The National Institute of Environmental Medicine

Furred animals are not allowed inside schools in Sweden. However, high level of pet allergens can be found in classrooms and other public places, as has been shown in several studies (1-5). There is a strong relationship between cat allergen levels and the number of cat owners in the class, which has been explained by the indirect transfer of allergens between homes with cats and schools or other public places, mainly via clothing (4, 6, 7). However, increased attention has been drawn to the conditions for allergic children at school since the incidence of allergy is increasing, and some schools in Sweden are allocating resources to allergen avoidance measures. This may include increased cleaning, sometimes in combination with removal of upholstery and curtains and the replacement of bookshelves with cupboards in order to minimize dust and allergen load. These measures, recommended by the Swedish National Institute of Public Health and Swedish Asthma and Allergy Association can be difficult to put into

Inhalation of dust from swine confinement buildings induces airway inflammation with an increase in both inflammatory cell numbers and secretion of proinflammatory cytokines in the lungs. It is not known whether anti-asthma drugs, which influence airway inflammation in asthma, also influence the airway reaction to inhaled organic dust. In the present study we examined the effects of a û 2-agonist (salmeterol) and an inhaled steroid (fluticasone) on the swine dust-induced cell and cytokine content of the lower airways, and cytokine release in cultured alveolar macrophages. Healthy volunteers were pretreated with inhaled salmeterol (n 8), fluticasone propionate (n 8) or placebo (n 8) for about 2 weeks and exposed to dust in a pig house. Bronchoalveolar lavage was performed both before medication and after dust exposure. Cell differential counts and cytokine analyses in bronchoalveolar lavage fluid (BALF) were examined. Alveolar macrophages were cultured and cytokine release was studied, both in unstimulated cells and after lipopolysaccharide (LPS) stimulation. Unstimulated alveolar macrophages from swine dust-exposed individuals released less IL-6, IL-8 and tumour necrosis factor-alpha (TNF-a) after, than before, exposure (P , 0´01). Medication did not influence basal cytokine production. Fluticasone inhibited LPS-induced IL-6 and IL-8 release (P , 0´05). There was no significant difference between the groups. There was a large and significant increase (P , 0´05) in alveolar macrophage, granulocyte, lymphocyte numbers, and IL-6 and TNF-a content in BALF in all three groups following dust exposure, with no significant difference between the groups. These findings suggest that drugs which are known to influence and control airway inflammation in asthma do not have major effects on airway inflammation induced by the inhalation of organic dust.

Objective: Expression of tumor necrosis factor alpha (TNF), TNF receptors 1 and 2 and TNFalpha converting enzyme (TACE) was studied in A549 human alveolar epithelial cells exposed to organic dust from a swine barn. Additional objectives were to elucidate whether 8-bromo-cAMP affected TNF and TNF receptor mRNA expression by activation of protein kinase A (PKA) and whether it increased phosphorylation of cAMP-responsive elementbinding protein (CREB). Materials and methods: Reverse transcriptase-(RT-) PCR was performed on unexposed cells and cells exposed to a dust-suspension, with and without 8-bromo-cAMP (1 mM). H-89 was used to inhibit PKA. To further investigate mRNA expression of TNF, staurosporine was used. Immunolabeling was applied for detection of TNF, TNFR1, TNFR2 and phosphorylation of CREB. Results: TNF mRNA and protein was expressed after 1-3 h in dust-exposed cells. TNFR2 mRNA and protein expression was induced by dust-exposure, whereas expression of TNFR1 and TACE was constitutive. After 1-1.5 h incubation, mRNA expression of TNF was (PKA-independently) attenuated by 8-bromo-cAMP (p < 0.05), whereas that of TNFR1 was PKA-dependently stimulated (p < 0.05). Staurosporine attenuated mRNA expression of TNF (p < 0.05), but not interleukin (IL)-6, which was detected prior to TNF. Conclusion: Expression of TNF and its receptors in alveolar epithelial cells may contribute to the response to organic dust. 8-bromo-cAMP, which increased the number of cells exhibiting phosphorylation of CREB exerted opposite effects on TNF and TNFR1 mRNA expression. The mechanism by which cAMP attenuates TNF mRNA expression remains to be established. Dust-induced expression of IL-6 precedes that of TNF and the induction pathways differ with regard to staurosporine sensitivity.

