Inhaled corticosteroids for bronchiectasis

Nitin Kapur; Helen L Petsky; Scott Bell; John Kolbe; Anne B Chang

doi:10.1002/14651858.CD000996.pub3

Cochrane Database of Systematic Reviews

Inhaled corticosteroids for bronchiectasis

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DOI:

https://doi.org/10.1002/14651858.CD000996.pub3 Copy DOI

Database:

Cochrane Database of Systematic Reviews

Version published:

16 May 2018see what's new

Type:

Intervention

Stage:

Review

Cochrane Editorial Group:

Cochrane Airways Group

Copyright:

Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

Nitin Kapur

Correspondence to: Department of Respiratory and Sleep Medicine, Children's Health Queensland, Lady Cilento Children's Hospital, Brisbane, Australia

[email protected]

[email protected]

School of Clinical Medicine, The University of Queensland, Brisbane, Australia
Helen L Petsky

School of Nursing and Midwifery, Griffith University and Menzies Health Institute Queensland, Griffith University, Brisbane, Australia
Scott Bell

The Prince Charles Hospital, Brisbane, Australia
John Kolbe

Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
Anne B Chang

Child Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, Australia

Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

Contributions of authors

The protocol was written by NK and AC based on previous protocols on cough in children. For the review update: NK and AC performed selection of articles from the search, data extraction, data analysis and writing of the review. HP prepared the manuscript. SB and JK reviewed the manuscript.

Sources of support

Internal sources

Royal Children's Hospital Foundation, Brisbane, Australia.

Salary support from the Foundation for the 2009 version of this review

External sources

National Health and Medical Research Council, Australia.

AC's Practitioner Fellowship and Project Grant
Asthma Australia, Australia.

HP is supported through an Early Career Fellowship

Declarations of interest

Nitin Kapur: none known.
Helen Petsky: none known.
Scott Bell: has received travel and accommodation support to attend investigator meetings (Vertex, Rempex), to participate in advisory boards and to speak at sponsored Symposia. Speakers fees and support to participate in preparation of educational materials and in advisory board have been paid to his Institution.
John Kolbe: has received funds of approximately NZ $500 from Novartis for lecture to GPs as part of an educational symposium. John also received funds to attend investigator meetings from Aradigm, GSK, Insmed, and Corus.
Anne Chang: grant provided by GSK is unrelated to this topic.

Acknowledgements

We thank Elizabeth Stovold for performing the search and Dr Chris Cates and the Cochrane Airways Group for their support.

Rebecca Normansell was the Editor for this review and commented critically on the review.

The Background and Methods sections of this review are based on a standard template used by Cochrane Airways.

This project was supported by the National Institute for Health Research (NIHR), via Cochrane Infrastructure funding to the Cochrane Airways Group. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service (NHS), or the Department of Health.

Version history

Published

Title

Stage

Authors

Version

2018 May 16

Inhaled corticosteroids for bronchiectasis

Review

Nitin Kapur, Helen L Petsky, Scott Bell, John Kolbe, Anne B Chang

https://doi.org/10.1002/14651858.CD000996.pub3

2009 Jan 21

Inhaled steroids for bronchiectasis

Review

Nitin Kapur, Scott Bell, John Kolbe, Anne B Chang

https://doi.org/10.1002/14651858.CD000996.pub2

2000 Apr 24

Inhaled steroids for bronchiectasis

Review

Felix S F Ram, Athol Wells, John Kolbe

https://doi.org/10.1002/14651858.CD000996

Differences between protocol and review

In the original protocol, we defined 'long‐term effect' as that measured at more than 12 months duration. We changed this to more than six months duration in the first review undertaken by the current group of review authors.
We included data from the Martinez‐Garcia 2006 study in the review, although the comparison between the untreated and the inhaled corticosteroids (ICS) groups were not blinded. Also, for clinical severity assessment in the Martinez‐Garcia 2006 study, we used outcome variables of sputum reduction > 50% and dyspnoea score improvement > 1 posthoc, since these were the ones available from the study.
We moved lung function to a primary outcome.
We included 'Summary of findings' tables in the review.
We added a study flow diagram.
We specified the methods in more detail following the MECIR standards.
We redrafted all sections under recommended headings.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adult; Humans;

PICOs

Population

Intervention

Comparison

Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 1 Lung function (spirometry indices).

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Analysis 1.2

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 2 Lung function (other indices).

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Analysis 1.3

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 3 Clinical severity indices.

