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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.)

Numerous oral indigenous microorganisms are constantly introduced into the stomach via the laryngopharynx, and a portion of these microorganisms irregularly reaches the lower airways and lungs. This study investigated the association between airflow limitation and the status of tongue microbiota, which is a primary source of ingested oral bacterial populations. The study population consisted of 484 community-dwelling adults aged 70-80 years inhabiting Hisayama town, Japan, who underwent a regular health examination including dental examination and spirometry test in 2016. The bacterial density and composition of their tongue microbiota were determined using a previously used 16S rRNA gene to understand their relationship with oral health conditions. The present cross-sectional study compared the tongue microbiota status between elderly individuals with airflow limitation and those with normal airflow. The total bacterial density of the tongue microbiota of individuals with airflow limitation was significantly higher than that of individuals with normal airflow. Logistic regression analysis demonstrated that a high-biomass tongue microbiota was significantly associated with airflow limitation after adjustment for smoking intensity and other covariates (adjusted OR 1.61, 95% CI 1.01-2.60). Of the predominant commensals, higher amounts of Prevotella melaninogenica and Actinomyces odontolyticus were associated with a higher prevalence of airflow limitation. These results indicate that increased bacterial burden in the tongue microbiota is associated with a higher prevalence of airflow limitation., Competing Interests: Conflict of interest: T. Takeshita has nothing to disclose. Conflict of interest: K. Matsumoto has nothing to disclose. Conflict of interest: M. Furuta has nothing to disclose. Conflict of interest: S. Fukuyama has nothing to disclose. Conflict of interest: K. Takeuchi has nothing to disclose. Conflict of interest: H. Ogata has nothing to disclose. Conflict of interest: M. Asakawa has nothing to disclose. Conflict of interest: S. Kageyama has nothing to disclose. Conflict of interest: J. Hata has nothing to disclose. Conflict of interest: T. Ninomiya has nothing to disclose. Conflict of interest: H. Inoue has nothing to disclose. Conflict of interest: Y. Yamashita has nothing to disclose., (Copyright ©The authors 2021.)

Background: Lung function is an important predictor of health and a marker of physical functioning at older ages. This study aimed to quantify the years of lung function lost according to disadvantaged socioeconomic conditions across the life-course., Methods: This multicohort study used harmonised individual-level data from six European cohorts with information on life-course socioeconomic disadvantage and lung function assessed by forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC). 70 496 participants (51% female) aged 18-93 years were included. Socioeconomic disadvantage was measured in early life (low paternal occupational position), early adulthood (low educational level) and adulthood (low occupational position). Risk factors for poor lung function ( e.g. smoking, obesity, sedentary behaviour, cardiovascular and respiratory diseases) were included as potential mediators. The years of lung function lost due to socioeconomic disadvantage were computed at each life stage., Results: Socioeconomic disadvantage during the life-course was associated with a lower FEV 1 . By the age of 45 years, individuals experiencing disadvantaged socioeconomic conditions had lost 4-5 years of healthy lung function versus their more advantaged counterparts (low educational level -4.36 (95% CI -7.33--2.37) for males and -5.14 (-10.32--2.71) for females; low occupational position -5.62 (-7.98--4.90) for males and -4.32 (-13.31--2.27) for females), after accounting for the risk factors for lung function. By the ages of 65 years and 85 years, the years of lung function lost due to socioeconomic disadvantage decreased by 2-4 years, depending on the socioeconomic indicator. Sensitivity analysis using FVC yielded similar results to those using FEV 1 ., Conclusion: Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages., Competing Interests: Conflict of interest: V. Rocha reports grants from Fundação para a Ciência e Tecnologia, during the conduct of the study. Conflict of interest: S. Fraga reports grants from Fundação para a Ciência e Tecnologia, during the conduct of the study. Conflict of interest: C. Moreira has nothing to disclose. Conflict of interest: C. Carmeli has nothing to disclose. Conflict of interest: A. Lenoir has nothing to disclose. Conflict of interest: A. Steptoe has nothing to disclose. Conflict of interest: G. Giles has nothing to disclose. Conflict of interest: M. Goldberg has nothing to disclose. Conflict of interest: M. Zins has nothing to disclose. Conflict of interest: M. Kivimäki reports grants from Medical Research Council, US National Institute on Aging, NordForsk, the Academy of Finland and Helsinki Institute of Life Science, during the conduct of the study. Conflict of interest: P. Vineis has nothing to disclose. Conflict of interest: P. Vollenweider has nothing to disclose. Conflict of interest: H. Barros has nothing to disclose. Conflict of interest: S. Stringhini reports grants from University of Lausanne, during the conduct of the study., (Copyright ©ERS 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.)

