Urinary pesticide mixture patterns and exposure determinants in the adult population from the Netherlands and Switzerland: Application of a suspect screening approach.

INTRODUCTION: Non-occupational sources of pesticide exposure may include domestic pesticide usage, diet, occupational exposure of household members, and agricultural activities in the residential area. We conducted a study with the ambition to characterize pesticide mixture patterns in a sample of the adult population of the Netherlands and Switzerland, using a suspect screening approach and to identify related exposure determinants. METHODS: A total of 105 and 295 adults participated in the Dutch and Swiss studies, respectively. First morning void urine samples were collected and analyzed in the same laboratory. Harmonized questionnaires about personal characteristics, pesticide-related activities, and diet were administered. Detection rates and co-occurrence patterns were calculated to explore internal pesticide exposure patterns. Censored linear and logistic regression models were constructed to investigate the association between exposure and domestic pesticide usage, consumption of homegrown and organic foods, household members' exposure, and distance to agricultural and forest areas. RESULTS: From the 37 detected biomarkers, 3 (acetamiprid (-CH2), chlorpropham (4-HSA), and flonicamid (-C2HN)) were detected in ≥40% of samples. The most frequent combination of biomarkers (acetamiprid-flonicamid) was detected in 22 (5.5%) samples. Regression models revealed an inverse association between high organic vegetable and fruit consumption and exposure to acetamiprid, chlorpropham, propamocarb (+O), and pyrimethanil (+O + SO3). Within-individual correlations in repeated samples (summer/winter) from the Netherlands were low (≤0.3), and no seasonal differences in average exposures were observed in Switzerland. CONCLUSION: High consumption of organic fruit and vegetables was associated with lower pesticide exposure. In the two countries, detection rates and co-occurrence were typically low, and within-person variability was high. Our study results provide an indication for target biomarkers to include in future studies aimed at quantifying urinary exposure levels in European adult populations.

Microbial characteristics in homes of asthmatic and non-asthmatic adults in the ECRHS cohort.

Microbial exposures in homes of asthmatic adults have been rarely investigated; specificities and implications for respiratory health are not well understood. The objectives of this study were to investigate associations of microbial levels with asthma status, asthma symptoms, bronchial hyperresponsiveness (BHR), and atopy. Mattress dust samples of 199 asthmatics and 198 control subjects from 7 European countries participating in the European Community Respiratory Health Survey II study were analyzed for fungal and bacterial cell wall components and individual taxa. We observed trends for protective associations of higher levels of mostly bacterial markers. Increased levels of muramic acid, a cell wall component predominant in Gram-positive bacteria, tended to be inversely associated with asthma (OR's for different quartiles: II 0.71 [0.39-1.30], III 0.44 [0.23-0.82], and IV 0.60 [0.31-1.18] P for trend .07) and with asthma score (P for trend .06) and with atopy (P for trend .02). These associations were more pronounced in northern Europe. This study among adults across Europe supports a potential protective effect of Gram-positive bacteria in mattress dust and points out that this may be more pronounced in areas where microbial exposure levels are generally lower.

Development of a job-task-exposure matrix to assess occupational exposure to disinfectants among US nurses.

OBJECTIVES: Occupational exposure to disinfectants is associated with work-related asthma, especially in healthcare workers. However, little is known about the specific products involved. To evaluate disinfectant exposures, we designed job-exposure (JEM) and job-task-exposure (JTEM) matrices, which are thought to be less prone to differential misclassification bias than self-reported exposure. We then compared the three assessment methods: self-reported exposure, JEM and JTEM. METHODS: Disinfectant use was assessed by an occupational questionnaire in 9073 US female registered nurses without asthma, aged 49-68 years, drawn from the Nurses' Health Study II. A JEM was created based on self-reported frequency of use (1-3, 4-7 days/week) of 7 disinfectants and sprays in 8 nursing jobs. We then created a JTEM combining jobs and disinfection tasks to further reduce misclassification. Exposure was evaluated in 3 classes (low, medium, high) using product-specific cut-offs (eg, <30%, 30-49.9%, ≥50%, respectively, for alcohol); the cut-offs were defined from the distribution of self-reported exposure per job/task. RESULTS: The most frequently reported disinfectants were alcohol (weekly use: 39%), bleach (22%) and sprays (20%). More nurses were classified as highly exposed by JTEM (alcohol 41%, sprays 41%, bleach 34%) than by JEM (21%, 30%, 26%, respectively). Agreement between JEM and JTEM was fair-to-moderate (κ 0.3-0.5) for most disinfectants. JEM and JTEM exposure estimates were heterogeneous in most nursing jobs, except in emergency room and education/administration. CONCLUSIONS: The JTEM may provide more accurate estimates than the JEM, especially for nursing jobs with heterogeneous tasks. Use of the JTEM is likely to reduce exposure misclassification.

