More information about text formats
We are grateful to Levy et al for their comments on our paper.
Much of the response to the paper has been to the media coverage and potential consequences of this. That MDIs have a large carbon footprint is hardly news within technical and academic literature. (1) It’s fair to say we were taken aback by the media response. Any guilt induced by headlines which focussed on individual change is deeply regrettable. Our paper was focussed on modelling at the NHS level. In-line with other previous reports we included an individual level comparison to provide context to our findings. (1-3) The “180-mile car journey” ascribed to us by Levy et al. originates from a story about NICE asthma inhalers decision aid.(4) Clearly we can’t control the media and have tried to correct errors in media reporting where possible. It is our opinion that it would be unethical and paternalistic to withhold significant information about treatment options from patients. As academic authors we are reflecting on how best to communicate information of the environmental impact of healthcare to the public and media, and considering how we might improve this in the future.
Levy et al. highlight concerns “that all patients can be summarily switched from pMDIs to DPIs” or that patients are “deprived of access to pMDI therapy”. We do not propose this in the paper. In fact we make suggestions on how to reduce the greenhouse gas emissions from MDIs where their continuing use is necessary by prio...
Levy et al. highlight concerns “that all patients can be summarily switched from pMDIs to DPIs” or that patients are “deprived of access to pMDI therapy”. We do not propose this in the paper. In fact we make suggestions on how to reduce the greenhouse gas emissions from MDIs where their continuing use is necessary by prioritising smaller volume HFA134a inhalers. We would join with Levy et al. in opposing universal switches to DPI therapy or switching inhalers without patient consent. We are grateful to Levy et al. for raising the important issue of SABA overuse as well, and agree there are further potential opportunities here to improve asthma control and reduce greenhouse gas release. For patients who need MDIs for rapid relief of symptoms in emergency situations, including a MDI + spacer in a rescue pack has been proposed as an effective strategy.(5)
Whilst our paper focusses on population level effects, Levy et al. are quite right to raise the issue of what happens at an individual level and the potential risks when switching inhalers. Levy et al. provide anecdotal reports of chaos, discontinuation of inhalers and an increase in exacerbations following inhaler switches. In 2016 it is estimated that 6% of asthma patients and 10% of COPD patients had their inhalers switched purely for cost reasons.(6) We are aware of two relevant UK studies examining the impact of inhaler switches on disease control. Thomas et al. researched the impact of switching ICS for asthma patients without a clinical consultation.(7) Most of these switches were from DPI to MDI and none were from MDI to DPI. They found increased SABA use in the switched group compared to the control group, but no increase in asthma consultations, hospitalisations or oral corticosteroid use. Their findings illustrate the importance of inhaler technique training and assessment for any inhaler switch, but the increased SABA use seen may have been due to inappropriately selecting MDIs, which the authors describe as especially difficult to use. The switches were likely made for financial reasons (without considering greenhouse gas impact) and this may help to explain the near universal use of MDI for ICS inhalers in England. A more recent and more comprehensive study by Bloom et al. found that, contrary to Levy et al’s concerns, adherence improved and exacerbations decreased after switching inhalers.(6) Their analysis included MDI to DPI switches and 95% of patients continued with the inhalers they were switched to. Whilst we agree switching inhalers potentially risks disrupting care, it also represents an opportunity to improve adherence and inhaler technique provided it is accompanied by a clinical consultation.