In primary care, asthma is usually assessed by means of the patients' history regarding symptoms and simple lungfunction testing. These outcomes may, however, not be related to other estimates of asthma control such as quality of life. In the present study quality of life was studied in relation to symptoms (visual analogue scale, VAS) and lung function in adult patients with asthma in a primary-care setting. In a healthcare centre in Stockholm, 405 individuals diagnosed as having asthma were identified. Out of this number, 120 patients completed the study. Patients were categorized into four groups according to lung function and their response to a question regarding asthma symptoms on the VAS. Quality of life was evaluated with the Asthma Quality of Life Questionnaire (AQLQ) and current treatment was recorded. Quality of life differed significantly between the groups with regard to all domains and overall score; overall score was 6?0 (0?12)-(mean SEM) in group A (VAS 2, normal FEV 1), 5?4 (0?24) in group B (VAS 2, low FEV 1), 4?8 (0?25) in group C (VAS42, normal FEV 1) and 4?6 (0?24) in group D (VAS42, low FEV 1) (P 50?0001). In general a gradient, with group A having the highest and group D the lowest score, was detected. Experience of symptoms (VAS42) was highly related to lower scores in the environmental domain (P50?0001). The correlation between FEV 1 and quality of life was generally low whereas there was a fairly good correlation between VAS and quality of life (P50?0001 for all domains). Patients without steroid treatment had higher quality of life scores than patients treated with steroids. The majority of asthma patients in primary care have high quality of life scores, indicating a low prevalence of symptoms and only slight activity limitations. Evaluation of quality of life enables a more careful grading of asthma status. Furthermore, this measure provides information concerning asthma control that is not revealed by spirometry and simple questions regarding symptoms.

Background-Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear. Methods-Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E 4 (LTE 4) and 9 ,11-PGF 2 , the earliest appearing urinary metabolite of prostaglandin D 2 (PGD 2), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure. Results-Methacholine PD 20 FEV 1 decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p<0.01). Associated with the increase in bronchial responsiveness there was a significant mean diVerence between post-and prechallenge levels of LTE 4 (diVerence 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p<0.01) and 9 ,11-PGF 2 (diVerence 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p<0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB 4 and LTE 4 in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. Conclusions-The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.

Obesity and asthma are common chronic diseases in the industrialised world.The aim of the present study was to investigate a possible relationship between asthma and obesity among persons on sick leave due to respiratory disorder. The diagnosis of asthma (n=237) was made in a three-stage model (questionnaire, telephone interview and clinical examination) in persons on sick leave due to any respiratory disorder. Persons on sick leave due to non-specific spinal pain, (n=1231) and a general population sample (n=5092) were used as references. Obesity (body mass index 430 kg/m 2) was found in 20.7% of the asthmatic patients on sick leave compared with 13.7% in the non-specific pain patients on sick leave and in 6.5% of the controls (Po0.001). It is not clear whether the increased prevalence of obesity among asthmatics reflects a true increase in asthma in obese persons or whether asthma-like symptoms occur because of obesity.Weight reduction schemes and weight maintenance programmes should be important components in treatment and rehabilitation plans for persons with asthma.

