Rationale: Epidemiological studies have reported on the detrimental effects on lung function after natural, thus limited, weight gain in time in unselected populations. Studies on bariatric surgery, on the other hand, have indicated large improvements of lung function after substantial weight loss. Objective: To study the associations between a profound weight loss or gain and pulmonary function within the same population. A second objective was to investigate the effect of weight cycling on pulmonary function. Methods: We selected records from our lung function database, on subjects in the follow-up of CPAP therapy for sleep apnea, with a weight change ≥ 20 kg within 5 years. Lung function (n= 255) at baseline was normal, except for a tendency of mild restriction in morbid obesity. Within this selection, 73 subjects were identified with significant "weight cycling", defined as a ≥ 10 kg opposite change in body weight prior to or following the ≥ 20 kg weight change. Results: Weight change affected pulmonary function more in males than in females (p< 0.001). In males, FVC increased on average 1.4% predicted/BMI after weight loss, and the reverse after weight gain, whereas females exhibited a smaller change of 0.9% predicted/BMI. Weight loss slightly increased the FEV1/FVC-ratio and decreased the specific airway resistance, whereas the opposite occurred with weight gain. Larger effects of weight change on lung function were observed in leaner subjects (p= 0.02) and in older subjects (p< 0.002). Changes in TLC followed that of FVC with no change in RV, while the largest change was observed in FRC. In subjects with weight cycling, the improvement in lung function due to weight loss was reversed by subsequent weight gain and vice versa. Conclusion: This study provides evidence that the detrimental effect of obesity on lung function is a passive and reversible process.

Good research is driven by study design encompassing theoretical design, design of data collection and design of data processing. In epidemiological research, theoretical design is based on a functional relationship between the occurrence and determinants studied (occurrence function) and should also define that part of the theoretical population and the context to which the results pertain (domain). Both are essential for the design of data collection, the design of data processing and the interpretation of the study results and should be explicitly reported. In order to gain insight into the role of theoretical design in the entire research process before publication, it was decided to informally question the corresponding authors of a selection of 30 articles (20 most recent and 10 less recent) reporting on causal observational epidemiological studies on asthma and early life exposure to antibiotics. The objective was to appraise the perceived knowledgeability of theoretical design among the authors of the selected articles. Fifteen authors responded. Authors were asked to indicate their knowledgeability with the concepts of theoretical design, causal theory, confounding and effect modification on a 5-level Likert scale. Other questions were related to the theoretical design of their study. The vast majority of the authors perceived themselves to be moderately to extremely knowledgeable with confounding and effect modification. Perceived knowledgeability of theoretical design and causal theory was more diverse. When provided with options for an occurrence function, almost all authors indicated "current occurrence as a function of past exposure" for their study. Nevertheless, half of these authors conducted their study based on "future occurrence as a function of current exposure". Even though the authors perceive themselves to be knowledgeable with theoretical design, this is not reflected in their articles. Theoretical design should be well known, implemented and explicitly reported.

Abstract Background Results of studies evaluating the relationship between asthma occurrence and early life antibiotic use have been conflicting. The aim of this study was to investigate the relationship between occurrence of asthma in children and systemic antibiotic use in the first year of life based on an incidence density study with careful consideration of the temporal aspects of the determinant-outcome relationship. Methods We conducted an incidence density study nested in a data collection project with information on 1128 mother–child pairs. Systemic antibiotic use in the first year of life was defined as excessive (≥ 4 courses) vs. non-excessive (< 4 courses) use based on information from weekly diaries. Events (cases) were defined as the first parent-reported occurrence of asthma in a child between 1 and 10 years of age. Population time ‘at risk’ was probed by sampling population moments (controls). Missing data were imputed. Multiple logistic regression was used to assess the association between current first asthma occurrence (incidence density) and systemic antibiotic use in the first year of life, to evaluate effect modification and adjust for confounding. Results Forty-seven first asthma events and 147 population moments were included. Excessive systemic antibiotic use in the first year of life showed more than twice the incidence density of asthma compared to non-excessive use (adjusted IDR [95% CI]: 2.18 [0.98, 4.87], p = 0.06). The association was more pronounced in children who have had lower respiratory tract infections (LRTIs) in the first year of life compared to children who had no LRTIs in the first year of life (adjusted IDR [95% CI]: 5.17 [1.19, 22.52] versus 1.49 [0.54, 4.14]). Conclusions Excessive use of systemic antibiotics in the first year of life may play a role in the genesis of asthma in children. This effect is modified by the occurrence of LRTIs in the first year of life, with a stronger association observed in children experiencing LRTIs in the first year of life.

