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Inhaled Corticosteroids

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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).

Indications for use in asthma1

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 in adults and children:

  • Beta 2 agonist more than 3 times a week
  • Symptoms disturbing sleep once a week or more
  • Symptomatic three times a week or more

In addition, inhaled steroids should be considered in adults and children aged 5-12 who have had an exacerbation in the last 2 years requiring oral steroids.

Other issues:

  • Consider which device is most appropriate for the patient - see our dedicated record Which Device in Asthma
  • Corticosteroid inhalers must be used regularly for maximum benefit.
  • Alleviation of symptoms usually occurs 3 to 7 days after initiation.
  • Beclometasone dipropionate (BDP), 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.
Available preparations
Standard Dose Inhaler
50mcg per inhalation

100mcg per inhalation
High Dose Inhaler
200mcg per inhalation
250mcg per inhalation Compound Inhalers
(Steroid + long-acting Beta Agonist)
Beclometasone Qvar® Pulmicort® Beclometasone Symbicort®
(Budesonide
+ formoterol) 100/6, 200/6 or 400/12
AeroBec® (withdrawn) Budesonide   Aerobec® (withdrawn) Seretide®, Seretide Evohaler®
(Fluticasone+ salmeterol) 50, 100, 125, 250 and 500.
Asmabec Clickhaler®     Becloforte®  
Beclazone Easi-breathe®     Beclazone Easi-Breathe®  
Becodisks®     Becodisks®  
Becotide®        
Flixotide Accuhaler® Flixotide Accuhaler®   Flixotide Accuhaler®  
Flixotide Diskhaler® Flixotide Diskhaler®   Flixotide Diskhaler®  
Flixotide Evohaler®     Flixotide Evohaler®*  
Qvar®        
Pulmicort®        
*Also comes in 125mcg per inhalation strength

Comparison of inhaled steroids1

  • Beclometasone dipropionate (BDP) and budesonide are approximately equivalent in clinical practice, although different delivery devices may cause some variation. Fluticasone provides equal clinical activity; there is limited evidence that it causes fewer side effects at equivalent doses.
  • Mometasone appears to provide equal clinical activity to BDP and budesonide at half the dosage.
  • Ciclesonide is a new inhaled steroid. Evidence from clinical trials suggests that it has less systemic activity and fewer local oropharyngeal side effects than conventional inhaled steroids, but the efficacy to safety ratio has not been fully established.

Effect of CFC-free propellant on dose equivalence

  • HFA (hydrofluoroalkane) BDP pressurised metered dose inhaler (Qvar) may be substituted for CFC BDP pMDI at 1:2. dosing. This ratio does not apply to reformulated HFA BDP pMDIs.
  • Fluticasone HFA can be substituted for fluticasone CFC at 1:1 dosing.
Dosing1

The British Guidelines 2008 (Step 2 )recommend that inhaled corticosteroids should be used twice a day. In mild to moderate asthma, dosage should be appropriate to the severity of the disease, and no benefit is conferred by starting with a high dose and then stepping down. 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
  • In children under 5, higher doses may be needed if there is difficulty maintaining consistent dosage

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. The recommended method is to reduce the dosage by 25-50% every 3 months when stable.

High dose inhalers

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.

The British Guidelines 2008 (Step 4) recommends maximum dose of inhaled corticosteroids:1

  • 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, should be prescribed in conjunction with specialist advice)

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. Consider the possibility of adrenal insufficiency in any child maintained on inhaled steroids presenting with shock or a decreased level of consciousness; serum biochemistry and blood glucose levels should be checked urgently. Consider whether intramuscular (IM) hydrocortisone is required.

Combination inhalers1

There is no difference in efficacy between a combination inhaler containing long-acting beta2 agonist (LABA) and inhaled steroid, and the same drugs given in separate inhalers. However, once the patient is stable, a combined inhaler ensures that the steroid is always taken with the LABA.

In adult patients at step 3 who are poorly controlled, the use of budesonide/formoterol in a single inhaler as rescue medication instead of a short-acting beta2 agonist has been shown to be an effective treatment option. This management technique has not been investigated with other combination inhalers.

Common problems

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

The safety of corticosteroids should be considered, and a risk-benefit analysis should be done for all patients.

  • 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.
Osteoporosis

The effect of ICS on bone mineral density (BMD) and osteoporosis is currently unclear. One systematic review reported no effect on bone density at doses up to 1,000 mcg per day.1 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 BMD3,4,5
  • 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.

Adrenal suppression

A recent systematic review provides evidence that at high doses of ICS (equivalent to 1.5 mg/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 survey suggests that acute adrenal crisis associated with inhaled corticosteroids might be more frequent in children than has previously been supposed.9
Presenting 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.

Childhood growth1

The British Guidelines state that in children, administration of inhaled steroids at or above 400 mcg a day of beclometasone or equivalent may be associated with systemic side effects, including growth failure and adrenal suppression. 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

In 2002, the Committee on Safety of Medicines strongly advised that the paediatric licensed doses of all inhaled corticosteroids should not be exceeded.11 Use the lowest dose of ICS that will maintain disease control. If adequate control is not achieved, consider using add-on agents.

COPD

NICE guidelines (2004)12 on management of COPD in 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.13 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


Document references
  1. British Guideline on the Management of Asthma, British Thoracic Society and SIGN (May 2008)
  2. Radzik D, Pavanello L; Inhaled steroids in the treatment of mild to moderate persistent asthma in children: once or twice daily administration? Arch Dis Child. 2002 Nov;87(5):415-6.
  3. Cave A, Arlett P, Lee E; Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects. Pharmacol Ther. 1999 Sep;83(3):153-79. [abstract]
  4. No authors listed; The use of inhaled corticosteroids in adults with asthma. Drug Ther Bull. 2000 Jan;38(1):5-8. [abstract]
  5. Royal College of Physicians of London (2002) Glucocorticoid-induced osteoporosis
  6. Agertoft L, Pedersen S; Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. N Engl J Med. 2000 Oct 12;343(15):1064-9. [abstract]
  7. EBM (1999) High-dose inhaled corticosteroids increase the risk for some systemic adverse effects in asthma. Evidence Based Medicine 4(6), 191.
  8. CSM (2001); Current Problems in Pharmacovigilance: Volume 27 (pages 9-16) August 2001
  9. Todd GR, Acerini CL, Ross-Russell R, et al; Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child. 2002 Dec;87(6):457-61. [abstract]
  10. McCowan C, Neville RG, Thomas GE, et al; Effect of asthma and its treatment on growth: four year follow up of cohort of children from general practices in Tayside, Scotland. BMJ. 1998 Feb 28;316(7132):668-72. [abstract]
  11. Inhaled corticosteroids: children are at risk from high doses; MeRec Extra March 2007
  12. Chronic obstructive pulmonary disease, NICE Clinical Guideline (2004); Management of chronic obstructive pulmonary disease in adults in primary and secondary care
  13. Jarad NA, Wedzicha JA, Burge PS, et al; An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. ISOLDE Study Group. Respir Med. 1999 Mar;93(3):161-6. [abstract]

Internet and further reading AcknowledgementsEMIS is grateful to Dr Laurence Knott for writing this article and to Dr Hayley Willacy for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 463
Document Version: 3
Document Reference: bgp25115
Last Updated: 18 Jul 2008
Planned Review: 18 Jul 2009

The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.

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