- Email: [email protected]
Aerosol drug delivery: developments in device design and clinical use
Correspondence
5
de Koning JP. Dry powder inhalation: technical and physiological aspects, prescribing and use. Groningen: University of Groningen, 2001: 29–80. http://dissertations.ub.rug.nl/ faculties/science/2001/j.p.de.koning/ (accessed Aug 23, 2011).
NHS Sustainable Development Unit, Cambridge CB21 HXB, UK (JS); and Faculty of Pharmaceutical Medicine, London, UK (RT) 1
2
Science Photo Library
We consider there to be insufficient recognition in the Review by Myrna Dolovich and Rajiv Dhand1 of the importance of environmental sustainability when selecting an inhaler device. The propellants used in metereddose inhalers are hydrofluorocarbons (HFCs). These are potent greenhouse gases with global warming potential of, in many cases, more than 1000 times that of carbon dioxide.2 A report for the UK Department for Environment, Food and Rural Affairs3 has projected the fall in emissions that might be achieved by reductions in HFC use. A projected shift of 75% use of metered-dose inhalers to a dry-powder alternative by 2025, is predicted to result in a fall in related HFC emissions of 1·308 Mt CO2 eq in 2025. The most recent estimated carbon footprint of the English National Health Service (NHS), not including HFC use, is 21 Mt CO2 eq, so this emissions reduction would be similar to a fall of 6% of NHS emissions.4 We recognise that of the utmost importance is clinical outcome for patients, but expect that there are many patients who use metered-dose inhalers when dry-powder inhalers would be equally effective. Dolovich and Dhand’s Review concludes by listing a series of questions that should be asked before selection of a particular device. To this list we would add: “Is there a more sustainable alternative?” Only if patients, clinicians, and policy makers start to ask this question when choosing treatments will we start to make choices that give not only the best outcome for the patient but for society as well. We declare that we have no conflicts of interest.
*James Smith, Richard Tiner [email protected]
982
3
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Dolovich MB, Dhand R. Aerosol drug delivery: developments in device design and clinical use. Lancet 2011; 377: 1032–45. Solomon S, Qin D, Manning M, et al, eds. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change, 2007. Cambridge and New York: Cambridge University Press, 2007. http://www.ipcc.ch/publications_and_data/ar4/ wg1/en/contents.html (accessed Aug 23, 2011). Okamura S, Ashford P, Jackson J, Watterson J. HFC consumption and emissions forecasting. Harwell: AEA Technology, 2011. http://archive. defra.gov.uk/environment/quality/air/fgas/ documents/fgas-hfc-forecasting.pdf (accessed Aug 23, 2011). NHS Sustainable Development Unit. Saving carbon, improving health: NHS Carbon Reduction Strategy Update. Cambridge: NHS Sustainable Development Unit, 2010. http:// www.sdu.nhs.uk/documents/publications/ UPDATE_NHS_Carbon_Reduction_Strategy_ (web).pdf (accessed Aug 23, 2011).
Authors’ reply Overall, one wants an inhaler to provide a powder cloud that can be inhaled with an inspiratory flow rate (IFR) that will not deposit most of the dose in the mouth and upper airways. This is not always possible. In a scintigraphic study of radiolabelled deposition from the ASTA Medica device,1 total lung deposition increased with increasing IFR owing to better dispersion of the powder. The distribution of the drug within the central, intermediate, and peripheral regions of the lung, however, remained unchanged.1 Additionally, the time at which peak IFR is achieved during the inhalation is important and differs between drypowder inhalers (DPIs) that dispense powder from a capsule versus those that use a drug reservoir.2 The Diskus DPI provides a consistent emitted dose at the mouth over an IFR range of 15–60 L/min.3 However, the fine particle fraction increases as the IFR through the device increases from 30 to 60 L/min.4 The ability of the aerosol to bypass the upper airway and deposit in the lung is dependent on both the IFR and the size distribution of the inhaled aerosol. Thus, similarly to other DPIs, a greater proportion of the dose of drug generated with the Diskus at lower IFRs
is likely to deposit in the upper airway, with less available for the lung.1 Further studies are needed to elucidate the pulmonary deposition and therapeutic responses at various IFRs. The issue of whether patients with obstructive lung disease can generate a sufficient pressure drop across a selected DPI is a concern. In the clinic, a patient’s ability to generate a sufficient IFR to dispense the DPI dose as a fine powder cloud can be determined by measuring peak IFR. If patients are unable to generate the optimum pressure drop or peak IFR, an alternative delivery device should be considered. The use of hydrofluorocarbon propellants is undoubtedly an important environmental issue, but space constraints allowed only a brief mention in our paper (page 1034 and table 1). We agree that environmental concerns must be considered in selecting an appropriate device. However, although breath-actuated DPIs provide an alternative type of inhaler, children younger than 4 or 5 years tend not to benefit from them.5 Innovative device designs are already addressing these important functional and environmental concerns. We declare that we have no conflicts of interest other than those stated in the original paper.