Levy et al. report the large carbon footprint of aspects of emergency medical care. The healthcare sector needs to find ways to address these issues. It is entirely feasible that we could reduce the need for emergency care and improve disease control whilst switching to lower global warming potential inhalers. It is perhaps also worth noting that the carbon footprint of the using a single dose of treatment from an electronic nebuliser it is roughly half that of a dose of a small-volume HFA134 reliever inhaler.(8)
Levy et al. argue that our paper is “heavily biased in favour of DPIs”. They reference one paper comparing Seretide Evohaler and Seretide Accuhaler as evidence that patients with stable asthma do better on MDIs than DPIs.(9) We referenced this paper in our article, along with other evidence favouring the use of DPIs. We would argue that UK prescriptions as a whole are heavily biased towards MDI. We note 97% of prescriptions for SABAs and 94% of ICS in England are MDI.(10) The UK is a clear outlier compared to the rest of Europe in this regard (11) and the fact that UK has one of the worst asthma mortality rates in Europe makes it hard to argue that our high rates of MDI use bring any systematic benefits to patients. We recognise that differences in demographics and disease profiles between different countries, such as between the UK and Sweden, could influence the need for different therapies. The Netherlands as another example has some of the best asthma mortality rates in Europe has approximately 75% DPI usage overall and 50% DPI use for reliever inhalers in 2011. (11) We note also significant geographical variations within the UK in DPI prescription rates (12) and that some CCGs don’t include any DPI options for their recommended inhalers in some steps of asthma treatment.(13) Levy et al. are concerned about depriving patients of MDIs, but the reality on the ground is that patients are effectively being deprived of DPI treatments in the UK. Research consistently shows that a significant proportion of patients are unable to use MDIs correctly.(14) This suggests to us that prescribers follow the default path of prescribing MDIs a lot of the time, but better care could be offered by more carefully selecting the correct inhaler device to match patients’ abilities and preferences. If prescribers did carefully verify the ability of individual patients to use inhalers effectively before prescribing, we anticipate that we would see large increases in DPI prescription rates, improvements in asthma control and reduction in greenhouse gas emissions.
Our analysis did not include the cost of retraining patients to use different types of inhaler. This is not a straightforward calculation and depends which strategy is adopted to reduce greenhouse gas emissions, which we were not prescriptive about. Further research will attempt to address this issue. Changing the types of inhalers started de novo incurs no additional training cost, neither does switching to a near identical inhaler containing less propellant. There could be additional costs involved with retraining some patients although these would be partly offset by the fact that all patients should be having their inhaler technique regularly assessed as part of good routine practice.
Levy et al. point to other potential environmental impacts of inhalers. We focused on the greenhouse gas impact of inhalers, as we believe it represents the most pressing environmental issue. It is also the one issue that differs most dramatically between different types of inhalers.
Levy et al. commend the analysis of Jeswani & Azapagic (3) which we agree has many strengths, particularly its comprehensive life-cycle analysis. Levy et al. argue in favour of their more comprehensive assessment of impacts and whilst we would agree with this, it can be difficult to know the clinical relevance of information such as the greater proportion of potentially carcinogenic compounds in DPI manufacture. The greenhouse gas findings of Jeswani & Azapagic are largely in agreement with our own, in particular the conclusion that the overwhelming majority of the carbon footprint of MDIs derives from the HFA propellant. We have concerns about their method of relying on information from patient information leaflets to estimate the volume of propellants within MDIs. For instance, Jeswani & Azapagic report that a Salamol MDI contains 16.54g of HFA propellant which can’t be correct as the combined weight of the canister and contents of a new Salamol inhaler is only 15.6g. (15)
Levy et al. point to weaknesses in our analysis of the carbon footprint of DPIs and whilst we agree there is limited information in this area, the information that is available is concordant.(3,16) We are reliant on manufacturers for much of this information and would encourage more companies to release life cycle analyses into the public domain.
Levy points out that SMART/MART regimens have potential to improve patient care, reduce SABA use limit greenhouse gas emissions. If as Levy et al. argue this strategy is a safer and more effective strategy then this is to be welcomed. This strategy has been recommended by GINA guidelines, but we would like to see more real-world evidence of effectiveness before whole-heartedly supporting it. We are also less confident that it will be adopted worldwide, particularly in low and middle income countries as combination inhalers may be considered too expensive.
