Occupation, socioeconomic status and chronic obstructive respiratory diseases - The EpiLung study in Finland, Estonia and Sweden.

OBJECTIVE: To study occupational groups and occupational exposure in association with chronic obstructive respiratory diseases. METHODS: In early 2000s, structured interviews on chronic respiratory diseases and measurements of lung function as well as fractional expiratory nitric oxide (FENO) were performed in adult random population samples of Finland, Sweden and Estonia. Occupations were categorized according to three classification systems. Occupational exposure to vapours, gases, dusts and fumes (VGDF) was assessed by a Job-Exposure Matrix (JEM). The data from the countries were combined. RESULTS: COPD, smoking and occupational exposure were most common in Estonia, while asthma and occupations requiring higher educational levels in Sweden and Finland. In an adjusted regression model, non-manual workers had a three-fold risk for physician-diagnosed asthma (OR 3.18, 95%CI 1.07-9.47) compared to professionals and executives, and the risk was two-fold for healthcare & social workers (OR 2.28, 95%CI 1.14-4.59) compared to administration and sales. An increased risk for physician-diagnosed COPD was seen in manual workers, regardless of classification system, but in contrast to asthma, the risk was mostly explained by smoking and less by occupational exposure to VGDF. For FENO, no associations with occupation were observed. CONCLUSIONS: In this multicenter study from Finland, Sweden and Estonia, COPD was consistently associated with manual occupations with high smoking prevalence, highlighting the need to control for tobacco smoking in studies on occupational associations. In contrast, asthma tended to associate with non-manual occupations requiring higher educational levels. The occupational associations with asthma were not driven by eosinophilic inflammation presented by increased FENO.

Parallel gradients in FENO and in the prevalences of asthma and atopy in adult general populations of Sweden, Finland and Estonia - A Nordic EpiLung study.

The prevalence of asthma is higher in Sweden and Finland than in neighbouring eastern countries including Estonia. Corresponding difference in bronchial eosinophilic inflammation could be studied by FENO measurements. We aimed to compare FENO in adult general populations of Sweden, Finland, and Estonia, to test the plausibility of the west-east disparity hypothesis of allergic diseases. We conducted clinical interviews (N = 2658) with participants randomly selected from the general populations in Sweden (Stockholm and Örebro), Finland (Helsinki), and Estonia (Narva and Saaremaa), and performed FENO (n = 1498) and skin prick tests (SPT) in 1997-2003. The median (interquartile range) of FENO (ppb) was 15.5 (9.3) in Sweden, 15.4 (13.6) in Finland and 12.5 (9.6) in Estonia. We found the lowest median FENO values in the Estonian centres Saaremaa 13.1 (9.5) and Narva 11.8 (8.6). In the pooled population, asthma was associated with FENO ≥25 ppb, odds ratio (OR) 3.91 (95% confidence intervals: 2.29-6.32) after adjusting for SPT result, smoking, gender and study centre. A positive SPT test increased the likelihood of asthma OR 3.19 (2.02-5.11). Compared to Saaremaa, the likelihood of having asthma was higher in Helsinki OR 2.40 (1.04-6.02), Narva OR 2.45 (1.05-6.19), Örebro OR 3.38 (1.59-8.09), and Stockholm OR 5.54 (2.18-14.79). There was a higher prevalence of asthma and allergic airway inflammation in adult general populations of Sweden and Finland compared to those of Estonia. Atopy and elevated FENO level were independently associated with an increased risk of asthma. In conclusion, the findings support the earlier west-east disparity hypothesis of allergic diseases.

Measurement of bronchial hyperreactivity: comparison of three Nordic dosimetric methods.

Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijärvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijärvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijärvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijärvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.

Cholinergic mechanisms in an organic dust model simulating an acute exacerbation in patients with COPD.

