Chest
Volume 144, Issue 6, December 2013, Pages 1827-1838
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Original Research
Signs and Symptoms of Chest Diseases
Efficacy and Tolerability of Treatments for Chronic Cough: A Systematic Review and Meta-analysis

https://doi.org/10.1378/chest.13-0490Get rights and content

Background

Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population.

Methods

We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments.

Results

We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied.

Conclusions

Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

Section snippets

Materials and Methods

This article summarizes a comparative effectiveness review commissioned by the Agency for Healthcare Research and Quality.14 Further details of the topic refinement, literature search, methods, and conclusions can be found in the full report.

Results

Figure 1 shows the flow of literature through the search and screening process. Forty-three articles describing 49 separate studies met the inclusion criteria (Table 1).15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57 One article15 reported results for six separate studies, whereas another37 described results for two separate studies. Only three studies39, 50, 56 were

Discussion

In studies that included an active or placebo comparison, we found evidence of relative efficacy for the reduction of frequency and severity of chronic cough only for codeine and dextromethorphan. Because of the small number of head-to-head comparisons and inconsistency and imprecision of results, however, we were unable to draw conclusions about the comparative effectiveness of these two agents. Tolerability concerns were found only for opioids.

The applicability of the findings to the United

Conclusions

A wide variety of pharmaceutical agents have been used to treat the symptom of chronic cough. However, there were relatively few good-quality studies that used reliable outcome measurements over pertinent durations of follow-up. The opioid and certain nonopioid and nonanesthetic antitussives most frequently demonstrated efficacy for managing the symptom of chronic cough, but there were insufficient data to draw conclusions about their relative efficacy. Data on nonpharmacologic therapies are

Acknowledgments

Author contributions: Dr Yancy had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Yancy: contributed to the study conception and design; data acquisition, analysis, and interpretation; drafting of the submitted manuscript; critical revision of the manuscript for important intellectual content; and final approval of the version to be published.

Dr McCrory: contributed to the study conception and design;

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  • Cited by (0)

    Funding/Support: This project was funded by the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services [Contract 290-2007-10066-I]. Dr Goode is supported by the AHRQ K-12 Comparative Effectiveness Career Development Award [Grant HS19479-01].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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