School attendance and daily respiratory symptoms in children: influence of moisture damage.

We investigated the effect of weekends and school holidays on the daily frequency and severity of respiratory and other symptoms among children attending schools with (index) or without (reference) moisture damage in Spain, the Netherlands, and Finland. Throughout 1 year, parents of 419 children with a respiratory condition attending index (n=15) or reference (n=10) primary schools completed three symptom diaries. We assessed associations between lower respiratory tract, upper respiratory tract or allergy, and other symptom scores and school day, weekend, or summer holiday using mixed regression models stratified by country and moisture damage. We evaluated interactions between moisture damage and type of day. We combined country-specific estimates (incidence rate ratios [IRRs] and 95% confidence interval [CI]) in meta-analyses. Symptom scores were lower during weekends and holiday. Lower respiratory tract symptoms were statistically significantly less common during holiday with strongest effect in index schools (IRR=0.7; CI=0.6-0.8). Reporting of other symptoms was more reduced during holiday in index (IRR=0.6; CI=0.4-0.9) than in reference (IRR=0.95; CI=0.8-1.2) schools (interaction P<.01). In conclusion, symptoms were less frequent and/or severe during summer holiday and weekends. This pattern was stronger among children attending moisture-damaged schools, suggesting potential improvement in moisture damage-related symptoms during school breaks.

Building dampness and mold in European homes in relation to climate, building characteristics and socio-economic status: The European Community Respiratory Health Survey ECRHS II.

We studied dampness and mold in homes in relation to climate, building characteristics and socio-economic status (SES) across Europe, for 7127 homes in 22 centers. A subsample of 3118 homes was inspected. Multilevel analysis was applied, including age, gender, center, SES, climate, and building factors. Self-reported water damage (10%), damp spots (21%), and mold (16%) in past year were similar as observed data (19% dampness and 14% mold). Ambient temperature was associated with self-reported water damage (OR=1.63 per 10°C; 95% CI 1.02-2.63), damp spots (OR=2.95; 95% CI 1.98-4.39), and mold (OR=2.28; 95% CI 1.04-4.67). Precipitation was associated with water damage (OR=1.12 per 100 mm; 95% CI 1.02-1.23) and damp spots (OR=1.11; 95% CI 1.02-1.20). Ambient relative air humidity was not associated with indoor dampness and mold. Older buildings had more dampness and mold (P<.001). Manual workers reported less water damage (OR=0.69; 95% CI 0.53-0.89) but more mold (OR=1.27; 95% CI 1.03-1.55) as compared to managerial/professional workers. There were correlations between reported and observed data at center level (Spearman rho 0.61 for dampness and 0.73 for mold). In conclusion, high ambient temperature and precipitation and high building age can be risk factors for dampness and mold in homes in Europe.

Inflammatory potential in relation to the microbial content of settled dust samples collected from moisture-damaged and reference schools: results of HITEA study.

Aiming to identify factors causing the adverse health effects associated with moisture-damaged indoor environments, we analyzed immunotoxicological potential of settled dust from moisture-damaged and reference schools in relation to their microbiological composition. Mouse RAW264.7 macrophages were exposed to settled dust samples (n = 25) collected from moisture-damaged and reference schools in Spain, the Netherlands, and Finland. After exposure, we analyzed production of inflammatory markers [nitric oxide (NO), tumor necrosis factor-α (TNF-)α, interleukin (IL)-6, and macrophage inflammatory protein (MIP)2] as well as mitochondrial activity, viability, apoptosis, and cell cycle arrest. Furthermore, particle counts, concentration of selected microbial groups as well as chemical markers such as ergosterol, 3-hydroxy fatty acids, muramic acid, endotoxins, and glucans were measured as markers of exposure. Dust from moisture-damaged schools in Spain and the Netherlands induced stronger immunotoxicological responses compared to samples from reference schools; the responses to Finnish samples were generally lower with no difference between the schools. In multivariate analysis, IL-6 and apoptosis responses were most strongly associated with moisture status of the school. The measured responses correlated with several microbial markers and numbers of particles, but the most important predictor of the immunotoxicological potential of settled dust was muramic acid concentration, a marker of Gram-positive bacteria.

