This information is taken from the revised 2007 GINA Report, Global Strategy for Asthma Management and Prevention, available on the Global Initiative for Asthma (GINA) website. Please refer to the full guideline document1 for more detailed information.
The goal of asthma treatment is to achieve and maintain clinical control. Medications to treat asthma can be classified as controllers or relievers. Controllers are medications taken daily on a long-term basis to keep asthma under clinical control chiefly through their antiinflammatory effects. They include inhaled and systemic glucocorticosteroids, leukotriene modifiers, long-acting inhaled ß2-agonists in combination with inhaled glucocorticosteroids, sustained-release theophylline, cromones, anti-IgE, and other systemic steroid-sparing therapies. Inhaled glucocorticosteroids are the most effective controller medications currently availquality of life1, improving lung function1, decreasing airway hyperresponsiveness2, controlling airway inflammation3, reducing frequency and severity of exacerbations4, and reducing asthma mortality5. However, they do not cure asthma, and when they are discontinued deterioration of clinical control follows within weeks to months in a proportion of patients6,7.
Inhaled glucocorticosteroids differ in potency and bioavailability, but because of relatively flat dose-response relationships in asthma relatively few studies have been able to confirm the clinical relevance of these differences8. Figure 1 lists approximately equipotent able. Relievers are medications used on an as-needed basis that act quickly to reverse bronchoconstriction and relieve its symptoms. They include rapid-acting inhaled ß2- agonists, inhaled anticholinergics, short-acting theophylline, and short-acting oral ß2-agonists.
Inhaled glucocorticosteroids*
Role in therapy - Inhaled glucocorticosteroids are currently the most effective anti-inflammatory medications for the treatment of persistent asthma. Studies have demonstrated their efficacy in reducing asthma symptoms1, improving doses of different inhaled glucocorticosteroids based upon the available efficacy literature, but the categorization into dosage categories does not imply that clear dose-response relationships have been demonstrated for each drug.
| Drug | Low Daily Dose (μg) | Medium Daily Dose (μg) | High Daily Dose (μg)‡ |
|---|---|---|---|
| Beclomethasone dipropionate | 200 - 500 | >500 - 1000 | >1000 - 2000 |
| Budesonide* | 200 - 400 | >400 - 800 | >800 - 1600 |
| Ciclesonide* | 80 - 160 | >160 - 320 | >320 - 1280 |
| Flunisolide | 500 - 1000 | >1000 - 2000 | >2000 |
| Fluticasone | 100 - 250 | >250 - 500 | >500 - 1000 |
| Mometasone furoate* | 200 - 400 | >400 - 800 | >800 - 1200 |
| Triamcinolone acetonide | 400 - 1000 | >1000 - 2000 | >2000 |
|
†Comparisons based upon efficacy data. *In this section recommendations for doses of inhaled glucocorticosteroids are given as “μ/day budesonide or |
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The efficacy of some products varies when administered via different inhaler devices9. Most of the benefit from inhaled glucocorticosteroids is achieved in adults at relatively low doses, equivalent to 400 ug of budesonide per day10. Increasing to higher doses provides little further benefit in terms of asthma control but increases the risk of side effects10,11. However, there is marked individual variability of responsiveness to inhaled glucocorticosteroids and because of this and the recognized poor adherence to treatment with inhaled glucocorticosteroids, many patients will require higher doses to achieve full therapeutic benefit. As tobacco smoking reduces the responsiveness to inhaled glucocorticosteroids, higher doses may be required in patients who smoke.
To reach clinical control, add-on therapy with another class of controller is preferred over increasing the dose of inhaled glucocorticosteroids. There is, however, a clear relationship between the dose of inhaled glucocorticosteroids and the prevention of severe acute exacerbations of asthma12. Therefore, some patients with severe asthma may benefit from long-term treatment with higher doses of inhaled glucocorticosteroids.
Side effects: Local adverse effects from inhaled glucocorticosteroids include oropharyngeal candidiasis, dysphonia, and occasionally coughing from upper airway irritation. For pressurized MDIs the prevalence of these effects may be reduced by using certain spacer devices13. Mouth washing (rinsing with water, gargling, and spitting out) after inhalation may reduce oral candidiasis. The use of prodrugs that are activated in the lungs but not in the pharynx (e.g., ciclesonide)14, and new formulations and devices that reduce oropharyngeal deposition, may minimize such effects without the need for a spacer or mouth washing.
