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Rapid Responses: Rapid Responses published:
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Elderly people's use of dry powder inhalers: where was the connection with Influenza?
- Andrew Martin (9 March 2001)
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Which inhaler device ? Which patient ?
- Jonathan Bell (9 March 2001)
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Zanamavir and Unreason
- G H Hall (10 March 2001)
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Re: Elderly people's use of dry powder inhalers: where was the connection with Influenza?
- Paul Diggory, Valerie Jones (12 March 2001)
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New Inhaler devices infrequently used by older people in the community
- Lindsey Dow (18 March 2001)
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Competing interests - a comment to the Turbuhaler Diskhaler influenza article
- Lars Borgström (19 March 2001)
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Dry powder inhaler and elderly patients
- Dominique Vanpee (21 March 2001)
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Re: Competing interests - Professor Borgstrom's comments, or AstraZeneca's defence of Turbohaler ?
- Jonathan Bell (9 April 2001)
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Andrew Martin, Prescribing Support Pharmacist Bury North Primary Care Group
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I have just read the article by Diggory et al with some amazement. This study shows that Turbohalers are easier to use than Diskhalers for elderly people and the result is likely to be applicable to all elderly using dry powder inhalers for airways disease. However, the article showed no outcome evidence in patients with Influenza and at the end we find that placebo dry powder inhalers were actually used. Thus it should have been titled "elderly people are more likely to remember how to use Turbohalers than Diskhalers" and a point made that this should be borne in mind when prescribing Zanamivir as it is only available in a Diskhaler presentation. The title given is erroneous as Zanamivir was not delivered using two dry powder inhalers! |
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Jonathan Bell, Project Manager - Device Development Harlow, Essex
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We note with interest the findings of Diggory’s work, and applaud the comment in the Discussion - “Better delivery systems for inhalers should be used or developed”. However, we are concerned that an opportunity has been missed, because the original objective sought to identify the most problematic aspects of inhaler technique - but the five aspects of technique that were scored did not include an objective measure of whether the patient actually inhaled the medication efficiently. Diggory’s argument that “loading and priming is a crucial aspect of inhaler use because if this is incorrectly done no drug can be delivered” is agreed, but arguably it is just as crucial for patients to inhale properly – particularly so with dry powder inhalers such as Turbohaler, whose total drug delivery to the lungs is reduced by 50% when inspiratory flow rates drop from 60 l/min to 30 l/min (ref 1). Concerns also exist with breath-actuated pMDIs, such as 3M’s Autohaler, which will not release any aerosol until the patient reaches an inhalation speed of 30 l/min. By comparison, inhaling too fast frequently compromises pMDI usage, yet for many years we have known of the improved pulmonary deposition and reduced oropharyngeal side-effect profile when inhalation speeds are below 60 l/min for this type of device. Any research in this area must surely also address the relative difference in internal resistance that patients encounter when inhaling through the various inhalers, which in turn will determine the effort needed to achieve a given inspiratory flow rate - as much as three times the inspiratory effort is needed to achieve a given flow through a Turbohaler than through the Diskhaler (ref 2). Previous work by Diggory and colleagues has already highlighted the lower flows achieved by elderly patients through Turbohaler, where 17/26 (65%) could achieve 30 l/min, but only 1 patient (0.5%) could achieve the optimum flow of 60 l/min (ref 3). To think that it may be better to have zanamivir delivered through a Turbohaler, rather than the Diskhaler device,for this group of people, is clearly wrong. If this research is just added to the existing library on the subject, then we will continue to want new and different delivery devices – but are there not already enough different delivery systems available, but just that patients are often prescribed an inappropriate device ? Maybe, because rarely do we take into account manual dexterity, cognitive function and ability to inhale at an optimum flow rate ? Jon Bell
Refs: 1. Borgstrom L. J Aerosol Med 1994;7(suppl 1):S49-S53 2. Richards, R and Saunders, M. Need for a comparative performance standard for dry powder inhalers. Thorax 1993;48:1186-7 3. Peacock K., Diggory P., Jones V., and Treml J. Ability of elderly patients to generate adequate inspiratory flow rates to use Turbohaler, Clickhaler, Autohaler or EasiBreathe inhalers (Presentation at the British Geriatrics Society Spring Meeting 2000). |
