Endocrine Effects of Inhaled Corticosteroids in Children

Kapadia, Chirag; Nebesio, Todd D.; Myers, Susan E.; Willi, Steven M.; Miller, Bradley S.; Allen, David B.; Jacobson-Dickman, Elka

doi:10.1001/jamapediatrics.2015.3526

Cited by 70 publications

(62 citation statements)

References 78 publications

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“…22 Limited studies suggest that the risk of systemic side effects increases dramatically when high-dose ICS are used and that children and adolescents are particularly vulnerable to effects on linear growth, bone mineral density and adrenal function. 23 For this reason, the prescribing of long-term high-dose ICS for children and adults should be limited to specialists. 5 …”

Section: Corticosteroid-dependent Asthmamentioning

confidence: 99%

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma. OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches. METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomized controlled trials. The proposed key messages, based on scientific evidence and expert opinion, were agreed upon by unanimous consensus. MAIN RESULTS: We defined severe asthma and outlined its significant impact from the societal and patient perspectives. We outlined a practical approach to distinguish severe from uncontrolled but not severe asthma, based on stepwise investigation and management of potential reasons for uncontrolled asthma. After reviewing the current evidence we concluded that: 1) Several biomarkers (e.g. sputum or blood eosinophil count, total IgE, or FeNO) can help identify potential responders to new therapeutic options; 2) Tiotropium may be considered as an add-on therapy for individuals 12 years of age and over with severe asthma uncontrolled despite combination ICS/LABA therapy; 3) The chronic use of macrolides may decrease asthma exacerbations in individuals 18 years of age and over with severe asthma independent of their inflammatory profile; 4) Children aged 6 years and older and adults who are sensitized to at least one relevant perennial allergen and who remain poorly controlled asthmatics despite high dose ICS and a second controller can benefit from the addition of anti-IgE therapy to reduce asthma exacerbations; due to the known risk of side effects associated with high-dose ICS in children, omalizumab should also be considered in children and adolescents who repeatedly exacerbate or have poor control when therapy is stepped down from high-dose to moderate-dose ICS and at least one other controller; 5) Anti-IL5 therapies may be considered for adults 18 years of age and over with severe eosinophilic asthma who experience recurrent asthma exacerbations in spite of high doses of ICS in addition to at least one other controller; and 6) Although bronchial thermoplasty has shown a decrease in asthma exacerbations in one study, its role in the treatment of severe asthma remains uncertain. CONCLUSIONS: After reviewing existing and emerging therapies for severe asthma, we developed ke...

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Section: Corticosteroid-dependent Asthmamentioning

confidence: 99%

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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“…Children with asthma, another atopic condition commonly treated with CS, show a higher percentage of HPA axis suppression following the use of inhaled CS at rates of 7.7–42% depending on the potency and duration of use [39-43]. These findings prompted new Pediatric Endocrine Society guidelines recommending dynamic HPA axis testing for children with asthma treated with chronic high-dose inhaled CS or those with specific clinical features suggestive of AI [44, 45]. Unlike inhaled CS, there are currently no specific monitoring guidelines for AI in children following topical CS use, but formal testing is recommended if clinical signs of AI are noted [46].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis

et al. 2018

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Background/Aims: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. Methods: All published pediatric clinical trials evaluating TCS use with pre- and post-treatment HPA axis assessment by cosyntropin stimulation testing were included. Results: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA axis suppression (3.8%, 95% CI 2.4–5.8). The percentage of HPA axis suppression with low- (classes 6–7), medium- (classes 3–5) and high-potency (classes 1–2) TCS use was 2% (3 of 148 patients, 95% CI 0.7–5.8), 3.1% (7 of 223 patients, 95% CI 1.5–6.3), and 6.6% (10 of 151 patients, 95% CI 3.6–11.8), respectively. Conclusion: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.

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“…Factors affecting individual variation in the growth suppressing effect of ICS include age, pubertal status, adherence to therapy, timing of administration, and concomitant use of other medications that suppress growth. The most serious potential adverse effect associated with ICS therapy is adrenal insufficiency (51), and requires constant vigilance. Children with growth suppression or other systemic effects from ICS should be screened for adrenal insufficiency by obtaining AM cortisol and plasma adrenocorticotrophic hormone (ACTH).…”

Section: Discussionmentioning

confidence: 99%

Growth perturbations from stimulant medications and inhaled corticosteroids

Richardson¹,

Seibert²,

Uli³

2017

Transl. Pediatr

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Stimulant medications for the treatment of attention deficit hyperactivity disorder (ADHD) and inhaled corticosteroids (ICS) for the treatment of asthma are two classes of medications that are commonly prescribed in pediatrics. Among other adverse effects of these medications, growth attenuation has long been a focus of investigation. With stimulants, growth deficits of 1-1.4 cm/year have been observed in the short term, mainly in the first 2 years of treatment, in a dose-dependent manner. Long-term studies on stimulants have reported divergent effects on growth, with many studies showing no clinically significant height deficits by adulthood. The study that followed the largest cohort of children on stimulants, however, reported an overall adult height deficit of 1.29 cm in subjects who had received stimulant medications, with mean adult height deficit of 4.7 cm among those taking the medication consistently. With ICS use, mild growth suppression is seen in the short term (particularly in the first year of therapy) with growth rates reduced by 0.4-1.5 cm/year. Available current evidence indicates that the impact of ICS use on adult height is not clinically significant, with effects limited to 1.2 cm or less. There is significant individual variability in growth suppression with ICS use, with the specific pharmacologic agent, formulation, dose exposure, age, puberty, medication adherence, and timing of administration being important modifying factors. Based on currently available evidence, the therapeutic benefits of ICS for management of asthma and stimulant medications for management of ADHD outweigh the potential risk for growth suppression. Strategies to minimize growth attenuation and other potential adverse effects of these medications include using the lowest efficacious dose, frequent assessments and dose titration. Particular vigilance is essential with concomitant use of multiple medications that can attenuate growth and to evaluate for potential adrenal insufficiency from ICS use.

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Endocrine Effects of Inhaled Corticosteroids in Children

Cited by 70 publications

References 78 publications

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis

Growth perturbations from stimulant medications and inhaled corticosteroids

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