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Open Access Review

Mechanisms and impact of the frequent exacerbator phenotype in chronic obstructive pulmonary disease

Jadwiga A Wedzicha*, Simon E Brill, James P Allinson and Gavin C Donaldson

Author Affiliations

Centre for Respiratory Medicine, Royal Free Campus, University College London, Rowland Hill Street, Hampstead, London NW3 2PF, UK

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BMC Medicine 2013, 11:181  doi:10.1186/1741-7015-11-181

Published: 14 August 2013

Abstract

Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients. Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype. This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes. These patients are therefore a priority for research and treatment. The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection. Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment. Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype. This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.

Keywords:
Chronic obstructive pulmonary disease (COPD); Exacerbations; Frequent exacerbator phenotype; Comorbidities