Pulmonary Research

Lung cancer or also known as carcinoma of the lung or pulmonary carcinoma, is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung.

If left untreated, this growth can spread beyond the lung by process of metastasis into nearby tissue or other parts of the body.

Most cancers that start in the lung, known as primary lung cancers, are carcinomas that derive from epithelial cells. The main primary types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.

To examine effects of a rowing exercise regimen versus a chest physical therapy program on pulmonary function in children with Down syndrome. Methods: Twenty-nine participants of both sexes, between 8 to 12 years of age, participated in this study. They were assigned randomly into 2 study groups. The first group (A) received a chest physical therapy program, while the second group (B) received an aerobic exercise regimen using a rowing ergometer. Vital capacity, forced vital capacity, forced expiratory volume after 1 second, and peak expiratory flow rate were measured before and after 12 successive weeks of treatment. Results: Significant improvements in all measured variables were found posttreatment in both study groups. No significant difference between the 2 groups was found posttreatment. Conclusion: Rowing exercise could be effective in improving pulmonary functions in children with Down syndrome. (Pediatr Phys Ther 2014;26:437-445)

Background: There is an urgent need to develop new outcome measures for respiratory therapy to evaluate its effectiveness. Added sounds generated from the lungs (crackles and wheezes), can now be quantified and characterized objectively with computer technology. This is the first reported study designed to assess any change in lung crackles before and after a single session of airway clearance therapy.
Methods: Twenty-three stable bronchiectasis patients were recruited from UK out-patient clinics and treated with a single session of airway clearance therapy using the active cycle of breathing technique. Sound recordings were made before and after the session at seven anatomical chest locations. Computerized lung sound analysis was used to measure crackle parameters (two cycle deflection width (2CD), and crackle number per breath cycle (nBC)). Perceived breathlessness, lung function and oxygen saturation data were also recorded.
Results: Crackle mean 2CD and mean nBC increased post intervention. Sixteen participants (70%) showed a statistically significant difference in mean crackle 2CD before and after the session at ≥1 chest location. Thirteen (57%) participants had a difference between mean crackle 2CD before and after the intervention greater than one Smallest Real Difference (mean SRD = 2.23ms) at ≥1 chest location. Differences in mean crackle nBC before and after the intervention did not exceed the SRD (mean SRD =32 crackles per breath cycle) in any participant. Perceived breathlessness was significantly reduced post intervention; no significant changes were observed in either lung function or oxygen saturation.
Conclusions: Crackle duration (2CD) was found to change after a single session of airway clearance therapy and shows promise as a new outcome measure for respiratory therapy interventions.

Given the lack of knowledge of the etiology, pathogenesis and natural history of
IPF, it is perhaps not surprising that that there is a lack of high quality evidence
for the 'standard' treatments currently in use. In such a scenario the ideal therapy
for IPF is still awaited. The present article reviews the potential role of
doxycycline as a novel therapeutic option in the treatment of IPF substantiated by
results of relevant studies on doxycycline. The Matrix metalloproteinases (MMP)
inhibitor property of doxycycline may help it gain its role in IPF in years to come.

Examination of the thoracic rib and vertebral anatomy of extant archosaurs indicates a relationship between the postcranial axial skeleton and pulmonary anatomy. Lung ventilation in extant crocodilians is primarily achieved with a hepatic piston pump and costal rotation. The tubercula and capitula of the ribs lie on the horizontal plane, forming a smooth thoracic ''ceiling'' facilitating movement of the viscera. Although the parietal pleura is anchored to the dorsal thoracic wall, the dorsal visceral pleura exhibits a greater freedom of movement. The air sac system and lungs of birds are associated with bicapitate ribs with a ventrally positioned capitular articulation, generating a rigid and furrowed rib cage that minimizes dorsoventral changes in volume in the dorsal thorax. The thin walled bronchi are kept from collapsing by fusion of the lung to the thorax on all sides. Data from this study suggest a progression from a dorsally rigid, heterogeneously partitioned, multichambered lung in basal dinosauriform archosaurs towards the small entirely rigid avian-style lung that was likely present in saurischian dinosaurs, consistent with a constant volume cavum pulmonale, thin walled parabronchi, and distinct air sacs. There is no vertebral evidence for a crocodilian hepatic piston pump in any of the taxa reviewed. The evidence for both a rigid lung and unidirectional airflow in dinosauriformes raises the possibility that these animals had a highly efficient lung relative to other Mesozoic vertebrates, which may have contributed to their successful radiation during this time period. Anat Rec, 00:000-000,

Context: Recent studies provide ample evidence of the benefits of yoga in various chronic disorders. Diabetes mellitus is a group of metabolic diseases characterized by chronic hyperglycemia and Sandler coined the term “Diabetic Lung” for the abnormal pulmonary function detected in diabetic patients due underlying pulmonary dysfunction. Yoga therapy may help in achieving better pulmonary function along with enhanced glycaemic control and overall health benefits. Aim: To study the effect of adjuvant yoga therapy in diabetic lung through spirometry. Settings and Design: Randomized control trial was made as interdisciplinary collaborative work between departments of Yoga Therapy, Pulmonary Medicine and Endocrinology, of MGMC & RI, Sri Balaji Vidyapeeth Puducherry. Materials and Methods: 72 patients of diabetic lung as confirmed by spirometry (<70% of expected) were randomized into control group (n=36) who received only standard medical treatment and yoga group (n=36) who received yoga training thrice weekly for 4 months along with standard medical management. Yoga therapy protocol included yogic counseling, preparatory practices, Asanas or static postures, Pranayama or breathing techniques and relaxation techniques. Hathenas of the Gitananda Yoga tradition were the main practices used. Spirometry was done at the end of the study period. Data was analyzed by Student's paired and unpaired 't' test as it passed normality. Results: There was a statistically significant (P < 0.05) reduction in weight, and BMI along with a significant (P < 0.01) improvement in pulmonary function (FEV1, FVC) in yoga group as compared to control group where parameters worsened over study period. Conclusion: It is concluded from the present RCT that yoga has a definite role as an adjuvant therapy as it enhances standard medical care and hence is even more significant in routine clinical management of diabetes, improving physical condition and pulmonary function.

Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO2/FiO2 measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS.
Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO2/FiO2. The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death.
Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO2/FiO2 values. Median SpO2/FiO2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO2/FiO2 and ARDS (P ≤ .001). The SpO2/FiO2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO2/FiO2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO2/FiO2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO2/FiO2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO2/FiO2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively.
Conclusions: The SpO2/FiO2, measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. Disease severity evaluation was based on airflow limitation for many years. However, it is now obvious that no single parameter can describe the complexity of COPD and a more holistic approach should be utilised. For this reason, newer classifications of the disease are based on multiple clinical characteristics or biomarkers that can predict different clinically meaningful outcomes, such as symptoms, frequency of exacerbations, progression of disease, response to different medications and mortality. Ongoing research highlights such biomarkers, while guidelines have already incorporated them, as the basis of clinical phenotypes. GOLD highlights the need for more intensive treatment of frequent exacerbators and COPD patients whose disease significantly burdens their quality of life. Moreover, a COPD-asthma overlap syndrome with a different prognosis and potentially different therapeutic approach is also recognised. Spanish guidelines also group frequent exacerbators to predominantly emphysematic versus predominantly bronchitic. Another approach aims to create scoring systems, or multidimensional indices, based on multiple biomarkers which evaluate different aspects of the disease. The recognition of all these prognostic and therapeutic patient subgroups lead to a more personalised approach to each patient and also provides data to the –omics to uncover the pathogenetic background of this diversity and develop new targeted treatments.

The aim of this study was to evaluate the influence of novel engineered fine mannitol particles (4.7%, w/w) on the performance of lactose–salbutamol sulphate dry powder inhaler (DPI) formulations to obtain promising aerosolisation properties. The results showed that the more elongated the fine mannitol particles, the weaker the drug–carrier adhesion, the better the drug content homogeneity, the higher the amount of drug expected to be delivered to the lower airways and the higher the total DPI formulation desirability. Linear relationships were established showing that mannitol particles with a more elongated shape generated powders with broader size distributions and that were less uniform in shape. The weaker the drug–carrier adhesion, the higher the fine particle fraction of the drug is upon aerosolisation. It is believed that more elongated fine mannitol particles reduce the number of drug–carrier and drug–drug physical contact points and increase the ability of the drug particles to travel into the lower airways. Additionally, a lower drug–carrier contact area, lower drug–carrier press-on forces and easier drug–carrier detachment are suggested in the case of formulations containing more elongated fine mannitol particles. Ternary ‘drug-coarse carrier-elongated fine ternary component’ DPI formulations were more favourable than both ‘drug-coarse carrier’ and ‘drug-elongated coarse carrier’ binary formulations. This study provides a comprehensive approach for formulators to overcome the undesirable properties of dry powder inhalers, as both improved aerosolisation performance and reasonable flow characteristics were obtained using only a small amount of elongated engineered fine mannitol particles.

ABSTRACT
Introduction: Respiratory physiotherapy includes rehabilitation techniques such as percussions, vibrations, postural drainage, autogenic drainage, ETGOL, Huffing & Puffing. The treatment protocol is used in patients with pulmonary disease, intensive therapy, cardiopathy, neurological diseases and damage to the locomotor apparatus, which change the rhythm and the respiratory balance.
Objective: The main objective of the study is to identify the effects of respiratory physiotherapy in patients with pneumological problems in enhancing vital capacity and improving the patient's overall condition.
Methodology: The study is a prospective, experimental type, realised over a six-month period from January to June 2017 at the Vlora Regional Hospital and Fizio Life Clinic with 40 patients in the pneumology and pediatric ward. Treated diseases include bronchial asthma, bronchitis and pneumonia. The rehabilitation protocol used is the postural and autogenic drainage techniques 2 times a day for 20 minutes; and 30 minutes Huffing & Puffing for children. The measurement is used with spirometry for vital capacity and BORG scale for dispnea.
Results: Of the patients studied, the most affected are children 50% of the cases, and the highest prevalence is in males with 60% of cases. After physiotherapy, respiratory frequency normalization, increased vital capacity, and reduction of hospital stay were observed.
Conclusions: Postural and autogenic drainage regulate the respiratory cycle, improve ventilation, aspirate secretions, and normalize the general condition of the patient. Huffing & Puffing techniques are ideal in treating pediatric patients with pulmonary problems.
Keywords: respiratory physiotherapy, postural drainage, pneumology

OBJECTIVE:  Vaping has been marketed as a “safe” or “safer” alternative to smoking.  It has become a very lucrative market and has experienced a surge of interest, especially among the younger generations.  There are many who theorize that there is a health benefit in switching from smoking to vaping, and numerous studies seem to corroborated this.  However, few studies have gone into any depth on the possible harmful effects that vaping can have on individuals.  This paper reviews three studies that were designed to analyze the possible harmful effects of vaping.

