Inhaled Corticosteroids Particle Size and Risk of Hospitalization Due to Exacerbations and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Nationwide Cohort Study

Int J Chron Obstruct Pulmon Dis. 2024 Sep 29:19:2169-2179. doi: 10.2147/COPD.S453524. eCollection 2024.

Abstract

Background: Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear.

Methods: This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis.

Results: Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82-1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85-1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63-0.82, p<0.001) and all-cause mortality (HR 0.72, 95% CI 0.61-0.86, p<0.001).

Conclusion: The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.

Keywords: COPD; COPD exacerbations; Inhaled Corticosteroids; Particle size.

Publication types

  • Observational Study
  • Comparative Study

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones* / administration & dosage
  • Adrenal Cortex Hormones* / adverse effects
  • Aged
  • Aged, 80 and over
  • Cause of Death
  • Disease Progression*
  • Female
  • Hospitalization* / statistics & numerical data
  • Humans
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Metered Dose Inhalers
  • Middle Aged
  • Particle Size*
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / mortality
  • Republic of Korea / epidemiology
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones

Grants and funding

Grants from Novo Nordisk Fonden (NO. NNF20OC0060657) were used to fund the study. The study’s design, data collection, analysis, and reporting of results were unaffected by the funding source.