In previous studies, the strength of the association between childhood asthma and environmental tobacco smoke (ETS) differed depending on the way ETS was assessed and the type of study conducted. We investigated the relationship between asthma occurrence in children and recent exposure to ETS based on an incidence-density study driven by the explicit formulation of a theoretical design. Additionally, we assessed whether the relationship is modified by perinatal ETS exposure and parental inhalation atopy. The event was conceptualized as 'first doctor's diagnosis of asthma'. Population time was probed by sampling population moments. Exposure to ETS was conceptualized as recent exposure (1 year prior to diagnosis or at sampling) and perinatal exposure (in utero and/or during the first year of life). Thirty-nine events and 117 population moments were included. There was no indication for effect modification by perinatal exposure to ETS or parental inhalation atopy. After adjustment for confounding, an association was observed between occurrence of a first asthma diagnosis and recent ETS exposure: incidence-density ratio 4.94 (95% confidence interval 1.21, 20.13). Asthma occurrence in children is associated with recent exposure to ETS, and this association seems not to be modified by perinatal ETS exposure or parental inhalation atopy.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

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) atfollow-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 FEV(1 )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.

"Theoretical design" comprises the development of an occurrence relation and the specification of the study domain. In explanatory research, the occurrence relation causally relates one determinant to the occurrence (of an event or a state) taking into account other relevant characteristics (confounders and modifiers). Conflicting results in explanatory research might be (partially) explained by differences in the "theoretical design" or by a mismatch between the "theoretical design" and the "design of data collection". In this critical review, the reporting of "theoretical design" is assessed in articles on the association between early life antibiotic use and the occurrence of asthma. Articles investigating a relationship between early life antibiotic use and the occurrence of asthma were searched in PubMed and systematically selected for critical review. The full text was read and important elements of study design were extracted (the research question/hypothesis, seven key elements of "theoretical design" (measure of occurrence, case (event or state) definition, conceptualization (and operationalization) of the exposure, temporal relation between outcome and exposure, confounders and effect modifiers taken into account and the domain of the study), the method of data collection and the method of data processing). A comparison was made between articles published before and after the publication of the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement (2007). Sixty-three articles were included for review. Thirteen articles reported the seven key elements of "theoretical design" that were questioned. No marked differences in reporting were observed pre- and post-STROBE. All articles reported some key elements of "theoretical design"; however, the reporting is not structured and not linked to the concept of "theoretical design". Conceptualizing, delineating and explicit reporting of "theoretical design" is quintessential for the quality and transparency of explanatory research.

BACKGROUND: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few. OBJECTIVE: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma. METHODS: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for <1.3, 1.3-8, and >8 years) and FEV1 decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV1 decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium). RESULTS: FEV1 decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (P-interaction = .006): in the group treated for more than 8 years, FEV1 decline was on average 27 mL/y (95% CIBonferroni-adjusted, 11-42) lower for subjects with sensitization compared with nonsensitized subjects. CONCLUSIONS: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.

Surgical smoke produced by electrosurgery contains various chemical substances such as volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs). The aim of this study is to investigate airborne concentrations of VOCs and PAHs during electrosurgery in an operating room, in relation to metabolites in urine in order to assess the absorbed dose. A 5-day exposure study was set up in a general surgery operation room including surgeons, scrub assistants and circulation nurses (n = 15). Stationary and personal air sampling for VOCs and PAHs were carried out. Pre-, mid- and end-shift analysis of urinary S-phenylmercapturic acid (SPMA), o-cresol, mandelic acid and 1-hydroxypyrene was performed to assess the internal exposure to respectively benzene, toluene, styrene and PAHs. Several VOCs (styrene, ethyl benzene, benzene and toluene), ranging from 0.7 to 3.27 μg/m3 were detected in the air samples, along with one PAH (naphthalene, ranging from 0.012 to 0.39 μg/m3). There was no significant correlation between air monitoring and urinary biomonitoring. O-cresol levels were increased, especially among assistants and nurses at mid- and end-shift, exceeding current biological exposure indices several times. External and internal exposure for assistants and nurses was substantially more, compared to surgeons. This study confirms the presence of VOCs and PAHs in surgical smoke and shows the presence of their metabolites in urine, but the association is unclear. Urinary biomonitoring shows especially high concentrations of o-cresol.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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 (FEV 1 )) 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 FEV 1 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 FEV 1 declines. We found no association between weight change profiles and FEV 1 /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.

