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Bringing Stability to the Chronic Obstructive Pulmonary Disease Patient: Clinical and Pharmacological Considerations for Frequent Exacerbators

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Abstract

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are critical events associated with an accelerated loss of lung function, increased morbidity, and excess mortality. AECOPD are heterogeneous in nature and this may directly impact clinical decision making, specifically in patients with frequent exacerbations. A ‘frequent exacerbator’ is a sub-phenotype of chronic obstructive pulmonary disease (COPD) and is defined as an individual who experiences two or more moderate-to-severe exacerbations per year. This distinct subgroup has higher mortality and accounts for more than half of COPD-related hospitalizations annually. Thus, it is imperative to identify individuals at risk for frequent exacerbations and choose optimal strategies to minimize risk for these events. New paradigms for using combination inhalers and the introduction of novel oral compounds provide expanded treatment options to reduce the risk and frequency of exacerbations. The goals of managing frequent exacerbators or patients at risk for AECOPD are: (1) maximizing bronchodilation; (2) reducing inflammation; and (3) targeting specific molecular pathways implicated in COPD and AECOPD pathogenesis. Novel inhaler therapies including combination long-acting muscarinic agents plus long-acting beta agonists show promising results compared with monotherapy or a long-acting beta agonist inhaled corticosteroid combination in reducing exacerbation risk among individuals at risk for exacerbations and among frequent exacerbators. Likewise, oral medications including macrolides and phosphodiesterase-4 inhibitors reduce the risk for AECOPD in select groups of individuals at high risk for exacerbation. Future direction in COPD management is based on the identification of various subtypes or ‘endotypes’ and targeting therapies based on their pathophysiology. This review describes the impact of AECOPD and the challenges posed by frequent exacerbators, and explores the rationale for different pharmacologic approaches to preventing AECOPD in these individuals.

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Authors and Affiliations

  1. Division of Pulmonary, Allergy and Critical Care, Lung Health Center, University of Alabama Birmingham, Birmingham, AL, USA

    Swati Gulati & J. Michael Wells

  2. Birmingham VA Medical Center, Birmingham, AL, USA

    J. Michael Wells

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  1. Swati Gulati
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S.G. has no conflict of interest to disclose. J.M.W. receives grant funding from the National Institutes of Health/National Heart, Lung, and Blood Institute (K08 123940) and the Cystic Fibrosis Foundation; has contracts to conduct clinical trials from GlaxoSmithKline, AstraZeneca, and Gilead; and is a consultant for Mylan and Quintiles.

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Gulati, S., Wells, J.M. Bringing Stability to the Chronic Obstructive Pulmonary Disease Patient: Clinical and Pharmacological Considerations for Frequent Exacerbators. Drugs 77, 651–670 (2017). https://doi.org/10.1007/s40265-017-0713-5

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