BACKGROUND: Exposure in a pig barn induces airway inflammation that has similarities with the response observed in acute exacerbations in COPD. METHODS: A total of 15 smokers with COPD and 15 healthy non-smokers were exposed for 2 hours in a pig barn (in vivo exposure). Symptoms were assessed, lung function measured, and blood and sputum samples taken before and after exposure. Blood neutrophils were isolated and stimulated ex vivo with dust from a pig barn and acetylcholine, and inflammatory markers were analyzed. RESULTS: In vivo exposure caused more symptoms and greater lung function fall in COPD patients than in controls. Baseline concentrations of MMP9, TIMP1, IL6, CXCL8, in sputum and neutrophil blood count were higher in COPD patients than in controls. In vivo exposure increased MMP9, TIMP1, IL6, CXCL8, TNFα, and LTB4 in sputum and MMP9 and IL6 in blood, with no difference between the groups, and serum CRP increased more in COPD subjects. Expression of choline acetyltransferase and acetylcholinesterase on sputum and blood cells was similar in the groups and uninfluenced by in vivo exposure. Dust exposure ex vivo increased choline acetyltransferase expression in neutrophils, but the dust and acetylcholine response did not differ between the groups before and after in vivo exposure. CONCLUSION: COPD patients exposed in a pig barn experience symptoms similar to those in acute exacerbations and lung function deterioration that is unrelated to bronchial responsiveness. Cholinergic mechanisms are involved in the inflammatory response to dust, with no difference between COPD and non-smokers.

Comparing human respiratory adverse effects after acute exposure to particulate matter in conventional and particle-reduced swine building environments.

OBJECTIVES: To evaluate innate immunity responses, lung function and symptoms in volunteers acutely exposed to organic dust in swine buildings after installing particle separators aimed to reduce particulate matter exposure. METHODS: 11 healthy participants were exposed in 2 different facilities, with and without installed particle separators, in a cross-over design including 2-3 weeks wash-out between the 2 exposures. Size, distribution and composition of particulate matter and endotoxins in the air were measured. Lung function (spirometry), bronchial responsiveness, symptoms questionnaire and markers of innate immunity in blood and nasal lavage were measured before and after the 3-hour exposures. RESULTS: The number of particles, in particular fine particles sized 0.3-0.5 µm, was reduced in the particle-separated swine building environment (PSE) compared with that in the conventional building (CE). In the PSE, headache (p=0.03) and increased body temperature (p=0.016) were less pronounced than in the CE. The expression of toll-like receptors (TLR)2 and TLR4 on blood monocytes significantly increased (p=0.016 and 0.017, respectively) while cluster of differentiation (CD)14 on neutrophils decreased (p=0.05) after exposure in the CE, yet with no difference between the 2 exposures. Compared with the conventional environment, exposure to the PSE yielded lower interleukin (IL)-6 (p=0.02) and IL-8 (p=0.04) levels in the upper respiratory tract, as assessed by nasal lavage. CONCLUSIONS: Particulate matter and organic dust in the swine building were reduced after installing particle separators, which, in naïve never exposed volunteers, in turn reduced adverse health effects caused by acute exposure in swine buildings compared with exposure to the conventional swine building environment.

Extracellular cadmium in the bronchoalveolar space of long-term tobacco smokers with and without COPD and its association with inflammation.

