The Pharmaceutical Journal Vol 264 No 7091 p546-556
April 8, 2000 Special feature

Pharmaceutical care

(8) Asthma

By Anne Boyter, MSc, MRPharmS, Janice Currie, BSc, MRPharmS, Kenneth Dagg, MB ChB, MRCP, Felice Groundland, BSc, MRPharmS, and Steve Hudson, MPharm, FRPharmS

Asthma is a disease characterised by variable airways obstruction, either spontaneously or following bronchodilator therapy, and bronchial hyper-responsiveness (BHR).¹ It is a common disease, affecting 20 per cent of children aged eight to 13 and 7 per cent of adults in the United Kingdom. Despite the introduction of widely accepted evidence-based guidelines, asthma remains under-diagnosed and under-treated in many patients.² The incidence of asthma is rising and over the past 20 years a dramatic increase in rates of hospital admissions and general practitioner consultations for both adults and children with asthma has been seen.³ Air pollution, allergen exposure, tobacco smoke and diet have all been implicated in this increase but evidence in support of these factors is conflicting.
Patients with asthma are a target for improved pharmaceutical care. Disease-specific primary care clinics for common chronic diseases, such as asthma, provide pharmaceutical care through improved multidisciplinary collaboration. There is evidence that pharmacists can contribute to better clinical and economic outcome within multidisciplinary care.⁴ Community and hospital pharmacists have the opportunity to co-operate with each other and the multidisciplinary team, and, in doing so, to contribute towards improving asthma care and preventing hospitalisations.
Among patients dying from acute exacerbations of asthma, avoidable factors are present in more than 80 per cent of cases.⁵ An increase in asthma deaths soon after the introduction of inhaled bronchodilators in the 1960s pointed to the potential for misuse of these agents. A further period of increased mortality in the 1970s pointed to under-treatment of the chronic condition and delays in emergency treatment due to the patient's tendency to underestimate the severity of an attack.³ A recent confidential inquiry into asthma deaths in Scotland (SCIAD) reports that during the period January, 1994, to December, 1996, the number of deaths assessed as being caused by asthma halved compared with the number found by a similar study carried out in 1979.⁶ This new study involved a confidential review of all deaths with a principal diagnosis of asthma, resulting in 95 being confirmed as attributable to asthma. The routine management of chronic asthma in these patients was assessed as being satisfactory in only 59 per cent of patients and the acute management of the final attack was unsatisfactory in 30 per cent, suggesting further improvements in asthma management can still be made. Patient factors said to have contributed to sub-optimal management included poor compliance, lack of peak expiratory flow rate (PEFR) monitoring, overuse of reliever medication without adequate anti-inflammatory therapy and psychosocial problems, particularly depression.⁶ The study suggested that further improvements in asthma management would require greater use of PEFR recording, prescription monitoring for underuse of inhaled corticosteroids and overuse of inhaled bronchodilators, and the use of combined preparations (containing bronchodil-ator and corticosteroid) to reduce the abuse of bronchodilators.

Chronic asthma

The initial management of chronic asthma is the use of an "as required" short-acting inhaled b2-agonist.² If a patient is using their bronchodilator inhaler more than once daily, or has nocturnal symptoms more than twice weekly, low-dose inhaled corticosteroids should be added, moving the patient on to step two of the guidelines. Patients who remain symptomatic despite low-dose inhaled corticosteroids, providing that there is evidence of compliance, should either increase the dose of inhaled corticosteroid or add a second-line agent such as a long-acting b2-agonist or leukotriene inhibitor.¹⁴ The fourth step in the guidelines² includes the use of high-dose inhaled corticosteroids, a short-acting b2-agonist when required and sequential trials of a long-acting b2-agonist, a leukotriene receptor antagonist, oral theophylline, an inhaled anticholinergic agent, a mast cell stabiliser or an oral b2-agonist. The final step of the guidelines is the introduction of a regular oral corticosteroid. At any time when an increase in therapy is considered, an evaluation of the patient's inhaler technique and compliance with therapy should be undertaken.
It is emphasised throughout the guidelines that the treatment of asthmatic patients should be reviewed regularly and, when possible, their therapy should be stepped down to the minimum required for control of their symptoms. In addition, patients should be prescribed a peak flow meter and encouraged to keep diaries to allow them to monitor their response to therapy. It is important to remember that rescue courses of steroids can be added at any step of the guidelines to achieve control, following which treatment can be stepped down to an appropriate level.
The management of asthma in both adults and children follows the same guidelines, although the use of inhaled steroids in children who are still growing should be limited unless the child is under the care of a paediatrician with a special interest in the management of asthma. The management of children under the age of five is similar but includes the use of mast cell stabilisers at step two as an alternative to inhaled corticosteroids and the use of regular oral steroids is not advocated (Table 3). Emphasis is also made that this group of patients should be cared for by a specialist in paediatric respiratory medicine.²

