Case-Based Review

Management of Stable Chronic Obstructive Pulmonary Disease

Journal of Clinical Outcomes Management. 2017 June;24(6)

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How is acute exacerbation of COPD defined?

COPD exacerbation is defined as a baseline change of the patient’s dyspnea, cough, and/or sputum that is acute in onset, and may warrant a change in regular medication in a patient with underlying COPD [65]. Exacerbation in clinical trials has been defined on the basis of whether an increase in the level of care beyond regular care is required primarily in the hospital or ED [66]. Frequent exacerbations are defined as 3 symptom-defined exacerbations per year or 2 per year if defined by the need for therapy with corticosteroids, antibiotics, or both [67].

What is the underlying pathophysiology?

AECOPD is associated with enhanced upper and lower airway and systemic inflammation. The bronchial mucosa of stable COPD patients have increased numbers of CD8+ lymphocytes and macrophages. In mild AECOPD, eosinophils are increased in the bronchial mucosa and modest elevation of neutrophils, T lymphocytes (CD3), and TNF alpha positive cells has also been reported [62]. With more severe AECOPD, airway neutrophils are increased. Oxidative stress is a key factor in the development of airway inflammation in COPD [61]. Patients with severe exacerbations have augmented large airway interleukin-8 (IL-8) levels and increased oxidative stress as demonstrated by markers such as hydrogen peroxide and 8-isoprostane [66].

How do acute exacerbations affect the course of the disease?

In general, as the severity of the underlying COPD increases, exacerbations become both more severe and more frequent. The quality of life of patients with frequent exacerbations is worse than patients with a history of less frequent exacerbations [68]. Frequent exacerbations have also been linked to a decline in lung function, with studies suggesting that there might be a decline of 7 mL in FEV1 per lower respiratory tract infection per year [59,69] and approxi-mately 8 mL per year in patients with frequent exacerbations as compared to those with sporadic exacerbations [70].

What are the triggers for COPD exacerbation?

Respiratory infections are estimated to trigger approximately two-thirds of exacerbations [62]. Viral and bacterial infections cause most exacerbations. The effect of the infective triggers is to increase inflammation, cause bronchoconstriction, edema, and mucus production, with a resultant increase in dynamic hyperinflation [71]. Thus, any intervention that reduces inflammation in COPD reduces the number and severity of exacerbations, whereas bronchodilators have an impact on exacerbation by their effects on reducing dynamic hyperinflation. The triggers for the one-third of exacerbations not triggered by infection are postulated to be related to other medical conditions, including pulmonary embolism, aspiration, heart failure, and myocardial ischemia [66].

What are the pharmacologic options available for prevention of AECOPD?

In recognition of the importance of preventing COPD exacerbations, the American College of Chest Physicians and Canadian Thoracic Society [65] have published an evidence-informed clinical guideline specifically examining the prevention of AECOPD, with the goal of assisting clinicians in providing optimal management for COPD patients. The following pharmacologic agents have been recognized as being effective at reducing the frequency of acute exacerbations without any impact on the severity of COPD itself.