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Background: Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO. Methods: We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes—VGDF; solvents; pesticides; metals), adjusting for potential confounders. Results: The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04–1.78) for low levels and 1.41 (95%CI: 1.11–1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures. Conclusion: Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control. [ABSTRACT FROM AUTHOR]

The Burden of Obstructive Lung Disease (BOLD) study is a comprehensive research project that aims to assess the prevalence and risk factors of chronic obstructive pulmonary disease (COPD) in adults aged 40 and above from different regions worldwide. The study collected spirometry data from over 28,000 participants across 41 sites in Africa, Asia, Europe, North America, the Caribbean, and Oceania. The follow-up study further investigated lung function decline, risk factors, and the relationship between lung function and mortality. The study provides valuable insights into COPD prevalence and risk factors, particularly in low- and middle-income countries. The study data are not freely accessible, but collaboration proposals can be submitted to the project lead. [Extracted from the article]

Background Observational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males. Methods and findings MR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 x 10.sup.-5) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 x 10.sup.-4 ), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking. Conclusions This large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide., Author(s): Cosetta Minelli 1,*, Diana A. van der Plaat 2,3, Bénédicte Leynaert 2,3, Raquel Granell 4,5, Andre F. S. Amaral 1, Miguel Pereira 1, Osama Mahmoud 5, James Potts 1, [...]

Smoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised. [ABSTRACT FROM AUTHOR]