Looking beyond MART, we see many opportunities in the UK to improve care alongside a switch to low global warming potential inhalers. For SABAs there is currently near universal (97%) use of MDIs with opportunities to improve care and reduce MDI use. This could be achieved by using DPIs instead where appropriate, promoting regular preventer therapies such as MART, but also low GWP LAMA/LABA inhalers in COPD. For SAMAs, regular long-acting controller therapies have better evidence for improved disease control, preventing exacerbations and with lower greenhouse gas emissions. As described above ICS inhalers in the UK are almost universally (94%) MDIs. This is not compatible with the idea that we are carefully matching inhalers to patients’ preferences and abilities. None of these MDI SABA, SAMA or ICS inhalers have dose counters, leading to the dangerous and common phenomenon of patients using MDIs that are effectively empty (17). DPI counterpart inhalers all include dose counters. For ICS+LABA inhalers, in addition to MART, there is very widespread overuse of high dose ICS in COPD, with subsequent risks of pneumonia, oral thrush, and probably diabetes and bone fractures.(18) We see huge scope for improvements in patient care alongside financial and greenhouse gas savings by switching to more appropriate inhalers.(19) Reducing greenhouse gas emissions could be a happy coincidence of these improvements, an opportunity seized alongside improving disease control, or a catalyst providing renewed impetus to drive improvements in patient care.
Levy et al. raise concerns about the contribution of lactose monohydrate to the carbon footprint of DPIs. Lactose was included in the carbon footprint analyses of GSK’s DPIs (16) and by Jeswani and Azapagic.(3) Even applying the comparatively high GWP figures quoted by Levy et al. of 13.1kg CO2e/kg of Whey powder, the contribution to the carbon footprint is still very small. Seretide Accuhaler contains 12.5mg lactose per blister, or 0.75g per inhaler.(19) The carbon footprint contribution from lactose is therefore less than 10g CO2e per inhaler (13.1 x 0.75 = 9.83gCO2e per inhaler). This amounts to approximately 1% of the total carbon footprint of the inhaler.
We’d agree with the conclusion of Levy et al. that “asthma and COPD management should focus on prescribing appropriate inhaler devices …. that individual patients are able to use efficiently after appropriate education and in the context of management plans agreed with appropriately trained health care professionals.” As we’ve argued above, if we did this we’d see large switches to low global warming potential inhalers. We would additionally suggest that information on environmental impact should be considered and shared with patients whenever inahlers are being reviewed, or switched for other reasons, and that where all other considerations are equipoised then the treatment with the lowest carbon footprint should be selected.
1.Montreal Protocol On Substances that Deplete the Ozone Layer Report of the UNEP Medical Technical Options Committee 2014 Assessment. Nairobi, Kenya, 2010.
2.NICE Patient decision aid. Inhalers for asthma. London, 2019.
3.Jeswani HK, Azapagic A. Life cycle environmental impacts of inhalers. Journal of Cleaner Production. 2019;237:117733.
5.Emergency MDI and spacer packs for asthma and COPD Keeley, Duncan et al.The Lancet Respiratory Medicine, Volume 7, Issue 5, 380 - 382
6.Bloom CI, Douglas I, Olney J, et al. Cost saving of switching to equivalent inhalers and its effect on health outcomes Thorax 2019;74:1078-1086.
7.Thomas, M., Price, D., Chrystyn, H. et al. Inhaled corticosteroids for asthma: impact of practice level device switching on asthma control. BMC Pulm Med 9, 1 (2009) doi:10.1186/1471-2466-9-1
8.Goulet B, Olson L, Mayer B. A Comparative Life Cycle Assessment between a Metered Dose Inhaler and Electric Nebulizer. Sustainability 2017; 9: 1725.
9.Price D , Roche N , Christian Virchow J , et al . Device type and real-world effectiveness of asthma combination therapy: an observational study. Respir Med 2011;105:1457–66.doi:10.1016/j.rmed.2011.04.010
10.NHS England. NHS digital. 2017. https://digital.nhs.uk/prescribing (accessed July 17, 2018).
