Impact of Study Design on the Evaluation of Inhaled and Intranasal Corticosteroids’ Effect on Hypothalamic-Pituitary-Adrenal Axis Function, Part I: General Overview of HPA Axis Study Design

Fan, Ying; Ma, Lian; Pippins, Jennifer R.; Limb, Susan L.; Xu, Yun; Sahajwalla, Chandrahas

doi:10.1002/jps.23689

Cited by 8 publications

(21 citation statements)

References 93 publications

(116 reference statements)

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“…In such studies, the ICS is compared with a placebo or with the same drug used with another delivery device or two different ICS are compared [5,9,13,21,26,33]. In the current study, several Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In this retrospective analysis, the inclusion criteria were (i) being 0-18 years old and diagnosed with asthma, (ii) being treated with moderate-to-high-dose ICS (>176 μg FP-HFA equivalent for children 0-11 years, >264 μg for adolescents ≥12 years, Table 1) [25] for more than 6 weeks and being HPA axis investigated, and (iii) no requirement for systemic CS during the 6 weeks preceding HPA axis evaluation. Using ICS for longer than 6 weeks was a requirement for inclusion in the study which was in line with the other relevant studies reviewed previously [9]. The patients who had not used systemic steroids during the previous 6 weeks before assessment for HPA axis suppression were included to get fully rid of the HPA axis-suppressive effect of the drug [40].…”

Section: Study Participantsmentioning

confidence: 99%

“…The adrenal function loss may be clinically obvious, as in the case of a recognizable crisis [32], or more predominantly, it may be subclinical in patients undergoing regular ICS treatment. Several different tests have been investigated for assessing HPA axis function in asthmatic children using ICS such as measurement of basal serum, salivary, or urinary cortisol; serum dehydroepiandrosterone sulfate; and earlymorning serum ACTH levels and the other dynamic tests [9,27,36,39]. Accurate assessment of subclinical HPA-AS through dynamic tests is a way to yield information about adrenal functions.…”

Section: Introductionmentioning

confidence: 99%

“…A relatively small number of trials concentrated on HPA-AS in children and/or adolescents up to date [9], and there is limited clear-cut data in such studies about the dose and time period of ICS consumed, which pose a danger for HPA-AS. The hypothesis of this study was that the use of ICS at moderate to high doses might end up in HPA axis suppression.…”

Section: Introductionmentioning

confidence: 99%

“…Accurate assessment of subclinical HPA-AS through dynamic tests is a way to yield information about adrenal functions. The low-dose ACTH stimulation test (LDAT) is considered to be one of the standard measures among the dynamic tests [9]. LDAT (0.5 μg/m 2 ) is a practical and convenient test for measuring HPA-AS, especially in the pediatric age group [15], and more sensitive to detect mild HPA-AS compared to the standard-dose ACTH test [3,26].…”

Section: Introductionmentioning

confidence: 99%

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Evidence of hypothalamic-pituitary-adrenal axis suppression during moderate-to-high-dose inhaled corticosteroid use

et al. 2015

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The possible risk of adverse effects due to regular use of inhaled corticosteroids (ICS) is a real concern. Our aim was to describe the factors that have an impact on hypothalamic-pituitary-adrenal axis suppression (HPA-AS) in children and adolescents taking ICS regularly. The HPA axis status of patients who were on moderate-to-high-dose ICS [>176 and >264 μg/day fluticasone propionate-hydrofluoroalkane (FP-HFA) for patients 0-11 and ≥12 years, respectively] was investigated. Various types of ICS were converted to FP-HFA equivalent according to National Asthma Education and Prevention Program (NAEPP) guidelines. Participants with a baseline (8 a.m.) serum cortisol <15 μg/dL underwent a low-dose ACTH stimulation test (LDAT) to diagnose HPA-AS. Among 91 patients, 60 (75.9 %) participants underwent LDAT, and seven (7.7, 95 % CI 3.5-15.3 %) were diagnosed with HPA-AS. Ciclesonide was more frequently used by the participants with HPA-AS compared to patients with a normal HPA axis (42.9 vs. 4.8 %, p = 0.009). Use of ICS at moderate-to-high doses for at least 7 months distinguished participants with HPA-AS from those with a normal HPA axis. Among the duration, type, and dose of ICS, solely the use of ICS with a body mass index (BMI)-adjusted daily dose of ≥22 μg FP was found to increase the risk for HPA-AS (odds ratio (OR) 7.22, 95 % confidence interval (CI) 1.23-42.26, p = 0.028). The receiver operating characteristics (ROC) curve analysis revealed a cutoff value of 291 μg/day FP (area under the curve (AUC) = 0.840, p = 0.003) for predicting HPA-AS Conclusion: The prevalence of HPA-AS was found to be 7.7 % in children taking not only high-dose ICS but also moderate-dose ICS. Dose alone was found to be an actual risk factor for HPA-AS.

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