Background: Small airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases, and progression to COPD over time. Whether SAO predicts mortality is largely unknown., Research Question: Is spirometry-defined SAO associated with increased mortality?, Methods: Data were analyzed from 252,877 adult participants, aged 40 to 69 years at baseline, in the UK Biobank who had provided good-quality spirometry measurements. SAO was defined as the ratio of the forced expiratory volume in 3 s to the forced expiratory volume in 6 s less than the lower limit of normal. SAO was considered to be isolated if present when the FEV 1 /forced expiratory volume in 6 s ratio was normal (ie, greater than the lower limit of normal). A multivariable Cox regression model was used to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. Sex differences were investigated in these associations, and the primary analysis was repeated, excluding those who ever smoked. All models were adjusted for potential confounders such as sex, BMI, smoking status, smoking pack-years, assessment center, Townsend deprivation index, and ethnicity., Results: A total of 59,744 participants with SAO were identified, of whom 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (hazard ratio [HR], 1.31; 95% CI, 1.26-1.36), cardiovascular (HR, 1.39; 95% CI, 1.29-1.51), respiratory (HR, 2.20; 95% CI, 1.92-2.51), and neoplasm (HR, 1.23; 95% CI, 1.17-1.29) mortality risk. These associations were not modified by sex. However, in those who never smoked, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR, 1.14; 95% CI, 1.07-1.20)., Interpretation: Individuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Contemporary data on the burden of chronic respiratory diseases in sub-Saharan Africa is limited. More so, their economic burden is not well described. This study aims to establish a chronic respiratory disease observatory for Africa. Specific study aims are (1) to describe the prevalence and determinants of asthma with a target to screen up to 4000 children and adolescents across four African cities; (2) to determine the prevalence and determinants of chronic obstructive pulmonary disease (COPD) with a target to screen up to 3000 adults (≥18 years) across five African cities; (3) to describe the disease burden by assessing the frequency and severity of symptoms and exacerbations, medication use, emergency healthcare utilisation and hospitalisation; and (4) to assess the economic burden and affordability of the medicines for these diseases., Methods and Analysis: Surveys will be conducted in schools to identify children and adolescents with asthma using the Global Asthma Network screening questionnaire in Ghana, Nigeria, the Democratic Republic of Congo, and Uganda. Community surveys will be conducted among adults using an adapted version of the Burden of Obstructive Lung Disease Questionnaire to identify persons with COPD symptoms in Nigeria, Burkina Faso, Mozambique, Rwanda, and Sierra Leone. Fractional exhaled nitric oxide and pre-bronchodilator and post-bronchodilator spirometry will be done for children with asthma or asthma symptoms and for all adult participants. Children and adults with respiratory symptoms or diagnoses will complete the health economic questionnaires. Statistical analysis will involve descriptive and analytical statistics to determine outcomes., Ethics and Dissemination: Ethical approval has been obtained from participating institutions. This study's results will inform deliberations at the United Nations General Assembly high-level meeting on non-communicable diseases in 2025. The results will be shared through academic conferences and journals and communicated to the schools and the communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic cough is a common respiratory symptom with an impact on daily activities and quality of life. Global prevalence data are scarce and derive mainly from European and Asian countries and studies with outcomes other than chronic cough. In this study, we aimed to estimate the prevalence of chronic cough across a large number of study sites as well as to identify its main risk factors using a standardised protocol and definition., Methods: We analysed cross-sectional data from 33,983 adults (≥40 years), recruited between Jan 2, 2003 and Dec 26, 2016, in 41 sites (34 countries) from the Burden of Obstructive Lung Disease (BOLD) study. We estimated the prevalence of chronic cough for each site accounting for sampling design. To identify risk factors, we conducted multivariable logistic regression analysis within each site and then pooled estimates using random-effects meta-analysis. We also calculated the population attributable risk (PAR) associated with each of the identifed risk factors., Findings: The prevalence of chronic cough varied from 3% in India (rural Pune) to 24% in the United States of America (Lexington,KY). Chronic cough was more common among females, both current and passive smokers, those working in a dusty job, those with a history of tuberculosis, those who were obese, those with a low level of education and those with hypertension or airflow limitation. The most influential risk factors were current smoking and working in a dusty job., Interpretation: Our findings suggested that the prevalence of chronic cough varies widely across sites in different world regions. Cigarette smoking and exposure to dust in the workplace are its major risk factors., Funding: Wellcome Trust., Competing Interests: Fatima Rodrigues declares grants and personal fees from A. Menarini, Boehringer Ingelheim, Teva Pharma, Novartis, GlaxoSmithKline, AstraZeneca, VitalAire and Nippon Gases outside the submitted work. Wan C. Tan received grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93,326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., Pfizer Canada Ltd. for conducting the longitudinal population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study on COPD. David Mannino is a consultant to GSK, AstraZeneca, Regeneron, Genentech, COPD Foundation, and expert witness on behalf of people suing Tobacco Industry (Schlesinger Law Firm). Sonia Buist is Chair of the Data Safety & Monitoring Board for the RELIANCE Clinical Trial. Frits Franssen declares personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, MSD, Pieris, and Verona Pharma. Robab Breyer-Kohansal declares consulting fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, Novartis Pharma, and Sanofi, and participation on advisory boards for AstraZeneca, Menarini, and Sanofi. Thorarinn Gislason received a grant from the Icelandic Research Fund. Kevin Mortimer declares participation on advisory boards for AstraZeneca and GlaxoSmithKline. Sylvia Hartl declares grants from GSK, Chiesi Farma, Menarini Pharma, and AstraZeneca, and participation on advisory boards for Menarini Pharma and GSK. AFSA declares a grant from the COLT Foundation (CF/01/21)., (© 2024 The Author(s).)