11.Lavorini F, Corrigan CJ, Barnes PJ, et al. Retail sales of inhalation devices in European countries: So much for a global policy. Respir Med 2016; 105: 1099–103.
14.Sanchis J, Gich I, Pedersen S. Systematic review of errors in inhaler use: Has patient technique improved over time? Chest 2016; 150: 394–406.
15.Sellers WFS. Asthma pressurised metered dose inhaler performance: propellant effect studies in delivery systems. Allergy Asthma Clin Immunol 2017; 13: 30.
16.Janson C, Henderson R, Löfdahl M, et al Carbon footprint impact of the choice of inhalers for asthma and COPD Thorax Published Online First: 07 November 2019. doi: 10.1136/thoraxjnl-2019-213744
17.Conner JB, Buck PO. Improving asthma management: the case for mandatory inclusion of dose counters on all rescue bronchodilators. J Asthma. 2013;50(6):658–663. doi:10.3109/02770903.2013.789056
18.Cataldo D, Derom E, Liistro G, et al. Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice. Int J Chron Obstruct Pulmon Dis. 2018;13:2089–2099. Published 2018 Jul 5. doi:10.2147/COPD.S164259
19.d’Ancona G, Patel I, Saleem A, et al P29 Impact Of Respiratory Virtual Clinics In Primary Care On Responsible Respiratory Prescribing And Inhaled Corticosteroid Withdrawal In Patients With Copd: A Feasibility Study Thorax 2014;69:A90.
Many thanks for bringing this to our attention. Unfortunately that report has been removed from their website and we are unable to add it now as a supplementary file. Here is an alternative reference published more recently which contains the same information:
Janson C, Henderson R, Löfdahl M, et al. Carbon footprint impact of the choice of inhalers for asthma and COPD Thorax doi: 10.1136/thoraxjnl-2019-213744
The findings presented here on the carbon footprint of inhalers are entirely concordant with other previous reports.
Mark L Levy,1,9 Darragh Murnane2, Peter J Barnes,3,9 Mark Sanders,4 Louise Fleming,5 Jane Scullion,6,9 Chris Corrigan,7,9 Omar S Usmani8,9
1. Locum general practitioner, Clinical Lead NRAD (2011-2014)
2. King’s College London Faculty of Life Sciences & Medicine, School of Immunology & Microbial Sciences ; School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Hertfordshire
3. National Heart & Lung Institute, Imperial College, London
4. Clement Clarke international Ltd (CCI) and founder of online museum of inhaler devices, www.inhalatorium.com.
5. Imperial College, London and the Royal Brompton and Harefield, NHS Foundation Trust
6. University Hospitals of Leicester
7. King’s College London Faculty of Life Sciences & Medicine, School of Immunology & Microbial Sciences
8. Imperial College London & Royal Brompton Hospital
9. Aerosol Drug ManagementImprovement Team (ADMIT), www.inhalers4u.org
In an attempt to address issues related to global warming contributed to by the use of pressurised, metered-dose inhalers (pMDIs), Wilkinson et al (1) have succeeded in generating a great deal of negative, potentially harmful media interest for patients who currently rely on these devices. They analysed the potential impact of switching therapy from pMDIs to dry powder inhalers (DPIs) in terms of both c...
In an attempt to address issues related to global warming contributed to by the use of pressurised, metered-dose inhalers (pMDIs), Wilkinson et al (1) have succeeded in generating a great deal of negative, potentially harmful media interest for patients who currently rely on these devices. They analysed the potential impact of switching therapy from pMDIs to dry powder inhalers (DPIs) in terms of both changes in greenhouse gas emissions and costs to the UK National Health Service based on prescribing information in England alone. This strategy was apparently devised in a vacuum, without regard to implications for threats to patient wellbeing and safety as a consequence of their being deprived of access to pMDI therapy for obstructive airways disease (asthma and COPD). Physicians are obliged to consider many factors when selecting the most appropriate inhaler device for patients other than the cost to the health care system if they wish the treatment to be effective; (2) these issues were not mentioned in this paper which, in our view, was heavily biased in favour of DPIs, which are seldom appropriate for use in young children, children, the elderly and infirm and those with considerable, irreversible airways obstruction. (3) In addition many patients rely on pMDIs for rapid relief of symptoms.
