Inhaled corticosteroids for adults with cough lasting over three weeks

Background
There is often no obvious cause for coughs that last more than three weeks. Lack of a clear cause makes the cough difficult to treat. Current guidelines recommend that in many cases people with cough lasting longer than three weeks be given inhaled corticosteroids (ICS), which are commonly used to treat asthma and other diseases involving airway inflammation.

Review question
We wanted to find out if taking inhaled steroids in adults with cough lasting three weeks or longer were beneficial.

We looked at evidence from clinical trials. We analysed the effects of ICS compared with placebo on cough severity, lung function, complications of cough and airway inflammation, as well as the safety of this treatment.

Study characteristics
We found eight studies on 570 people with cough lasting over three weeks. Studies included different types of participants in terms of age, duration of coughing and risk factors for cough. Studies also varied in types of ICS, doses, treatment lengths and types of inhaler used. Cough severity was measured using different scales.

Key results
We looked at the proportion of people who were clinically cured or showed a significant improvement in cough severity as our primary outcome, but the data were too mixed to be able draw any conclusions. These differences between studies also prevented meaningful pooling of study results for proportion of people showing improvement in cough and average improvement in one specific type of cough scale. There was low quality evidence that ICS reduced cough severity score. There was not enough data about changes in pulmonary function, complications of cough and markers of inflammation to allow pooling of results.There was evidence of moderate quality that ICS treatment did not increase the risk of adverse events.

Conclusion and future work
This review has shown that the effects of ICS for subacute and chronic cough are inconsistent. Further studies with more consistent patient populations, interventions, outcome measures and reporting are needed to determine whether ICS help subacute and chronic cough in adults.

This Cochrane plain language summary was written in December 2012.

Authors' conclusions: 

The studies were highly heterogeneous and results were inconsistent. Heterogeneity in study design needs to be addressed in future research in order to test the efficacy of this intervention. International cough guidelines recommend that a trial of ICS should only be considered in patients after thorough evaluation including chest X-ray and consideration of spirometry and other appropriate investigations.

Read the full abstract...
Background: 

Persistent cough is a common clinical problem. Despite thorough investigation and empirical management, a considerable proportion of those people with subacute and chronic cough have unexplained cough, for which treatment options are limited. While current guidelines recommend inhaled corticosteroids (ICS), the research evidence for this intervention is conflicting.

Objectives: 

To assess the effects of ICS for subacute and chronic cough in adults.

Search strategy: 

We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and ClinicalTrials.gov in December 2012 and conducted handsearches.

Selection criteria: 

Two authors independently assessed all potentially relevant trials. All published and unpublished randomised comparisons of ICS versus placebo in adults with subacute or chronic cough were included. Participants with known chronic respiratory disease and asthma were excluded. Studies of cough-variant asthma and eosinophilic bronchitis were eligible.

Data collection and analysis: 

Two authors independently extracted data pertaining to pre-defined outcomes. The primary outcome was the proportion of participants with clinical cure or significant improvement (over 70% reduction in cough severity measure) at follow up (clinical success). The secondary outcomes included proportion of participants with clinical cure or over 50% reduction in cough severity measure at follow up, mean change in cough severity measures, complications of cough, biomarkers of inflammation and adverse effects. We requested additional data from study authors.

Main results: 

Eight primary studies, including 570 participants, were included. The overall methodological quality of studies was good. Significant clinical heterogeneity resulting from differences in participants and interventions, as well as variation in outcome measures, limited the validity of comparisons between studies for most outcomes. Data for the primary outcome of clinical cure or significant (> 70%) improvement were available for only three studies, which were too heterogeneous to pool. Similarly, heterogeneity in study characteristics limited the validity of meta-analysis for the secondary outcomes of proportion of participants with clinical cure or over 50% reduction in cough severity measure and clinical cure. One parallel group trial of chronic cough which identified a significant treatment effect contributed the majority of statistical heterogeneity for these outcomes. While ICS treatment resulted in a mean decrease in cough score of 0.34 standard deviations (SMD -0.34; 95% CI -0.56 to -0.13; 346 participants), the quality of evidence was low. Heterogeneity also prevented meta-analysis for the outcome of mean change in visual analogue scale score. Meta-analysis was not possible for the outcomes of pulmonary function, complications of cough or biomarkers of inflammation due to insufficient data. There was moderate quality evidence that treatment with ICS did not significantly increase the odds of experiencing an adverse event (OR 1.67; 95% CI 0.92 to 3.04).