Abstract
Objective Inhalation therapy is the cornerstone of COPD, together with non-pharmacological treatments. Long-acting muscarinic antagonists (LAMAs), alone or in combination with long-acting β-agonists (LABAs), are commonly used. Pressurised metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and soft-mist inhalers (SMIs) are used, each with different carbon footprints. This study aimed to assess the carbon footprint of hypothetically replacing LAMA or LAMA/LABA inhalers with an SMI, Respimat Reusable, within the same therapeutic class.
Methods An environmental impact model was established to assess the change in carbon footprint of replacing pMDIs/DPIs with Respimat Reusable within the same therapeutic class (LAMA or LAMA/LABA) across 12 European countries and the USA over 5 years. Inhaler use for country and disease-specific populations was derived from international prescribing data and the associated carbon footprint (CO2 equivalents (CO2e)) was identified from published sources.
Results Over 5 years and across all countries, replacing LAMA inhalers with Spiriva Respimat Reusable reduced CO2e emissions by 13.3–50.9%, saving 93–6228 tonnes of CO2e in the different countries studied. Replacing LAMA/LABA inhalers with Spiolto Respimat Reusable reduced CO2e emissions by 9.5–92.6%, saving 31–50 843 tonnes of CO2e. In scenario analyses, which included total replacement of DPIs/pMDIs, consistent CO2e savings were estimated. Sensitivity analyses showed that results were sensitive to changes in several parameters including varying assumptions around reusability of inhalers and potential CO2e impact.
Conclusion Replacement of pMDIs and DPIs with Respimat Reusable within the same therapeutic class would result in substantial reductions in CO2e emissions.
Abstract
Replacement of pressurised metered-dose and dry-powder inhalers with soft-mist inhalers in the LAMA or LAMA/LABA drug classes results in substantial reductions in CO2e emissions and waste, and supports global environmental goals https://bit.ly/40UIYXJ
Introduction
COPD and asthma are chronic respiratory conditions with increasing global prevalence [1, 2]. Currently, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) [3] recommend the use of inhaled therapies such as long-acting muscarinic antagonists (LAMAs), alone or in combination with long-acting β-agonists (LABAs) as maintenance treatment for the majority of COPD patients [3].
Three types of inhalation devices can be used to administer LAMA and LAMA/LABA therapy: pressurised metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and soft-mist inhalers (SMIs) [4]. The carbon footprint, expressed in carbon dioxide equivalents (CO2e), of these three devices differs, with pMDIs being higher than DPIs or SMIs due to use of hydrofluorocarbon (HFC) propellants. The use of HFC is currently being phased down under the Kigali Amendment to the Montreal Protocol (2016) [5]. This stimulus to switch away from HFC pMDIs has prompted innovation of inhaler design, including reusable inhalers and SMIs, with potential to further reduce the carbon footprint [6]. Several global and regional organisations and governments have started to design and implement measures to reduce emissions in the healthcare sector, including the Netherlands [7] and the NHS in the UK, as outlined in its Long-Term Plan, 2019 [8]. Furthermore, the British Thoracic Society's national guidance has recommended offering patients low-carbon alternatives to pMDI, where clinically appropriate [9].
To exemplify the high carbon footprint of pMDIs, it was estimated that using 50% of inhaler devices with a low carbon footprint, such as DPIs, would save the equivalent of 288 000 tonnes of CO2e every year, equivalent to taking >61 000 cars off the road [10]. No such comparison has been made regarding the carbon footprint of switching pMDIs or DPIs for SMIs, with one study grouping DPIs and SMIs together for analysis [11]. As the carbon footprint is different for every inhaler, robust quantification is needed to assess the current impact of the three types of inhaler devices. This study aimed to compare the carbon footprint, measured in terms of CO2e emissions, of switching the COPD patient population to the SMI, Respimat Reusable. The main analysis focused on switching within the same therapeutic class, and additional scenarios were conducted to complement the main analysis.