DESIGN: Case based, multi-study review of three randomized control trials.

METHODS:  Keyword searches performed in Scopus, TRIP Database, and PubMed to find up-to-date information and clinical trials.

RESULTS: Review of three randomized control trials reveals that at present there is still not sufficient information to determine the unique harms and health risks posed by vaping.  Present evidence, at best, is inconclusive.

The organic dust of sugarcane contains high concentrations of bioaerosols such as bacteria, actinomycetes, and fungi of plant and animal origin cause pulmonary impairment among sugar factory workers. Aim: 1) To find out the overall prevalence of pulmonary impairment of sugar factory workers. Study Design: A cross-sectional study was conducted on 152 permanent sugar factory workers at the factory. Simple Random Sampling is used. Materials and Method: A semi-structured questionnaire is used for collecting data and their medical history. The pulmonary function Forced Vital Capacity (FVC), FEV1 is the amount of air you can force from your lungs in one second. FEV1/FVC %) was recorded by a portable computerized digital Spirometer. To access the effect of occupational exposure, the workers were divided into three groups based upon their experience i.e. 6-10 years, 11-15 years, and 16-20 years. Results: The overall prevalence of pulmonary impairments was found to be 31.06%. Among impairments, 58.3% are restrictive 33.3% are obstructive and 8.3% are disease caused by mixed impairments. Among diseased 63% are non-smokers and 37% are smokers. Conclusions: This study illustrated there is an association between years of experience and pulmonary impairment. The sugar factory workers have to know awareness about safety standards and measures like wearing Masks, Gloves while working, thereby reducing pulmonary impairments. By adopting modern innovative technologies by the management in the sugar factory, thus reducing pulmonary impairments is possible.

A B S T R A C T Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids. Investigations have led to the recommendation that the presence of fat-soluble antioxidant is necessary during SLN preparation to protect the drug at high temperature. Meanwhile, physiological buffers as well as simulated fluids should be supplemented with stabilizers as tween 80 and Poloxamer 407, in addition to water-soluble antioxidant such as sodium sulfite. Interestingly, mucin-containing fluids are suggested to provide better protection to MYR, in contrast, cell culture media do not guarantee MYR stability. The degradation kinetics changed from 1st to 2nd order mechanism after MYR nanoencapsulation. In presence of the aforementioned additives, MYR-SLNs significantly reduced the drug degradation rate constant up to 300-folds and prolonged the half-life time up to 4500-folds compared to free MYR in physiological buffers (One-way ANOVA, p < 0.05). As a proof of concept, in vitro release experiment in presence of phosphate buffer (pH 7.4) supplemented with these additives ensured sustained release of MYR over > 8 h with no signs of degradation. The study emphasizes virtuous guidance regarding appropriate nanoencapsulation conditions and evaluation attributes ensuing MYR physicochemical stability.

There has been a veritable efflorescence of interest in sporting embodiment in recent years, including more phenomenologically inspired sociological analyses.  A sociology of the senses is, however, a very recent sub-discipline, which provides an interesting new dimension to studies of sporting embodiment, focusing inter alia upon the sensory elements of ‘somatic work’; the ways in which we go about making sense of our senses within a socio-cultural (and sub-cultural) framework.  The present article contributes to a developing sociological-phenomenological empirical corpus of literature by addressing the lived experience of asthma in non-élite sports participants. Despite the prevalence of asthma and exercise-induced asthma/bronchoconstriction, there is a distinct lacuna in terms of qualitative research into living with asthma, and specifically in relation to sports participation. Here we focus upon the aural dimension of asthma experiences, examining the role of ‘auditory attunement’ and ‘auditory work’ in sporting embodiment.

Cationically modified poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles have recently been introduced as novel carriers for DNA/RNA delivery. The colloidal characteristics of the nanoparticles-particle size and surface charge-are considered the most significant determinants in the cellular uptake and trafficking of the nanoparticles. Therefore, our aim was to introduce chitosan-coated PLGA nanoparticles, whose size and charge are tunable to adapt for a specific task. The results showed that biodegradable nanoparticles as small as 130 nm and adjustable surface charge can be tailored controlling the process parameters. As a proof of concept, the overall potential of these particulate carriers to bind the antisense oligonucleotides, 2′-O-methyl-RNA, and improve their cellular uptake was demonstrated. The study proved the efficacy of chitosan-coated PLGA nanoparticles as a flexible and efficient delivery system for antisense oligonucleotides to lung cancer cells.

Asbestos is a recognized human carcinogen, causally related to pleural and peritoneal mesothelioma and to lung cancer
Mesothelioma is of particular interest, as it is a specific outcomeof asbestos exposure and no other causal factor except for exposure to asbestos
We examine the epidemiologic data that confirm the risks of Pleural Calcifications and Malignant pleural mesothelioma  associated with non-occupational exposure to asbestos , especially in the area of Metsovo, Greece.
Both pathologies were attributed to household use of asbestos during 1940 to 1950, more specifically a whitewash that was found to contain tremolite. The condition was named “Metsovo lung”It’s been also shown  with certainty that there are many areas of “Metsovo lung” in Greece. It is added to several previous studies mainly from Turkey and several countries of easten Europe demonstrating a very similar problem.