Their study addressed two possible switching scenarios in the United Kingdom (UK): (i) from pMDIs to currently prescribed DPIs, and (ii) to the cheapest available ‘equivalent’ DPIs based on drug content but not the instrinsic characteristics of the devices. While we agree with one of their conclusions that, with immediate effect, smaller volume HFA134a inhalers (e.g. Salamol) should be prioritised over larger volume or HFA227ea-containing inhalers (e.g. Ventolin) we have major reservations about their remaining assertions, and in particular their conclusion that switching patients’ medication from pMDIs to the cheapest available equivalent DPIs would result in large carbon savings, while ignoring the possible consequences for loss of disease control and consequent morbidity and mortality from obstructive airways diseases such as asthma, which might result in considerable patient harm.
In addition to potential harm from loss of disease control, the burden of suffering and anxiety to patients from this sort of approach to reporting is potentially further amplified by the “guilt factor” already instilled by recent headlines in the media prompted by the report, such as “Asthma inhalers are as bad for the environment as a 180-mile car journey”, “Asthma sufferers should switch to “green” inhalers to help the environment and save millions for the NHS” and “Some asthma inhalers are as bad for the environment as eating meat”. These messages clearly have the potential to stigmatise patients with asthma and COPD for taking their essential medication, and there are anecdotal reports of children, many of whom benefit particularly from pMDI therapy, not wanting to be seen using their inhalers in public. We know of no other situation in the National Health Service where patients are stigmatised for using licensed and approved medications, and the situation will doubtless further impact on the issue of compliance with therapy, which if undermined is another potential threat to their well-being, as well as impacting on morbidity and mortality. (4) Conversely, there was no mention in this commentary, or indeed in the media, that correct delivery of inhaled drugs by an inhaler device which can be used efficiently and reliably by individual patients improves symptoms and quality of life and reduces morbidity, mortality and hospital acute care costs. (5, 6) (3, 7-9)
Further to this last issue, there was correspondingly no mention or consideration of the potential consequences where switching “goes wrong”, resulting in disease destabilisation and the associated “carbon cost” of unnecessary emergency and hospital inpatient management (10); Goulet et al (11) estimated that the carbon footprint of a single bronchodilator dose administered with an electric nebuliser is a considerable 0.0294-0.0477 kg CO¬2-eq. Moorfields Eye Hospital estimate that the carbon footprint of a single patient visit is between 8-10 kg CO2-eq per patient, per visit. It is difficult to assess the current carbon footprint of medical air/oxygen supply, however the European Industry Gas Association lifecycle appraisal framework (document 167/11) identified that the majority of the carbon footprint for liquid gases arises during production and distribution, not during the use of those gases by the end-user. Therefore, unlike the propellant in pMDIs, it is difficult to reduce the carbon footprint of therapeutic gases simply by altering the in-use conditions. (12) One supplier of compressed gases, Linde, in their Corporate Responsibility report of 2017, reported that 5.7 million tonnes of CO2 were produced during liquid gas production, or 52% of their Scope 1 Direct emissions. So the footprint for air therapies is also likely to be significant.