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G H Hall, retired
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Zanamavir's effect on 'flu is disputed but there's no doubt about it's capacity - or rather the idea of its capacity- to paralyse logic. First NICE rejects it then recommends it. However, it can only be used in an arbitrarily defined epidemic. If you happen to have 'flu at other times that's just too bad. Now it appears that if some people can't use it properly, then it should'nt be used by anyone. The next step will probably be to deny its use to those who haven't been vaccinated. In fact it would almost certainly have been cheaper not to use mass vaccination for the majority who won't get 'flu than to prescribe Relenza to those who do. But what would the other drug firms say to that- or indeed the DH whose officials refuse access to safety information on this year's batch of vaccines. Political correctness is an evidence free zone. |
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Paul Diggory, Consultants mayday Hospital, Valerie Jones
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We agree the title is not clear. Our original title was 'A randomised controlled study of elderly peoples inhaler technique with the dry powder inhaler device (Diskhaler) used to deliver zanamivir.' It was pointed out to us, at the proof reading stage, that this title contained a dangling modifier and we substituted the title that has amazed you. We apologise for any amazement caused by the title. We had hoped people would be amazed at the unsuitability of the Diskhaler as a delivery system for elderly people to use and wonder that this was not considered by NICE. Perhaps a better title would have been: 'Zanamivir, NICE idea but Relenza fails to deliver.' We did not wish to suggest that Turbohaler was our prefered inhaler device, we used it as a control. It was chosed as it is the most widely used of the dry powder devices in the UK. We agree that when assessing the suitability of an inhaler delivery system the resistance to flow through the device should be considered.. Turbohaler has a high resistance to flow and we have published work, (quoted by Mr Bell) suggesting that elderly people may not be able to generate sufficient inspiratory flow to use that device. We have also published randomised trials compairing Turbohaler to other devices including the dry powder inhaler Clickhaler. This latter device proved just as easy for elderly people to use as the Turbohaler and it has the advantage of requiring a lower inspiratory flow rate to deliver the drug to the lungs than the Turbohaler. We declare that we have no competing interests |
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Lindsey Dow, Consultant Senior Lecturer in Care of the Elderly and General Internal Medicine Bristol University and North Bristol NHS Trust
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Newer inhaler devices infrequently used in older people in the community Dow L1, Fowler L1, Lamb H1 1Care of the Elderly, Division of Medicine, Bristol University Correspondence to: Dr Dow Care of the Elderly Frenchay Hospital Bristol BS16 1LE Email: Lindsey.Dow@bristol.ac.uk EDITOR-Diggory et al report on inhaler technique of inhaler-naive older adults using two dry powder devices, the diskhaler and turbohaler.1 Greater competence was found with the turbohaler and this device was also shown to be superior in an earlier study when comparison was made with the pressurised metered-dose inhaler (pMDI) attached to a spacer device.2 Satisfactory inhaler technique is influenced by cognitive function and since more recently developed devices require less steps prior to lung inhalation and inspiration and actuation may not require simultaneous co- ordination, theoretical advantages exist for older patients with cognitive impairment. We have investigated use of different inhaler devices and technique in community dwelling elderly. A stratified random sampling method was used to select 6000 adults aged 65 years and over from 21 general practices in North Bristol. Each subject was sent a respiratory questionnaire in 1997 and 4792 (80%) responded with 662 indicating use of inhalers.3 We then randomly selected 556 from those reporting any therapy for airways disease (n=708) for investigation in 1998-2000. The type of device(s) was recorded and technique assessed using a standardised approach.4 Altogether, 244/556 participated (mean age 74 range 65-96), 185 declined, 81 had died since questionnaire completion, 38 had moved and 8 were too unwell for study. Of those seen, 221 were currently using an inhaler. The pMDI with a spacer (pMDI-S) was used by 98(44%), the pMDI without a spacer by 81(36%), breath actuated device (BAD) by 8(4%), dry powder devices (DPD) by 8(4%) and combinations of above including nebulisers by 26(12%). Altogether only 5 subjects were using a turbohaler to deliver some or all of their inhaled therapy. Unsatisfactory technique was found in 53% using pMDI alone, 32% using pMDI-S alone, 50% using BAD alone, 38% using DPD alone and 46% in those