication a short acting ß2 agonist Salbutamol a 0,1 mg was
prescribed on as needed base. Lung function was assessed with PowerCube spirometer and asthma control was assessed with asthma control
test (ACT-TM).
Results
There was no statistic difference in both groups according to age,
asthma duration and FEV1 values before treatment. There was a statistic difference between the two groups concerning ACT before treatment (p<0,5). After 6 weeks of treatment we found a positive effect
(p<0,01) concerning FEV1 in nonsmoker-asthmatics compared to
smoker-asthmatics. Positive effect (p<0,5) was found in ACT values
compared between two groups.
Conclusions
Although we have analyzed very small group of patients in a relatively
short period of time, we can conclude that median dose of inhaled corticosteroids results in good therapeutic response in nonsmokerasthmatics. On the other hand, these doses are insufficient to achieve
the same result in smoker-asthmatics and maybe the higher dose or
additional therapy is needed.
A56
Factors for therapy adherence in Chronic Urticaria
Vesna Grivcheva-Panovska
School of Medicine, University St. Cyril and Methodius University, Clinic
of Dermatology, Skopje, Macedonia
World Allergy Organization Journal 2017, 10(Suppl 1):A56
Background
Adherence to self administered medications is a major challenge both
for patients with Chronic Urticaria, as well as treating physicians.
Objective
To determine the adherence to self administered medications and to
analyze underlying associated factors using Medication Adherence
Scale (MARS), Brief Adherence Rating Scale (BARS), Urticaria Activity
World Allergy Organization Journal 2017, 10(Suppl 1):25
Score and Visual Analogue Scale (VAS) regarding Chronic Urticaria
treatment.
Methods
Questionnaires were performed by 296 Urticaria patients treated from
January 2015 to June 2016 at the University Hospital of Dermatology,
Unit of Allergy and Clinical Immunology as outpatients (163 female,
133 male, age 42+-5), 151 of them were Chronic Urticaria patients (98
female, 53 male, age 39+-3.5).
Education for patients with Chronic Urticaria encouraging them to
take active approach as well as regular checkups are necessary in
order to achieve a potentially good therapeutic outcome by increasing the adherence.
The v2 -test for categorical variables or parametric analysis for
continuous variables was used to evaluate the differences in the
study variables among the adherence groups. Internal consistency
was assessed using Cronbach’s alpha. An acceptable Cronbach’s
alpha value is considered to be 0.7 or more. Known group validity
was assessed through the association of items and MARS and BARS
categories using correlation coefficient and covariance. The significance level was set at P < 0.05. Mean adherence scores by MARS
and BARS were 4.5 for self-administered medication.
Results
The reliability scores (i.e. Cronbach’s alpha) were 0.783 for self administered drugs, 75 of all Urticaria patients (25.3%) admitted that they
ignored doctors’ instructions, whereas 84 of Chronic Urticaria patients
(55.6%) did so. 18.5% (28/151) of Chronic Urticaria patients with disease duration longer than 1 year discontinued medications because
they had self assessed themselves as cured, versus 32.45.0% (49/151)
with disease duration longer than 6 months but less than one year.
Patients’ gender, educational level, work position, marital status, disease
activity, type of dietary regimen, patient’s anticipation regarding outcome, as well as patient’s estimate of treating physicians’ competence,
availability and dedication did not have impact on the level of adherence to therapy.
Adherence to self-administered medications was influenced by the age
of the patient and duration of the symptom free phase of the disease.
Adherence to self administered medications was significantly associated with the frequency of hospital visits.
Conclusions
Education for patients with Chronic Urticaria encouraging them to take
active approach as well as regular checkups are necessary in order to
achieve a good therapeutic outcome by increasing the adherence.
A57
Molecular characterization, gene expression profile and
histopathology of fungal spore causing allergies in Southwestern
Nigeria
Adeyinka Odebode1, Adedotun Adekunle1, Peter Adeonipekun1,
Ebenezer Farombi2
1
University of Lagos, Botany, Akoka, Nigeria; 2University of Ibadan,
Biochemistry, Ibadan, Nigeria
Correspondence: Adeyinka Odebode
World Allergy Organization Journal 2017, 10(Suppl 1):A57
Background
The application of molecular technique could solve the challenges
associated with the treatment of fungi allergy therefore the study
aimed at assessing the molecular diversity of fungal spores using culture dependent approach.
Objective
A comparative survey of airborne fungal spores in ten different environments in Lagos and Oyo States, Nigeria was carried out for a
period of Eighteen months between Jan 2015 – June 2016.
Methods
Using sedimentation plates (Dichloran glycerol 18 and Potato Dextrose Agar culture plate). A total of 44 spore types were identified.
Genotypic identifications were accomplished through sequencing of
amplified ITS1 and 4 of rDNA gene.
Results
The fungal strains identified belong to Ascomycetes, Deuteromycetes
and Basidiomycetes. The results revealed lowest count during
Page 21 of 39
summer and maximum during the rainy season. Aspergillus was
quite abundant in all the environments surveyed. The predominance
of Aspergillus, Curvularia, Alternaria, Cladosporium, Fusarium and
Penicillium in all the surveyed environments has been attributed to
their ability to grow in various substrata. The mean relative gene expression values ranged from 18.95 – 31.28 for Actin, 17.38 – 26.77 for
β tubulin and 19.74 – 30.63 for P. oxalicum and 30.22 – 37.56 for P.
citrinum. All genes were significantly correlated to the Bestkeeper
index (p< 0.001). Histopathology showed that Aspergillus flavus on
mice lung had mild thickening of the alveolar interstitium. Alveoli are
clear and devoid of exudates while there was is however moderate
haemorrhages and multiple foci of alveolar macrophages laden
with dark pigment materials for Penicillium citrinum. There is accumulation of inflammatory cells around blood vessels suggestive of
vasculitis for Cladosporium spp while Aspergillus tamari showed
widespread haemorrhage and over-distension of the alveoli indicative of pulmonary emphysema. For Penicillium chrysogenum multiple foci of necrosis and accumulation of necrotic debris was
observed. A correlation has been made between the volumetric
composition of airspora and the incidence of seasonal fungi allergy.
Conclusions
Data on the abundance/prevalence of fungi species in the atmosphere of sub-Saharan Africa is limited which necessitated this study
for forecasting the prevalence of allergenic fungi in the environment
at various seasons.
A58
Temporary henna tattoos: fashion or nightmare?
Nadezhda Camacho-Ordoñez1, Alejandrina Josefina Martinez- Vázquez2,
María de la Luz H García-Cruz3
1
Londres Clinic Allergy and Clinical Immunology, Mexico City, Mexico;
2
Dalinde Medical Center Allergy and Clinical Immunology, Mexico
City, Mexico; 3National Institute of Respiratory Diseases Allergy and
Immunogenetic Research Department, Mexico City, Mexico
Correspondence: María de la Luz H García-Cruz
World Allergy Organization Journal 2017, 10(Suppl 1):A58
Background
Nowadays temporary paint-on tattoos have become popular worldwide. A common dye for such tattoos is henna (Lawsonia inermis).
Para-phenylendiamine (PPD) is a coloring agent and potent sensitizer
commonly added to henna tattoos to darken tattoo color. Contact allergy to temporary henna it is progressively more common reported.
Objective
To describe three cases of allergic contact dermatitis (ACD) to temporary tattoos with positive PPD reactions. They were followed 2
years after treatment.
Clinical cases
Case 1: a 33-year-old male presented with a 6-month history of an
erythematous, pruritic, papulovesicular rash on his right upper arm
after daily contact with a henna tattoo of a friend. He had history of
a similar reaction 2 years ago; 3 days after application of a temporary
black henna tattoo while he was on holiday. Case 2: a 32- year-old female had two black henna tattoos on arms while holiday in Cancun
Mexico in August 2013. 2 hours later tattoos became hot, red raised
and itchy. Case 3: a 22-year-old girl with previous history of erythematous and pruritic plaques on the back 5 hours after application
of a temporary tattoo one month ago. She presented with a severe
ACD on the scalp an hour after application of hair dye. All three patients were patch tested and they were positive to PPD. They were
treated with antihistamines, topical corticosteroids and emollients.
An improvement was noted after 48h hours. After 2-year follow-up,
we documented hyperpigmentation in 2 patients and hipopigmentary changes in one. We could not say if this is a prolonged postinflamatory reaction, or in the case of hypopigmentation, the henna dye
is acting as a sunblock agent.
Conclusions
In most cases allergic reactions are caused by the mixtures, which
contain not only natural henna but also many chemical coloring
agents such as PPD. Patients who developed an allergic reaction to
PPD should be advised by physicians to avoid any further exposure
World Allergy Organization Journal 2017, 10(Suppl 1):25
to PPD, which is contained in cosmetic products such as hair-dyes or
semi permanent eyebrow make-up; as has been described with our
third patient. Besides, skin tattoos with black henna should be
avoided, especially during foreign travel, as this can make a health
management challenge.
Consent
The authors received informed consent from the patients to publish.
A59
Immunological and clinical effects of rhIL-2 therapy in patients
with MDR-TB
Qi Tan, Rui Min, Guan-qun Dai, Wei-Ping Xie, Huang Mao, Hong Wang
The First Affiliated Hospital of Nanjing Medical University, Department of
Respiratory and Critical Care Medicine, Nanjing, China
Correspondence: Qi Tan
World Allergy Organization Journal 2017, 10(Suppl 1):A59
Background
Multidrug-resistant tuberculosis(MDR-TB) has emerged as a lethal
global threat and the treatment of MDR-TB is a challenge worldwide.
Thus, it is urgent to find an optimised therapy regimen for the control of MDR-TB globally.
Objective
We launched the study to investigate the clinical outcome and
immunomodulation mechanisms induced by recombinant human
interleukin-2 (rhIL-2) treatment in MDR-TB patients.
Methods
From 2009.1 to 2013.3, MDR-TB cases were enroled and followed up in
this prospective, randomised, controlled multicentre study (2008zx100
03-014), study group were administered rhIL-2 with the standard
chemotherapy of 18-month duration while control group under the
standard chemotherapy of 24-months duration. Clinical and safety outcomes and immune function observation were compared between the
two groups.
Results
Of 124 enroled MDR-TB patients, 64 in control group, 16 cured
(25%), with 1 died(3%), 9 default(15%), while 60 in rhIL-2 group, 32
cured (53%), with 3 died(5%), 10 default(16%). Adverse events were
generally those commonly associated with MDR-TB treatment. Rates
for any of the adverse events(AE) in two groups were similar(p>0.05).
Patients from study group under rhIL-2 treatment showed increasing
Th1 expression and decreasing Th17 and Treg expressions while the
relative levels of IL-17A mRNA, ROR-γt mRNA, and Foxp3 mRNA decreased and their level of IFN-γ mRNA increased in PBMCs, compared
with control group.
Conclusions
The study revealed that adjunctive treatment with rIL-2 induced an
outcome improvement with safty in MDR-TB patients and was associated with recovery of Th1/Th17 balance.
A60
Bronchospasmoltyic evaluation of synthesized 8-pyraozle
substituted xanthine derivatives
Rakesh Yadav, Sneha Singh, Divya Yadav
Banasthali University, Pharmaceutical Chemistry, Banasthali, India
Correspondence: Rakesh Yadav
World Allergy Organization Journal 2017, 10(Suppl 1):A60
Background
Asthma and chronic obstructive pulmonary disease (COPD) are categorized as chronic disease all over the globe and its pervasiveness is
increasing especially in the pediatric population. It is easily diagnosed
by the accumulation of mucus in the lumen of the airways and is not
a disease with a single etiology but a very complex syndrome. Several positions of xanthine skeleton with different substituents have
been explored to obtain a variety of potent derivatives.
Objective
Present investigation has been made to evaluate the synthesized 8pyraozle substituted xanthine derivatives for bronchospasmoltyic activity (in vivo)
Page 22 of 39
Methods
Synthesis-Number of new 8-pyrazole substituted xanthine derivatives
has been synthesized as per the reported literature.Substituted pyrazoles (1-6) were prepared by thermal fusion with appropriate amines
like morpholine, pyrrolidine, piperidine, piperazine, 1-methylpiperazine,
dimethylamine and diethylamine. The completion of the reaction was
monitored by thin layer chromatography (TLC). The residue so obtained
was washed with diethyl ether and the compound obtained was used
as such for further reaction. These pyrazole derivatives (1-6) were further reacted with 5,6-diamino-1,3-dimethyluracil in the presence of 1ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI) and methanol at
room temperature to yield the carboxamide derivatives (7-12)which on
subsequent ring closure yielded the titled compounds (13-18).
Biological activity- The newly synthesized xanthine derivatives were
evaluated for in vivo bronchospasmolytic activity against histamine
aerosol induced bronchospasm in guinea pig as per Yadav et al. The
morpholine and dimethylamine substituted derivatives showed pronounced bronchospasmolytic effect in comparison to the standard
drug theophylline in guinea pig animal model.
Results & Conclusions
The chemical sturucture of synthesized 8-pyrazole substituted xanthines were characterized using various spectral techniques viz. FT-IR,
NMR etc. The effects of varying substituents and their location on
the 8-pyrazole ring are clearly visible in the pharmacological characteristics of these novel xanthine derivatives. Suitable introduction of
8-pyrazole substituents on the xanthine scaffold results an important
trait for potent bronchospasmolytic effects.
References:
1. Rakesh Yadav, Ranju Bansal, Suman Rohilla, Sonja Kachler, K. N. Klotz.
Synthesis and pharmacological characterization of novel xanthine
carboxylate amides as A2A adenosine receptor ligands exhibiting
bronchospasmolytic activity. Bioorganic Chemistry, 2016, 65, 26-37.
2. Rakesh Yadav, Ranju Bansal, Sonja Kachler, K. N. Klotz. Novel
8-(p-substituted-phenyl/benzyl)xanthines with selectivity for the A2A
adenosine receptor possess bronchospasmolytic activity. European
Journal of Medicinal Chemistry 03/2014; 75:327–335. DOI:10.1016/
j.ejmech.2014.01.045
3. Rakesh Yadav, Divya Yadav, Ranju Bansal and Anurag Kuhad. Synthesis
and pharmacological evaluation of 8-substituted phenyl xanthines for
asthma therapy. Frontiers in Immunology 01/2013; 4. DOI:10.3389/
conf.fimmu.2013.02.00645
A61
Peri-anaesthetic anaphylaxis; comparisons between cardiovascular
manifestations in children and adults
Ekaterina Khaleva1, Henry T. Bahnson2, Amber Franz3, Lene Heise Garvey4,
Nicola Jay5, Rubaiyat Haque6, Adam Fox1, Gideon Lack1, George du Toit1
1
Guy’s and St Thomas’ NHS Foundation Trust, Children’s Drug Allergy
Clinic, London, UK; 2Benaroya Research Institute, Seattle, WA, USA;
3
Seattle Children’s Hospital, Seattle, WA, USA; 4University Hospital
Gentofte, Danish Anaesthesia Allergy Centre, Allergy Clinic, Department
of Dermato-Allergology, Gentofte, Denmark; 5Sheffield Children,
Sheffield, UK; 6Guy’s and St Thomas’ NHS Foundation Trust, Adult’s Drug
Allergy Clinic, London, UK
Correspondence: Ekaterina Khaleva
World Allergy Organization Journal 2017, 10(Suppl 1):A61
Background
Anaphylaxis during anaesthesia is rare, sometimes difficult to diagnose, and may have life-threatening consequences if untreated. Relatively little is known of the cardiovascular sequence of anaphylaxis
and how children and adults may be different.
Objective
The aim of this retrospective audit was to document time-dependent
cardiovascular symptoms and signs that occur during anaphylaxis in
the peri-anaesthetic environment.
Methods
We performed a retrospective study of all patients with suspected
perioperative anaphylaxis in the GSTT during 2008-2014. The time sequence of cardiovascular symptoms including lower systolic and
World Allergy Organization Journal 2017, 10(Suppl 1):25
diastolic blood pressure (BP), heart rate (HR) and time from causative
drug to treatment of anaphylaxis with epinephrine were noted.
Results
A total of 49 patients with confirmed peri-anaesthetic anaphylaxis were
included. 16 were excluded due to missing or incomplete anaesthetic
charts. Out of 49, 15 were children (6yo average age) and 34 adults
(52yo average age); 22 males and 27 females. In children the lowest recorded systolic BP was 35 mm Hg (mean 53.1 mm Hg) and diastolic 15
mm Hg (mean 26.64 mm Hg), while in adults 30 mm Hg (mean 52.78
mm Hg) and 12 mm Hg (mean 30.08 mm Hg) respectively. The mean
time of documented hypotention after induction of anaesthesia was
8.7 min (SD ±9.5) in children and 27.47 min (SD ±14.33) in adults and
after administration of the causative drug (when known) was 4.67 min
(SD ±6.43) in children and 11.45 min (SD ±17.33) in adults. Of the 49
cases of anaphylaxis, 24 (49%) were accompanied by tachycardia, the
mean highest HR in children was 147.2 bpm and 125.06 bpm in adults.
