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

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.

Figure 1

Association of disease severity with the frequency and severity of exacerbations. Reproduced from Hurst et al. [3] with permission.

Figure 2

Schematic illustration of the frequent exacerbator phenotype. While many patients with chronic obstructive pulmonary disease (COPD) experience exacerbations, there is a subgroup of patients who enter a destructive cycle of frequent exacerbations with associated poorer outcome. This phenotype appears to be maintained over time.

Figure 3

Annual rate of myocardial infarction against the annual rate of exacerbation (defined as prescription of steroids and antibiotics together). Reproduced from Donaldson et al. [86] with permission.