Guidance on the use of inhaler systems (devices) in children under the age of 5 years with chronic asthma

# Guidance
For children under the age of 5 years with chronic stable asthma both corticosteroids and bronchodilator therapy should be routinely delivered by pressurised metered dose inhaler (pMDI) and spacer system, with a facemask where necessary.
Where this combination is not clinically effective for the child and depending on the child's condition, nebulised therapy may be considered and in the case of children aged 3 to 5 years, a dry powder inhaler (DPI) may also be considered.
Choice of device to be made within the pMDI and spacer range should be primarily governed by specific individual need and the likelihood of good compliance. Once these factors have been taken into account, choice should be made on the basis of cost minimisation.# Clinical Need and Practice
Asthma is a common disease that produces symptoms of wheezing and breathlessness. It affects the lower airways and results in narrowing (bronchoconstriction) of the airways with consequent reduction in the flow of gases between the airways and lung alveoli. It can be triggered by a variety of environmental factors such as infection, allergy, airborne chemicals and also exercise. There are a number of patterns of lower airways disease in early childhood that results in two predominant clinical patterns (acute wheezy episodes and recurrent day to day symptoms) that may occur separately or together in the child.
The overall prevalence of asthma in England and Wales is around 8% to 10% although not all cases are currently being treated. In all children under the age of 5 years about 9% of boys and 6% of girls are prescribed inhalers. There is a strong genetic component in the aetiology of this disease. There is also wide geographical variation in prevalence, with asthma being more common in, for example, urban rather than rural communities. It has a wide range of severity, is the cause of considerable morbidity and a rare cause of death.
The primary objective of asthma treatment is to achieve optimal control of the disease by reducing exacerbations, increasing lung function and limiting symptoms in order to maximise the quality of life of the child. This is currently best achieved by delivering both symptom relieving (bronchodilators  including 2 agonists and anticholinergics) and preventive anti-inflammatory drugs (typically corticosteroids) by inhalation. In the UK, asthma treatment is strongly influenced by the 1997 guidelines of the British Thoracic Society (BTS), which promote step-wise management of increasingly severe asthma. The 1997 BTS guidelines are mainly based on a consensus of expert opinion.
The estimated annual drug cost for asthma to the NHS in England and Wales in all age groups is approximately 115 million. In children under the age of 5 years this cost is about 8 million.# The Technology
It is important to ensure that an inhaler device delivers the drugs to the airways consistently and in the appropriate quantity. There are a variety of inhaler devices that can be used in the management of asthma: hand held inhalers i.e. pressurised metered dose inhalers (pMDIs) (which can be breath activated or manual) and dry-powder inhalation systems (DPIs) and nebulisers. All the metered dose inhaler systems require co-ordination of activation and inhalation and may be difficult to use, particularly for younger children. For this reason a pMDI should be combined with a spacer device in young children. The purpose of the spacer device is to act as an intermediary chamber into which the pMDI can discharge the drug allowing the child to inhale over several breaths.
The inhalation devices have different mechanical characteristics which, combined with child and carer factors, leads to variation in both the quantity of drug delivered by the device and the amount actually deposited in the lung. Using the appropriate inhalation device is important to ensure reproducibility and consistency of drug dosing, as well as compliance for which child and carer acceptability and education regarding device usage may also be major factors.
The 1997 BTS Guidelines recommend the following device choices for children of under 5 years of age:
Age Group
st Choice Device
nd Choice Device
rd Choice Device
Breath-actuated
Dry-powder
-2 years inclusive
MDI + spacer + face mask
MDI + spacer
Nebuliser (rarely needed)
Avoid
Avoid
-5 years inclusive
MDI + spacer
MDI + spacer + face mask
Nebuliser (rarely needed)
Not proven
Possible use for 2-agonist but not recommended for corticosteroids
Interpretation of the evidence base for effectiveness of inhaler devices is influenced by a number of potential factors  the drug being delivered by the device, the severity of asthma, whether the condition is acute or chronic and the ability of the child/carer to effectively use the device. Moreover it is not possible to directly extrapolate to children under the age of five years, data collected in older children and adults, as the young child's anatomy and physiology may substantially alter the amount of drug delivered.# Evidence
Delivery of corticosteriods by a hand held device
    The evidence base for pressurised metered dose inhalers (pMDIs) plus spacer versus dry-powder inhalation systems (DPI) for the delivery of corticosteriods in children with chronic asthma is relatively small and of poor quality. Two randomised controlled trials were identified, which recruited children of 5 years or under. These trials involved a total of 140 children, although the majority of these recruited children of 5 years or older. One of these trials was inadequately powered and compared a pMDI alone (not recommended by current BTS guidelines) versus DPI. The second and largest trial demonstrated no difference in steroid delivery via a pMDI plus spacer compared to DPI (at half MDI dosage).