Finally, Wilkinson’s comparison between the UK (70%) and Sweden (10%) pMDI use fails to account for potential differences in disease therapy indications in both countries. For example, both NICE (13) and SIGN/BTS (14) guidelines advocate the use of short-acting, beta-agonist (SABA) use as first line therapy for asthma, which may account for the high levels of prescribing in England. While they acknowledge that they have no idea what disease(s) are being treated in their analysis of prescribing in England, Wilkinson and colleagues have assumed that all patients can be summarily switched from pMDIs to DPIs irrespective of their age, the nature and severity of their disease, their ability to use DPIs efficiently (not all patients can use DPIs efficiently whereas all patients can use pMDIs efficiently if well instructed, with a spacer device), or their satisfaction or preference for the switched device which is a another known factor influencing therapeutic outcome.(15)They have also failed to discuss the fact that not all DPI drugs have clinically equivalent efficacy compared with that of the pMDIs currently in use. It is well known that poor inhaler technique and poor disease outcome are closely related and both NICE (13) and SIGN/BTS (14) guidelines emphasise the necessity of and carefully verifying the ability of individual patients to use inhalers efficiently before prescribing, yet the authors have omitted to address the cost effectiveness and possible carbon footprint of the workload involved in switching and training patients. Furthermore, there was no mention of the chaos familiar to many GPs when patients’ inhalers are switched to “cheaper equivalents” by Clinical Commissioning Group (CCG) employed pharmacists without face to face education and checking technique. Patients become confused when given an unfamiliar device, typically stop using it and in some cases require urgent health care as a consequence. What then often happens is that their GPs will reinstate the original medication. Perhaps the authors could have cited some of the disadvantages arising from switches of medication on non-medical grounds without the patient’s consent, with deterioration of disease control and increased health care utilization. (16) (5) Indeed, data show that stable patients on pMDI maintenance treatment for asthma (17) and COPD (18) achieve better healthcare outcomes than the same drug in a DPI.
While the authors do mention the use of maintenance and reliever regimes (MART and SMART) they do not emphasise the implications, for patient welfare or global warming, of the concerns raised by over usage of short-acting beta-agonists (SABA) as a result of poor education and/or poor overall disease control in patients with asthma. (19, 20) Clearly, simply switching from one SABA to another in this situation will not alter the considerable risk of poor health outcomes, including asthma deaths. (21-23) A strategy is required to eliminate the over usage of SABA by every patient. Combinations of inhaled corticosteroids and long-acting beta-agonists such as formoterol taken “as needed” for the management of mild/moderate asthma are now licensed in five countries based on evidence that they are safer than SABA, (24-27) and it seems very likely that this strategy will be implemented worldwide in the near future, and that it will prove safer and clinically more cost effective. As most of these combination drugs are currently delivered in DPIs this will have an impact on global warming and manufacturers will need to focus on reducing the effect of these on the carbon footprint.
There are considerable shortcomings in carbon footprint modelling in the Wilkinson et al paper. There is relatively scant justification for the carbon footprint of the DPI inhalers included as comparators in this study: in fact, all of the DPIs included in their modelling are assumed to possess the same global warming potential (GWP) as the Ellipta and Diskus devices of ~1kg CO2-eq per device. This is despite the widely different structures and contents of many DPI devices, in terms of parts and plastics involved in their manufacture. In their evidence and subsequent discussion on usage, Wilkinson et al also failed to mention the differential effects on the environment related to the stages of manufacture of pMDIs and DPIs. For example, in the case of GlaxoSmithKline products, the majority of the CO2 emissions from this company’s DPI devices arise from the production of the plastic container and the active pharmaceutical ingredients (APIs) fluticasone propionate (FP) and salmeterol xinafoate (SX), whereas the primary contributors with pMDIs are emissions resulting from actual usage of the devices, and at the end of the life of the device when it is disposed of. (28)
Furthermore it is not apparent that the lactose monohydrate included in DPI formulations is ever included in the Wilkinson or other models of GWP. Lactose monohydrate is a product of the dairy industry contributing considerably to the carbon footprint: for example one study (29) reported that the total carbon required to produce Whey Powder from raw milk is 13.1 kg CO2-eq per kg of Whey Powder product, a value apparently similar to other, international GWP estimates of Whey Powder production (in the USA). Dairy farming is well known to be carbon intensive, not least due to methane production by the herd, but also from the transport and processing of the Whey Powder products
Wilkinson’s approach of simply addressing the GWP of Inhaled Products is misleading; preferably the methodology of Jolliet et al(30) of a holistic Life Cycle Assessment should also be made. This was performed by Jeswani and Azapagic (31)for pMDIs made with HFA134, HFA227, HFA152 and a GSK dry powder inhaler Diskus device. Although the DPI outperformed the HFA134 and HFA227 inhaled devices for Global Warming Potential as expected, however human toxicity, marine eutrophication and fossil depletion are all worse for DPIs than HFA-based pMDIs, when the holistic life-cycle analysis is undertaken. Thus it may be the case that GWP is better for DPIs, but the full long-term environmental effects were actually worse for eight out of fourteen environmental impact metrics for DPIs than pMDIs. It was also noted by the authors (31) that once HFA152a switchover has been made, that pMDIs will have an equivalent carbon footprint to DPIs, but have improved environmental impact profile than DPIs.
