Greenhouse Gas Emissions from Respiratory Treatments: Results from the SABA CARBON International Study

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In an effort to tackle the climate crisis, countries are increasingly seeking to decarbonise their economies by establishing carbon reduction targets in accordance with international treaties on climate change, such as the Paris Agreement [1, 2]. The healthcare sector is one of the largest public sector sources of greenhouse gas (GHG) emissions, accounting for 4.6% of global GHG emissions [3]; therefore, it is a key target for decarbonisation. In 2022, over 60 countries committed to build climate-resilient and low-carbon healthcare systems, with over 20 of these countries aiming to achieve ‘net zero’ carbon emissions from their healthcare systems by 2050 [4]. Approximately 60% of the global healthcare carbon footprint is emitted from countries outside of North America and the European Union [5]. Under-resourced and fragmented healthcare services in lower-middle-income countries (LMICs) are more carbon-intensive in economic terms than those in upper-middle-income countries (UMICs) and high-income countries (HICs), which may be explained in part by inefficient and non-sustainable energy supplies and poor access to care [6]. Thus, to achieve carbon reductions in these healthcare systems, it is imperative to identify tangible targets for decarbonisation that are simple to implement and have a positive impact on patient care.

Despite the availability of effective inhaler therapies, both asthma and chronic obstructive pulmonary disease (COPD) remain poorly controlled among a substantial proportion of patients worldwide [7, 8]. This is particularly evident in LMICs, where access to and affordability of medications are limited, which in turn may foster suboptimal patient management [9, 10]. Inhaled corticosteroids (ICS) and bronchodilators represent the mainstay of respiratory care and are delivered via pressurised metered-dose inhalers (pMDIs) or dry powder inhalers (DPIs) [11]. Medication costs largely influence treatment decisions in many countries. In developing countries where patients are required to purchase medications as an out-of-pocket expense, patients tend to address their acute need for rapid symptom relief rather than long-term asthma control [12]. To date, in respiratory care, the environmental impact of controller inhalers delivered via pMDIs has been the focus of attention [11]. This is due to the global warming potential (GWP) of the hydrofluoroalkane (HFA) propellants used in pMDIs that result in a comparatively higher carbon footprint than DPIs [13]. However, the contributions of short-acting β₂-agonist (SABA) reliever use and other asthma medications to the carbon footprint have not yet been investigated, providing an incomplete picture of the carbon footprint of respiratory care.

Findings from the real-world SABA use IN Asthma (SABINA) programme [14] report widespread SABA overuse (defined as ≥ 3 canisters/year) in the UK and other European countries and its link with an increased risk of exacerbations and healthcare resource utilisation (HCRU) [15‐17], all of which carry a carbon footprint. Similarly, in SABINA III, which included 24 countries outside of Europe, ≥ 3 (versus 1–2) SABA prescriptions/year were associated with lower odds of at least partly controlled asthma and higher rates of severe exacerbations [18]. Evaluating the contribution of controller and SABA inhalers to the carbon footprint of respiratory treatments and the excess carbon footprint associated with SABA inhaler use and overuse globally may help identify targets for decarbonisation in respiratory care. As part of the healthCARe-Based envirONmental cost of treatment (CARBON) programme [19], the SABA CARBON International study quantified the carbon footprint associated with (1) SABA use as a proportion of total inhaler use across all respiratory indications and (2) SABA overuse in asthma in Africa, Asia Pacific, Latin America and the Middle East.

Our findings, based on inhaler sales data, indicate high SABA use among patients with respiratory diseases, accounting for > 50% of total inhaler use and inhaler-related GHG emissions in most countries assessed. Per capita SABA use and associated GHG emissions were the greatest in Australia, in the Middle East and among HICs. Moreover, an analysis of SABINA III data revealed that SABA overuse (≥ 3 canisters/year) drove most SABA prescribing in asthma (> 90%). Per capita SABA overuse-related GHG emissions with and without SABA OTC were more pronounced in Africa and Latin America, respectively, and among HICs. Furthermore, the impact of SABA OTC purchase on per capita GHG emissions was greater among LMICs than among UMICs and HICs. Overall, regardless of the economic status of the countries studied, SABAs were the most commonly used inhalers, indicating suboptimal management of respiratory conditions [32], and contributed substantially to the carbon footprint of inhaler treatment. Therefore, efforts to optimise the management of respiratory diseases to curtail high SABA use could improve patient outcomes and result in substantial carbon savings in the healthcare sector.