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Analysis 1.4

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 4 Exacerbations.

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Analysis 1.5

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 5 Sputum and biomarkers characteristics.

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Analysis 1.6

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 6 Pseudomonas aeruginosa colonisation.

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Analysis 1.7

Comparison 1 Stable state bronchiectasis (6 months or less), Outcome 7 St George HRQoL (end of study minus baseline).

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Analysis 2.1

Comparison 2 Stable state (> 6 months), Outcome 1 Lung function indices.

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Analysis 2.2

Comparison 2 Stable state (> 6 months), Outcome 2 Exacerbations.

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Analysis 2.3

Comparison 2 Stable state (> 6 months), Outcome 3 Sputum and biomarker characteristics.

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Summary of findings for the main comparison. Inhaled corticosteroids compared to placebo for bronchiectasis (short‐term use of 6 months or less)

Inhaled corticosteroids compared to placebo for bronchiectasis (< 6 months)
Patient or population: people with bronchiectasis Setting: university hospital Intervention: inhaled corticosteroids Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with placebo	Risk with Inhaled corticosteroids	Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Lung function (spirometry indices) ‐ FEV₁ (in L, end study minus baseline values)	Mean change from baseline ranged from ‐0.038 to 0.805	MD 0.09 lower (0.26 lower to 0.09 higher)	‐	156 (2 studies)	⊕⊕⊝⊝ Low^1,2,3
Lung function (spirometry indices) ‐ FVC (in L, end study minus baseline values)	Mean change from baseline ranged from ‐0.062 to 0.0218	MD 0.01 higher (0.16 lower to 0.17 higher)	‐	156 (2 studies)	⊕⊕⊝⊝ Low^1,2,3
Lung function (other indices) ‐ diffusion capacity % predicted (end of study)	Mean end of study value 84.2	MD 2.70 higher (2.49 lower to 7.89 higher)	‐	57 (1 study)	⊕⊕⊝⊝ Low^1,2,3
Lung function (other indices) ‐ RV % predicted (end of study values)	Mean end of study value 106	MD 2.00 higher (9.41 lower to 13.41 higher)	‐	57 (1 study)	⊕⊕⊝⊝ Low^1,2,3
Lung function (other indices) ‐ TLC % predicted (end of study values)	Mean end of study value 86.4	MD 3.20 higher (1.99 lower to 8.39 higher)	‐	57 (1 study)	⊕⊕⊝⊝ Low^1,2,3
Average number of exacerbations per participant	Average number of exacerbations per patient ranged from 0.97 to 1.31	MD 0.17 lower (0.56 lower to 0.22 higher)	‐	127 (2 studies)	⊕⊕⊝⊝ Low^1,2,3
Pseudomonas aeruginosa (P aeruginosa) colonisation	410 per 1000	395 per 1000 (238 to 576)	OR 0.94 (0.45 to 1.96)	156 (2 studies)	⊕⊕⊝⊝ Low^1,2,3
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity; MD: mean difference; OR: odds ratio; RV: residual volume; TLC: total lung capacity
GRADE Working Group grades of evidence High‐certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate‐certainty: we are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low‐certainty: our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low‐certainty: we have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
¹The largest study was not a placebo controlled trial (Martinez‐Garcia 2006). ²Study participant numbers are small; outcome downgraded one point for imprecision. ³One study had an issue with directness (Joshi 2004), but did not contribute to this outcome.

Summary of findings for the main comparison. Inhaled corticosteroids compared to placebo for bronchiectasis (short‐term use of 6 months or less)

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Summary of findings 2. Inhaled corticosteroids compared to placebo for bronchiectasis (longer‐term use of > 6 months)

Inhaled corticosteroids compared to placebo for bronchiectasis (medium‐ to long‐term outcomes)
Patient or population: people with bronchiectasis Setting: university hospital Intervention: inhaled corticosteroids Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with placebo	Risk with Inhaled corticosteroids
Lung function indices ‐ FEV₁% predicted (end study minus baseline values)	Mean change from baseline 0	MD 0.30 higher (17.43 lower to 18.03 higher)	‐	86 (1 study)	⊕⊕⊝⊝ Low^1,2
Lung function indices ‐ FVC % predicted (end study minus baseline values)	Mean change from baseline 0.9	MD 0.90 lower (14.59 lower to 12.79 higher)	‐	86 (1 study)	⊕⊕⊝⊝ Low^1,2
Number of participants improved	628 per 1000	490 per 1000 (288 to 693)	OR 0.57 (0.24 to 1.34)	86 (1 study)	⊕⊕⊝⊝ Low^1,2
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; FEV₁: forced expiratory volume in 1 second; FVC: forced vital capacity; MD: mean difference; OR: odds ratio
GRADE Working Group grades of evidence High‐certainty: we are very confident that the true effect lies close to that of the estimate of the effect Moderate‐certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low‐certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect Very low‐certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect
¹Only a single study with small participant numbers; we downgraded outcome one point for imprecision. ²Single study with high/unclear risk of bias in several domains; we downgraded outcome one point for limitations.

