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      Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function.

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          Abstract

          Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms.

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          Most cited references 14

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          Physiology of obesity and effects on lung function.

          In obese people, the presence of adipose tissue around the rib cage and abdomen and in the visceral cavity loads the chest wall and reduces functional residual capacity (FRC). The reduction in FRC and in expiratory reserve volume is detectable, even at a modest increase in weight. However, obesity has little direct effect on airway caliber. Spirometric variables decrease in proportion to lung volumes, but are rarely below the normal range, even in the extremely obese, while reductions in expiratory flows and increases in airway resistance are largely normalized by adjusting for lung volumes. Nevertheless, the reduction in FRC has consequences for other aspects of lung function. A low FRC increases the risk of both expiratory flow limitation and airway closure. Marked reductions in expiratory reserve volume may lead to abnormalities in ventilation distribution, with closure of airways in the dependent zones of the lung and ventilation perfusion inequalities. Greater airway closure during tidal breathing is associated with lower arterial oxygen saturation in some subjects, even though lung CO-diffusing capacity is normal or increased in the obese. Bronchoconstriction has the potential to enhance the effects of obesity on airway closure and thus on ventilation distribution. Thus obesity has effects on lung function that can reduce respiratory well-being, even in the absence of specific respiratory disease, and may also exaggerate the effects of existing airway disease.
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            Clinical and Radiologic Disease in Smokers With Normal Spirometry.

            Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.
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              Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS).

              Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multicentre observational study of chronic obstructive pulmonary disease (COPD) designed to guide future development of therapies for COPD by providing robust criteria for subclassifying COPD participants into groups most likely to benefit from a given therapy during a clinical trial, and identifying biomarkers/phenotypes that can be used as intermediate outcomes to reliably predict clinical benefit during therapeutic trials. The goal is to enrol 3200 participants in four strata. Participants undergo a baseline visit and three annual follow-up examinations, with quarterly telephone calls. Adjudication of exacerbations and mortality will be undertaken.
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                Author and article information

                Journal
                N. Engl. J. Med.
                The New England journal of medicine
                1533-4406
                0028-4793
                May 12 2016
                : 374
                : 19
                Affiliations
                [1 ] From the Cardiovascular Research Institute (P.G.W., S.C.L.) and the Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy (P.G.W., S.A.C., S.C.L.), University of California at San Francisco, San Francisco; the Departments of Medicine and Epidemiology, Columbia University Medical Center (R.G.B.), and the Department of Medicine, Weill-Cornell Medical College (F.J.M.) - both in New York; the Department of Medicine, Center for Genomics and Personalized Medicine Research, Wake Forest University, Winston-Salem (E.B.), and the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (D.C., N.A.G.) - both in North Carolina; the Section of Pulmonary and Critical Care Medicine, Medical Service, Veterans Affairs Ann Arbor Healthcare System (J.L.C.), and the Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan (J.L.C., M.K.H.) - both in Ann Arbor; the Department of Medicine, Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore (N.N.H.); the Department of Radiology, University of Iowa Carver College of Medicine, Iowa City (E.A.H.); the Department of Medicine, University of Utah Hospitals and Clinics, Salt Lake City (R.E.K., R.P.); the Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles (E.K., D.P.T.); the Department of Medicine, University of Nebraska Medical Center, Omaha (S.R.); and the Clinical Discovery Unit, AstraZeneca, Cambridge, United Kingdom (S.R.).
                Article
                NIHMS802615
                10.1056/NEJMoa1505971
                4968204
                27168432

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