Our aim is to review all the  literature concerning Metsovo Lung and  simiral cases in other areas ( especially Eastern europe ) that demonstrate the strong relationship between enviromental exposure to asbestos and lung diseases.
About Metsovo the end of the mesothilioma epidemic is expected in a few decades. Beyond that studying the effects of nonoccupational asbestos exposure on mesothelioma risk could provide information about the nature of the exposure–response relationship and it would be of utmost importance, from a scientific and public health point of view, to know whether exposure to low levels of asbestos is able to induce pleural mesothelioma.

The present study refers to the exploration of the respiratory function of patients who presented acute symptoms of chronic obstructive pulmonary disease. In the medical specialty units, examination was performed using a standard chest X-ray imaging investigation; followed by a spirometry test, according to the patient's severity of symptoms, using the betamimetics test. Both the X-ray result and the imaging investigation of spirometry showed changes. Changes varied according to the patients from different investigate disease groups in relation to chronic obstructive pulmonary disease.

A chest x-ray screening system for pulmonary pathologies such as tuberculosis (TB) is of paramount importance due to the increasing mortality rate of patients with undiagnosed TB, especially in densely-populated developing countries. As a first step toward developing such screening systems, this paper presents a novel computer vision module that automatically segments the lungs from posteroanterior digital chest x-ray images. The segmentation task is non-trivial, due to poor image contrast and occlusion of the lung region by ribs, clavicle, heart, and by non-TB abnormalities associated with pulmonary diseases. In the proposed procedure, we first compute a lung shape model by employing a level set based technique for registration up to a homography. Next, we use this computed mean lung shape to initialize the level set that is based on a best fit measure obtained in a heuristically estimated search space for the projective transform parameters. Once the level set is initialized, a suite of customized lower level image features and higher level shape features up to a homography evolve the level set function at a lower resolution in order to achieve a coarse segmentation of the lungs. Finally, a fine segmentation step is performed by adding additional shape variation constraints and evolving the level set in a higher resolution. We processed the standard Japanese Society of Radiological Technology (JSRT) dataset, comprised of 247 images, using this scheme. The promising results (92% accuracy) demonstrate the viability and efficacy of the proposed approach. © (2013) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Introduction: Non-resolving pneumonia is always a challenging clinical scenario where various diagnostic modalities are greatly required to reach the diagnosis. We aimed to study the role of fiberoptic bronchoscopy in non-resolving pneumonia along with the various comorbidities associated with the disease condition. Materials and Methods: A cross sectional study in a tertiary care hospital was undertaken. A total of 60 patients diagnosed with non-resolving consolidation were recruited for diagnostic fiberoptic bronchoscopy. Results: The overall diagnostic yield of fiberoptic bronchoscopy in non-resolving pneumonia was 96.66%. The causes of non-resolving pneumonia were tuberculosis (40 (66.67 %), bacterial pneumonia (8 (13.33 %)), malignancy (6 (10%)), fungal pneumonia (3 (5 %)) and foreign body (1 (1.66 %) in order of decreasing proportions. 2 cases (3.33 %) were undiagnosed. 29 (48.33%) patients had a significant past history which also revealed associated co morbid conditions. Chronic obstructive pulmonary disease (COPD) (14 (23.33 %)) and diabetes (10 (16.66%)) were the leading comorbid conditions. Conclusion: Fiberoptic bronchoscopy is a great utility tool in reaching the diagnosis in patients with non-resolving pneumonias.

PURPOSE:

The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery.

METHODS:

Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ((L)-arginine and (L)-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug.

RESULTS:

Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, (L)-leucine was significantly superior in enhancing the aerosolization performance ((L-)arginine:%FPF 27.61 ± 4.49-26.57 ± 1.85; FPD 12.40 ± 0.99-19.54 ± 0.16 μg and MMAD 2.18 ± 0.35-2.98 ± 0.25 μm, (L)-leucine:%FPF 36.90 ± 3.6-43.38 ± 5.6; FPD 18.66 ± 2.90-21.58 ± 2.46 μg and MMAD 2.55 ± 0.03-3.68 ± 0.12 μm). Incorporating (L)-leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with (L)-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment.

CONCLUSION:

The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery.

Despite effective pharmacotherapy, asthma continues to impair quality of life for most patients. Non-pharmacological approaches, including breathing retraining, are therefore of great interest to patients. However, clinicians rarely advocate breathing retraining and access to this intervention is restricted for most patients due to the limited availability of suitable physiotherapists and poor integration of breathing retraining into standard care. We aimed to assess the effectiveness of a digital self-guided breathing retraining intervention. In this randomised controlled trial, we recruited patients from 34 general practices in the UK. Eligibility criteria for patients with asthma were broad, comprising a physician diagnosis of asthma, age of 16-70 years, receipt of at least one anti-asthma medication in the previous year, and impaired asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ] score of &lt;5·5). We developed a self-guided intervention, which was d...

