Disscusion of A One-Year Trial of Triamcinolone Acetonide Aerosol in Severe Steroid-Dependent Asthma

severe asthmaTriamcinolone acetonide aerosol as long-term treatment for severe asthma is effective in reducing requirements for oral therapy with corticosteroids while maintaining constant average levels of FEVi, FVC, FEF25-75%, FEF508S, and FEF75% over the course of one year. Although there were exceptions, in general the patients responding most favorably to triamcinolone acetonide aerosol were those who initially required smaller oral doses of corticosteroids and those who were maintained on altemate-day therapy. There did not appear to be any relation between the response of triamcinolone acetonide aerosol and the age of the patients, duration of asthma, duration of steroid dependence, factors provoking asthma, other associated symptoms (sensitivity to aspirin, atopic dermatitis, and rhinitis), or response to aerosol therapy with isoproterenol, atropine, or cromolyn.

Maximum reduction in the oral therapy with steroids was safely achieved within four months after beginning the program of aerosol steroid therapy. Little additional reduction in the oral dosage of steroids was achieved between 4 and 12 months, but perhaps it could be if the dose of the aerosol were increased or the period of treatment extended. Even so, most patients who continued to need oral therapy with steroids during the study tolerated reduction of their oral dosage of steroids to 2.5 to 5 mg of prednisone on alternate days.

The mild transient side effects of the aerosol did not require stopping the treatment in any patient. Hoarseness, coated tongue, and sore throat were the most frequent complaints in the study, and they were not related to the dose. A short-term double-blind comparison of triamcinolone acetonide aerosol and its vehicle demonstrated no difference in the frequency of hoarseness or sore throat. This suggests that these symptoms might be due to the alcohol in the aerosol, the requirement for frequent deep inspiration, or the hyperventilation associated with symptoms of asthma. Such an explanation would be consistent with the 55-percent incidence of transient hoarseness (six patients) in the 21 patients treated with triamcinolone acetonide aerosol by Williams et al. The irritative effect of the alcohol in the aerosol could cause the “relatively dry larynx“” seen with the laryngoscopic examination in six of his hoarse patients.

The 5-percent incidence (one patient) of oral thrush in this study contrasts with the incidences of 13 to 77 percent reported in studies of aerosol therapy with beclomethasone diproprionate. The occurrence of thrush in the only patient with precipitins to С albicans agrees with data presented by Lehner and Ward that show a predisposition to Candida growth in patients with raised Candida antibody levels. Although data reported by Cayton et al and by Gwynn and Smith suggested that the risk of oral candidiasis can be reduced by decreasing the dose of aerosol therapy with laryngoscopic examinationbeclomethasone dipropionate, the patient in our study with oral thrush was using only 400/xg to 1,200/tg of triamcinolone acetonide aerosol daily. Indirect laryngoscopic examination did not reveal any visible deleterious effects on the larynx. Nevertheless, the known association between long-term topical application of corticosteroids to the skin and the development of cutaneous atrophy and striae should alert physicians to continue close observation of patients on daily doses of aerosol corticosteroids. Although the potential of developing endobronchial disease must be kept in mind, it may be helpful to regularly examine the mouth, pharynx, and larynx, the areas likely to be exposed to great amounts of aerosol deposition.

Symptoms from steroid withdrawal were much more troublesome than side effects of the aerosol, and they were sufficiently disabling to require resumption of oral therapy with steroids in two patients. The most frequent complaints were lethargy, myalgia, and arthralgia. The patients most susceptible to increases in atopic eczema or rhinitis during withdrawal of oral therapy with steroids were, not surprisingly, those who had past histories of mild to moderate eczema, rhinitis, or nasal polyps. In most cases, these symptoms improved during the year, and treatment was attempted with other medications, eg,topical therapy with corticosteroids for eczema and antihistaminic drugs and exhalation of triamcinolone acetonide aerosol through the nose for rhinitis and nasal polyps.

A potentially unfortunate consequence of the patient’s reduced oral requirement for steroids was a feeling of overconfidence and security that the patients experienced with the new drug. Although they received much attention and close follow-up by the physicians conducting the study, the patients had a tendency to neglect exacerbations of asthma or symptoms of steroid withdrawal, and the absence of oral support with steroids resulted occasionally in profound and rapid deterioration of asthma, especially during respiratory infections. Many of these patients required high oral doses of steroids for several weeks. The best example of this was patient 13, who required hospitalization twice dining the study and required three week courses of prednisone (20 mg four times daily) because of exacerbations of asthma related to respiratory infection. When free of such exacerbations, this patient was able to maintain control of asthma with 15 to 20 mg of prednisone on alternate days. The patients also had a tendency to discard their more conventional bronchodilator drugs in favor of their new medication. Two patients regarded themselves as “cured” and attempted to taper or discontinue the steroid aerosol. Symptoms of asthma reappeared in both patients within three to seven days, but relief was again obtained from resumption of the steroid aerosol.

The failure to demonstrate any increase in the fasting plasma cortisol level and the persistence of symptoms of steroid withdrawal suggest that the patients studied have experienced no appreciable return of adrenal function over the course of one year. We were unable to identify anything different about the eight patients who demonstrated an increase in the plasma cortisol level at the tenth or 12th month. The fact that our patients had taken large oral doses of steroids for many years may be a reason for their delayed adrenal recovery. It is most probable that frequent oral courses of steroids during the year for exacerbations of asthma related to respiratory infection or other provocation may have also delayed adrenal recovery. Controlling the patients’ supplies of canisters of triamcinolone acetonide aerosol verified that it is unlikely that any patients violated the protocol of the study by using doses of this drug in excess of those prescribed.

Previous studies on human volunteers suggest that it is unlikely that up to 2,000/ug daily of triamcinolone acetonide aerosol would suppress adrenal function. Prior studies with triamcinolone acetonide aerosol have suggested that there is a rapid return of adrenal function in steroid-dependent patients who are weaned from oral therapy with steroids.» Perhaps a longer period of systemic steroid withdrawal may be necessary for the appearance of adrenal recovery in our patients. As a consequence, the physician should be cautious when reducing a patient’s oral dose of steroids, especially for those patients who have been dependent on high doses for many years. Such patients are in a precarious state when exposed to trauma, infection, or similar stress. They should be cautioned to resume high daily oral doses of steroids when necessary, without necessarily awaiting medical advice. An overconfident patient and a disinterested physician provide the prescription for disaster.

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