Summary of findings 2. Inhaled corticosteroids compared to placebo for bronchiectasis (longer‐term use of > 6 months)

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Table 1. Summary of included studies characteristics

Study ID	Intervention	Control	Duration of intervention
Elborn 1992	Beclomethasone dipropionate 750 µg twice daily by MDI	Placebo	6 weeks
Hernando 2012	Budesonide 400 µg twice daily	Placebo	6 months
Joshi 2004	Beclomethasone 800 µg per day over 2 doses	Placebo	4 weeks
Martinez‐Garcia 2006	Fluticasone 500 µg twice daily by MDI or 250 µg fluticasone twice daily	No treatment	6 months
Tsang 1998	Fluticasone 500 µg twice daily by accuhaler	Placebo	4 weeks
Tsang 2004	Fluticasone 500 µg twice daily by accuhaler	Placebo	52 weeks
Tsang 2005	Fluticasone 500 µg twice daily by accuhaler	Placebo	52 weeks
MDI: metered dose inhaler

Table 1. Summary of included studies characteristics

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Comparison 1. Stable state bronchiectasis (6 months or less)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Lung function (spirometry indices) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 FEV1 (in L, end study minus baseline values)	2	156	Mean Difference (IV, Fixed, 95% CI)	‐0.09 [‐0.26, 0.09]
1.2 FVC (in L, end study minus baseline values)	2	156	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.16, 0.17]
2 Lung function (other indices) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 Diffusion capacity % predicted (end of study)	1	57	Mean Difference (IV, Fixed, 95% CI)	2.70 [‐2.49, 7.89]
2.2 RV % predicted (end of study values)	1	57	Mean Difference (IV, Fixed, 95% CI)	2.0 [‐9.41, 13.41]
2.3 TLC % predicted (end of study values)	1	57	Mean Difference (IV, Fixed, 95% CI)	3.20 [‐1.99, 8.39]
3 Clinical severity indices Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 Number of participants with regular wheeze (combined)	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Number of participants without sputum reduction of > 50% (combined)	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Number of participants with no improvement in dyspnoea score > 1 (min important difference) (1000F)	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.4 Number of participants with no clinically significant improvement in HRQoL	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Exacerbations Show forest plot	2	127	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐0.56, 0.22]

4.1 Average number of exacerbations per participant	2	127	Mean Difference (IV, Fixed, 95% CI)	‐0.17 [‐0.56, 0.22]
5 Sputum and biomarkers characteristics Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 Sputum volume or weight (per day)	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
6 Pseudomonas aeruginosa colonisation Show forest plot	2	156	Odds Ratio (M‐H, Fixed, 95% CI)	0.94 [0.45, 1.96]

7 St George HRQoL (end of study minus baseline) Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

7.1 Total score	2	127	Mean Difference (IV, Fixed, 95% CI)	‐3.54 [‐8.00, 0.92]
7.2 Symptom score	2	127	Mean Difference (IV, Fixed, 95% CI)	‐4.75 [‐10.42, 0.92]
7.3 Activity score	2	127	Mean Difference (IV, Fixed, 95% CI)	‐6.21 [‐12.40, ‐0.01]
7.4 Impact score	1	70	Mean Difference (IV, Fixed, 95% CI)	‐3.63 [‐9.35, 2.09]

Comparison 1. Stable state bronchiectasis (6 months or less)

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Comparison 2. Stable state (> 6 months)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Lung function indices Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 FEV1% predicted (end study minus baseline values)	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 FVC % predicted (end study minus baseline values)	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 Exacerbations Show forest plot	1		Odds Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Number of participants improved	1		Odds Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Sputum and biomarker characteristics Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Sputum purulence score	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 2. Stable state (> 6 months)

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Inhaled corticosteroids for bronchiectasis

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