Concerns exist that the positive association of physical activity with better lung function, which has been suggested in previous longitudinal studies in smokers, is due to reverse causation. To investigate this, we applied structural equation modeling (SEM), an exploratory approach, and marginal structural modeling (MSM), an approach from the causal inference framework that corrects for reverse causation and time-dependent confounding and estimates causal effects, on data from participants in the European Community Respiratory Health Survey (ECRHS, a multicentre European cohort study initiated in 1991-1993 with ECRHS I, and with two follow-ups: ECRHS II in 1999-2003, and ECRHS III in 2010-2014). 753 subjects who reported current smoking at ECRHS II, with repeated data on lung function at ECRHS I, II and III, physical activity at ECRHS II and III, and potential confounders at ECRHS I and II, were included in the analyses. SEM showed positive associations between physical activity and lung function in both directions. MSM suggested a protective causal effect of physical activity on lung function (overall difference in mean β (95% CI), comparing active versus non-active individuals: 58 mL (21-95) for forced expiratory volume in one second and 83 mL (36-130) for forced vital capacity). Our results suggest bi-directional causation and support a true protective effect of physical activity on lung function in smokers, after accounting for reverse causation and time-dependent confounding.

We estimated the association between regular physical activity and the incidence of restrictive spirometry pattern. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and physical activity were assessed in 2 population-based European cohorts (European Community Respiratory Health Survey: n = 2,757, aged 39-67 years; and Swiss Study on Air Pollution and Lung and Heart Diseases in Adults: n = 2,610, aged 36-82 years) first in 2000-2002 and again approximately 10 years later (2010-2013). Subjects with restrictive or obstructive spirometry pattern at baseline were excluded. We assessed the association of being active at baseline (defined as being physically active at least 2-3 times/week for >= 1 hour) with restrictive spirometry pattern at follow-up (defined as a postbronchodilation FEV1/FVC ratio of at least the lower limit of normal and FVC of <80% predicted) using modified Poisson regression, adjusting for relevant confounders. After 10 years of follow-up, 3.3% of participants had developed restrictive spirometry pattern. Being physically active was associated with a lower risk of developing this phenotype (relative risk = 0.76, 95% confidence interval: 0.59, 0.98). This association was stronger among those who were overweight and obese than among those of normal weight (P for interaction = 0.06). In 2 large European studies, adults practicing regular physical activity were at lower risk of developing restrictive spirometry pattern over 10 years.

Asthma often remains uncontrolled, despite the fact that the pharmacological treatment has undergone large changes. We studied changes in the treatment of asthma over a 20-year period and identified factors associated with the regular use of inhaled corticosteroid (ICS) treatment. Changes in the use of medication were determined in 4617 randomly selected subjects, while changes in adults with persistent asthma were analysed in 369 participants. The study compares data from three surveys in 24 centres in 11 countries. The use of ICSs increased from 1.7% to 5.9% in the general population and the regular use of ICSs increased from 19% to 34% among persistent asthmatic subjects. The proportion of asthmatic subjects reporting asthma attacks in the last 12 months decreased, while the proportion that had seen a doctor in the last 12 months remained unchanged (42%). Subjects with asthma who had experienced attacks or had seen a doctor were more likely to use ICSs on a regular basis. Although ICS use has increased, only one-third of subjects with persistent asthma take ICSs on a regular basis. Less than half had seen a doctor during the last year. This indicates that underuse of ICSs and lack of regular healthcare contacts remains a problem in the management of asthma.

We explored the association between residential greenness and lung function in 6209 adults from 22 centres of the population-based European Community Respiratory Health Survey. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were measured by spirometry pre-bronchodilation at ages 35.2±6.0 (1990-1993), 44.1±6.0 (1998-2002) and 55.3±6.1 (2009-2013) years. Greenness was assessed by the satellite-derived Normalized Difference Vegetation Index (NDVI, range from -1 to 1) in a 500m circular buffer around the residential addresses at the time of each lung function measurement, and then averaged to estimate cumulative exposure. Associations of greenness with the level and rate of lung function change were assessed by adjusted linear mixed effects regression models which include random intercepts for subjects nested within centres. Higher greenness was associated with higher FEV1 levels and a larger decline of FVC. These associations were stronger after co-adjustment for air pollution (PM2.5). In asthmatics, the association with FEV1 levels was 4-fold higher than in the general population while no association with FVC change was present. In conclusion, average lung function levels were higher among residents of greener areas. No beneficial longitudinal associations between lung function change and greenness were detected.

