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

TY - JOUR

T1 - 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

AU - Heerfordt, Christian Kjer

AU - Rønn, Christian

AU - Eklöf, Josefin

AU - Sivapalan, Pradeesh

AU - Harboe, Zitta Barrella

AU - Hyldgaard, Charlotte

AU - Fløe, Andreas

AU - Mathioudakis, Alexander G

AU - Lassen, Mats Christian Højbjerg

AU - Biering-Sørensen, Tor

AU - Jensen, Jens-Ulrik Stæhr

N1 - © 2024 Heerfordt et al.

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

KW - Administration, Inhalation

KW - Adrenal Cortex Hormones/administration & dosage

KW - Aged

KW - Aged, 80 and over

KW - Cause of Death

KW - Disease Progression

KW - Female

KW - Hospitalization/statistics & numerical data

KW - Humans

KW - Lung/drug effects

KW - Male

KW - Metered Dose Inhalers

KW - Middle Aged

KW - Particle Size

KW - Pulmonary Disease, Chronic Obstructive/mortality

KW - Republic of Korea/epidemiology

KW - Risk Assessment

KW - Risk Factors

KW - Time Factors

KW - Treatment Outcome

KW - Particle size

KW - COPD exacerbations

KW - Inhaled Corticosteroids

KW - COPD

UR - http://www.scopus.com/inward/record.url?scp=85205605732&partnerID=8YFLogxK

U2 - 10.2147/COPD.S453524

DO - 10.2147/COPD.S453524

M3 - Journal article

C2 - 39364225

SN - 1178-2005

VL - 19

SP - 2169

EP - 2179

JO - International Journal of Chronic Obstructive Pulmonary Disease

JF - International Journal of Chronic Obstructive Pulmonary Disease

ER -