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      International Journal of COPD (submit here)

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      Prediction of first acute exacerbation using COPD subtypes identified by cluster analysis

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          Abstract

          Purpose

          In patients with COPD, acute exacerbation (AE) is not only an important determinant of prognosis, but also an important factor in choosing therapeutic agents. In this study, we evaluated the usefulness of COPD subtypes identified through cluster analysis to predict the first AE.

          Patients and methods

          Among COPD patients in the Korea COPD Subgroup Study (KOCOSS) cohort, 1,195 who had follow-up data for AE were included in our study. We selected seven variables for cluster analysis – age, body mass index, smoking status, history of asthma, COPD assessment test (CAT) score, post-bronchodilator (BD) FEV 1 % predicted, and diffusing capacity of carbon monoxide % predicted.

          Results

          K-means clustering identified four clusters for COPD that we named putative asthma-COPD overlap (ACO), mild COPD, moderate COPD, and severe COPD subtypes. The ACO group (n=196) showed the second-best post-BD FEV 1 (75.5% vs 80.9% [mild COPD, n=313] vs 52.4% [moderate COPD, n=345] vs 46.7% [severe COPD, n=341] predicted), the longest 6-min walking distance (424 m vs 405 m vs 389  m vs 365 m), and the lowest CAT score (12.2 vs 13.7 vs 15.6 vs 17.5) among the four groups. ACO group had greater risk for first AE compared to the mild COPD group (HR, 1.683; 95% CI, 1.175–2.410). The moderate COPD and severe COPD group HR values were 1.587 (95% CI, 1.145–2.200) and 1.664 (95% CI, 1.203–2.302), respectively. In addition, St. George’s Respiratory Questionnaire score (HR: 1.019; 95% CI, 1.014–1.024) and gastroesophageal reflux disease were independent factors associated with the first AE (HR: 1.535; 95% CI, 1.116–2.112).

          Conclusion

          Our cluster analysis revealed an exacerbator subtype of COPD independent of FEV 1. Since these patients are susceptible to AE, a more aggressive treatment strategy is needed in these patients.

          Most cited references29

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          Susceptibility to exacerbation in chronic obstructive pulmonary disease.

          Although we know that exacerbations are key events in chronic obstructive pulmonary disease (COPD), our understanding of their frequency, determinants, and effects is incomplete. In a large observational cohort, we tested the hypothesis that there is a frequent-exacerbation phenotype of COPD that is independent of disease severity. We analyzed the frequency and associations of exacerbation in 2138 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Exacerbations were defined as events that led a care provider to prescribe antibiotics or corticosteroids (or both) or that led to hospitalization (severe exacerbations). Exacerbation frequency was observed over a period of 3 years. Exacerbations became more frequent (and more severe) as the severity of COPD increased; exacerbation rates in the first year of follow-up were 0.85 per person for patients with stage 2 COPD (with stage defined in accordance with Global Initiative for Chronic Obstructive Lung Disease [GOLD] stages), 1.34 for patients with stage 3, and 2.00 for patients with stage 4. Overall, 22% of patients with stage 2 disease, 33% with stage 3, and 47% with stage 4 had frequent exacerbations (two or more in the first year of follow-up). The single best predictor of exacerbations, across all GOLD stages, was a history of exacerbations. The frequent-exacerbation phenotype appeared to be relatively stable over a period of 3 years and could be predicted on the basis of the patient's recall of previous treated events. In addition to its association with more severe disease and prior exacerbations, the phenotype was independently associated with a history of gastroesophageal reflux or heartburn, poorer quality of life, and elevated white-cell count. Although exacerbations become more frequent and more severe as COPD progresses, the rate at which they occur appears to reflect an independent susceptibility phenotype. This has implications for the targeting of exacerbation-prevention strategies across the spectrum of disease severity. (Funded by GlaxoSmithKline; ClinicalTrials.gov number, NCT00292552.)
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            Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. GOLD Executive Summary

            American Journal of Respiratory and Critical Care Medicine, 195(5), 557-582
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              Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial.

              To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease. Double blind, placebo controlled study. Eighteen UK hospitals. 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second (FEV(1)) 50% of predicted normal. Inhaled fluticasone propionate 500 microgram twice daily from a metered dose inhaler or identical placebo. Efficacy measures: rate of decline in FEV(1) after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events. There was no significant difference in the annual rate of decline in FEV(1 )(P=0.16). Mean FEV(1) after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P<0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P=0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P=0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P=0.034). Fluticasone propionate 500 microgram twice daily did not affect the rate of decline in FEV(1) but did produce a small increase in FEV(1). Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                COPD
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                28 June 2019
                2019
                : 14
                : 1389-1397
                Affiliations
                [1 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans Seoul Hospital, Ewha Womans University , Seoul, Korea
                [2 ]Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital , Seoul, Korea
                [3 ]Division of Pulmonary Medicine, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Yonsei University Health System , Seoul, Korea
                [4 ]Division of Pulmonology, Department of Internal Medicine, Soonchunhyang University, College of Medicine , Cheonan, Korea
                [5 ]Department of Pulmonary and Critical Care Medicine, Asan Medical Centre, University of Ulsan College of Medicine , Seoul, Korea
                [6 ]Department of Internal Medicine, Wonju Christian Hospital, Yonsei University Wonju College of Medicine , Wonju, Korea
                [7 ]Department of Internal Medicine, Konkuk University College of Medicine , Seoul, Korea
                [8 ]Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine , Anyang, Korea
                Author notes
                Correspondence: Jin Hwa LeeDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University , 260 Gonghang-daero Gangseo-gu, Seoul07804, KoreaTel +8 226 986 1631Email jinhwalee@ 123456ewha.ac.kr
                Article
                205517
                10.2147/COPD.S205517
                6607981
                31388298
                282f085e-3f45-4ed5-981f-b528a7b0b6aa
                © 2019 Yoon 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 15 February 2019
                : 17 May 2019
                Page count
                Figures: 2, Tables: 5, References: 40, Pages: 9
                Categories
                Original Research

                Respiratory medicine
                clustering,prognosis,phenotype,asthma-copd overlap,exacerbation,comorbidity
                Respiratory medicine
                clustering, prognosis, phenotype, asthma-copd overlap, exacerbation, comorbidity

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