The Science Journal of the American Association for Respiratory Care

1997 OPEN FORUM Abstracts

Safety and Efficacy of Steroids in Asthma

Allen T. Lusken, MD, Tuesday, December 9, 1997.

The use of oral and inhaled corticosteroid (ICS) therapy long antedated the definition of the immunopathologic features of asthma that make it seem such an appropriate target for steroid therapy. The current view of asthma's pathogenesis (as a disease mediated by specific, Th_{2} lymphocyte-derived cytokines that promote mast cell proliferation, IgE production, and eosinophil attraction and activation) fits well with current concepts of the mechanism of action of corticosteroids: reduction in vascular permeability and inhibition of cytokine production.

Clinical studies have established the efficacy of ICS therapy, showing it to reduce the frequency and severity of symptoms, improve tests of airway caliber (e.g., PF and FEV_{1}), reduce rescue use of beta-agonist inhalers, reduce bronchial reactivity, reduce the frequency and severity of asthma exacerbations, lower oral corticosteroid requirements, and possibly prevent development of irreversible airway narrowing (attributed to "airway wall remodeling"). The improvement achievable with ICS therapy appears roughly to be inversely related to the duration of symptoms before it introduction.

Although the clinical benefits of standard doses of ICS ( < 1000 mcg/d of BDP in adults, < 400 mcg/d in children) were easily demonstrated, it has not been as easily shown that higher doses necessarily have greater effect. It appears that maximal effect on asthmatic symptoms, peak expiratory flow, and rescue use of beta-agonists may be achieved with low doses, whereas higher doses are necessary for maximal reduction in bronchial reactivity. The doses required for maximal effect in preventing exacerbations or airway wall remodeling are not known.

The ease of demonstrating does-dependency of an ICS may depend on the severity of illness of the population studied; but even in asthmatics with symptoms inadequately controlled by standard doses of beclomethasone, doubling the dose of beclomethasone was much less effective than adding twice daily salmeterol. Even for the end-point of reduction in prednisone dependency, dose dependency was not found for beclomethasone (300 vs 1500 mcg/d) but was found for fluticasone (1500 vd 2000 mcg/d). Individual variability in steroid responsiveness may also be important. In survivors of near-fatal asthma, aggressive use of ICS has had little effect on bronchial reactivity in some patients while normalizing it in others.

As powerful as ICS are for treating asthma, they are not curative: even among patients with mild asthma well controlled on ICS, 50% have an exacerbation within three weeks of their withdrawal.

Local toxicities of oropharyngeal candidiasis and hoarseness are largely (but not entirely) preventable by using holding chambers, slowing inspiratory flow on inhaling from MDI, and rinsing the mouth and throat afterward. Systemic toxicities are a function of absorption from the GI and respiratory tracts. Enhanced "first pass" metabolism reduces systemic levels from GI absorption but does not affect levels from respiratory tract absorption.

Anxiety over serious systemic toxicity from long-term use -- osteoporosis and cataracts -- seems misplaced so long as usual doses ( < = 400 mcg/d in adults; < = 400 mcg/d in children) are taken. Bruising and thinning of the skin may occur, especially in older women.

Worry over the effects of ICS on growth in children has been largely -- but, again, not entirely -- laid to rest by clinical trials. This anxiety should be considered in the context of what is known from studies of asthmatic children: uncontrolled asthma itself potently delays puberty and inhibits growth.

AARC 50th Anniversary, December 6 - 9, 1997, New Orleans, Louisiana.

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