ACO may have different risk factors and clinical course compared to asthma or COPD alone. As part of the ALEC study (EU Horizon 2020 Grant #633212) we aim at describing the characteristics of subjects aged 40–68 with and without asthma and COPD, from early adulthood to middle age. We analysed data collected in 1991-94, 1998-2002 and 2011-13 in the ECRHS study. At the last time point we classified subjects as having current (n=808) or past (n=263) asthma alone, COPD alone (n=112), ACO (n=178), or none of them (n=3477). ACO was defined as a combination of COPD (post-bronchodilator FEV1/FVC 15 pack-years (41 vs 70%, poverall<0.001) and to report occupational exposures (41 vs 52%, poverall=0.05) than those with COPD alone, but they reported childhood respiratory infections more frequently (18 vs 13%, poverall<0.001). Compared with the subjects with current asthma alone, they were more likely to have a history of airway hyperresponsiveness (95 vs 78%, poverall<0.001) or a history of serum total IgE >100 kU/L (68 vs 56%, poverall<0.001). The subjects with ACO had the lowest FEV1 in their twenties, but the fastest FEV1 decline was seen among people with COPD alone (Figure 1). In the general population ACO is a severe respiratory phenotype characterised by an impaired lung function in young adulthood.

Previous longitudinal studies have suggested a protective role of physical activity on lung function in active smokers, but potential reverse causation remains a common criticism. To investigate this, we applied an exploratory approach: structural equation modeling (SEM), and a causal inference approach that allows to estimate causal effects by adjusting for potential time-dependent confounding and reverse causation: marginal structural modeling (MSM), using repeated data from 753 participants of the European Community Respiratory Health Survey (ECRHS). The associations between being physically active at time t and lung function (FEV1 and FVC) at time t were considered as the causal effects to investigate, taking into account the associations between lung function at time t-1 and physical activity at time t (t being both ECRHSII and III); number of pack-years smoked, passive smoking exposure, weight, height, age and age-squared were considered as time-dependent confounders; sex, education, occupation, the AHEI-2010 dietary score and respiratory infection in childhood were considered as time-fixed covariates. When SEM was conducted, associations in both directions were found between physical activity and lung function. When MSM was conducted, a positive causal effect of physical activity on lung function was suggested (overall difference in mean β (95% CI), comparing active versus non-active individuals: 61 mL (22-100) for FEV1 and 95 mL (44-146) for FVC). Although bidirectional causation was suggested, our results support causal interpretation of the protective effect of physical activity on lung function in active smokers.

INTRODUCTION:The fractional exhaled nitric oxide (FE NO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FE NO as a reliable biomarker, it is important to investigate factors that influence FE NO in healthy individuals. Men have higher levels of FE NO than women, but it is unclear whether determinants of FE NO differ by sex. OBJECTIVE:To identify determinants of FE NO in men and women without lung diseases. METHOD:Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. RESULTS:Exhaled NO levels were 21.3% higher in men compared with women P < 0.001. Being in the upper age quartile (60.3-67.6 years), men had 19.2 ppb (95% CI: 18.3, 20.2) higher FE NO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = <0.001 higher FE NO, compared with the lowest age quartile. Height was related to 8% higher FE NO level in men (P < 0.001) and 5% higher FE NO levels in women (P = 0.008). Men who smoked had 37% lower FE NO levels and women had 30% lower levels compared with never-smokers (P < 0.001 for both). Men and women sensitized to both grass and perennial allergens had higher FE NO levels compared with non-sensitized subjects 26% and 29%, P < 0.001 for both. CONCLUSION AND CLINICAL RELEVANCE:Fractional exhaled nitric oxide levels were higher in men than women. Similar effects of current smoking, height, and IgE sensitization were found in both sexes. FE NO started increasing at lower age in women than in men, suggesting that interpretation of FE NO levels in adults aged over 50 years should take into account age and sex.

ObjectivesChronic 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.MethodsPopulation 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.Results8794 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.ConclusionsOccupational 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.