Inhaled Corticosteroids

Corticosteroids are very effective in asthma. They reduce airway inflammation and reduce oedema and secretion of mucus into the airway.
Inhaled corticosteroid treatment reduces exacerbations in moderate to severe chronic obstructive pulmonary disease (COPD).

Before initiating a new drug therapy:

• Re-check compliance
• Check inhaler technique
• Consider eliminating trigger factors

Inhaled corticosteroids (ICS) are recommended for prophylactic treatment of asthma when:

• Patients are using a beta 2 agonist more than 3 times a week
• If symptoms disturb sleep more than once a week
• If the patient has suffered exacerbations in the last 2 years requiring a systemic corticosteroid or a nebulised bronchodilator

Regular use of inhaled corticosteroids reduces the risk of exacerbation of asthma.

• Consider which device is most appropriate for the patient
• Corticosteroid inhalers must be used regularly for maximum benefit
• Alleviation of symptoms usually occurs 3 to 7 days after initiation
• Beclometasone dipropionate (beclomethasone dipropionate), budesonide and fluticasone propionate appear to be equally effective.
• Preparations that combine a corticosteroid with a long-acting beta 2 agonist may be helpful for patients stabilised on the individual components in the same proportion.

SIGN/BTS Guidelines 2005¹ (Step 2)recommends that inhaled corticosteroids should be used twice a day. For beclometasone the appropriate dose to start with is often:

• 400 micrograms per day in adults and children over the age of 12 years
• 200 micrograms per day in children up to the age of 12 years

Patients taking long-term oral corticosteroids for asthma can often be transferred to an inhaled corticosteroid but the transfer must be slow, with gradual reduction in the dose of the oral corticosteroid, and at a time when the asthma is well controlled.
If good control is established consider decreasing frequency of ICS to once a day at the same total daily dose, although the evidence from studies in children is inconsistent.² Use the lowest dose at which effective control of asthma is maintained; i.e. reduce the dose of ICS in people whose asthma is well controlled.

If control of asthma is inadequate, carry out trials of add-on treatments before increasing the dose of ICS above the usual starting dose.

• High-dose corticosteroid inhalers are suitable for patients who respond only partially to standard-dose inhalers and long-acting beta 2 agonists or other long-acting bronchodilators
• High doses should be continued only if there is clear benefit over the lower dose
• The recommended maximum dose of an inhaled corticosteroid should not generally be exceeded
• However, if higher doses are required (e.g. fluticasone in a dose above 500 micrograms twice daily in an adult or 200 micrograms twice daily in a child aged 4 to 16 years), then they should be initiated by specialists.

SIGN/BTS Guidelines 2005¹ (Step 4)recommends maximum dose of inhaled corticosteroids;

• 2000 micrograms per day for beclometasone, in adults and children over the age of 12 years
• 800 micrograms per day in children up to the age of 12 years, (off-label use)

Return to previous dose if no benefit is evident. Systemic corticosteroid therapy may be necessary during episodes of infection or if the asthma is worsening. Patients may need a reserve supply of tablets.

Doses for CFC-free corticosteroid inhalers may be different from those that contain CFCs.

• If the inhaled corticosteroid causes coughing, the use of a beta 2 agonist beforehand may help
• Candidiasis can be reduced by using spacer and it responds to antifungal lozenges without discontinuation of therapy. Rinsing the mouth with water (or cleaning child's teeth) after inhalation of a dose may also be helpful.
• ICS are more effective than other agents used for long-term prevention of asthma. Sometimes, however, there are concerns about adverse effects, such as growth retardation in children. In these cases consider a trial of another preventer agent, i.e. leukotriene receptor antagonist, nedocromil (5 to 12 year olds only), sodium cromoglicate (adults only), inhaled long-acting beta 2 agonist, or modified-release theophylline.

The effect of ICS on bone mineral density (BMD) and osteoporosis is currently unclear. Epidemiological studies examining the relationship between ICS and BMD give conflicting results and are difficult to interpret due to confounding factors. However, they tend to show that;

• With long-term use of ICS at high doses (above 800 micrograms per day of beclometasone or equivalent) there may be a decrease in BMD^3,4,5
• The clinical significance of these changes in BMD is not known, as there is a lack of long-term studies
• In people who require high doses of ICS for prolonged periods of time, general measures to counteract osteoporosis (such as regular exercise, smoking cessation, adequate dietary calcium) are prudent.

One long-term study in children with chronic asthma treated with ICS suggests no adverse effect of inhaled corticosteroids on bone mineral density.⁶ Further long-term studies are needed to confirm this.

A recent systematic review provides evidence that at high doses of ICS (equivalent to 1.5mg/day chlorofluorocarbon [CFC]-containing beclometasone), significant adrenal suppression occurs.⁷ The Committee on Safety of Medicines (CSM) has advised that adrenal suppression is a dose-related class effect of inhaled corticosteroids and that, because of its greater potency, fluticasone should be used at half the dose of budesonide or CFC-containing beclometasone.⁸ A recent survey suggests that acute adrenal crisis associated with inhaled corticosteroids might be more frequent in children than has previously been supposed.⁹Presenting symptoms of adrenal crisis are non-specific and include:

• Anorexia, abdominal pain, weight loss
• Tiredness, headache, nausea, vomiting
• Decreased level of consciousness, hypoglycaemia and seizures.

Acute adrenal crisis may be precipitated by infection, trauma, surgery, or rapid reduction in corticosteroid dosage. Consider the possibility of adrenal insufficiency in any child maintained on ICS presenting with a decreased level of consciousness. Blood glucose levels should be checked urgently. Consider whether intramuscular hydrocortisone is required.

There may be some initial slowing of growth in children who have used ICS, but final adult height does not appear to be affected.^8,9 The CSM have advised that all children receiving prolonged treatment with ICS should have their height regularly monitored. Any slowing of growth should prompt a reduction in dose if possible, and referral to a specialist, or both. There is evidence that poorly controlled asthma, particularly in association with social deprivation, is likely to affect height.¹⁰
The Committee on Safety of Medicines has strongly advised that the paediatric licensed doses of all inhaled corticosteroids should not be exceeded. Use the lowest dose of ICS that will maintain disease control. If adequate control is not achieved, consider using add-on agents.

NICE guidelines (2004)¹¹ on management of COPDn adults states that:
"Inhaled steroids can be prescribed for patients with moderate to severe COPD who have had:

• 2 or more exacerbations in the last year
• Or whose symptoms are not controlled by a combination of short and long-acting bronchodilators

If symptoms have not improved after 4 weeks, discontinue the treatment. A recent observational study suggests that rapid withdrawal of inhaled corticosteroids may increase the risk of early exacerbation.¹² People should therefore be carefully monitored when they withdraw from inhaled corticosteroids.
Efficacy:

• The response to inhaled corticosteroids cannot be predicted by the response to a short course of oral corticosteroids
• They have been found to have no effect on exacerbation rates in mild COPD
• They have been found to have no effect on the rate of decline of FEV1
• They have been found to have no effect on symptom scores
• They have been found to reduce exacerbation rates in more severe COPD