Problem asthma

In severe chronic asthma, where symptoms remain uncontrolled despite maximal oral and inhaler therapy, long-term oral corticosteroids may need to be considered. The risks of long-term oral corticosteroid treatment need to be balanced against the potential benefits of symptom control and reduced hospital admissions. The dose of corticosteroid should be titrated to the lowest necessary to control the symptoms and should be in addition to, rather than a replacement for, inhaled steroids. A single morning dose or alternate day dosing will minimise the disturbance to circadian cortisol secretion.¹⁵ Doses greater than the equivalent of 7.5mg prednisolone each day can lead to an increased risk of steroid-induced osteoporosis. Recent UK consensus guidelines give details of the management of this condition.¹⁶ Once control is established, the gradual withdrawal of oral corticosteroid should be considered as part of the step down of therapy.¹⁵
"Brittle asthma" is thought to affect 0.05 per cent of the asthmatic population.¹⁷ It is characterised by a wide diurnal variation in the PEFR and can lead to frequent severe asthma attacks, often with a rapid onset, despite maximal treatment. These patients may exhibit a degree of steroid resistance. A proportion of brittle asthmatics may experience an improvement in symptoms and PEFR variability if a subcutaneous infusion of terbutaline is added to their therapy.¹⁷ The effect appears to be in addition to that derived from inhaled b-agonists. Side effects, such as muscle cramps, are common and the lowest effective dose (3-12mg/day) should be used. This use of terbutaline is currently unlicensed and the treatment is only suitable for well motivated patients capable of learning the techniques involved.

Acute exacerbations of asthma

Uncontrolled asthma may easily be managed in the community by GPs and includes the use of nebulised b2-agonists, oral corticosteroids and a step up in the patient's normal treatment. In contrast, the management of acute severe asthma requires prompt referral to hospital. Immediate management includes the administration of high flow oxygen, provision of nebulised b2-agonists and commencement of oral or intravenous corticosteroids² (Tables 4 and 5). If a patient has any life-threatening features, nebulised anticholinergics and intravenous theophylline, terbutaline or salbutamol should be added to the above. Subsequent management is tailored to the individual patient's symptoms and response to treatment. Referral to intensive care should be considered when hypoxia persists (despite high flow oxygen), hypercapnia develops, PEFR continues to fall, or the patient becomes exhausted, confused or suffers a respiratory arrest. Blood gas analysis should be performed in patients with an oxygen saturation of less than 92 per cent or if any life-threatening features are present. Oxygen saturation should continue to be monitored regularly.

Table 4: Immediate management of acute asthma
Assessment*	Treatment
Uncontrolled asthma	May be managed at home Nebulised b-agonist Oral corticosteroid - prednisolone 30-60mg daily Step up normal treatment
Acute severe asthma	Prompt referral to hospital Oxygen 40-60 per cent Nebulised b-agonist Oral corticosteroid - prednisolone 30-60mg daily or intravenous hydrocortisone 200mg
Life-threatening asthma	Immediate admission to hospital Oral corticosteroid - prednisolone 30-60mg daily or intravenous hydrocortisone 200mg Nebulised b-agonists and ipratropium bromide Intravenous aminophylline, salbutamol or terbutaline
* defined by BTS guidelines