Tobacco contains cadmium, and this metal has been attributed a causative role in pulmonary emphysema among smokers, although extracellular cadmium has not to date been quantified in the bronchoalveolar space of tobacco smokers with or without COPD. We determined whether cadmium is enhanced in the bronchoalveolar space of long-term tobacco smokers with or without COPD in vivo, its association with inflammation, and its effect on chemokine release in macrophage-like cells in vitro. Bronchoalveolar lavage (BAL), sputum, and blood samples were collected from current, long-term smokers with and without COPD and from healthy nonsmokers. Cadmium concentrations were determined in cell-free BAL fluid using inductively coupled plasma mass spectrometry. Blood monocyte-derived macrophages were exposed to cadmium chloride in vitro. Depending upon the type of sample, molecular markers of inflammation were quantified either as protein (enzyme-linked immunosorbent assay) or as mRNA (real-time polymerase chain reaction). Cadmium concentrations were markedly increased in cell-free BAL fluid of smokers compared to that of nonsmokers (n=19-29; P<0.001), irrespective of COPD. In these smokers, the measured cadmium displayed positive correlations with macrophage TNF-α mRNA in BAL, neutrophil and CD8(+) cell concentrations in blood, and finally with IL-6, IL-8, and MMP-9 protein in sputum (n=10-20; P<0.05). The cadmium chloride exposure caused a concentration-dependent increase in extracellular IL-8 protein in monocyte-derived macrophages in vitro. In conclusion, extracellular cadmium is enhanced in the bronchoalveolar space of long-term smokers and displays pro-inflammatory features. Its pathogenic role in tobacco-induced disease deserves further evaluation.

Urinary excretion of lipid mediators in response to repeated eucapnic voluntary hyperpnea in asthmatic subjects.

Exercise-induced bronchoconstriction displays refractoriness manifested as a decreased response to repeated exercise challenge within hours. The refractoriness may be attenuated by inhibition of the biosynthesis of prostaglandins (PG). The aim of the study was to determine which PGs and other lipid mediators are excreted during the refractory period. First, 16 subjects with mild stable asthma performed two repeated 4-min challenges with eucapnic voluntary hyperpnea (EVH) 1 and 3 h apart. There was a similar degree of refractoriness in both protocols (∼15% protection). The 1-h interval was too short to study mediator excretion because the urinary levels did not return to baseline before the second challenge. With the 3-h protocol, there was increased urinary excretion of cysteinyl-leukotrienes and metabolites of the mast cell product PGD2 after both challenges. Next, another eight subjects performed two 6-min challenges with EVH 3 h apart, which produced a greater bronchoconstrictor response than the 4-min protocol (30.0 ± 5.4 vs. 17.7 ± 1.5%; P = 0.0029) and a greater degree of refractoriness (∼30%). Analysis by ultra-performance liquid chromatography triple quadrupole mass spectrometry confirmed excretion of the bronchoconstrictor cysteinyl-leukotrienes and PGD2 during both challenges. In addition, there was increased excretion of the bronchoprotective PGE2, and also of the main metabolite of PGI2. This is the first report of excretion of PGE2 and PGI2 during the refractory period to EVH challenge, suggesting that they may mediate the refractoriness. Maintained excretion of PGD2 and leukotriene E4 following the repeat challenge argues against mast cell mediator depletion as the mechanism of refractoriness.

Long term effect and allergic sensitization in newly employed workers in laboratory animal facilities.

OBJECTIVE: The aim of this study was to identify targets predicting allergic sensitization to laboratory animals using shift in skin prick test to laboratory animals as primary outcome variable. METHODS: In a prospective longitudinal study, personnel who were employed to work with laboratory animals at a medical university were investigated before and 6, 12 and 24 month after the start of employment. Lung function, bronchial challenges, exhaled NO and nasal lavage were performed and blood samples were drawn at all visits. RESULTS: Seventy subjects attended all four visits and 13 (19%) became sensitized to laboratory animals during the two years of follow up. Lung function (VC and FEV1) deteriorated and blood levels of eosinophils and IL-2 producing lymphocytes increased after 24 months. An increased risk of developing laboratory animal allergy was significantly associated with female sex, atopy, symptoms associated with exposure to laboratory animals, low proportion of blood CD4+ cells, specific IgE to rat and mouse and high total IgE when starting to work with laboratory animals. CONCLUSIONS: A sensitization rate of 19% in 2 years, were demonstrated in laboratory animal workers. Atopy, increased total and specific IgE levels (rat and mouse) were the strongest predictors for laboratory animal sensitization. The progressive lung function impairment over time, observed in the whole study population may indicate that exposure in animal facilities induces harmful effects, irrespective to allergic sensitization.

