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BACKGROUND: The particle size of inhaled corticosteroids (ICSs) may affect airway drug deposition and effectiveness.

OBJECTIVE: To compare the effectiveness of extrafine ICSs (mass median aerodynamic diameter, <2 μm) versus fine-particle ICSs administered as ICS monotherapy or ICS-long-acting β-agonist combination therapy by conducting a meta-analysis of observational real-life asthma studies to estimate the treatment effect of extrafine ICSs.

METHODS: MEDLINE and EMBASE databases were reviewed for asthma observational comparative effectiveness studies from January 2004 to June 2016. Studies were included if they reported odds and relative risk ratios and met all inclusion criteria (Respiratory Effectiveness Group/European Academy of Allergy and Clinical Immunology quality standards, comparison of extrafine ICSs with same or different ICS molecule, ≥12-month follow-up). End-point data (asthma control, exacerbations, prescribed ICS dose) were pooled. Random-effects meta-analysis modeling was used. The study protocol is published in the PROSPERO register CRD42016039137.

RESULTS: Seven studies with 33,453 subjects aged 5 to 80 years met eligibility criteria for inclusion. Six studies used extrafine beclometasone propionate and 1 study used both extrafine beclometasone propionate and extrafine ciclesonide as comparators with fine-particle ICSs. The overall odds of achieving asthma control were significantly higher for extrafine ICSs compared with fine-particle ICSs (odds ratio, 1.34; 95% CI, 1.22-1.46). Overall exacerbation rate ratios (0.84; 95% CI, 0.73-0.97) and ICS dose (weighted mean difference, -170 μg; 95% CI, -222 to -118 μg) were significantly lower for extrafine ICSs compared with fine-particle ICSs.

CONCLUSIONS: This meta-analysis demonstrates that extrafine ICSs have significantly higher odds of achieving asthma control with lower exacerbation rates at significantly lower prescribed doses than fine-particle ICSs.

Original languageEnglish
Pages (from-to)907-915.e7
Number of pages16
JournalThe journal of allergy and clinical immunology. In practice
Issue number3
Early online date20 Sept 2017
Publication statusPublished - 30 May 2018

Bibliographical note

This systematic review and meta-analysis was jointly supported by Respiratory Effectiveness Ltd, the Observational and Pragmatic Research Institute Pte Ltd, and Chiesi Farmaceutici SpA on behalf of the Respiratory Effectiveness Group's Small Airways Working Group.


  • Journal Article
  • asthma control
  • Conventional ICS
  • Extrafine beclometasone dipropionate
  • Extrafine ciclesonide
  • Extrafine-particle ICS
  • Fine-particle ICS
  • Inhaled corticosteroids
  • Observational studies
  • Real-life


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