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      Recent advances in understanding lung function development

      review-article
      a , 1 , 2 , 3 , 4 , 5
      F1000Research
      F1000Research
      Asthma, children, COPD, FEV1, genetics, lung function, tobacco smoke, trajectories

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          Abstract

          Recent years have witnessed critical contributions to our understanding of the determinants and long-term implications of lung function development. In this article, we review studies that have contributed to advances in understanding lung function development and its critical importance for lung health into adult life. In particular, we have focused on early life determinants that include genetic factors, perinatal events, environmental exposures, lifestyle, infancy lower respiratory tract infections, and persistent asthma phenotypes. Longitudinal studies have conclusively demonstrated that lung function deficits that are established by school age may track into adult life and increase the risk of adult lung obstructive diseases, such as chronic obstructive pulmonary disease. Furthermore, these contributions have provided initial evidence in support of a direct influence by early life events on an accelerated decline of lung function and an increased susceptibility to its environmental determinants well into adult life. As such, we argue that future health-care programs based on precision medicine approaches that integrate deep phenotyping with tailored medication and advice to patients should also foster optimal lung function growth to be fully effective.

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          Most cited references74

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          Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus

          Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects. Viral RNA expression and late virus release into supernatant was increased 50- and 7-fold, respectively in asthmatic cells compared with healthy controls. Virus infection induced late cell lysis in asthmatic cells but not in normal cells. Examination of the early cellular response to infection revealed impairment of virus induced caspase 3/7 activity and of apoptotic responses in the asthmatic cultures. Inhibition of apoptosis in normal cultures resulted in enhanced viral yield, comparable to that seen in infected asthmatic cultures. Examination of early innate immune responses revealed profound impairment of virus-induced interferon-β mRNA expression in asthmatic cultures and they produced >2.5 times less interferon-β protein. In infected asthmatic cells, exogenous interferon-β induced apoptosis and reduced virus replication, demonstrating a causal link between deficient interferon-β, impaired apoptosis and increased virus replication. These data suggest a novel use for type I interferons in the treatment or prevention of virus-induced asthma exacerbations.
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            The natural history of chronic airflow obstruction.

            A prospective epidemiological study of the early stages of the development of chronic obstructive pulmonary disease was performed on London working men. The findings showed that forced expiratory volume in one second (FEV1) falls gradually over a lifetime, but in most non-smokers and many smokers clinically significant airflow obstruction never develops. In susceptible people, however, smoking causes irreversible obstructive changes. If a susceptible smoker stops smoking he will not recover his lung function, but the average further rates of loss of FEV1 will revert to normal. Therefore, severe or fatal obstructive lung disease could be prevented by screening smokers' lung function in early middle age if those with reduced function could be induced to stop smoking. Infective processes and chronic mucus hypersecretion do not cause chronic airflow obstruction to progress more rapidly. There are thus two largely unrelated disease processes, chronic airflow obstruction and the hypersecretory disorder (including infective processes).
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              Rhinovirus illnesses during infancy predict subsequent childhood wheezing.

              The contribution of viral respiratory infections during infancy to the development of subsequent wheezing and/or allergic diseases in early childhood is not established. To evaluate these relationships prospectively from birth to 3 years of age in 285 children genetically at high risk for developing allergic respiratory diseases. By using nasal lavage, the relationship of timing, severity, and etiology of viral respiratory infections during infancy to wheezing in the 3rd year of life was evaluated. In addition, genetic and environmental factors that could modify risk of infections and wheezing prevalence were analyzed. Risk factors for 3rd year wheezing were passive smoke exposure (odds ratio [OR]=2.1), older siblings (OR=2.5), allergic sensitization to foods at age 1 year (OR=2.0), any moderate to severe respiratory illness without wheezing during infancy (OR=3.6), and at least 1 wheezing illness with respiratory syncytial virus (RSV; OR=3.0), rhinovirus (OR=10) and/or non-rhinovirus/RSV pathogens (OR=3.9) during infancy. When viral etiology was considered, 1st-year wheezing illnesses caused by rhinovirus infection were the strongest predictor of subsequent 3rd year wheezing (OR=6.6; P < .0001). Moreover, 63% of infants who wheezed during rhinovirus seasons continued to wheeze in the 3rd year of life, compared with only 20% of all other infants (OR=6.6; P < .0001). In this population of children at increased risk of developing allergies and asthma, the most significant risk factor for the development of preschool childhood wheezing is the occurrence of symptomatic rhinovirus illnesses during infancy that are clinically and prognostically informative based on their seasonal nature.
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                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                19 May 2017
                2017
                : 6
                : 726
                Affiliations
                [1 ]Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [2 ]Sachs’ Children’s Hospital, Södersjukhuset, Stockholm, Sweden
                [3 ]Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden
                [4 ]Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, USA
                [5 ]ISGlobal Center for Research in Environmental Epidemiology, Barcelona, Spain
                Author notes

                EM and SG contributed equally to the design, research, and writing of the manuscript.

                Competing interests: The authors declare that they have no competing interests.

                Author information
                http://orcid.org/0000-0002-8248-0663
                Article
                10.12688/f1000research.11185.1
                5461903
                28620467
                ca0651e2-9161-4d5b-b8ea-6707064c96b3
                Copyright: © 2017 Melén E and Guerra S

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 May 2017
                Funding
                Award ID: Swedish Heart-Lung Foundation
                Award ID: Swedish Research Council
                Award ID: Stockholm County Council
                Award ID: Karolinska Institutet
                Award ID: National Institutes of Health
                EM is supported by research grants from the Swedish Heart-Lung Foundation, the Swedish Research Council, the Stockholm County Council (ALF), and the Strategic Research Programme (SFO) in Epidemiology at Karolinska Institutet. SG is supported by research grants from the National Institutes of Health.
                The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Review
                Articles
                Airway/Respiratory Physiology
                Asthma & Allergic Rhinitis
                COPD & Allied Disorders
                Environmental & Occupational Lung Diseases
                Integrative Physiology
                Medical Genetics
                Pediatric Infectious Diseases
                Physiogenomics
                Preventive Medicine
                Respiratory Pediatrics
                Social & Behavioral Determinants of Health

                asthma,children,copd,fev1,genetics,lung function,tobacco smoke,trajectories

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