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Meta-Analysis
. 2013 Mar 28;2013(3):CD009305.
doi: 10.1002/14651858.CD009305.pub2.

Inhaled corticosteroids for subacute and chronic cough in adults

Kate J Johnstone  1 , Anne B Chang, Kwun M Fong, Rayleen V Bowman, Ian A Yang
Affiliations
Meta-Analysis

Inhaled corticosteroids for subacute and chronic cough in adults

Kate J Johnstone et al. Cochrane Database Syst Rev. .

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 methods: 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 All published and unpublished randomised comparisons of ICS versus placebo in adults with subacute or chronic cough were included.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 predominantly chronic cough with 'cough-variant asthma' identified a significant treatment effect and contributed to 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).

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.

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Conflict of interest statement

KJ, AC and RB declare no conflicts of interest.

Professor Fong declares that he has received travel and accommodation sponsorship several times to speak at or participate in educational meetings, which have been organised by an independent organising committee and sponsored by industry. Professor Fong is involved with the Lung Cancer Consultative Group of the Australian Lung Foundation (not‐for‐profit, public benevolent institution) and attends professional scientific meetings including those organised by the Thoracic Society of Australia and New Zealand, where some unrestricted sponsorship is usually provided by industry.

Dr Yang declares that he has received travel and accommodation sponsorship several times to speak at or participate in educational meetings, which have been organised by an independent organising committee and sponsored by industry. Dr Yang is involved with the National COPD Executive of the Australian Lung Foundation (not‐for‐profit, public benevolent institution) and attends professional scientific meetings including those organised by the Thoracic Society of Australia and New Zealand, where some unrestricted sponsorship is usually provided by industry.

Figures

1
1
Study flow diagram showing study selection process.
2
2
Summary of included studies. Abbreviations BHR = bronchial hyper‐responsiveness cells = sputum total and/or differential cell counts dose = budesonide equivalent daily dose DPI = dry powder inhaler ECP = eosinophilic cationic protein FEF25‐75% = forced expiratory flow 25%‐75% FEV1 = forced expiratory volume in 1 second FVC = forced vital capacity gases = exhaled gases (CO, NO) meds = additional medication use MDI = metered dose inhaler night = nocturnal awakenings other = other sputum biomarkers (MPO, PGE2, LTB4, Cys‐LT, IL‐8, TNF‐alpha, fibrinogen, albumin, substance P) PEF = peak expiratory flow URTI = upper respiratory tract infection
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 ICS versus Placebo, outcome: 1.4 Mean change in cough score.
5
5
Forest plot of comparison: 1 ICS versus Placebo, outcome: 1.31 Proportion with adverse effects.
1.1
1.1. Analysis
Comparison 1 ICS versus Placebo, Outcome 1 Proportion of participants with clinical cure or significant improvement (> 70% reduction in cough severity measure) at follow up (clinical success).
1.2
1.2. Analysis
Comparison 1 ICS versus Placebo, Outcome 2 Proportion of participants with clinical cure or > 50% reduction in cough severity measure at follow up.
1.3
1.3. Analysis
Comparison 1 ICS versus Placebo, Outcome 3 Proportion of participants with clinical cure at follow up.
1.4
1.4. Analysis
Comparison 1 ICS versus Placebo, Outcome 4 Mean change in cough score.
1.5
1.5. Analysis
Comparison 1 ICS versus Placebo, Outcome 5 Mean change in cough measures on VAS.
1.6
1.6. Analysis
Comparison 1 ICS versus Placebo, Outcome 6 Mean change in VAS after 2 weeks by final diagnosis [cm].
1.7
1.7. Analysis
Comparison 1 ICS versus Placebo, Outcome 7 Mean change in morning and evening cough score.
1.8
1.8. Analysis
Comparison 1 ICS versus Placebo, Outcome 8 Mean change in morning and evening total symptom score.
1.9
1.9. Analysis
Comparison 1 ICS versus Placebo, Outcome 9 Mean change in cough frequency.
1.10
1.10. Analysis
Comparison 1 ICS versus Placebo, Outcome 10 Mean change in cough severity.
1.11
1.11. Analysis
Comparison 1 ICS versus Placebo, Outcome 11 Mean change in cough time of day.
1.12
1.12. Analysis
Comparison 1 ICS versus Placebo, Outcome 12 Proportion without BHR after treatment.
1.13
1.13. Analysis
Comparison 1 ICS versus Placebo, Outcome 13 Mean change in BHR.
1.14
1.14. Analysis
Comparison 1 ICS versus Placebo, Outcome 14 Change in FEV1.
1.15
1.15. Analysis
Comparison 1 ICS versus Placebo, Outcome 15 Proportion requiring additional medication.
1.16
1.16. Analysis
Comparison 1 ICS versus Placebo, Outcome 16 Mean change in sleep interruption.
1.17
1.17. Analysis
Comparison 1 ICS versus Placebo, Outcome 17 Mean change in sputum ECP [ng/mL].
1.18
1.18. Analysis
Comparison 1 ICS versus Placebo, Outcome 18 Mean change in sputum ECP by final diagnosis [ng/mL].
1.19
1.19. Analysis
Comparison 1 ICS versus Placebo, Outcome 19 Change in sputum total cells [×106].
1.20
1.20. Analysis
Comparison 1 ICS versus Placebo, Outcome 20 Change in sputum neutrophils [%].
1.21
1.21. Analysis
Comparison 1 ICS versus Placebo, Outcome 21 Change in sputum eosinophils [%].
1.22
1.22. Analysis
Comparison 1 ICS versus Placebo, Outcome 22 Change in sputum lymphocytes [%].
1.23
1.23. Analysis
Comparison 1 ICS versus Placebo, Outcome 23 Change in sputum MPO [µg/mL].
1.24
1.24. Analysis
Comparison 1 ICS versus Placebo, Outcome 24 Change in sputum PGE2 [ng/mL].
1.25
1.25. Analysis
Comparison 1 ICS versus Placebo, Outcome 25 Change in sputum LTB4 [ng/mL].
1.26
1.26. Analysis
Comparison 1 ICS versus Placebo, Outcome 26 Change in sputum Cys‐LT [ng/mL].
1.27
1.27. Analysis
Comparison 1 ICS versus Placebo, Outcome 27 Change in sputum IL‐8 [ng/mL].
1.28
1.28. Analysis
Comparison 1 ICS versus Placebo, Outcome 28 Change in sputum TNF‐α [ng/mL].
1.29
1.29. Analysis
Comparison 1 ICS versus Placebo, Outcome 29 Change in eNO [ppb].
1.30
1.30. Analysis
Comparison 1 ICS versus Placebo, Outcome 30 Change in exhaled CO [ppm].
1.31
1.31. Analysis
Comparison 1 ICS versus Placebo, Outcome 31 Proportion with adverse effects.
1.32
1.32. Analysis
Comparison 1 ICS versus Placebo, Outcome 32 Proportion with specific adverse effects.
1.33
1.33. Analysis
Comparison 1 ICS versus Placebo, Outcome 33 Proportion with severe adverse effects.
See this image and copyright information in PMC

Update of

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