Occupational exposure to endocrine disruptors and lymphoma risk in a multi-centric European study.

BACKGROUND: Incidence rates of lymphoma are usually higher in men than in women, and oestrogens may protect against lymphoma. METHODS: We evaluated occupational exposure to endocrine disrupting chemicals (EDCs) among 2457 controls and 2178 incident lymphoma cases and subtypes from the European Epilymph study. RESULTS: Over 30 years of exposure to EDCs compared to no exposure was associated with a 24% increased risk of mature B-cell neoplasms (P-trend=0.02). Associations were observed among men, but not women. CONCLUSIONS: Prolonged occupational exposure to endocrine disruptors seems to be moderately associated with some lymphoma subtypes.

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56 years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed.

EAACI position paper: irritant-induced asthma.

The term irritant-induced (occupational) asthma (IIA) has been used to denote various clinical forms of asthma related to irritant exposure at work. The causal relationship between irritant exposure(s) and the development of asthma can be substantiated by the temporal association between the onset of asthma symptoms and a single or multiple high-level exposure(s) to irritants, whereas this relationship can only be inferred from epidemiological data for workers chronically exposed to moderate levels of irritants. Accordingly, the following clinical phenotypes should be distinguished within the wide spectrum of irritant-related asthma: (i) definite IIA, that is acute-onset IIA characterized by the rapid onset of asthma within a few hours after a single exposure to very high levels of irritant substances; (ii) probable IIA, that is asthma that develops in workers with multiple symptomatic high-level exposures to irritants; and (iii) possible IIA, that is asthma occurring with a delayed-onset after chronic exposure to moderate levels of irritants. This document prepared by a panel of experts summarizes our current knowledge on the diagnostic approach, epidemiology, pathophysiology, and management of the various phenotypes of IIA.

Endotoxin levels in settled airborne dust in European schools: the HITEA school study.

Indoor exposure to microbial agents is known to influence respiratory health. Besides home exposure, exposure in schools can affect respiratory health. In this study, we measured endotoxin in settled dust in primary schools in three European countries from three different geographical regions with different climates. Our aim was to characterize endotoxin levels in primary schools and evaluate associations with potential determinants. Endotoxin levels were repeatedly assessed in 23 schools in Spain (n = 7), the Netherlands (n = 10), and Finland (n = 6) using electrostatic dustfall collectors. In total, 645 measurements were taken in 237 classrooms. Endotoxin levels differed significantly between countries; Dutch schools had the highest levels, while Finnish schools showed the lowest levels. In each country, differences in endotoxin levels were observed between schools and over the sampling periods. Estimates improved after adjustment for sampling period. Factors affecting endotoxin levels in a school differed per country. In general, endotoxin levels were higher in lower grades and in classrooms with higher occupancy. School endotoxin levels may contribute significantly to total endotoxin exposure in children and teachers. As the correlation between the repeated measurements is reasonable, single endotoxin measurements form a reasonable basis for estimating annual endotoxin levels in schools.

Asthma and exposure to cleaning products - a European Academy of Allergy and Clinical Immunology task force consensus statement.

Professional and domestic cleaning is associated with work-related asthma (WRA). This position paper reviews the literature linking exposure to cleaning products and the risk of asthma and focuses on prevention. Increased risk of asthma has been shown in many epidemiological and surveillance studies, and several case reports describe the relationship between exposure to one or more cleaning agents and WRA. Cleaning sprays, bleach, ammonia, disinfectants, mixing products, and specific job tasks have been identified as specific causes and/or triggers of asthma. Because research conclusions and policy suggestions have remained unheeded by manufactures, vendors, and commercial cleaning companies, it is time for a multifaceted intervention. Possible preventive measures encompass the following: substitution of cleaning sprays, bleach, and ammonia; minimizing the use of disinfectants; avoidance of mixing products; use of respiratory protective devices; and worker education. Moreover, we suggest the education of unions, consumer, and public interest groups to encourage safer products. In addition, information activities for the general population with the purpose of improving the knowledge of professional and domestic cleaners regarding risks and available preventive measures and to promote strict collaboration between scientific communities and safety and health agencies are urgently needed.

