title: Impact of study design on the evaluation of inhaled and intranasal corticosteroids' effect on hypothalamic-pituitary-adrenal axis function.
abstract: In part I of this review, an overview of the designs of hypothalamic-pituitary-adrenal (HPA) axis studies in the setting of inhaled corticosteroids (ICS) or intranasal corticosteroids (INS) use was discussed. Part II provides detailed discussion on the HPA axis evaluation results for each common ICS and INS, and how these results are possibly affected by the factors of study design. Significant adrenal suppression at conventional ICS/INS doses appears to be rare in clinical settings. The magnitude of cortisol suppression varies widely among different study designs. Factors potentially impacting this variability include: the choice of dose, dosing duration, assay sensitivity, statistical methodology, study population, and compliance. All of these factors have the potential to affect the extent of HPA axis effects detected and should be considered when designing or interpreting the results of a HPA axis study.
authors.affiliation: Division of Clinical Pharmacology II, Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Ying
authors.initials: Y
authors.lastname: Fan
authors.forename: Lian
authors.initials: L
authors.lastname: Ma
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pippins
authors.forename: Susan
authors.initials: S
authors.lastname: Limb
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.forename: Chandrahas G
authors.initials: CG
authors.lastname: Sahajwalla
mesh_terms: D000280:Administration, Inhalation; D000281:Administration, Intranasal; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000494:pharmacology; D000328:Adult; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects*
chemical_list: D000305:Adrenal Cortex Hormones
keywords: hypothalamic-pituitary-adrenal (HPA) axis; inhaled corticosteroids; intranasal corticosteroids; pediatrics; pharmacodynamics; pulmonary; regulatory science; study design; toxicity