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Carbon footprint of inhalers in Brazil and Porto Alegre: impacts and alternatives.

ABSTRACT
Objective: To calculate the carbon footprint of metered-dose inhalers used for asthma and chronic obstructive pulmonary disease management, distributed by the Brazilian National Health Service in Brazil and in the city of Porto Alegre, Brazil, in the year 2019. Method: Data regarding the dispensation of salbutamol and beclomethasone were obtained upon request from the Ministry of Health. The dispensations were multiplied by the proportional carbon footprint of each device. Results: The prescription of the metered-dose inhalers resulted in between 24,889,141 and 60,878,728 tons of CO2-eq released into the atmosphere in Brazil (equivalent to traveling 23 to 57 million times the north-to-south distance of Brazil in a standard gasoline car); and between 459,830 and 1,151,008 tons of CO2-eq in the city of Porto Alegre. The study demonstrated the substantial amount of GreenHouse Gas emissions associated with these devices in Brazil. The substitution with dry powder inhalers or Soft mist inhalers in appropriate situations would prevent significant environmental harm, while also providing clinical benefits to patients, as they are currently the first-line choice recommended by clinical guidelines for the treatment of respiratory diseases, promoting both public health and planetary health.
KEY WORDS: Asthma; Beclomethasone; Albuterol; Carbon Footprint; Climate Change

INTRODUCTION
Climate change (CC) is considered the greatest threat and, consequently, the greatest opportunity for public health in the 21st century1,2 . It stems from the increasing anthropogenic emission of greenhouse gases (GHG) into the atmosphere3, 4, 5, 6. This effect has impacted humanity in various ways, including the rise of extreme events such as heatwaves, droughts, wildfires, floods, and cyclones, which intensify socio-environmental inequalities and health inequities5.
Each year, The Lancet Countdown publishes data from 44 indicators on the impacts of CC on health, based on studies by more than 120 scientists world6. Among the diseases related to CC are the rise of waterborne, vector-borne, and other zoonotic diseases (such as dengue and malaria), cardiorespiratory conditions, heat stress, malnutrition, obesity, non-communicable chronic diseases, and various mental health disorders5, 6, 7. These and other data demonstrate the delayed and inconsistent response from countries, providing "a clear imperative for accelerated action that places the health of people and the planet above other agendas." 6
Although healthcare services attend to populations affected by CC impacts, paradoxically, they also contribute to worsening this scenario through the environmental impact and significant carbon footprint (CF) they generate. If all health systems in the world were united as a single country, they would rank fifth globally in GHG emissions, as they are responsible for 4.4% of total global emissions, equivalent to 514 coal-fired power plants9. Moreover, the healthcare system plays an essential role in setting an example for society8.
The medicines are part of the CF of healthcare services, with the largest component of the CF for primary healthcare (PHC) professionals being their prescriptions. The most significant contribution comes from bronchodilators and inhaled corticosteroids (ICS) in the form of pressurized metered-dose inhalers (pMDI), used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). These are widely available in the Brazilian Unified Health System (SUS), both in the Popular Pharmacies and in the pharmacies from Primary care /Family Health Strategy 10, 11, 12. In England, for instance, pMDI inhalers are responsible for 3% of the total carbon footprint of the healthcare system12,13. They have an extremely high global warming potential (GWP) and are used at a rate that could be optimized, making them a critical point of concern14.