Background: Chronic airflow obstruction is a key characteristic of chronic obstructive pulmonary disease. We investigated whether isolated small airways obstruction is associated with chronic airflow obstruction later in life., Methods: We used longitudinal data from 3957 participants of the multinational Burden of Obstructive Lung Disease study. We defined isolated small airways obstruction using the prebronchodilator mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FVC) (FEF 25-75 ) if a result was less than the lower limit of normal (1 /FVC). We also used the forced expiratory volume in 3 s to FVC ratio (FEV 3 /FVC) to define small airways obstruction. We defined chronic airflow obstruction as post-bronchodilator FEV 1 /FVC25-75 less than the LLN, OR: 2.95, 95% CI 1.02 to 8.54; FEV 3 /FVC less than the LLN, OR: 1.94, 95% CI 1.05 to 3.62). FEF 25-75 was better than the FEV 3 /FVC ratio to discriminate future chronic airflow obstruction (AUC: 0.764 vs 0.692). Results were similar among participants of the UK Biobank study., Conclusion: Measurements of small airways obstruction can be used as early markers of future obstructive lung disease., Competing Interests: Competing interests: RN reports grants and personal fees from AstraZeneca and GlaxoSmithKline and grants from Boehringer Ingelheim and Novartis, outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Spirometric small airway obstruction is associated with impaired ventilatory response to exercise independently of FEV 1 /FVC ratio https://bit.ly/3pre4sk., Competing Interests: Conflict of interest: B. Knox-Brown has nothing to disclose. Conflict of interest: K. Sylvester has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose., (Copyright ©The authors 2023.)

Background: Small airways obstruction (SAO) is a key feature of both COPD and asthma, which have been associated with workplace exposures. Whether SAO, which may occur early in the development of obstructive lung disease and without symptoms, also associates with occupational exposures is unknown., Methods: Using UK Biobank data, we derived measurements of SAO from the 65 145 participants with high-quality spirometry and lifetime occupational histories. The ALOHA+ Job Exposure Matrix was used to assign lifetime occupational exposures to each participant. The association between SAO and lifetime occupational exposures was evaluated using a logistic regression model adjusted for potential confounders. A second logistic regression model was also run to account for potential co-exposures., Results: SAO was present in varying proportions of the population depending on definition used: 5.6% (forced expiratory flow between 25 and 75% of the forced vital capacity (FEF 25-75 ) < lower limit of normal (LLN)) and 21.4% (forced expiratory volume in 3 s (FEV 3 )/forced expiratory volume in 6 s (FEV 6 ) 3 /FEV 6 3 /FEV 6 3 /FEV 6

Background: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study., Methods: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 )/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income., Results: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (β=0.02 L, 95% CI -0.02-0.06 L) or lower FEV 1 /FVC (β=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income., Conclusion: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries., Competing Interests: Conflict of interest: J. Ratanachina, A.F.S. Amaral, S. De Matteis, H. Lawin, K. Mortimer, D.O. Obaseki, I. Harrabi, M. Denguezli, E.F.M. Wouters, C. Janson, A. Gulsvik, H.H. Cherkaski, F. Mejza, P.A. Mahesh, A. Elsony, R. Ahmed, W. Tan, L.C. Loh, A. Rashid, M. Studnicka, A.A. Nafees, T. Seemungal, A. Aquart-Stewart, M. Al Ghobain, J. Zheng, S. Juvekar, S. Salvi, R. Jogi, T. Gislason, A.S. Buist, P. Cullinan and P. Burney have no conflict of interest to disclose. R. Nielsen reports grants from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and Novartis, and receipt of equipment/material/services from ResMed Norway; and is President of the Norwegian Respiratory Society. D. Mannino reports royalties from Up to Date; personal fees from GlaxoSmithKline, AstraZeneca and Schlesinger Law Firm; honoraria from American Association of Respiratory Care; and stock in GlaxoSmithKline; and is the Medical Director of the COPD Foundation., (Copyright ©The authors 2023.)

