The delivery of therapeutic vapors and aerosols through inhalation has been used for thousands of years in various cultures. The inhalation of Datura stramonium, a leafy flowering plant (Hyoscyamus niger), whose therapeutic properties are attributed to tropane alkaloids, including atropine, for treatment of asthma, comes from circa 2000 BC with early traditional Ayurvedic medicine.(1) The most prominent ancient form of respiratory drug delivery was the smoking of opium for recreational and therapeutic purposes including analgesia, and treatment of diarrhea and of severe cough, with one of the earliest known references dating back to 1100 BC in China.(2) It is clearly recognized that, in comparison with oral or parenteral formulations, the inhaled route allows the therapeutic drug to be directly delivered topically to the airways leading to quicker local efficacy within the lungs, using lower therapeutic doses, and minimizing their systemic effects.(3)
 
In many respects, the introduction of the pressurized metered dose inhaler (pMDI) in 1956 marked the beginning of the modern pharmaceutical aerosol industry, when Riker Laboratories Inc. (becoming 3M Drug Delivery Systems) introduced the pMDI. The pMDI was the first truly portable and convenient inhaler that delivered drugs to the lungs effectively, and quickly gained widespread acceptance.(4) When originally developed, pMDIs utilized chlorofluorocarbon (CFC) propellants, but they have an effect on depleting the stratospheric ozone layer. So, in the 1990s, the Montreal Protocol led to the phasing out of ozone-damaging CFCs in inhalers. The replacement propellants were hydrofluorocarbons (HFCs). Unlike CFCs, HFCs are not ozone-depleting substances, but they are recognized as greenhouse gases that have a high global warming potential (GWP). The current HFCs in pMDIs are hydrofluoroalkane (HFA)-134a and HFA-227ea, which are 1,000-3,000 times more potent than carbon dioxide and can persist in the atmosphere for 14 years, contributing to worsening climate change. The carbon footprint from 1 pMDI (200 doses) is estimated to be equivalent to a 290-km automobile ride. Figure 1 shows the carbon footprint of different medications and inhaler devices.(5)

 
According to the IQVIA database (Durham, NC, USA), in the preceding 12 months until June of 2019, there were over 480 million pMDI packs prescribed, equating to 2,400 doses taken every second across the world.(6) In Brazil, the number of pMDI short-acting β2 agonist (SABA) units sold has been increasing, from 24,849,295 units in 2019 to 31,156,295 units in 2023; a growth of 25.4%.(7) With regard to the existing propellants, there is now development for transitioning to newer propellants, such as HFA-152a that has a lower GWP, and pharmaceutical companies have committed to launch newer pMDIs with this propellant by 2025-6.
 
Dry powder inhaler (DPI) devices do not contain greenhouse gas propellants and have a lower GWP when compared with pMDIs (Figure 1). However, DPIs are dependent on the inspiratory effort of the patient to effectively activate the dry powder to be inhaled into the lungs, and it has been shown that many patients with asthma and COPD have suboptimal inspiratory effort. Indeed, poor inspiratory effort is recognized in the young, in the elderly, and in patients with an acute exacerbation of asthma or COPD, when DPIs may not be effective. Globally, DPIs represent only 3% of the doses of SABAs, which are the mainstay of reliever medication.(6) Of critical importance, DPIs are not free from having an impact on planetary health due to their plastic content. Indeed, in the whole lifecycle assessment of pMDIs and DPIs, DPIs have a greater adverse effect on marine ecology through their plastic content. Since there is a global policy to curtail the effect of plastics on the environment, we must be careful in our choice of inhalers. The costs of DPIs are greater than those of pMDIs in Brazil. Soft mist inhalers are small portable devices, which are an additional class of inhalers that produce aerosols of breathable diameter from aqueous formulations. They are more environmentally friendly (Figure 1), but are currently more expensive than pMDIs and DPIs.(8)
 
Another important consideration is the recycling of inhalers. Of the estimated 35 million inhalers prescribed in the UK every year, only about 0.5% is recycled appropriately. Thus, millions of inhalers end up in landfills every year, where DPIs do not only significantly contribute to plastic waste, but also pMDIs release residual HFCs into the atmosphere over time.(9)
 
