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Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials.

Dave Singh·Italo Poggesi·Stephen Weng·David Slade·Laura Clow·Andrew Patterson·Litza McKenzie·Beth Brickhill·Christopher Roe·Emin Ibrahimov·Job van der Palen·Alison Donald·Maximilian Plank
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Abstract

BACKGROUND: To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. METHODS: Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4 h (AUC0-4h) after nebulised 99mTc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV1 (litres), 15 min post dose (95% confidence intervals [CI]: lower limit >-10%, upper limit >0%). Both studies assessed safety. RESULTS: In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC0-4h geometric mean ratio [90% CI]: 1.00 [0.99, 1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV1 at 15 min: -0.37% [HFA-152a] vs -0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [-3.61, 4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. CONCLUSION: HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.

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HumansMetered Dose InhalersMucociliary ClearanceCross-Over StudiesFemaleHydrocarbons, FluorinatedMaleBronchoconstrictionAdultFluorocarbonsAerosol PropellantsAdministration, InhalationAsthmaMiddle AgedYoung AdultChronic obstructive pulmonary diseaseEnvironmental sustainabilityHFA-152aMetered-dose inhalersMucociliary clearanceJournal ArticleRandomized Controlled TrialClinical Trial, Phase I

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Dave Singh, Italo Poggesi, Stephen Weng, David Slade, Laura Clow, Andrew Patterson, Litza McKenzie, Beth Brickhill, Christopher Roe, Emin Ibrahimov, Job van der Palen, Alison Donald, Maximilian Plank. 2026-07-21. Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials.. https://doi.org/10.1016/j.rmed.2026.109053

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Adult subjectClinical Trial, Phase I subjectCross-Over Studies subjectFemale subjectHumans subjectJournal Article subjectMale subjectMiddle Aged subjectRandomized controlled trials study

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