Recorded hypotension preceded recorded tachycardia in 3 adults and
mean time of this to occur was 5 min. Arrhythmia was observed in 3
(9%) adults but not in children. One adult and one child experienced
cardiac arrest and required cardiopulmonary resuscitation. Both adrenaline and metaraminol were administered in 12 cases. The overall median time from causative drug administration to adrenaline was 6 min
(range, 1-30).
Conclusions
Our retrospective evaluation of cardiovascular manifestations during
peri-anaesthetic anaphylaxis demonstrates severe hypotension (in both
adults and children). Anaphylaxis and tachycardia can develop rapidly
after induction, and may develop sooner in children as compared to
adults.
A62
Allergic rhinitis among university students in Belgrade
Snezana Radic1, Branislava Milenkovic2, Ana Neskovic1, Ljiljana Danojevic3
1
Clinical Hospital Center Dr Dragisa Misovic Dedinje Children’s Hospital
for Respiratory Diseases and TB, Belgrade, Serbia; 2Clinical Centre of
Serbia,Faculty of Medicine, University of Belgrade Clinic for Pulmonary
Diseases, Belgrade, Serbia; 3Gerontology Center Belzanijska kosa Medical
practice, Belgrade, Serbia
Correspondence: Snezana Radic
World Allergy Organization Journal 2017, 10(Suppl 1):A62
Background
Allergic rhinitis is one of the most common chronic disease, and its
prevalence has been increasing in many parts of the world in recent
decades, especially in developed countries. It is a desease caused by
IgE interference following contact with allergens. Allergic rhinits may
be seasonal, perennial, or episodic. It is the condition which could
strongly interfere with patients well being and quality of life. There
were few studies about prevalence of allergic rhinitis among university students in the world.
Objective
To estimate the prevalence of of allergic rhinitis, respiratory symptoms and smoking habits among population of university students in
Belgrade, Serbia.
Methods
Questionnaire based on the European Community Respiratory Health
Survey (ERCHS) protocol was used to obtain data.
Results
We have analysed 14 questions about respiratory symptoms in 5045
university students in Belgrade, mean age 21.5±1.7 years. There were
2259 (44.8%) of male and 2786 (55.2%) of female studets. The prevalence of allergic rhinitis was 20.8% (N 1048). The majority of respondents were non-smokers (73.6%), 26.4% current and 3.3% were ex
smokers. Allergic rhinitis was more prevalent in males (22.8% vs 19.1%,
p<0.001). There were 71.4% non-smoking and 28.6% smoking studets
with allergic rhinitis. There were 18.0% of subjects with allergic rhinitis
who use asthma medication, which was sifnificantelly more than 5%
who use asthma medications in general population of students.
Page 23 of 39
Conclusions
There is a high prevalence of allergic rhinitis among university students in Belgrade, Serbia, which is in consistency with findings of
other studies.
A63
Safety and efficacy of first versus subsequent foods oral
immunotherapy
Liat Nachshon, Michael Goldberg, Michael Levy, Yitzhak Katz,
Arnon Elizur
Assaf Harofeh Medical Center Allergy and Immunology, Zerifin, Israel
Correspondence: Liat Nachshon
World Allergy Organization Journal 2017, 10(Suppl 1):A63
Background
We previously described a treatment program of oral immunotherapy
(OIT) for desensitization to milk (Levy et al. Ann Allergy Asthma Immunol. 2014 Jan;112(1):58–63), which has expanded to include peanut,
egg and sesame OIT. In some patients with multiple food allergies, sequential OIT treatments for the different foods may be required.
Objective
We aimed to determine whether the clinical course and results of patients undergoing sequential OIT treatments differed from those who
completed their first OIT treatment program.
Methods
Patients (n=21, ages 4-23 years) with multiple food allergies to a
combination of milk, peanuts, egg and sesame, were enrolled into an
OIT treatment program. A starting dose below the eliciting dose was
determined and increased on a monthly basis while under medical
supervision, until the goal of 3.0 gram food protein was achieved
and consumed daily. While continuing to consume the initial desensitized food, patients were enrolled in sequential OIT treatments. Except for sesame OIT (only available since 2014), the decision for
which food was to be treated first was individualized based on the
patient’s respective difficulties in maintaining avoidance to a particular food.
Results
No significant differences were noted in achieving the final target
dose between those in their sequential OIT treatments (6 each for
milk and peanut, and 5 each for egg and sesame) and those during
their first OIT treatment (10 to milk, 7 to egg and 4 to peanut) (77%
(17/22) versus 85.7% (18/21), respectively). However, the average
number of reactions during home treatment and overall treatment
reactions was significantly lower during the sequential OIT programs
compared to the first OIT desensitization (10 versus 27, p=0.04, and
17 versus 30, p=0.05, respectively). Furthermore, the treatment duration was significantly shorter during sequential OIT desensitizations
as compared to the first OIT program (5 months versus 8.4 months
(p<0.0001), perhaps related to the median starting dose achieved
during the first induction (90mg versus 25mg, sequential versus first
OIT, respectively, p=ns)
Conclusions
Although similarly efficacious, sequential OIT treatments to the subsequent food are of shorter duration and involve a lower risk for reactions than the first OIT treatment.
A64
Hereditary Angiedema (HAE) in children and adolescents
Cristine Rosario, Juliana Kasper, Herbeto Chong-Neto, Carlos Riedi,
Nelson Rosario
Federal university of Parana Allergy and Immunology, Curitiba, Brazil
Correspondence: Cristine Rosario
World Allergy Organization Journal 2017, 10(Suppl 1):A64
Background
Hereditary Angioedema (HAE) is a difficult to treat disease, characterized by recurrent edema attacks and low serum complement levels.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Objectives
To report clinical and laboratory features of children and adolescents
and their treatment in a specialized clinic in Brazil.
Methods
Retrospective analysis of 11 cases of HAE in children and adolescents
by chart review and laboratory results.
Results
11 cases of HAE due to C1 inhibitor (C1-INH) deficiency in children
and adolescents have been followed-up at the University Clinic.
Symptoms first appeared between the age of 1 and 8 years (median
2.5 years-old). Eight children were male (73%). All patients had family
history of angioedema. Duration of crisis varied from 0.25 to 7 days
(average 2.4 days). Nine children had complained of abdominal pain,
seven presented limb edema, five had facial edema and two had
laryngeal edema. Serum C4 levels ranged from 5.4 to 7.3mg/dL
(median 6.2mg/dL), quantitative C1-INH from 4 to 24.7mg/dL
(median 8.6mg/dL) and CH50 from 8.4 to 89U/mL (median 29.5U/mL).
Two patients had normal C1-INH levels, but both had family history of
angioedema and one of them had low C4 levels. Four children had
been on prophylactic danazol with partial control of the symptoms (less
frequent attacks) and five had used tranexamic acid.
Conclusion
HAE manifestations may begin in childhood though less symptomatic in this age group. Patients had C1-INH deficiency and low serum
levels of C4 and CH50. Early diagnosis and prompt initiation of treatment lower the burden of the disease. First-line medications are
available in Brazil but hardly accessible to most patients.
A65
Determination of multiple tree nut allergies among tree nut
allergic patients
Arnon Elizur, Michael B Levy, Ronly Har-Even, Liat Nachshon,
Mor Carmel, Michael R. Goldberg
Assaf Harofeh Medical Center Allergy and Immunology, Beer Yaakov,
Israel
Correspondence: Arnon Elizur
World Allergy Organization Journal 2017, 10(Suppl 1):A65
Background
Patients with a single tree-nut allergy are often instructed to avoid
multiple tree-nuts for fear of cross-sensitization. However, the actual
percentage of co-allergy between different tree-nuts has not been
well studied. The goal of this study was to examine the frequency of
allergies to other tree-nuts in single tree-nut allergic patients.
Methods
Patients (n=44, median age of 8.7 years (range, 2.3 – 22.2) referred for
tree-nut oral immunotherapy (OIT), were evaluated for sensitization (by
SPT) and allergy to six nuts: walnut, pecan, cashew, pistachio, hazelnut
and almond. Determination of the clinical allergic status was determined by an oral food challenge (OFC) unless a significant recent reaction (within the previous 2 years) was noted.
Results
Walnut was the most frequent allergen with 28 allergic patients, 16
were allergic to pecan, 13 to cashew, 8 to hazelnut, 5 to pistachio.
None were allergic to almond. Among those tested by OFC, anaphylaxis occurred in 8/21 (38%) of walnut (eliciting dose (ED) range, 54200 mg), 2/5 (40%) of hazelnut (ED range, 12-3840 mg), 7/14 (50%)
of pecan (ED range 18-2500 mg), 8/13 (61.5%) of cashew (ED range,
9-4000 mg), and 1/4 (25%) of pistachio (ED range, 100-2200 mg),
positive oral food challenges. Treatment with IM adrenaline was
required in 33% (19/57) positive OFCs. Of the 23 patients who were
challenged to all six tree-nuts, 35% (8/23) had single tree-nut allergy,
while 65% (15/23) had multiple nut allergy (5 to two nuts, 6 to three
nuts, 3 to four nuts, and 1 with proven allergy to five tree nuts).
Among walnut-allergic patients, 60% were co-allergic to pecan, 38%
to cashew, 19% to pistachio and 24% to hazelnut. All pecan-allergic
patients were also allergic to walnut, while co-allergy with the other
tree-nuts was lower (25-43%). Among cashew allergic patients, 69%
were also allergic to walnut, 55% to pecan, 55% to pistachio and
24% to hazelnut. All pistachio allergic patients were co-allergic to
Page 24 of 39
cashew. Nineteen out of the 23 (83%) tree nut allergic patients were
allergic to half or fewer of the six nuts tested.
Conclusions
While multiple tree nut allergy was common in our referred population, the majority of tree nut allergic patients tolerated at least half
of the six nuts tested, suggesting the elimination of all nuts is unwarranted and should first be evaluated by OFC. Future studies will determine whether walnut and cashew OIT, will cross-desensitize for
pecan and pistachio allergy, respectively.
A66
Clinical symptoms and development of infants with cow’s milk
allergy fed with hydrolyzed formula
Maia Kherkheulidze, Nani Kavlashvili, Eka Kandelaki
State Medical Universitym, Pediatrics, Tbilisi, Georgia
Correspondence: Maia Kherkheulidze
World Allergy Organization Journal 2017, 10(Suppl 1):A66
Background
Between 5% and 15% of infants show symptoms suggesting adverse
reactions to cow’s milk protein (CMP), while estimates of the prevalence of cow’s milk protein allergy (CMPA) vary from 2% to 7.5%.
Objective
Assessment of clinical symptoms physical development of infants
with cow’s milk allergy, fed with extensively hydrolyzed formula.
Methods
Prospective study was conducted at outpatient department of Iashvili
children’s central hospital. Cow’s milk related Symptom score (COMiss),
full medical history was used for assessment and Specific IgE (RAST) for
CMP was used for diagnosing CMPA. Assessment of development was
based on Bayley test and physical development was evaluate based on
WHO Z score growth charts. We followed until 1 year studied 34 infants
with proved CMPA who was fed with exclusively hydrolyzed formula.
We used SPSS 19 for statistical analyses.
Results
The hydrolyzed formula was well tolerated. In 14,5% (n=5) during the
first week were seen feeding problems. The CoMiSS shows significantly decrease of clinical scores after 2 weeks starting hydrolyzed
formula: total score decreases from 24.44 + 4,2 to 12.3 + 2,9. (T-=
11.46328. p < .00001); Crying scores (4.26+2.87) and regurgitation
scores (2,56+1,41) significantly decreased by 1.9 ±0.6 (t= 8.24216. p <
.00001). and 1.36 ± 0.5 (t= 3.08527, The p<. 001) respectively. The
percentage of infants having normal stool consistency (soft or
formed stools) significantly improved from 51.2% at inclusion to
92.0% after 14 days of feeding (P<0,05). The Bayley scores for development do not show any significant difference from same age population data and growth z-scores, negative at study inclusion,
significantly improved after starting exclusively hydrolyzed formula.
At 1-year age all infants’ anthropometric parameters was between +2
Z scores. No adverse event was related to the exclusively hydrolyzed
formula.
Conclusions
Extensively hydrolyzed formula is well tolerated and improved
clinical symptoms rapidly. The improvement of growth indices and
absence of related adverse events confirmed its safety.
A67
Prevalence and risk factors of allergic diseases
Nino Adamai, Maia Kherkheulidze, Lia Jorjoliani, Irma Ubiria
Tbilisi State Medical University, Department of Pediatrics, Tbilisi, Georgia
Correspondence: Maia Kherkheulidze
World Allergy Organization Journal 2017, 10(Suppl 1):A67
Background
Allergic diseases have an increasing tendency.
Objective
Correlation between prevalence of atopic dermatitis, hives, herpes,
diseases with angiodermatitis in children’s population.
Methods
Research was conducted in 2015, on the basis of questioning of random and representative population of children in Tbilisi and Kutaisi.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Studied population included 2035 children aged from 6 to 15. Risk
factors were studied through interviewing, with specially developed
map-questionnaire, clinical-laboratory data; for assessment of the risk
factors the case control method was applied. Statistical processing of
the materials was provided by means of SPSS/v12 software. IgE study
was performed as well, for the specific allergens, skin samples were
taken for identification of the allergen (prink test).
Results
Based on the analysis of risk factors in the studied population - frequencies of presence of the dust collectors, moisture and mildew,
active tobacco consumption. Frequencies of the identified variables
were reliably higher (p<0.5) in the families of children with allergies,
compared with the healthy population. Atopic dermatitis was diagnosed in 6.5% of cases, frequencies of hives (8.9%), angiodermatitis
was identified in 3.2% of the adolescents, medication-caused allergy
was indicated in 2.6% of children’s population, congenital herpes viral
infection was indicated in 0.7% of the population. 41.3% of the studied
population had positive skin prick-test. In 3.9% of the studied population IgE value was 6 times higher than norm (p=0.01).
Conclusions
Regarding the obtained results we can conclude that there is increased allergen load p=0.05 that could be managed based on the
early and targeted prevention program, taking into consideration the
regional characteristics.
A68
Hamilton stock epinephrine pilot study: facilitators and barriers to
implementation
Andrea Burke1, Ernie Avilla2, Monika Kastner3, Susan Waserman1
1
McMaster University, Clinical Immunology & Allergy, Hamilton, Canada;
2
McMaster University, Medicine, Hamilton, Canada; 3North York General
Hospital, Knowledge Translation and Implementation, Toronto, Canada
Correspondence: Andrea Burke
World Allergy Organization Journal 2017, 10(Suppl 1):A68
Background
The scope of accidental exposure in food allergic individuals dining
out is unknown. Risk for these individuals is accentuated when they
forget to carry their epinephrine auto-injector (EAI) or do not have it
at the time of a reaction. Our aim was to identify facilitators and
barriers to implementing a stock epinephrine program at a shopping
mall food court and stand-alone restaurants. This was part of the first
pilot study of such a program in Canada.
Methods
We conducted a qualitative study to evaluate facilitators and barriers
of implementing a stock epinephrine program at a shopping mall
and two stand-alone restaurants. A purposive sampling strategy was
used to recruit program implementation team members (security
guards, food service workers, mall administration, representatives of
Food Allergy Canada, and the City of Hamilton) to participate in oneon-one qualitative interviews. Analysis involved content analysis of
qualitative data.
Results
A total of eight participants identified four key factors that contributed to organizational compatibility of providing stock epinephrine. These included (1) a shared passion for food allergy
and anaphylaxis; (2) ease of program implementation (clear emergency protocols); (3) the fact that the program was neither resource nor time intensive and (4) low overhead costs. The
majority of respondents were “very optimistic” about the program rolling out in other settings and identified program benefits
such as providing access to emergency medication to those in
need. Other benefits included the potential to reduce healthcare
costs through early administration of epinephrine and improved
health outcomes, and providing a template for others who may
want to implement a stock epinephrine program. One of the key
barriers to widespread acceptance of this pilot study, and for any
future initiatives, was fear and lack of understanding of liability
and how existing legislation applied to malls and food service
establishments.
Page 25 of 39
Conclusions
To our knowledge there are no studies that describe a stock epinephrine program in public settings. In spite of its positive attributes, food service establishments remain reluctant to participate
because of fears related to liability. It is important to reinforce, that
a stock epinephrine program is meant to complement and not replace a food allergic individual’s responsibility to self-manage and
carry an EAI.