While we are concerned about the environment and the effect humans are having on global warming, we are concerned that this article lacks balance in its discussion and conclusions and puts patients with asthma at risk of an attack through inappropriately stopping or switching inhalers. In our view, asthma and COPD management should focus on prescribing appropriate inhaler devices and ancillary equipment such as spacers that individual patients are able to use efficiently after appropriate education and in the context of management plans agreed with appropriately trained health care professionals. These factors should take priority. (32) There may be suitable opportunities to consider the “greenest” alternatives when patients commence therapy or alter it for reasons of poor disease control or inadequate inhaler technique.
1. 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.
2. Bjermer L. The Importance of Continuity in Inhaler Device Choice for Asthma and Chronic Obstructive Pulmonary Disease. Respiration. 2014;88(4):346-52.
3. Giraud V, Roche N. Misuse of corticosteroid metered-dose inhaler is associated with decreased asthma stability. European respiratory Journal. 2002;19(2):246-51.
4. Why asthma still kills: the National Review of Asthma Deaths (NRAD) Confidential Enquiry report: Royal College of Physicians. London; 2014 [Available from: http://www.rcplondon.ac.uk/sites/default/files/why-asthma-still-kills-fu....
5. 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.
6. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respiratory Medicine. 2011;105(6):930-8.
7. Giraud V, Allaert FA. Improved asthma control with breath-actuated pressurized Metered Dose Inhaler (pMDI): The SYSTER survey. European Review for Medical and Pharmacological Sciences. 2009;13(5):323-30.
8. Molimard M, Gros VL. Impact of patient-related factors on asthma control. Journal of Asthma. 2008;45(2):109-13.
9. Haughney J, Price D, Kaplan A, Chrystyn H, Horne R, May N, et al. Achieving asthma control in practice: Understanding the reasons for poor control. Respiratory Medicine. 2008;102(12):1681-93.
10. Moorfields Hospital Foundation Trust. Sustainable Development Management Plan 2017 [Available from: https://www.moorfields.nhs.uk/sites/default/files/Item%2009%20Sustainabl....
11. Goulet B, Olson L, Mayer BK. A Comparative Life Cycle Assessment between a Metered Dose Inhaler and Electric Nebulizer. Sustainability. 2017;9(10):1725.
12. EUROPEAN INDUSTRIAL GASES ASSOCIATION AISBL. METHODOLOGY TO ESTABLISH A “PRODUCT CARBON FOOTPRINT: IGC Doc 167/11/E 2007 [Available from: https://www.eiga.eu/index.php?eID=dumpFile&t=f&f=2580&token=c87996bc2e26....
13. Commissioned by the 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
14. Scottish Intercollegiate Guideline Network (SIGN), the British Thoracic society (BTS). British guideline on the management of asthma 2019 [Available from: https://www.sign.ac.uk/sign-158-british-guideline-on-the-management-of-a....