using combinations. Failure to shake the device, poor co-ordination of actuation and inhalation and absence of breath holding were the most common errors. Despite favourable findings supporting use of newer devices in other studies, they were rarely used in this Bristol population of older people- why? Factors influencing choice of inhaler device are unclear but cost is likely to be a major issue with newer devices. Furthermore from the perspective of the prescriber, we believe there is insufficient comparative data on the relation between optimising inhaler technique through use of different inhaler devices and disease control and health care utilisation over time. References 1. Diggory P, Fernandez C, Humphrey A, Jones V, Murphy M. Comparison of elderly people’s technique in using two dry powder inhalers to deliver zanamivir:randomised controlled trial. BMJ 2001; 322:577-579. 2. Jones VA, Fernanadez C, Diggory P. A comparison of large volume spacer, breath-activated and dry powder inhalers in older people. Age Ageing 1999;28:481-484. 3. Dow L, Phelps L, Fowler L, Waters K, Coggon D, Holgate ST. Respiratory symptoms in older people and use of domestic gas appliances. Thorax 1999;54:1104-1106. 4. National Asthma and Respiratory Training Centre. (1998 8th edition) Guidelines for Inhaler Technique, Diploma in Asthma Care, Stratford Repro, Stratford on Avon. Acknowledgements This study has been funded by the NHS Research & Development Programme in Asthma Care Competing interests: LD, LF, HL have received educational grants from 3M, MSD, Boehringer Ingelheim, and Glaxo-Wellcome supporting attendance at respiratory meetings. |
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Lars Borgström, Senior Scientific Advisor AstraZeneca R&D, Lund, Sweden
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I have just read with interest the article by Diggory et al., 1 and agree that inhaled medication can in some patient groups be complicated to use and would like to underline the neccessity of training the patients as was also done in the study performed. With some interest I also read the comment by Mr Jonathan Bell from Clement Clarke International Inc. a company that, by the way, is heavily marketing an inhalation trainer/flow meter to sort out patients to use a specific device. A device where the information regarding Turbuhaler was recently judged incorrect and misleading by NBL (Case 543/00. Nämnden för Bedöming av Läkemedelsinformation, NBL, Box 17608, SE-118 92 Stockholm, Sweden). NBL is the Swedish opposite to UK ABPI. The observed difference in lung deposition from Turbuhaler at the two different inhalation flows is probably a class phenomenon as when other dry powder inhalers have been investigated at a low and a typical inhalation flow a similar difference in lung deposition was observed 2. Mr Bell argues that three times more effort is needed to generate the same inhalation flow through Turbuhaler as through Diskhaler to achieve the same inhalation flow. This is probably true but is beside the point as dry powder inhalers should, as Mr Bell should be well aware of, not be compared at the same inhalation flow but at the same inhalation effort. A 60 L/min inhalation through Turbuhaler requires a similar effort as an about 120 L/min inhalation through Diskhaler. The important parameter to study is of course the clinical outcome and in that arena it has been shown, both in children and adults, that Turbuhaler will give very similar effect outcomes when used at 30 and 60 L/min 3 4. Similar data exists for Diskus in children 5. Lars Borgström, Ph.D.
1. Diggory P, Fernandez C, Humphrey A, Jones V, Murphy M. Comparison of elderly people´s technique in using two dry powder inhalers to deliver zanamivir: randomised controlled trial. Br Med J 2001;322:1-4. 2. Olsson B, Borgström L, Asking L, Bondesson E. Effect of inlet throat on the correlation between measured fine particle dose and lung deposition. In: Dalby R, Byron P, Farr S, editors. Respiratory Drug Delivery V. Buffalo Grove: Interpharm Press Inc, 1996:273-281. 3. Pedersen S, Hansen O, Fuglsang G. Influence of inspiratory flow rate upon the effect of a Turbuhaler. Arch Dis Child 1990;65:308-310. 4. Engel T, Scharling B, Skovstedt B, Heining J. Effects, side effects and plasma concentrations of terbutaline in adult asthmatics after inhaling from a dry powder inhaler device at different inhalation flows and volumes. Br J Clin Pharmacol 1992;33:439-444. 5. Nielsen K, Auk I, Bojsen K, Ifversen M, Klug B, Bisgaard H. Clinical effect of DiskusTM dry-powder inhaler at low and high inspiratory flow- rates in asthmatic children. Eur Respir J 1998;11:350-354. |
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Dominique Vanpee, geriatric physician Université Catholique de Louvain, Mont-Godinne Hospital