Delivery of 
    agonists by a hand held device  
    The evidence base for pressurised metered dose inhalers (pMDIs) alone or pMDI plus spacer compared to dry-powder inhalation systems (DPI) in children with chronic asthma is poor. Four randomised controlled trials were identified that recruited children of 5 years or less. These trials involved a total of 278 children, some of which were aged 5 years or more. The remaining three studies demonstrated no difference when comparing 2 agonist delivery via pMDI plus spacer with 2 agonist delivery by DPI.
Delivery of 
     agonists or anticholinergics by nebuliser  
    The evidence for nebulised bronchodilators compared with bronchodilator delivery via hand held device in children with chronic asthma is also poor. Three randomised controlled trials which recruited children aged 5 years or less, were identified. These trials were small and involved a total of 51 children, although many of the children were aged 5 years or older. No differences were found between nebulisation, pMDIs or dry powder devices. These trials are likely to be of insufficient size to detect small differences between devices.
Cost Effectiveness  
    There is currently a wide range in the cost of drug/inhaler combinations. No cost effectiveness studies were identified that make direct comparison between asthma devices in children under the age of 5 years with chronic asthma.
The documentation and opinion available to the Appraisal Committee is set out in Appendix B.# Implications for the NHS
Where the 1997 BTS guidelines are currently being applied in practice, the guidance is unlikely to result in substantial change in NHS costs. The impact of referral patterns is difficult to predict. It is likely however to strengthen and improve the quality of primary care based asthma therapy, thereby reducing the need for admission or outpatient referral.# Further research
At present there is insufficient evidence regarding the most clinically and cost effective spacer (e.g. small or large volume). This is reflected in the current lack of standardisation and variations in the usage of these devices. Further research in this area should be carried out in relation to optimising the reproducibility, consistency and acceptability of these delivery systems as well as their overall clinical and cost effectiveness.
Well conducted community based trials in the management of asthma in young children and studies to investigate factors determining compliance (including health education and the acceptability of devices) in this group of children would enhance the future evidence base.# Review of Guidance
Information on the review of the guidance on this technology is available on the NICE website
Andrew DillonChief ExecutiveAugust 2000# Appendix B: Sources of Evidence
i) The following documentation and opinion was made available to the Committee:
a) Assessment Report The effectiveness of inhaler devices for young children with asthma; Prepared by Payne N & Beard S, Trent Institute for Health Services Research, School of Health & Related Research, University of Sheffield;Wright, Brocklebank,D & Ram F, Bradford Hospitals NHS Trust; Taylor RS, National Institute for Clinical Excellence. March 2000.
b) Manufacturer/Sponsor submissions:
i. AstraZeneca
ii. Boehringer Inglheim Ltd.
iii. Aventis Pharma (formerly Rhone-Poulenc Rorer)
iv. Boehringer Inglheim Ltd.
v. Glaxo Wellcome
vi. 3M Health Care Ltd.
vii. Norton Healthcare
viii.Yamanouchi Pharma Ltd.
c) Professional/specialist group, patient/carer group and trade association submissions;
i. Association of British Health-Care Industries
ii. British Medical Association
iii. British Thoracic Society
iv. National Asthma Campaign
v. Royal College of Nursing
vi. Royal College of Paediatrics & Child Health
vii. Royal College of Physicians
ii) The following experts were invited to make submissions to the Committee:
a) Dr Andrew Bush, Reader in Paediatric Respirology & Honorary Consultant Paediatric Chest Physician, Royal Brompton Hospital, London.
b) Dr C O'Callaghan, Senior Lecturer & Consultant Paediatrician,University of Leicester & Leicester Royal Infirmary Children's Hospital.# Appendix C: Guidance on inhalers for childhood asthma  patient information
'Understanding NICE Guidance'
    , a summary of this guidance for patients and carers can be found on our website.# Changes after publication
March 2012: minor maintenance# About this guidance
NICE technology appraisal guidance is about the use of new and existing medicines and treatments in the NHS in England and Wales.
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This guidance represents the views of NICE and was arrived at after careful consideration of the evidence available. Healthcare professionals are expected to take it fully into account when exercising their clinical judgement. However, the guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer.
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 National Institute for Health and Clinical Excellence 2000. All rights reserved. NICE copyright material can be downloaded for private research and study, and may be reproduced for educational and not-for-profit purposes. No reproduction by or for commercial organisations, or for commercial purposes, is allowed without the written permission of NICE.
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