Inhalation of dust from swine confinement buildings results in an acute inflammatory reaction in the respiratory tract. The dust has a high microbial content, dominated by Gram positive bacteria. The aim of the present study was to evaluate the significance of bacteria in the induction of IL-6 and IL-8 release from respiratory epithelial cells and alveolar macrophages. The results would give an indication to what extent the bacteria contribute to the toxic inflammation following exposure to swine dust. Epithelial cells from a human lung carcinoma cell line (A549) and human alveolar macrophages obtained from healthy subjects by bronchoalveolar lavage, were stimulated with swine dust, LPS, one Gram negative and four Gram positive bacteria strains. The dose-response release of IL-6 and IL-8 were studied. In addition, a bacteria-free supernatant was prepared from each strain and used for stimulation. With a few exceptions, a dose-dependent IL-6 and IL-8 release was demonstrated from bot...

Only limited data are available about the incidence of asthma based on longitudinal prospective studies. Further, the results from different studies on incidence vary considerably depending on the age composition of the cohorts under study, the used methods and the criteria for disease. Also among adults high incidence rates have been reported during recent years. The aim of this study was to examine to what extent the incidence of physician-diagnosed asthma could be explained by a real incidence of the disease, and to what extend by an increased diagnostic activity or altered diagnostic praxis. Another aim was to study risk factors for asthma based on incident cases. Three cross-sectional surveys have been performed in the same population sample living in the northern-most province of Sweden, Norrbotten. The first survey was performed in 1986, and 5698 subjects, 86% of those invited, responded to a postal questionnaire. Of these, 4754 subjects (83%) participated at the third survey...

Chronic obstructive pulmonary disease (COPD) is identified as an inflammatory disorder characterised by airway and lung inflammation and destruction with systemic involvement of multiple organ systems. The inflammatory reaction could be monitored not only in the airways by the use of bronchoalveolar lavage (BAL), sputum, exhaled air, and exhaled breath condensate but also in blood and urine as well as in tissue obtained at surgery or autopsy. There is a large number of cytokines, chemoattractants and other mediators that are of importance for the interplay of inflammatory mechanisms in COPD. Neutrophilic granulocytes are key players in the inflammatory reaction and the most important chemoattractants for these cells seem to be IL-8 (CXCL8) and leukotriene B(4) (LTB(4)). Also, the macrophages and chemoattractants for mononuclear cells (CCL2, CCL3) are of importance as are T-lymphocytes, predominantly of the cytotoxic subtype (CD8+). Analyses in exhaled breath condensates and exhaled ...

Objectives-To study the prevalence of asthma (asthma symptoms and bronchial hyperresponsiveness) in Swedish cross country skiers compared with non-skiers and monitor changes in symptoms and bronchial hyperresponsiveness during the year. Design-Cross sectional study during the winter ski season and in the summer. Setting-Six ski clubs for 6lite skiers (total 47) in two different areas ofSweden. Subjects-42 elite cross country skiers and 29 nonskiing referents. Main outcome measures-Bronchial responsiveness, asthma symptoms, and lung function. Results-Bronchial responsiveness was significantly greater and asthma symptoms more prevalent in the skiers than in the referents. There was no difference in bronchial responsiveness within either group between winter and summer. 15 of the 42 skiers used antiasthmatic drugs regularly and 23 had a combination of asthma symptoms and hyperresponsive airways or physician diagnosed asthma, or both. Altogether 33 skiers had symptoms of asthma or bronchial hyperresponsiveness. One of the referents had symptoms ofasthma and bronchial hyperresponsiveness, and none used antiasthmatic drugs regularly. Conclusions-Asthma, asthma-like symptoms, and bronchial hyperresponsiveness are much more common in cross country skiers than in the general population and non-skiers. Strenuous exercise at low temperatures entailing breathing large volumes of cold air is the most probable explanation of persistent asthma in skiers.

Farmers and smokers are repeatedly exposed to airborne organic material. We hypothesised that farmers and smokers show altered airway responses to inhaled organic, proinflammatory agents. A total of 11 farmers, 12 smokers and 12 controls underwent lipopolysaccharide (LPS) bronchial challenge and spent 3 h in a pig barn. Lung function, exhaled nitric oxide and bronchial responsiveness were assessed and nasal lavage fluid and induced sputum were also collected. Symptoms and body temperature were recorded before and after exposures. Following exposure to the pig barn, bronchial responsiveness, exhaled nitric oxide, sputum interleukin (IL)-6, nasal lavage cell count and IL-8 were increased to a greater extent in controls compared to farmers. The sputum IL-6 response was also attenuated in farmers after LPS challenge. The response shown by smokers following exposure to the pig barn was similar to that of controls regarding measurements of exhaled nitric oxide, IL-8 in nasal lavage and IL-6 in sputum, but more similar to farmers concerning bronchial responsiveness and the cell numbers present in nasal lavage. Sputum IL-8 showed a greater increase in smokers than in the other groups following LPS challenge. We conclude that individuals who are repeatedly exposed to organic material develop an adaptation to the effects of acute exposure to inhaled organic material.

In healthy subjects, acute inhalation of swine dust causes an influx of inflammatory cells into the airways and increased bronchial responsiveness. The exposure may also cause fever and generalized symptoms. It seems likely that proinflammatory cytokines are involved in the response to inhaled swine dust. Nasal and bronchoalveolar lavage (BAL) were performed before, and 7 and 24 h after the start of 3 h exposure to swine dust, during a period of work in a swine confinement building, in 22 healthy subjects. Lavage fluids were analysed with regard to the cellular response and concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Each subject carried personal samplers for exposure measurements. Inhalable dust and airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic acid were measured. Bronchial responsiveness to methacholine was investigated 1-2 weeks before and 7 h after the start of the exposure. Exposure caused fever (&...

Inhalation of swine dust causes intense alveolar inflammation, with recruitment of inflammatory cells, predominantly neutrophils, but also alveolar macrophages and lymphocytes. The present study focuses on the lymphocyte response to inhaled swine dust. Twenty four healthy, nonsmoking, nonallergic subjects were exposed to swine dust for 3 h in a swine confinement building. Bronchoalveolar lavage (BAL) was performed before and 24 h after the start of exposure, and blood samples were drawn before, and at 7 and 24 h after exposure. Total and differential cell counts were carried out. Monoclonal antibodies recognizing T-cells, T-cell subsets, T-cell activation markers, and B-cells were analysed by flow cytometry. The number of granulocytes increased more than 50 times and alveolar macrophages and lymphocytes increased two- to three-fold in BAL fluid. The exposure did not alter the proportion of T-cells but increased the number of activated T-cells in BAL fluid. The interleukin-2 (IL-2) r...

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Deep inhalations cause a transient relaxation of the peripheral airways smooth muscles in non-asthmatic subjects.It has been claimed thatthe airway response to deep inhalations may be different in asthmatic subjects in whom deep inhalations should rather cause bronchoconstriction.The aim of the present study was to find out whether deep inhalations discriminate between asthmatic and non-asthmatic subjects with pre-constricted airways, usinga methacholine provocation test protocol with deep inhalations following the lastdose of methacholine.In164 adults, a methacholine provocationwas performed.Directly after the FEV 1 measurement atthe highest metacholine concentration, the subjects took one deep breath and another three deep inhalations 20 s later.One minute after the inhalation of the highest concentration FEV 1 was measured twice. Thirty-three asthmatics PD 20 FEV 1 =0.24 mg (0.13^0.39) (median, 25^75th 75th percentiles) and 131 non-asthmatics PD 20 FEV 1 =2.05 mg (0.72^10.1) participated. The mean maximal decrease in FEV 1 after the provocationtest was 36% inthe asthmatics and 27% inthe non-asthmatics.Corresponding values after the deep inhalations were 18% in the asthmatics and 12% in the non-asthmatics. In conclusion, deep inhalations attenuate the methacholine-induced bronchoconstriction in both asthmatic and non-asthmatic subjects.Thus, the e¡ect of deep inhalations did not discriminate between asthmatic and non-asthmatic subjects.