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We have read with great interest the study by Diggory et al concerning the use of dry powder inhaler to deliver zanamivir in elderly patients(1). We agree fully with the author on the fact that most elderly patients have a lot of difficulties with inhaler technique devices. In chronic obstructive pulmonary disease also, inefficient inhaler technique is a common problem resulting in poor drug delivery and decreased disease control. Chronic obstructive pulmonary disease and asthma have a high prevalence in elderly people and are responsible for a great deal of morbidity and significant mortality(2). In our clinical experience, to avoid inadequate therapy due to difficulties with inhaler technique, in elderly without significant cognitive impairement, we use more and more dry powder inhaler especially turbohaler and aerolizer instead of metered dose inhaler. Dry powder inhalers are easy to use because no co-ordination between actuation and inhalation is required by the patient. With this technique, the majority of the obstacles can be overcome if the patient is properly instructed, cognitively intact and motivated. This has been clearly shown in different studies(3-5). Nevertheless, it remains very important with these devices to appropriately reinforce the handling by repeated training. Therefore, we are particularly interested by the results of this study and ask the authors in what extent these observations are transposable for elderly in other conditions requiring this device. Dominique Vanpee, Christian Swine,
1.Diggory P, Fernandez C, Humphrey A, Jones V, Murphy M. comparison of elderly people's technique in using two dry powder inhalers to deliver zanamivir: randomised controlled trial. BMJ. 2001, 10;322:577. 2.Dow L, Coggon D, Osmond C, Holgate ST A population survey of respiratory symptoms in the elderly. Eur Respir J. 1991 ;4:267-72. 3.Jones V, Fernandez C, Diggory P. A comparison of large volume spacer, breath-activated and dry powder inhalers in older people.Age Ageing. 1999 ;28:481-4. 4.Harvey J, Williams JG Randomised cross-over comparison of five inhaler systems for bronchodilator therapy. Br J Clin Pract. 1992;46:249- 51. 5. Diggory P, Bailey R, Vallon A.Effectiveness of inhaled bronchodilator delivery systems for elderly patients.Age Ageing. 1991;20:379-82 |
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Jonathan Bell, Project Manager, Device Development Clement Clarke International, Harlow
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Any comment from Professor Borgstrom relevant to inhaler performance and training should be welcomed, as for the past year our contact with this global pharmaceutical company (AstraZeneca) has been through their lawyers threatening litigation over our inhaler assessment and training product, In-Check DIAL (although the threatened legal action has not been pursued). Our training product was conceived in 1996, to both help improve inhaler use in existing patients, and identify unsuitable devices - based on objective measurements and available data. We are surprised at Professor Borgstrom's statement that the product is heavily marketed - our total worldwide promotional spend since launch in October 1998 is likely to be only a fraction of one week's advertising spend on Turbohaler. To have AstraZeneca's Senior Scientific Advisor comment in such a negative way about the product is in stark contrast to the response from other pharmaceutical companies involved in pulmonary drug delivery. We believe that Professor Borgstrom is mistaken in regarding the interest in an inhaler trainer as a function of our marketing efforts - perhaps the desire by numerous health professionals to teach better inhaler technique to patients has nothing to do with it ? He fails to mention that the Swedish authority (NBL) ruling concerning information relating to Turbohaler only found fault with the way this information was presented - not the original research that supported the flow-dependency of the Turbohaler device itself (refs 1,2,3,4,5). Professor Borgstrom must also acknowledge that the ruling may have been very different if AstraZeneca had supplied the NBL with the full documentation that accompanies every "In-Check DIAL" sold in Sweden - documentation that included detailed operator instructions in Swedish. The product has already been found useful, and relevant to clinical practice by Diggory and other researchers (ref 6,7,8,9,10). Independent scientific advisors and our lawyers and have reassured us that our product is based on sound, documented scientific research, and through an obligation to physicians and patients, there is good reason not to concede to AstraZeneca's demands to change the representation that "Optimum Inspiratory Flow" for the Turbohaler product is other than between 60 and 90 l/min. Documentation of the principle of this product is on-line, at www.inspiratory.com. We are in agreement that inhaler performance ought to be assessed at the same inhalation effort, but Professor Borgstrom must acknowledge that patients are not an homogenous group, and a range of efforts are to be expected. If a delivery device (such as Turbohaler) is not consistent in the amount of drug both released, and delivered to the lungs, then it is right to highlight the importance of knowing what inspiratory flow is actually achieved by the patient - because the link between the quality and quantity of aerosol release, and the amount delivered, has already been documented against the speed of air through the inhaler. Without this information, the dose the patient receives may be between 