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      Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years

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          Abstract

          Objectives

          Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied.

          Methods

          Spirometry data from two time points (follow-up time 9–11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28–73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV 1) decline were analysed using mixed-effects linear regression.

          Results

          Early life exposures were significantly associated with FEV 1 decline, with estimates almost as large as personal smoking. FEV 1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV 1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV 1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age.

          Conclusion

          Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.

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          Most cited references39

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          Exposure to environmental microorganisms and childhood asthma.

          Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study--PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle)--samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study--GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study)--samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.).
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            Impact of maternal age on obstetric outcome.

            To estimate the effect of maternal age on obstetric outcomes. A prospective database from a multicenter investigation of singletons, the FASTER trial, was studied. Subjects were divided into 3 age groups: 1) less than 35 years, 2) 35-39 years, and 3) 40 years and older. Multivariable logistic regression analysis was used to assess the effect of age on outcomes after adjusting for race, parity, body mass index, education, marital status, smoking, medical history, use of assisted conception, and patient's study site. A total of 36,056 women with complete data were available: 28,398 (79%) less than 35 years of age; 6,294 (17%) 35-39 years; and 1,364 (4%) 40 years and older. Increasing age was significantly associated with miscarriage (adjusted odds ratio [adjOR]2.0 and 2.4 for ages 35-39 years and age 40 years and older, respectively), chromosomal abnormalities (adjOR 4.0 and 9.9), congenital anomalies (adjOR 1.4 and 1.7), gestational diabetes (adjOR 1.8 and 2.4), placenta previa (adjOR 1.8 and 2.8), and cesarean delivery (adjOR 1.6 and 2.0). Patients aged 35-39 years were at increased risk for macrosomia (adjOR 1.4). Increased risk for abruption (adjOR 2.3), preterm delivery (adjOR 1.4), low birth weight (adjOR 1.6), and perinatal mortality (adjOR 2.2) was noted in women aged 40 years and older. Increasing maternal age is independently associated with specific adverse pregnancy outcomes. Increasing age is a continuum rather than a threshold effect.
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              Gender differences in airway behaviour over the human life span.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                26 January 2016
                2016
                : 11
                : 1
                : e0145127
                Affiliations
                [1 ]Swiss Tropical and Public Health Institute, Dept. Epidemiology and Public Health, Basel, Switzerland
                [2 ]University of Basel, Basel, Switzerland
                [3 ]Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia
                [4 ]Unit of Epidemiology and Medical Statistics, Department of Public Health and Community Medicine, University of Verona, Verona, Italy
                [5 ]Hôpital Intercantonal de la Broye, Payerne, Switzerland
                [6 ]Dept. of Respiratory Medicine and Sleep, Landspitali University Hospital Reykjavik, Reykjavik, Iceland
                [7 ]Helmholtz Center Munich, National Research Centre for Environmental Health, Munich, Germany
                [8 ]Ludwig Maximilians University Munich, University Hospital Munich, Institute and Outpatient Clinic for Occupational, Social and Environmental Medicine and German Center for Lung Research (DZL), Munich, Germany
                [9 ]Department of Medical Sciences: Respiratory Medicine & Allergology, Uppsala University, Uppsala, Sweden
                [10 ]Department of Public Health Sciences, Imperial College London, London, United Kingdom
                [11 ]Department of Medical Sciences: Occupational & Environmental Medicine, Uppsala University, Uppsala, Sweden
                [12 ]Division of Pulmonary Medicine, Regional Hospital of Lugano, Lugano, Switzerland
                [13 ]Department of Clinical Science, University of Bergen, Bergen, Norway
                [14 ]Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway
                [15 ]Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
                [16 ]University of Pavia, Faculty of Medicine, Dept. of Public Health, Neurosciences, Experimental and Legal Medicine, Pavia, Italy
                [17 ]Bergen Respiratory Research Group, Centre for International Health, University of Bergen, Bergen, Norway
                [18 ]Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway
                University Children's Hospital Basel, SWITZERLAND
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JD CS SD. Performed the experiments: EZ SD SA LB TG JH CJ DJ RM DN MP JS SV NP CS. Analyzed the data: JD CS. Wrote the paper: JD EZ SD SA LB TG JH CJ DJ RM DN MP JS SV NP CS FGR.

                Article
                PONE-D-15-30352
                10.1371/journal.pone.0145127
                4728209
                26811913
                8deecfdf-1cde-4e01-b23f-b143ad3950e7
                © 2016 Dratva et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 July 2015
                : 27 November 2015
                Page count
                Figures: 1, Tables: 4, Pages: 14
                Funding
                The first author was supported by a Marie Heim-Vögtlin grant from the Swiss National Science Foundation (grant # PMPDP3_129021/1; # PMPDP3_141671/1), the Lung league Beider Basel, Lung league Graubünden, the Stiftung ehemals Bündner Heilstätten and the COST action BM1201. Research support received by the SAPALDIA and ECRHS cohorts can be found in the online supplement (e-supplement). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pulmonology
                Asthma
                People and Places
                Population Groupings
                Age Groups
                Adults
                Biology and Life Sciences
                Behavior
                Habits
                Smoking Habits
                Medicine and Health Sciences
                Pulmonology
                Respiratory Infections
                Biology and Life Sciences
                Developmental Biology
                Organism Development
                Aging
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Aging
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Aging
                Medicine and Health Sciences
                Pulmonology
                Environmental and Occupational Lung Diseases
                Biology and Life Sciences
                Physiology
                Respiratory Physiology
                Medicine and Health Sciences
                Physiology
                Respiratory Physiology
                Ecology and Environmental Sciences
                Terrestrial Environments
                Urban Environments
                Custom metadata
                ECRHS and SAPALDIA cohort studies are bound to the local ethical and legal restrictions with respect to study data. At the time of SAPALDIA 1 and 2, and ECRHS I and II providing data publically was not considered and participants were not asked for consent to provide individual data to the public. The data are available on request to scientists. Requests are to be addressed to the study primary investigators ( www.ecrhs.org/; www.sapaldia.ch) or via the first and/or last authors of the manuscript.

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