The pMDIs contain a propellant gas with a GWP approximately 1,300 times greater than the more widely known greenhouse gas, carbon dioxide (CO2). This greenhouse gas is called norflurane (HFA-134a), which belongs to the hydrofluoroalkanes (HFA) family, a subtype of fluorinated gases (F-gases). To illustrate, 100 puffs of a Salbutamol pMDI are equivalent to driving a car for approximately 290 km in terms of GHG emissions15.
The F-gases were introduced into inhaler devices (ID) to replace chlorofluorocarbon (CFC) gases, which deplete the ozone layer. The Montreal Protocol in 1986 banned CFC gases. However, in 2016, an amendment was added to the protocol: the “Kigali Amendment,” which encourages nations to reduce F-gas emissions by 85% between 2019 and 2036 for developed countries and by 80% between 2024 and 2045 for developing countries. Globally, if all countries met the F-gas reduction targets, this would reduce the global temperature rise by 0.5°C during this century, substantially decreasing the impacts of CC16. There are alternatives to pMDIs: dry powder inhalers (DPIs) and soft mist inhalers (SMIs). Both do not contain a propellant gas and are therefore more sustainable; however, they are less frequently prescribed.
Although the perspective holds that it is impossible to think about human health without considering the health of the planet on which humans depend3, it would be problematic for healthcare professionals to opt for prescribing a more sustainable medication if it did not offer the greatest clinical benefit. However, the latest update from the main guideline for asthma treatment, GINA (Global Initiative for Asthma) 17, highlights as first-line treatment medications available in DPIs, such as Formoterol + Budesonide (step 1 in asthma), which reduce hospitalizations and severe disease exacerbations, benefiting both patients and the planet18. Additionally, the most recommended treatments for COPD, such as long-acting beta-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs), are also available in DPI forms19.
To build a more sustainable and healthier healthcare system, the first step is to identify where the GHG emissions are coming from and quantify them20. However, in Brazil, data in the literature quantifying this environmental impact related to healthcare is scarce. This study offers an unprecedented contribution to understanding the carbon footprint of pMDI inhalers dispensed by the SUS in Brazil as a whole and specifically in Porto Alegre (RS). To date, no studies have investigated this data on such a scale.
When the environmental, health, and economic costs related to medications are not well known and quantified, it can be difficult for public policy decisions to determine which medications offer the best cost-benefit for the population and are best suited for inclusion in the basket of medicines provided by the SUS. Furthermore, it is essential nowadays for institutions to incorporate ESG (Environmental, Social, and Governance) practices to promote health21.
The United Nations (UN) is concerned about the climate crisis and calls for the rapid transformation of societies22. At the same time, more than two-thirds of the global health workforce—45 million doctors and healthcare professionals worldwide—signed an open letter, urging national and international leaders at the Conference of the Parties (COP) to intensify climate action plans. Healthcare professionals stated that they are already dealing with the health damages caused by CC in their care for the population and, therefore, advocate for climate action22, 23.
This research aims to estimate the carbon footprint of inhalers for asthma and COPD, specifically pressurized metered-dose inhalers (pMDIs), dispensed by the Popular Pharmacy Program and the SUS as a whole (excluding the Popular Pharmacy) in Brazil and, specifically, in Porto Alegre (POA - RS), in the year 2019.

METHODS
Study design
This is an ecological study. The primary study location, Brazil, was chosen to represent the entire country. The secondary study location, the city of Porto Alegre, was selected for convenience. The year 2019 was chosen as it is the year immediately preceding the COVID-19 pandemic, during which the prescription of medications for asthma and COPD occurred under normal circumstances.
The sample consisted of the total amount of salbutamol sulfate and beclometasone dipropionate pMDIs with recorded dispensation in the SUS network as a whole and the Popular Pharmacy Program, in both Brazil and Porto Alegre, in the year 2019.
This study was approved by the Ethics Committee of the Nossa Senhora da Conceição Hospital - Conceição Hospital Group under the number 70361623.5.0000.5530.

Estimated Carbon Footprint Calculation
The carbon footprint (CF) of inhaler devices (IDs) was calculated by multiplying the mass of the greenhouse gas (GHG) by its global warming potential (GWP)—a measure of the heating capacity of a gas relative to carbon dioxide (CO2). The result was expressed in CO2 equivalent (CO2-eq), a term used to estimate the amount of CO2 mass that would be needed to cause the same level of warming over a given period as the GHG in question. CO2-equivalent emissions provide a common scale for comparing different GHG emissions, though it does not imply an equivalence in the corresponding climate change impact, since the gases have different atmospheric lifetimes (CO2 and HFA remain for different lengths of time, but both for a few centuries) 16, 24. For example, the GWP of HFA-134a is 1,300, meaning that 1 ton of HFA-134a warms the atmosphere 1,300 times more than 1 ton of CO2. The lifetime of this gas in the atmosphere is approximately 14 years, meaning that the heat would remain trapped in the atmosphere for 14 years25.
For a more comprehensive analysis of the CF of a product, beyond assessing the quantity of GHGs present and their respective GWP, all emissions from the product\'s production chain (such as the CO2 emitted by the industry during manufacturing and transportation to end consumers) could be evaluated. However, a life-cycle analysis is complex and beyond the scope of this study. Therefore, this research focused solely on the CF related to the GHG present in pMDI-type IDs, calculating the CO2-eq.
The mass of the HFA-134a gas in inhaler devices (IDs) can vary depending on the manufacturer and the presence or absence of alcohol in their composition, but this information is not publicly available from the various laboratories supplying the SUS. Therefore, it was necessary to explore the literature to determine the average quantity (mass) of HFA-134a gas in each ID, and thus estimate its carbon footprint (CF). Based on studies that analyzed IDs in vitro, comparing their full and empty states to estimate the amount (mass) of HFA-134a gas, it is known that devices containing alcohol require less HFA-134a propellant gas (categorized as small-volume devices—6.68–8.5g), whereas devices without alcohol contain more HFA-134a (categorized as large-volume devices—17.32–19.8g), and the latter have a higher CF18.
The CF estimate for both large-volume (without alcohol) and small-volume (with alcohol) devices was calculated by multiplying the mass of the HFA-134a gas by its GWP, as published in the Fifth Assessment Report of the IPCC.

Data Acquisition for Medication Dispensation

Data on the quantity of Salbutamol Sulfate and Beclometasone Dipropionate devices dispensed within the SUS network (including the Popular Pharmacy Program and the SUS as a whole) in Brazil and Porto Alegre in 2019 were requested through the integrated platform for citizen services and access to information of the federal government (Fala.BR portal) 27, in accordance with the Data Transparency Law. Information regarding dispensations from the Popular Pharmacy Program was made available on May 23, 2022, by the Coordination of the Popular Pharmacy Program of the Department of Pharmaceutical Assistance and Strategic Inputs and the General Coordination of Basic Pharmaceutical Assistance (CGAFB/DAF/SCTIE/MS), both linked to the Ministry of Health (MS)/Department of Pharmaceutical Assistance and Strategic Inputs/Secretariat of Science, Technology, Innovation, and Strategic Health Inputs.
On August 12, 2022, data regarding dispensations from the “SUS as a whole” network in Brazil and Porto Alegre for the year 2019 were made available. This data was extracted by these agencies from the National Database of Pharmaceutical Assistance Actions and Services (BNAFAR) and provided to the researchers, presented in the Supplementary Materials (Appendices A and B). Dispensation data categorized as “SUS as a whole” refers to the records of dispensations that predominantly occur within SUS pharmacies that assist primary healthcare, excluding medications from the Popular Pharmacy Program, and there may be an underestimation of records from some municipalities.

Data Analysis

The data provided by the Ministry of Health (MS) referred to the total dispensations of inhaler devices (IDs) for each medication (Salbutamol 100 mcg; Beclometasone 250 mcg; Beclometasone 200 mcg; and Beclometasone 50 mcg), not specifying which laboratory or whether they are large or small volume.
The total amount of Salbutamol and Beclomethasone dispensed by SUS and Farmácia Popular in Brazil and in POA (RS) was added up separately. To estimate the carbon footprint (CF) of Salbutamol pMDIs in Brazil and Porto Alegre, the CF of each large-volume Salbutamol device was first multiplied by the total dispensations of Salbutamol across the SUS and the Popular Pharmacy in Brazil and separately in Porto Alegre. Secondly, the CF of each small-volume Salbutamol device was multiplied by the same total dispensations, considering, alternatively to the previous hypothesis, that all Salbutamol dispensations were of small-volume subtype. The same process was repeated for Beclometasone. The various formulations of Beclometasone (50 mcg, 200 mcg, and 250 mcg) refer to different amounts of medication in the device, not to the quantity of HFA-134a; thus, for the CF calculation, they can be summed as equivalent. After this, the CF of the Salbutamol and Beclometasone devices was summed, hypothetically considering them all to be large-volume, resulting in the CF of dispensations of pMDIs if all were large-volume. Sequentially, the CF of Salbutamol and Beclometasone devices was summed again, considering all to be small-volume. Within the interval between these values lies the data sought in this study: the CF of pMDI-type IDs provided by the SUS and the Popular Pharmacy Program in Brazil and Porto Alegre in 2019.

Calculation of Carbon Footprint Equivalences

To calculate the carbon footprint equivalences of the inhaler devices (IDs) used for the treatment of asthma and COPD, specifically pMDIs (Salbutamol and Beclometasone) in Brazil, for both small and large volumes, the following factors were analyzed: (a) greenhouse gas emissions, (b) CO2 emissions, (c) avoidance of greenhouse gas emissions, and (d) carbon sequestration.
An online calculator from the United States was utilized for this purpose. The measures from the calculator were adapted to equivalents used in Brazil (e.g., converting miles to kilometers). To calculate the distance between the most extreme points in Brazil, from North (Cabraí) to South (Chuí), a straight-line distance of 4,378.41 km was considered.

Cost Analysis

To estimate the financial cost of replacing pMDIs with DPIs, Salbutamol and Beclometasone were chosen as pMDIs, while Formoterol + Budesonide was selected as the DPI, focusing on asthma treatment. The prices that the SUS can pay generally, considering the lowest and highest possible prices per dose, are as follows:
• Beclometasone 250 mcg: R$ 0.16 - 0.22 per dose (puff) (with higher or lower prices for doses of Beclometasone 50 mcg or 200 mcg).
• Salbutamol 100 mcg: R$ 0.083 - 0.11 per dose (puff).
• Formoterol + Budesonide: R$ 1.05 - 1.83 per dose (capsule) (averaging the lowest and highest prices based on doses of 6 mcg + 200 mcg or 12 mcg + 400 mcg).
The absolute values per bottle were extracted from the maximum selling price table to the government (PMVG) provided by the National Health Surveillance Agency (ANVISA) 29 and divided by the number of doses in each bottle.
The number of doses used for asthma treatment varies greatly based on age, disease stage, and level of control. Therefore, it was decided to consider that, on average, an individual uses 181 doses (puffs) of Salbutamol and 60 doses (puffs) of Beclometasone per month, which could be substituted with 60 doses (capsules) of Formoterol + Budesonide. These monthly doses were estimated because Formoterol + Budesonide is commonly used at a dose of 1 capsule twice daily (totaling 60 doses/month). Beclometasone is usually used at a dose of 1 puff twice daily (it can be used from 0 to 4 doses per application twice a day), while Salbutamol is used on a non-fixed basis (typically 4 puffs per application as needed, up to every 4 hours). The additional amount of Salbutamol prescribed compared to Beclometasone follows the dispensing ratio of these medications by the SUS overall for the year found in this research: 3.02 times more Salbutamol is dispensed than Beclometasone.
To estimate the reduction in hospitalization costs due to asthma resulting from the switch to DPIs, a 37% reduction rate (the rate of reduced hospitalizations associated with the substitution of Salbutamol and Beclometasone with Formoterol + Budesonide) 17 was applied to the total cost of asthma hospitalizations in 2013, which is the most recent data in the literature from a study analyzing the DATASUS database30.


RESULTS
The calculations of the quantities of units and their corresponding carbon footprints were performed according to the medication (Salbutamol or Beclometasone), geographic location, dispensing pharmacy, and considering them as all being high/large or low/small volume HFA-134a. It is observed that the highest dispensing occurs at the Farmácia Popular, and Salbutamol consequently has the highest carbon footprint compared to Beclometasone, both in Brazil and in Porto Alegre (POA), proportionally.
Table 1

The prescription of pMDI inhalers within the SUS in 2019 resulted in CO2-eq emissions ranging from 24,889,141 to 60,878,728 tons across the entire Brazilian territory (Table 2; values considering whether all devices were of low/small or high/large-volume), which is equivalent to traveling between 23 to 57 million times the distance from the northernmost to the southernmost point of Brazil in a conventional gasoline vehicle, among other comparisons with emission or carbon sink measures (Figure 1 - Supplementary Table Annex C).
Table 2
Figure 1

Additionally, in Porto Alegre, the prescription of these devices resulted in emissions between 459,830 and 1,151,008 tons (Table 2), corresponding to traveling the distance between the north and south of Brazil between 433 thousand and 1 million times in a conventional gasoline vehicle (Figure 2 - Supplementary Table Annex C).
Figure 2

Regarding the estimated cost of replacing all the pMDIs dispensed annually by the SUS considering all of Brazil (R$ 45,225,797,274.60 to R$ 60,813,582,654.00) with DPIs (Formoterol + Budesonide), this would increase by 155.86% to 231.62%, totaling R$ 115,642,641,030.00 to R$ 201,671,137,886.11, always considering the lowest and highest values for each medication.
On the other hand, the total cost of the 129,728 hospitalizations for asthma across all age groups, excluding indirect costs (loss of productivity due to absences from work and school and premature mortality), in the year 2013, was R$ 69,566,007.37 (an average of R$ 519.57 per hospitalization) 30. Conversely, considering the hospitalization reduction rate associated with the daily use of Beclometasone combined with rescue Salbutamol replaced by the use of Formoterol + Budesonide available in DPI, which is 37%17, 31, it can be estimated that it would reduce R$ 25,739,422.00 in hospitalization costs for the health system annually.

DISCUSSION
It is estimated that the prescription of pMDIs for the treatment of respiratory conditions such as asthma and COPD in the SUS in 2019 resulted in approximately 24,889 - 60,878 kilotonnes (kt) of CO2 equivalent released into the atmosphere across Brazil and 459 - 1,151 kt CO2eq specifically in Porto Alegre. This value reflects a prescribing pattern related to the use of Salbutamol (available in the SUS in the form of pMDI) as a first-choice treatment for rapid symptom relief/rescue, and Beclometasone as the first option for maintenance treatment (also more available in the SUS in the form of pMDI).
In comparison, domestic emissions in 2019 were: 1,300 kt CO2eq in the United Kingdom, 520 kt CO2eq in France, and 450 kt CO2eq in Germany32. In Europe, the proportion of pMDIs among inhalers is approximately 40%-50%, about 70% in the United Kingdom, 22.6% in Japan, and 13% in Sweden, with the latter being examples of countries that already have a predominance of other, more sustainable types of inhalers32. The proportion of pMDIs in Brazil\'s SUS is likely much higher than in these countries, and the number of medications dispensed is proportionally higher due to Brazil\'s larger population, which would justify the country\'s pMDI inhalers having a significantly higher carbon footprint compared to other countries.
In regard to the experience of other countries on the subject, it is observed that emissions are often avoidable by switching to less polluting devices. Comparing the proportion of pMDI prescriptions in England (70%) to Sweden (13%), it is estimated that if England adopted the Swedish prescription standard (favoring DPIs whenever appropriate for the patient), it would avoid the emission of 422 kg CO2 equivalent per patient per year33. Comparatively, the individual action of switching a pMDI for a DPI could prevent 150 to 400 kg CO2 equivalent from being released into the atmosphere annually, which is environmentally equivalent to that individual adopting a recycling habit, implementing selective waste collection, or cutting down on red meat consumption during the treatment period34. Furthermore, the English healthcare system (NHS) set a goal that by 2022, at least 50% of prescribed inhalers would be of low global warming potential16, with the aim of achieving zero emissions by 204535. A coalition of health institutions has followed their commitment to the goal of “zero emissions” in Brazil through the Healthy Hospitals Project and the Global Health Without Harm Network. Seven health institutions have joined the challenge, aiming to reduce greenhouse gas emissions by 50% by 2030 and achieve zero emissions by 205036.
Beyond the carbon footprint, cost is a concern in this regard, as DPIs are more expensive compared to pMDIs. Regarding the increased cost for transitioning from pMDIs to DPIs, it should be considered that Formoterol + Budesonide, available in DPIs, reduce hospital admission rates by 37% compared to the daily use of Beclometasone combined with rescue Salbutamol17,31, which would generate a savings of R$ 25,739,422.00 for the healthcare system in one year. Additional savings should also be considered from indirect costs associated with reduced hospitalizations, such as decreased productivity due to absenteeism from work and school, and premature mortality. It should also be noted that there will likely be a reduction in outpatient consultations and the use of oral corticosteroids since patients achieve better disease control with the use of Formoterol + Budesonide, which is the first choice in asthma treatment and reduces the risk of severe exacerbations19.
Other countries have made this cost estimation for the replacement of pMDIs to DPIs by switching exactly the same medication from its pMDI format to DPI; however, this is not the reality of the medications available in the Brazilian SUS. Thus, the United Kingdom, which has a 70% prescription rate for pMDIs37, found that switching 10% of its pMDI medications to DPIs could result in either a reduction (£8.2 million per year) or an increase (£12.7 million per year) in costs, depending on the brand of the medication used, with some options being cheaper than others on the market18. In Japan, it is estimated that a 10% reduction in pMDI prescriptions among the population aged 14 to 74, which is already low (22.6%), would prevent the emission of 12.4 kt CO2 equivalent and would result in a 1.4% increase in costs due to the substitution of pMDIs for DPIs32.
Furthermore, for an adequate cost-effectiveness analysis, other aspects must also be considered, such as the utilization/waste of medication related to inhalation technique and the impacts of chronic diseases on long-term economics, making it important to have a broader perspective within public health18. Studies show that 65% to 72% of patients make errors when using inhalers, and in 30% to 32% of cases, these errors are significant enough to impair treatment effectiveness38. Comparing the error rates in inhalation technique among different devices, 96% of patients can perform the steps correctly when using DPIs compared to only 24% in the pMDI group39.
Some issues are identified regarding the use of pMDIs: the inhalation technique requires coordination between the activation of the medication release and simultaneous slow and prolonged inhalation, and some patients do not inhale long enough after activating the device, leading to oropharyngeal deposition of the drug and resulting in inefficient administration of the medication. Furthermore, those containing inhaled corticosteroids (ICS) can lead to the proliferation of fungi and oral candidiasis. It is estimated that, in most patients, only about 10% of the dose reaches the lungs, while 80% remains in the oropharynx, although this varies depending on the preparation and application device40.
Additionally, in the most common pMDIs dispensed by the SUS, it is not possible to visualize how many doses remain in the device, which can cause some patients to continue using the device despite the absence of medication, or to discard the inhaler with unused remaining doses, resulting in waste41,42. One study found an alarming statistic revealing that 40% of patients believe they are using their asthma medication when they are actually activating an empty pMDI canister, which is very relevant to health43. Regarding DPIs, it is important to note that adequate lung capacity is needed to generate sufficient inspiratory flow, which can be challenging for small children, many elderly individuals, or patients with strength disorders, limiting their use in these groups44,45. However, the issue present in pMDIs regarding the need to coordinate inspiration with the manual activation of the device in a synchronized manner is excluded since inhalation itself is the activation mechanism46.
Considering the pillars of ESG (Environmental, Social, and Governance), in relation to the social aspect associated with financial implications, there is the "social cost of carbon" (SCC), measured in dollars per ton of carbon, which is an estimate of the monetary damages associated with increased carbon emissions in a year. An analysis by the American agency responsible for this issue estimated an average of approximately $25.80 per ton of carbon for the year 201947. According to a UN report, every dollar invested in restoration creates up to $30 in economic benefits48. Thus, it is likely that reducing greenhouse gas emissions from inhaled medications will result in significant economic benefits, avoiding costs related to the preservation or recovery of the health of the planet and people due to climate change.
For comparison purposes, the most recent climate disaster in Brazil, the floods in Rio Grande do Sul, cost the government R$ 12.8 billion, according to data from the National Confederation of Municipalities49. Therefore, if we consider the costs of the negative externalities of pMDIs on the planet and, consequently, on people\'s health, the cost of pMDIs could exceed the cost of DPIs. In other words, the social cost of carbon (SCC) should also be taken into account in the cost analysis when choosing medications dispensed by the SUS.
In addition to cost, there is another pillar of ESG: corporate governance, in which institutions must adopt a sustainable approach in their management, considering the environmental and social impacts of their operations, as well as ensuring transparency and accountability in corporate management21.
Regarding asthma, the therapeutic option of Salbutamol and/or Beclometasone (pMDI) has not been the first choice of treatment since 2020, when GINA50 pointed out, based on scientific findings with an adequate level of evidence, an advancement in treatment toward better outcomes in asthma health indicators. Among the first-step options for asthma, the use of Formoterol + Budesonide (available in the form of DPI) is the most recommended and preferred option by the current guideline, instead of relying solely on medications in pMDI form. This recommendation arose from the observed clinical benefit of its use: a 37% reduction in hospitalizations and severe asthma exacerbations requiring oral corticosteroid use51. Regarding COPD, the treatment for both maintenance and prevention as well as for quick relief is based on long-acting beta-agonists and antimuscarinics (LABAs and LAMAs, respectively), which are widely available in DPI form and some in SMI19.