Our results align with those of the SABA CARBON-Europe and Canada study, where SABA use generated 66% of total inhaler-related GHG emissions [33]. Moreover, the present study extended these findings worldwide to include geographical regions not commonly explored. Overall, the Middle East produced the highest per capita SABA use and related GHG emissions across all respiratory indications, chiefly contributed by Saudi Arabia. This aligns with previous reports from the Middle East documenting poor asthma control and non-adherence to prescribed ICS medication in most patients investigated [34, 35]. Indeed, suboptimal disease control has been reported in Turkey [36] and Saudi Arabia [37], with the Turkish study citing inadequate patient understanding of the role of ICS in attaining asthma control [36].

The greatest per capita SABA use and associated GHG emissions were from HICs; the highest emissions were observed from Australia and NZ, where despite an epidemic of asthma-related deaths (including children aged 5–17 years) in both countries during the 1960s and 1980s, which was attributed to inappropriate use of β-agonists [38‐40], SABAs continue to be widely prescribed [41‐43]. Although SABAs are not available for OTC purchase in NZ [44], with national dispensing data documenting a progressive decrease in SABA use following publication of National Asthma Guidelines in 2020 [45], a national report revealed that 47% of patients with asthma who were dispensed an ICS and SABA were given more SABA than ICS [43]. The high per capita reliever use in Australia may be explained by government regulations permitting dispensing of up to 1 months’ supply of prescribed SABAs and OTC sale of one canister per purchase to patients with asthma, with automatic repeat prescriptions via electronic medical records valid for up to 12 months [46, 47]. Interestingly, although both Australia and NZ report a similarly high asthma prevalence (10.7% and 11.4% in 2020–2021, respectively), with both countries having universal public health systems and subsidised access to ICS-containing therapies [48‐50], a higher per capita SABA use and lower per capita controller use were reported in Australia than in NZ. This finding is likely attributable to better self-reported adherence to ICS-containing therapies in NZ, possibly enhanced by lower patient co-payments and availability of SABA OTC in Australia since 1983 to reduce delays in accessing reliever inhalers for patients with acute symptoms [41, 48, 51]. In November 2016 in Melbourne, Australia, the convergence of environmental and patient factors triggered a thunderstorm asthma epidemic of unprecedented severity that resulted in several thousand acute respiratory presentations to emergency departments and ten deaths, for which health services, emergency services and the community were not prepared [52‐54]. Given the need to ensure optimal management of any future epidemic thunderstorm asthma events and the need to protect at-risk asthma populations [51], it is unlikely that purchase of SABA OTC in Australia will be subject to regulation, despite results from an Australian community pharmacy-based survey classifying 70.1% of participants who purchased SABA OTC from community pharmacies as over-users (reporting SABA use more than twice weekly during the 4 weeks before the study) [41]. Such patients were more likely to experience uncontrolled asthma and require oral corticosteroids (OCS) to manage poor symptom control and exacerbations than those who did not overuse SABA [41]. These findings raise concern, as even intermittent OCS use (3–7 days) is associated with greater odds of adverse outcomes once a lifetime cumulative OCS exposure of 1000 mg is exceeded [55‐57].

Analyses of the SABINA III study [18] revealed that most SABA prescriptions (> 90%) were given to patients overusing SABA, a finding comparable with that observed in the SABA CARBON-Europe and Canada study, where the proportion of SABA prescriptions given to patients overusing SABA ranged from 69% (Italy and Sweden) to 94% (Canada [Nova Scotia]) [33]. Such findings suggest improper prescription practices globally, underscoring the need for healthcare providers (HCPs) to evaluate the volume and frequency of SABA use in patients during routine reviews to assess risk before prescribing additional SABA. Overall, the percent difference between per capita SABA overuse-related GHG emissions with and without SABA OTC purchase was higher among LMICs than among UMICs and HICs. Thus, unregulated OTC availability of SABA in LMICs [58] might further provoke SABA overuse and expand the carbon footprint of asthma treatment in these countries. Notably, although the Asia-Pacific region had the lowest per capita SABA overuse-related GHG emissions with and without SABA OTC, this may not be indicative of good disease control or optimised treatment, as patients prefer oral therapies over inhaled medication in these countries [59].