Table 5: Symptoms of severe and life-threatening asthma
Patient	Severe	Life-threatening
Adults	PEFR <50 per cent of predicted or best Unable to talk in sentences Respiration >25 breaths per minute Pulse >110 beats per minute Oxygen saturation <92 per cent Mild hypoxaemia PaO2 >8.0 is common in acute severe asthma. PaCO2 often reduced	PEFR <33 per cent of predicted or best Silent chest, cyanosis or poor respiratory effort Bradycardia or hypotension Exhaustion, confusion or coma Normal or high PaCO2 and PaO2 <8kPa suggests a severe or life-threatening attack
Children aged five to 15 years	Unable to talk Unable to eat Respiration >40 breaths per minute Pulse>120 beats per minute PEFR <50 per cent of predicted or best	PEFR <33 per cent of predicted or best Silent chest, cyanosis or poor respiratory effort Fatigue or exhaustion Agitation or reduction in level of consciousness Arterial blood gases are rarely helpful
Children less than five years old	Unable to talk Unable to eat Respiration>50 breaths per minute Pulse >140 beats per minute Use of accessory muscles of breathing	Silent chest, cyanosis or poor respiratory effort Fatigue or exhaustion Agitation or reduction in level of consciousness

Before discharge, patients should be on their maintenance medication for 24 hours and should have their inhaler technique checked and recorded. PEFR should be greater than 75 per cent of the predicted level or the patient's best and diurnal variation less than 25 per cent.
Follow-up appointments with the patient's GP and the hospital should also be arranged. A plan for the withdrawal of oral corticosteroids and the reintroduction of inhaled corticosteroids should be confirmed before the patient is discharged from hospital.²

Delivery devices

The pressurised metered dose inhaler (pMDI) has traditionally been the device of choice in the delivery of drugs to the lungs. In the past 10-15 years, however, the range of delivery devices available has increased dramatically and pharmacists play an important role in ensuring that the most appropriate device is chosen and supplied, with accurate information on use, storage and cleaning. Common devices available are summarised in Table 6.

Table 6: Summary of inhaler devices
Type	Device	Advantages	Disadvantages
Aerosols	Metered dose inhaler with or without integral spacer	Inexpensive	Difficult for patients to co-ordinate actuation and inspiration. Inefficient drug delivery as a result of poor technique. Some still contain CFCs.* Local side effects because of drug deposition in the mouth
	Breath actuated metered dose inhaler. Small volume spacer available for some devices	No requirement for co-ordination. Portable. Simple to use with minimal effort	Click on actuation may be off-putting. Some devices may be expensive
Dry powder	Turbohaler Clickhaler Accuhaler	Simple to use with minimal inspiratory effort. Indicator of number of doses remaining. Portable. Robust devices	Devices may be expensive. Not refillable
	Diskhaler Spinhaler Rotahaler Aerochamber		Difficult for some patients to load or prime. Requirement to protect the capsules against extremes of temperature and humidity
Nebuliser	Compressor	Simple to use. Can deliver high doses	Over-reliance may be a problem. Inefficient drug delivery. Steroids require a mouthpiece rather than a mask. Expensive
* Some metered dose inhalers are now available as CFC-free inhalers. Patients may experience a change in taste, sound and feel of the inhaler. When changing to a CFC-free inhaler the manufacturer's literature must be consulted for dose equivalence