Pulmonary diffusing capacity for nitric oxide (DL,NO) and carbon monoxide (DL,CO) measured at rest (mL/min/mmHg) is strongly associated with aerobic capacity (cardiorespiratory fitness or peak oxygen uptake, VO 2peak) measured in L/min. Data from healthy, non-obese individuals from various studies (n = 121 males and 81 females) were combined to examine this association. Subjects that were above the upper limit of normal (ULN, 97.5th percentile for age and sex and height) for DL,NO and DLCO had a higher median VO 2peak compared to subjects below the ULN (Above the ULN = 4.2–4.5 L/min or 54–56 mL/kg/min; below the ULN = 3.0–3.2 L/min, 45–46 mL/kg/min, p < 0.001). Those that were classified as Superior or Excellent in cardiorespiratory fitness (≥80th percentile in VO 2peak for the person's age and sex) increased their odds of being above the ULN for DL,NO and DL,CO by about 6-fold and 8-fold, respectively, compared to those not classified as being Superior or Excellent in cardiorespiratory fitness. Approximately 65–68% of the variance in DL,NO and DL,CO, respectively, was shared by VO 2peak (L/min) (p < 0.001). However, after controlling for alveolar volume, sex, height, body mass, and age, the shared variance between pulmonary diffusing capacity and VO 2peak decreased to 16–20% (95% CI = 8–30%), and yet, remained statistically significant (p < 0.001). The reasons for the shared variance between pulmonary diffusing capacity and VO 2peak are discussed.

Cystic fibrosis (CF) is a genetic disease mainly manifested in the respiratory tract. Pseudomonas aeruginosa
(P. aeruginosa) is the most common pathogen identified in cultures of the CF airways, however, its eradication
with antibiotics remains challenging as it grows in biofilms that counterwork human immune response and
dramatically decrease susceptibility to antibiotics. P. aeruginosa regulates pathogenicity via a cell-to-cell communication
systemknown as quorumsensing (QS) involving the virulence factor (pyocyanin), thus representing an
attractive target for coping with bacterial pathogenicity. The first in vivo potent QS inhibitor (QSI) was recently
developed. Nevertheless, its lipophilic nature might hamper its penetration of non-cellular barriers such as
mucus and bacterial biofilms, which limits its biomedical application.
Successful anti-infective inhalation therapy necessitates proper design of a biodegradable nanocarrier allowing:
1) high loading and prolonged release, 2) mucus penetration, 3) effective pulmonary delivery, and 4) maintenance
of the anti-virulence activity of the QSI.
In this context, various pharmaceutical lipidswere used to prepare ultra-small solid lipid nanoparticles (us-SLNs)
by hot melt homogenization. Plain and QSI-loaded SLNs were characterized in terms of colloidal properties,
drug loading, in vitro release and acute toxicity on Calu-3 cells. Mucus penetration was studied using a newlydeveloped
confocalmicroscopy technique based on 3D-time-lapse imaging. For pulmonary application, nebulization
efficiency of SLNs and lung deposition using next generation impactor (NGI) were performed. The anti-virulence
efficacy was investigated by pyocyanin formation in P. aeruginosa cultures.
Ultra-small SLNs (b100nmdiameter) provided high encapsulation efficiency (68–95%) according to SLN composition,
high burst in phosphate buffer saline compared to prolonged release of the payload over N8 h in simulated
lung fluidwith minor burst. All types and concentrations of plain and QSI-loaded SLNs maintained the viability of
Calu-3 cells. 3D time-lapse confocal imaging proved the ability of SLNs to penetrate into artificial sputum model.
SLNs were efficiently nebulized; NGI experiments revealed their deposition in the bronchial region. Overall,
nanoencapsulated QSI showed up to sevenfold superior anti-virulence activity to the free compound. Most
interestingly, the plain SLNs exhibited anti-virulence properties themselves, which was shown to be related to
anti-virulence effects of the emulsifiers used. These startling findings represent a new perspective of ultimate
significance in the area of nano-based delivery of novel anti-infectives.

Despite effective pharmacotherapy, asthma continues to impair quality of life for most patients. Non-pharmacological approaches, including breathing retraining, are therefore of great interest to patients. However, clinicians rarely advocate breathing retraining and access to this intervention is restricted for most patients due to the limited availability of suitable physiotherapists and poor integration of breathing retraining into standard care. We aimed to assess the effectiveness of a digital self-guided breathing retraining intervention. In this randomised controlled trial, we recruited patients from 34 general practices in the UK. Eligibility criteria for patients with asthma were broad, comprising a physician diagnosis of asthma, age of 16-70 years, receipt of at least one anti-asthma medication in the previous year, and impaired asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ] score of &lt;5·5). We developed a self-guided intervention, which was d...

Pulmonary alveolar microlithiasis is a rare disease with an almost unheard of pathogenesis. With very few cases to document worldwide, predominantly being discovered in Turkey, Italy, and America, it has been nearly impossible to determine a concrete etiology. However, one standout biochemical finding most cases of PAM have in common is a mutation in the SLC34A2 gene coding for the sodium-phosphate cotransporter found in Type II alveolar cells. This cotransporter is responsible for maintaining equilibrium of phosphorus which is a vital component of surfactant. Diagnostic exploration is achieved via radiological imaging, bronchoalveolar lavage and above all, transbronchial lung biopsy. However, in this particular case, due to the patient’s hypoxic condition, Technetium 99m diphosphonate scanning was employed in place of the biopsy. A non-invasive procedure, technetium 99m can detect extensive pulmonary uptake, hereby diagnosing the patient and protect against the physical damage and ...

