Spirometric patterns in young and middle-aged adults: a 20-year European study.

BACKGROUND: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). METHODS: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV1/FVC≥LLN and FVC<10th percentile, obstructive if FEV1/FVC

Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study.

BACKGROUND: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). METHODS: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. RESULTS: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (<-0.25 kg/year) exhibited an attenuation of FVC and FEV1 declines. We found no association between weight change profiles and FEV1/FVC decline. CONCLUSION: Moderate and high weight gain over 20 years was associated with accelerated lung function decline, while weight loss was related to its attenuation. Control of weight gain is important for maintaining good lung function in adult life.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

Effects of smoking bans on passive smoking exposure at work and at home. The European Community respiratory health survey.

This longitudinal study investigated whether smoking bans influence passive smoking at work and/or at home in the same subjects. Passive smoking at work and/or at home was investigated in random population samples (European Community Respiratory Health Survey) in 1990-1995, with follow-up interviews in 1998-2003 and 2010-2014. National smoking bans were classified as partial (restricted to public workplaces) or global (extended to private workplaces). Multivariable analysis was accomplished by three-level logistic regression models, where level-1, level-2, and level-3 units were, respectively, questionnaire responses, subjects, and centers. Passive smoking at work was reported by 31.9% in 1990-1995, 17.5% in 1998-2003, and 2.5% in 2010-2014. Concurrently, passive smoking at home decreased from 28.9% to 18.2% and 8.8%. When controlling for sex, age, education, smoking status, and ECHRS wave, the odds of passive smoking at work was markedly reduced after global smoking bans (OR = 0.45, 95% CI 0.25-0.81), particularly among non-smokers, while the protective effect of global smoking bans on passive smoking at home was only detected in non-smokers. Smoking bans both in public and private workplaces were effective in reducing passive smoking at work in Europe. However, given the inefficacy of smoking bans in current smokers' dwellings, better strategies are needed to avoid smoking indoors.

Cleaning at Home and at Work in Relation to Lung Function Decline and Airway Obstruction.

RATIONALE: Cleaning tasks may imply exposure to chemical agents with potential harmful effects to the respiratory system, and increased risk of asthma and respiratory symptoms among professional cleaners and in persons cleaning at home has been reported. Long-term consequences of cleaning agents on respiratory health are, however, not well described. OBJECTIVES: This study aimed to investigate long-term effects of occupational cleaning and cleaning at home on lung function decline and airway obstruction. METHODS: The European Community Respiratory Health Survey (ECRHS) investigated a multicenter population-based cohort at three time points over 20 years. A total of 6,235 participants with at least one lung function measurement from 22 study centers, who in ECRHS II responded to questionnaire modules concerning cleaning activities between ECRHS I and ECRHS II, were included. The data were analyzed with mixed linear models adjusting for potential confounders. MEASUREMENTS AND MAIN RESULTS: As compared with women not engaged in cleaning (ΔFEV1 = -18.5 ml/yr), FEV1 declined more rapidly in women responsible for cleaning at home (-22.1; P = 0.01) and occupational cleaners (-22.4; P = 0.03). The same was found for decline in FVC (ΔFVC = -8.8 ml/yr; -13.1, P = 0.02; and -15.9, P = 0.002; respectively). Both cleaning sprays and other cleaning agents were associated with accelerated FEV1 decline (-22.0, P = 0.04; and -22.9, P = 0.004; respectively). Cleaning was not significantly associated with lung function decline in men or with FEV1/FVC decline or airway obstruction. CONCLUSIONS: Women cleaning at home or working as occupational cleaners had accelerated decline in lung function, suggesting that exposures related to cleaning activities may constitute a risk to long-term respiratory health.

Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study.

BACKGROUND: It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. OBJECTIVE: We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. METHODS: We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st-3rd quartiles: 29-44) by their level of airway responsiveness using quintiles of methacholine dose-response slope at the first examination (1991-1994). Then, we excluded subjects with airflow obstruction at the second examination (1999-2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010-2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. RESULTS: We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose-response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. CONCLUSIONS: Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression.

Prevalence of asthma-like symptoms with ageing.

BACKGROUND: Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy. METHODS: The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20-44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates. FINDINGS: Over 20 years the prevalence of 'wheeze' and 'wheeze in the absence of a cold' decreased (-2.4%, 95% CI -3.5 to -1.3%; -1.5%, 95% CI -2.4 to -0.6%, respectively) but the prevalence of asthma attacks, use of asthma medication and hay fever/nasal allergies increased (0.6%, 95% CI 0.1 to 1.11; 3.6%, 95% CI 3.0 to 4.2; 2.7%, 95% CI 1.7 to 3.7). Changes were similar in the first 10 years compared with the second 10 years, except for hay fever/nasal allergies (increase seen in the first 10 years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hay fever/nasal allergies at baseline. INTERPRETATION: European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hay fever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing.