Patients who are maintained on high-dose inhaled corticosteroids delivered by a pMDI should always use a large volume spacer to increase the lung deposition and decrease the oropharyngeal deposition. It has been shown, using urinary excretion as a surrogate marker, that the use of a large volume spacer increases the respirable dose by up to 100 per cent.^18-20
In studies measuring lung deposition using a gamma camera, the dose deposited in the lungs rose from 39 per cent to 57 per cent when a large volume spacer was used. The use of a spacer also increased deposition to the periphery of the lungs.²¹ These studies used patients with optimised inhaler technique which is rarely achieved in practice.²²
Patients should be encouraged to clean their large volume spacer regularly by washing it in detergent and leaving it to dry naturally.^23,24 This prevents a build-up of electrostatic charge, which reduces the output of the spacer. In children, the use of inhalers may be difficult as they may not be able to comply with the co-ordination required for successful delivery of the drug. Spacers with integral masks have been developed for young children and in many cases oral liquid preparations are used to ensure drug delivery.
Following the Montreal protocol of 1987, which called for a phasing out of all chlorofluorocarbon (CFC) propellants, there has been a move to produce non-CFC containing aerosol inhalers. These are now being introduced, although a temporary exemption has been granted for inhalers and medicinal uses of CFC propellants. The current recommendations are that there is no change in the dose of b2-agonist required on switching to a CFC-free device but that the dose of inhaled corticosteroids may require modification. The manufacturers' recommendations should be consulted before the change is made.
Nebulisers are frequently used in the delivery of drug to the lungs but these devices may not be the most efficient method of delivery of drugs for many patients.²⁵ They are cumbersome to use and the variation in drug delivery in terms of particle size, nebulisation time and drug output (respirable fraction of the nebuliser) may have an effect on the clinical outcome.There is evidence that the use of multiple actuations of a pMDI via a spacer is as effective as a nebuliser in adult asthmatics^26,27 and, therefore, occasional requests to community pharmacists for the purchase of a compressor should be referred to either the patient's GP or hospital consultant for assessment before prescribing. Nebulisers do, however, have a place in the acute management of severe asthma.

Individualised pharmaceutical care

The successful outcome of the treatment of a patient with asthma depends on continued compliance with their inhaled therapy, even when they are feeling well and suffering no overt symptoms of their disease. The importance of regular inhaled corticosteroids should be emphasised. Patient education should stress the differences between reliever, preventer and controller medication. Patients should be informed of measures, including rinsing their mouth or brushing their teeth after using their corticosteroid inhaler, to minimise local side effects.
Pharmacists in both community and hospital practice are well placed to provide continued information and reinforcement of key messages to improve compliance with medication and the outcomes of asthma management plans.

Self-management plans

Asthmatic patients may benefit from the introduction of self-management plans which provide an individually tailored care plan to cope with variations in their asthma severity. These plans, based on PEFR monitoring and symptom recording, allow patients to alter their drug therapy without consulting their GP or hospital consultant.^28-30 They may include the administration of short courses of oral corticosteroids or an increase in the dose of inhaled corticosteroid and are normally instituted when the patient's PEFR falls below 80 per cent of their predicted or best value. It must be stressed, however, that when symptoms continue to deteriorate, patients should seek specialist help.

Monitoring of asthma

Some patients with asthma are encouraged to record twice daily PEFR measurements, clinical symptoms and b2-agonist use in a diary. The early recognition of a deterioration of their PEFR may trigger the commencement of a course of oral corticosteroids, an increase in their inhaled corticosteroid dose or early presentation to their doctor for clinical assessment. Peak flow meters are available on an NHS prescription and, in line with the SCIAD recommendations,⁶ more patients should be encouraged to use this method of monitoring their disease. As with inhaler devices, the technique used in measuring a PEFR should be checked and reinforced.
Patients on either inhaled or oral corticosteroids should be monitored for adverse effects of these drugs. The local adverse effects include oral thrush, hoarseness and dysphonia and, at higher doses, systemic adverse effects include adrenal suppression, effects on bone mineral density and the possibility of potentiating cataracts.
Patients receiving high-dose inhaled corticosteroids (more than 1mg daily of budesonide or equivalent) should be issued with a steroid warning card.³¹ Patients receiving either prolonged oral corticosteroids or intermittent courses of oral corticosteroids should be monitored for hyperglycaemia and loss of diabetic control, gastrointestinal side effects, adrenal suppression, neuropsychiatric side effects and osteoporosis. These patients may also be more susceptible to infection. Patients who receive courses of oral corticosteroids which extend for longer than 21 days should have the dose gradually reduced but for short courses the dose may be stopped abruptly.³¹

