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Impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review

Sonnex, Kimberley; Alleemudder, Hanna; Knaggs, Roger


Hanna Alleemudder


Objectives: Inhaled corticosteroids (ICS) reduce exacerbation rates and the decline in lung function in people with chronic obstructive pulmonary disease (COPD). There is evidence that smoking causes ‘steroid resistance’ and thus reduces the effect of ICS. This systematic review aimed to investigate the effect of smoking on efficacy of ICS in COPD in terms of lung function and exacerbation rates.

Design: Systematic review

Data Sources: An electronic database search of PubMed, Ovid Medline, Ovid Embase and Cochrane Library (Jan 2000-Jan 2020).

Eligibility criteria: Fully published RCTs, in the English language, evaluating the use of ICS in COPD adults that stratified the participants by smoking status. Trials that included participants with asthma, lung cancer and pneumonia were excluded. The primary outcome measures were changes in lung function and yearly exacerbation rates.

Data extraction and synthesis: Two independent reviewers extracted data and assessed risk of bias using the Cochrane Collaboration’s tool.

Results: Eight studies were identified. Five trials (17,999 participants) recorded change in forced expiratory volume (FEV1) from baseline to up to 30 months after starting treatment. Heavier smokers (>36 pack years) using ICS had a greater decline in FEV1 that ranged from -22ml to -75ml in comparison to lighter smokers. Ex-smokers using ICS had a lesser decline in FEV1 that was +8ml to +110ml in comparison to current smokers. Three trials (21,270 participants) recorded difference in COPD exacerbation rates at 52 weeks. The rate ratios favoured more exacerbations in ICS users who were current or heavier smokers than those who were ex- or lighter smokers (0.81 to 0.99 versus 0.92 to 1.29).

Conclusions: In COPD, heavier or current smokers do not gain the same benefit from ICS use on lung function and exacerbation rates as lighter or ex-smokers do, however effects may not be clinically important.


Sonnex, K., Alleemudder, H., & Knaggs, R. (2020). Impact of smoking status on the efficacy of inhaled corticosteroids in chronic obstructive pulmonary disease: a systematic review. BMJ Open, 10(4),

Journal Article Type Article
Acceptance Date Mar 10, 2020
Online Publication Date Apr 15, 2020
Publication Date Apr 15, 2020
Deposit Date Mar 16, 2020
Publicly Available Date Apr 15, 2020
Journal BMJ Open
Electronic ISSN 2044-6055
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 10
Issue 4
Article Number e037509
Keywords General Medicine
Public URL
Publisher URL


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