Occupational exposures and 20-year incidence of COPD: the European Community Respiratory Health Survey.

BACKGROUND: Occupational exposures have been associated with an increased risk of COPD. However, few studies have related objectively assessed occupational exposures to prospectively assessed incidence of COPD, using postbronchodilator lung function tests. Our objective was to examine the effect of occupational exposures on COPD incidence in the European Community Respiratory Health Survey. METHODS: General population samples aged 20-44 were randomly selected in 1991-1993 and followed up 20 years later (2010-2012). Spirometry was performed at baseline and at follow-up, with incident COPD defined using a lower limit of normal criterion for postbronchodilator FEV1/FVC. Only participants without COPD and without current asthma at baseline were included. Coded job histories during follow-up were linked to a Job-Exposure Matrix, generating occupational exposure estimates to 12 categories of agents. Their association with COPD incidence was examined in log-binomial models fitted in a Bayesian framework. FINDINGS: 3343 participants fulfilled the inclusion criteria; 89 of them had COPD at follow-up (1.4 cases/1000 person-years). Participants exposed to biological dust had a higher incidence of COPD compared with those unexposed (relative risk (RR) 1.6, 95% CI 1.1 to 2.3), as did those exposed to gases and fumes (RR 1.5, 95% CI 1.0 to 2.2) and pesticides (RR 2.2, 95% CI 1.1 to 3.8). The combined population attributable fraction for these exposures was 21.0%. INTERPRETATION: These results substantially strengthen the evidence base for occupational exposures as an important risk factor for COPD.

Absolute values of lung function explain the sex difference in breathlessness in the general population.

Activity-related breathlessness is twice as common among females as males in the general population and is associated with adverse health outcomes. We tested whether this sex difference is explained by the lower absolute forced expiratory volume in 1 s (FEV1) or forced vital capacity (FVC) in females.This was a cross-sectional analysis of 3250 subjects (51% female) aged 38-67 years across 13 countries in the population-based third European Community Respiratory Health Survey. Activity-related breathlessness was measured using the modified Medical Research Council (mMRC) scale. Associations with mMRC were analysed using ordered logistic regression clustering on centre, adjusting for post-bronchodilator spirometry, body mass index, pack-years smoking, cardiopulmonary diseases, depression and level of exercise.Activity-related breathlessness (mMRC ≥1) was twice as common in females (27%) as in males (14%) (odds ratio (OR) 2.21, 95% CI 1.79-2.72). The sex difference was not reduced when controlling for FEV1 % predicted (OR 2.33), but disappeared when controlling for absolute FEV1 (OR 0.89, 95% CI 0.69-1.14). Absolute FEV1 explained 98-100% of the sex difference adjusting for confounders. The effect was similar within males and females, when using FVC instead of FEV1 and in healthy never-smokers.The markedly more severe activity-related breathlessness among females in the general population is explained by their smaller spirometric lung volumes.

Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II.

Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3-2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma.

Obtaining patient phenotypes in SARS-CoV-2 pneumonia, and their association with clinical severity and mortality.

