Inhaled Corticosteroids and Placebo Treatment Effects in Adult Patients With Cough: A Systematic Review and Meta-analysis

Abstract

Purpose: Inhaled corticosteroids (ICSs) are often considered an empirical therapy in the management of patients with cough. However, ICS responsiveness is difficult to interpret in daily clinical practice, as the improvements may include placebo effects or self-remission. We aimed to evaluate ICS and placebo treatment effects in adult patients with cough.

Methods: Electronic databases were searched for studies published until June 2018, without language restriction. Randomized controlled trials reporting the effects of ICSs compared with placebo in adult patients with cough were included. Random effects meta-analyses were conducted to estimate the treatment effects. Therapeutic gain was calculated by subtracting the percentage change from baseline in the cough score in the ICS treatment group from that in the placebo treatment group.

Results: A total of 9 studies were identified and 8 studies measuring cough severity outcomes were included for meta-analyses. Therapeutic gain from ICSs ranged from -5.0% to +94.6% across the studies included; however, it did not exceed +22%, except for an outlier reporting very high therapeutic gains (+45.6% to +94.6%, depending on outcomes). Overall ICS treatment effects in cough severity outcomes were small-to-moderate (standardized mean difference [SMD], -0.38; 95% confidence interval [CI], -0.54, -0.23), which were comparable between subacute and chronic coughs. However, pooled placebo treatment effects were very large in subacute cough (SMD, -2.58; 95% CI, -3.03, -2.1), and modest but significant in chronic cough (SMD, -0.46; 95% CI, -0.72, -0.21).

Conclusions: Overall therapeutic gain from ICSs is small-to-moderate. However, placebo treatment effects of ICS are large in subacute cough, and modest but still significant in chronic cough. These findings indicate the need for careful interpretation of ICS responsiveness in the management of cough patients in the clinic, and also for rigorous patient selection to identify ICS-responders.

Keywords: Cough; meta-analysis; placebo effect; steroids.

Fig. 1. Flow chart of the study selection.

Fig. 2. Scatter plot of ICS and placebo treatment effects (relative change from baseline) in cough severity outcomes at final endpoints. Red solid line indicates linear prediction. Blue shadow represents a 95% confidence interval of the prediction.

ICS, inhaled corticosteroids.

Fig. 3. Forest plot of ICS treatment effects stratified by cough duration (subacute vs. chronic cough). Green squares indicate effect size and weight of each study for standard mean differences. Black diamonds represent the pooled effect size and 95% CI.

SD, standard deviation; CI, confidence interval; ICS, inhaled corticosteroids.

Fig. 4. Forest plot of placebo treatment effects stratified by cough duration (subacute cough vs. chronic cough). Red squares indicate effect size and weight of each study for standard mean differences. Black diamonds represent the pooled effect size and 95% CIs.

SE, standard error; CI, confidence interval.