*Myrna Dolovich, Rajiv Dhand [email protected] St Joseph’s Healthcare/McMaster University, Hamilton, ON L8N 4A6 Canada (MD); and University of Missouri, Columbia, MO, USA (RD) 1
2
3
4
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Newman SP, Pitcairn GR, Hirst PH, et al. Scintigraphic comparison of budesonide deposition from two dry powder inhalers. Eur Respir J 2000; 16: 178–83. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011; 37: 1308–417. Bisgaard H, Klug B, Sumby BS, Burnell PK. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma. Eur Respir J 1998; 11: 1111–15. Palander A, Mattila T, Karhu M, Muttonen E. In vitro comparison of three salbutamolcontaining multidose dry powder inhalers. Clin Drug Invest 2000; 20: 25–33. Agertoft L, Pedersen S, Nikander K. Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma. J Aerosol Med 1999; 12: 161–69.
www.thelancet.com Vol 378 September 10, 2011
5
de Koning JP. Dry powder inhalation: technical and physiological aspects, prescribing and use. Groningen: University of Groningen, 2001: 29–80. http://dissertations.ub.rug.nl/ faculties/science/2001/j.p.de.koning/ (accessed Aug 23, 2011).
NHS Sustainable Development Unit, Cambridge CB21 HXB, UK (JS); and Faculty of Pharmaceutical Medicine, London, UK (RT) 1
2
Science Photo Library
We consider there to be insufficient recognition in the Review by Myrna Dolovich and Rajiv Dhand1 of the importance of environmental sustainability when selecting an inhaler device. The propellants used in metereddose inhalers are hydrofluorocarbons (HFCs). These are potent greenhouse gases with global warming potential of, in many cases, more than 1000 times that of carbon dioxide.2 A report for the UK Department for Environment, Food and Rural Affairs3 has projected the fall in emissions that might be achieved by reductions in HFC use. A projected shift of 75% use of metered-dose inhalers to a dry-powder alternative by 2025, is predicted to result in a fall in related HFC emissions of 1·308 Mt CO2 eq in 2025. The most recent estimated carbon footprint of the English National Health Service (NHS), not including HFC use, is 21 Mt CO2 eq, so this emissions reduction would be similar to a fall of 6% of NHS emissions.4 We recognise that of the utmost importance is clinical outcome for patients, but expect that there are many patients who use metered-dose inhalers when dry-powder inhalers would be equally effective. Dolovich and Dhand’s Review concludes by listing a series of questions that should be asked before selection of a particular device. To this list we would add: “Is there a more sustainable alternative?” Only if patients, clinicians, and policy makers start to ask this question when choosing treatments will we start to make choices that give not only the best outcome for the patient but for society as well. We declare that we have no conflicts of interest.