Chronic obstructive pulmonary disease (COPD) during the two last years of life--a retrospective study of decedents.

BACKGROUND: Little is known about the management of patients suffering from chronic obstructive pulmonary disease (COPD) during the last years of life. The aim of the study was to describe how management of COPD is performed in Sweden during the last two years of life. METHODS: From the nationwide Cause of Death register all individuals with COPD as the underlying cause of death during two years were identified in one sparsely and one densely populated area of Sweden. Data were collected from medical records using a pre-defined protocol, especially developed for this purpose. RESULTS: Of 822 individuals with COPD as underlying cause of death, medical records from 729 were available. The COPD diagnosis was based on lung function measurements in approximately half of the patients and median age at COPD diagnosis was 74 years (range 34-95). Women died at younger age, median 78 years (range 52-96) than did men (80 years (51-99)). The median survival time from diagnosis to death was 6 years in men and women in both areas. Among women and men 8.3% and 4.3% were never smokers, respectively. The structure of COPD management differed between the two areas, with utilization of physiotherapists, dieticians and working therapists being more used in the northern area, likely because of differences in accessibility to care institutions. CONCLUSIONS: In Sweden COPD is mostly diagnosed late in life and often not verified by lung function measurements. Opposite to the general population, women with COPD die at a lower age than men.

Dental health in smokers with and without COPD.

The association between chronic obstructive pulmonary disease (COPD) and periodontal disease is sparsely studied. The aim was to describe the co-variation of periodontitis and lung function impairment in smokers. The hypothesis was that the destructive processes in the mouth and the lungs are interdependent due to a general individual susceptibility to detrimental effects of tobacco smoke. Smokers with COPD (n = 28) stage II and III according to GOLD guidelines and smokers without COPD (n = 29) and healthy non-smokers (n = 23) participated in the study. The groups of smokers were matched for cumulative exposure to tobacco smoke. Radiographic, general and dental clinical examination, lung function measurements and quality of life (SF-36) assessment were conducted. The relationship between respiratory and dental outcomes was analyzed. Dental health, assessed by plaque, gingival bleeding, periodontal pocket depth and loss of teeth was impaired in the smokers compared with non-smokers with no major differences between smokers with and without COPD. There was, however, a weak correlation between periodontitis and emphysema/impaired diffusion capacity. Impaired quality of life was associated with smoking and impaired lung function but not influenced by dental status. In conclusion periodontitis was strongly associated with smoking, weakly associated with lung tissue destruction and very weakly or even not at all associated with chronic airflow limitation. The results indicate that, although there was a co-variation between periodontitis and pathologic lung processes in smokers, the risk of developing COPD, as defined by spirometric outcomes, is not associated with the risk of impaired dental health in smokers.

Incidence and prevalence of adult asthma is associated with low socio-economic status.

BACKGROUND: Low socio-economic status is often related to health problems; however, previous studies on asthma, usually cross-sectional, yield inconsistent results. In this study, longitudinal and cross-sectional data on the association between socio-economic status and asthma as well as respiratory symptoms among adults are presented. METHODS: A postal questionnaire was sent on two occasions, 1996 and 2006, to a randomly selected sample of subjects aged 20-69 years in 1996. In total, 4479 subjects participated in both surveys. The questionnaire included questions on asthma, respiratory symptoms and possible determinants. Logistic regression analysis, adjusted for potential confounders, was used to study the association between asthma, respiratory symptoms and socio-economic status. RESULTS: Manual workers in service had the highest prevalence and cumulative incidence for all investigated symptoms and asthma. Despite a large decrease in smokers, the increase in incident bronchitic symptoms was higher than the increase of incident asthma and incident asthmatic symptoms. Low socio-economic status, rhinitis and a family history of asthma were risk factors for having and developing asthma and respiratory symptoms. CONCLUSION: Low socio-economic status is significantly associated with an increased risk for prevalent and incident asthma and respiratory symptoms in this longitudinal population-based survey. The increase in risk was most pronounced in manual workers. Several studies have recently shown an association between low socio-economic status and respiratory symptoms and we conclude that asthma can not be considered as a disease that mainly affects the middle and upper socio-economic classes.