Respiratory health and endotoxin: associations and modification by CD14/-260 genotype.

Exposure to endotoxin has been associated with increased respiratory symptoms and decrements in lung function in occupational settings but little is known about the health effects of domestic exposure in adults. Here, we describe the association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial reactivity and lung function with mattress endotoxin levels in adults, and determine whether these associations are modified by polymorphisms in CD14. Endotoxin levels in mattress dust from a population-based sample of 972 adults were measured. Associations were examined using generalised linear mixed models, adjusting for individual and household confounders. Effect modification of these associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels varied from 0.1 to 402.6 EU · mg(-1). Although there was no overall association of lung function with endotoxin exposure, there was evidence that the association of forced expiratory volume in 1 s and forced vital capacity with endotoxin was modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013, respectively). There was no evidence that symptoms, IgE sensitisation or bronchial reactivity were associated with mattress endotoxin levels. In this large epidemiological study of adults, there was no evidence that mattress endotoxin level was associated with respiratory symptoms or IgE sensitisation but the association of lung function with endotoxin levels may be modified by CD14 genotype.

Geographical variation and the determinants of domestic endotoxin levels in mattress dust in Europe.

UNLABELLED: Endotoxin exposures have manifold effects on human health. The geographical variation and determinants of domestic endotoxin levels in Europe have not yet been extensively described. To investigate the geographical variation and determinants of domestic endotoxin concentrations in mattress dust in Europe using data collected in the European Community Respiratory Health Survey follow-up (ECRHS II). Endotoxin levels were measured in mattress dust from 974 ECRHS II participants from 22 study centers using an immunoassay. Information on demographic, lifestyle, and housing characteristics of the participants was obtained in face-to-face interviews. The median endotoxin concentration in mattress dust ranged from 772 endotoxin units per gram (EU/g) dust in Reykjavik, Iceland, to 4806 EU/g in Turin, Italy. High average outdoor summer temperature of study center, cat or dog keeping, a high household crowding index, and visible damp patches in the bedroom were significantly associated with a higher endotoxin concentrations in mattress dust. There is a large variability in domestic endotoxin levels across Europe. Average outdoor summer temperature of study center, which explains only 10% of the variation in domestic endotoxin level by center, is the strongest meteorological determinant. The observed variation needs to be taken into account when evaluating the health effects of endotoxin exposures in international contexts. PRACTICAL IMPLICATIONS: The incoherent observations of the health effects of endotoxin may be partly owing to the geographical heterogeneity of endotoxin exposure. Therefore, the observed variation should be considered in further studies. Measurements of indoor endotoxin are recommended as an indicator for the level of exposures of individual domestic environments.

Occurrence of moisture problems in schools in three countries from different climatic regions of Europe based on questionnaires and building inspections - the HITEA study.

UNLABELLED: The aim of this study was to assess occurrence of dampness and mold in school buildings in three European countries (the Netherlands, Spain, and Finland), representing different climatic regions. An assessment was performed utilizing both questionnaires and on-site building investigations, and the agreement between these two methods was evaluated for validation purposes. On the basis of questionnaire data from a representative sample of schools, different types of moisture problems were reported in 24-47% of all school buildings at the time of the study. Most commonly reported was dampness in the Netherlands, moisture/water damage in Spain, and mold odor in Finland. Subsequently, 20-24 schools per country were selected for on-site inspections by trained staff. The overall agreement between the questionnaire and inspection data was good (kappa-value 0.62), however, with large differences (0.39-0.91) between countries. Extrapolating from the inspection data, the minimum estimates for prevalence of moisture problems in school buildings are 20% in the Netherlands, 41% in Spain, and 24% in Finland. In conclusion, moisture problems (such as moisture damage, dampness, and mold) are relatively common in schools. The occurrence and severity may vary across geographical areas, which can be partly explained by building characteristics. PRACTICAL IMPLICATIONS: On the basis of this study, the prevalence of verified moisture problems in school buildings was highest in Spain, but lower and similar in Finland and the Netherlands. Questionnaire-based surveys can be used to assess moisture problems in school buildings, but because of large variation in agreement with inspection data, the questionnaire needs to be validated by on-site inspections in a subsample of the surveyed buildings.

Healthy hire effect, job selection and inhalation exposure among young adults with asthma.

The aim of the present study was to assess whether asthma onset prior to entering the workforce influences whether a person holds a subsequent job with asthma-related inhalation exposures. The data of 19,784 adults from the European Community Respiratory Health Survey were analysed. For each respondent, a current or previously held job was linked to a job exposure matrix assigning high, low or no exposure to dust, gases or fumes. Jobs were also categorised according to the risk of exposures related to occupational asthma. Associations between asthma and subsequent occupational exposures were assessed using logistic regression models, with a random intercept for study centre and fixed adjustment for age, sex, type of study sample and smoking status. Of the respondents, 8% (n = 1,619) reported asthma with onset before completion of full-time education. This population was at decreased risk of having a job with high (odds ratio 0.79; 95% confidence interval 0.68-0.92) or low (0.91; 0.80-1.03) exposure to dust, gases or fumes. The associations were consistent across exposure types (dusts, gases or fumes) and for jobs with a high risk of occupational asthma. Adults with asthma onset prior to entering the workforce may be less likely to hold jobs involving inhalation exposures.

The occupational contribution to severe exacerbation of asthma.

The goal of this study was to identify occupational risk factors for severe exacerbation of asthma and estimate the extent to which occupation contributes to these events. The 966 participants were working adults with current asthma who participated in the follow-up phase of the European Community Respiratory Health Survey. Severe exacerbation of asthma was defined as self-reported unplanned care for asthma in the past 12 months. Occupations held in the same period were combined with a general population job-exposure matrix to assess occupational exposures. 74 participants reported having had at least one severe exacerbation event, for a 1-yr cumulative incidence of 7.7%. From regression models that controlled for confounders, the relative risk (RR) was statistically significant for low (RR 1.7, 95% CI 1.1-2.6) and high (RR 3.6, 95% CI 2.2-5.8) biological dust exposure, high mineral dust exposure (RR 1.8, 95% CI 1.02-3.2), and high gas and fumes exposure (RR 2.5, 95% CI 1.2-5.5). The summary category of high dust, gas, or fumes exposure had RR 3.1 (95% CI 1.9-5.1). Based on this RR, the population attributable risk was 14.7% among workers with current asthma. These results suggest occupation contributes to approximately one in seven cases of severe exacerbation of asthma in a working population, and various agents play a role.

An international prospective general population-based study of respiratory work disability.

BACKGROUND: Previous cross-sectional studies have shown that job change due to breathing problems at the workplace (respiratory work disability) is common among adults of working age. That research indicated that occupational exposure to gases, dust and fumes was associated with job change due to breathing problems, although causal inferences have been tempered by the cross-sectional nature of previously available data. There is a need for general population-based prospective studies to assess the incidence of respiratory work disability and to delineate better the roles of potential predictors of respiratory work disability. METHODS: A prospective general population cohort study was performed in 25 centres in 11 European countries and one centre in the USA. A longitudinal analysis was undertaken of the European Community Respiratory Health Survey including all participants employed at any point since the baseline survey, 6659 subjects randomly sampled and 779 subjects comprising all subjects reporting physician-diagnosed asthma. The main outcome measure was new-onset respiratory work disability, defined as a reported job change during follow-up attributed to breathing problems. Exposure to dusts (biological or mineral), gases or fumes during follow-up was recorded using a job-exposure matrix. Cox proportional hazard regression modelling was used to analyse such exposure as a predictor of time until job change due to breathing problems. RESULTS: The incidence rate of respiratory work disability was 1.2/1000 person-years of observation in the random sample (95% CI 1.0 to 1.5) and 5.7/1000 person-years in the asthma cohort (95% CI 4.1 to 7.8). In the random population sample, as well as in the asthma cohort, high occupational exposure to biological dust, mineral dust or gases or fumes predicted increased risk of respiratory work disability. In the random sample, sex was not associated with increased risk of work disability while, in the asthma cohort, female sex was associated with an increased disability risk (hazard ratio 2.8, 95% CI 1.3 to 5.9). CONCLUSIONS: Respiratory work disability is common overall. It is associated with workplace exposures that could be controlled through preventive measures.