15. Plaza V, Giner J, Calle M, Rytila P, Campo C, Ribo P, et al. Impact of patient satisfaction with his or her inhaler on adherence and asthma control. Allergy Asthma Proc. 2018;39(6):437-44.
16. Björnsdóttir 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. 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.
18. Jones R, Martin J, Thomas V, Skinner D, Marshall J, Stagno d'Alcontres M, 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. Int J Chron Obstruct Pulmon Dis. 2017;12:2445-54.
19. The Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA).2019. Available from: http://www.ginasthma.org.
20. Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, et al. GINA 2019: a fundamental change in asthma management: Treatment of asthma with short-acting bronchodilators alone is no longer recommended for adults and adolescents 2019 [updated Jun. 2019/06/30:[Available from: https://erj.ersjournals.com/content/53/6/1901046.long.
21. Suissa S, Ernst P, Boivin JF, Horwitz RI, Habbick B, Cockroft D, et al. A cohort analysis of excess mortality in asthma and the use of inhaled beta-agonists. Am J Respir Crit Care Med. 1994;149(3 Pt 1):604-10.
22. Suissa S, Blais L, Ernst P. Patterns of increasing beta-2-agonist use and the risk of fatal or near-fatal asthma. European Respiratory Journal. 1994;7(9):1602-9.
23. Reddel HK, Ampon RD, Sawyer SM, Peters MJ. Risks associated with managing asthma without a preventer: urgent healthcare, poor asthma control and over-the-counter reliever use in a cross-sectional population survey. BMJ Open. 2017;7.
24. Beasley R, Holliday M, Reddel HK, Braithwaite I, Ebmeier S, Hancox RJ, et al. Controlled Trial of Budesonide-Formoterol as Needed for Mild Asthma. N Engl J Med. 2019;380(21):2020-30.
25. Hardy J, Baggott C, Fingleton J, Reddel HK, Hancox RJ, Harwood M, et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial. The Lancet. 2019;394(10202):919-28.
26. O’Byrne PM, FitzGerald JM, Bateman ED, Barnes PJ, Zhong N, Keen C, et al. Inhaled Combined Budesonide–Formoterol as Needed in Mild Asthma. New England Journal of Medicine. 2018;378(20):1865-76.
27. Bateman ED, Reddel HK, O’Byrne PM, Barnes PJ, Zhong N, Keen C, et al. As-Needed Budesonide–Formoterol versus Maintenance Budesonide in Mild Asthma. New England Journal of Medicine. 2018;378(20):1877-87.
28. Carbon Trust. GlaxoSmithKline PLC. Product Carbon Footprint Certification Summary Report 2014 [Available from: https://networks.sustainablehealthcare.org.uk/sites/default/files/media/....
29. Finnegan W, Goggins J, Zhan X. Assessing the environmental impact of the dairy processing industry in the Republic of Ireland. Journal of Dairy Research. 2018;85:1-4.
30. Jolliet O, Margni M, Charles R, Humbert S, Payet J, Rebitzer G, et al. IMPACT 2002+: a new life cycle assessment methodology. Int J Life Cycle Assess 8:324-330. The International Journal of Life Cycle Assessment. 2003;8:324-30.
31. Jeswani HK, Azapagic A. Life cycle environmental impacts of inhalers. Journal of Cleaner Production. 2019;237:117733.
32. Usmani OS, Scullion J, Keeley D. Our planet or our patients-is the sky the limit for inhaler choice? Lancet Respir Med. 2019;7(1):11-3.
Probably the most important reference cannot be reached, number 23:
Attempting to follow it gives the message: "Sorry - we can't find the page you are looking for"
This is the reference which provides the justification for what seems to be the extremely high carbon footprint for each inhaler. Without this, it is difficult to have any faith in the conclusions of this paper.
In general, it is bad practice to provide a citation to a non-permanent web resource.