Olivier Le Rouzic1, Nicolas Roche2, Alexis B Cortot3, Isabelle Tillie-Leblond3, Frédéric Masure4, Thierry Perez3, Isabelle Boucot5, Latifa Hamouti6, Juliette Ostinelli7, Céline Pribil8, Christine Poutchnine9, Stéphane Schück10, Mathilde Pouriel10, Bruno Housset11. 1. Department of Respiratory Diseases, University of Lille, CHU Lille, Lille. Electronic address: olivier.lerouzic@univ-lille2.fr. 2. Department of Respiratory Diseases, AP-HP, Hôpital Cochin,tmen EA2511, Université Paris Descartes, Sorbonne Paris Cité, Paris. 3. Department of Respiratory Diseases, University of Lille, CHU Lille, Lille. 4. Department of Respiratory Diseases, Groupe Medical Saint Remi, Reims. 5. GlaxoSmithKline, Brentford, England. 6. Boehringer Ingelheim, Paris. 7. AstraZeneca, Rueil-Malmaison. 8. GlaxoSmithKline, Marly Le Roi. 9. Pfizer, Paris. 10. Kappa Santé, Paris. 11. Centre hospitalier intercommunal de Créteil, Service Pneumologie, UPEC, Université Paris-Est, UMR S955, Créteil, France.
Abstract
BACKGROUND: The COPD "frequent exacerbator" phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations. METHODS: Data from patients with COPD from the French cohort in Exacerbations of COPD Patients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters. RESULTS: Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations. CONCLUSIONS: These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype.
BACKGROUND: The COPD "frequent exacerbator" phenotype is usually defined by at least two treated exacerbations per year and is associated with a huge impact on patient health. However, existence of this phenotype and corresponding thresholds still need to be formally confirmed by statistical methods analyzing exacerbation profiles with no specific a priori hypothesis. The aim of this study was to confirm the existence of the frequent exacerbator phenotype with an innovative unbiased statistical analysis of prospectively recorded exacerbations. METHODS: Data from patients with COPD from the French cohort in Exacerbations of COPDPatients (EXACO) were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic (ROC) curve analysis to determine the best threshold to allocate patients to identified clusters. Univariate and multivariate analyses were performed to study characteristics associated with different clusters. RESULTS: Two clusters of patients were identified based on exacerbation frequency over time, with 2.89 exacerbations per year on average in the first cluster (n = 348) and 0.71 on average in the second cluster (n = 116). The best threshold to distinguish these clusters was two moderate to severe exacerbations per year. Frequent exacerbators had more airflow limitation, symptoms, and health-related quality of life impairment. A simple clinical score was derived to help identify patients at risk of exacerbations. CONCLUSIONS: These analyses confirmed the existence and clinical relevance of a frequent exacerbator subgroup of patients with COPD and the currently used threshold to define this phenotype.
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