Inhaler devices for the treatment of asthma and chronic obstructive airways disease (COPD). (Effectiveness Bulletin).

The research evidence on the effectiveness of inhaler devices for the treatment of asthma and chronic obstructive pulmonary disease published in a recent issue of Effective Health Care is reviewed.

This article summarises the research evidence presented in a recent issue of Effective Health Care on inhaler devices for the treatment of asthma and chronic obstructive airways disease (COPD). (1)

BACKGROUND

Inhaled therapy delivering bronchodilator and corticosteroid drugs in various doses has become accepted as the mainstay of treatment for patients with asthma and chronic COPD. (2) It allows low doses of medication to be delivered directly to the site of action in the airways, significantly reducing systemic side effects compared with oral therapy. The aim of inhaled therapy is to reverse and prevent airway inflammation and constriction and minimise symptoms. The two main categories of inhaled drugs are bronchodilators and corticosteroids. Bronchodilators (short and long acting [[beta].sub.2] agonists and antimuscarinic drugs) relieve symptoms of bronchoconstriction. Corticosteroids reduce airways inflammation to prevent symptoms of asthma.

A number of different inhalation devices are available. The pressurised metered dose inhaler (pMDI) is the most commonly used and cheapest device, which may also be used in conjunction with a spacer device. Newer chlorofluorocarbon (CFC)-free inhaler devices using hydrofluoroalkanes (HFAs) have also been developed. The drug is dissolved or suspended in the propellant under pressure. When activated, a valve system releases a metered volume of drug and propellant. Spacer chambers can be attached to pMDIs to make them easier to use.

Other devices include breath actuated pMDIs such as Autohaler and Easibreathe. They enable the patient to prime the inhaler which is then only actuated when the patient takes a breath, avoiding the need to coordinate actuation with breathing. Dry powder inhalers (DPI) such as Turbohaler, Diskhaler, Accuhaler and Clickhaler are also activated by inspiration by the patient. The powdered drug is dispersed into particles by the inspiration.

Nebulisers use oxygen, compressed air, or ultrasonic power to break up solutions or suspensions of medication into droplets for inhalation. The aerosol is administered by a mask or mouthpiece. However, nebulisers are more expensive than pMDIs, require a power source, and need regular maintenance.

There is a confusing array of inhaler devices available for the treatment of asthma and COPD. The competing claims of pharmaceutical companies make it difficult for prescribers to choose the best device for different patients. This article summarises the current research evidence on the clinical and cost effectiveness of these pMDIs (with or without a spacer device) compared with other hand held inhaler devices. It updates the evidence from a number of systematic reviews carried out by the Cochrane Airways Group and funded by the NHS Health Technology Assessment Programme. (4) The original reviews were used as supporting evidence for two technology appraisal guidance reports for the National Institute for Clinical Excellence (5 6) and for forthcoming guidance from the British Thoracic Society. Details of the additional randomised controlled trials (RCTs) included in the update can be found in table 1.

RANGE AND COSTS OF DRUGS AND DEVICES

The annual cost to the NHS for asthma drugs is over [pounds sterling]500 million. (7) A large number of inhaler devices and drug/device combinations are commercially available. There are considerable differences in the costs of the same drug using different inhaler devices and of the drugs used in specific devices. (8) The use of a specific inhaler device may limit prescribing choice to more expensive proprietary drugs. In addition, some inhaler and drug combinations are limited by commercial availability.

Clinical guidelines on the use of inhalers for asthma and COPD have been published from a number of sources. (2 3 9 10) However, the recommendations for inhaler devices from these guidelines are either absent, vague, or inconsistent. Evidence based guidelines are currently being developed by the British Thoracic Society.

EFFECTIVENESS OF HAND HELD INHALER DEVICES FOR ASTHMA

Delivery of corticosteroids in stable asthma

Three studies in children comparing different devices failed to show significant differences in pulmonary function between the devices. (11-13)

Three further studies in children were identified, (14-16) but the heterogeneity of the original studies precluded any pooling of results. This remains the case with the addition of the new studies. Farmer et al (14) studied 229 children with asthma aged 7-12 years and compared a CFC and HFA Easibreathe (breath actuated inhaler) delivering beclomethasone dipropionate. No differences were found in diary card peak flow expiratory rate (PEFR), forced expiratory volume in 1 second ([FEV.sub.1]), symptoms scores, adverse events, and serum cortisol levels from 19% of the population. Pearlman et al (15) studied 473 children aged 6-13 years with asthma. Triamcinolone (not licensed in the UK) was given at 150, 300 and 600 [micro]g daily by CFC and HFA pMDI devices. No clinically significant differences were found in [beta] agonist use, forced expiratory mid flow ([FEF.sub.25-75%]), PEFR, night-time wakening, symptom scores, and adverse events. Rufin et al (16) studied 127 5-15 year old children with asthma. Beclometha sone dipropionate was delivered 1000 [micro]g daily via a pMDI plus large volume spacer versus an Autohaler (breath actuated inhaler). No clinically significant differences were found in [FEV.sub.1] and expiratory mid flow rates.

Twenty one studies in adults found no significant difference in measures of pulmonary function, symptom scores, exacerbation rates, and adverse effects such as hoarse voice, oral thrush, and effects on the hypothalamic-adrenal axis (serum cortisol) between a pMDI and a dry powder inhaler, hydrofluoroalkane pMDI, or breath actuated pMDI for the delivery of corticosteroids. (17-38) Figure 1 shows the absolute difference in [FEV.sub.1] between pMDI and dry powder inhaler for the delivery of corticosteroids in stable asthma. (21 22 32 33 35 36 39) Statistically significant differences were found for three outcomes for dry powder inhalers, but these were either within clinically equivalent limits or the differences were not apparent once baseline characteristics were taken into account.

Four further studies have since been identified. (39-42) Juniper and Buist (42) reported asthma related quality of life questionnaire scores from a previous study. (30) No significant differences were found between inhaler devices. In the study by Crompton et al (40) 51 patients with asthma were studied to evaluate the effect on voice changes rather than asthma control between pMDI+Nebuhaler vs Thrbohaler for the delivery of budesonide. Clinical outcomes were also measured but no significant differences were found between the devices. Goldin et al (41) studied 34 asthmatics taking beclomethasone 200 [micro]g daily via a CFC or HFA pMDI. The primary outcome of the study was air trapping as measured by CT imaging. Other clinical outcomes were measured and no significant differences were found. Stradling et al (39) included 204 asthmatics taking beclomethasone at their "usual" dose via pMDI+spacer or Clickhaler. No significant differences were found.

The addition of data from these four studies to the original meta-analysis made no significant change to the results, For the delivery of inhaled steroids in stable asthma in children over 5 years and adults, pMDI (with or without spacer) is as effective as other hand held inhaler devices. There is no evidence to demonstrate differences in drug delivery between non-CFC pMDI and CFC pMDI at equivalent doses.

Delivery of short acting [[beta].sup.2] agonist bronchodilators in chronic asthma

A Cochrane review and meta-analysis of 84 RCTs…