Introduction: In recent years, there has been increasing interest in the use of spirometry for the assessment of small airways obstruction (SAO) driven by the idea that these changes occur prior to development of established obstructive lung disease. Maximal mid-expiratory and distal flow rates have been widely used despite a lack of agreement regarding parameter selection or definition of an abnormal result. We aim to provide evidence from population-based studies, describing the different parameters, definitions of normal range and the resulting impact on prevalence estimates for SAO. Summarising this evidence is important to inform development of future studies in this area., Methods and Analysis: A systematic review of population-based studies will be conducted. MEDLINE, Web of Science and Google Scholar will be searched from database inception to May 2021. Primary outcomes will include the spirometry parameter used to define SAO, and the definition of an abnormal result. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed for study selection. Study methods will be assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation working group methodology. Narrative synthesis will be conducted for all included studies. Meta-analysis will also be conducted for prevalence estimates and associated risk factors where data quality and availability allow. Random effects models will be used to conduct the meta-analysis and I 2 statistics will be used to assess heterogeneity across studies. Where appropriate subgroup analysis will be conducted to explore heterogeneity., Ethics and Dissemination: There is no requirement for ethical approval for this project. Findings will be disseminated via peer-reviewed publications and other formats, for example, conferences, congresses or symposia., Prospero Registration Number: CRD42021250206., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although there are many health benefits from being active, there was no benefit observed in this study from vigorous physical activity in reducing the risk of asthma onset in middle-aged adults https://bit.ly/3bEtHDn., Competing Interests: Conflict of interest: M.A. Russell has nothing to disclose. Conflict of interest: S. Dharmage has nothing to disclose. Conflict of interest: E. Fuertes has nothing to disclose. Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: A-E. Carsin has nothing to disclose. Conflict of interest: S. Pascual Erquicia has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose. Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: M.J. Abramson has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: I. Cerveri has nothing to disclose. Conflict of interest: P. Demoly reports board fees from Chiesi, IQVIA, Ménarini and Sanofi; board and speaker bureau fees from AstraZeneca, Bausch & Lomb and ThermoFisher Scientific; and speaker fees from Mylan and Novartis, all outside the submitted work. Conflict of interest: V. Garcia-Larsen has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: J. Martinez-Moratalla has nothing to disclose. Conflict of interest: D. Nowak has nothing to disclose. Conflict of interest: L. Palacios-Gómez has nothing to disclose. Conflict of interest: G. Squillacioti has nothing to disclose. Conflict of interest: W. Raza has nothing to disclose. Conflict of interest: M. Emtner has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose., (Copyright ©The authors 2021.)

Studies reporting on associations between short-term exposure to outdoor fine (PM 2.5 ), and ultrafine particles (UFP) and blood pressure and lung function have been inconsistent. Few studies have characterized exposure by personal monitoring, which especially for UFP may have resulted in substantial exposure measurement error. We investigated the association between 24-h average personal UFP, PM 2.5 , and soot exposure and dose and the health parameters blood pressure and lung function. We further assessed the short-term associations between outdoor concentrations measured at a central monitoring site and near the residences and these health outcomes. We performed three 24-h personal exposure measurements for UFP, PM 2.5 , and soot in 132 healthy adults from Basel (Switzerland), Amsterdam and Utrecht (the Netherlands), and Turin (Italy). Monitoring of each subject was conducted in different seasons in a one-year study period. Subject's activity levels and associated ventilation rates were measured using actigraphy to calculate the inhaled dose. After each 24-h monitoring session, blood pressure and lung function were measured. Contemporaneously with personal measurements, UFP, PM 2.5 and soot were measured outdoor at the subject's residential address and at a central site in the research area. Associations between short-term personal and outdoor exposure and dose to UFP, PM 2.5 , and soot and health outcomes were tested using linear mixed effect models. The 24-h mean personal, residential and central site outdoor UFP exposures were not associated with blood pressure or lung function. UFP mean exposures in the 2-h prior to the health test was also not associated with blood pressure and lung function. Personal, central site and residential PM 2.5 exposure were positively associated with systolic blood pressure (about 1.4 mmHg increase per Interquartile range). Personal soot exposure and dose were positively associated with diastolic blood pressure (1.2 and 0.9 mmHg increase per Interquartile range). No consistent associations between PM 2.5 or soot exposure and lung function were observed. Short-term personal, residential outdoor or central site exposure to UFP was not associated with blood pressure or lung function. Short-term personal PM 2.5 and soot exposures were associated with blood pressure, but not lung function., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Lung function, strongly associated with morbidity and mortality, decreases with age. This study examines whether poor adult lung function is associated with age accelerations (AAs). DNA methylation (DNAm) based AAs, lifespan predictors (GrimAge and plasminogen activator inhibitor 1-PAI1) and their related age-adjusted measures were estimated from peripheral blood at two time points (8-to-11 years apart) in adults from two cohorts: SAPALDIA (n=987) and ECRHS (n=509). Within each cohort and stratified by gender (except for estimators from GrimAge and PAI1), AAs were used as predictors in multivariate linear regression with cross-sectional lung function parameters, and in covariate-adjusted mixed linear regression with longitudinal change in lung function and meta-analysed.AAs were found cross-sectionally associated with lower mean FEV1 (Forced Expiratory Volume in one second) (AA-residuals:P-value=4x10 -4 ; Intrinsic Epigenetic AA:P-value=2x10 -4 ) in females at the follow-up time point only, and the same trend was observed for FVC (Forced Vital Capacity). Both lifespan and plasma level predictors were observed strongly associated with lung function decline and the decline was stronger in the follow-up time points (strongest association between FEV1 and DNAmAge GrimAge:P-value=1.25x10 -17 ).This study suggests that DNAm based lifespan and plasma level predictors can be utilised as important factors to assess lung health in adults.