Methods
Model design
An environmental impact model was developed to assess the change in carbon footprint of 47 different inhalers, including all inhaled treatment classes used in COPD and asthma across 13 countries in Europe and the USA. The carbon footprint of replacing DPIs and pMDIs with Respimat Reusable within the same therapeutic class over a time horizon of 5 years (2021–2025) in Europe and USA was calculated (figure 1). This hypothetical replacement did not consider further treatment settings and excluded short-acting β-agonists (SABAs). The model was developed in accordance with ISPOR best practice guidelines for budget impact modelling [12].
Model design for primary analysis. BI: Boehringer Ingelheim; LABA: long-acting β-agonist; LAMA: long-acting muscarinic antagonist.
The geographic scope of this study was 13 countries spanning Europe (Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Norway, Portugal, Spain, Sweden, UK) and the USA. These countries were grouped according to the United Nations geoscheme: Northern Europe (Denmark, Norway, Sweden, UK), Southern Europe (Greece, Italy, Spain, Portugal), Western Europe (Belgium, Germany, Netherlands, France) and USA [13].
Patient population
In the model, the eligible population was adults with COPD and asthma on maintenance inhaled therapies. Volumes (number of units) and market shares for each product were derived from IQVIA MIDAS® international data (2021) (supplementary table S1). In the model, market share data were not altered over the time horizon of 2021–2025 and no population growth was applied. For each country, the size of the eligible population was estimated as the sold yearly dosages based on market share data.
Main analysis and scenario analyses
The main analysis assessed the carbon footprint of replacing DPI and pMDI with Spiriva Respimat Reusable within the LAMA treatment class and replacing DPIs and pMDIs with Spiolto Respimat Reusable within the LAMA/LABA treatment class. Additional scenario analyses were conducted for replacing clinically relevant therapeutic class or DPIs/pMDIs with Respimat Reusable over 5 years (2021–2025). A total of five scenario analyses were conducted, as outlined in table 1.
Main analyses and scenario analyses
Carbon footprint
A targeted literature review was undertaken to estimate the carbon footprint of DPIs, pMDIs and Respimat Reusable. Searches were run using key search terms for disease, intervention and outcomes on the PubMed database. Inclusion criteria included full text studies published from the year 2000 onwards reporting data on carbon footprint and greenhouse gases, environmental or global warming impact of DPIs, pMDIs or SMIs for use in COPD, asthma or other respiratory diseases. Where necessary, outcomes were converted to annual CO2e based on recommended administration frequency. Hand searching of relevant websites and databases (Google Scholar, National Health Service (NHS), United Nations, World Health Organization, and the European Union) was also conducted for carbon emissions, carbon footprint and climate change of DPIs or pMDIs, along with data on inhalers and sustainable prescribing.
At the time of the literature review, published estimates on carbon footprint were available for Ellipta, Breezhaler, Accuhaler, Nexthaler, Evohaler, Foster and Flutiform (table 2). The carbon footprint of Respimat Reusable has been previously reported by Hänsel et al. (2019) [14]. Spiolto Respimat Reusable and Spiriva Respimat Reusable have equivalent carbon footprints.
Carbon footprint of the different types and classes of inhaler used as model inputs
To estimate the carbon footprint of inhalers with no available data, the mean, by inhaler type, was taken between the available estimates and attributed to those inhalers (table 2). As previously reported by Janson et al. (2020) [15] and Hänsel et al. (2019) [14], 17% of total carbon footprint was attributed to refill based on the proportion of active pharmaceutical ingredients and distribution. A weighted mean by therapeutic class/inhaler class was calculated based on the units sold and the associated carbon footprint. The carbon footprint of DPIs was split between the inhaler device and the refill package.
Inhaler use
Annual use of disposable and reusable DPIs and disposable pMDIs was estimated based on the following assumptions: each patient must cover their annual drug consumption either by using inhalers or refills and each device (inhaler or refill) is assumed to cover 1 month of drug consumption. It was assumed that each patient on disposable pMDI devices used 12 units per year, those prescribed Respimat Reusable used two inhalers and 12 refills per patient per annum, and IQVIA MIDAS® data on refill rates were used to calculate the mean number of DPIs per country. The mean number of inhalers used per year and patient by therapeutic and inhaler class was calculated based on these assumptions (supplementary table S2). This mean was weighted by the number of sold units of each product, in each country.
Sensitivity analyses
The robustness of the results was assessed by carrying out several sensitivity analyses. These included varying assumptions around the extent of inhaler reuse in practice, changing the carbon footprint per inhaler, market shares for devices and therapeutic classes, and the extent of switching from 100% in the base case to alternative switching assumptions.
Results
Main analyses
Replacement of LAMA inhalers with Spiriva Respimat Reusable
Over 5 years, inhalers used in the LAMA class (a combination of pMDI, DPI, SMI) were estimated to contribute 0.05 mega tonnes of CO2e emissions across all countries (table 3). A hypothetical replacement of DPIs and pMDIs in the LAMA class with Spiriva Respimat Reusable could reduce CO2e emissions by 37.2%, over 5 years. These reductions varied by country, due to device ratio differences and ranged between 13.3% and 50.9%, saving between 93 and 6228 tonnes of CO2e emissions (figure 2). In Northern Europe CO2e emissions were reduced by 33.9% (3450 tonnes), in Southern Europe CO2e emissions were reduced by 42.2% (5692 tonnes), in Western Europe CO2e emissions were reduced by 23.1% (2374 tonnes) and in the USA CO2e emissions were reduced by 45.3% (6228 tonnes) when replaced with Spiriva Respimat Reusable.
Reduction in carbon footprint when replacing either inhalers as used in the LAMA or LAMA/LABA class to Spiriva Respimat Reusable and Spiolto Respimat Reusable, respectively, over 5 years (2021–2025)
Cumulative reduction in carbon dioxide equivalent (CO2e) emissions over 5 years using Spiriva Respimat Reusable over alternative inhalers used in the LAMA class in a) Northern Europe, b) Southern Europe, c) Western Europe and d) USA. LAMA: long-acting muscarinic antagonist. a) Northern Europe: Denmark, Norway, Sweden and UK; b) Southern Europe: Greece, Italy, Portugal and Spain; c) Western Europe: Belgium, France, Germany and the Netherlands; d) USA.
Replacement of LAMA/LABA inhalers with Spiolto Respimat Reusable
Over 5 years, inhalers as used in the LAMA/LABA class (combination of pMDI, DPI and SMI; ratios differ per country) were estimated to contribute 0.08 mega tonnes of CO2e emissions across all countries (table 3). A hypothetical replacement of LAMA/LABA inhalers with Spiolto Respimat Reusable could reduce CO2e emissions by 77.8%, over 5 years. These reductions varied by country, due to device ratio differences and ranged between 9.5% and 92.6%, saving between 31 and 50 843 tonnes of CO2e emissions (figure 3). In Northern Europe CO2e emissions were reduced by 64.4% (5223 tonnes), in Southern Europe CO2e emissions were reduced by 28.7% (1598 tonnes), in Western Europe CO2e emissions were reduced by 42.6% (5179 tonnes) and in the USA CO2e emissions were reduced by 92.6% (50 843 tonnes) when LAMA/LABA inhalers were replaced with Spiolto Respimat Reusable.
Cumulative reduction in CO2e emissions over 5 years using Spiolto Respimat Reusable over alternative inhalers used in the LAMA/LABA class in a) Northern Europe, b) Southern Europe, c) Western Europe and d) USA. CO2e: carbon dioxide equivalents; LABA; long-acting β-agonists; LAMA: long-acting muscarinic antagonist. a) Northern Europe: Denmark, Norway, Sweden and UK; b) Southern Europe: Greece, Italy, Portugal and Spain; c) Western Europe: Belgium, France, Germany and the Netherlands; d) USA.
Scenario analyses
Replacement of LABA/inhaled corticosteroid inhalers with Spiolto Respimat Reusable
Over 5 years, LABA/inhaled corticosteroid (ICS) inhalers were estimated to contribute 2.0 mega tonnes of CO2 emissions across all countries (supplementary table S3). A hypothetical switch from these devices to Respimat Reusable could reduce this emission by 93.5% (to 0.1 mega tonnes). Owing to device ratio differences among countries, these results vary between 71.8% and 95.3%, saving between 7683 and 807 077 tonnes of CO2e (supplementary figure S1).
Replacement of triple fixed dose combination inhalers with Spiolto Respimat Reusable
Over 5 years, triple therapy with LAMA/LABA/ICS through fixed dose combination (FDC) inhalers was estimated to contribute 0.3 mega tonnes of CO2e emissions across all countries (supplementary table S3). A hypothetical switch from these devices to Respimat Reusable could reduce this emission by 95.9% (to 0.01 mega tonnes). Owing to device ratio differences among countries, these results vary between 70.7% and 98.4%, saving between 277 and 118 079 tonnes of CO2e in the countries included in the analysis (supplementary figure S2).
Replacement of DPI with Respimat Reusable
Over 5 years, DPIs were estimated to contribute 0.4 mega tonnes of CO2e emissions across all countries (supplementary table S4). A hypothetical replacement of DPIs with Respimat Reusable could reduce this emission by 64.7% (to 0.1 mega tonnes). Owing to device ratio differences among countries, these results vary between 59.4 and 69.2%, saving between 2207 and 66 334 tonnes of CO2e (supplementary figure S3).
Replacement of pMDIs with Respimat Reusable
Over 5 years, pMDIs were estimated to contribute 2.1 mega tonnes of CO2e emissions across all countries (supplementary table S4). A hypothetical replacement of pMDIs with Respimat Reusable could reduce this emission by 97.1% (to <0.1 mega tonnes). Owing to device ratio differences among countries, these results vary between 94.3% and 98.3%, saving between 7729.3 and 847 218.4 tonnes of CO2e (supplementary figure S4).
Replacement of DPIs and pMDIs with Respimat Reusable
Over 5 years, both pMDIs and DPIs were estimated to contribute 2.5 mega tonnes CO2e emissions across all countries (supplementary table S4). A hypothetical replacement of pMDIs and DPIs with Respimat Reusable could reduce this emission by 92.2% (to 0.2 mega tonnes). Owing to device ratio differences among countries, these results vary between 75.9% and 94.5%, saving between 13 136 and 913 548 tonnes of CO2e (supplementary figure S5). Figure 4 summarises the absolute and annual per patient CO2e savings across the different countries if all DPIs and pMDIs were switched to Respimat Reusable.
5-year absolute and per patient carbon dioxide equivalents (CO2e) savings across the different countries if all dry powder inhalers and pressurised metered-dose inhalers were switched to Respimat Reusable. Shading in figure represents absolute CO2e savings (tonnes).
Sensitivity analyses
The details of the sensitivity analyses for the main and scenario analyses are shown in supplementary tables S5–S17. Data show that the main analyses were most sensitive to changes in number of Respimat Reusable inhalers reused. The scenario analyses were most sensitive to changes to the extent of switching and the reusability of the different inhalers.
Discussion
The objective of this study was to assess the carbon footprint of adopting SMIs (Respimat Reusable) across 13 countries in Europe and the USA instead of DPIs and pMDIs. This study shows that Respimat Reusable offers considerable environmental benefits in terms of decreased CO2e emissions when replacing disposable and reusable DPIs and pMDIs of the same therapeutic class. These data extend the previous findings of Hänsel et al. (2019) [14], Ortsäter et al. (2019) [16], Janson et al. (2020) [15] and Wachtel et al. (2020) [17], which show the environmental benefits of switching from pMDIs to devices with a lower carbon footprint and a reusable option. In a study by Pernigotti et al. (2021) [11], replacing pMDIs with DPIs/SMIs (classed as a single group) resulted in a 68% reduction in the carbon footprint across the UK, Italy, France, Germany and Spain when 80% of pMDIs were substituted with DPI or SMIs by 2030. While Pernigotti et al. (2021) [11] assessed a total replacement of pMDIs, our study focused on the replacement of pMDIs and DPIs within the same therapeutic class, making the findings applicable in clinical practice. Over 5 years, replacing alternative LAMA DPIs and pMDIs with Spiriva Respimat Reusable saved 0.02 mega tonnes of CO2e, equivalent to the annual carbon footprint of 2648 EU citizens. Similarly, replacing alternative LAMA/LABA DPIs and pMDIs with Spiolto Respimat Reusable saved 0.06 mega tonnes of CO2e, equivalent to the annual carbon footprint of 9380 EU citizens. These data show that substantial CO2e savings can be made with the clinically relevant replacement of inhaler devices.
Based on data from this study, the countries that would benefit most from implementing changes to inhaler use based on CO2e emissions are the UK, USA and Germany, which is aligned with these countries having the highest prevalence of COPD and the highest ratio of pMDI prescribed. Environmental pressures have prompted governments to introduce targets to reduce the use of inhalers with a high carbon footprint, including the UK Government's Environmental Audit Committee setting the NHS the challenge of reducing the carbon footprint of inhaler use by 50% before 2028 [18]. Consequently, NICE (UK) published a Patient Decision Aid on asthma inhalers in 2019 that highlights carbon footprint as a factor in inhaler choice, favouring a switch to DPIs or reusable SMIs [19]. In the UK, pMDIs account for a higher proportion of inhaler use (>50%) compared with other European countries and the USA (<50%), as indicated by both the market shares used in this study and the high carbon footprint of pMDIs, and as shown in scenario analyses performed. Prescribing data from England show that the usage of pMDIs has remained consistent at around 55% since 2021 [20]. Earlier estimates of pMDI use in the UK were 70% in 2011 [21], suggesting that implementation of these NHS policies and efforts to limit CO2 emissions are working. NHS England are reported to be on track to hit the first year carbon reduction target, though what impact pMDI replacement played in this success is unclear [22]. While successes in the UK have been gained, this continued variation in pMDI prescribing practices between the UK and other countries suggests that there is still room for a reduction in the use of pMDI in the UK. Nonetheless, the implementation of the UK-like policies elsewhere could potentially reduce the carbon footprint in the healthcare sector overall.
This study was a theoretical exercise, and while it is a clinically relevant replacement, an indiscriminate switch of the entire patient population using LAMA or LAMA/LABA DPIs and pMDIs to Respimat Reusable is not feasible as not all patients would be eligible. In our analyses of additional scenarios, we also analysed the carbon footprint of switching to LAMA/LABA administered by SMI from ICS/LABA or ICS/LABA/LAMA therapy. As with the main analyses, the scenario analyses present an ideal scenario where all patients are eligible to switch, and in clinical practice some patients will benefit from ICS. Sensitivity analysis showed that when 50% of the population in each scenario were switched to Respimat Reusable, there was a minimum 47.1% decrease in carbon footprint after switch. Switching all COPD patients to SMIs is not clinically appropriate as some COPD patients, such as those with high blood eosinophils and a history of exacerbations [3], are recommended to be treated with ICS, which is not available in an SMI. Similarly, there are limited asthma maintenance treatments available in SMI. However, several studies have shown that overuse of ICS-containing treatment in COPD is common [23, 24] and studies have shown that withdrawal of ICS in many COPD patients can be done without negative clinical consequences [25, 26]. Our results show that the benefits of replacing ICS-containing therapy with LAMA/LABA in COPD patients inappropriately treated with ICS could be two-fold, reducing the risk of side-effects like pneumonia, alongside a reduced carbon footprint.
Nevertheless, the use of DPI and pMDI will continue based on clinical need and as per ERS recommendations, patients should not be switched between devices purely for environmental reasons [27]. It is also important to note that some DPI devices assessed in the environmental impact model are single-dose reusable DPIs, with similar carbon footprints to Respimat Reusable and provide comparable environmental benefits. The GOLD group advocate choosing a tailored and personalised approach in clinical practice and choosing the most appropriate inhaler to meet individual patient needs [3]. When considering a switch for clinical need, patient engagement and preference is essential. Durability, ergonomics and ease of use are attributes that influence patient satisfaction and outcome and should be criteria that are factored into switching [4, 28, 29]. Reusability and carbon footprint of the device are strong drivers of patient preference [30, 31], and when patients are made aware of the carbon footprint of their inhalers, many are willing to try a more environmentally friendly device [32]. Patient education on carbon footprint must also be coupled with that of education of clinicians, where it has been shown that few understand the carbon footprint of devices and the presence or absence of propellants [33]. Ultimately, the greenest inhaler is a clinically appropriate device that gives patients clinical benefit [34].
