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      Chronic cough as a novel phenotype of chronic obstructive pulmonary disease

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          Abstract

          Background and purpose

          Chronic cough can be a dominant symptom of chronic obstructive pulmonary disease (COPD), although its clinical impact remains unclear. The aim of our study was to identify phenotypic differences according to the presence of chronic cough or sputum and evaluate the impact of chronic cough on the risk of acute exacerbation of COPD (AECOPD).

          Methods

          In a nationwide COPD cohort including 1,613 COPD patients, patients with chronic cough only, those with sputum only, those with chronic bronchitis (CB), and those without cough and sputum were compared with regard to dyspnea, lung function, quality of life (QoL), and risk of AECOPD.

          Results

          The rates of chronic cough, chronic sputum, and both were 23.4%, 32.4%, and 18.2%, respectively. Compared with patients without chronic cough, those with chronic cough exhibited a lower forced expiratory volume in 1 second (% predicted) and diffusing capacity of the lungs for carbon monoxide (% predicted), more frequent AECOPD, more severe dyspnea, and worse QoL. Pulmonary function, dyspnea severity, and QoL worsened in the following order: without cough or sputum, with sputum only, with cough only, and with CB. Multivariate analyses revealed chronic cough as an independent risk factor for a lower lung function, more severe dyspnea, and a poor QoL. Moreover, the risk of future AECOPD was significantly associated with chronic cough (odds ratio 1.56, 95% CI 1.08–2.24), but not with chronic sputum.

          Conclusion

          Our results suggest that chronic cough should be considered as an important phenotype during the determination of high-risk groups of COPD patients.

          Related collections

          Most cited references 24

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          Not 15 but 50% of smokers develop COPD?--Report from the Obstructive Lung Disease in Northern Sweden Studies.

          The prevalence of chronic obstructive pulmonary disease (COPD) according to guidelines of today seems considerably higher than has been reported also in recent literature. To estimate the prevalence of COPD as defined by British Thoracic Society (BTS) criteria and the recent global initiative for chronic obstructive lung disease (GOLD) criteria. Further aims were to assess the proportion of underdiagnosis and of symptoms in subjects with COPD, and to study risk factors for COPD. In 1996, 5892 of the Obstructive Lung Disease in Northern Sweden (OLIN) Study's first cohort could be traced to a third follow-up survey, and 5189 completed responses (88%) were received corresponding to 79% of the original cohort from December 1985. Of the responders, a random sample of 1500 subjects were invited to a structured interview and a lung function test, and 1237 of the invited completed a lung function test with acceptable quality. In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, while it was 14% according to the GOLD criteria. The absolutely dominating risk factors were increasing age and smoking, and approximately a half of elderly smokers fulfilled the criteria for COPD according to both the BTS and the GOLD criteria. Family history of obstructive airway disease was also a risk factor, while gender was not. Of those fulfilling the BTS criteria for COPD, 94% were symptomatics, 69% had chronic productive cough, but only 31% had prior to the study been diagnosed as having either chronic bronchitis, emphysema, or COPD. The corresponding figures for COPD according GOLD were 88, 51, and 18%. In ages >45 years, the prevalence of COPD according to the BTS guidelines was 8%, and it was 14% according to the GOLD criteria. Fifty percent of elderly smokers had developed COPD. The large majority of subjects having COPD were symptomatic, while the proportion of those diagnosed as having COPD or similar diagnoses was small.
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            Prevalence, pathogenesis, and causes of chronic cough.

            Cough is a reflex action of the respiratory tract that is used to clear the upper airways. Chronic cough lasting for more than 8 weeks is common in the community. The causes include cigarette smoking, exposure to cigarette smoke, and exposure to environmental pollution, especially particulates. Diseases causing chronic cough include asthma, eosinophilic bronchitis, gastro-oesophageal reflux disease, postnasal drip syndrome or rhinosinusitis, chronic obstructive pulmonary disease, pulmonary fibrosis, and bronchiectasis. Doctors should always work towards a clear diagnosis, considering common and rare illnesses. In some patients, no cause is identified, leading to the diagnosis of idiopathic cough. Chronic cough is often associated with an increased response to tussive agents such as capsaicin. Plastic changes in intrinsic and synaptic excitability in the brainstem, spine, or airway nerves can enhance the cough reflex, and can persist in the absence of the initiating cough event. Structural and inflammatory airway mucosal changes in non-asthmatic chronic cough could represent the cause or the traumatic response to repetitive coughing. Effective control of cough requires not only controlling the disease causing the cough but also desensitisation of cough pathways.
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              Incidence of chronic obstructive pulmonary disease in a cohort of young adults according to the presence of chronic cough and phlegm.

              The few prospective studies aimed at assessing the incidence of chronic obstructive pulmonary disease (COPD) in relation to the presence of chronic cough/phlegm have produced contrasting results. To assess the incidence of COPD in a cohort of young adults and to test whether chronic cough/phlegm and dyspnea are independent predictors of COPD. An international cohort of 5,002 subjects without asthma (ages 20-44 yr) with normal lung function (FEV(1)/FVC ratio >/= 70%) from 12 countries was followed from 1991-2002 in the frame of the European Community Respiratory Health Survey II. Incident cases of COPD were those who had an FEV(1)/FVC ratio less than 70% at the end of the follow-up, but did not report having had a doctor diagnose asthma during the follow-up. The incidence rate of COPD was 2.8 cases/1,000/yr (95% confidence interval [CI], 2.3-3.3). Chronic cough/phlegm was an independent and statistically significant predictor of COPD (incidence rate ratio [IRR], 1.85; 95% CI, 1.17-2.93) after adjusting for smoking habits and other potential confounders, whereas dyspnea was not associated with the disease (IRR = 0.98; 95% CI, 0.64-1.50). Subjects who reported chronic cough/phlegm both at baseline and at the follow-up had a nearly threefold-increased risk of developing COPD with respect to asymptomatic subjects (IRR = 2.88; 95% CI, 1.44-5.79). The incidence of COPD is substantial even in young adults. The presence of chronic cough/phlegm identifies a subgroup of subjects with a high risk of developing COPD, independently of smoking habits.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                International Journal of COPD
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove Medical Press
                1176-9106
                1178-2005
                2018
                30 May 2018
                : 13
                : 1793-1801
                Affiliations
                [1 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Ilsan, Republic of Korea
                [2 ]Division of Allergy and Respiratory Medicine, Department of Internal Medicine, Soon Chun Hyang University Bucheon Hospital, Bucheon, Republic of Korea
                [3 ]Department of Pulmonary and Critical Care Medicine, Gachon University, Gil Medical Center, Incheon, Republic of Korea
                [4 ]Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea
                [5 ]Division of Pulmonary and Critical Care Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Republic of Korea
                [6 ]Department of Internal Medicine, The Catholic University of Korea, Yeouido St Mary’s Hospital, Seoul, Republic of Korea
                [7 ]Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea
                [8 ]Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
                [9 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea
                Author notes
                Correspondence: Deog Kyeom Kim, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, 20 Boramaero-5-Gil, Dongjak-gu, Seoul, 156-707, Republic of Korea, Tel +82 2 870 2228, Fax +82 2 831 2826, Email kimdkmd@ 123456snu.ac.kr
                Article
                copd-13-1793
                10.2147/COPD.S153821
                5985853
                © 2018 Koo et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Respiratory medicine

                pulmonary disease, chronic obstructive, cough, exacerbation, severity

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