A meta-analysis determined whether capillary blood gases accurately reflect arterial blood samples. A mixed effects model was used on 29 relevant studies obtained from a PubMed/Medline search. From 664 and 222 paired samples obtained from the earlobe and fingertip, respectively, earlobe compared to fingertip sampling shows that the standard deviation of the difference is about 2.5× less (or the precision is 2.5× better) in resembling arterial PO 2 over a wide range of arterial PO 2 's (21-155 mmHg). The lower the arterial PO 2 , the more accurate it is when predicting arterial PO 2 from any capillary sample (p < 0.05). However, while earlobe sampling predicts arterial PO 2 (adjusted r 2 = 0.88, mean bias = 3.8 mmHg compared to arterial), fingertip sampling does not (adjusted r 2 = 0.48, mean bias = 11.5 mmHg compared to arterial). Earlobe sampling is slightly more accurate compared to fingertip sampling in resembling arterial PCO 2 (arterial versus earlobe, adjusted r 2 = 0.94, mean bias = 1.9 mmHg; arterial versus fingertip, adjusted r 2 = 0.95, mean bias = 2.2 mmHg compared to arterial) but both sites can closely reflect arterial PCO 2 (880 total paired samples, range 10-114 mmHg). No real difference between sampling from the earlobe or fingertip were found for pH as both sites accurately reflect arterial pH over a wide range of pH (587 total paired samples, range 6.77-7.74, adjusted r 2 = 0.90-0.94, mean bias = 0.02). In conclusion, sampling blood from the fingertip or earlobe (preferably) accurately reflects arterial PCO 2 and pH over a wide range of values. Sampling blood, too, from earlobe (but never the fingertip) may be appropriate as a replacement for arterial PO 2 , unless precision is required as the residual standard error is 6 mmHg when predicting arterial PO 2 from an earlobe capillary sample.

The measurement of maximal inspiratory and expiratory pressures at the mouth (MIP and MEP, respectively) provides a noninvasive clinical method for evaluating the strength of respiratory muscles. In an attempt to reconcile the widely divergent normal values reported in the literature for healthy adolescents, we have measured, using simple manometry, MIP and MEP in 112 white subjects, 76 adolescents and 36 healthy adults. For female adolescents the values for MIP and MEP were 76 +/- 25 and 86 +/- 22 cm H2O, respectively, and were significantly less than those for male adolescents (p less than 0.01), whose mean values were 107 +/- 26 and 114 +/- 35 cm H2O, respectively. Mean values for adolescents were comparable to values measured in adult control subjects, and for both adolescents and adults, mean values approximated the lower end of the previously reported ranges of normal values in healthy subjects. Thus, MIP and MEP in healthy adolescents are significantly greater in male subjects than female subjects, but are comparable to those of healthy adults of the same sex. Furthermore, these studies suggest that the choice of normal values for MIP and MEP must take into account significant methodologic differences among laboratories.

Pulmonary drug delivery is a non-invasive, non-systemic delivery approach for both local and systemic drugs and a method to directly target disorders of lung. The albumin nanoparticles were prepared by modified desolvation method using different concentration of albumin as biodegradable polymer for lungs. The prepared albumin nanoparticles were evaluated for entrapment efficiency, particle size, polydispersity index, zeta potential, transmission electron microscopy, in-vitro drug release, stability study and in-vivo study. The entrapment efficiency of all albumin nanoparticles formulations were found to be in the range of 61.74 % - 73.45 %. The particle size of albumin nanoparticle formulations were found to be in range 81.6 nm - 148.4 nm. The  zeta potential of albumin nanoparticles found to exhibit stability due to negative charge on the surface. The transmission electron microscopy indicated the spherical surface of the albumin nanoparticles. The in vitro release was found to follow higuchi plot as compared to zero order plot, first order plot and krosmeyer peppas plot. Stability studies showed that albumin nanoparticle formulation ANps5 was stable according to ICH guidelines for 6 months. In-vivo study using rat model indicated the localization of albumin nanoparticles in the lungs of rat.

Mucociliary clearance (MC), designed by evolution to eliminate inhaled and possibly noxious material from the airways, considerably limits the benefit of inhalation therapy. Although the principles of MC seem to be understood, there are still many open questions on mucociliary particle clearance. In this study a tracheabased in vitro model was used to investigate the effect of particle size, zeta-potential, and mucoadhesive particle properties on mucociliary particle clearance. As different sized particles (50-6000 nm) were tested at equal mass concentrations, size related factors, namely particle number and particle surface area, varied by several orders of magnitude between the experiments. Surprisingly, particle clearance for 50 nm up to 6000 nm-sized polystyrene particles did not differ significantly ( p < 0.05): 50 nm (2.9 AE 0.6 mm=min); 100 nm (3.8 AE 0.9 mm=min); 1000 nm (3.8 AE 0.8 mm=min); 6000 nm (3.2 AE 0.6 mm=min). In clear contrast, particles prepared from different PLGA-based copolymers (polylactic-co-glycolic acid) showed a significant effect on particle transport. PEG-PLGA particles (polyethylene glycol) showed the fastest and normal transport rates (5.9 AE 1.7 mm=min) compared to the ICRP's (International Commission of Radiological Protection) standard value for average tracheal transport rates (5.5 mm=min). Mucoadhesive chitosan-PLGA particles were transported at the slowest rate (0.7 AE 0.3 mm=min) of all particles tested. Overall, particle size and zeta-potential seem to be relatively uncritical, whereas material properties and the related particle surface chemistry significantly influence mucociliary particle clearance. Considering these findings in future drug formulation seems to be a promising strategy to improve inhalation therapy by prolonged particle=drug residence time within the airways.

AIM: The aim of this study was to explore, using qualitative research methods, how pulmonary rehabilitation (PR) programmes affect the experience of activity and breathlessness of people with COPD.

METHODS: A qualitative, interview-based approach was employed. Participants were interviewed pre- and post-PR. Data were analysed using systematic strategies informed by grounded theory methods.

RESULTS: Nine participants (three female) took part. A change in participants' perception of breathlessness and lessening of fear of activity were the main themes identified. PR appeared to impact on the experience of physical social activities, allowing participants to overcome feelings of social isolation.

CONCLUSIONS: Prior to PR, participants associated activities with breathlessness and panic; post PR, participants reported reduced fear and felt able to increase their activities. These findings add to our understanding of the impact of PR on individuals' experience of activity and may contribute to improved programmes by addressing patients' needs.

Subclinical primary Pneumocystis infection is the most common pulmonary infection in early infancy, making it important to determine whether it damages the lung. Pneumocystis peaks at 2 to 5 months of age, when respiratory morbidity coincidently increases. We have documented that Pneumocystis increases mucus production in infant lungs, and animal models reveal lung lesions that warrant characterization. Herein, immunocompetent rats infected at birth with Pneumocystis by cohabitation, to resemble community-acquired infection, underwent lung assessments at 45, 60, and 75 days of age. Lungs fixed by vascular perfusion to prevent collapse during necropsy were used for morphometry evaluations of mucus production, airway epithelial thickening, perivascular and peribronchiolar inflammation, and structural airway remod-eling. Changes in these histologic features indicate lung disease. Selected immune markers were assessed in parallel using fresh-frozen lung tissue from sibling rats of the same cages. Sequential activation of NF-kB and an increased Gata3/T-bet mRNA level ratio, consistent with a type 2 helper T-celletype inflammatory response, and subacute fibrosis were recognized. Therefore, documenting subclinical Pneumocystis infection induces lung disease in the immunocompetent host. Taken together with the peak age of primary Pneu-mocystis infection, results warrant investigating the clinical impact of this often subclinical infection on the severity of respiratory diseases in early infancy. This model can also be used to assess the effects of airway insults, including coinfections by recognized respiratory pathogens. (Am J Pathol 2018, 188: 417e431; https://doi.

Background
Despite effective pharmacotherapy, asthma continues to impair quality of life for most patients. Non-pharmacological approaches, including breathing retraining, are therefore of great interest to patients. However, clinicians rarely advocate breathing retraining and access to this intervention is restricted for most patients due to the limited availability of suitable physiotherapists and poor integration of breathing retraining into standard care. We aimed to assess the effectiveness of a digital self-guided breathing retraining intervention.

Methods
In this randomised controlled trial, we recruited patients from 34 general practices in the UK. Eligibility criteria for patients with asthma were broad, comprising a physician diagnosis of asthma, age of 16–70 years, receipt of at least one anti-asthma medication in the previous year, and impaired asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ] score of <5·5). We developed a self-guided intervention, which was delivered as a DVD plus a printed booklet (DVDB). Participants were randomly assigned to receive either the DVDB intervention, three face-to-face breathing retraining sessions, or standard care, in a 2:1:2 ratio, for 12 months. Randomisation was achieved using the Southampton Clinical Trials Unit telephone randomisation service by use of random number generators. The primary outcome was the AQLQ score in the intention-to-treat population at 12 months. The trial was powered to show equivalence between the two active intervention groups, and superiority of both intervention groups over usual care. Secondary outcomes included patient-reported and physiological measures of asthma control, patient acceptability, and health-care costs. This trial was registered with International Standard Randomised Controlled Trial Number registry, number ISRCTN88318003.

Findings
Between Nov 5, 2012 and Jan 28, 2014, invitations to participate in the study were sent to 15 203 patients with general practitioner-diagnosed asthma, of whom 655 were recruited into the study. AQLQ scores at 12 months were significantly higher in the DVDB group (mean 5·40, SD 1·14) than in the usual care group (5·12, SD 1·17; adjusted mean difference 0·28, 95% CI 0·11 to 0·44), and in the face-to-face group (5·33, SD 1·06) than in the usual care group (adjusted mean difference 0·24, 95% CI 0·04 to 0·44); AQLQ scores were similar between the DVDB group and the face-to-face group (0·04, 95% CI −0·16 to 0·24). There were no significant differences between the randomisation groups in FEV1 or fraction of exhaled nitric oxide. 744 adverse events occurred in 272 patients: 101 (39%) of 261 patients in the DVDB group, 55 (42%) of 132 patients in the face-to-face group, and 132 (50%) of 262 in the usual care group, with patients reporting one or more event. 11 (4%) patients in the DVDB group, four (3%) patients in the face-to-face group, and 20 (8%) patients in the usual care group had a serious adverse event.

Interpretation
Breathing retraining programmes improve quality of life in patients with incompletely controlled asthma despite having little effect on lung function or airway inflammation. Such programmes can be delivered conveniently and cost-effectively as a self-guided digital audiovisual programme, so might also reduce health-care costs.

