In a recent publication in Scientific Reports, researchers conducted a systematic review and meta-analysis to evaluate the effects of acid-suppressive drugs in adults with nonspecific chronic cough based on placebo-controlled, randomized trials and also sought to explore the impact of acid-suppressive drugs on quality of life.

The authors wrote, “The Montreal consensus recognizes chronic cough as an extra-esophageal manifestation of gastroesophageal reflux disease. Given this association, acid-suppressive medications have been proposed as a therapeutic option in managing chronic cough after excluding other potential aetiologic factors. However, clinical studies investigating this intervention have yielded inconclusive results.”

The systematic search was conducted on November 1, 2022, and researchers employed three medical databases: MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL). The meta-analysis included 11 double-blinded, placebo-controlled, randomized trials.

The researchers utilized a random-effects model for calculations in this systematic review and meta-analysis. The effect size was the standardized mean difference (SMD) with a 95% CI.

The intervention was acid-suppressive medication, regardless of dose, frequency of administration, or duration of therapy, with a placebo as the comparator. The outcomes of interest were the impact on cough severity and quality of life, which were measured by comparing changes in cough-related quality-of-life questionnaire scores.

The authors noted that based on the results of nine double-blinded, placebo-controlled RCTs, their findings demonstrate that acid-suppressive medications, namely proton pump inhibitors (PPIs), can marginally decrease the severity of cough.

The data revealed that when compared with placebo, the use of PPIs diminished the severity of cough (SMD 0.33; CI 0.05; 0.61), and there were no variances in therapeutic response in patients with a nonspecific chronic cough only, compared with those with laryngopharyngeal reflux. Additionally, prolonged treatment durations did not result in greater symptomatic improvement, with SMD following 4, 6, 8, and 12 weeks of treatment, respectively, reported as 0.33, 0.31, 0.32, and 0.34, and the pooled analysis of the improvement in quality of life with PPIs revealed an SMD of 0.39 (CI –0.51; 1.29).

The authors wrote, “Identifying subjects most likely to benefit from acid-suppressive treatment is essential. To that end, our results found that the improvement in cough scores with PPIs may be greater in subjects with chronic cough and abnormal reflux on pH monitoring.”

The authors concluded, “PPIs may marginally improve cough severity in some patients with non-specific chronic cough, which could be related to gastroesophageal reflux disease. Longer treatment durations are not associated with a more pronounced decrease in cough severity. Therefore, extending the duration of therapy is unlikely to result in marked symptomatic improvement.”

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