Bronchodilator response (BDR) testing is used as a diagnostic method in obstructive airway diseases. The aim of this investigation was to compare different methods for measuring BDR in participants with asthma and chronic obstructive pulmonary disease (COPD) and to study to the extent to which BDR was related to symptom burden and phenotypic characteristics.Forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were measured before and 15 min after 200 μg of salbutamol in 35 628 subjects aged ≥16 years from three large international population studies. The subjects were categorised in three groups: current asthma (n=2833), COPD (n=1146) and no airway disease (n=31 649). Three definitions for flow-related reversibility (increase in FEV 1 ) and three for volume-related reversibility (increase in FVC) were used.The prevalence of bronchodilator reversibility expressed as increase FEV 1 ≥12% and 200 mL was 17.3% and 18.4% in participants with asthma and COPD, respectively, while the corresponding prevalence was 5.1% in those with no airway disease. In asthma, bronchodilator reversibility was associated with wheeze (OR 1.36, 95% CI 1.04-1.79), atopy (OR 1.36, 95% CI 1.04-1.79) and higher exhaled nitric oxide fraction, while in COPD neither flow- nor volume-related bronchodilator reversibility was associated with symptom burden, exacerbations or health status after adjusting for pre-bronchodilator FEV 1 Bronchodilator reversibility was at least as common in participants with COPD as those with asthma. This indicates that measures of reversibility are of limited value for distinguishing asthma from COPD in population studies. However, in asthma, bronchodilator reversibility may be a phenotypic marker., Competing Interests: Conflict of interest: C. Janson has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: S. Accordini has nothing to disclose. Conflict of interest: J. Bousquet reports personal fees and other funding from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva and Uriach, and other funding from Kyomed, outside the submitted work. Conflict of interest: S.A. Buist has nothing to disclose. Conflict of interest: G.W. Canonica has nothing to disclose. Conflict of interest: B. Dahlen has received personal fees from TEVA, Sanofi, GSK and AstraZeneca, outside the submitted work. Conflict of interest: J. Garcia Aymerich has nothing to disclose. Conflict of interest: L. Gnatiuc has nothing to disclose. Conflict of interest: M.L. Kowalski has nothing to disclose. Conflict of interest: J. Patel has nothing to disclose. Conflict of interest: W. Tan has nothing to disclose. Conflict of interest: K. Torén has nothing to disclose. Conflict of interest: T. Zuberbier has received consultancy fees from Bayer Health Care, FAES, Novartis and Henkel; has received grants/has grants pensing form Novartis and Henkel, and has received lecture fees from AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer HealthCare, Bencradm Berlin Chemie, FAES, HAL, Leti, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Stallergenes, Takeda, TEVA, UCB, Henkel, Kryolan and L'Oreal, outside the submitted work. Conflict of interest: P. Burney has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose., (Copyright ©ERS 2019.)

