In July 2021, the VHA replaced the budesonide-formoterol MDI with the propellant-free fluticasone-salmeterol DPI across its national formulary for treating asthma and chronic obstructive pulmonary disease (COPD). This research evaluated outcomes from 2,60,000 U.S. veterans before and after the switch using a self-controlled case series (SCCS) and a matched cohort study design.
The primary outcomes measured included rescue medication use (albuterol and prednisone), emergency department (ED) visits, and hospitalizations (all-cause, respiratory-related, and pneumonia-specific).
Among patients who transitioned inhalers and experienced adverse events, the SCCS found a 10% decrease in albuterol prescriptions, which indicated potentially fewer acute breathing episodes requiring rescue inhalers. However, that benefit was offset by a 2% rise in prednisone use, typically a marker of worsening respiratory symptoms.
More concerning was the 5% increase in all-cause ED visits, an 8% increase in overall hospitalizations, a 10% increase in respiratory-related hospitalizations, and a significant 24% jump in pneumonia-related hospitalizations after switching to the DPI. The matched cohort analysis, which included 2,58,557 patients, showed no meaningful difference in 6-month mortality (1.89% vs 1.90%). However, it echoed the SCCS in showing increases in health care utilization:
All-cause hospitalizations rose from 15.64% to 16.14%, respiratory-related hospitalizations increased from 2.74% to 3.15%, and pneumonia-specific admissions grew from 1.03% to 1.15%. These absolute increases may appear small, but given the large number of patients affected, the implications are significant. A total of 0.49 percentage point increase in all-cause hospitalizations translates to over 1,200 additional hospital admissions in this population.
Despite dry-powder inhalers being more environmentally sustainable, this study highlighted a trade-off between ecological benefits and patient outcomes. Overall, the findings suggest that while reducing greenhouse gas emissions is crucial, health systems must closely monitor patient outcomes and consider individual clinical needs when implementing large-scale therapeutic switches.
Reference:
Rabin, A. S., Seelye, S. M., Weinstein, J. B., Hogan, C. K., Whittington, T. N., Cano, J., Miller, S. A., Kelley, C., & Prescott, H. C. (2025). Budesonide-formoterol metered-dose inhaler vs fluticasone-salmeterol dry-powder inhaler. JAMA Internal Medicine. https://doi.org/10.1001/jamainternmed.2025.2299
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