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Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV 1 /FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood., Competing Interests: Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: F. Locatelli has nothing to disclose. Conflict of interest: S.C. Dharmage has nothing to disclose. Conflict of interest: C. Svanes has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose. Conflict of interest: B. Leynaert has nothing to disclose. Conflict of interest: P. Burney has nothing to disclose. Conflict of interest: A. Corsico has nothing to disclose. Conflict of interest: G. Caliskan has nothing to disclose. Conflict of interest: L. Calciano has nothing to disclose. Conflict of interest: T. Gislason has nothing to disclose. Conflict of interest: C. Janson has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: R. Jõgi received grants from the Estonian Research Council (Personal Research Grant n. 562), and personal fees for consultancy and lecturing from GSK, Boehringer and Novartis, and for travels/accommodation/meetings from GSK and Boehringer. Conflict of interest: T. Lytras has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: N. Probst-Hensch has nothing to disclose. Conflict of interest: K. Toren has nothing to disclose. Conflict of interest: L. Casas has nothing to disclose. Conflict of interest: G. Verlato has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose. Conflict of interest: S. Accordini has nothing to disclose., (Copyright ©The authors 2021.)

Epigenome-wide studies of methylation in children support a role for epigenetic mechanisms in asthma; however, studies in adults are rare and few have examined non-atopic asthma. We conducted the largest epigenome-wide association study (EWAS) of blood DNA methylation in adults in relation to non-atopic and atopic asthma.We measured DNA methylation in blood using the Illumina MethylationEPIC array among 2286 participants in a case-control study of current adult asthma nested within a United States agricultural cohort. Atopy was defined by serum specific immunoglobulin E (IgE). Participants were categorised as atopy without asthma (n=185), non-atopic asthma (n=673), atopic asthma (n=271), or a reference group of neither atopy nor asthma (n=1157). Analyses were conducted using logistic regression.No associations were observed with atopy without asthma. Numerous cytosine-phosphate-guanine (CpG) sites were differentially methylated in non-atopic asthma (eight at family-wise error rate (FWER) p<9×10 -8 , 524 at false discovery rate (FDR) less than 0.05) and implicated 382 novel genes. More CpG sites were identified in atopic asthma (181 at FWER, 1086 at FDR) and implicated 569 novel genes. 104 FDR CpG sites overlapped. 35% of CpG sites in non-atopic asthma and 91% in atopic asthma replicated in studies of whole blood, eosinophils, airway epithelium, or nasal epithelium. Implicated genes were enriched in pathways related to the nervous system or inflammation.We identified numerous, distinct differentially methylated CpG sites in non-atopic and atopic asthma. Many CpG sites from blood replicated in asthma-relevant tissues. These circulating biomarkers reflect risk and sequelae of disease, as well as implicate novel genes associated with non-atopic and atopic asthma., Competing Interests: Conflict of interest: T.T. Hoang has nothing to disclose. Conflict of interest: S. Sikdar has nothing to disclose. Conflict of interest: C-J. Xu has nothing to disclose. Conflict of interest: M.K. Lee has nothing to disclose. Conflict of interest: J. Cardwell has nothing to disclose. Conflict of interest: E. Forno has nothing to disclose. Conflict of interest: M. Imboden has nothing to disclose. Conflict of interest: A. Jeong has nothing to disclose. Conflict of interest: A-M. Madore has nothing to disclose. Conflict of interest: C. Qi has nothing to disclose. Conflict of interest: T. Wang has nothing to disclose. Conflict of interest: B.D. Bennett has nothing to disclose. Conflict of interest: J.M. Ward has nothing to disclose. Conflict of interest: C.G. Parks has nothing to disclose. Conflict of interest: L.E. Beane-Freeman has nothing to disclose. Conflict of interest: D. King has nothing to disclose. Conflict of interest: A. Motsinger-Reif reports intramural research funding from the National Institute of Environmental Health Sciences, during the conduct of the study. Conflict of interest: D.M. Umbach has nothing to disclose. Conflict of interest: A.B. Wyss has nothing to disclose. Conflict of interest: D.A. Schwartz reports grants from the National Institutes of Health/National Heart, Lung, and Blood Institute (R38-HL143511, T32-HL007085, UG3/UH3-HL151865 and R01-HL149836) and the Dept of Defense Focused Program (12899593), during the conduct of the study; personal fees for consultancy from Eleven P15 Inc., outside the submitted work; and has a patent “Compositions and methods of treating or preventing fibrotic diseases” pending, a patent “Biomarkers for the diagnosis and treatment of fibrotic lung disease” pending and a patent “Methods and compositions for risk prediction, diagnosis, prognosis, and treatment of pulmonary disorders” issued. Conflict of interest: J.C. Celedón has received research materials from Pharmavite (vitamin D and placebo capsules) and GSK (inhaled steroids), in order to provide medications free of cost to participants in National Institutes of Health funded studies, unrelated to the current work. Conflict of interest: C. Laprise has nothing to disclose. Conflict of interest: C. Ober has nothing to disclose. Conflict of interest: N. Probst-Hensch has nothing to disclose. Conflict of interest: I.V. Yang is a consultant to Eleven P15 Inc., a start-up company that is focused on the early recognition and treatment of pulmonary fibrosis. Conflict of interest: G.H. Koppelman reports grants from the Lung Foundation of the Netherlands, the TETRI Foundation, TEVA the Netherlands, GSK, Vertex and the Ubbo Emmius Foundation, outside the submitted work; and has participated in advisory boards for GSK and PURE IMS, outside the submitted work. Conflict of interest: S.J. London has nothing to disclose., (Copyright ©ERS 2020.)

Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation.A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays.15 out of 37 bands detected with DGGE, which had at least a suggestive association (p<0.25) with asthma, were sequenced. Of the four targeted qPCRs, Clostridium cluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22-0.84) for the fourth versus first quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used.In this large international study, the level of Clostridium cluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

A higher incidence of asthma is reported in women compared with men, but evidence in later adulthood is limited. We aimed to determine the 20-year cumulative incidence of adult asthma in Switzerland and its relation to sex, taking into account age and allergic sensitisation.We assessed incidence of self-report of doctor-diagnosed asthma between 1991/1992 and 2010/2011 in 5128 subjects without asthma, aged 18-60 years at baseline. The age-related probability of asthma onset was analysed by logistic regression adjusting for potential confounders and stratified by sex and allergic sensitisation at baseline.Over 20 years, 128 (5.1%) men and 198 (7.5%) women newly reported doctor-diagnosed asthma. The adjusted odds ratio for female sex was 1.99 (95% CI 1.54-2.57) overall, 3.21 (95% CI 2.12-4.85) among nonsensitised subjects, and 1.43 (95% CI 1.02-2.02) in sensitised subjects. The probability of asthma onset decreased with increasing baseline age in women but not in men. The higher probability of new asthma in sensitised compared with nonsensitised men was unrelated to age, whereas in women it decreased with age.Asthma incidence was higher in women than in men but decreased with increasing age. The female predominance was considerably stronger in nonsensitised adults compared with those with allergic sensitisation., (Copyright ©ERS 2015.)

Asthma and chronic obstructive pulmonary disease (COPD) are thought to share a genetic background ("Dutch hypothesis"). We investigated whether asthma and COPD have common underlying genetic factors, performing genome-wide association studies for both asthma and COPD and combining the results in meta-analyses. Three loci showed potential involvement in both diseases: chr2p24.3, chr5q23.1 and chr13q14.2, containing DDX1, COMMD10 (both participating in the nuclear factor (NF) κβ pathway) and GNG5P5, respectively. Single nucleotide polymorphisms (SNPs) rs9534578 in GNG5P5 reached genome-wide significance after first replication phase (p=9.96×10(-9)). The second replication phase, in seven independent cohorts, provided no significant replication. Expression quantitative trait loci (eQTL) analysis in blood cells and lung tissue on the top 20 associated SNPs identified two SNPs in COMMD10 that influenced gene expression. Inflammatory processes differ in asthma and COPD and are mediated by NF-κβ, which could be driven by the same underlying genes, COMMD10 and DDX1. None of the SNPs reached genome-wide significance. Our eQTL studies support a functional role for two COMMD10 SNPs, since they influence gene expression in both blood cells and lung tissue. Our findings suggest that there is either no common genetic component in asthma and COPD or, alternatively, different environmental factors, e.g. lifestyle and occupation in different countries and continents, which may have obscured the genetic common contribution., (The content of this work is not subject to copyright. Designand branding are ©ERS 2014.)

