Patients with asthma and Chronic Obstructive Respiratory Disease (COPD) rely on three main device classes for inhalation therapy: metered-dose inhalers (MDIs), dry powder inhalers (DPIs) and soft-mist inhalers (SMIs). The carbon footprint (CF) of these inhalers differs with MDIs having a higher impact than DPIs and SMIs due to the propellant in MDIs. However, the certified CF of specific MDI products may differ significantly. MDIs still represent an essential option for many patients. Consequently, novel approaches shall be considered to balance environmental goals with patient health and well-being while maintaining a diverse range of choices for patients and physicians.
Cytochrome c oxidases are members of the heme-copper oxidase superfamily. These enzymes have different subunits, cofactors, and primary electron acceptors, yet they all contain identical heme-copper (CuB) binuclear centers within their catalytic subunits. The uptake and delivery pathways of the CuB atom incorporated into this active site, where oxygen is reduced to water, are not well understood. Our previous work with the facultative phototrophic bacterium Rhodobacter capsulatus indicated that the copper atom needed for the CuB site of cbb3-type cytochrome c oxidase (cbb3-Cox) is imported to the cytoplasm by a major facilitator superfamily-type transporter, CcoA. In this study, a comparative genomic analysis of CcoA orthologs in alphaproteobacterial genomes showed that CcoA is widespread among organisms and frequently co-occurs with cytochrome c oxidases. To define the specificity of CcoA activity, we investigated its function in Rhodobacter sphaeroides, a close relative of R. capsulatus that contains both cbb3- and aa3-Cox. Phenotypic, genetic, and biochemical characterization of mutants lacking CcoA showed that in its absence, or even in the presence of its bypass suppressors, only the production of cbb3-Cox and not that of aa3-Cox was affected. We therefore concluded that CcoA is dedicated solely to cbb3-Cox biogenesis, establishing that distinct copper uptake systems provide the CuB atoms to the catalytic sites of these two similar cytochrome c oxidases. These findings illustrate the large variety of strategies that organisms employ to ensure homeostasis and fine control of copper trafficking and delivery to the target cuproproteins under different physiological conditions.
BackgroundInhaled therapies are key components of asthma and chronic obstructive pulmonary disease (COPD) treatments. Although the use of pressurised metered-dose inhalers (pMDIs) accounts for <0.1% of global greenhouse gas emissions, their contribution to global warming has been debated and efforts are underway to reduce the carbon footprint of pMDIs. Our aim was to establish the extent to which different scenarios led to reductions in greenhouse gas emissions associated with inhaler use, and their clinical implications.MethodsWe conducted a series of scenario analyses using asthma and COPD inhaler usage data from 2019 to model carbon dioxide equivalent (CO2e) emissions reductions over a 10-year period (2020–2030) in the UK, Italy, France, Germany and Spain: switching propellant-driven pMDIs for propellant-free dry-powder inhalers (DPIs)/soft mist inhalers (SMIs); transitioning to low global warming potential (GWP) propellant (hydrofluoroalkane (HFA)-152a) pMDIs; reducing short-acting β2-agonist (SABA) use; and inhaler recycling.ResultsTransition to low-GWP pMDIs and forced switching to DPI/SMIs (excluding SABA inhalers) would reduce annual CO2e emissions by 68%–84% and 64%–71%, respectively, but with different clinical implications. Emission reductions would be greatest (82%–89%) with transition of both maintenance and SABA inhalers to low-GWP propellant. Only minimising SABA inhaler use would reduce CO2e emissions by 17%–48%. Although significant greenhouse gas emission reductions would be achieved with high rates of end-of-life recycling (81%–87% of the inhalers), transition to a low-GWP propellant would still result in greater reductions.ConclusionsWhile the absolute contribution of pMDIs to global warming is very small, substantial reductions in the carbon footprint of pMDIs can be achieved with transition to low-GWP propellant (HFA-152a) inhalers. This approach outperforms the substitution of pMDIs with DPI/SMIs while preserving patient access and choice, which are essential for optimising treatment and outcomes. These findings require confirmation in independent studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.