Phenotypes, Etiotypes, and Endotypes of Exacerbations of Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease is a major health problem with a high prevalence, a rising incidence, and substantial morbidity and mortality. Its course is punctuated by acute episodes of increased respiratory symptoms, termed exacerbations of chronic obstructive pulmonary disease (ECOPD). ECOPD are important events in the natural history of the disease, as they are associated with lung function decline and prolonged negative effects on quality of life. The present-day therapy for ECOPD with short courses of antibiotics and steroids and escalation of bronchodilators has resulted in only modest improvements in outcomes. Recent data indicate that ECOPD are heterogeneous, raising the need to identify distinct etioendophenotypes, incorporating traits of the acute event and of patients who experience recurrent events, to develop novel and targeted therapies. These characterizations can provide a complete clinical picture, the severity of which will dictate acute pharmacological treatment, and may also indicate whether a change in maintenance therapy is needed to reduce the risk of future exacerbations. In this review we discuss the latest knowledge of ECOPD types on the basis of clinical presentation, etiology, natural history, frequency, severity, and biomarkers in an attempt to characterize these events.

Keywords: COPD; endotyping; etiotyping; exacerbations; phenotyping.

Figure 1.

Daily variability in symptoms versus exacerbation. Representative examples are shown in orange and blue of two patients with differences in daily fluctuation and within-day fluctuation of symptoms.

Figure 2.

Etioendophenotypes of exacerbations.

Figure 3.

Treatment paradigm for ECOPD. * = Severity classification; BEC = blood eosinophil count; CRP = C-reactive protein; ECOPD = exacerbation of chronic obstructive pulmonary disease; Fe_NO = fractional exhaled nitric oxide; HR = heart rate; ICS = inhaled corticosteroid; PDE = phosphodiesterase; RR = respiratory rate; SABA = short-acting β₂-agonist; SAMA = short-acting antimuscarinic agent; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; Sp_O2 = oxygen saturation as measured by pulse oximetry; VAS = visual analogue scale.