BACKGROUND: There exists consistent empirical evidence in the literature pointing out ample heterogeneity in terms of the clinical evolution of patients with COVID-19. The identification of specific phenotypes underlying in the population might contribute towards a better understanding and characterization of the different courses of the disease. The aim of this study was to identify distinct clinical phenotypes among hospitalized patients with SARS-CoV-2 pneumonia using machine learning clustering, and to study their association with subsequent clinical outcomes as severity and mortality. METHODS: Multicentric observational, prospective, longitudinal, cohort study conducted in four hospitals in Spain. We included adult patients admitted for in-hospital stay due to SARS-CoV-2 pneumonia. We collected a broad spectrum of variables to describe exhaustively each case: patient demographics, comorbidities, symptoms, physiological status, baseline examinations (blood analytics, arterial gas test), etc. For the development and internal validation of the clustering/phenotype models, the dataset was split into training and test sets (50% each). We proposed a sequence of machine learning stages: feature scaling, missing data imputation, reduction of data dimensionality via Kernel Principal Component Analysis (KPCA), and clustering with the k-means algorithm. The optimal cluster model parameters -including k, the number of phenotypes- were chosen automatically, by maximizing the average Silhouette score across the training set. RESULTS: We enrolled 1548 patients, each of them characterized by 92 clinical attributes (d=109 features after variable encoding). Our clustering algorithm identified k=3 distinct phenotypes and 18 strongly informative variables: Phenotype A (788 cases [50.9% prevalence] - age ∼ 57, Charlson comorbidity ∼ 1, pneumonia CURB-65 score ∼ 0 to 1, respiratory rate at admission ∼ 18 min-1, FiO2 ∼ 21%, C-reactive protein CRP ∼ 49.5 mg/dL [median within cluster]); phenotype B (620 cases [40.0%] - age ∼ 75, Charlson ∼ 5, CURB-65 ∼ 1 to 2, respiration ∼ 20 min-1, FiO2 ∼ 21%, CRP ∼ 101.5 mg/dL); and phenotype C (140 cases [9.0%] - age ∼ 71, Charlson ∼ 4, CURB-65 ∼ 0 to 2, respiration ∼ 30 min-1, FiO2 ∼ 38%, CRP ∼ 152.3 mg/dL). Hypothesis testing provided solid statistical evidence supporting an interaction between phenotype and each clinical outcome: severity and mortality. By computing their corresponding odds ratios, a clear trend was found for higher frequencies of unfavourable evolution in phenotype C with respect to B, as well as more unfavourable in phenotype B than in A. CONCLUSION: A compound unsupervised clustering technique (including a fully-automated optimization of its internal parameters) revealed the existence of three distinct groups of patients - phenotypes. In turn, these showed strong associations with the clinical severity in the progression of pneumonia, and with mortality.

Gas cooking indoors and respiratory symptoms in the ECRHS cohort.

BACKGROUND: Gas cooking is an important source of indoor air pollutants, and there is some limited evidence that it might adversely be associated with respiratory health. Using repeated cross-sectional data from the multi-centre international European Community Respiratory Health Survey, we assessed whether adults using gas cookers have increased risk of respiratory symptoms compared to those using electric cookers and tested whether there was effect modification by a priori selected factors. METHODS: Data on respiratory symptoms and gas cooking were collected from participants at 26-55 and 38-67 years (median time between examinations 11.4 years) from interviewer-led questionnaires. Repeated associations between gas cooking (versus electric) and respiratory symptoms were estimated using multivariable mixed-effects logistic regression models adjusted for age, sex, study arm, smoking status, education level, and included random intercepts for participants within study centres. Analyses were repeated using a 3-level variable for type of cooker and gas source. Effect modification by ventilation habits, cooking duration, sex, age atopy, asthma, and study arm were examined. RESULTS: The sample included 4337 adults (43.7% males) from 19 centres in 9 countries. Gas cooking increased the risk of "shortness of breath whilst at rest" (OR = 1.38; 95%CI: 1.06-1.79) and "wheeze with breathlessness" (1.32; 1.00-1.74). For several other symptoms, effect estimates were larger in those who used both gas hobs and ovens, had a bottled gas source and cooked for over 60 min per day. Stratifying results by sex and age found stronger associations in females and younger adults. CONCLUSION: This multi-centre international study, using repeat data, suggested using gas cookers in the home was more strongly associated than electric cookers with certain respiratory symptoms in adults. As gas cooking is common, these results may play an important role in population respiratory health.

Asthma control and concordance of opinions between patients and pulmonologists.

UNLABELLED: Patient-physician opinion concordance could play a key role in asthma control. There have been no studies evaluating this association in large samples of patients. OBJECTIVES: To determine opinion concordance between asthma patients and their pulmonologists on the impact of the disease and to correlate concordance to asthma control. METHODS: This was a cross-sectional multicentre study including 1160 patients and 300 pulmonologists. Patient-physician concordance rates were assessed by two semi-structured qualitative questionnaires: (1) impact of the disease and (2) treatment satisfaction. Subsequently, participating pulmonologists determined the concordance between their perceptions and their patient's. Sociodemographic and clinical data were recorded for all patients. RESULTS: In 53.6% of cases, asthma was controlled. The rate of patient-pulmonologist concordance on disease impact on patient daily life was 57%, with physicians underestimating the impact (compared to patients) in 26% of cases. Concordance on satisfaction with treatment was 56%, with physicians underestimating satisfaction in 26% of cases. Patient-physician discordance rates were significantly lower among patients with controlled asthma (29 and 32.1%) than those with poor control (73.7 and 73.1%). CONCLUSIONS: Patient-pulmonologist concordance on perceptions of disease impact is low, particularly in uncontrolled asthma. This poor concordance should be addressed in education programmes, particularly for patients with uncontrolled symptoms.

Predictors of respiratory sickness absence: an international population-based study.

