Portela and colleagues found that compared with MDI, DPI was associated with a 14% lower hazard of a first moderate or severe exacerbation (hazard ratio [HR], 0.86; 95% CI, 0.81-0.91), corresponding to a number needed to treat (NNT) of 17.¹ SMI was associated with a 6% lower hazard compared with the MDI (HR, 0.94; 95% CI, 0.89-1.00).¹
In a direct comparison between the 2 lower-emission devices, DPI was associated with a 3% lower hazard than tiotropium–olodaterol (HR, 0.97; 95% CI, 0.94-0.99), with an NNT of 100.¹ Absolute differences were modest across comparisons.1
Key Facts
Study Design: Retrospective matched cohort analysis (2016–2025 claims data)
Population: Adults ≥40 years initiating LAMA–LABA therapy
Primary outcome: First moderate or severe COPD exacerbation
DPI vs MDI: HR 0.86 (95% CI, 0.81-0.91); NNT 17
SMI vs MDI: HR 0.94 (95% CI, 0.89-1.00)
DPI vs SMI: HR 0.97 (95% CI, 0.94-0.99); NNT 100
Safety: Similar risks of MACE, UTI, pneumonia hospitalization
Environmental impact: DPIs and SMIs avoid high–global warming potential propellants
Safety outcomes were similar across all 3 cohorts, with no meaningful differences in risks of major adverse cardiovascular events, urinary tract infections, or pneumonia hospitalization.¹
Although randomized trials have established the efficacy of dual bronchodilators, head-to-head comparisons across inhaler platforms are limited.⁵ The present study suggests that, in routine practice, certain lower-emission inhalers may be associated with slightly fewer exacerbations without added safety risk.
However, as an observational analysis, the findings are subject to residual confounding. Claims data lack spirometry, symptom burden, and inhaler technique measures, and adherence patterns may differ by device. The modest hazard differences—particularly the 3% relative reduction between DPI and SMI—should be interpreted cautiously.
“This combination makes a strong case for using DPIs when possible,” Feldman said.2 “Although some patients may require MDIs, DPIs and SMIs are a safe and effective option for most patients with COPD.”
From an environmental standpoint, inhaler propellants contribute to healthcare-associated greenhouse gas emissions. When clinical outcomes are comparable, device selection may reasonably incorporate environmental considerations alongside patient ability, inspiratory flow capacity, and cost.
Altogether, the study supports consideration of DPIs or SMIs when appropriate from a clinical and patient-centered standpoint. While the magnitude of benefit was small, the absence of increased safety risk and the lower carbon footprint of these devices may inform shared decision-making in COPD management.
References
Feldman WB, et al. Comparative effectiveness and environmental impact of LAMA–LABA inhalers in chronic obstructive pulmonary disease. JAMA Intern Med. Published online 2026. doi:10.1001/jamainternmed.2025.8087. https://doi.org/10.1001/jamainternmed.2025.8087
Centers for Disease Control and Prevention. Chronic obstructive pulmonary disease (COPD). Updated 2024. https://www.cdc.gov/copd
Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for Prevention, Diagnosis and Management of COPD, 2024 Report. https://goldcopd.org/2024-gold-report