Keywords: Transfer factor of the lung for CO Transfer factor of the lung for NO Lung diffusing capacity Pulmonary function tests Nitrogen monoxide a b s t r a c t Pulmonary diffusing capacity for carbon monoxide (DLCO) has been an important pulmonary function test used since the 1950's. It measures the uptake of CO from the alveolar space into pulmonary capillary blood, following the same path as oxygen. It's used to evaluate/follow the progress of various lung diseases. In the eighties, a new test was developed similar to the DLCO test: pulmonary diffusing capacity for nitric oxide (DLNO). About 81–90% of the variance in DLNO is shared by DLCO in patients with cardiopulmonary disease and in healthy subjects. When DLNO is abnormally low, so is DLCO, and when DLNO is normal, so is DLCO (Kappa Statistic = 0.69, n = 251). The probability that DLNO and DLCO will be abnormally low when a cardiopulmonary disease is present (sensitivity) is 79% and 68%, respectively. The DLNO test avoids many technical issues associated with the measurement of DLCO: (1) DLNO is relatively unaffected by inspired oxygen concentration or ambient pressure, (2) DLNO is unaffected by carboxyhemoglobin, (3) DLNO is minimally affected by hemoglobin (Hb) concentration, thus correcting for Hb is not needed. (4) DLNO is more affected by lung volume compared to DLCO, thus DLNO divided by alveolar volume (KNO) is a better measure than KCO in those with restrictive lung disease, and (5) DLNO is a more stable measure over time compared to DLCO. Therefore, DLNO has several advantages over DLCO in the management of patients and could replace the DLCO test in most cases moving forward.

This article explores the lived experience of asthma in a specific population of sport and exercise participants, drawing on an approach currently under-utilised in studies of asthma: vignettes. These were used as an elicitation technique in research with 19 frequent exercisers and sports participants with asthma, eight of whom responded to vignettes.  We describe and evaluate this approach as deployed in relation to a phenomenological study of the lived experience of asthma, and consider how employing vignette-based research can encourage people with asthma to reflect critically on their experiences and ways of being-in-the-world.  This was found to be a powerful way of challenging taken-for-granted assumptions, and stimulating consideration of behaviour change. The findings we report here cohere around two principal themes that emerged as salient: 1) somatic empathy; and 2) the power of sharing stories and opening up dialogues. Understanding the complexity of asthma experiences can, we argue, be of great practical value both to those with asthma and also to healthcare and exercise professionals in tailoring more effective treatments.

Lung sounds provide useful information for assessing and monitoring respiratory patients, but standard auscultation is subjective. Computer aided lung sound analysis (CALSA) enables the quantification and characterisation of added lung sounds (e.g. crackles). At present, little is known about the reliability of these sound characteristics. Therefore, the aim of this study was to explore the reliability of crackle initial deflection width (IDW) and two-cycle deflection (2CD) in a clinical population. Fifty-four subjects (37 bronchiectasis, 17 cystic fibrosis) were recruited from out-patient clinics. Three repeated lung sound recordings were taken at seven anatomical sites with a digital stethoscope connected to a laptop computer. The intra-subject reliability of crackle IDW and 2CD was found to be 'good' to 'excellent', estimated by the analysis of variance, intraclass correlation coefficient (IDW 0.76;0.85, 2CD 0.83;0.94), Bland and Altman 95% limits of agreement (IDW -0.50;0.47 ms, 2CD -2.12;1.87 ms) and smallest real difference (IDW 0.30;0.66 ms, 2CD 1.57;2.42 ms). Crackle 2CD was found to be more reliable than IDW. It is concluded that crackle IDW and 2CD characterized by CALSA have good test-retest reliability. This technique requires further evaluation since CALSA has potential to diagnose or monitor respiratory conditions, and provide an objective physiological measure for respiratory interventions

The Purpose of these studies was to investigate the ability of surface energy measurements and rates of mixing in dry powder inhaler formulations to predict aerosol dispersion performance. Two lactose carrier systems comprising either spray dried or milled particles were developed such that they had identical physical characteristics except for surface morphology and surface energies avoiding confounding variables common in other studies. Surface energy measurements confirmed significant differences between the powder systems. Spray dried lactose had a higher surface entropy (0.20 vs. 0.13 mJ/m2K) and surface enthalpy (103.2 vs. 79.2 mJ/m2) compared to milled lactose. Mixing rates of budesonide or fluorescein were assessed dynamically and significant differences in blending were observed between lactose systems for both drugs. Surface energies of the lactose carriers were inversely proportional to dispersion performance. In addition, the root mean square of blending rates correlated positively with aerosol dispersion performance. Both techniques have potential utility in routine screening dry powder inhaler formulations.

ABSTRAK Pendahuluan: Asap rokok dapat mempengaruhi kerja makrofag alveolar sebagai sistem imun nonspesifik. Metode: Penelitian bersifat eksperimental dengan model post test only. Subjek penelitian studi in vitro adalah kelompok yang diinduksi asap rokok. Makrofag dari bilasan paru dikultur dan dilakukan uji bakterisidal terhadap bakteri Klebsiella pneumonia. Subjek penelitian studi in vivo adalah kelompok yang diinduksi asap rokok, diinjeksikan Escherichia coli di paru, hasil suspensi paru dikultur, dan dihitung koloni bakteri yang terbentuk. Hasil: Studi in vitro menunjukkan terjadi penurunan kemampuan bakterisidal makrofag yang bermakna (P=0,030), sedangkan melalui studi in vivo menunjukkan terjadi penurunan fungsi proteksi terhadap infeksi bakteri yang tidak bermakna (P=0,796).