The DPI Formoterol + Budesonide and Umeclidinium + Vilanterol, as well as the SMI Olodaterol + Tiotropium, are available through the SUS in Special Medication Pharmacies in some states of Brazil, such as Rio Grande do Sul, for the ICDs of asthma (only Formoterol + Budesonide) and COPD (all the aforementioned medications), upon presentation of reports and tests. This process requires greater bureaucratic work from the prescriber and delays the release of medication for the patient. In a context like that of Primary Health Care (APS) within the SUS, where professionals need to manage consultation times, this process may bias the prescriber\'s preferred choice, which is a practically vital perspective.
This study has some limitations. Firstly, the amount of HFA-134a present in the inhalers is not publicly available in the drug package inserts, and there is a risk that it varies by manufacturer. For its estimation, data from English literature were used26,52,53,54,55. Therefore, it is important to reiterate that the result will be an estimate, as the SUS dispenses medications from different laboratories and, consequently, there may be slight differences in their formulas and the amount of gas in the final product.
Additionally, the dispensing data obtained for “the SUS as a whole" from BNAFAR, which excludes dispensations from the Popular Pharmacy, are primarily related to dispensations in Primary Care. However, depending on local organization and management, it cannot be excluded that some locations count the data dispensed in Urgent Care Centers or Hospitals. It is worth noting that during severe acute exacerbations of asthma and COPD in emergency settings, the use of short-acting bronchodilators as rescue (available as Salbutamol pMDI) is the most studied and is appropriate. Furthermore, not all municipalities transmit their data to BNAFAR, leading to an underestimation of the number of dispensations. It is known that dispensations related to the Popular Pharmacy correspond to prescriptions at the outpatient level.
Secondly, for the calculation of the carbon footprint (CF), the amount of propellant gas was multiplied by its Global Warming Potential (GWP). The total CF of the medications, which accounts for the energy consumed in their manufacture and transportation, was not calculated. Thus, the data presented here can be considered significantly underestimated, although if there were a switch to DPI or SMI, the CF of their manufacture and transportation would likely be comparable. We hope that by identifying the gap in the absence of these data in the Brazilian context, this study will encourage further research.
Thirdly, unfortunately, data on the dispensing of all the different types of inhalers dispensed through the SUS in Brazil, such as those for Formoterol with Budesonide (DPI) or Olodaterol with Tiotropium (SMI), were not provided. Therefore, it was not possible to calculate the percentage of pMDI dispensations in relation to the total and, additionally, estimate the reduction that could occur if Brazil adopted a standard similar to that of other countries. It was also impossible to calculate the CO2 emissions per patient and compare this data with that of other countries, as the information provided by the Brazilian government describes only the number of devices dispensed without detailing how many individuals received the medications.
Finally, the cost calculation for the substitution of pMDIs for DPIs is an estimate (which could be over or underestimated), given that information on how many individuals benefited from the prescription of Salbutamol and/or Beclometasone was not provided, nor is there knowledge of the prescription pattern indicated for each individual based on their asthma staging. Future projects are also suggested to conduct more detailed cost calculations considering the negative externalities of pMDIs.
The primary material and the methodological details used to arrive at the results presented in this article will be shared in a certified data repository (https://data.scielo.org/), as part of the process known as Open Science.
This research had the innovative character of seeking to unveil the significant carbon footprint associated with asthma treatment in the SUS due to the preferential dispensing of pMDIs, in addition to making cost estimates. The substitution of pMDIs for DPIs or SMIs brings clinical benefits for asthma and COPD control and would be an effective measure for healthcare services in relation to climate change, promoting better public and planetary health for all.

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