In clinical practice, the choice of drug and its dosage, treatment strategy, and inhalation device are crucial to control and prevent asthma and COPD exacerbations. Healthcare professionals, patient organizations, and the pharmaceutical industry should take the lead in health policies to provide environmentally healthier alternatives. Indeed, the greenest inhaler is the one that the patient can use (inhaler technique), will use (inhaler adherence), and has been taught how to use it properly (inhaler mastery) in order to mitigate these planet-warming greenhouse gas emissions. Ideally, prescribing physicians should educate their patients to discard used inhalation devices at pharmacies. If disposed of in regular waste, they can contaminate soil, water, and the atmosphere. However, effective recycling requires investment and policies at the governmental level to support pharmacies with appropriate equipment and clear pathways of disassembling the various parts of inhalers and their safe disposal at factories. Decree No. 10,388,(10) published by the President of the Republic of Brazil on June 5th, 2020, regulated the reverse logistics system for expired or unused household medications for human use, both industrially manufactured and compounded, as well as their packaging. These should be disposed of at pharmacies, where they will later be collected and sent for environmentally safe disposal. In this regard, the Brazilian Thoracic Society is conducting a campaign with the aim of educating doctors, other healthcare professionals, and patients about the importance of correct inhalation treatment for prevalent diseases such as asthma and COPD, as well as proper disposal of inhalation devices at pharmacies.
 
It is time to put the brakes on greenhouse gas emissions and global warming. Choose the better inhaler device for each patient and teach them about the correct disposal. Let’s do it now!
 
AUTHOR CONTRIBUTIONS
 
Both authors equally contributed to this work.
 
CONFLICTS OF INTEREST
 
None declared.
 
REFERENCES
 
1.            Gandevia B. Historical review of the use of parasympatholytic agents in the treatment of respiratory disorders. Postgrad Med J. 1975;51(7 SUPPL):13-20.
2.            Kritikos PG, Papadaki SP: The early history of the poppy and opium. Bull Narcotics. 1967;19(3):17-38.
3.            Lavorini F, Fontana GA, Usmani OS. New inhaler devices - the good, the bad and the ugly. Respiration. 2014;88(1):3-15. https://doi.org/10.1159/000363390
4.            Stein SW, Thiel CG. The History of Therapeutic Aerosols: A Chronological Review. J Aerosol Med Pulm Drug Deliv. 2017;30(1):20-41. https://doi.org/10.1089/jamp.2016.1297
5.            National Institute for Health and Care Excellence (NICE) [homepage on the Internet]. London:. NICE; c2019 [updated 2021 Mar 22; cited 2024 Feb 1]..  Patient decision aid on asthma inhalers and climate change. [Adobe Acrobat document, 8p.]. Available from: https://www.nice.org.uk/guidance/ng80/resources/patient-decision-aid-on-asthma-inhalers-and-climate-change-pdf-6727144573
6.            Pritchard JN. The Climate is Changing for Metered-Dose Inhalers and Action is Needed. Drug Des Devel Ther. 2020;14:3043-3055. https://doi.org/10.2147/DDDT.S262141
7.            Scabello RT, Cançado JED, Fonseca JDAV, Bergamini FB, Zung S. Análise da tendência de comercialização dos broncodilatadores de curta duração (SABA) no Brasil. J Bras Pneumol. 2023;49(Suppl.1R):R27.
8.            Urrutia-Pereira M, Chong-Neto HJ, Winders TA, Solé D. Environmental impact of inhaler devices on respiratory care: a narrative review. J Bras Pneumol. 2023;48(6):e20220270. https://doi.org/10.36416/1806-3756/e20220270
9.            www.parliament.uk [homepage on the Internet]. London: the Parliament; c2024 [updated 2018 Apr 25; cited 2024 Feb 18]. UK progress on reducing F-gas emissions Contents [about 3 screens]. Available from: https://publications.parliament.uk/pa/cm201719/cmselect/cmenvaud/469/46902.htm
10.          Brasil. Presidência da República. Secretaria-Geral. Subchefia para Assuntos Jurídicos [homepage on the Internet]. Brasília: a Presidência; c2020 [cited 2024 Feb 18]. Decre-to no. 10.388 de 5 de junho de 2020. Regulamenta o § 1º do caput do art. 33 da Lei nº 12.305, de 2 de agosto de 2010, e institui o sistema de logística reversa de medica-mentos domiciliares vencidos ou em desuso, de uso humano, industrializados e ma-nipulados, e de suas embalagens após o descarte pelos consumidores [about 11 screens]. Available from: https://www.planalto.gov.br/ccivil_03/_ato2019-2022/2020/decreto/d10388.htm