McCrory, D. C., Coeytaux, R. R., Yancy, W. S., Schmit, K. M., Kemper, A. R., Goode, A., Hasselblad, V., Heidenfelder, B. L., Irvine, R. J., Musty, M. D., Gray, R., and Sanders, G. D.
Abstract:
Cough is the most common complaint for patients seeking medical attention in the United States. Although the most common cause of cough is acute self-limited viral infections, chronic cough (cough that lasts more than 4 weeks in children <14 years of age or more than 8 weeks in adolescents and adults) has a significant impact on quality of life and is responsible for up to 38 percent of pulmonary outpatient visits. Furthermore, a treatable cause is absent in up to 46 percent of patients with chronic cough despite a thorough diagnostic investigation. The comparative value of tools for assessing cough and the comparative effectiveness of treatments for unexplained or refractory cough are uncertain. We searched PubMed(R), Embase(R), and the Cochrane Database of Systematic Reviews (June 4, 2012) for relevant English-language comparative studies. Two investigators screened each abstract and full-text article for inclusion, abstracted data, rated quality and applicability, and graded evidence. Random-effects models were used to compute summary estimates of effects. We supplemented the meta-analysis of direct comparisons with a mixed treatment meta-analysis that incorporated data from placebo comparisons and head-to-head comparisons. To evaluate instruments for assessing cough, we considered the dimensions of cough frequency, cough severity, and cough-specific quality of life (QOL). We sought to measure the validity, reliability, and responsiveness of various instruments used to assess each of these dimensions. Seventy-eight studies (5,927 subjects) evaluated instruments for assessing cough. The Leicester Cough Questionnaire (LCQ) and Cough-specific Quality of Life Questionnaire (CQLQ) were the most widely studied instruments in adults; there is moderate strength of evidence (SOE) to support both the LCQ's and the CQLQ's validity in assessing severity/QOL of cough. For pediatric populations, there is moderate SOE to support the Parent Cough-specific Quality of Life questionnaire's (PC-QOL) validity in assessing severity/QOL of cough. Electronic recording devices are accurate for assessing cough frequency, but show variable correlation with other tools. Although visual analog scales (VAS) are easy to administer and have face validity, we did not identify any studies to formally validate their accuracy in assessing cough. We identified no studies exploring the impact of cough assessment instruments on therapeutic efficacy or patient outcome efficacy. Forty-eight studies (2,923 patients) evaluated 67 therapeutic comparisons for patients with chronic cough. Classes of drugs evaluated included opioid, anesthetic, and nonopioid/nonanesthetic antitussives; expectorant and mucolytic protussives; antihistamines; antibiotics; inhaled corticosteroids; and inhaled anticholinergics. The opioid and certain nonopioid/nonanesthetic antitussives most frequently demonstrated efficacy for managing chronic cough in adults. In particular, codeine and dextromethorphan reduced cough severity and frequency. Relative to placebo, the effect of dextromethorphan on cough severity was 0.54 (95% confidence interval [CI], 0.27 to 0.80; p=0.0008), and the effect of opiates was 0.63 (95% CI, 0.40 to 0.86; p<0.0001). Relative to placebo, the effect of dextromethorphan on cough frequency was 0.40 (95% CI, 0.18 to 0.85; p=0.0248), and the effect of codeine was 0.57 (95% CI, 0.36 to 0.91; p=0.0260). However, due to inconsistency and imprecision of results, and small numbers of direct comparisons, the overall SOE is insufficient to draw firm conclusions about the comparative effectiveness of these agents. Very few studies evaluated nonpharmacological therapies (two studies) or the management of cough in children (three studies). Several instruments for assessing cough severity, frequency, and impact on cough-specific quality of life show good internal consistency but variable correlation with other cough measurement tools, meaning that a number of instruments are precise but their accuracy is less clear. Although the evidence is sparse, the opioid and certain nonopioid/nonanesthetic antitussives most frequently demonstrated efficacy for managing the symptom of chronic cough in adults. Our review highlights the need for further studies in patient populations with unexplained or refractory chronic cough as determined by current diagnostic and empiric treatment recommendations. Further, it shows the need for more systematic design and reporting of these studies and assessment of their patient-centered outcomes. This is in contrast to the more extensive literature on the management of acute cough
