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.

Impact of Chronic Cough on Health-Related Quality of Life in the Korean Adult General Population: The Korean National Health and Nutrition Examination Survey 2010–2016

“…They were selected on the basis of the literature about their impact on QoL or frequent overlaps with chronic cough. 27 28 31 32 The presence of each of these chronic conditions was defined using the combination of physician diagnostic history and current disease status ( i.e., “Have you ever been diagnosed with [a specific disease] by a physician?”, followed by “Do you still have [that specific disease]?”). Because allergic rhinitis was assessed only in the KNHANES 2013–2015, it was included only in a sensitivity analysis.…”

The Powerful Placebo Effect in Cough: Relevance to Treatment and Clinical Trials

“…It is also a problem to researchers as with such a large placebo effect it is difficult to demonstrate that any new cough medicine is superior to placebo treatment in cough clinical trials. The magnitude of the placebo effect in the treatment of cough with inhaled steroids has recently been highlighted and the authors conclude that clinicians should be cautious about attributing the response of patients on inhaled steroids to anything more than a placebo effect [6]. This review will discuss the significance of the placebo effect in the development of new cough treatments and its importance in cough clinical trials.…”

Recent progress in the management of chronic cough

“…35, No. 4, July 2020 servational studies [71,72]. Cough is frequently self-limiting and prone to placebo effects [73], which may underlie the large discrepancy between placebo-controlled and uncontrolled (observational) studies.…”

“…To date, the key focus in controlling cough has centered on treating conditions such as asthma, rhinitis, or gastroesophageal reflux disease (GERD). However, placebo-controlled studies indicate that true therapeutic benefits gained from treating these conditions may be much less than the findings suggested from observational studies [ 71 , 72 ]. Cough is frequently self-limiting and prone to placebo effects [ 73 ], which may underlie the large discrepancy between placebo-controlled and uncontrolled (observational) studies.…”