Case-Based Review

Management of Stable Chronic Obstructive Pulmonary Disease

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

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Macrolides

Continuous prophylactic use of antibiotics in older studies had no effect on the frequency of AECOPD [82,83]. But it is known that macrolide antibiotics have several antimicrobial, anti-inflammatory and immunomodulating effects and have been used for many years in the management of other chronic airway disease, including diffuse pan-bronchiolitis and cystic fibrosis [65]. One recent study showed that the use of once-daily, generic azithromycin 5 days/week appeared to have an impact on AECOPD incidence [84]. In this study, AECOPD was reduced from 1.83 to 1.48 per patient-year (RR, 0.83; 95% CI, 0.72–0.95: P = 0.01). Azithromycin also prevented severe AECOPD. Greater benefit was obtained with milder forms of the disease and in the elderly. Azithromycin did not appear to provide any benefit in those who continued to smoke (hazard ratio, 0.99) [85]. Other studies have shown that azithromycin was associated with an increased incidence of bacterial resistance and impaired hearing [86]. Overall data from the available clinical trials are robust and demonstrate that regular macrolide therapy definitely reduces the risk of AECOPD. But due to potential side effects macrolide therapy is an option rather than a strong recommendation [65]. The prescribing clinician also needs to consider the potential of prolongation of the QT interval [84].

Immunostimulants

Immunostimulants have also been reported to reduce frequency of AECOPD [87,88]. Bacterial lysates, reconstituted mixtures of bacterial antigens present in the lower airways of COPD patients, act as immuno-stimulants through the induction of cellular maturation, stimulating lymphocyte chemotaxis, and increasing opsonization when administered to individuals with COPD [66]. Studies have demonstrated a reduction in the severe complications of exacerbations and hospital admissions in COPD patients with OM-85, a detoxified oral immunoactive bacterial extract [87,88]. However, most of these trials were conducted prior to the routine use of long-acting bronchodilators and ICS in COPD. A recent study by Braido et al evaluated the efficacy of ismigen, a bacterial lysate, in reducing AECOPD [89] and found no difference in the exacerbation rate between ismigen and placebo or the time to first exacerbation. Additional studies are needed to examine the long-term effects of this therapy in patients receiving currently recommended COPD maintenance therapy [66].

β Blockers

Observational studies of beta-blocker use in preventing AECOPD have yielded encouraging results, with one study showing a reduction in AECOPD risk (incidence risk ratio, 0.73; CI 0.60–0.90) in patients receiving beta blockers versus those not on beta blockers [90]. Based on these findings, a clinical trial investigating the impact of metoprolol on risk of AECOPD is ongoing [91].

Proton Pump Inhibitors

Gastroesophageal reflux disease is an independent risk factor for exacerbations [92]. Two small, single-center studies [93,94] have shown that use of lansoprazole decreases the risk and frequency of AECOPD. However, data from the Predicting Outcome using Systemic Markers in Severe Exacerbations of COPD (PROMISE-COPD) study [66], which was a multicenter prospective observational study, suggested that patients with stable COPD receiving a proton pump inhibitor were at high risk of frequent and severe exacerbations [95]. Thus, at this stage, their definitive role needs to be defined, possibly with a randomized, placebo-controlled study.