*James Smith, Richard Tiner [email protected]
982
3
4
Dolovich MB, Dhand R. Aerosol drug delivery: developments in device design and clinical use. Lancet 2011; 377: 1032–45. Solomon S, Qin D, Manning M, et al, eds. Contribution of Working Group I to the Fourth Assessment Report of the Intergovernmental Panel on Climate Change, 2007. Cambridge and New York: Cambridge University Press, 2007. http://www.ipcc.ch/publications_and_data/ar4/ wg1/en/contents.html (accessed Aug 23, 2011). Okamura S, Ashford P, Jackson J, Watterson J. HFC consumption and emissions forecasting. Harwell: AEA Technology, 2011. http://archive. defra.gov.uk/environment/quality/air/fgas/ documents/fgas-hfc-forecasting.pdf (accessed Aug 23, 2011). NHS Sustainable Development Unit. Saving carbon, improving health: NHS Carbon Reduction Strategy Update. Cambridge: NHS Sustainable Development Unit, 2010. http:// www.sdu.nhs.uk/documents/publications/ UPDATE_NHS_Carbon_Reduction_Strategy_ (web).pdf (accessed Aug 23, 2011).
Authors’ reply Overall, one wants an inhaler to provide a powder cloud that can be inhaled with an inspiratory flow rate (IFR) that will not deposit most of the dose in the mouth and upper airways. This is not always possible. In a scintigraphic study of radiolabelled deposition from the ASTA Medica device,1 total lung deposition increased with increasing IFR owing to better dispersion of the powder. The distribution of the drug within the central, intermediate, and peripheral regions of the lung, however, remained unchanged.1 Additionally, the time at which peak IFR is achieved during the inhalation is important and differs between drypowder inhalers (DPIs) that dispense powder from a capsule versus those that use a drug reservoir.2 The Diskus DPI provides a consistent emitted dose at the mouth over an IFR range of 15–60 L/min.3 However, the fine particle fraction increases as the IFR through the device increases from 30 to 60 L/min.4 The ability of the aerosol to bypass the upper airway and deposit in the lung is dependent on both the IFR and the size distribution of the inhaled aerosol. Thus, similarly to other DPIs, a greater proportion of the dose of drug generated with the Diskus at lower IFRs
is likely to deposit in the upper airway, with less available for the lung.1 Further studies are needed to elucidate the pulmonary deposition and therapeutic responses at various IFRs. The issue of whether patients with obstructive lung disease can generate a sufficient pressure drop across a selected DPI is a concern. In the clinic, a patient’s ability to generate a sufficient IFR to dispense the DPI dose as a fine powder cloud can be determined by measuring peak IFR. If patients are unable to generate the optimum pressure drop or peak IFR, an alternative delivery device should be considered. The use of hydrofluorocarbon propellants is undoubtedly an important environmental issue, but space constraints allowed only a brief mention in our paper (page 1034 and table 1). We agree that environmental concerns must be considered in selecting an appropriate device. However, although breath-actuated DPIs provide an alternative type of inhaler, children younger than 4 or 5 years tend not to benefit from them.5 Innovative device designs are already addressing these important functional and environmental concerns. We declare that we have no conflicts of interest other than those stated in the original paper.
*Myrna Dolovich, Rajiv Dhand [email protected] St Joseph’s Healthcare/McMaster University, Hamilton, ON L8N 4A6 Canada (MD); and University of Missouri, Columbia, MO, USA (RD) 1
2
3
4
5
Newman SP, Pitcairn GR, Hirst PH, et al. Scintigraphic comparison of budesonide deposition from two dry powder inhalers. Eur Respir J 2000; 16: 178–83. Laube BL, Janssens HM, de Jongh FHC, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J 2011; 37: 1308–417. Bisgaard H, Klug B, Sumby BS, Burnell PK. Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma. Eur Respir J 1998; 11: 1111–15. Palander A, Mattila T, Karhu M, Muttonen E. In vitro comparison of three salbutamolcontaining multidose dry powder inhalers. Clin Drug Invest 2000; 20: 25–33. Agertoft L, Pedersen S, Nikander K. Drug delivery from the Turbuhaler and Nebuhaler pressurized metered dose inhaler to various age groups of children with asthma. J Aerosol Med 1999; 12: 161–69.
www.thelancet.com Vol 378 September 10, 2011