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Claims study suggests dry powder and soft mist COPD inhalers cut exacerbations versus MDIs, offering greener care without added safety risks.
Dry powder and soft mist inhalers in the long-acting muscarinic antagonist–long-acting β-agonist (LAMA–LABA) class were associated with modestly lower exacerbation risk in people with chronic obstructive pulmonary disease (COPD) compared with a metered-dose inhaler (MDI) in a large US claims-based study published in JAMA Internal Medicine.¹
“The inhalers we studied are the first line treatment for many patients with COPD, so it’s reassuring to see evidence that lower-emission inhalers may also be associated with slightly better clinical outcomes,” William Feldman, a pulmonologist and health services researcher at UCLA Health and the study’s senior author, wrote.2 “These findings highlight the opportunity to reduce healthcare-related emissions while potentially improving patient care.”
COPD affects more than 16 million US adults and remains a leading cause of hospitalization and death.3 Prevention of moderate and severe exacerbations is central to management, and dual bronchodilator therapy with LAMA–LABA combinations is recommended for many symptomatic patients.4 MDIs commonly use hydrofluoroalkane propellants, which have high global warming potential, whereas dry powder inhalers (DPIs) and soft mist inhalers (SMIs) do not require propellants and have substantially lower associated emissions.1 The new study’s findings add comparative effectiveness data to ongoing discussions about inhaler selection in COPD, including consideration of environmental impact.
Feldman and colleagues conducted a retrospective, matched cohort study using commercial and Medicare Advantage claims from 2016 through 2025, including adults aged 40 years or older initiating a LAMA–LABA inhaler.¹ Three pairwise matched cohorts were constructed:
The primary outcome was time to first moderate or severe COPD exacerbation. Safety outcomes included first major adverse cardiovascular event, urinary tract infection, and pneumonia hospitalization.
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
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
Results:
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.
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