Background: COPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established., Methods: We identified 4521 COPD patients in the United Network for Organ Sharing (UNOS) dataset transplanted from May 2005 to August 2016, and 604 patients assigned to receive pulmonary rehabilitation and medical management in the National Emphysema Treatment Trial (NETT). After trimming the populations for NETT eligibility criteria and data completeness, 1337 UNOS and 596 NETT patients remained. Kaplan-Meier estimates of transplant-free survival from transplantation for UNOS, and NETT randomisation, were compared between propensity score-matched UNOS (n=401) and NETT (n=262) patients., Results: In propensity-matched analyses, transplanted patients had better survival compared to medically managed patients in NETT (p=0.003). Stratifying on 6 min walk distance (6 MWD) and FEV 1 , UNOS patients with 6 MWD <1000 ft (∼300 m) or FEV 1 <20% of predicted had better survival than NETT counterparts (median survival 5.0 years UNOS versus 3.4 years NETT; log-rank p<0.0001), while UNOS patients with 6 MWD ≥1000 ft (∼300 m) and FEV 1 ≥20% had similar survival to NETT counterparts (median survival, 5.4 years UNOS versus 4.9 years NETT; log-rank p=0.73), interaction p=0.01., Conclusions: Overall survival is better for matched lung transplant patients compared with medical management alone. Patients who derive maximum benefit are those with 6 MWD <1000 ft (∼300 m) or FEV 1 <20% of predicted, compared with pulmonary rehabilitation and medical management., Competing Interests: Conflict of interest: I. Timofte has nothing to disclose. Conflict of interest: M. Wijesinha has nothing to disclose. Conflict of interest: R. Vesselinov has nothing to disclose. Conflict of interest: J. Kim has nothing to disclose. Conflict of interest: R. Reed reports grants from the Dept of Defense and the Flight Attendant Medical Research Institute during the conduct of the study; and grants from the National Institutes of Health, the COPD Foundation, Janssen Research & Development LLC and the University of Maryland Institute for Clinical and Translational Research outside the submitted work. Conflict of interest: P.G. Sanchez has nothing to disclose. Conflict of interest: N. Ladikos has nothing to disclose. Conflict of interest: S. Pham has nothing to disclose. Conflict of interest: Z. Kon reports consulting and speaking fees from Medtronic, Inc., and consulting fees from Breethe, Inc., outside the submitted work. Conflict of interest: K. Rajagopal has nothing to disclose. Conflict of interest: S.M. Scharf has nothing to disclose. Conflict of interest: R. Wise reports grants, and personal fees for data monitoring committees and consulting from AstraZeneca, Medimmune, Pearl and Boehringer Ingelheim; personal fees for a clinical endpoint committee from Contrafect; personal fees for data safety monitoring committees from Pulmonx, Roche, Merck and AbbVie; personal fees for a steering committee from Spiration; personal fees for a workshop and consulting from Sunovion; research grants from Pearl Therapeutics and Sanofi-Aventis; personal fees for consultancy from Circassia, Pneuma, Verona, Mylan/Theravance and Propelleor Health; grants, and personal fees for a data monitoring committee, consultancy, a scientific advisory board and a clinical endpoint committee from GSK, outside the submitted work. Conflict of interest: A.L. Sternberg reports that the NETT was supported by contracts from the NHLBI during the conduct of the study. Conflict of interest: D. Kaczorowski has nothing to disclose. Conflict of interest: B. Griffith has nothing to disclose. Conflict of interest: M. Terrin has nothing to disclose. Conflict of interest: A. Iacono has nothing to disclose., (Copyright ©ERS 2020.)