Effect of fluticasone on markers of inflammation and quality of life in steroid-naive patients with mild asthma.

BACKGROUND AND AIMS: Patients with mild asthma may adapt to symptoms that may be neglected at a medical consultation. Despite active airway inflammation, indicating need for treatment symptoms may be poorly perceived and influence on quality of life. The aim was to find out if markers of asthma activity and quality of life are influenced by inhaled steroids in patients who regard themselves as free of symptoms. METHODS: Seventy steroid-free patients with mild asthma were treated with inhaled fluticasone (250 microg twice daily) or placebo for 3 months in a randomised, double-blind, study. Spirometry with reversibility test, exhaled nitric oxide (NO), bronchial responsiveness to methacholine and eucapnic dry air hyperventilation and quality of life [(Asthma Quality of Life Questionnaire (AQLQ)] were assessed before and after treatment. RESULTS: Fluticasone, but not placebo, decreased methacholine responsiveness. Bronchial responsiveness to dry air and exhaled NO levels was significantly lowered by fluticasone compared with placebo. Quality-of-life scores were high already before treatment and were not significantly altered by treatment. CONCLUSION: Treatment with an inhaled steroid in mild asthmatics altered bronchial responsiveness and exhaled NO levels but did not improve quality of life. In mild asthma, there is thus a space for improvement with regard to inflammatory parameters in patients who have only minor symptoms that are not influenced by treatment. In a long-term perspective, the indication for treatment of surrogate markers remains, however, unclear.

Lung function testing influences the attitude toward smoking cessation.

INTRODUCTION: Smoking cessation is the single most effective way to prevent or delay the development of airflow limitation or to reduce its progression in subjects with chronic obstructive pulmonary disease (COPD). The aim of the study was to explore whether performing a spirometry changes attitudes toward smoking cessation. METHOD: A random sample of 513 smokers, of whom 77 had COPD, answered a questionnaire before, shortly after (less than 4 weeks), and 3 months after performing a lung function test. RESULTS: Prior to spirometry, 57% of the smokers with COPD and 52% of those with normal spirometry claimed that they were not planning to quit smoking within the next 6 months. After the spirometry, 9% (p < .0001) of those with COPD and 38% (p = .009) of those with normal spirometry had no intention to stop smoking. Three months later, corresponding figures were 28% in COPD and 48% in smokers with normal spirometry, and the point prevalence of quitters was 30% for the COPD group and 14% for the normal group (p = .02). DISCUSSION: We conclude that performing spirometry changes the attitude toward smoking for a short time. We hypothesize that smokers may be more susceptible to smoking cessation activities during this period.

Evaluation of respiratory effects related to high-pressure cleaning in a piggery with and without robot pre-cleaning.

OBJECTIVE: Exposure in connection with cleaning piggeries induces airway inflammation. The aim of this study was to compare the health effects related to two different cleaning processes in a piggery. METHODS: In a cross-over study design, 12 subjects were randomly exposed for three hours during the cleaning of a piggery with a high pressure water jet, with and without pre-cleaning using a robot. We assessed lung function, bronchial responsiveness, symptoms, body temperature, and exhaled nitric oxide, and performed blood sampling and nasal lavage before and after both exposures. RESULTS: Compared with ordinary cleaning without the use of a robot, pre-cleaning with a robot significantly reduced the increase in bronchial responsiveness (P=0.049), total cell number (P=0.0029), and pro-inflammatory cytokines (IL-8 level [P=0.016]) in nasal lavage, and diminished the increase in neutrophils (P=0.0029) in the blood. CONCLUSION: Pre-cleaning of a piggery with a robot reduced exposure to dust and endotoxin, and resulted in an attenuation of the increase in bronchial responsiveness and the airway inflammatory response compared pre-cleaning without a robot.

