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November 2007:New developments in the treatment of asthma

What is the latest guidance on inhaled corticosteroids?

How is occupational asthma diagnosed?

What new therapeutic options are available?

What is the latest guidance on inhaled corticosteroids?

How is occupational asthma diagnosed?

What new therapeutic options are available?

Asthma remains one of the most common chronic disorders, at all ages, in the Western world. Around 100 million people in Europe and North America have asthma,1,2 equating to 6% of adults and 10% of children. In the UK, approximately 5.2 million patients (1.1 million children and 4.1 million adults) are currently receiving treatment for asthma and eight million have been diagnosed with asthma at some stage in their lives. The UK currently has the highest frequency of self-reported asthma symptoms among children aged 13-14 years in the world. One in five UK households has at least one affected member. Asthma is more common in urban than rural areas.

Although the understanding of the triggers and cell biology of asthma is increasing, and there are a multitude of effective drugs and inhalers, asthma is not under control. In the UK, 80 million working days are lost and 69,000 hospital admissions occur each year because of asthma. One in six people receiving emergency treatment for asthma will need emergency treatment again within two weeks and, on average, one person dies of asthma every seven hours in the UK.

The reasons for this continuing morbidity and mortality are complex, but may involve low patient expectations, leading to an acceptance of continuing symptoms, and the belief among patients and some doctors that asthma only requires treatment when there are symptoms.

Guidelines

The first British guideline on asthma management in adults was published in the British Medical Journal in 1990. Since 1999, the British Thoracic Society (BTS) and the Scottish Intercollegiate Guidelines Network (SIGN) have collaborated to produce the British Guideline on the Management of Asthma.3 This is available on the BTS and SIGN websites. The guideline uses rigorous evidence-based methodology, covering all aspects of asthma care, and contains graded recommendations supported by evidence tables.

Occupational asthma

In 2005 the section in the BTS/SIGN asthma guideline on occupational asthma was completely revised with the help of the British Occupational Health Research Foundation.

 

 

41159074Occupational asthma is often not recognised and it is estimated that 9-15% of adult-onset asthma has an occupational cause.4 The update emphasised the importance of enquiring about occupation in all adults presenting with symptoms of airways obstruction (see table 1, attached and box 1, above).

Inhaled corticosteroids

Inhaled corticosteroids remain the most effective drugs for the prevention of asthma attacks in adults and older children. There is an increasing body of evidence demonstrating that they are also safe and effective in infants and younger children with asthma.5

The exact threshold for the introduction of inhaled corticosteroids has never been firmly established, but recent studies have shown benefit in patients with mild asthma and an FEV1 of 90% predicted.6

Therefore inhaled corticosteroids should now be considered for patients who are:

• Using short-acting beta-agonists three or more times per week
• Symptomatic three or more times per week
• Waking one night or more per week with respiratory symptoms.

Beclometasone dipropionate (BDP) and budesonide are approximately equivalent, although there may be variations between different delivery devices. Fluticasone provides equal clinical activity to BDP and budesonide at half the dosage.

Ciclesonide, a new inhaled corticosteroid, is probably equivalent to BDP and appears to be effective as a single daily dose. It is a prodrug, activated by esterases within the lung. Evidence from clinical trials suggests that it has less systemic activity and fewer local oropharyngeal side-effects than conventional inhaled corticosteroids. However, the benefit of this is unclear, as the exact efficacy to safety ratio compared with other inhaled steroids has not been fully established.

The suggested starting dose of an inhaled corticosteroid is 400µg/day BDP or equivalent in adults and 200µg/day in children older than five years. Initially, inhaled corticosteroids should be given twice daily, except ciclesonide, which is given once daily.

In children younger than five years, higher doses may be necessary if there are problems in drug delivery. In these circumstances referral to a local paediatric respiratory service is advised.

In all patients the dose of inhaled corticosteroid should be adjusted to the lowest at which effective control of asthma is maintained. In mild to moderate asthma, starting at very high doses of inhaled corticosteroids and ‘stepping down' confers no benefit.