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.In a discovery-replication EWAS design, DNAme in blood and spirometry were measured twice, 6-15 years apart, in the same participants of three adult population-based discovery cohorts (n=2043). Associated DNAme markers (p<5×10 -7 ) were tested in seven replication cohorts (adult: n=3327; childhood: n=420). Technical bias-adjusted residuals of a regression of the normalised absolute β-values on control probe-derived principle components were regressed on level and change of forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC) and their ratio (FEV 1 /FVC) in the covariate-adjusted discovery EWAS. Inverse-variance-weighted meta-analyses were performed on results from discovery and replication samples in all participants and never-smokers.EWAS signals were enriched for smoking-related DNAme. We replicated 57 lung function DNAme markers in adult, but not childhood samples, all previously associated with smoking. Markers not previously associated with smoking failed replication. cg05575921 ( AHRR (aryl hydrocarbon receptor repressor)) showed the statistically most significant association with cross-sectional lung function (FEV 1 /FVC: p discovery =3.96×10 -21 and p combined =7.22×10 -50 ). A score combining 10 DNAme markers previously reported to mediate the effect of smoking on lung function was associated with lung function (FEV 1 /FVC: p=2.65×10 -20 ).Our results reveal that lung function-associated methylation signals in adults are predominantly smoking related, and possibly of clinical utility in identifying poor lung function and accelerated decline. Larger studies with more repeat time-points are needed to identify lung function DNAme in never-smokers and in children., Competing Interests: Conflict of interest: M. Imboden has nothing to disclose. Conflict of interest: M. Wielscher has nothing to disclose. Conflict of interest: F.I. Rezwan has nothing to disclose. Conflict of interest: A.F.S. Amaral has nothing to disclose. Conflict of interest: E. Schaffner has nothing to disclose. Conflict of interest: A. Jeong has nothing to disclose. Conflict of interest: A. Beckmeyer-Borowko has nothing to disclose. Conflict of interest: S.E. Harris reports grants from Medical Research Council, Biotechnology and Biological Sciences Research Council, Age UK and The Wellcome Trust, during the conduct of the study. Conflict of interest: J.M. Starr has nothing to disclose. Conflict of interest: I.J. Deary reports grants from Age UK and Medical Research Council, during the conduct of the study. Conflict of interest: C. Flexeder has nothing to disclose. Conflict of interest: M. Waldenberger has nothing to disclose. Conflict of interest: A. Peters has nothing to disclose. Conflict of interest: H. Schulz reports grants from German Federal Ministry of Education and Research (BMBF), during the conduct of the study. Conflict of interest: S. Chen has nothing to disclose. Conflict of interest: S.K. Sunny has nothing to disclose. Conflict of interest: W.J.J. Karmaus has nothing to disclose. Conflict of interest: Y. Jiang has nothing to disclose. Conflict of interest: G. Erhart has nothing to disclose. Conflict of interest: F. Kronenberg has nothing to disclose. Conflict of interest: R. Arathimos has nothing to disclose. Conflict of interest: G.C. Sharp has nothing to disclose. Conflict of interest: A.J. Henderson reports grants from Medical Research Council and Wellcome Trust, during the conduct of the study. Conflict of interest: Y. Fu has nothing to disclose. Conflict of interest: P. Piirilä has nothing to disclose. Conflict of interest: K.H. Pietiläinen has nothing to disclose. Conflict of interest: M. Ollikainen has nothing to disclose. Conflict of interest: A. Johansson has nothing to disclose. Conflict of interest: U. Gyllensten has nothing to disclose. Conflict of interest: M de Vries has nothing to disclose. Conflict of interest: D.A. van der Plaat has nothing to disclose. Conflict of interest: K. de Jong has nothing to disclose. Conflict of interest: H.M. Boezen has nothing to disclose. Conflict of interest: I.P. Hall reports grants from GSK and Boehringer Ingelheim, outside the submitted work. Conflict of interest: M.D. Tobin reports grants from Pfizer and GSK, outside the submitted work. Conflict of interest: M-R. Jarvelin has nothing to disclose. Conflict of interest: J.W. Holloway reports grants from European Union and National Institutes of Health, during the conduct of the study. Conflict of interest: D. Jarvis reports grants from European Union, Medical Research Council and Asthma UK, during the conduct of the study. Conflict of interest: N.M. Probst-Hensch has nothing to disclose., (Copyright ©ERS 2019.)