Swimming pool attendance and risk of asthma and allergic symptoms in children.

Increased asthma risk has been associated with pool attendance in children but evidence is inconsistent and inconclusive. A survey was conducted of 3,223 9-12-yr-old children in Sabadell (Spain) to evaluate association between swimming pool attendance and prevalence of asthma and allergic conditions and symptoms. Parents completed a questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis), ever having asthma and eczema, and potential confounders. Indicators of indoor and outdoor swimming pool attendance early in life, cumulatively and currently were calculated. Swimming pool attendance before the age of 2 yrs was associated with slightly lower prevalence of current asthma (OR 0.79, 95% CI 0.43-1.46), rhinitis (OR 0.86, 95% CI 0.68-1.08) and allergic rhinitis symptoms (OR 0.72, 95% CI 0.54-0.96) compared to those who started attending swimming pools after 4 yrs of age. An increased prevalence of eczema was associated with duration of lifetime pool attendance (OR 1.71, 95%CI 1.38-2.12 for >5 yrs versus 0 yrs). Swimming pool attendance in Spanish children was associated with slightly less upper and lower respiratory tract symptoms and with more eczema. Longitudinal studies are required to confirm these findings and avoid potential reverse causation.

Occupational exposures and COPD: an ecological analysis of international data.

The occupational contribution to chronic obstructive pulmonary disease (COPD) has yet to be put in a global perspective. In the present study, an ecological approach to this question was used, analysing group-level data from 90 sex-specific strata from 45 sites of the Burden of Obstructive Lung Disease study, the Latin American Project for the Investigation of Obstructive Lung Disease and the European Community Respiratory Health Survey follow-up. These data were used to study the association between occupational exposures and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or above. Regression analysis of the sex-specific group-level prevalence rates of COPD at each site against the prevalence of occupational exposure and ever-smoking was performed, taking into account mean smoking pack-yrs and mean age by site, sex, study cohort and sample size. For the entire data set, the prevalence of exposures predicted COPD prevalence (0.8% increase in COPD prevalence per 10% increase in exposure prevalence). By comparison, for every 10% increase in the proportion of the ever-smoking population, the prevalence of COPD GOLD stage II or above increased by 1.3%. Given the observed median population COPD prevalence of 3.4%, the model predicted that a 20% relative reduction in the disease burden (i.e. to a COPD prevalence of 2.7%) could be achieved by a 5.4% reduction in overall smoking rates or an 8.8% reduction in the prevalence of occupational exposures. When the data set was analysed by sex-specific site data, among males, the occupational effect was a 0.8% COPD prevalence increase per 10% change in exposure prevalence; among females, a 1.0% increase in COPD per 10% change in exposure prevalence was observed. Within the limitations of an ecological analysis, these findings support a worldwide association between dusty trades and chronic obstructive pulmonary disease for both females and males, placing this within the context of the dominant role of cigarette smoking in chronic obstructive pulmonary disease causation.

GA2LEN (Global Allergy and Asthma European Network) addresses the allergy and asthma 'epidemic'.

Allergic diseases represent a major health problem in Europe. They are increasing in prevalence, severity and costs. The Global Allergy and Asthma European Network (GA(2)LEN), a Sixth EU Framework Program for Research and Technological Development (FP6) Network of Excellence, was created in 2005 as a vehicle to ensure excellence in research bringing together research and clinical institutions to combat fragmentation in the European research area and to tackle allergy in its globality. The Global Allergy and Asthma European Network has benefited greatly from the voluntary efforts of researchers who are strongly committed to this model of pan-European collaboration. The network was organized in order to increase networking for scientific projects in allergy and asthma around Europe and to make GA(2)LEN the world leader in the field. Besides these activities, research has also been carried out and the first papers are being published. Achievements of the Global Allergy and Asthma European Network can be grouped as follows: (i) those for a durable infrastructure built up during the project phase, (ii) those which are project-related and based on these novel infrastructures, and (iii) the development and implementation of guidelines. The major achievements of GA(2)LEN are reported in this paper.