Other pharmaceutical care issues

The use of theophylline-containing preparations remains common in the management of asthma despite the high incidence of side effects, the narrow therapeutic index and the emergence of newer treatment options. Theophylline is now classified as a second line controller, add-on therapy to inhaled corticosteroids.^32,33
Theophylline preparations may be used either intravenously in the management of an acute attack, or orally in the management of chronic asthma.² In the case of intravenous therapy, to avoid the possibility of toxicity, patients should only receive a loading dose if they have not previously been maintained on oral theophylline. Caution should be exercised when theophylline is co-administered with antibiotics, antiarrhythmics, some cardiac drugs (including calcium channel blockers) and cimetidine, which may all affect the plasma theophylline level. Changes in smoking habit may also affect theophylline metabolism. Patients should always be maintained on the same brand of theophylline as pharmacokinetic characteristics may vary from one brand to another. It is essential that patients prescribed theophylline avoid the concomitant use of any pharmacy preparations containing theophylline. Preparations available, such as Do-Do Chesteze or Franol preparations, contain 100-120mg of theophylline per tablet and may precipitate theophylline toxicity.
Patients on nebulised drugs should have their compressor serviced regularly (at least once a year) and the chamber and tubing should be replaced when required. The successful delivery of the nebuliser solution depends on the type of chamber used (in terms of respirable volume and particle size).²⁵ Patients on nebulised steroids should be supplied with a mouthpiece rather than a mask to prevent the deposition of steroid on the area of their face around the mouth or eyes. Patients receiving nebulised b-agonists should be monitored for hypokalaemia, particularly if they are maintained on any other drugs which may potentiate this effect. Care is required when ipratropium is administered by nebulisation, particularly when used in combination with salbutamol. There have been reports, although rarely, of nebulised ipratropium causing glaucoma in patients with no previous eye problems. It is therefore important to ensure that the mask is correctly positioned and that the nebulised drug does not reach the eyes. In patients with pre-existing glaucoma, a mouthpiece should be used in preference to a mask.^34,35
Leukotriene receptor antagonists are a novel class of anti-asthma drug recently licensed for use in the UK. Oral LTRAs are available and this may overcome the problem of poor inhaler technique in some patients. Clinical benefits of these agents are often seen within the first 24 hours of therapy although some patients may not respond. The drugs have both anti-inflammatory and bronchodilator actions. Their role in the management of chronic asthma has not yet been established. Further long term randomised studies comparing them with low-dose inhaled corticosteroids at step two, and studies comparing them with long-acting b2-agonists at step three, are currently under way. Their role in the management of acute exacerbations of asthma is also under investigation. A rare but major adverse effect seen in some patients commenced on an LTRA is a Churg-Strauss like syndrome.³⁶ Churg-Strauss syndrome is characterised by a history of asthma, associated with rhinitis, sinusitis, systemic vasculitis and eosinophilia. This complication probably reflects the unmasking of a pre-existing syndrome following a reduction in the oral corticosteroid doses of patients with asthma who are started on LTRAs rather than a true adverse effect.¹⁴ These drugs should not be used as an alternative to corticosteroids in patients with severe asthma dependent on oral corticosteroids.
There have been few studies which document improved outcomes in the management of asthma where either a pharmacist or other health care professional has been involved in the development of self-management plans or in other contributions within pharmaceutical care. A study by Knoell et al,⁴ however, suggested that when pharmacists became involved in asthma care, improvements in symptom control and patient satisfaction were noted. Patients in this study had a consultation with a pharmacist which lasted up to 60 minutes, had an individualised self-management plan intro-duced and had at least one follow-up visit. Other studies have also shown that patients report an increased level of satisfaction with a service which includes a pharmacist and that increased patient education, coupled with a comprehensive asthma health management programme, improves both the process of care and the outcomes of treatment.^37-40

Ms Boyter is lecturer in clinical practice, department of pharmaceutical sciences, University of Strathclyde and principal pharmacist, Glasgow Royal infirmary and Greater Glasgow practice unit; Mrs Currie is Lloyds teacher-practitioner, pharmaceutical care health service unit, University of Strathclyde; Dr Dagg is specialist registrar in respiratory medicine, Glasgow Royal infirmary; Mrs Groundland is Boots teacher-practitioner, pharmaceutical care health service unit, University of Strathclyde; and Professor Hudson is Boots professor of pharmaceutical care, pharmaceutical care health service unit and Scottish Office national specialist in pharmaceutical care