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.)

Poverty is strongly associated with mortality from COPD, but little is known of its relation to airflow obstruction.In a cross-sectional study of adults aged ≥40 years from 12 sites (N=9255), participating in the Burden of Obstructive Lung Disease (BOLD) study, poverty was evaluated using a wealth score (0-10) based on household assets. Obstruction, measured as forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) (%) after administration of 200 μg salbutamol, and prevalence of FEV 1 /FVC1 /FVC increased by 0.36% (absolute change) (95%CI: 0.22, 0.49; p<0.001) per unit increase in wealth score. Adjustments for other confounders reduced this effect to 0.23% (0.11, 0.34), but even this value remained highly significant (p<0.001). Results were consistent across sites (I 2 =1%; p het =0.44). Mean wealth scores explained 38% of the variation in mean FEV 1 /FVC between sites (r 2 =0.385, p=0.031).Airflow obstruction is consistently associated with poverty at individual and community levels across several countries., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

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.)

The aim of this study was to derive new spirometric reference equations for the English population, using the 1995/1996 Health Survey for England, a large nationally representative cross-sectional study. The measurements used were the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of a sample of 6,053 "healthy" (nonsmokers with no reported diagnosis of asthma or respiratory symptoms) White people aged > or = 16 yrs. Multiple regression analysis, with age and height as predictors, was carried out to estimate prediction equations for mean FEV1, FVC and FEV1/FVC, separately for males and females. A method based on smoothing multiple estimates of the fifth percentiles of residuals was used to derive prediction equations for the lower limit of normal lung function. The new equations fit the current English adult population considerably better than the European Coal and Steel Community equations, and the proportions of people with "low" (below the fifth percentile) lung function are closer to those expected throughout the whole adult age range (16 to > 75 yrs). For the age ranges the studies share in common, the new equations give estimates close to those derived from other nonlinear equations in recent studies. It is, therefore, suggested that these newly developed prediction equations be used for the White English population in both epidemiological studies and clinical practice.

There is a growing body of evidence to support the hypothesised links between consumption of antioxidant rich foods and the occurrence of obstructive airway disease. The main research question was to examine the relationships between two types of dietary exposure and two indicators of respiratory morbidity in Scottish adults. The relationships between dietary consumption of fruit, vegetables and fish, and plasma levels of vitamins A, C, E and beta-carotene, and pulmonary function (forced expiratory volume in one second (FEV1)) and symptoms (phlegm production and shortness of breath with wheezing), were examined in a random population sample of adults. A dose/response relationship was found between fruit consumption and pulmonary function. In comparison with eating fruit rarely or never, eating fruit at least once per day, 1-6 times per week, and 1-3 times per month were associated with differences of 132, 100 and 63 mL in FEV1, after adjustment for known confounders and dietary intake of vegetables and fish (n=6186). An SD score change in plasma vitamin C was associated with a 49 mL difference in FEV1 (n=930). Fruit and vitamin E were associated with a reduced prevalence of phlegm production for 3 months or more per year. The most beneficial combination of dietary components may be found in natural foodstuffs, particularly fresh fruit.