The clinical implications of this study are wide ranging and provide an understanding of how, based on inhaler sales data, high SABA use drives the carbon footprint associated with respiratory treatment. Overall, the real-world variations in total inhaler-related GHG emissions observed across countries may be explained by differing healthcare policies, the non-availability of ICS-containing controller medications in many LICs, medications costs, healthcare insurance coverage [60, 61] and sociocultural contexts, all of which may have influenced HCP and patient preferences for inhaler use. Our findings from the SABINA III study indicate that SABA over-reliance is highly prevalent among both patients and HCPs. Since 2019, GINA has not recommended as-needed SABA monotherapy, based on evidence of increased morbidity and mortality [62]. Consequently, it is essential to implement the latest evidence-based treatment recommendations in clinical practice while fostering a strong partnership between HCPs and patients through shared treatment decision-making to improve clinical outcomes. This may also involve regulation of prescribing, dispensing and OTC sales of SABA, in parallel with improved access to ICS-containing medication, healthcare and affordable alternatives to SABA relievers, especially in countries with fragmented healthcare systems. Furthermore, factors that contribute to suboptimal disease control and drive increased demand for HCRU, such as incorrect inhaler technique, inappropriate medication use and poor treatment adherence [63], must be addressed to improve clinical outcomes and contain GHG emissions from the healthcare sector. This, coupled with asthma awareness campaigns, health promotion programmes and continuing medical education to facilitate adoption and application of treatment recommendations among HCPs [64], should help reduce the inequities that exist within healthcare systems, especially in LMICs, and reduce their respective healthcare sector-related emissions.

Several limitations of this study should be acknowledged. This study does not provide a complete quantification of the carbon footprint of inhalers to respiratory care within a single dataset; however, two distinct data sources were used, IQVIA MIDAS and SABINA III, to determine total inhaler use across all respiratory indications and SABA overuse in asthma, respectively. Most patients from SABINA III were recruited from specialist care and were therefore classified as having moderate-to-severe asthma [18]; thus, the study population may not be truly representative of the overall asthma patient population or reflect the way asthma is currently being managed across countries and regions. Nonetheless, data from the SABINA III study provided valuable insights on the carbon footprint of asthma medications, especially SABA prescriptions by practicing physicians, across a broad range of LMICs, UMICs and HICs on a global scale. Inhaler sales and prescription/dispensing data may not reflect actual medication use or treatment adherence and do not consider medication stockpiling; therefore, GHG emissions may have been overestimated. Inhaler-related CO₂e emissions were derived from published guidelines and studies and pharmaceutical LCAs and, therefore, are subject to variability over time. However, these uncertainties were overcome, at least in part, by performing a sensitivity analysis that considered updated guidelines, product LCAs and recently published studies [23‐28] and reported relatively small increases of up to approximately 8% in inhaler-related GHG estimates. Data on the use of other SABA formulations and inhaled reliever medication other than SABAs and their associated emissions were not assessed in this study. Lastly, the small sample size of the regional analyses in SABINA III poses a challenge in identifying the principal country-by-country GHG contributors, as they do not afford further stratification to that level. However, despite these limitations, the global IQVIA sales data reflect most channels through which inhaled medications may be accessed. In addition, a standardised methodology was applied to quantify the carbon footprint of inhaled medications and to prevent confounding from differences in dose and actuation counts across inhalers, and data from > 8000 patients from SABINA III [18] enabled an assessment of the global environmental impact of SABA overuse.

In conclusion, this retrospective cohort study is the first to quantify inhaled medication use and associated GHG emissions across Africa, Asia Pacific, Latin America and the Middle East. Overall, across all respiratory indications, SABAs accounted for > 50% of total inhaler use and inhaler-related GHG emissions in most countries analysed. Moreover, > 90% of SABA prescriptions for asthma were given to patients overusing SABA, highlighting a definable population to target. These findings suggest that implementing international recommendations that reduce high SABA use in respiratory care, especially in asthma, and adopting patient-centric principles of improving disease management would optimise patient outcomes while enabling healthcare systems to meet their carbon reduction targets.