Background: One of the potential mechanisms linking air pollution to health effects is through changes in DNA-methylation, which so far has mainly been analyzed globally or at candidate sites., Objective: We investigated the association of personal and ambient air pollution exposure measures with genome-wide DNA-methylation changes., Methods: We collected repeated 24-hour personal and ambient exposure measurements of particulate matter (PM 2.5 ), PM 2.5 absorbance, and ultrafine particles (UFP) and peripheral blood samples from a panel of 157 healthy non-smoking adults living in four European countries. We applied univariate mixed-effects models to investigate the association between air pollution and genome-wide DNA-methylation perturbations at single CpG (cytosine-guanine dinucleotide) sites and in Differentially Methylated Regions (DMRs). Subsequently, we explored the association of air pollution-induced methylation alterations with gene expression and serum immune marker levels measured in the same subjects., Results: Personal exposure to PM 2.5 was associated with methylation changes at 13 CpG sites and 69 DMRs. Two of the 13 identified CpG sites (mapped to genes KNDC1 and FAM50B) were located within these DMRs. In addition, 42 DMRs were associated with personal PM 2.5 absorbance exposure, 16 DMRs with personal exposure to UFP, 4 DMRs with ambient exposure to PM 2.5 , 16 DMRs with ambient PM 2.5 absorbance exposure, and 15 DMRs with ambient UFP exposure. Correlation between methylation levels at identified CpG sites and gene expression and immune markers was generally moderate., Conclusion: This study provides evidence for an association between 24-hour exposure to air pollution and DNA-methylation at single sites and regional clusters of CpGs. Analysis of differentially methylated regions provides a promising avenue to further explore the subtle impact of environmental exposures on DNA-methylation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries 1,2 . To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world.Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) study were used to analyse effects of CAO on unemployment. Odds ratios for unemployment in subjects aged 40-65 years were estimated using a multilevel mixed-effects generalised linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses.Out of 18 710 participants, 11.3% had CAO. The ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, although these were no longer significant after adjusting for age, sex, smoking and education. The site-adjusted odds ratio (95% CI) for unemployment was 1.79 (1.41-2.27) for CAO cases, decreasing to 1.43 (1.14-1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (4.02 (3.53-4.57) and 3.86 (2.80-5.30), respectively), while female sex was important in low- to middle-income sites (3.23 (2.66-3.91)).In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

The incidence and rate of recurrence of bladder cancer is high, particularly in developed countries, however current methods for diagnosis are limited to detecting high-grade tumours using often invasive methods. A panel of biomarkers to characterise tumours of different grades that could also distinguish between patients exhibiting the disease with first incidence or recurrence could be useful for bladder cancer diagnostics. In this study, potential metabolic biomarkers have been discovered through mass spectrometry based metabolomics of urine. Pre-treatment urine samples were collected from 48 patients diagnosed of urothelial bladder cancer. Patients were followed-up through the hospital pathological charts to identify whether and when the disease recurred or progressed. Subsequently, they were classified according to whether or not they suffered a tumour recurrence (recurrent or stable) as well as their risk group according to tumour grade and stage. Identified metabolites have been analysed in terms of disease characteristics (tumour stage and recurrence) and have provided an insight into bladder cancer progression. Using both liquid chromatography and capillary electrophoresis-mass spectrometry, a total of 27 metabolite features were highlighted as significantly different between patient groups. Some, for example histidine, phenylalanine, tyrosine and tryptophan have been previously linked with bladder cancer, however until now their connection with bladder cancer progression has not been previously reported. The candidate biomarkers revealed in this study could be useful in the clinic for diagnosis of bladder cancer and, through characterising the stage of the disease, could also be useful in prognostics., (Copyright © 2013 Elsevier B.V. All rights reserved.)