No further increase of incidence of asthma: incidence, remission and relapse of adult asthma in Sweden.

BACKGROUND: Knowledge about time trends of disease patterns in society is essential for planning and prioritizing health care resources. Longitudinal population-based studies on asthma are scarce but provide an opportunity to assess incidence, remission and relapse of asthma, and their determinants, which were the objectives of the present study. METHODS: A postal questionnaire was sent on two occasions, 1996 and 2006, to a randomly selected sample of subjects aged 20-69 years in 1996. The response rates were 72% and 83%, respectively, and in total 4479 subjects participated in both surveys. The questionnaire included questions on asthma, respiratory symptoms and possible determinants. Logistic regression was used to assess determinants. RESULTS: Cumulative incidence of asthma was 2.4% (men 1.9%; women 2.8%, p=0.06). Family histories of asthma (OR 2.31, CI 95% 1.42-3.76), rhinitis (OR 2.25, CI 95% 1.43-3.53) and being an ex-smoker (OR 2.17, CI 95% 1.27-3.71) were determinants for incident asthma. The 10-year remission of asthma was 14.6% and inversely associated with rhinitis. Relapse was found in 38% of eligible subjects. CONCLUSIONS: The current study with high participation rates concludes that the incidence of asthma among adults has been stable in Sweden for the past two decades. Remission was associated with mild disease at study start. Relapse in adults has rarely been reported previously and provide new insight in the course of asthma. Low remission and high relapse further support the view of asthma as a chronic disease; possibly representing fluctuations of the disease over time.

High rate of smoking abstinence in COPD patients: Smoking cessation by hospitalization.

Chronic obstructive pulmonary disease (COPD) is mainly caused by smoking, and smoking cessation is the single most important intervention to prevent disease progression. Most studies show that many initially successful quitters relapse within 1 year. Our aim was to study the outcome of a smoking cessation program after 1 and 3 years. Abstinence outcomes in a group of COPD patients who participated in a 1-year smoking cessation program (N = 247) were compared with those of a group of COPD patients who received usual care (N = 231). The smoking cessation program included a 2-week period of hospitalization. Nicotine replacement therapy and physical exercise were recommended, and education was given in group sessions. Feedback and encouraging comments by phone from the specially trained staff continued during the full year. Follow-ups were performed 1 and 3 years after the start of the smoking cessation program. In the intervention group, 52% were smoke free after 1 year and 38% after 3 years. Corresponding quit rates in the control group were 7% after 1 year and 10% after 3 years. We found no significant differences between subjects who had low or high baseline scores on the Fagerström Test for Nicotine Dependence in regard to their ability to stop smoking successfully. This comprehensive smoking cessation program with hospitalization and a long follow-up period resulted in high quit rates even after 3 years. Despite high costs for this aggressive smoking cessation program, beneficial economic effects are likely to be obtained in the long run.

Low awareness of COPD among physicians.

INTRODUCTION: Early identification of patients with chronic obstructive pulmonary disease (COPD) in the health care system followed by successful smoking cessation may prevent rapid lung function deterioration, development of severe COPD and respiratory failure. OBJECTIVES: The aim of this study was to determine the frequency of under-diagnosed chronic obstructive lung diseases among current smokers. MATERIALS AND METHODS: The under-diagnosis of COPD among smokers was determined in subjects who participated in a screening procedure aimed at recruiting COPD patients for a smoking cessation programme. In order to identify current smokers, a questionnaire was sent out to persons who had been on sick leave for various reasons certified by a physician for more than 2 weeks. Subjects who stated that they currently smoked more than eight cigarettes per day were invited to perform a lung function test. RESULTS: A total of 3887 subjects performed spirometry, i.e. forced expiratory volume in 1 s and forced expirations, and among these, 674 (17.3%) had COPD according to the European Respiratory Society (ERS) consensus guidelines. Of those, 103 (17.3%) had physician-diagnosed COPD. Productive cough was reported by 16.6% of the COPD subjects. Despite the fact that smokers were on sick leave certified by a physician, more than 80% of those with COPD had no previous diagnosis. As the COPD diagnosis cannot be based on reported symptoms, a spirometry on persons at risk must be performed. CONCLUSION: The awareness of COPD among primary care physicians has to increase and smokers above the age of 40, with and without respiratory symptoms, have to undergo spirometry if it is regarded important to establish the COPD diagnosis at an early stage.