Current and previous cigarette smoking reduces the effect of inhaled corticosteroids.7 Clinicians should be aware that higher doses of inhaled corticosteroids may be needed in patients who are smokers or ex-smokers.

Safety

In adults, there is little evidence that doses of inhaled corticosteroids less than 800µg/day BDP or equivalent cause any short-term detrimental effects, apart from the local side-effects of dysphonia and oral candidiasis.

Although there have been concerns about possible long-term effects on bone, one recent systematic review reported no effect on bone density at doses up to 1,000µg/day.8

In children, doses of inhaled corticosteroid of ? 400µg/day BDP or equivalent may be associated with systemic side-effects.9 These include growth failure and adrenal suppression. Isolated growth failure is not a reliable indicator of adrenal suppression and conversely monitoring growth cannot be used as a screening test of adrenal function.10

Clinical adrenal insufficiency has been identified in a small number of children who have become acutely unwell during an intercurrent illness. Most of these children had been treated with high doses of inhaled corticosteroids.

The dose of inhaled corticosteroid, and duration of treatment, required to place a child at risk of clinical adrenal insufficiency is unknown, but the dose is likely to be at least 800µg/day BDP or equivalent and the duration of treatment may be around six weeks.

It is therefore advised that specific written advice about steroid replacement in the event of a severe intercurrent illness should be part of the management for children prescribed more than 800µg BDP or equivalent per day. Any child on this dose should be under the care of a respiratory paediatrician. Steroid warning cards may be helpful in this situation.

Anti-IgE monoclonal antibodies

Omalizumab is a humanised monoclonal antibody that binds to circulating IgE, reducing levels of free IgE.11,12 It is given by subcutaneous injection every two to four weeks. The dose and dose frequency are determined by baseline IgE, measured before treatment, and body weight. For treatment, a patient's total IgE must be less than 700 IU/l, which effectively excludes highly atopic patients with severe asthma. At IgE levels below 76 IU/l the beneficial effect is reduced.

Although rare, anaphylaxis, presenting as bronchospasm, hypotension, syncope and angiooedema, has been reported.

This can occur after the first dose or after a year's treatment. Therefore omalizumab should only be administered to patients in secondary care under direct medical supervision.

Omalizumab is licensed in the UK for adults and children older than 12 years with "severe persistent allergic asthma" – that is, those on high-dose inhaled corticosteroids and long-acting beta-agonists, who have impaired lung function with frequent exacerbations and allergy is an important cause of their asthma. A recent appraisal by NICE13 advises that omalizumab add-on therapy should only be considered for patients with two or more severe exacerbations requiring hospital admission within the previous year. In contrast, the Scottish Medicines Consortium advises restriction to patients who are taking long-term maintenance oral corticosteroids and for whom all other treatments have failed. There are no active comparative studies with other drugs used for asthma and therefore at present it is not possible to place omalizumab in the BTS/SIGN stepwise treatment of asthma.

The 2008 update

The BTS/SIGN asthma guideline will be updated extensively next year. It will be published both on the BTS and SIGN websites and as a supplement in Thorax. The 2008 guideline will contain a completely rewritten section on diagnosis and monitoring in both adults and children; a new section on ‘difficult asthma'; updated sections on pharmacological and non-pharmacological management and amalgamated sections on patient education and compliance, and organisation of care and audit. It is hoped that the new guideline, based on papers published up to March 2007, will stimulate research into gaps in evidence as well as lead to improvements in care for all those with asthma.

Key points Patient using a peak flow meter Table 1: Work-related asthma and rhinitis: case finding and management in primary care Asthmabox1 Useful information

The BTS/SIGN guideline on the management of asthma is available from both the BTS and SIGN websites
www.brit-thoracic.org.uk
www.sign.ac.uk

Author

Dr Graham Douglas
BSc FRCPE
consultant physician, Aberdeen Royal Infirmary and co-chair, BTS/SIGN Asthma Guideline Development Group

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