A69
Dermatological toxicities after targeted anti-tumor therapy
Denica Zheleva, Razvigor Darlenski
Tokuda Hospital Sofia, Dermatology and venereology, Sofia, Bulgaria
Correspondence: Denica Zheleva
World Allergy Organization Journal 2017, 10(Suppl 1):A69
Background
In the past decade a plethora of targeted anti-tumor therapies has
been introduced. Herein we report two cases of dermatological adverse efects after treatment with epidermal growth factor inhibitors
(EGFRIs).
Clinical case 1:
A 52-year-old female Caucasian with colorectal adenocarcinoma
(pT3N2M1), developed severe skin rash 2 months after the start of
therapy with the tyrosine kinase inhibitor- Erolitinib. The dermatological examination revealed generalized papulopustular reaction, accompanied by severe pruritus, xerosis, trichomegaly of the eyelashes
and hypertrichosis of the face, fissures and hyperkeratosis of the
palmes.
Therapy included topical emolients and high-potencycorticosteroid
cream- Betamethasone dipropionate 0,05% with slight improvement
in the dermatological status.
Clinical case 2:
A 32-year-old female from India was diagonsed with lung cancer and
multi-organ metastases. She has started target therapy with the human IgG2 monoclonal antibody- Pantimumab. One month later she
developed acneiform eruption of the face. The therapy has started
with Doxycycilne 100mg BID and topical gel nadifloxacin 1%.2 weeks
later a new flare up was observed and clindamycin 1% soutiion and
topical cream with special Fluidactiv® patent were prescribed. Poor
therapeutic response was observed.
Results
In both cases, the mild character of the adverse skin reactions requested no withdraw of EGFRI treatment. However, both patients decided to discontinue therapy.
Conclusions
The most common adverse reactions associated with EGFRIs, occurring in more than 50% of patients who receive treatment include dry
skin, pruritus, papulo-pustular eruption, paronychia and fissuring, trichomegaly and curling of eyelashes and eyebrows and hypertrichosis
of the face. There is a positive correlation between the occurrence
and severity of cutaneous adverse effects and tumor response. Our
cases corroborate these observations. To avoid therapy discontinuation in such cases it is worth to provide reactive or proactive management strategies.
Consent
The authors received informed consent from the patients to publish.
A70
Anti-IgE therapy in Chronic Spontaneous Urticaria
Konstantinos Bozinakis1, Anastasios Kriebardis2, Sofia Styliara1, Aikaterini
Karastathi1, Nikolaos Farmakas1
1
General Hospital of Nikea-piraeus, Allergy and immunology, NikeaPiraeus, Greece; 2Tei Tei, Aigaleo, Greece
Correspondence: Nikolaos Farmakas
World Allergy Organization Journal 2017, 10(Suppl 1):A70
Background
Urticaria is a relatively common phenomenon. Chronic Spotaneous Urticaria (CSU) lasts for longer than 6 weeks.The recommended first line
treatment of CSU is new generation, nonsedating H1-Antihistamines. If
World Allergy Organization Journal 2017, 10(Suppl 1):25
standard dosing is not effective, increasing the dosage up to fourfold
and after this there are a number of adjunct therapy options (e.g
addition of an leucotriene receptor antagonist). If this therapy failures
we can use anti-IgE therapy (omalizumab)
Objective
We want to evaluate the effectiveness and safety of the anti-IgE therapy in CSU patients who are refractory to fourfold anti-Histamines
(+/- leucotrienes antagonist) for more than 2 months.
Methods
Fifty patients (14: men, 36: women) with CSU (age 12 -85 years old,
mean age 52 years were observed. A dose of 2x150 PFS of Omalizumab
administrated per month.
Results
The mean age of treatment (scorad 0) was 3,064 months. None of
the patients had serious side effects.
Conclusions
Omalizumab appears to be a very safety and promising therapeutic
alternative for refractory chronic spontaneous urticaria.
A71
Anaphylaxis: a life-threatening emergency, but still improperly
managed
Maria Luiza Kraft Kohler Ribeiro1, Ana Carolina Barcellos2, Hannah Gabriele
Ferreira Silva2, Luís Henrique Mattei Carletto2, Marcela Carolina Bet2,
Nathalia Zorze Rossetto2, Nelson Augusto Rosario2,
Herberto Jose Chong-Neto2
1
Federal University of Paraná, Healthy Community, Curitiba, Brazil;
2
Federal University of Paraná, Pediatrics, Curitiba, Brazil
Correspondence: Herberto Jose Chong-Neto
World Allergy Organization Journal 2017, 10(Suppl 1):A71
Background
Anaphylaxis is a life-threatening disease, need a fast recognizing and
properly management.
Objective
To verify the level of knowledge of physicians in emergency departments in Curitiba on the management of anaphylaxis.
Methods
Cross-sectional study applying written questionnaire (WQ) containing
questions about clinical aspects, diagnosis and treatment of anaphylaxis to physicians in public and private emergency services in Curitiba
from April to July / 2016.
Results
There were 199 physicians invited to participate and 104 (52.3%)
answer the WQ. Fifty (48.1%) working in hospitals and 54 (51.9%) in
Emergency Care Units (ECU). Regarding professional experience,
20.4% was represented by physicians who graduated more than 10
years, 21.4% between 5 and 10 years of graduation and 58.2% were
graduated less than five years. Sixty-five (62.5%) reported ever seen
at least one case of anaphylaxis. Forty-two physicians (40.4%) answered that anaphylaxis affects at least two systems simultaneously
(skin and subcutaneous tissue, respiratory, cardiovascular and
gastrointestinal). Forty-five (43.3%) responded that intramuscular
epinephrine is the drug and route of first choice to treat anaphylaxis, 37 (35.6%) subcutaneous epinephrine and 22 (21.1%) choice
other drugs, such as corticosteroids or antihistamines, oral or injectable. Eleven (10.6%) answered that glucagon is the drug of choice
for treating anaphylaxis in patients using beta-blockers drugs.
Conclusions
Anaphylaxis is a life-threatening condition and remains underdiagnosed and improperly managed in emergency room.
A72
Quality of life in patients with food allergy before and after
resolution
Fernanda Valença, Marina Novaes, Mariana Gomes, Carla Seifert,
Alfredo Neto, Flavia Loyola, José Rios, Tatiana Silva
Policlinica Geral do Rio de Janeiro, Allergy, Rio de Janeiro, Brazil
Correspondence: Marina Novaes
World Allergy Organization Journal 2017, 10(Suppl 1):A72
Page 26 of 39
Background
Some patients which have food allergy have a bad life quality.
Objective
To compare the quality of life (QOL) of patients with allergy to cow's
milk proteins (CMPA) before and after oral challenge test (TPO) and /
or oral desensitization.
Methods
A prospective study was donne, using validated QOL questionnaire
analysis, developed by DunnGalvin. The questionnaire was
responded by patients (or guardians) who underwent negative TPO
(n = 47), before this procedure (pre group), and another group diagnosed with CMPA who had been submitted to the oral
desensitization protocol (n = 19) (post group) in the period May2013 to May-2016. The items were divided in three areas: Emotional
impact, Food and Social Anxiety and Dietary Restrictions (, each
one with 10 to 13 questions). The responses varied from 0 to 6
(Likert scale), according impact intensity. It was added to the each
domain issues set points and divided by the number of issues
thereby obtaining a score of symptoms of each individual. Mean
scores of individuals in each group formed the average score of
each domain.
Results
The mean scores were obtained for each field of pre and post groups
and the results were compared. Regarding the Emotional Impact, the
average score was 2.69 (pre) and 1.27 (post). In Food Anxiety domain
mean scores were 3.16 and 0.97, respectively, and for Social and
Dietary limitations was obtained pre mean score of 3.21 and to 0.71
post.
Conclusions
The quality of life measures are important to evaluate the daily impact on pacient allergy and their families. The CMPA and the consequent restrictive diet profoundly affect the quality of life of affected
individuals (pre group). Overcoming this condition spontaneously
measured by TPO, or procedure for oral desensibilization, significantly improves QOL, with the release of social and dietary restrictions, which reduce food anxiety and emotional impact (post group).
A73
Evaluation of life quality in patients with cow milk allergy
Aline Neves, Marina Novaes, Fernanda Valença, Mariana Gomes, Alfredo
Neto, Flavia Loyola, José Rios
Policlínica Geral do Rio de Janeiro, Allergy, Rio de Janeiro, Brazil
Correspondence: Aline Neves
World Allergy Organization Journal 2017, 10(Suppl 1):A73
Background
Some patients which have cow milk allergy have problems in life
quality.
Objective
To evaluate the life quality of patients with diagnosis of allergy to
cow’s milk.
Methods
A retrospective study based on questionnaire validated QOL developed by DunnGalvin and employees responded by patients (or
guardians) who are allergic to cow’s milk, candidates for oral food
challenge or desensitization, from May-2013 to May-2016. The questionnaires were divided into seven areas: emotional impact, symptoms of the disease, adverse disease effects, social and dietary
restrictions, personal problems by food allergy, personal expectations
regarding the disease and future expectations regarding the improvement of the disease. For each domain, the responses were considered low, moderate or severe criteria based on Likert Scale.
Results
The data generated for the fields “emotional impact” and “symptoms
of disease”, 24 respondents answered that food allergies affected
your life in moderation (45.28%). To “negative repercussions of the
disease”, 52.83% (n = 28) are affected lightly and 49.05% (n = 26)
responded that the “impact on the social and dietary restrictions” is
serious. As for “personal problems caused by food allergy”, 23 respondents (43.39%) reported being affected lightly. As for “personal expectations regarding the disease and its repercussions”,
World Allergy Organization Journal 2017, 10(Suppl 1):25
Page 27 of 39
54.71% (n = 29) are slightly affected. Among the 53 respondents,
38 (71.69%) have only discrete “future expectations regarding the
improvement of the disease.”
Conclusions
Life quality measures are important to evaluate the daily impact on
patient lives with food allergy and determine effects of diagnosis
and treatment instituted. Monitoring the quality of life of patients
and their parents or caregivers is an important role in the treatment
of food allergy. Life quality questionnaires have become important
tools to assess the impact of the disease and take measures to
minimize them.
compared to NS (74,2+/-0,8% vs 78,0+/-0,6%, p=0.00, respectively
and 64,3% vs 73,7%, p=0,013; 71,9% vs 80,8%, p=0,013, respectively). Frequency of both coronary artery disease and hypertension
were higher in ES group compared to S (8,4% vs 2,6%, p=0,001;
18,6% vs 9,3%, p=0,010, respectively).
Conclusions
We reached three remarkable results: 28% of newly diagnosed
asthma patients were active smokers. Percentage of noncompliance
to the treatment was higher in S group compared to other groups
and ICS+LAB2A combination was the most preferred treatment in
this group.
A74
The effect of smoking on the course of disease in newly diagnosed
asthma patients: results from multicenter observational study
Oznur Abadoglu1, Bilun Gemicioglu2, Hasan Bayram3, Arif Cimrin4,
Levent Akyildiz5, Aykut Cilli6, Hakan Gunen7, Tevfik Ozlu8,
Mecit Suerdem9, Esra Uzaslan10, Zeynep Misirligil11
1
Cumhuriyet University, Faculty of Medicine, Department of Pulmonary
Diseases, Sivas, Turkey; 2Istanbul University, Cerrahpasa Faculty of
Medicine, Department of Pulmonary Diseases, Istanbul, Turkey;
3
Gaziantep University, Faculty of Medicine, Department of Pulmonary
Diseases, Gaziantep, Turkey; 4Dokuz Eylul University, Faculty of Medicine,
Department of Pulmonary Diseases, Izmir, Turkey; 5Mardin Medical Park
Hospital, Department of Pulmonary Diseases, Mardin, Turkey; 6Akdeniz
University, Faculty of Medicine, Department of Pulmonary Diseases,
Antalya, Turkey; 7Sureyyapasa Pulmonary Diseases Hospital and Research
Centre, Department of Pulmonary Diseases, Istanbul, Turkey; 8Karadeniz
Technical University, Faculty of Medicine, Department of Pulmonary
Diseases, Trabzon, Turkey; 9Selcuk University, Faculty of Medicine,
Department of Pulmonary Diseases, Konya, Turkey; 10Uludag University,
Faculty of Medicine, Department of Pulmonary Diseases, Bursa, Turkey;
11
Ankara University, Faculty of Medicine, Department of Pulmonary
Diseases, Ankara, Turkey
Correspondence: Oznur Abadoglu
World Allergy Organization Journal 2017, 10(Suppl 1):A74
A75
Asthma prevalence among university students in Belgrade
Branislava Milenkovic1, Snezana Radic2, Snezana Ristic-Stojanovic3,
A Milicevic3, A. Milenkovic3, Jelena Cvejic1, Jelena Jankovic1,
Sanja Dimic-Janjic1, Natasa Djurdjevic1
1
Clinical Centre of Serbia, Clinic for Pulmonary Diseases, Belgrade, Serbia;
2
Clinical Hospital Center “Dr Dragisa Misovic-Dedinje”, Children’s Hospital
for Respiratory Diseases and TB, Belgrade, Serbia; 3Institute Student’s
Health Care Institute, Belgrade, Serbia
Correspondence: Branislava Milenkovic
World Allergy Organization Journal 2017, 10(Suppl 1):A75
Background
Smoking is one of the most significant triggers for asthma patients.
There are no sufficient data on the effects of smoking in newly diagnosed asthma patients in our country.
Objective
To evaluate the prevalence of active smoking and factors related to
its effects on newly diagnosed asthma patients from different regions
of Turkey.
Methods
A total of 1113 newly diagnosed adult asthma patients from 122 centers are registered to the study and a questionnaire is applied between July 2012 and March 2014. Patients are categorized in three
groups: smoker (S), ex-smoking (ES) and nonsmoker (NS). Demographic data are compared by means of atopy, living in urban/rural
area, effects of the region, pulmonary function tests, comorbid diseases, asthma medications and additional treatments.
Results
The number of patients according to the groups was as follows: S;
316, ES; 168 and NS; 629. Percentages of smoker female and male
patients were similar (50,3% vs 49,7%, respectively). The number of
smoker patients living in Marmara region was significantly higher
than other regions (26,1%, p=0.00). FEV1% before bronchodilator and
FEV1/FVC rate were significantly lower in S group compared to NS
group (70,9+/-1,1 vs 74,3+/-0,9, p=0,017; 74,8+/-0,7 vs 77,7+/-0,5,
p=0,01, respectively). There found no significant difference, in first
visit, by means of disease severity and control level between three
groups. The number of patients taking inhaled corticosteroid (ICS)+long acting beta2 agonist (LAB2A) treatment was significantly higher
in S group compared to NS group (88,6% vs 81,7%, p=0,014, respectively). However, percentage of regular medication use was significantly lower in S group compared to both NS and ES group
(67,6%, 81,0% and 84,5%, p=0,003, respectively). FEV1/FVC rate in
patients mostly lived in urban area and FEV1 and FVC rates in
patients mostly lived in urban/rural area were lower in S group
Background
Over the last three decades the prevalence of respiratory disease has
been increasing worldwide thus increasing economic burden on the
healthcare system. Recent studies have been shown that the prevalence of asthma in West European ranges from 6 to 9%, while of
chronic obstructive pulmonary diseases (COPD) is 8% worldwide. Despite the large number of epidemiological studies, there are only a few
studies about the prevarence of chronic respiratory diseases among
students.
Objective
The aim of the study was to estimate the prevalence of asthma among
University Students in Belgrade, Serbia.
Methods
We used a questionnaire based on the European Community Respiratory Health Survey (ERCHS) protocol to collect data.
Results
We have analysed respiratory symptoms in 5045 university students
in Belgrade. There were 44.8% male and 55.2% female participants;
mean age: 21.6±1.7 years for males and 21.3±1.6 years for females.
There were 26.4% smokers and 3.3% ex-smokers. The most frequent symptoms were longstanding cough (15.5%) and sputum
production (11.4%). Asthma attacks were reported in 2.4% of subjects and 5.0% of subjects were using asthma medications. Women
reported using asthma medication more frequently than men (6.2%
vs 4.3%, p=0.02). Allergic rhinitis was reported in 71.3% participants
with asthma.
Conclusions
There is a high prevalence of asthma among university students in
Belgrade, Serbia.