Effect of respirators equipped with particle or particle-and-gas filters during exposure in a pig confinement building.

OBJECTIVES: This study compared the protective effect of two respiratory protection devices during exposure in a pig confinement building. METHODS: Thirty-six healthy persons were exposed for 3 hours in the building, 12 without any protection, 12 with a particle-filter mask, and 12 with a mask filtering both particles and gases. Symptoms, body temperature, nasal lavage fluid, exhaled nitric oxide, and bronchial responsiveness to methacholine were assessed before and after the exposure. Pre- and postexposure urine and blood samples were collected. RESULTS: After the exposure, the participants with respirators reported fewer symptoms than those without. Wearing a mask also reduced the inflammatory response assessed with nasal lavage (cell concentration, interleukins 6 and 8) and peripheral blood (cell number). Lung function was significantly impaired only in the unprotected group; postexposure vital capacity and forced expiratory volume in 1 second showed a decrease of 3-4% from the preexposure levels (P=0.006 and P=0.002, respectively). Bronchial responsiveness (P<0.01) and body temperature (P<0.001) increased similarly in the three groups. Bronchial responsiveness to methacholine increased 2.7, 2.4, and 2.1 doubling concentration steps for those unprotected, those using a particle-filter mask, and those using a mask with particle and gas filters, respectively. The prostaglandin D2 metabolite, 9a, 11b-PGF2 increased significantly (P=0.003) only in those unprotected. CONCLUSIONS: Wearing a respirator in a pig confinement building reduces the inflammatory reaction but does not influence the increase in bronchial responsiveness, with no difference between the use of a particle-filter mask or a mask with a particle-gas filter combination.

Quality of life and inflammatory markers in mild asthma.

STUDY OBJECTIVES: The aim of this study was to explore the relationship between quality of life and measures of asthma, such as lung function, reversibility to bronchodilation, exhaled nitric oxide (NO), and bronchial responsiveness to direct and indirect stimulus in patients with mild asthma in a primary care setting. PATIENTS AND MEASUREMENTS: Seventy-seven asthmatic patients not treated with glucocorticosteroids completed the Asthma Quality of Life Questionnaire. Spirometry was performed before and after bronchodilation, and bronchial challenges with methacholine and eucapnic dry air hyperventilation were conducted on separate days. NO in exhaled air and serum IgE were also analyzed. RESULTS: We found no correlation between quality of life and any of the other parameters. There was a significant covariation between exhaled NO and bronchial responsiveness to methacholine and dry air, and also between FEV(1) (percentage of predicted) and reversibility to a bronchodilator. The levels of exhaled NO were higher in the asthmatic subjects with atopy than in the nonatopic asthmatics. CONCLUSIONS: The measures used in our study do not reflect health-related quality of life in subjects with mild asthma. We conclude that in the clinical situation, quality of life and other measures of asthma provide complementary information.

Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects.

BACKGROUND: Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. OBJECTIVE: The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. METHODS: Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600 mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. RESULTS: The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2-3 doubling concentration steps, no significant difference between treatments. Leukotriene E(4) in urine increased significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05 vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two-fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects (P<0.05 and P<0.001, respectively compared to placebo). CONCLUSIONS: Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB(4) release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects.