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We thank Professor Murnane and co-authors for their comments on our paper: “The carbon footprint impact of the choice of inhalers for asthma and COPD” . Unfortunately, there are some misunderstandings in their letter and we are happy to try to resolve them.
1. Our study was intended to look at a high-level model for carbon savings in respiratory care, using existing device options with recognised limitations for wider application. It is not a blueprint for system change or a fully costed recommendation for health decision makers. We do not think that it is realistic to change the prescribing patterns from the current 70% pMDIs in England to Swedish levels. We do, however, think it is important to illustrate the potential GWP gains that can achieved if the suggestions in the BTS statement on ‘the environment and lung health’ and the sustainability ambitions of NHS England in its Long Term Plan (7) are followed: “Complete elimination of pMDIs may not be possible due to patient preference and the need to generate sufficient inspiratory flow to activate the DPIs. However, BTS encourages all prescribers and patients to consider switching pMDIs to DPIs whenever they are likely to be equally effective.” (5).
2. The Murnane et al response refers to content which is not in our paper, such as ‘switching pMDIs to the cheapest DPIs’. The paper does not analyse or compare the costs of switching as this is outside the scope of the study. While th...
2. The Murnane et al response refers to content which is not in our paper, such as ‘switching pMDIs to the cheapest DPIs’. The paper does not analyse or compare the costs of switching as this is outside the scope of the study. While this fact invalidates the Murnane response on this issue, it does not invalidate the important consideration of costs. We note the analysis from the Committee on Climate Change Net Zero technical report which notes that “it is feasible and cost-effective to switch MDIs to DPIs and low-GWP alternatives by 2027”.
3. We agree on the need of introducing therapies with a low Global Warming Potential (GWP) into the clinic. This is especially important as a recent report from the World Meteorological Organisation shows that the greenhouse gas concentration in the atmosphere has now reached another high (2). We welcome research to develop metered dose inhalers that could use propellants with lower GWP, but given the length of time taken to switch from using CFC to HFA propellants previously, it is therefore important to point out that we already have devices with a lower GWP than the currently available pMDIs such as DPIs (1) and aqueous/soft mist inhalers (3). We also agree that different patients need different devices and that the choice of device should be based on multiple factors where the GWP of the device is only one. This approach is in line with the 2019 guidance published by NICE (8) and BTS where clinical factors are addressed first and foremost, and only when clinically appropriate are environmental impacts of device choice discussed. Other important things to consider are, as we write in our paper, healthcare professional knowledge of all the devices, inhalation manoeuvre achieved; airway disease severity, patient’s ability to use their device correctly and their personal preferences (1).
4. By stating that the authors may represent GSK, Murane et al. misunderstands the role of studies such as this and ignores the explicitly stated limitation of the paper. The authors interests are declared and funding and resource for the report is clearly stated. GSK data was used to provide consistency between the carbon footprinting methodologies used and to the authors’ knowledge there were no other independently verified carbon footprint data of inhaler devices in the public domain. The authors would request that companies publish their inhaler product footprint data for both MDI and DPI so it can be equally scrutinised. We are not promoting a switch to GSK products we are simply describing the data available exemplified by the products described in the paper.
5. Murane et al. comment that the carbon footprints of API used in DPI are a significant contributor to the carbon footprint of a DPI. The carbon footprints of the API used in an MDI are of similar magnitude to the carbon footprints of the API used in a DPI, given the dose strengths of the products analysed. The carbon footprint of the API and other components in an MDI are simply overshadowed by the > 96% contribution of the HFA propellant to the carbon footprint of the MDI which dominates the analysis. A focus on this element is important from a wider environmental perspective but is a very small part of the carbon question we sought to address in our paper.
6. Our paper uses references to other carbon footprint benchmarks, such as eating meat, as a comparison only and we have not presented any narrative to the contrary. This type of comparison and contextualisation is commonplace and is indeed covered in reports published in 2014 and 2018 by the Medical and Chemical Technology Options Committee of the United Nations Environment Programme (9). We suspect the authors of the Murnane response are confusing recent media coverage, which may suggest flippancy on the topic, with the evidenced content of our paper. We note the evidence itself is not challenged, rather it is the third-party interpretation which is the concern. We agree any sensationalist coverage of our paper or similar papers is unhelpful.
7. Murane et al highlight a very recent paper (Azapagic et al. Nov 2019) which concludes that there are some negative environmental impacts of DPI devices. It should be noted that from a carbon perspective, the impact of the manufacturing and use of propellant gases in MDIs far outweigh the impact from the manufacturing and use of DPIs (or SMIs). Ours is a narrow study on the carbon footprint of inhalers where the propellant makes up the vast majority of this and the model looks at existing options that could reduce this. We accept and support valid work that adds to rational scientific debate on the wider sustainability of pharmaceuticals.
1. Janson C, Henderson R, Löfdahl M, Hedberg M, Sharma R, Wilkinson AJK. Carbon footprint impact of the choice of inhalers for asthma and COPD. Published Online First: 07 November 2019. doi: 10.1136/thoraxjnl-2019-213744
2. World Meteorological Organization. Greenhouse gas concentrations in atmosphere reach yet another high https://public.wmo.int/en/media/press-release/greenhouse-gas-concentrati.... Accessed 28 November 2019
3. Hänsel M, Bambach T, Wachtel H.Reduced Environmental Impact of the Reusable Respimat® Soft Mist™ Inhaler Compared with Pressurised Metered-Dose Inhalers.
4. Adv Ther. 2019 Sep;36(9):2487-2492.
5. National Institute for Health and Care Excellence. NICE encourages use of greener asthma inhalers. https://www.nice.org.uk/news/article/nice-encourages-use-of-greener-asth... Accessed 28November 2019.
6. British Thoracic Society. The environment and lung health. https://www.brit-thoracic.org.uk/document-library/governance-and-policy-... Accessed 3 May2019.
7. NHS England Long Term Plan - https://www.longtermplan.nhs.uk/
8. NICE Asthma Inhaler Shared Decision Aid - https://www.nice.org.uk/guidance/ng80/resources/inhalers-for-asthma-pati...
9. UNEP MCTOC 2018 Assessment Report - https://ozone.unep.org/sites/default/files/2019-04/MCTOC-Assessment-Repo...
It was with great interest and not a little concern that we read the recent Brief Communication by Janson and colleagues  into the impact of pressurised metered dose inhalers (pMDIs) on the global warming potential (GWP) of respiratory care. We note the tenacity of one of the authors who has succeeded in publishing a second paper  based on a similar, flawed logic just two weeks later. The sense of proportion that is missing in both reports has, thankfully, been identified in the press this week. However, we feel it essential to scrutinise the current contribution scientifically.
The authors report the carbon footprints of a range of devices marketed by GlaxoSmithKline (GSK) following analysis undertaken by the Carbon Trust (a UK not-for dividend company). Subsequently, calculations were undertaken aimed to determine how the carbon footprint of inhalation therapy in the UK’s National Health Service (NHS) might be reduced by altering the prescribing patterns of UK physicians (where more pMDIs are prescribed than dry powder inhalers (DPIs)) to resemble those of Swedish physicians (where the converse holds). While we acknowledge the authors’ declaration that their data are potentially flawed by the fact that their calculations are based on extrapolating the carbon footprints of just three device formats manufactured by one company to predict the effects of total DPI and pMDI usage in the UK when the carbon footprints of most other devices are unknown, we wou...
The authors report the carbon footprints of a range of devices marketed by GlaxoSmithKline (GSK) following analysis undertaken by the Carbon Trust (a UK not-for dividend company). Subsequently, calculations were undertaken aimed to determine how the carbon footprint of inhalation therapy in the UK’s National Health Service (NHS) might be reduced by altering the prescribing patterns of UK physicians (where more pMDIs are prescribed than dry powder inhalers (DPIs)) to resemble those of Swedish physicians (where the converse holds). While we acknowledge the authors’ declaration that their data are potentially flawed by the fact that their calculations are based on extrapolating the carbon footprints of just three device formats manufactured by one company to predict the effects of total DPI and pMDI usage in the UK when the carbon footprints of most other devices are unknown, we would suggest that this is not the only potential weakness of the analysis. It is also erroneous to compare the UK to Sweden by looking solely at prescribing data for England, and not the entire UK. The modelling of GSK-GSK product switches ignored that there may be both lower GWP and lower cost alternative DPIs or inhalation device formats. Indeed, we are deeply concerned the reports by such respected authors could be interpreted as promoting a commercial bias of one company recommending switching patients to their own – frequently more expensive – products to save the planet, where there could be both lower carbon footprint and lower cost from alternatives.
This is the second occasion that we have felt obliged to respond to such analysis and invite scientists and clinicians to clamour for independent assessment of the multiple ramifications of developing medicine that is both effective and environmentally sustainable. An additional incorrect assumption perpetuated in this second article, that has direct clinical consequences for respiratory disease patients, is that all patients can be summarily switched from pMDIs to DPI therapy irrespective of their age, the nature and severity of their obstructive airway disease, or ability to use DPIs efficiently. We would remind readers that healthcare professionals must consider many therapeutic factors when selecting the most appropriate inhaler device for individual patients if they wish treatment to be effective. For example, DPIs, are seldom appropriate for use in young children, the elderly and infirm and those with considerable, irreversible airways obstruction. The authors’ data does not differentiate between asthma and COPD prescriptions. Several clinical modelling assumptions in the current Brief Communication are therefore unrealistic and undermine the data in their article. Of significant concern is their calculation based on 2 doses of short-acting beta agonist (SABA) a day. If these are asthma patients, then the pMDI-DPI switch is poor practice and the prescribing signifies uncontrolled asthma (likely because regular inhaled corticosteroids (ICS) are not being taken, or device use is incorrect), and it further indicates the need for an urgent healthcare professional review to reassess medication, inhaler device, inhaler technique, adherence and patient motivation.[6, 7]
We agree wholeheartedly with the authors that it is necessary to take an environmentally sustainable approach to prescribing. However we have grave reservations about the assertion that switching patients’ from pMDIs to the cheapest DPIs would result in large carbon savings, while ignoring the carbon impact during manufacture of devices (not included in their limited modelling), and possible consequences for loss of disease control and consequent morbidity and mortality from obstructive airways diseases such as asthma.
We note that the authors only report the carbon footprint of several of GSK’s product range, rather than undertaking an holistic lifecycle analysis of the products. Such an analysis was performed by Jeswani and Azapagic for pMDIs made with the propellants HFA134, HFA227, HFA152 and a GSK DPI-Diskus device. Although the DPI outperformed the HFA134 and HFA227 pMDIs for GWP; human toxicity, marine eutrophication and fossil depletion were all concluded to be worse for DPI-Diskus than HFA-based pMDIs. In fact, the full spectrum of long-term environmental effects of DPI-Diskus were actually worse for eight out of fourteen environmental impact metrics than for pMDIs. The inhaled pharmaceutical development sector is currently examining the switchover of HFA134 and HFA227 to a low GWP alternative propellant HFA152a. Once the HFA152a switchover has been made, pMDIs will have an equivalent carbon footprint to DPIs, but have improved environmental impact profile. Switchover may also present an opportunity to reduce the extent of manufacturing overfill (many “200 dose” inhalers are currently filled to between 220-240 dosages to ensure through-life stability) which would also have an impact on GWP.
When undertaking their analysis of the potential reductions in carbon emissions for individual patients and for the NHS if a pMDI-DPI switch were enacted, the authors used data from the Carbon Footprint Certification Summary Report for several GSK inhalation products  included in their supplementary material. While we recognise and acknowledge the invaluable and sector-leading work of the Carbon Trust, we note the authors of the current study have not facilitated close scrutiny of the primary carbon calculation methodologies, in contrast to other studies in the scientific literature (e.g. [9, 11]). Indeed, we note one of the Carbon Footprint Report’s 'Recommended Further Actions' was to: “collect accurate, recent primary data”. Since we have no access to them, it is impossible for the reader to know how old and complete the data are that were presented to the Carbon Trust. Given this shortcoming, we believe it is at best unjustified, and at worst thoroughly inappropriate to predict the GWP reduction for inhalation therapy by assuming that all pMDI products on the market have the same carbon footprint as GSK’s Evohaler (20 kg CO2e), and that all prescribed DPIs possess the same GWP as the Ellipta and Diskus devices of ~1kg CO2e per device. This is patently untrue in the case of the Salamol salbutamol pMDI, for example, which has a carbon footprint which is approximately half that modelled in the current communication.[8, 11] All DPIs have widely different structures and contents in terms of parts and plastics involved in their manufacture, or the number of dose units contained in the device. As a significant contributor to GWP in DPIs is the active pharmaceutical ingredient (API), it follows that the move from mono-therapy towards double and triple combinations is therefore more likely to be a move for DPIs towards higher GWP.
The authors’ comparisons between the percentage of patients prescribed pMDIs in the UK (70%) compared to Sweden (10%) extends no further than the pharmacological category of prescribed inhaler numbers in England; and does not take into account the prescribed brand (and its corresponding carbon footprint), nor the indication for the prescribed therapy. Such an assessment is a blunt tool and fails to account for potential differences in disease care pathways in each country. For example, NICE  and SIGN/BTS  guidelines advocate the use of SABA use as first line therapy for asthma, and as pMDIs are cheapest, this may account for the high levels of prescribing in England compared to other countries. There is no assessment as to whether the SABAs prescribed in Sweden are identical to those in the UK. The exercise of replicating the Swedish prescribing patterns in the UK context is undertaken with no regard to the disease(s) being treated in which (sub)-populations of patients. The authors summarily assert that that the reasons underpinning the different prescribing patterns “could be related to marketing strategies and prescribers’ and patients’ biases”. This is a remarkable conclusion from authors representing one of the world’s leading producers of inhalation medicines regarding the prescribing of their own products. Indeed, we note that the economic cost to the NHS of the switches recommended in this article would be substantial, given the higher cost of many of GSK’s DPIs compared with pMDI. 
We have pointed out that Janson and colleagues have assumed in their analysis that all patients in the UK can be switched from pMDI to DPI therapy regardless of fact that not all patients can use DPIs effectively (because of their age, and/or the nature or severity of their disease) and the influence of their own satisfaction with – or preference for – the switched device which is a known factor influencing therapeutic outcome. In contrast to DPIs, all patients with sufficient hand motor function can use pMDIs effectively in combination with a spacer device, when well-instructed. Indeed, the pMDI combination compounds of salmeterol xinafoate with fluticasone propionate, marketed by this company, have been shown to be more effective in real life studies on improving asthma control  and COPD  disease exacerbations than the very same combination given as a DPI.
In light of the potential for loss of disease control when switching devices, it seems imperative that the carbon footprint of potential loss of disease control also be presented to healthcare professionals alongside the carbon footprint implications of the switchover itself. [16, 17] There is no assessment of the carbon footprint of the clinical visits involved in switching and re-training patients. Disease destabilisation and the associated “carbon cost” of unnecessary emergency and secondary care disease management would also be significant. For example, Goulet et al.  estimated that the carbon footprint of a single bronchodilator dose administered with an electric nebuliser is a considerable 0.0294-0.0477 kg CO2e, while Moorfields Eye Hospital estimated that the carbon footprint of a single patient visit was between 8-10 kg CO2e per patient, per visit.  Therefore, the carbon reductions described by the authors may not reflect the full costs of the switchover. We advocate face-to-face training and assessment of optimal inhaler technique to ensure patients are prescribed an inhaler device that they are able to use in order to manage their asthma or COPD, before examining the carbon footprint of a patient’s inhalation therapy as the secondary prescribing assessment.
Our final substantive objection to the approach taken by the authors in this manuscript is the comparison of the carbon footprint of a patient’s inhalation therapy to reductions achievable by lifestyle choices, such as changing from a meat-based to plant-based diet, changing transport modalities or how clothes are washed. Patients with lung disease or any other disease do not choose to have their condition, nor is it a lifestyle choice to use therapy with which best manages the condition for each individual. The flippant comparisons made in the recent report  resulted in newspaper headlines that potentially add to the burden of anxiety of patients by amplifying the “guilt” of contributing to climate change when taking an essential medicine. There is a need for balanced, articulate and, most importantly, accurate analysis that avoids the stigmatisation of patients with asthma and COPD through news headlines that do not address the nuances of planning the reduction of healthcare impact on climate change.
We are all concerned about the environmental impact of human activity on global warming and the environment.  Several of us are engaged in research to accelerate the introduction of low GWP therapies into the clinic, or improve our management of lung disease through appropriate device utilization. However, this communication lacks balance in its discussion, while potentially pressurizing healthcare professionals and patients inappropriately to stop or switch successful therapeutic plans. There are undoubtedly opportunities to consider the “greenest” product when patients commence therapy or alter it for reasons of poor disease control or inadequate inhaler technique.
‘Greening’ healthcare requires a more holistic assessment of the impact of inhaler choice on wider environmental metrics, as well as the consequences of possible destabilisation of patients’ conditions, and the carbon-intensiveness of the consequent extra emergency and follow-up care. While the authors correctly state that: “Key considerations for inhaler selection include healthcare professional knowledge of all the devices; inhalation manoeuvre achieved; airway disease severity, patient’s ability to use their device correctly and their personal preferences” we feel that publications such as the current report have potential to create carbon targets for prescribing in isolation from such nuanced considerations. Healthcare practitioners will welcome evidence-based approaches for identifying suitable patients and strategies for switching devices. If the burden of reducing the GWP of healthcare in the NHS is to be placed on respiratory physicians, it is essential that they have access to prescribing tools that allow appropriate stratification of product choices for patients to manage their therapeutic carbon footprint. There is no one-size-fits-all approach in respiratory care, and we believe the current Brief Communication contributes little to our ability to deliver the changes necessary to manage the environmental impact of inhalation therapies.
1. Janson C, Henderson R, Löfdahl M, Hedberg M, Sharma R, Wilkinson AJK. Carbon footprint impact of the choice of inhalers for asthma and COPD. Published Online First: 07 November 2019. doi: 10.1136/thoraxjnl-2019-213744
2. Wilkinson AJK, Braggins R, Steinbach I, Smith J. Costs of switching to low global warming potential inhalers. An economic and carbon footprint analysis of NHS prescription data in England. BMJ Open. 2019;9(10).
3. Ingraham C. No, asthma inhalers are not ‘choking the planet’. Washington Post. 2019 11 Nov 2019 https://www.washingtonpost.com/business/2019/11/11/no-asthma-inhalers-ar....
4. Levy M, Murnane D, Barnes PJ, Sanders M, Fleming L, Scullion J, et al. Inhaler devices and global warming: Flawed arguments - A Response to Wilkinson et al. Costs of switching to low global warming potential inhalers. An economic and carbon footprint analysis of NHS prescription data in England. BMJ Open. 2019. Available from: https://bmjopen.bmj.com/content/9/10/e028763.responses#inhaler-devices-a....
5. Giraud V, Roche N. Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. European Respiratory Journal. 2002;19(2):246-51.
6. Global Initiative for Asthma (GINA). The Global Strategy for Asthma Management and Prevention 2019. Available from: http://www.ginasthma.org.
7. Scottish Intercollegiate Guideline Network (SIGN), The British Thoracic Society British guideline on the management of asthma 2019. Available from: https://www.sign.ac.uk/sign-158-british-guideline-on-the-management-of-a...
8. Jolliet O, Margni M, Charles R, Humbert S, Payet J, Rebitzer G, et al. IMPACT 2002+: A new life cycle impact assessment methodology. International Journal of Life Cycle Assessment. 2003;8(6):324.
9. Jeswani HK, Azapagic A. Life cycle environmental impacts of inhalers. Journal of Cleaner Production. 2019;237.
10. Trust C. Carbon Trust. GlaxoSmithKline PLC. Product Carbon Footprint Certification Summary Report 2017 (Supplementary Material to Janson et al. Thorax, 2019). Available from: https://thorax.bmj.com/content/thoraxjnl/early/2019/11/07/thoraxjnl-2019....
11. Goulet B, Olson L, Mayer BK. A comparative life cycle assessment between a metered dose inhaler and electric nebulizer. Sustainability (Switzerland). 2017;9(10).
12. National Institute for Health and Care Excellence (NICE). Asthma: diagnosis, monitoring and chronic asthma management. NICE guideline [NG80]. 2017. Available from: https://www.nice.org.uk/guidance/ng80
13. Plaza V, Giner J, Calle M, Rytilä P, Campo C, Ribó P, et al. Impact of patient satisfaction with his or her inhaler on adherence and asthma control. Allergy and Asthma Proceedings. 2018;39(6):437-44.
14. Price D, Roche N, Christian Virchow J, Burden A, Ali M, Chisholm A, et al. Device type and real-world effectiveness of asthma combination therapy: An observational study. Respiratory Medicine. 2011;105(10):1457-66.
15. Jones R, Martin J, Thomas V, Skinner D, Marshall J, d’Alcontres MS, et al. The comparative effectiveness of initiating fluticasone/salmeterol combination therapy via pMDI versus DPI in reducing exacerbations and treatment escalation in COPD: A UK database study. International Journal of COPD. 2017;12:2445-54.
16. Björnsdõttir US, Gizurarson S, Sabale U. Potential negative consequences of non-consented switch of inhaled medications and devices in asthma patients. International Journal of Clinical Practice. 2013;67(9):904-10.
17. Melani AS, Paleari D. Maintaining control of chronic obstructive airway disease: Adherence to inhaled therapy and risks and benefits of switching devices. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2016;13(2):241-50.
18. Moorfields Hospital Foundation Trust. Sustainable Development Management Plan 2017 – Page 9. Available from: https://www.moorfields.nhs.uk/sites/default/files/Item%2009%20Sustainabl...
19. Usmani OS, Scullion J, Keeley D. Our planet or our patients—is the sky the limit for inhaler choice? The Lancet Respiratory Medicine. 2019;7(1):11-3.