A76
Efficiency of the SIT to the house dust mite allergens in children
with atopic dermatitis
Vladyslava Barzylovych1, Tetiana Umanets2, Anastasia Barzylovych3
1
Bohomolets National Medical Univercity, Pediatrician departemen, Kiev,
Ukraine; 2Institute of Pediatrics, Obstetrics and Gynecology, Drug Allergy
Center, Kiev, Ukraine; 3Oberig clinic, Pediatrician department, Kiev,
Ukraine
Correspondence: Vladyslava Barzylovych
World Allergy Organization Journal 2017, 10(Suppl 1):A76
Background
Nowadays allergen specific immunotherapy (SIT) is widely used in
the treatment of asthma and allergic rhinitis. PubMed analysis shown
that the role of SIT in the treatment of atopic dermatitis (AD) is still
uncleare and need more reserch especially in childhood.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Objective
The aim of the study was to determine role of SIT using house dust
mite (HDM) allergens in the treatment of AD in children.
Methods
Under our supervision were 23 3-years old children with moderate
atopic dermatitis. All children received treatment according to the
WAO Guideline including avoidance of causative food allergens and
local therapy with insufficient results. All children had isolated
sensitization to the Derp1 or/and Derp2 (ImmunoCAP). The children
were divided in two groups. In the second group (12 children) the
treatment was supplemented with SIT to the HDM. Children were
under observation up to two years.
Results
During first 6 months there were no significant difference in the severity and the frequency of exacerbations of AD in two groups.
In the analysis of long-term results (after 1,5-2 year of treatment)
there are significant different in severity of AD: (3 mild and 8 moderate in the 1-st group and 7 mild, 2 moderate and 3 children without
clinical signs in the 2-nd group).
Also, in the 2-nd group the presentation of dermato respiratory syndrome was significantly lower (8 children with bronchial asthma in
the 1-st and 3 children in the 2-nd group).
Conclusions
The role of SIT to the HDM in the treatment of AD need more investigation and could be considered like prophylactic of dermato respiratory syndrome realization.
A77
Melatonin alters nitric oxide production by IFN-gamma/Vitamin D3
stimulated peripheral blood mononuclear cells (PBMC) from
healthy adults and patients with allergy/asthma
Karyn Winkler1,2, Jessica Margarinos3, Dylan Martin3, Maja Nowakowski1,4,
Rauno Joks1,5
1
State University Of New York Downstate Medical Center, Center for
Allergy and Asthma Research, Brooklyn, New York, NY, USA; 2State
University Of New York Downstate Medical Center, Department of
Pediatrics, Brooklyn, New York, NY, USA; 3State University Of New York
Downstate Medical Center, College of Medicine, Brooklyn, New York, NY,
USA; 4State University Of New York Downstate Medical Center,
Department of Pathology, Brooklyn, New York, NY, USA; 5State University
Of New York Downstate Medical Center, Department of Medicine,
Brooklyn, New York, NY, USA
Correspondence: Karyn Winkler
World Allergy Organization Journal 2017, 10(Suppl 1):A77
Background
We have previously reported that low levels of melatonin increased
the amounts of nitric oxide produced in vitro by peripheral blood
mononuclear cells (PBMC) from healthy adults.We related these data
to our earlier observation of a seasonal increase in angioedema in
the summer months, peaking in June. Melatonin, a factor responsible
for sleep-wake cycles, is decreased with long summer days. As melatonin is known to suppress eNOS, which is upregulated by bradykinin,
we hypothesized that decreased melatonin is associated with increased
nitric oxide production from stimulated PBMC.
Methods
Blood was drawn from healthy subjects (n=6) between 8 - 11 AM and
PBMC (3x106/ml) were stimulated with bradykinin (100 nmol/ml), ±
hIL-15 (1 μg/ml), ±IL-18 (1 ug/ml), +/-IFN-gamma (10 ng/ml)/ Vitamin
D3 (20 pmol/ml) for five days, and then incubated for 4 hrs in the absence or presence of recombinant human melatonin(1 pmol/m). Nitric
oxide levels in the culture supernatants were determined using Griess
reaction.
Results
Stimulation with bradykinin, hIL-15 and hIL-18 did not increase NO
production above baseline (base: 0.61±0.76 μM: bradykinin+hIL-15
+hIL-18: 0.63±0.76 μM, p=0.62). Addition of melatonin did not alter
NO production (0.59±0.76μM) (p=ns). However, addition of melatonin
to PBMC cultures stimulated with IFN-gamma and Vitamin D3 resulted in significant increase in NO: (1.84±0.21 μM) (p<0.01). When
PBMC were obtained from patients with allergy/asthma, the effects
Page 28 of 39
of melatonin depended on the time of blood collection and PBMC
isolation. PBMC isolated in the morning (9-10 AM), after overnight
period of sleep-associated elevation in endogenous melatonin levels,
did not respond to added melatonin with any increase in NO production (below detection). In contrast, when PBMC were isolated from
blood collected in the afternoon (5-6 PM), NO production was high
in cultures stimulated with bradykinin and with melatonin (1.45±
0.16 μM and 1.43± 0.07 μM, respectively).
Conclusions
Prolonged, low daytime levels of melatonin increase nitric oxide production from Interferon-gamma/Vitamin D3 stimulated leukocytes
and may contribute to seasonal angioedema. Adding melatonin to
PBMC isolated from allergy/asthma subjects in the morning did not
cause any increase in nitric oxide production above that observed in
the presence of bradykinin, hIL-15 + hIL-18, and Interferon-gamma/
Vitamin D3. This is likely to be an effect of increased overnight endogenous melatonin levels in vivo.
A78
Eosinophilic Esophagitis: review of the Israeli experience in an
allergy reference center
Miguel Stein1, Tsili Zangen2, Olga Bernadsky3, Mona Boaz4,
Gratiana Hermann5, Yoram Faitelson1, Ilan Dalal1, Rachel Aviv1,
Olga Kuperboim1, Larisa Ramichanov1, Efrat Broide6, Raanan Shamir7,
Noam Zevit7, Ron Shaoul8, Alex Fich9, Arie Levine2
1
E. Wolfson Medical Center, Allergy/Immunology Unit, Holon, Israel; 2E.
Wolfson Medical Center, Pediatric Gastroenterology, Holon, Israel; 3E.
Wolfson Medical Center, Pathology, Holon, Israel; 4E. Wolfson Medical
Center, Biostatistics, Holon, Israel; 5Assaf Harofeh, Pathology, Zerifin,
Israel; 6Assaf Harofeh Medical Center, Pediatric Gastroenterology, Zerifin,
Israel; 7Schneider Children, Pediatric Gastroenterology, Petach Tikva,
Israel; 8Rambam Medical Center, Pediatric Gastroenterology, Haifa, Israel;
9
Soroka Medical Center, Gastroenterology, Beer Sheva, Israel
Correspondence: Miguel Stein
World Allergy Organization Journal 2017, 10(Suppl 1):A78
Background
Eosinophilic Esophagitis (EoE) is a clinicopathologic condition characterized by esophageal dysfunction and eosinophilic inflammation.
Identification of food allergens is crucial for the management, and
delaying diagnosis can lead to esophageal strictures and morbidity.
Objective
A descriptive analysis of EoE in Israel, to increase awareness for an
early diagnosis, and the proper testing for a better management.
Methods
Eighty six consecutive patients derived for EoE allergic evaluation,
were tested for at least 30 food allergens by skin prick (SPT) and
Atopy Patch (APT) Testing. Clinical history was taken in each individual or their parents, for allergic and gastrointestinal complaints, and
pathological data were revised. Patients with full EoE diagnostic criteria, tested and interviewed in the allergy clinic, were included in
the analysis.
Results
Fourty five EoE patients were available for the analysis, 26 (57.8%)
children’s and 19 (42.2%) adults, (age 2.5-17 and 18-67 years old, respectively). Patients were predominantly males 36 (80%) and
atopics 34 (76%). The first EoE presenting symptom was at age 6
(1-16) and 23.4 (5-59) years old for children’s and adults, respectively, being principally vomiting (45%), abdominal pain (38%), food
impaction (38%), dysphagia (24%) and failure to thrive (24%) for
kids, and dysphagia (68%), partial or complete food impaction
(68%) and vomiting (58%) for adults. Delay in the diagnosis was between 0.3-13 (average 3.5) years for children’s and 0.9-23 (average 8)
years for adults.
Food related anaphylaxis was found in 7 (16%) individuals. Positive
food SPT was observed in 25/44 (56.8%) most commonly to peanuts, tree nuts and soy. Positive APT observed in 24/38 (63%) individuals, most commonly to fish, peanuts wheat and chicken. The
combination of SPT+APT could identify food allergens in 35/44
(79.5%) individuals. Interestingly all the non-atopic EoE patients
had a positive APT.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Conclusions
•EoE is not uncommon in Israel and probably under-diagnosed.
•There is a big delay in the diagnosis of EoE, from 3 to 8 years in the
pediatric and adult population.
•The most common presenting symptoms for pediatric EoE are
vomiting, partial or complete food impaction and abdominal pain.
•The most common presenting symptoms for adult EoE are dysphagia, partial or complete food impaction and vomiting.
•Different food allergens are found by SPT and APT, and the best
yield is obtained with the combination of both (IgE & Non-IgE mediated testing).
•All non-atopic EoE should have an APT examination.
A79
STAT3 mutation presenting as autosomal dominant common
variable immunodeficiency (CVID), a novel presentation
Adi Ovadia, Yael Dinur Schejter, Chaim Roifman
Hospital for sick children, Immunology and Allergy, Toronto, Canada
Correspondence: Adi Ovadia
World Allergy Organization Journal 2017, 10(Suppl 1):A79
Background
STAT3 mutations have been traditionally associated with hyper-IgE syndrome. While loss of function mutations present in a typical fashion,
STAT3 gain of function mutations reported recently lead to lymphoproliferation and early-onset autoimmune disease.
Objective
We report of a father and a son with STAT3 gain of function mutation presenting as a common variable immunodeficiency (CVID).
Case report
A 47-year-old man initially presented at 3.5 years with recurrent chest
infections and normal immunoglobulin titers. At the age of 7.5 years,
he developed ITP and lymphadenopathy. Immunoglobulin levels were
once again normal including IgE. Lymph node biopsy demonstrated reduced plasma cells. At the age of 17 years, during an admission for
complicated pneumonia, he was noted to have hypogammaglobinemia and antibody deficiency, and was subsequently started on IVIG replacement. From the age of 35 years, he gradually deteriorated and
developed respiratory as well as liver failure ultimately requiring double
lung and liver transplant, which have completely reversed his disease
course. He is currently well. His son presented at the age of 15 months
with lymphadenopathy without hepatosplenomegaly. His initial investigations revealed normal immunoglobulin titers with variable antibody
response to vaccines. He was clinically well and suffered mainly from
upper respiratory tract infection but no significant bacterial sinopulmonary infections. At the age of 7 years, he was noted for the first time
to have hypogammaglobulinemia and a complete loss of specific antibodies, and was therefore given IVIG replacement therapy. Currently,
he is 14 years old, and remains well with no autoimmunity.Whole-exome sequencing identified heterozygous STAT3 mutation c.2147 C>T
predicting Threonine to Methionine amino acid change at position 716.
This mutation has been previously reported as a gain of function
mutation.
Conclusions
STAT3 gain of function mutations can present as autosomal dominant CVID.
Consent
The authors received informed consent from the first patient and
second patient’s guardian/parent.
A80
The role of C1 inhibitor in neuroimmune disease
Isaac Melamed
ImmunoE Immunology, Centennial, CO, USA
World Allergy Organization Journal 2017, 10(Suppl 1):A80
Background
The term neuroimmune disease (NID) refers to a group of illnesses that
are the result of acquired dysfunction cross talk between the immune
system and the nervous system and often result in lifelong disease and
disability. Symptoms may include cognitive changes, abdominal
Page 29 of 39
symptoms, and extreme fatigue. The diseases usually follow an infection or flu-like symptoms that never resolve. One of the pathogens
linked to the neuroimmune presentation is Lyme disease. The link between Lyme disease and neurocognitive disease has been a focus of research and multiple therapeutic approaches, but no clear mechanism
has been identified.
Objective
Here we present 3 case studies in patients with NID.
Methods
Our immune work up was divided into 3 layers: epigenetic infectious
activation, immune dysregulation, and neuroimmune presentation.
Epigenetic triggers included positive IgM western and PCR for Lyme.
Immune dysregulation was characterized by IgG3 subclass deficiency,
low response to T cell antigens, decrease activation of toll like receptor (TLR)-3, low memory B cells, and low C1 INH. Neuroimmune
markers were anti-GAD and anti-68 kDa, as well positive ANA and
phospholipid antibodies. Our patients presented with a complex of
neurological symptoms, including low C1, low IgG3, a decrease in
TLR 3, and evidence of neuroimmune auto-antibodies. All patients
were treated with IVIG or SCIG 600-800 mg/kg for 3 week intervals.
Results
With this treatment plan, we were able to see a major reversal in the
incidence of infections, but no major change in the neurological
presentation or the neuroimmune response to the disease. In 2 patients, we added C1 inhibitor (C1 INH) therapy (100 units twice a
week) to the treatment regimen. In these patients who received C1
INH and IVIG therapy, we were able to see some neurological improvement as well a reduction in neuroimmune markers.
Conclusions
Further studies are needed; however, the synergistic effect of IVIG
and C1 therapy may provide an optimal therapy in the future.
A81
CD48 on blood leukocytes and in serum of asthma patients varies
with severity
Roopesh Singh Gangwar1, Yael Minai-Fleminger1, Mansour Seaf1,
Amichai Gutgold1, Aarti Shikotra2, Anoop Chauhan3, Stephen Holgate4,
Peter Bradding2, Peter Howarth4, Ron Eliashar5, Neville Berkman6,
Francesca Levi-Schaffer1
1
The Hebrew University of Jerusalem Institute For Drug Research,
Portsmouth, Israel; 2University of Leicester Institute for Lung Health,
Leicester, UK; 3Portsmouth Hospitals NHS Trust Respiratory and General
Medicine, Portsmouth, UK; 4Southampton General Hospital NIHR
Respiratory Biomedical Research Unit, Southampton, UK; 5Hadassah
Hebrew University Medical Center Department of Otolaryngology/Head
and Neck Surgery, Jerusalem, Israel; 6Hadassah Hebrew University
Medical Center Institute of Pulmonary Medicine, Jerusalem, Israel
Correspondence: Roopesh Singh Gangwar
World Allergy Organization Journal 2017, 10(Suppl 1):A81
Background
CD48 is a membrane receptor (mCD48) on eosinophils and mast cells
and exists in a soluble form (sCD48). CD48 has a pivotal role in murine asthma and in the proinflammatory interactions of mast cells
with eosinophils via its ligand CD244. Thus CD48 might be important
in human asthma.
Objective
To investigate the expression and role of mCD48 on peripheral blood
leukocytes and sCD48 in serum in asthmatic patients with varying
disease severity.
Methods
Two separate cohorts (IL and UK) comprising mild, moderate, and severe asthma and healthy volunteers were evaluated for blood
leukocyte mCD48 expression and sCD48 in serum. Asthmatic bronchial
biopsies were immunostained for CD48. sCD48 effect on CD244dependent eosinophil activation was evaluated.
Results
Eosinophils mCD48 expression was significantly elevated in moderate
while downregulated in severe asthma. mCD48 expression on B, T,
NK cells and monocytes in severe asthma was significantly increased.
sCD48 levels were significantly higher in mild while reduced in
World Allergy Organization Journal 2017, 10(Suppl 1):25
severe asthma. sCD48 optimal cut-off values for differentiating
asthma from health were identified as >1482 pg/ml (IL) and >1619
pg/ml (UK). In asthmatic bronchial biopsies mCD48 was expressed
predominantly by eosinophils. sCD48 inhibited anti-CD244 induced
eosinophil activation.
Conclusions
mCD48 and sCD48 are differentially expressed in the peripheral
blood of asthma patients of varying severity. sCD48 inhibits CD244mediated eosinophil activation. These findings suggest that CD48
may play an important role in human asthma.
A82
Prognostic value of exhaled nitric oxide monitoring for asthma
prognosis in Korean children and asthma friendly school
Sung-il Woo
Chung-buk National University Hospital Department of Pediatrics,
Choeng-ju, South Korea
World Allergy Organization Journal 2017, 10(Suppl 1):A82
Background
The fractional exhaled nitric oxide (FeNO) measurements are useful
method of diagnosing asthma and monitoring tool for airway
inflammation.
Objective
We sought to evaluate the yield of FeNO monitoring on graft concept in asthma friendly school for asthma exacerbation and prognosis, so that could identify the usefulness of FeNO in children.
Methods
One hundred and seventy element school student aged 7-12 years
with agreement of parents in elementary school were included. Children were evaluated using FeNO measurement, questionnaire of
asthma symptom and control, history taking of asthma treatment,
skin prick test, sprirometries.
Results
One hundred fifty nine student (93.5%) had completed follow up
and monitoring of FeNO at each season over 1 year. Twenty five children had asthma exacerbation or uncontrolled asthma. These children had higher FeNO level than those without asthma exacerbation
or uncontrolled asthma. (27.7 ppb vs 22.7 ppb, P<0.05) There was
also significant difference of maximal level of FeNO. (P<0.05). Among
these children with inhalant allergen sensitization, mean of maximal
FeNO was 34ppb. Fifteen children had history of medical treatment
for asthma exacerbation and seven children had absence of school
associated with asthma exacerbation.
Conclusions
FeNO monitoring has prognostic value of asthma monitoring. It can
predict asthma exacerbation of children who has higher level of
FeNO, especially who has atopic asthma or aeroallergen sensitization.
A83
Human Epidydim Protein 4 may be a target for gene therapy in
patient with high grade serous carcinoma of the ovary
Betul Celik1, Tangul Bulut1, Arzu Didem Yalcin2
1
Antalya Training Hospital Pathology, Antalya, Turkey; 2Antalya Training
Hospital Allergy and Immunology, Antalya, Turkey
Correspondence: Arzu Didem Yalcin
World Allergy Organization Journal 2017, 10(Suppl 1):A83
Background
Human epididymis 4 (HE4) protein belongs to whey acidic 4-disulfide
center protein family (ref-5). The protein shows characteristics of a
secretory protein, with an acidic and cysteine-rich polypeptide. It is a
protease inhibitor and involved in the innate immunity defense of
the respiratory tract and nasal cavity. Formerly found in epididymis,
it is now shown that serum level is the most predictive marker detecting adnexial malignancy.
Objective
The aim of this study was to evaluate the presence of human epididymis secretory protein 4 (HE4) in patient with high grade serous
carcinoma of the ovary as to whether it may be a potential candidate
for gene therapy in ovarian cancer treatment.
Page 30 of 39
Methods
A total of 31 patients with a diagnosis of high grade serous ovarian
carcinoma were enrolled. All patients underwent surgical resection.
Final original diagnosis had been reached by histopathological
feature of the tumor and by combined immunohistopathological
stains using CA125, and p53. Concomitant tumor pathology blocks
were examined after HE4 immunohistopathological staining.
Results
Of the tumor tissues studied, HE4 immunostaining was seen in majority of the cases (28 out of 31 cases) (90,32%). Moreover, neither
CA125 nor p53 results were available in six cases based on pathology
reports, in which HE4 expression was observed in 5 cases.
Conclusions
Immunohistochemical staining pattern of HE4 protein 4 is expressed
in the majority of the high grade serous ovarian carcinoma and it
may be a potential candidate for gene therapy as well as it is a good
immune marker for detecting high grade serous ovarian carcinoma.
A84
Is Human Epididymis Protein 4a (HE4) a reliable screening
biomarker for detecting lung carcinoma patients.
Betul Celik1, Arzu Didem Yalcin2, Tangul Bulut1
1
Antalya Training Hospital Pathology, Antalya, Turkey; 2Antalya Training
Hospital Allergy and Immunology, Antalya, Turkey
Correspondence: Arzu Didem Yalcin
World Allergy Organization Journal 2017, 10(Suppl 1):A84
Background
Human epididymis 4 (HE4) protein belongs to whey acidic 4-disulfide
center protein family. The protein shows characteristics of a secretory
protein, with an acidic and cysteine-rich polypeptide. It is a protease
inhibitor involved in the innate immunity defense of the respiratory
tract and nasal cavity. HE4 has been detected in the malignant
pleural effusions of patients with lung carcinoma. As a serum and
pleural fluid biomarker, it has very high sensitivity (43.8-69.4%) and
specificity (78.5-95.0%) for lung cancer.
Objective
The value of HE4 among lung carcinoma subtypes are limited. The
aim of this study was to investigate the expression of human epididymis protein 4 (HE4) in small cell lung cancer (SCLC) and lung
adenocarcinoma cases.
Methods
Fifty-four patients with a diagnosis of SCLC and twenty-one adenocarcinoma (AC) from a bronchoscopic biopsy were enrolled in the
study. The tumors were classified as SCLC or AC based on histology
and immunohistopathology for CD56 and/or synaptophysin, Chromogranin, thyroid transcription factor-1 (TTF-1), CK7 immunostains. Representative blocks were immunostained with HE4.
Results
Using HE4 immunostain, the majority (90.1%) of the SCLC cases were
devoid of HE4. Only the 9.9% cases were positive for HE4 immunostain. HE4 positive staining was focal and moderate trough out the
tumor tissue. On the other hand, fifteen AC cases (71.4%) were positive with HE4, whereas 6 cases (28.6%) were negative with HE4.
Conclusions
This study showed that HE4 is expressed in the majority of the AC
but it is less frequently expressed in SCLC, that greatly limits the utility of HE4 as a screening tool.
A85
Off-label and concurrent use of an anti-asthma agent in the
treatment of a chronic kidney disease: a case report
Luiz Querino Caldas
Federal Fluminense University Pathology, Niterói, Brazil
World Allergy Organization Journal 2017, 10(Suppl 1):A85
Background
Since 2004, a 37-year-old female has been referring to our clinic for
multiple episodes of respiratory allergy including rhinitis, sinusitis,
cough, epistaxis, dyspnea, amongst other symptoms. Ten years ago
after severe episode of glomerulonephropathy postinfection she was
World Allergy Organization Journal 2017, 10(Suppl 1):25
reported with hematuria, hypertension, edema and renal insufficiency that led her to hemodialysis since then. Due to a lack of recovery of the renal function, her chronic kidney disease (CKD)
progressed gradually to a Stage V, being her glomerular filtration rate
lower than 15ml/min. In the meantime, her allergic episodes including pruritus have been treated with antihistamine drugs as well as
immunotherapy was used for a while, although antileucotriene
agents had never been under the scope of the treatment. In 2009,
she had a severe bone mineral disorder developing a spontaneous
and consecutive rupture of both Achilles tendons. In uremic patients
and on the patient’s lack of corticosteroid or fluoroquinolone use, it
seems that occurred to secondary hyperparathyroidism which was
the predisposing factor in this patient. A year ago, she fractured her
both femurs and seizure episodes outcome. The later may be related
to the high parathyroid hormone (PTH) serum level, which resulted
in osteolytic bone resorption and at the tendon insertion site. Additionally, she presented perforating dermatosis in both arms with hyperpigmented macules areas prior involvement that were related to
elevating plasma level of β-melanocyte-stimulating hormone.
Results
Treatment and prevention of such tendon ruptures included early
surgical repair and control of secondary hyperparathyroidism, by the
use of vitamin D analogs, although she remained hypercalcemic and
hyperphosphatemic occasionally. Objective: Lately, for allergic purposes, she was initially treated with sodium montelukast (5mg) and
as soon as this dose increased to 10mg/day she had slight improvement but significant (p <0.05)in her creatinine clearance (CockcroftGault Index -10.86) with the serum levels of glucose, calcium, potassium, urea post-dialysis, creatinine and phosphates a rather stable
without significant changes from normal values during the last 6
months. Supposedly, CRD is associated to production of reactive oxygen species and cytokine release that may be prevented by the concurrent long term use of a CysLTd1 receptor antagonist montelukast.
Conclusion
This activity can be attributed to its ability to inhibit neutrophil and
leucocyte apoptosis by balancing the cell oxidative status and regulating the proinflammatory mediators production. A renal transplantation was thus so far postponed as for an alternative treatment.
Consent to publish
The patient has signed the Term of Consent freely and due explained.
A86
Rush venom immunotherapy in children
Ronit Confino-Cohen, Yossi Rosman, Arnon Goldberg
Meir Medical Center Allergy and Clinical Immunology Unit, Kefar Saba,
Israel
Correspondence: Yossi Rosman
World Allergy Organization Journal 2017, 10(Suppl 1):A86
Background
Rush venom immunotherapy (VIT) is highly effective in Hymenoptera
venom allergy. Still, specific data regarding its safety and efficacy in
children are rather sparse.
Objective
To better evaluate the safety and efficacy of rush VIT in this specific
age group.
Methods
Children younger than 16 years with systemic reaction to insect sting
involving, at least, one body system other than skin and children
aged 16-18 years old with any kind of systemic reaction were offered
conventional or rush VIT with a build-up phase that lasted 3 days.
Results
Eighty-four out of 127 children chose to receive rush VIT. Seventy of
them were allergic to bee venom (BV) only. There was no difference
between the children receiving rush or conventional VIT in the
incidence of systemic reactions during the build-up phase (19% and
23.2%, respectively), nor was there any difference with regard to the
severity of these reactions. Efficacy was improved with rush VIT, as
reflected by higher number of patients achieving the 100 mcg maintenance dose with the primary protocol (83/84 patients, 98.8% and
39/43, 90.7%, respectively, P=0.04).
Page 31 of 39
Conclusions
Rush VIT in children is as safe and more efficient when compared
with conventional VIT.
A87
CD48 as a potential biomarker for allergic and non-allergic asthma
Oded Breuer1, Roopesh Singh2, Mansour Seaf2, Ahlam Barhoum2,
Eitan Kerem1, Francesca Levi-Schaffer2
1
Hadassah Hebrew University Medical Center Pediatric Pulmonology,
Jerusalem, Israel
2
The Hebrew University of Jerusalem Department of Pharmacology
and Experimental Therapeutics, Institute for Drug Research, Faculty
of Medicine, Jerusalem, Israel
Correspondence: Oded Breuer
World Allergy Organization Journal 2017, 10(Suppl 1):A87
Background
CD48 is a member of the CD2 subfamily of immunoglobulin-like receptors, present as membrane receptor on hematopoietic cells and
as a soluble (sCD48) form in serum. CD48 was found to be involved
in allergic eosinophilic airway inflammation and shown to be a potential target for the suppression of asthma in mice. The full significance of CD48 in patients with asthma has not yet been evaluated.
Objective
To evaluate the expression of sCD48 as a possible biomarker for
asthma and correlate its expression with other disease markers.
Methods
Volunteer patients completed an asthma and allergy questionnaire,
performed spirometry, methacholine (Mch) challenge test, a common
allergen skin prick test, a complete blood count. Moreover sCD48,IgE,
IL17A and IL33 levels were measured in their serum. Asthma was defined as positive Mch challenge test or a 15% increase in FEV1 post
bronchodilator administration in symptomatic individuals. Allergy
was defined as positive skin test or IgE levels > 200 IU/L in symptomatic individuals.
Results
137 individuals participated in the study with a mean age 37.9 ±
19.3 years (range 5-79), 47 (34%) were male and 82 (60%) were diagnosed with asthma of which 53 (64%) was allergic asthma. Levels of
sCD48 were significantly elevated in asthmatic patients but especially
in the non-allergic asthmatic patients when compared to control
(1468±360 pg/ml 1551±374 pg/ml vs. 1298± 315 pg/ml, p<0.01).
IL17A and IL33 levels were significantly elevated in allergic and nonallergic asthmatics when compared to control: IL17A; 100±75 pg/ml
and 132±86 pg/ml vs. 59±33 pg/ml, p<0.01, respectively; and IL33;
169±140 pg/ml and 175±35 pg/ml vs. 57±36 pg/ml, p<0.01, respectively). However, there was no correlation between sCD48 levels and,
eosinophil count, IgE, IL17A or IL33 levels in asthmatic or nonasthmatic patients.
Conclusions
sCD48 is possibly an independent biomarker for asthma. The significance of elevated sCD48 especially in non-allergic asthma is incompletely understood but may represent nonspecific airway inflammation.
Additional studies are required for understanding the role of sCD48 in
airway disease and non-allergic asthma.
A88
Immunological criteria for the activity of allergic inflammation and
prognosis of infectious complications in children with atopic
dermatitis
Tatiana Slavyanskaya, Revaz Sepiashvili
People’s Friendship University of Russia Allergy & Immunology, Moscow,
Russia
Correspondence: Revaz Sepiashvili
World Allergy Organization Journal 2017, 10(Suppl 1):A88
Background
The purpose of the study is to develop criteria for prognosis of infectious complications in children (Ch) with moderate to severe atopic
dermatitis (AD).
World Allergy Organization Journal 2017, 10(Suppl 1):25
Objective
The object of the study was 94 Ch aged 5-17 years with IgEmediated AD in remission with duration of the disease of 1-15 years.
Clinically, the AD had multiple and extensive inflammation with exudation or infiltration, lichenification, excoriation and severe itching,
which led to the accession of secondary infection. A control group
included 30 practically healthy Ch.
Methods
All patients underwent clinical and immunological and allergological
studies. SCORAD was evaluated on a scale of severity of clinical
symptoms. Particular attention was paid to the phagocytic immunity.
Results
The most distressing symptoms were pruritus (3.69±0.22), xerodermia
(3.34±0.23), physical discomfort (3.13±0.14) and sleep disorders. The
signs of immune imbalance in patients with AD: reductions of phagocytic activity of neutrophils (PhAN) - phagocytic index (PhI) and the
phagocytic number (PhN). In moderate and severe AD serum cytokine levels and cytokine regulatory indices were respectively: IL-4:
55.2±4.2 pg/ml; IL-13: 39.4±4.9 pg/ml; IFNγ: 11.4± 1.6 pg/ml; RIFNγ/
IL-4: 0.21±0.06; RIFNγ/IL-13: 0.29±0.05 (P<0.001 vs. controls). Both systemic and local IL-13 levels depended more on disease severity, its
extent and presence of secondary infection, rather than on IL-4 and
IFNγ concentrations. Severe and complicated AD presented with
serum IgE of 496.4+62.12 IU/ml and IL-13 of 1295.41±29.8 pg/ml
during exacerbation, and IgE of 484.8+60.14 IU/ml during remission.
IL-13 and IgE correlation index in saliva was r = +0.67, and in serum r =
+0.76. The SCORAD index before treatment of moderate AD was 42,57
±3.41 and severe AD - 48,2±5.7 points. It was found that immunocompromised Ch with AD and impaired function of the PhAN, the inclusion
of allergen-specific immunotherapy (AIT) in the comprehensive treatment (CT) in 78% of cases led to the development of pyodermia and
joining of viral infection. that complicates the course of the disease. In
the group of Ch with AD, which in CT plan has been included AIT and
immunomodulator that activates PhAN, there were no complications or
worsening of the clinical course of AD.
Conclusions
Thus, monitoring of the blood levels of PhI and PhN in IgE-mediated
AD predicts the development of infectious complications in Ch with
AD. Monitoring of cytokine profile along with other parameters during treatment course has certain diagnostic value in determination of
localization, severity, degree and activity of allergic inflammation.
A89
Programmed death-1 expression on T subsets in patients with
atopic dermatitis during autologous activated T cell
immunotherapy
Elena A. Blinova1, Ekaterina A. Pashkina1, Marina I. Leonova2,
Vera M. Nepomnyaschikh2, Darya V. Demina2, Vladimir A. Kozlov1
1
RIFCI laboratory of clinical immunopathology, Novosibirsk, Russia;
2
Clinic of Immunopathology RIFCI allergological department,
Novosibirsk, Russia
Correspondence: Elena A. Blinova
World Allergy Organization Journal 2017, 10(Suppl 1):A89
Predisposition to allergic diseases has been associated with dysfunction of regulatory cells. PD-1/PD-L1 pathway is involved in the generation of regulatory T-cells. Induction of the anti-ergotypic response
during immunotherapy with autologous cells allows to eliminate activated T cells, regardless of their antigenic specificity. This response
acts against activation markers (ergotopes).
The purpose of this study was to determine the expression of PD-1
in different subsets of T cells in patients with atopic dermatitis during
T-cell immunotherapy.
The study was approved by the ethical commission of RIFCI, Russia.
During immunotherapy patients was administered subcutaneously
with activated anti-CD3 antibody+IL-2 T cells (30*10^6 cells per dose)
according to scheme: 1 injection once a week - 4 times, then 1 injection per month - 6 times. Efficiency of treatment was determined as
a reduction of clinical symptoms, it was about 80%.
Patients with AD were characterized by significant increase (p <0,05,
Mann-Whitney test) in amount of peripheral blood Treg and rise
Page 32 of 39
expression of PD-1 on it compared to donors. Significant differences
in expression of PD-1 have been identified on CD4+ T-cells, but not
on CD8+ cells. Thus, in the peripheral blood of patients a large number of CD4+ cells bearing activation marker PD-1 circulated, which is
consistent with the pathogenesis of these diseases. The increased
Treg population indicates the absence of defects in the Treg generation; however, it is not clear how to relate the increase in the PD-1
expression on Treg and their functional activity.
On 10th injection CD4+ cells did not show significant differences of
PD-1 expression compared to the level before vaccination. There was
a decrease in PD-1 expression on CD4+, CD8+ T-cells expressed
CD25, and CD4+25high regulatory cells. The cell number in the investigated subpopulations before and after immunotherapy was not significantly change. Observed alterations possible indicate the
reduction of the number of activated T-cells, which involved in allergic reaction, as a result of anti-ergotypic response. PD-1 pathway
may negatively regulate its own functions: PD-1 signaling may result
in reduced PD-L1 expression and to downregulate Treg development
and/ or function.
The reported study was funded by RFBR, according to the research
project No. 16-34-60167 mol_a_dk.
A90
ROCK serve as negative regulators of degranulation of human and
mouse eosinophils
Revital Shamri1, Kristen M. Young2, Peter F. Weller2
1
Hebrew University of Jerusalem School of Pharmacy, Jerusalem, Israel;
2
Beth Israel Deaconess Medical Center, Harvard Medical School
Department of Medicine, Boston, MA, USA
Correspondence: Revital Shamri
World Allergy Organization Journal 2017, 10(Suppl 1):A90
Background
Eosinophils are innate immune granulocytes known for their cytotoxic
effector functions against pathogens and their involvement in host tissues damage in allergic diseases. A unique character of eosinophils is
their cytoplasmic granules which contain many preformed cationic
cytotoxic proteins that are not found elsewhere. Among these proteins
are eosinophil-associated RNases (EARs), which have been shown to be
involved in host defense, tissue remodeling, immunity regulation and
pathology in eosinophil-associated diseases. Rho-associated coiled-coil
forming kinases (ROCK) are known downstream effectors of Rho A, and
are involved in cytoskeletal reorganization, stress fiber and focal adhesion formation. ROCK inhibition was found to inhibit eosinophil chemotaxis and migration into lung during airway inflammation. However,
ROCKs role in granule content deposition (i.e. degranulation) from eosinophils was not addressed.
Objective
To examine the role of ROCK in eosinophil degranulation.
Methods
ROCKI and II involvement in CCL11-stimulated degranulation was examined by treatment of human or mouse eosinophils with the highly
potent and selective cell permeable inhibitor Y27632, that blocks
ROCKI and II with similar potency. Degranulation was assessed by
measuring RNase activity of secreted granule-associated RNases.
Results
Effective concentrations of Y27632, that blocked chemotaxis of
murine and human eosinophils, did not inhibit CCL11-mediated
degranulation and even increased it compared to vehicle. In
addition, the inhibitor Y27632 also increased spontaneous eosinophil degranulation. Moreover, degranulation enhancement by
Y27632 was not due to an effect on actin polymerization or surface expression of CCL11 receptor, CCR3. It was previously shown
by our studies and others that beta-2 integrin mediated spreading is essential for CCL11-mediated degranulation of eosinophils.
Along these lines, we found that Y27632 pretreatment of human
eosinophils increased the surface expression of CD11b, as well as
its active conformation in the presence and absence of CCL11.
Similar results with CD11b surface expression were also found
with mouse eosinophils.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Conclusions
Our results suggest that ROCK are playing a negative regulatory role
in degranulation of human and mouse eosinophils and that ROCK’s
inhibitory effect on degranulation is probably by increasing CD11b
expression and activation state.
A91
Purinergic signaling is involved in the beneficial effects of aerobic
exercise in a model of HDM-induced asthma
Rodolfo de Paula Vieira1, Manoel Carneiro Oliveira-Junior1,
Nilsa Regina Damasceno-Rodrigues2, Fernanda Magalhães Arantes-Costa3,
Milton Arruda Martins3, Ana Paula Ligeiro Oliveira1
1
Nove de Julho University Laboratory of Pulmonary and Exercise
Immunology, Sao José dos Campos, Brazil; 2School of Medicine,
University of Sao Paulo Pathology (LIM 59), Sao Paulo, Brazil; 3School of
Medicine, University of Sao Paulo Clinical Medicine (LIM 20), Sao Paulo,
Brazil
Correspondence: Rodolfo de Paula Vieira
World Allergy Organization Journal 2017, 10(Suppl 1):A91
Background
Purinergic signaling has emerged as a central pathway involved in
the asthma pathophysiology, occurring mainly through the accumulation of nucleotides in the extracellular milieu, resulting in activation
of purinergic receptors. On the other side, regular low to moderate
intensity aerobic exercise is shown to reduces asthma phenotype.
Objective
Investigate if the beneficial effects of aerobic exercise occur due to
modulation of purinergic signaling.
Methods
Forty C57Bl/6 mice were equally distributed in Control, Exercise,
house dust mite (HDM) and HDM+Exercise groups. HDM animals received intra-tracheal (days 0, 7, 14, 21, 28, 35, 42) HDM (dermatophagoydes pteronyssinus - 100ug/mouse) and were subjected to low
intensity aerobic treadmill physical training (AT) (for evaluation of
therapeutic effect), from day 17 for 4 weeks, 5x/week, 1hour/session.
Twenty-four hours after the last training session and challenge with
HDM, pulmonary inflammation was assessed through bronchoalveolar lavage (BAL) and histomorphometrical analysis, airway remodeling
(collagen and elastic fibers deposition, mucus production), airway
hyperresponsiveness (AHR) to methacholine (MCh), cytokines levels
in BAL and in re-estimulated lymphnodes, splenocytes and bone
marrow cells. Adenosine triphosphate (ATP) levels in BAL was also
measured. In addition, quantitative analysis of expression of P2X7 by
epithelial cells and by peribronchial leukocytes were done.
Results
The results demonstrated that AT in HDM mice resulted in reduced
number of total cells (p<0.001), eosinophils (p<0.001), neutrophils
(p<0.05), lymphocytes (p<0.05), macrophages (p<0.05) in BAL, in the
number of eosinophils (p<0.001), neutrophils (p<0.01), lymphocytes
(p<0.001) and macrophages (p<0.01) in airways wall. AT also reduced
HDM-induced airway remodeling, as demonstrated by reduced accumulation of collagen fibers (p<0.01), elastic fibers (p<0.01) and mucus
production (p<0.01). AHR was also reduced in HDM+exercised mice
for 6,25 mg/mL MCh (p<0.01), 12,5 mg/mL (p<0.01), 25 mg/mL
(p<0.001) and 50 mg/mL (p<0.01). In addition, the levels of IL-1beta
(p<0.001), IL-4 (<0.001), IL-5 (p<0.001), IL-6 (p<0.001), CXCL-1
(p<0.001), IL-13 (p<0.001), IL-17 (p<0.001), IL-23 (p<0.001), IL-33
(p<0.05) and TNF-alpha (p<0.001) were reduced in HDM+Exercise
mice, while the levels of IL-2 (p<0.05) and IL-10 (p<0.001) were increased in BAL. AE also reduced HDM-induced IGF-1 (p<0.01) and
VEGF (p<0.01) levels in lung homogenates. Furthermore, in restimulated mediastinal lymphnodes, splenocytes and in bone marrow
cells, AE reduced the production of IL-4 (p<0.001), IL-5 (p<0.001) and
IL-13 (p<0.001).
Conclusions
Aerobic exercise reduces asthma phenotype involving reduction of
P2X7 receptor expression and reduction of Th2 cytokines production
by lymphoid organs.
Page 33 of 39
A92
Nasal epithelium injury by chlorination products and other
stressors predicts persistent sensitization to aeroallergens in
young school children
Alfred Bernard, Antonia Sardella, Catherine Voisin
Catholic University of Louvain Toxicology, Brussels, Belgium
Correspondence: Alfred Bernard
World Allergy Organization Journal 2017, 10(Suppl 1):A92
Background
Allergic sensitization during childhood is a highly dynamic process
with a substantial rate of remission. Host or environmental factors influencing this process are largely unknown.
Objective
We tested the hypothesis of a link between aeroallergen sensitization
and airway barrier dysfunction using epithelial biomarkers in nasal
lavage fluid (NALF).
Methods
We conducted a two-year prospective study among 121 school children (mean age, 5.8 years; 64 boys). We measured club cell protein
(CC16), β2-microglobulin (β2-m) and albumin in NALF and specific
IgE to cat dander, pollen or house dust mite (HDM) in nasal mucosa.
Results
At follow-up, there were 26 children with new-onset, 24 with remitted and 16 with persistent sensitization to any aeroallergen. Odds of
persistent sensitization to any aeroallergen increased across baseline
ascending tertiles of urea-adjusted β2-m and albumin and descending tertiles of albumin-or β2-m-adjusted CC16 (P for trend = 0.006,
0.02, 0.044 and 0.006, respectively). Persistent sensitization to HDM
also increased across baseline descending tertiles of raw or ureaadjusted CC16 (both P for trend = 0.007). Such associations were not
seen with the new-onset or remitted aeroallergen sensitization or
with the raw NALF concentrations of urea, albumin or β2-m. House
cleaning with chlorine bleach and regular attendance of chlorinated
pools emerged as the strongest and most consistent predictors of
NALF biomarkers at baseline, being both associated with higher urea
and lower CC16 in NALF.
Conclusions
Early childhood exposure to chlorination products at home or in
swimming pools causes nasal epithelial barrier alterations predicting
persistent aeroallergen sensitization.
A93
Alterations in barrier integrity and inflammatory infiltrate are
present and largely reversed with treatment in eosinophilic
esophagitis
Simon Royce1, Hamish Philpott2, Sanjay Nandurkar3, Francis Thien4,
Peter Gibson2
1
Monash University Medicine, CCS, Melbourne, Australia; 2Monash
University Gastroenterology, CCS, Melbourne, Australia; 3Monash
University Gastroenterology, ECS, Melbourne, Australia; 4Monash
University Respiratory Medicine, Melbourne, Australia
Correspondence: Simon Royce
World Allergy Organization Journal 2017, 10(Suppl 1):A93
Background
Loss of epithelial barrier integrity plays an important role in the
process of allergic sensitization, as well as influencing subsequent
pathological processes including local inflammation and fibrosis.
Objective
Our aim was characterize the inflammatory infiltrate (including IgG
and IgE deposition) and changes in barrier integrity of patients with
eosinophilic esophagitis (EoE) treated with a range of modalities, and
normal controls.
Methods
Immunohistochemical analyses were performed on biopsies from 20
(>18y old) patients with EoE and then given 6wk dietary therapy with
proton pump inhibition (diet-PPI), 18 with PPI-responsive esophageal
eosinophilia (PPI-REE), 10 managed with Budesonide monotherapy
World Allergy Organization Journal 2017, 10(Suppl 1):25
(Bud) and 10 normal controls were analysed (recruited from the Box Hill
and The Alfred Hospitals, Melbourne, Australia).
Results
Patients with EoE had a higher mean eosinophil count in all esophageal regions and the intensity of staining of mast cell tryptase was
also increased except in the mid-esophagus. Expression of IgG and
IgE was increased in all esophageal regions (p=<.05). The expression
of caveolin was lower throughout the esophagus (p=<.05), but
desmoglein was only reduced in the lower esophagus. The mean
eosinophil count fell markedly in the patients treated successfully
(diet-PPI, Bud, PPI-REE) in all esophageal regions (p<.05). Mast cell
tryptase staining intensity decreased with the three treatments (p <.05)
(limited to lower esophagus in Bud, PPI-REE). Tissue IgG fell in response
to diet-PPI in the lower esophagus only (p<.05) but tissue IgE did not
change significantly with any of the treatments. The expression of both
measures of epithelial barrier integrity, caveolin and desmoglein, increased significantly with all treatments (p <.05 all areas, apart from
diet-PPI, limited to the lower and middle esophagus). As per the definition of a positive food antigen challenge, food antigen reintroduction
after the treatment period increased eosinophil and mast cell tryptase,
and decreased barrier markers (all p<.05) but did not alter IgG or IgE.
Conclusions
In conclusion, an inflammatory infiltrate typical of a Th-2 mediated
disease process is present in patients with EoE and those with PPI-REE.
Treatment with budesonide, diet and PPI (for EoE) or PPI alone (PPIREE) all largely resolve the changes associated with eosinophilia. The
inflammatory infiltrate and impairment in barrier integrity as determined by immunohistochemistry is produced by food antigen exposure. The lower esophagus appears particularly important in initiating
inflammation, whilst density of IgG and IgE deposition appear to relate
to the duration of the inflammatory response.
A94
AllergoOncology: the immune microenvironment, in allergy and
cancer, is critically shaped by macrophages not only in humans,
but also in dogs
Rodolfo Bianchini1, Franziska Roth-Walter1, Anna Ohradanova-Repic2,
Gerlinde Hofstetter1, Ina Herrmann3, Maria Isabel Carvalho4,
Karin Hufnagl1, Erika Bajna5, Georg Roth6, Hannes Stockinger2,
Erika Jensen-Jarolim5
1
The Interuniversity Messerli Research Institute; University of Veterinary
Medicine; Medical University of Vienna; University of Vienna Department
of Comparative Medicine, Vienna, Austria; 2Center for Pathophysiology,
Infectiology and Immunology, Medical University of Vienna Institute for
Hygiene and Applied Immunology, Vienna, Austria; 3University of
Veterinary Medicine Clinical Department of Small Animal Internal
Medicine, Vienna, Austria; 4University of Tràs-os-Montes and Alto Douro
Department of Veterinary Science, Vila Real, Portugal; 5Center of
Pathophysiology, Infectiology and Immunology, Medical University
Vienna Department of Pathophysiology and Allergy Research, Vienna,
Austria; 6General Intensive Care and Pain Medicine, Medical University
Vienna Department of Anesthesiology, Vienna, Austria
Correspondence: Erika Jensen-Jarolim
World Allergy Organization Journal 2017, 10(Suppl 1):A94
Background
Almost 10 million people in the world die of cancer, and about 50
million suffer from IgE-mediated allergies every year. Likewise, cancer
is a leading death cause in companion animals, - and they can also
develop allergies. Whereas IgE immunoglobulins are pathognomic in
allergies, the IgG4 class is typical in allergies that have been cured,
and it has only recently been correlated with bad prognosis in cancer. In both diseases the immune system is thus critically involved:
Whereas in allergies it is overreactive against harmless antigens, it is
hyporeactive in cancer through immune tolerance.
Methods
In this project we concentrate on the immunoregulatory function of
human and animal macrophages which in concert with immunoglobulins have a great plasticity of response. The in vitro polarization of macrophages into functional subtypes M1, M2a, -b or -c has been
established for human and - for the first time - canine cell lines, as well
Page 34 of 39
as peripheral blood mononuclear cells from donors, allergic patients or
cancer patients.
Results
When we investigated the immune cells surrounding the tumour mass
in human colon cancer specimens, we found that macrophages were
present not only at a highly density, but also in the vicinity of IgG4 expressing cells. When we investigated in vitro the capacity of macrophages to interact with IgG of different subclasses we found that only
IgG4, but not IgG1 drives macrophages into a non-responsive tolerogenic phenotype. IgG4 also led to an expression of several cytokines
and chemokines such as IL-10, IL-6, TNFa, or CCL1, and converted and
reinforced the M2b-like tolerogenic macrophages.
Conclusions
Our results highlight the similarities between human and animal
macrophage responses in cancer and allergy. The in vitro data based
on cell lines and on blood cells from allergic & cancer patients will
contribute to the understanding of the mechanisms and improve
treatment options and prognosis in animals and humans.
A95
Maternal evaluation knowledge on Epinephrine Auto-injector
usage in Israel
Meital Almog1, Aharon Kessel1, Larisa Apov2
1
Bnai Zion Medical Center Division of Allergy & Clinical Immunology,
Haifa, Israel; 2Bnai Zion Medical Center Division of Allergy & Clinical
Immunology, Haifa, Israel
Correspondence: Meital Almog
World Allergy Organization Journal 2017, 10(Suppl 1):A95
Background
Worldwide, there has been an increase of potentially life-threatening
food allergy events. In Israeli children, anaphylaxis occurs most frequently after ingestion of milk, sesame seeds, peanuts and tree nuts.
Correct use of the Epinephrine auto-injector is essential in order to
prevent death from anaphylaxis.
Objective
The aim of this study was to explore the knowledge and factors that
influence caregiver’s use of the Epinephrine among children with
food allergy.
Methods
The study population comprised 128 children up to 18 years of age
with known food allergy. Each caregiver was interviewed by a trained
physician who then completed a computer-based questionnaire including parameter as demographic attributes, the caregiver’s years of
education, date of their last visit to the allergy clinic, a previous
anaphylactic event. The clinical indications and the operation of the
Epinephrine auto-injector as recommended by the Israeli Association of
Allergy and Clinical Immunology were also assessed and scored.
Results
One hundred twenty-eight maternal care givers and 52 paternal care
givers participated in the study. The maternal caregiver Epinephrine
auto-injector usage and indication competency scores were significantly higher than the paternal caregiver scores, (69±30.7 versus
56.57±35.55, p=0.01, 86.15±16.03 versus 80±17.54, p=0.03, respectively). Forty-two percent of the maternal caregivers demonstrated
proficiency of the Epinephrine manual usage (3 out of 3 correct answers), 20% had a functional Epinephrine using (2 out of 3 essential
parameters to operate the Epinephrine device), and 37.5% of the
maternal care givers had a minimal knowledge which didn’t allow
them to operate the Epinephrine device functionally. A statistically negative correlation was found between the maternal caregivers Epinephrine usage score and the date of their last visit at
the allergy clinic (r=-0.66, p≤0.01). The mothers of those children
who experienced an anaphylactic event in the past had a significantly higher Epinephrine usage score compared to mothers of
children who didn’t experienced such an event (15/26 vs. 28/78,
p= 0.04). No correlation was found between the maternal Epinephrine usage score to maternal education, age of the child,
type of food allergen. Moreover, no correlation was found between maternal caregivers indication score and the date of their
last visit to the allergy clinic.
World Allergy Organization Journal 2017, 10(Suppl 1):25
Conclusions
The optimal use of Epinephrine auto-injector is related to the time
that elapsed from a patient’s last allergy clinic visit. Periodic refreshing training, every 4-6 months, for the caregiver, on the indications
and manual use of the Epinephrine device should be undertaken to
ameliorate food allergy anaphylaxis management.
A96
Omalizumab in desensitization food techniques
Carlos Sanchez Salguero, Alvaro Sanchez Chacon
University Hospital Puerto Real Pediatric, Puerto Real (Cadiz), Spain
Correspondence: Carlos Sanchez Salguero
World Allergy Organization Journal 2017, 10(Suppl 1):A96
Background
According to the Alergologica 2005 study, milk and egg are the
foods most often implicated in the diagnosis of allergy in patients
under 5 years of age. The estimated prevalence of CMPA in the first
year of life is 1.6-3%.
Until a few years, the only treatment accepted for this patients were
eliminated these food of the diet, but actually we have a new therapeutical way, the Specific Oral Tolerance Induction (SOTI).
Methods
During the period 2010-2016, we had treated with SOTI method a
total of 70 childs: 52 with cow’s milk allergy (CMA) and 18 with egg
allergy (EgA).
The SOTI protocol in CMA: a first phase with a dilution of 1 ml of
cow’s milk with 99 ml of juice, the patient drunk each 60 min 1-2-4-8
ml, after a new dilution 1/10 with the dosage of 1,6-3,2-6-12 ml and
finally the first day we finished with 2,5 ml of whole milk (total 4,8
ml). After, each week, we increased the dosage of whole milk: 10-2040-80-140-250 ml.
Group of CMA the values of the casein proteins were 3,5-500 IU/ml
and in this group we had a subgroup of 12 childs they were presented anaphylaxis. The SOTI protocol in EgA: capsules with doses of
ovomucoid: 4-20-50-100-225-450-900-1800-3600 mg. The first six
doses are capsule with the same dose per day during each week, the
last three doses each 3 days and finished with an oral provocation
with a omelette.
Group of EgA the values of ovomucoid were 5-100 IU/ml, and also a
subgroup of 5 childs with anapylaxis. All the patient with anaphylaxis
were treated with Omalizumab 300 mg per month, three months before the new desensitization, during all the time that lasted the second
desensitization and three months after finished the SOTI protocol.
Results
All patients underwent treatment with Omalizumab got both milk
and egg desensitization protocol end to end and now tolerate 250
ml of milk a day and 3 eggs a week respective form.
Conclusion
Omalizumab has been useful introducing oral immunotherapy in foodallergic patients. A pilot study in 11 children with cow’s milk allergy
showed the benefit of pretreatment with omalizumab from 9 weeks
before and during a combined two phases. In summary, we demonstrated that omalizumab treatment combined with oral milk and egg
desensitization in children with clinical anaphylactic reactions permitted rapid milk and egg dose escalation in the majority of subjects.
A97
Climatic conditions, food allergies
Abbos Nazarov1, Shaxbos Ergashev2
1
Tashkent Medical Academy Allergology, Tashkent, Uzbekistan; 2Medstar
Biology, Qarshi, Uzbekistan
Correspondence: Abbos Nazarov
World Allergy Organization Journal 2017, 10(Suppl 1):A97
Page 35 of 39
Background
Currently, food allergy, that is, cooking complicated and widespread intolerance of separate parameters sets. The development of allergies in
the present system of food products, artificial additives, plant cultivation and storage of chemicals used in a variety of different types of
drinking lead to the emergence of new allergens.
Objective
Patients to identify the types of food allergy and its meetings in accordance with the climatic conditions
Methods
Nutrition 60% of patients with diseases of the emergence of allergies,
allergic history, 20% of allergy symptoms and the presence of genetic susceptibility to other members of a special kind of plays and
plays, especially in patients with allergic rhinitis, seasonal or permanent type observed. In this way, members of diseases of the digestive
diseases, lack of digestive enzymes intestinal disbacteriosis lead to
unhealthy lifestyle and diet. RIIAM monitoring patients for surveillance and investigation results showed that Nutriv 25% of the cases,
the immune mechanisms associated with allergies. 10% of patients
with disease on the basis of immediate type allergic reactions often
cause blisters and angioedema from 13% to 45% of the cases. Nutriv
allergy is more often associated with skin changes, 60% of the erythematous vesicular dermatitis, food allergy can cause bronchial
asthma adults, 5% of patients, and other allergens as well as 22% of
patients with 10% of the cases, other kinds of toxicodermia.
Results
According to allergic patients with a history of food to 60% of honey,
walnuts 50%, 70% and 30% of the meat and milk of various colored
drinks, 18% vegetables, 25% fruits, 35% quziqorin, 33% of eggs, 12%
of fish products 3% of allergic reactions observed grasses.
Conclusions
Food allergy prone patients that must be hypoallergenic diet.
A98
The efficiency of the immunomodulatory therapy in treatment of
immunocompromised girls with recurrent chronic non-specific
vulvovaginitis associated with atopic dermatitis
Irina Nesterova, Svetlana Kovaleva, Galina Chudilova, Ludmila Lomtatidze
The Peoples’ Friendship University of Russia, Department of Allergology
and Immunology, Moscow, Russia
Correspondence: Irina Nesterova
World Allergy Organization Journal 2017, 10(Suppl 1):A98
Background
The treatment of recurrent chronic non-specific vulvovaginitis (CNSV)
associated with atopic dermatitis (AD) in girls in age from 2 to 4
years is very difficult problem because methods of the traditional
therapy are often ineffective. The development of new approaches
for the treatment of these patients are the actual problem.
Objective
We had conducted the clinical and immunological study of 25 girls
in age from 2 to 4 years, who were at the acute stage of recurrent
CNSV. Ten of these girls had AD and clinical features of immunodeficiency (ID): recurrent acute respiratory viral infections (ARVI) - more
than 8 times per year and frequent exacerbations of CNSV.
Methods
Different subpopulation of T-, B-lymphocytes, EKK, phagocytic, microbicidal functions of neutrophils (NG, the serum IgE, IgA, IgM, IgG,
were detected. The control group consisted of 12 healthy girls.
Results
It was found, that at the acute stage of recurrent CNSV and AD in ID’
girls the decrease of the absolute number of CD3+CD8+ (0,9 [0,83;
1,02] vs. 1,38 [0,91; 1,63] in the control, p<0,05), CD3-CD16+CD56+
(0,33 [0,24; 0,37] vs. 0,43 [0,31; 0,48] in the control, (p<0,05), CD3-
World Allergy Organization Journal 2017, 10(Suppl 1):25
CD19+ (0,62 [0,52; 0,71] vs. 1,01 [0,95; 1,24] in the control, p<0,05)
lymphocytes, deficiency of serum IgA (p<0,05), IgG (p<0,05) and IgM
(p<0,05), defects of phagocytic (44,86 [39; 51]% vs. 61,08 [53,8;
68,8]% in the control, p<0,05) and microbicidal activities of NG
(p<0,05) had occurred. It was revealed that 63% of girls suffered from
IgE independent, and 37% from IgE dependent food allergy with
clinical manifestations of atopic dermatitis. The level of IgE amounted
112,51 [96,4; 172,2] IU/ml against 26,83[10,4; 38,3] IU/ml in control
(p<0,05). The program of the prolonging combine immunotherapy
(PPCI) was created and was used in the complex of the traditional
therapy. The PPCI included local (gel) and systemic (suppositories)
treatment with recombinant interferon α2b (viferon) and glucosaminilmuramildipeptide (likopid). It was obtained positive clinical effects
using PPCI: the severity of the inflammatory process and the frequency, the duration of exacerbations of CNSV was decreased on 3-5
days and the significant reduction of frequency of ARVI and the regression of manifestations of the atopic dermatitis was obtained.
Conclusions
The peculiarities of the immunopathogenesis of CNSV and AD in ID
girls are causes of persistent recurrence of CNSV and it resistance
to the tradinional therapy.The use of PPCI had demonstrated the
good protective and positive clinical effect in ID girls with recurrent
CNSV, AD.
A99
START: Susceptibility to food allergies in a registry of twins
Sarah De Schryver1, Alizee Dery2, Ann Clarke3, Kari Nadeau4,
Laurie Harada5, Kimberly Weatherall6, Celia Greenwood7, Denise Daley8,
Yuka Asai9, Moshe Ben-Shoshan1
1
McGill University Pediatric Allergy and Immunology, Montreal, Canada;
2
McGill University Clinical Epidemiology, Montreal, Canada; 3University of
Calgary Rheumatology, Calgary, Canada; 4Stanford University Pediatric
Allergy, Immunology and Rheumatology, Palo Alto, CA, USA;
5
Anaphylaxis Canada, Toronto, Canada; 6Multiple Births Canada, Lefroy,
Canada; 7McGill University Oncology, Epidemiology, Biostatistics,
Occupational Health and Human Genetics, Montreal, Canada; 8University
of British Columbia Medicine, Vancouver, Canada; 9Queen’s University
Dermatology, Kingston, Canada
Correspondence: Moshe Ben-Shoshan
World Allergy Organization Journal 2017, 10(Suppl 1):A99
Background
To compare proband-concordance [(twice number concordant pairs)/
(twice number of concordant pairs+ number of non-concordant pairs)]
in MZ (monozygotic) and DZ (dizygotic) twins with food allergy.
Methods
Twins, with at least one member with IgE-mediated food allergy,
were recruited from Anaphylaxis Canada, Multiple-Births-Canada, a
US registry and the Montreal Children’s Hospital allergy clinics. Diagnosis of food allergy was based on a convincing clinical history AND
a skin prick test or allergen-specific IgE level beyond previously published thresholds or a positive food challenge.
Results
Among 17 pairs of DZ and 15 pairs of MZ twins with peanut allergy,
the concordance rate was 0.59 (95% CI 0.39, 0.77) and 0.52 (95% CI,
0.29, 0.75) respectively [difference=0.07 (95% CI 0.06, 0.40)].
Among 9 pairs of DZ twins and 12 pairs of MZ twins with cashew/pistachio allergy, the concordance-rate was 0.57 (95% CI 0.29, 0.81) and 0.50
(95% CI 0.27, 0.72) respectively [difference=0.07 (95% CI 0.02, 0.75)].
Among 4 pairs of DZ and 9 pairs of MZ twins with pecan/walnut allergy, the concordance rate was 0.57 (95% CI, 0.20, 0.89) and 0.54
(95% CI 0.25, 0.82) respectively [difference=0.03 (95% CI, -0.47, 0.52].
Page 36 of 39
Among 6 pairs of DZ and 8 pairs of MZ twins with hazelnut allergy
the concordance-rate was 0.33 (95% CI 0.06, 0.76) and 0.2 (95% CI
0.03, 0.55) respectively [difference=0.13 (95% CI -0.45, 0.72)].
Among 4 pairs of DZ and 5 pairs of MZ twins with almond allergy
the concordance rate was 0.5 (95% CI 0.15, 0.84) and 0.33 (95% CI
0.05, 0.75) respectively [difference=0.17 (95% CI -0.62, 0.95)].
Among 10 pairs of DZ and 8 pairs of MZ twins with egg allergy the
concordance-rate was 0.53 (95% CI 0.27, 0.77) and 0.22 (95% CI 0.03,
0.59) respectively [difference= 0.31 (95% CI 0.14, 0.77)].
Conclusions
For peanut, tree-nuts and egg allergy, the concordance among DZ
twins was higher compared to MZ twins. For other foods assessed
such as milk and shellfish, the difference was not conclusive. It is
likely that non-genetic factors play a major role in the development
of food allergy. However, our small sample size precludes definitive
conclusions.
A100
HIV and HCV co-infection: the order of HIV and HCV acquisition
and liver fibrosis
Irina Balmasova, Elena Malova
Peoples’ Friendship University of Russia Allergology & Immunology,
Moscow, Russia
Correspondence: Irina Balmasova
World Allergy Organization Journal 2017, 10(Suppl 1):A100
Background
Coinfection with human immunodeficiency virus (HIV) and hepatitis
C virus (HCV) is one of the most common pathological conditions
worldwide. Liver disease is a major cause of death for these patients.
We attempted to determine whether the order of HIV and HCV acquisition is important for the progression of liver fibrosis.
Objective
Four hundred twenty-five patients with verified HIV/HCV coinfection
were followed for 1 year. The order of HIV and HCV acquisition was
identified in 106 patients: in 61 patients HCV was acquired after
established HIV infection (i.e., the first pathogen was HIV) while in 45
patients HIV was acquired after established HCV infection (i.e., the
first pathogen was HCV).
Methods
The patients underwent transient elastometry to measure liver stiffness, viral load monitoring was performed by real-time PCR, CD3
+CD4+ cell count was measured by flow cytometry. SPSS was used
for statistical analyses.
Results
Among 106 patients with HIV/HCV coinfection, progressive liver fibrosis
was diagnosed in 21%, stable liver fibrosis in 48%, regressive liver fibrosis in 31%. It was found that the order of HIV and HCV acquisition has a
significant effect on the development of progressive liver fibrosis. It
was demonstrated that, when HIV was the first pathogen, progressive
liver fibrosis occurred in 27% of patients. When HCV was the first
pathogen, progressive liver fibrosis occurred in 13% of patients only.
the highest (30%) prevalence of progressive fibrosis was observed in
patients younger than 35 who acquired HIV as the first pathogen. In
high-risk patients, HIV viral load was significantly higher both by the
prevalence and absolute value as compared with minimum-risk patients. HCV viral load demonstrated no significant difference between
the groups. CD3+CD4+ cell count in the high-risk group was less than
in the control group.
Conclusions
The order of HIV and HCV acquisition has a significant effect on the
progression of liver fibrosis in co-infected patients. In was shown that
in patients younger than 35, the order of HIV and HCV acquisition has a
World Allergy Organization Journal 2017, 10(Suppl 1):25
crucial role in this process. In particular, the patients who acquired HIV
as the first pathogen are at higher risk of progressive liver fibrosis and
have higher HIV viral load and lower CD3+CD4+ cell count.
A101
The hyper-allergenic isoform Bet v 1a of the major birch pollen
allergen displays reduced allergenic potential after binding of
retinoic acid
Karin Hufnagl1, Stefanie Wagner1, Luis F. Pacios2, Michael Wallner3,
Markus Wiederstein3, Gerlinde Hofstetter1, Franziska Roth-Walter1,
Erika Jensen-Jarolim4
1
The interuniversity Messerli Research Institute of the University of
Veterinary Medicine, the Medical University and the University of Vienna
Comparative Medicine, Vienna, Austria; 2ETSI Montes, Technical
University of Madrid Department of Natural Systems and Resources,
Madrid, Spain; 3University of Salzburg Department of Molecular Biology,
Salzburg, Austria; 4Center of Pathophysiology, Infectiology and
Immunology, Medical University Vienna Department of Pathophysiology
and Allergy Research, Vienna, Austria
Correspondence: Erika Jensen-Jarolim
World Allergy Organization Journal 2017, 10(Suppl 1):A101
Background
Bet v 1a (Bet v 1.0101) represents the most typical allergen prototype. Its isoform Bet v 1d (Bet v 1.0102), however, is a hypoallergen
despite of being structurally highly homologous. We hypothesized
that the ligand-binding capacity of these lipocalin-like molecules
could discriminate the level of allergenicity.
Objective
We investigated thus whether the active vitamin A metabolite retinoic acid (RA) can bind to Bet v 1a or Bet v 1d, and how this affects
their allergenicity in vitro.
Methods
Binding of RA to Bet v 1 isoforms was determined by in silico docking analyses and ANS displacement assay. We measured antigenspecific IgE by ELISA and ß-hexosaminidase release from humanized
rat basophil leukemia cells (RBL) in sera from birch pollen allergics
using the “empty” birch pollen allergens (apo-Bet v 1a/d) or Bet v 1
isoforms loaded with RA (holo-Bet v 1a/d).