Exposure to some nonallergenic compounds has been shown to increase the risk of atopic sensitization and asthmatic symptoms. In order to gain more insight into the largely unknown aetiology of respiratory symptoms in pig farmers, we studied the role of nonallergic exposure. We evaluated associations between chronic respiratory symptoms, specific and total serum immunoglobulin E (IgE) levels, use of disinfectants, and endotoxin exposure levels in a population of 194 Dutch pig farmers. Atopic sensitization (defined as increased production of IgE to common allergens) was found to occur more frequently in farmers who used disinfectants containing quaternary ammonium compounds (QACs) (odds ratio (OR) 7.4; 95% confidence interval (95% CI) 1.3-43.1). ORs for other disinfectants ranged 2.3-4.1 (NS). Atopic sensitization was not found to occur more frequently in farmers with a high endotoxin exposure. The use of disinfectants was only related to respiratory symptoms consistent with asthma in atopics. This is illustrated by the significantly elevated ORs for farmers with IgE to common allergens (house dust mite, grass pollen, birch pollen), and who used disinfectants containing QACs, in the total population and in a subgroup of the total population restricted according to bronchial hyperresponsiveness to histamine (symptomatics with a provocation dose of histamine producing a > or = 10% decrease in forced expiratory volume in one second (PC10) < or = 16 mg.mL-1, compared with asymptomatics with a PC10 > 16 mg.mL-1) (OR 4.4, 95% CI 1.3-14.6; and OR 8.2, 95% CI 1.6-42.6, respectively). Atopy and use of QACs and endotoxin exposure level taken individually were not associated with respiratory symptoms. A combination of atopic sensitization and high endotoxin exposure (> 101 ng.m-3) was strongly associated with respiratory symptoms in the restricted population (OR 6.1; 95% CI 1.0-36.2). Our results suggest that occupational exposure to nonallergenic agents (disinfectants) may induce immunoglobulin E sensitization to common aeroallergens, and that the combination of atopy and exposure to nonallergenic agents (disinfectants and endotoxin) is an important risk factor for development of symptoms consistent with asthma.

The purpose of this study was to investigate the effects of house dust mite allergen in bedroom floor dust on respiratory health of children with asthmatic symptoms. Two hundred and twenty eight school children with reported attacks of shortness of breath with wheezing in the past year and/or with doctor-diagnosed asthma, were included in the study. Data on home characteristics, both past and present, were obtained. These included data on allergen avoidance measures because of the child's respiratory health. Dust samples were taken from the child's bedroom floor, and the allergen Der p I of the house dust mite Dermatophagoides pteronyssionus was measured. Health diaries were kept over 4 weeks. Acute respiratory symptoms and medication usage were recorded daily. Peak expiratory flow (PEF) was measured using Mini-Wright peak flow meters three times daily. Levels of Der p I in dust from carpeted floors were significantly higher than in dust from smooth floors. We found a positive relationship of Der p I levels, in floor dust collected from carpeted floors, with PEF-variability and also with the prevalence of wheeze, shortness of breath, and attacks of shortness of breath with wheezing during the observation period. The effects on peak flow variability was larger in children allergic to house dust than in children not allergic to house dust. Peak flow variability was significantly increased at exposure levels well below 10,000 ng Der p I.g-1 dust, which has been suggested to be a "threshold" for increased risk symptoms among sensitized asthmatics.(ABSTRACT TRUNCATED AT 250 WORDS)