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 relationship between the Dermatophagoides pteronyssinus (Der p) I content of house dust and the respiratory symptoms reported for young infants was studied. One hundred and four infants, aged 3-15 months, were selected during July-September 1993 through the Dutch postnatal health care service, using a short screening questionnaire to identify mothers with respiratory allergy to house dust and/or pets. Forty-eight were selected from this group of mothers ("high risk" infants) and 56 infants were selected when neither of the parents reported allergy or chronic respiratory symptoms ("low risk" infants). All homes were visited in October 1993. Dust samples were collected from the infant's mattress and from other places in the home, and the Der p I content was measured in dust extracts. The results indicate that on more than half of the mattresses, the Der p I level was over 2,000 ng.g-1, the level suggested to be associated with an increased risk of sensitization. Information on respiratory symptoms ("wheeze" and "prolonged cough") experienced since birth was obtained by questionnaire from one of the parents on the dust sampling day. The occurrence of respiratory symptoms in the infants appeared to be positively related to the Der p I concentration of the dust. Although no objective measurements of respiratory symptoms were available, the results of this study suggest that exposure to mite allergen in early life may lead to respiratory symptoms that are suggestive of airway obstruction in the first year of life.

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)

The influence of occupational exposures on total mortality and respiratory mortality and morbidity was examined, employing a population specific Job Exposure Matrix (JEM). Moreover, the relationship between time-related variables of exposure to dust and chronic nonspecific lung disease (CNSLD) incidence was analysed, using time since first exposure and duration of exposure. Occupational exposures in the Zutphen cohort were assessed by application of a JEM, arbitrarily considering jobs as exposed when at least 10% of men who had held the job of interest reported an exposure to one or more from a list of 27 chemical agents. None of the exposures was related to mortality due to CNSLD, although results were influenced by the healthy-worker effect and low mortality rates. Exposure to wood dust and a high probability of exposure to dust were associated with total mortality. Exposures to dust and solvents were statistically significantly related to CNSLD incidence. An exposure-response relationship was found for the probability of exposure to dust with CNSLD incidence. Time-related estimates of exposure to dust based on work history were negatively related to CNSLD incidence. The results suggest the presence of a healthy-worker effect, in a general population study, resulting in an underestimation of the relationship between occupational exposures and respiratory diseases based on the evidence published so far. The use of the full work history to determine exposure to dust leads to stronger relationships with CNSLD incidence, compared to conventional analyses using exposure at the start of follow-up.

The reproducibility of answers to childhood respiratory symptom questions was investigated by administering two childhood respiratory symptom questionnaires twice, with a one month interval, to the same population of Dutch school children. The questionnaires were completed by the parents of 410 children from 6-12 yrs old. One questionnaire was developed by the World Health Organization (WHO). The other questionnaire was developed for use by school health services and was based mainly on the American Thoracic Society (ATS) questionnaire for respiratory symptoms in childhood. It was called the Child Health Care (CHC) Questionnaire. Half of the parents received a questionnaire in which the WHO questions came first on both occasions, the other half a questionnaire in which the CHC questionnaire came first on both occasions. The reproducibility of the answers was assessed by calculating Cohen's Kappa, a chance-corrected measure of association. Questions about "wheeze", "asthma", "bronchitis", "cough and phlegm", and "pneumonia" were found to give good to excellent reproducibility, with Kappa values ranging from 0.60-0.96. Questions about "phlegm", "cough", "chest congestion" and "runny/congested nose" were less satisfactory in this respect, with Kappa values generally well below 0.60. The reproducibility of the answers did not depend on the order in which the questionnaires were administered, on the gender or age of the child, or on the smoking habits or educational level of the parents.

In a study on acute health effects of air pollution in the Netherlands, pulmonary function has been measured repeatedly in children aged 7-11 yrs. In study periods of approximately 3 months, 6-10 tests have been made in a group of 1,621 children. The spirometric data have been examined for the presence of trends of pulmonary function with day of study, independent of air pollution. Peak expiratory flow (PEF) increased more than expected from normal lung growth, whereas for maximal mid-expiratory flow (MMEF) a decrease with time was observed. For forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) a smaller than expected increase with time was observed. The observed deviation from the expected pattern was larger for the children with a one week interval between successive tests than for the children with a three week interval. For FVC and FEV1 a non-linear relationship with time was observed, for PEF and MMEF this relationship was approximately linear. The particular changes of spirometric variables with time need to be taken into account when repeated lung function tests are performed to investigate acute effects of air pollution exposure.