Strengths and limitations
A key strength of this study is that it evaluated several scenarios across 13 different countries using up-to-date prescribing data. It spans across all therapeutic classes of inhaler used in COPD treatment. A key limitation to acknowledge is that the base case presents an optimistic scenario, in which all patients are switched to a reusable SMI with optimal use of devices (two inhalers and 12 refills per patient per annum). In the USA, where Respimat is not available in a reusable format, switching all LAMA and all LAMA/LABA patients to Respimat would still save 28 857 tonnes of CO2e, mainly due to the current significant use of LAMA/LABA pMDI. Switching inhaler types depends on the clinical need of patients, preferences for inhaler technique and the availability of the inhaled drugs as an SMI. For this reason, fewer patients will be eligible to switch to SMI, and the maximum hypothetical carbon footprint reduction with switching to SMI is actually lower. However, both the eligibility and optimal use of devices have been accounted for in a sensitivity analysis, in which the eligible population was reduced to 50% and the number of devices was increased from two to six and 12. Second, the sensitivity analysis demonstrated uncertainty around the magnitude of the carbon footprint due to several assumptions. For example, if the reuse of inhalers (refill ratios) is overestimated, then potential CO2e reduction when switching from a disposable to a reusable device will be lower than reported. However, overall, the sensitivity analysis demonstrated the robustness of the results showing the reduction in carbon footprint when replacing DPIs and pMDIs with SMIs. Third, our analysis is based on carbon footprint data published at the time the environmental impact model was built. In this respect, the model does not consider any newer or forthcoming devices such as pMDIs with low global warming potential or new carbon footprint data published after conducting the literature review, e.g. for DPIs such as Breezhaler [35] or Easyhaler [36]. Equally, should current market shares change, e.g. an increase in use of LAMA/LABA pMDI, then the switch to Respimat would provide additional carbon footprint savings. While SABAs were also not included in the model, their availability in a Respimat device is limited to very few countries. Any switch from SABA pMDIs to a Respimat device may provide further environmental savings. Lastly, the analysed prescribing data does not distinguish between COPD and asthma.
Conclusions
This study shows that replacement of LAMA or LAMA/LABA pMDIs and DPIs with an SMI, Respimat Reusable, could result in substantial reductions in CO2e emissions. A step-change in COPD management and carbon footprint could be delivered through a collaborative partnership between clinicians and patients. This partnership would be driven primarily by patient characteristics and needs, followed by consideration of the carbon footprint of the inhalers.
Supplementary material
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
Supplementary material 00543-2022.SUPPLEMENT
Acknowledgements
The authors wish to thank Joao Malhadeiro, a former employee of Boehringer Ingelheim, Portugal, who performed literature research and helped design the environmental impact model.
Footnotes
Provenance: Submitted article, peer reviewed.
Support statement: This study was supported and funding from Boehringer Ingelheim, Ingelheim am Rhein, Germany. Funding information for this article has been deposited with the Crossref Funder Registry.
Author contributions: J. Hernando Platz, S. Soulard and E.S. Hartgers-Gubbels were responsible for developing the initial research question and design, and development of the model. L. Nicholson conducted the analyses. L. Nicholson and S. Langham drafted the manuscript. All authors were responsible for the interpretation of the data, revising the manuscript for important intellectual content and approving the final version for publication. All author(s) meet criteria for authorship as recommended by the International Committee of Medical Journal Editors. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.
Data availability statement: The data that support the findings of this study are available from IQVIA. Restrictions apply to the availability of these data, which were used under licence for this study. Data are available from the corresponding author, L. Nicholson, with the permission of IQVIA.
Conflict of interest: C. Janson has received honoraria for educational activities and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Orion and TEVA, and has served on advisory boards arranged by AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Orion, Sanofi and TEVA. L. Nicholson and S. Langham received consulting fees from Boehringer Ingelheim. J. Hernando Platz, S. Soulard and E.S. Hartgers-Gubbels are employees of Boehringer Ingelheim. The authors did not receive payment related to the development of the manuscript.
- Received October 14, 2022.
- Accepted February 9, 2023.
- Copyright ©The authors 2023
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References
