Immunostimulants versus placebo for preventing exacerbations in adults with chronic bronchitis or chronic obstructive pulmonary disease

Abstract

BACKGROUND: Individuals with chronic obstructive pulmonary disease (COPD) or chronic bronchitis may experience recurrent exacerbations, which negatively impact prognosis and quality of life, and can impose a significant socioeconomic burden on the individual and wider society. Immunostimulants are a broad category of therapies that may theoretically enhance non-specific immunity against several respiratory insults, thereby reducing exacerbation risk and severity. However, evidence to date for their use in this population is limited. OBJECTIVES: To determine the efficacy of immunostimulants in preventing respiratory exacerbations in adults with chronic obstructive pulmonary disease, chronic bronchitis, or both. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest literature search was conducted on 25 January 2022. SELECTION CRITERIA: We included parallel randomised controlled trials (RCTs) that compared immunostimulant therapy, administered by any method and with the intention of preventing (rather than treating) exacerbations, with placebo for a minimum treatment duration of one month in adults with chronic bronchitis or COPD, or both. We excluded participants with other respiratory conditions. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were number of participants with no exacerbations during the study period and all-cause mortality, secondary outcomes were respiratory-related mortality, quality of life, number of participants requiring antibiotics, exacerbation duration, respiratory-related hospitalisation duration and adverse events/side effects. We used GRADE to assess certainty of evidence for each outcome. MAIN RESULTS: = 83%). Results from an effect direction plot and binomial probability test for exacerbation duration indicated that a significant proportion of studies (94% (95% CI 73% to 99%); P = 0.0002) favoured intervention, possibly indicating that immunostimulants are efficacious in reducing the mean exacerbation duration compared to placebo. However, the degree of uncertainty associated with this estimate remained high due to data quality and heterogeneity. Three studies reported mean duration of respiratory-related hospitalisation, two of which demonstrated a direction of effect that favoured immunostimulant over placebo. AUTHORS' CONCLUSIONS: In participants with chronic bronchitis or COPD, we are moderately confident that treatment with immunostimulants is associated with a small reduction in the likelihood of having an exacerbation and a moderate reduction in the requirement for antibiotics. Low numbers of events limit interpretation of the effect of immunostimulants on all-cause and respiratory-related mortality. We are uncertain whether immunostimulants improve quality of life, and whether they are associated with a reduction in exacerbation and respiratory-related hospitalisation durations, although immunostimulants were generally associated with a positive effect direction in the studies that examined these outcomes. Immunostimulants appear to be safe and well-tolerated, and are not associated with an increased risk of adverse events.

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