Inhaled glucocorticosteroids are absorbed from the lung, accounting for some degree of systemic bioavailability. The risk of systemic adverse effects from an inhaled glucocorticosteroid depends upon its dose and potency, the delivery system, systemic bioavailability, first-pass metabolism (conversion to inactive metabolites) in the liver, and half-life of the fraction of systemically absorbed drug (from the lung and possibly gut)15. Therefore, the systemic effects differ among the various inhaled glucocorticosteroids. Several comparative studies have demonstrated that ciclesonide, budesonide, and fluticasone propionate at equipotent doses have less systemic effect15- 18. Current evidence suggests that in adults, systemic effects of inhaled glucocorticosteroids are not a problem at doses of 400 μg or less budesonide or equivalent daily.
The systemic side effects of long-term treatment with high doses of inhaled glucocorticosteroids include easy bruising21, adrenal suppression13,15, and decreased bone mineral density19,20. Inhaled glucocorticosteroids have also been associated with cataracts22 and glaucoma in cross-sectional studies23,24, but there is no evidence of posterior-subcapsular cataracts in prospective studies25-27. One difficulty in establishing the clinical significance of such adverse effects lies in dissociating the effect of highdose inhaled glucocorticosteroids from the effect of courses of oral glucocorticosteroids taken by patients with severe asthma. There is no evidence that use of inhaled glucocorticosteroids increases the risk of pulmonary infections, including tuberculosis, and inhaled glucocorticosteroids are not contraindicated in patients with active tuberculosis28.
Inhaled therapy is the cornerstone of asthma treatment for children of all ages. Almost all children can be taught to effectively use inhaled therapy. Different age groups require different inhalers for effective therapy, so the choice of inhaler must be individualized. Information about the lung dose for a particular drug formulation is seldom available for children, and marked differences exist between the various inhalers. This should be considered whenever one inhaler device is substituted with another. In addition, the choice of inhaler device should include consideration of the efficacy of drug delivery, cost, safety, ease of use, convenience, and documentation of its use in the patient's age group29-31. In general, a metered-dose inhaler (MDI) with spacer is preferable to nebulized therapy due to its greater convenience, more effective lung deposition, lower risk of side effects, and lower cost. Based on these considerations, a general strategy for choosing inhalers in children is given in Figure 2.
| Drug | Low Daily Dose (μg) | Medium Daily Dose (μg) | High Daily Dose (μg)‡ |
|---|---|---|---|
| Beclomethasone dipropionate | 100 - 200 | >200 - 400 | >400 |
| Budesonide* | 100 - 200 | >200 - 400 | >400 |
| Budesonide-Neb | 250 - 500 | >500 - 1000 | >1000 |
| Ciclesonide* | 80 - 160 | >160 - 320 | >320 |
| Flunisolide | 500 - 750 | >750 - 1250 | >1250 |
| Fluticasone | 100 - 200 | >200 - 500 | >500 |
| Mometasone furoate* | 100 - 200 | >200 - 400 | >400 |
| Triamcinolone acetonide | 400 - 800 | >800 - 1200 | >1200 |
| †Comparisons based upon efficacy data. ‡ Patients considered for high daily doses except for short periods should be referred to a specialist for assessment to consider alternative combinations of controllers. Maximum recommended doses are arbitrary but with prolonged use are associated with increased risk of systemic side effects. * Approved for once-daily dosing in mild patients. Notes • The most important determinant of appropriate dosing is the clinician's judgment of the patient's response to therapy. The clinician must monitor the patient's response in terms of clinical control and adjust the dose accordingly. Once control of asthma is achieved, the dose of medication should be carefully titrated to the minimum dose required to maintain control, thus reducing the potential for adverse effects. • Designation of low, medium, and high doses is provided from manufacturers' recommendations where possible. Clear demonstration of dose-response relationships is seldom provided or available. The principle is therefore to establish the minimum effective controlling dose in each patient, as higher doses may not be more effective and are likely to be associated with greater potential for adverse effects. • As CFC preparations are taken from the market, medication inserts for HFA preparations should be carefully reviewed by the clinician for the equivalent correct dosage. |
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