Results
In silico calculations predicted a high affinity energy (-8.7 kcal/mol) of
RA to both Bet v 1a and Bet v 1d, with an estimated dissociation constant (KD) of 0.364 μM. In vitro RA was able to dose-dependently displace ANS from both isoforms to a similar extent. In ELISA holo-Bet v 1a
loaded with RA showed significantly reduced binding of serum IgE
compared to the empty apo-Bet v 1a. In agreement, holo-Bet v 1a produced significantly less mediator release from RBL cells. In contrast,
both apo- and holo- Bet v 1d displayed much lower IgE binding capacity and preliminary data indicate that RA loading of Bet v 1d has no
effect on RBL releasability.
Conclusions
RA loaded into the intramolecular pocket of Bet v 1a reduces its
IgE-binding and IgE-crosslinking potential in vitro. Our data may
have implications for improving the safety of birch pollen allergen immunotherapy.
This work was supported by grant SFB F4606-B28 of the Austrian Science Fund FWF.
A102
Effect of immunotherapy autological activated T-cells on the
parameters of the immune status in patients with bronchial
asthma
Anna E. Tevs1, Ekaterina A. Pashkina2, Marina I. Leonova1,
Vera M. Nepomnyaschikh1, Darya V. Demina1, Vladimir A. Kozlov2,
Elena A. Blinova2
1
Clinic of Immunopathology RIFCI Allergological Department,
Novosibirsk, Russia; 2RIFCI Laboratory of Clinical Immunopathology,
Novosibirsk, Russia
Correspondence: Anna E. Tevs
World Allergy Organization Journal 2017, 10(Suppl 1):A102
Page 37 of 39
Background
Lack of effectiveness of standard treatment protocols for patients
with bronchial asthma served as the basis for the search new directions of systemic therapy of diseases affecting the pathogenetic links.
One of such area is a cellular immunotherapy aimed to activation
anti-ergotypic response realized in response to activated T cells, for
regulation of allergic inflammation.
Methods
The study included 10 patients with asthma, atopic and mixed etiology, moderate severity, and aged 23 to 49 years. Patients were
treated at the allergological department on Clinic immunopathology
RIFCI, with a basic therapy during the 12 weeks prior to entry to the
study. In the group, total IgE level estimated 1115 IU / ml, the rate of
FEV1 - 69%. After obtaining informed consent, patients were administered subcutaneously autologous activated T-cells with multiplicity
once a week 4 injections, and then once a month 6 injections, on
the background of basic asthma therapy (10 injections in total). Preparation protocol for autologous activated T-lymphocytes included activation of mononuclear cell from peripheral blood by anti-CD3
antibodies (1mkg/ml) and IL-2 (100IU/ml). It was used 30 million cells
per dose. Evaluation of the immune status was carried out in the dynamics of cellular immunotherapy (before and on 5th injection).
Results
There was a decrease of total IgE levels up to 257 IU/mL, as well as
rising of FEV1 to 88%. Positive effects of T-cell immunotherapy can
be expressed in enhancing natural regulation mechanisms on activated T-cells: reducing cell proliferation, changing the products of
Th1 and Th2 cytokines and immunoglobulins, especially IgE. On the
5th injection, patients showed a slight increase in the number of
CD8+ T-cells (27% to 35%), the number of CD19+ B-cells decreased
from 14% to 10%. Anti-ergotypic effectors are cytotoxic lymphocytes
(CD8), thus increasing their level during immunotherapy indicates
the induction of anti-ergotypic response. It is known that Th1-type
cytokines act on B-cells, leading to reduction in the number of
activated CD23+ B-lymphocytes with low affinity receptor IgE (FceRII).
Therefore, reducing the number of CD19+ B cells in the process of Tcell vaccination may occur by reducing the number of CD23+ Blymphocytes. There was no effect of immunotherapy by activated T
cells on the amount of CD4+ and NK-cells.
Conclusions
Thus, in the course of immunotherapy with autologous activated T
cells in asthmatic patients there was an increase of anti-ergotypic effector cells that clinically manifested in the reduction of total serum
IgE and improving respiratory function.
A103
Virus-associated allergic rhinitis as a phenotype and its clinicimmunological specifics
Nataly Tataurshchikova, Baigalmaa Sangidorj, Anna Ronzhina
Peoples Allergology and Immunology, Moscow, Russia
Correspondence: Nataly Tataurshchikova
World Allergy Organization Journal 2017, 10(Suppl 1):A103
Background
Persistent prevalence increase in torpid to traditional treatment
schemes forms of allergic rhinitis and worsening clinical symptomatics during the last years is connected to specifics of mucosal immunity functioning among patients. Mucosal barrier functioning
status among patients, suffering from allergic rhinitis, whose comorbid status is herpetic-viral infection, are the basis of clinical phenotype – virus-associated allergic rhinitis. Nasal mucosal among
patients with herpetic-viral infection loses immunological tolerance
to allergens, infectious pathogens, thus becoming a permanent palindromic inflammation process area.
Methods
During an open prospective research a clinic-immunological survey
was conducted among 63 patients (male and female both) aged 18 to
53, suffering from perennial allergic rhinitis for 3 to 10 years. All the patients received and standard basic therapy according to indications.
Glucocorticosteroids were excluded 1 month before survey start. 2
World Allergy Organization Journal 2017, 10(Suppl 1):25
groups of patients were formed as a result of clinic-immunological
survey – main group with perennial virus-associated allergic rhinitis
(HSV infections and/or CMV infections) - 42 patients and control group
- 21 patient with perennial allergic rhinitis. Alongside with standard
clinic-immunological survey a key specific cytokine content analysis
was made using immunoenzymic method (proinflammatory - (α-TNF –
tumor necrosis factor, IL-8, γ – INF) and antiphlogistic IL-4) of serum
and local fractures. Material blood serum, taken fasting in the morning
from ulnar vein and nasal lavage.
Results
Clinic-immunological changes analysis among group of patients, suffering from virus-associated allergic rhinitis showed the following
pathognomonic evidence. Clinic specifics – frequent ARD (more than
8 times a year, chronic ENT-pathology, herpetic infection. Among 31
patient (73,8%) an increase of IL-8 content in nasal lavage was stated.
Among 8 patients (19%) a sharp increase of α-TNF was stated,
accompanied by high herpetic infection titles (HSV infection and/or
CMV infection).
While investigating local cytokine status among patients, suffering
from perennial allergic rhinitis both for main and control groups an
increase in IL-4 level in nasal secret was stated, alongside with nonsignificant changes in blood serum. All the patients had multidirectional changes in γ interferone content for both serum and local fractures that shows a typical cytokine profile of an allergic rhinitis. No
reliable distinctions were stated among groups.
Conclusions
Presence of herpetic-viral infection among patients, suffering from allergic rhinitis leads to nasal mucosal inflammatory process specifics
and forms an allergic rhinitis clinical phenotype – virus-associated allergic rhinitis.
A104
Clinico-immunological and aeropolinologic monitoring in patients
with respiratory allergies
Revaz Sepiashvili1, Tatiana Slavyanskaya1, Manana Chikhladze2
1
Peoples’ Friendship University of Russia Allergy and Immunology,
Moscow, Russia; 2National Institute of Allergology, Asthma and Clinical
Immunology of Georgian Academy of Sciences Immunology and
Allergy, Tskhaltubo, Georgia
Correspondence: Revaz Sepiashvili
World Allergy Organization Journal 2017, 10(Suppl 1):A104
Clinico-epidemiologic study proves that the Western Georgia is characterized by frequency and variety of allergic diseases, especially respiratory allergies, determined by sharp features of eco-geographical
climate. Due to the above-mentioned, at this stage the study aimed to
establish the correlation between the concentrations of phadiatop,
general IgE and specific aeropollutants, taking into consideration the
annual calendar of plants blossoming for the reality of Imereti region.
In the study were involved 69 patients, 5-14 of ages, with allergic
rhinitis and asthma (34 boys and 35 women)
The study covered the following allegro-diagnostic stages:I stage For precise verification of the allergen, patient’s blood serum was examined on a particular specific-IgE antibodies by modern automated
system - “ImmunoCAP 100” (PHADIA). II stage - Monitoring of the
concentration of aeropoluments was conducted by using aeropolinometer “Burkard Trap” (Great Britain).
The analysis of the laboratory results revealed that the studied patients
had high titers of common IgE, which amounted to 380kU/I (Norm 60200kU/I) on average, while the concentration of the phadiatop was
above average (norm - negative). In parallel, the data obtained through
the aeropolinometris- “Burkard Trap” were specified in line with the annual calendar of distribution of aeroallergens, reflecting the concentrations of blossoming tree-plants and atmospheric aerosolsin air for the
Page 38 of 39
reality of Imereti region. From January to April, 2016, a high concentration of aeropollutants which are characterized with high allergenization
and at the same time widely spread in this region, was revealed. It
should be emphasized that especially high concentrations were detected in alder, birch-tree and nut-grove. Among the widely spread
aeropollutants of low allergenization were distinguished poplar, elm,
willow and plane trees. Every aforementioned diagnostic marker highly
correlated with each other. Increased concentrations of Immuno CAP/
Phadiatop in the blood as well as the high levels of IgE prove existence
of atopic allergy to the inhaled allergens. Aeropollinometer “Burkard
Trap” was used to detect he concentrations of various plant dust and
surrounding atmospheric aeropollutants at a given period of time and
to specify annual calendar of distribution of aeroallergens developed
by us for the reality of Imereti region, respectively. The strong correlation between the above mentioned diagnostic markers indicates to
their importance to the respiratory allergies.
A105
The role of B cells in rhinovirus infection
Oliver F. Wirz1, Willem van de Veen1, David Mirer1, Hideaki Morita2,
Can Altunbulakli1, Sebastian L. Johnston3, Nicholas Glanville3,
Nikolaos G. Papadopoulos4, Cezmi A. Akdis1, Mübeccel Akdis1
1
University of Zurich Swiss Institute of Allergy and Asthma Research
(SIAF), Davos Platz, Switzerland; 2University of Tokyo National Research
Institute for Child Health and Development, Tokyo, Japan; 3Imperial
College London Airway Disease Infection Section, National Heart and
Lung Institute, London, United Kingdom; 4University of Manchester
Division of Infection, Immunity and Respiratory Medicine, Manchester,
United Kingdom
Correspondence: Oliver F. Wirz
World Allergy Organization Journal 2017, 10(Suppl 1):A105
Background
Rhinoviruses (RV) play a major role in asthma exacerbations. Effects of
RV on many cell types have already been described including epithelial
cells and lymphocytes, such as CD4+ T cells. However, not much is
known about the interaction of rhinovirus with B lymphocytes.
Objective
The aim of this study was to investigate the role of B cells during
rhinovirus infection.
Methods
B cells were sorted using fluorescent-activated cell sorting. Viral RNA
was measured in these cells using qPCR. Antibodies produced by B
cells were measured using ELISA and multiplex assays.
Results
Peripheral blood mononuclear cells (PBMC) from non-allergic individuals were stimulated with RV16. A virus dose-related cellular proliferation was observed, which was particularly confined to B lymphocytes.
Proliferation was prevented by UV-irradiation of the virus. Blocking the
surface receptor for RV16 (ICAM-1) leads to reduced cell proliferation.
Blocking the endosomal Toll-like receptors (TLR) 3, 7 and 8 reduced the
proliferation and viability of the B cells. Using multiplex assays, we measured all antibody subclasses produced by B cells during rhinovirus
stimulation. We identified a change in antibody production towards elevated IgM, when cells were stimulated with rhinovirus. Positive (+)
and negative (-) strands of viral RNA of RV16 were detected by quantitative PCR. Virus load stayed constant in the B lymphocyte compartment over a period of seven days, while it decreased in PBMC.
Conclusions
This study shows for the first time that B cells can be infected with
RV by using ICAM-1 and induce proliferation through TLRs 3,7, and 8.
We found both (+) and (-) viral RNA strands, suggesting that there is
not only RV inside or attached to the cells, but also that RV is replicating in B cells. RV can be detected inside the B cells already within
World Allergy Organization Journal 2017, 10(Suppl 1):25
one day after infection. Unlike PBMC, the viral load stays mostly constant over an extended period of cell culture in B cells. Therefore, the
data suggest that B cells could be a natural reservoir of RV.
A106
Randomized, double-blind, placebo-controlled trial of recombinant
human C1 inhibitor for prophylaxis of hereditary angioedema
attacks
Avner Reshef1, Marc Riedl2, Vesna Grivcheva Panovska3, Dumitru Moldovan4,
James Baker5, William H. Yang6, Sladjana Andrejevic7, Richard F. Lockey8,
Roman Hakl9, Shmuel Kivity10, Luca Bellizzi11, Joseph R. Harper12,
Anurag Relan11, Marco Cicardi13
1
University of Tel Aviv Sheba Medical Center, Tel-Hashomer, Israel;
2
University of California, San Diego Department of Medicine, La Jolla, CA,
United States; 3Medical University of Skopje PHU Clinic for Dermatology,
Skopje, Macedonia; 4 Mures County Hospital University of Medicine and
Pharmacy, Tirgu Mures, Romania; 5Baker Allergy Asthma Dermatology
Departments of Allergy and Asthma, Lake Oswego, CA, United States;
6
Ottawa Allergy Research Corporation/University of Ottawa Medical
School Division of General Internal Medicine, Department of Medicine,
Ottawa, Canada; 7 Clinical Center of Serbia Clinical Center, Belgrade,
Serbia; 8University of South Florida Morsani College of Medicine Division
of Allergy and Immunology, Department of Internal Medicine, Tampa,
FL, United States; 9St. Anne’s University Medical Department, Brno, Czech
Republic; 10The Tel Aviv Medical Center, Sackler Medical School The
Allergy and Immunology Unit, Tel Aviv, Israel; 11Pharming Technologies
BV Department of Clinical Research and Medical Affairs, Leiden, The
Netherlands; 12Salix Pharmaceuticals Department of Medical Affairs,
Raleigh, NC, United States; 13Universita degli Studi di Milano Department
of Internal Medicine, Milan, Italy
Correspondence: Avner Reshef
World Allergy Organization Journal 2017, 10(Suppl 1):A106
Background
Recombinant human C1 inhibitor (rhC1INH) has been shown to effectively treat acute attacks of hereditary angioedema (HAE) and is currently
approved as on-demand therapy in several countries. Additionally, prevention of HAE attacks by rhC1INH has been demonstrated in a previous
open-label study.
Objective
To evaluate the efficacy and safety of rhC1INH as prophylaxis against
acute HAE attacks in adolescents and adults with HAE and frequent
attacks.
Page 39 of 39
Methods
In this phase 2, double-blind, 3-period crossover study, patients
(≥13 years of age) with functional C1INH levels <50% of normal
and history of ≥4 HAE attacks during the preceding 3 months received 1 of 3 treatments in 3 periods: intravenous rhC1INH 50
IU/kg (max, 4200 IU) once weekly, twice weekly, and placebo.
Each treatment was administered for 4 weeks, with a 1-week separation (wash-out) between treatments. All patients received each
of the dosing regimens as part of the crossover design of the
study. Symptoms of each HAE attack were recorded daily. The
primary endpoint was the number of HAE attacks per 4-week
treatment phase. The secondary endpoint was the percentage of
patients who had a clinical response (≥50% reduction in number
of attacks from treatment with placebo to treatment with
rhC1INH). Safety assessments included reports of adverse events
[AEs] and immunogenicity.
Results
Of the 35 patients enrolled, 32 (91.4%) were randomized to
treatment and included in the intent-to-treat population (all
randomized patients). Mean patient age (standard deviation)
was 45.9 (14.5) years, and most patients were female (81.3%).
The mean number of HAE attacks was significantly reduced with
rhC1INH twice weekly (2.7 attacks, P < 0.0001) and once weekly
(4.4 attacks, P = 0.0004) compared with placebo (7.2 attacks).
The percentage of patients who had a ≥50% reduction in number of HAE attacks was greater with rhC1INH twice weekly
(74.2%; 95% CI, 57-86) than rhC1INH once weekly (41.9%; 95%
CI, 26-59). The most commonly reported AEs were headache
(17.2% with twice weekly rhC1INH, 6.9% with once weekly
rhC1INH, 0% with placebo), nasopharyngitis (0%, 10.3%, 7.1%),
and anxiety (0% 6.9%, and 0%). No thrombotic or thromboembolic events, drug hypersensitivity or anaphylactic reactions,
or neutralizing antibodies were observed, and no patients withdrew because of AEs.
Conclusion
rhC1INH provided significant and clinically relevant reductions in
HAE attack frequency and was well-tolerated. Data support the continued development of rhC1INH for HAE prophylaxis.
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