Efficacy and tolerability of treatments for chronic cough: a systematic review and meta-analysis.
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 &lt; .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.
Department of Medicine, Duke University School of Medicine, Durham, NC; Center for Health Services Research in Primary Care, Veterans Affairs Medical Center, Durham, NC. Electronic address: yancy006@mc.duke.edu.
William S
WS
Yancy
Department of Medicine, Duke University School of Medicine, Durham, NC; Center for Health Services Research in Primary Care, Veterans Affairs Medical Center, Durham, NC; Duke Evidence-based Practice Center, Duke Clinical Research Institute, Durham, NC.
Douglas C
DC
McCrory
Doctor of Physical Therapy Division, Duke University School of Medicine, Durham, NC; Duke Evidence-based Practice Center, Duke Clinical Research Institute, Durham, NC.
Remy R
RR
Coeytaux
Department of Community and Family Medicine, Duke University School of Medicine, Durham, NC.
Kristine M
KM
Schmit
Department of Pediatrics, Duke University School of Medicine, Durham, NC.
Alex R
AR
Kemper
Doctor of Physical Therapy Division, Duke University School of Medicine, Durham, NC.
Adam
A
Goode
Department of Biostatistics & Bioinformatics, Duke University School of Medicine, Durham, NC.
Victor
V
Hasselblad
Duke Evidence-based Practice Center, Duke Clinical Research Institute, Durham, NC.
Brooke L
BL
Heidenfelder
Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Evidence-based Practice Center, Duke Clinical Research Institute, Durham, NC.
Gillian D
GD
Sanders
D000996:Antitussive Agents / Q000009:adverse effects* / Q000145:classification / Q000627:therapeutic use*; D002908:Chronic Disease; D003371:Cough / Q000188:drug therapy*; D006801:Humans; D017063:Outcome Assessment, Health Care; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000996:Antitussive Agents