Preventers

Preventer agents have anti-inflammatory properties and are generally taken regularly to reduce symptoms and exacerbations. These include:

• ICS: beclomethasone dipropionate, budesonide, fluticasone propionate and ciclesonide.
• Leukotriene receptor antagonists (LTRAs): montelukast
• Cromones: cromoglycate and nedocromil.

Oral or parenteral corticosteroid agents are potent anti-inflammatory agents reserved for use in acute or very severe chronic asthma.

Inhaled corticosteroids

e.g. beclomethasone dipropionate-HFA (Qvar) (brown inhaler); budesonide (Pulmicort) (brown inhaler); fluticasone propionate (Flixotide) (orange inhaler); ciclesonide (Alvesco) (rust-coloured inhaler)

ICS remain the most effective agents for gaining and maintaining control of asthma in adults and in children with persistent asthma.

• In Australia, the use of ICS has been associated with lower asthma mortality rates and a reduced need for hospitalisation, as well improvement in quality of life for children and adults with asthma.²
• Early treatment with ICS in people with persistent symptoms and impaired lung function leads to better lung function in the medium term, and may help prevent the development of irreversible airflow limitation.
• ICS have a relatively flat dose response curve for efficacy in symptoms and lung function.^3,4 At a group level, little additional benefit in symptoms or lung function is gained from doses above 320 mcg/day of CIC, 500 mcg/day of FP/BDP-HFA or 800 mcg/day of BUD.
• There is an increased risk of cataracts, reduced bone mineral density, osteoporosis, glaucoma and bruising of the skin with long-term treatment with high-dose ICS.
• In adults with asthma who have pre-existing conditions such as osteoporosis or cataracts, the need for high doses of ICS should be balanced against the risk of further systemic side effects.
• The daily dose should be titrated according to the patient's clinical response and lung function. The delivery device may influence the final dose.
• There is no need to routinely use a SABA immediately before taking preventer medication.

Safety of ICS

The risk of adverse effects is dose-related but there is also some individual patient sensitivity to the effects of corticosteroids. It is important to find a balance between benefits and risks for each patient. Consider the patient's use of other systemic steroids when assessing steroid risk.

Adults

• There is little evidence that doses below 500 mcg per day BDP-HFA or equivalent cause any short-term detrimental effects apart from the local side-effects of dysphonia and oral candidiasis.
• A systematic review of ICS found that number needed to harm (NNH) for development of hoarseness/dysphonia at 200 mcg FP daily was 131, whereas the NNH for a daily dose of 500 mcg FP was 23.⁴ Similarly, the NNH for oral candidiasis was 61 at 200 mcg FP daily, and 21 with 500 mcg FP daily.
• A systematic review reported no effect on long-term bone density at doses up to 500 mcg BDP-HFA daily or equivalent, although further studies are investigating long-term safety.⁵
• Osteoporosis screening is advised for adults on long-term high-dose ICS.
• The significance of small biochemical changes in adrenocortical function is unknown.⁵
• Cataracts may occur in older patients with high cumulative doses of ICS.

Children

• Administration of inhaled steroids at or above 200 mcg of BDP-HFA daily or equivalent may be associated with systemic side-effects e.g. growth failure and adrenal suppression, although isolated growth failure is not a reliable indicator of adrenal suppression.⁵
• The amount of growth suppression is likely to be a maximum of 1 cm and is non-progressive.
• Poorly controlled asthma can also cause growth suppression.
• Children using regular ICS should have their height monitored on a regular basis.
• Clinical adrenal insufficiency has recently been identified in a small number of children, who have become acutely unwell at the time of intercurrent infectious illness.⁶ Most of these children were over-treated with ICS often because of over-reliance on cough to diagnose asthma or to assess its severity.
• Consider the possibility of adrenal insufficiency in any child maintained on ICS presenting with shock or a decreased level of consciousness; serum biochemistry and blood glucose levels should be checked urgently. Consider whether parenteral hydrocortisone is required.
• The relative benefits and risks of inhaled corticosteroids in children should be assessed on an individual basis and must be balanced against the risks and morbidity of poorly controlled asthma.

Beclomethasone dipropionate-HFA (Qvar)

Beclomethasone has a low hepatic first-pass mechanism and an active metabolite, which results in some systemic bioavailability. Qvar is a CFC-free preparation. The finer particle size results in greater intrapulmonary deposition than the CFC preparations, so a lower dose is required.

Budesonide (Pulmicort)

Budesonide has been approved for once-daily use in adults with asthma controlled by 400 mcg or less of ICS per day. Its potency is approximately half that of BDP-HFA and FP. Budesonide has Category A listing for pregnancy.

Budesonide is available in a Turbuhaler device and a nebulised suspension. Budesonide combined with eformoterol is available as the combination inhaler Symbicort. See Combination medications for further information.

Fluticasone propionate (Flixotide)

Fluticasone propionate has equivalent potency to BDP-HFA and approximately twice the potency of budesonide when given through comparable devices. It has negligible oral bioavailability since the portion of the dose that is swallowed is subject to extensive first-pass metabolism.

Fluticasone is available as an MDI and a dry powder for inhalation via Accuhaler. Fluticasone combined with salmeterol is available in the combination inhaler Seretide. See Combination medications for further information.

Ciclesonide (Alvesco)

Ciclesonide, a relatively new corticosteroid agent, is indicated for the prophylactic management of asthma in adults and in children over 12 years of age. It is delivered as an ultra-fine aerosol, which may facilitate intrapulmonary deposition.

Clinical trials have shown that ciclesonide is well tolerated and effective in treating asthma of varying disease severity in adults and adolescents. Safety and efficacy was maintained over 12 months. Treatment within recommended doses did not cause HPA axis suppression as measured by 24-hour serum and urine cortisol concentrations or cosyntropin tests.

Content Created (Thursday, 16 November 2006)