Reviews and Feature ArticlesPotential adverse effects of the inhaled corticosteroids☆
Section snippets
Development of ICSs
The ICSs were developed to provide the beneficial therapeutic effects of corticosteroids while minimizing the potential for the known adverse consequences of chronic use, as listed in Table I. All corticosteroid actions are mediated through the stimulation of glucocorticoid receptors in the cytoplasm of cells throughout the many tissues in the body. There can be a significant heterogeneity of response in both the topical or antiasthmatic response and the systemic activity between individuals
Measures of safety of the ICSs
Until recently, the FDA used the standard tests of adrenal corticosteroid excretion (ie, morning plasma cortisol concentration) and hypothalamic-pituitary-adrenal (HPA) axis responsiveness (ie, high-dose cosyntropin stimulation) as the primary measures of safety for the ICSs in Phase 2 and 3 clinical trials. However, in 1998, the FDA convened a combined advisory panel of the Pulmonary and Allergy/Endocrinologic and Metabolic Advisory Committees to review data on the effect of both ICSs and
Measures of the HPA axis
The 8 am morning serum cortisol concentration and standard 250-μg cosyntropin stimulation test have been the standard methods for assessing basal cortisol secretion and HPA axis responsiveness, respectively.30, 31 These tests have been criticized for lack of sensitivity to detect low levels of HPA axis suppression, particularly that produced by ICSs.32, 33 The standard 250-μg cosyntropin test has been criticized because it uses a supraphysiologic dose of cosyntropin that would miss mild adrenal
ICSs and growth in children
This topic has been extensively reviewed, as well as subjected to a meta-analysis and a systematic review by the Blue Cross and Blue Shield Technology Evaluation Center for the NAEPP.8, 37, 40 Short-term sensitive studies of lower leg growth by means of knemometry have no relationship to long-term linear growth in children but can be used to assess systemic activity from ICSs.8 Intermediate-term studies (≤1 year) of growth velocity by using stadiometry demonstrate an average of a 1-cm (range,
ICSs and the risk of osteoporosis and fractures
Since the last review, there have been a significant number of studies, both randomized clinical trials and epidemiologic studies, on the potential increased risk for osteoporosis and fractures caused by ICSs. Corticosteroids have multiple effects on bone metabolism, including decreased osteoblast activity, increased bone resorption, decreased calcium absorption, decreased renal calcium reabsorption, and decreased sex hormone production.44 However, decreased osteoblastic function, evident by a
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