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Side Effects With Inhaled Corticosteroids: Local Side Effects of ICS Therapy

Published in Asthma

A systematic review compared the dose response for oral candidiasis for FP with the dose response for preventing an exacerbation. The authors calculated the number of patients that needed to be treated to prevent withdrawal of therapy due to worsening of asthma symptoms vs the risk of oral candidiasis. In this analysis, the number of patients who avoided asthma exacerbation by taking FP increased with increasing daily doses of FP, although the dose-response curve was relatively flat, with little benefit in efficacy between FP at 500 ^g and 1,000 ^g. However, as the dose of FP increased, so did the risk of oral candidiasis. At a dose of 100 ^g, the difference between the number of additional patients that would need to be treated to avoid a loss of efficacy vs the number of patients that would need to be treated in order to see an additional case of oral candidiasis was 87 patients (Fig 1). In comparison, at an FP dose of 1,000 ^g, this difference had fallen to 21 patients, a narrow margin of tolerability (Fig 1). Thus, when increasing the dose of FP, the risk of oral candidiasis will increase much faster than the risk of an exacerbation will decrease. read

Esophageal candidiasis due to ICS was not mentioned in the NAEPP guidelines and was thought to be uncommon. However, utilizing upper-GI endoscopy, Kanda et al reported a prevalence for this side effect of 37% in 49 patients receiving FP vs 0.3% for 700 control patients. Of the patients receiving FP, 36 were asthmatic and 13 had COPD; they had been receiving FP for a mean of 13.38 ± 7.38 (± SD) weeks (range, 5 to 42 weeks) at doses from 200 to 1,200 ^g/d. Although five patients had diabetes, there was no evidence of immunosuppression in any of the patients. The frequency of esophageal candidiasis was dose related, present in 40%, 19%, and 75% of patients receiving FP doses of < 600, 800, and 1,200 ^g/d, respectively (p < 0.05 for 1,200 ^g vs 800 ^g or < 600 ^g). A reduction in daily dose of FP from 1,200 or 800 ^g to 800 or 600 ^g, respectively, resolved the infection in four of five patients after 1 month. Esophageal candidiasis was also more frequent in patients with diabetes (29.5% without vs 100% with diabetes, p < 0.01). High-grade esophageal candidiasis with white moss was found by Shuto et al during GI endoscopy in two asthma patients receiving ICS. As a follow-up, Shuto et al examined 20 asthmatic patients who had been receiving long-term FP inhalation. Thirty-five percent of these patients had esophageal candidiasis, 43% had grade 1, 14% had grade 2, and 43% had grade 3.

Figure-1

Figure 1. Comparison of the relative effects of increasing FP dose in asthma on the number of patients needed to be treated for an additional patient to benefit (NNT) vs the number of patients needed to receive an intervention for an additional patient to experience harm (NNH), in this case oral candidiasis. Reproduced with permission from Powell and Gibson.