50% and 200% of that expected. The comment from the Drug and Therapeutics Bulletin last year (ref 11) summarises issues that run through relevant reviews and Guidelines (refs 12, 13 ,14) : "An ideal inhaler device should deliver a predetermined dose of drug to the lungs, in an easy-to-use, reproducible and cost-effective manner, with minimal deposition of drug in other sites". Finally, we would question whether the Senior Scientific Advisor for AstraZeneca can explain the following (given his comments about similar clinical effects being seen when the Turbohaler is used at 30 or 60 l/min) - AstraZeneca have found time to comment on the BMJ article, but appear to be too busy to answer, or acknowledge the issues raised in correspondence from our lawyers in May and July 2000:- 1. Why has AstraZeneca promoted good inhaler technique using a Turbohaler Usage Trainer (pictured below), where the patient is encouraged to achieve a minimum inspiratory flow of 60 l/min ? (Photograph 1)
(Photograph 2)
[Only when the flow through the Turbohaler reaches 60 l/min and above, do all three green lights on the trainer illuminate] 2. If the clinical effect is equal at 30 or 60 l/min, but the drug deposition at 60 l/min is twice that at 30 l/min (ref 15), then should AstraZeneca actually recommend people NOT to inhale at 60 l/min ? Surely the higher flow rate would result in overdosing - a waste of drug, at an increased cost to the Health Service, and of no benefit to the patient ? 3. How can AstraZeneca complain that our representation of the Turbohaler device was "incorrect and misleading" through use of the words "optimal inspiratory flow", when their own literature (e.g. Summary of Product Characteristics - Sweden ) states "Note - it is important to instruct the patient to breathe in forcefully and deeply to ensure that an optimal dose is obtained" ? Their data sheet can be found at:- http://www3.mpa.se/spc/SPC.O-Z/Oxis_Turbuhaler_4.5_ugdos.pdf As the Turbohaler delivery system is used for formoterol, budesonide and terbutaline, then I would presume that all literature would carry this information ? Professor Borgstrom's comments add little to the issues raised by Diggory's research, and have served to further the misinformation about a training product that was designed to improve the way patients use the increasingly wide variety of available inhalers - whether they be from AstraZeneca, Celltech Medeva, GlaxoSmithKline, Norton Healthcare, Novartis, 3M Healthcare or whoever. Jonathan Bell Project Manager - Device Development Clement Clarke International Ltd. References:- 1. Borgstrom L, Bondesson E, Moren F, Trofast E, Newman SP. Lung deposition of Budesonide inhaled via Turbohaler: a comparison with Terbutaline sulphate in normal subjects Eur Respir J 1994; 7:69-73 2. Hill LS, Slater AL . A comparison of the performance of two modern multidose dry powder asthma inhalers. Resp Med 1998; 92:105-110 3. Malton A, Sumby BS, Dandiker Y. A comparison of in-vitro drug delivery from salbutamol Diskus (TM) and terbutaline Turbohaler (TM) inhalers. J. Pharm. Med 1996; 6:35-48 4. Dolovich MB, Vanzieleghem M, Hidinger K-G, Newhouse M. Influence of inspiratory flow rate (VI) on the response to terbutaline (T) via the Turbuhaler(tm). NER Allergy Proc, 1988; 9: 380 5. Persson G, Gruvstad E, Stahl E. A new multiple dose powder inhaler, (Turbuhaler), compared with a pressurised inhaler in a study of terbutaline in asthmatics. Eur Respir J, 1988; 1: 681 -684 6. Nsour W, Alldred A, Corrado OJC, Chrystyn H Measurement of peak inspiratory flow (PIFR) may be useful before prescribing a dry powder inhaler. Eur Respir J 1999;30 339s P121 7. Job van der Palen Use of Peak Inspiratory Flow for inhaler selection Eur Respir J 1999;30 339s P2282 8. Peacock K, Diggory P, Jones V, Treml J Ability of elderly patients to generate adequate inspiratory flow rates to use Turbohaler, Clickhaler, Autohaler or EasiBreathe inhalers (Presentation at the British Geriatrics Society Spring Meeting 2000) 9. Emeryk A, Bartkowiak-Emeryk M, Kokot M, Czerwinska-Pawluk I Assessment of inspiratory flow rate (PIFR) is advisable before choosing dry powder inhaler for treatment of asthmatic children Eur Respir J 2000;16 s 31 3807 (1s-658s) 10. Brajnik VA, Sakharova GM, Makretskaja ON, Belevsky AS, Chuchalin AG The role of inspiratory flow measurement in choosing suitable inhaler device in asthmatic patients children Eur Respir J 2000;16 s 31 2206 (1s -658s) 11. Inhaler Devices for Asthma, Drug and Therapeutics Bulletin Vol 38, No. 2, February 2000 12. The British Guidelines on Asthma Management - British Thoracic Society, British Paediatric Association, Royal College of Physicians of London et al. British Guidelines for Asthma Management. Thorax 1997;52: S3/4 13. Guidance on the use of inhaler systems (devices) in children under the age of 5 years with chronic asthma (Technology Appraisal Guidance No. 10, Nice August 2000) 14. Note for Guidance on Dry Powder Inhalers (CPMP), European Agency for the Evaluation of Medicinal Products, December 1998 15. Borgstrom L. J Aerosol Med 1994;7(suppl 1) S49-s53 Competing Interests: Full-time Project Manager, Clement Clarke International |
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