BACKGROUND: Respiratory tract-related occupational disability is common among adults of working age. We examined occupational vapors, gas, dust, or fume (VGDF) exposure as a predictor of disability, based on respiratory sickness absence among the actively employed, at an early point at which prevention may be most relevant. METHODS: Currently employed European Community Respiratory Health Survey II participants (n = 6,988) were classified into three mutually exclusive, condition/symptom-based categories: physician-diagnosed asthma, self-reported rhinitis, and wheeze/breathlessness (n = 4,772). Logistic regression analysis estimated the odds of respiratory sickness absence (past 12 months) by VGDF exposure. RESULTS: In the condition/symptom groups, 327 (6.9%) reported respiratory sickness absence. Exposure to VGDF was associated with increased odds of respiratory sickness absence: asthma odds ratio [OR] 2.0 (95% confidence interval [CI] 1.1-3.6), wheeze/breathlessness OR 2.2 (95% CI 1.01-4.8); rhinitis OR 1.9 (95% CI 1.02-3.4). CONCLUSION: One in 15 currently employed with asthma, breathlessness, or rhinitis reported respiratory sickness absence. VGDF exposure doubled the odds of respiratory sickness absence, suggesting a focus for disability prevention.

Impact of anxiety and depression on disease control and quality of life in asthma patients.

INTRODUCTION: Patients with asthma also tend to have anxiety and depression. These comorbidities may affect asthma control and quality of life. The objective of this study was to assess the impact of anxiety and depression on asthma control and quality of life. PATIENTS AND METHODS: Cross-sectional study of asthma outpatients was conducted at two hospitals in the Basque Country (northern Spain). Data collected included sociodemographic variables, asthma symptoms, treatment, number of exacerbations, level of control, quality of life, presence of psychological morbidities, and level of physical activity. Spirometry was performed in accordance with the recommendations of the Spanish Society of Pneumology and Thoracic Surgery. RESULTS: Among 354 asthmatics, 77% had poor or partial control of their condition, 31% had anxiety alone, 2% had depression alone, and 10% had anxiety plus depression. Poor asthma control was associated with anxiety plus depression (odds ratio (OR): 3.61; 95% confidence interval (CI): 1.05-12.41) as well as with female patients (OR: 1.85; 95% CI: 1.11-3.10). Anxiety had an independent effect on reduced quality of life across all domains; anxiety plus depression had an even greater effect. CONCLUSION: Among patients with asthma, anxiety and depression adversely affect asthma control and quality of life, raising the possibility that treating these psychological comorbidities could improve asthma control and quality of life.

Expert consensus recommendations for the management of asthma in older adults. / Documento de consenso de expertos para el control del asma en personas mayores.

Asthma is a public health problem in patients of any age, although there is still a tendency to erroneously assume that it is almost always confined to children and young people. Epidemiological studies indicate that, from the sixth decade of life, the prevalence of this disease in countries such as Spain reaches 6-10%, with a higher prevalence among women aged 64 to 75 years. In addition, two-thirds of asthma deaths occur at this stage of life, resulting in a substantial number of hospital admissions, longer hospital stays and, from a finance point of view, significant direct economic costs. Asthma in older adults (65 years or older) is now a matter of great concern, the reality of which is underestimated and undertreated. It is therefore essential to establish appropriate recommendations for the diagnosis and treatment of asthma in the aging population. This consensus, which brings together the latest evidence available, was conceived with this objective. The proposed recommendations/conclusions are the result of a nominal consensus developed throughout 2019 and validated by panellists in successive rounds of voting.

Consensus on the treatment of allergic asthma with sublingual house dust mite immunotherapy in the field of pneumology.

Introduction: Many patients sensitized to mites remain symptomatic and uncontrolled despite traditional treatment. Sublingual immunotherapy (SLIT) has demonstrated to reduce the symptoms of allergic rhinitis, the need for additional drug treatments, and to reduce the number of moderate and severe exacerbations in patients with allergic asthma caused by mites that had not been adequately controlled.Areas covered: After reviewing the most recent literature, a scientific committee composed by five pneumologists experts in asthma proposed 41 items that addressed the diagnosis of allergic asthma caused by mites, the role of house dust mite (HDM) SLIT tablet in the therapeutic plan and in the control of the disease, and the profile of patients with asthma candidates for this therapy. Through a modified Delphi method, the items were send to 106 pneumologists involved in asthma to be agreed.Expert opinion: The high degree of consensus reached by the panel of pneumologists shows the importance of HDM SLIT tablet in the treatment of allergic asthma caused by mites, particularly taking into account that they barely use this therapy because until now they did not have a registered treatment with solid evidence of efficacy and safety.

Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status.

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. OBJECTIVES: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. METHODS: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. RESULTS: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. CONCLUSIONS: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.