Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that?

ORIGINAL ARTICLE Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that? Oral corticosteroids for asthma exacerbations might be associated with adrenal suppression: Are physicians aware of that? Cristina B. Barra1, Maria Jussara F. Fontes2, Marco Túlio G. Cintra3, Renata C. Cruz3, Janaína A. G. Rocha3, Maíla Cristina C. Guimarães3, Ivani Novato Silva1* Professor of the Department of Pediatrics, Pediatric Endocrinology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade Federal de Minas Gerais (HC-FM-UFMG), Belo Horizonte, MG, Brazil 1 2 Professor of the Department of Pediatrics, Pediatric Pneumology Division, HC-FM-UFMG, Belo Horizonte, MG, Brazil 3 Medical Student, FM-UFMG, Belo Horizonte, MG, Brazil Summary Study conducted at Endocrinology and Pneumology Division, Department of Pediatrics, Faculdade de Medicina/ Hospital das Clínicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil Article received: 12/8/2016 Accepted for publication: 2/5/2017 *Correspondence: Divisão de Endocrinologia Infantil e do Adolescente Departamento de Pediatria, Faculdade de Medicina/Hospital das Clínicas – UFMG Address: Av. Alfredo Balena, 190, sala 267 Belo Horizonte, MG – Brazil Postal code: 30130-100 http://dx.doi.org/10.1590/1806-9282.63.10.899 Introduction: Oral corticosteroids (OCS) are a mainstay of treatment for asthma exacerbations, and short-term OCS courses were generally considered to be safe. Nevertheless, frequent short-term OCS courses could lead to hypothalamicpituitary-adrenal (HPA) axis dysfunction. Our study aimed at investigating the integrity of the HPA axis in children with persistent asthma or recurrent wheezing at the beginning of an inhaled corticosteroids (ICS) trial. Method: Morning basal cortisol was assessed just before the beginning of ICS, and 30, 60, and 90 days later, using Immulite® Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay (Los Angeles, USA; 2006). Results: In all, 140 children (0.3-15 years old) with persistent asthma or recurrent wheezing have been evaluated and 40% of them reported short-term OCS courses for up to 30 days before evaluation. Out of these, 12.5% had biochemical adrenal suppression but showed adrenal recovery during a three-month ICS trial treatment. No significant differences were observed among children with or without adrenal suppression, neither in the number of days free of OCS treatment before cortisol evaluation (p=0.29) nor in the last OCS course duration (p=0.20). The number of short-term OCS courses reported in the year preceding the cortisol evaluation was also not different (p=0.89). Conclusion: Short-term systemic courses of corticosteroids at conventional doses can put children at risk of HPA axis dysfunction. ICS treatment does not impair adrenal recovery from occurring. Health practitioners should be aware of the risk of a blunted cortisol response upon exposure to stress during the follow-up of patients with persistent asthma or recurrent wheezing. Keywords: asthma, corticosteroids, suppression, child. Introduction Corticosteroids are a mainstay of treatment for asthma and in conjunction with inhaled short-acting beta2-agonists (SABA) are responsible for lower children hospitalization rates during flare-ups.1 Short-term oral corticosteroids (OCS) courses used in asthma exacerbations are normally considered to be safe and the possibility of adrenal failure was disregarded.2 But children who recurrently visit a health care provider and require multiple OCS courses may have hypothalamic-pituitary-adrenal (HPA) axis dysfunction.3 Rev Assoc Med Bras 2017; 63(10):899-903 Baseline cortisol measurements are classically performed to confirm the integrity of the HPA axis response in several clinical situations, such as suspected adrenal suppression (AS). Morning basal cortisol assessment is a simple, inexpensive method with good correlation with serum cortisol after corticotropin-releasing hormone (CRH) stimulus and could be a screening tool in children with asthma at risk of AS after corticosteroid withdrawal.4-6 The study aimed at investigating the integrity of the HPA axis in children with persistent asthma and infants 899 Barra CB et al. with recurrent wheezing at the beginning of a first inhaled corticosteroids (ICS) trial. Method This four-year prospective study was approved by the Research Ethics Committee of Federal University of Minas Gerais (UFMG), in Belo Horizonte, Brazil. The children, adolescents and legal guardians agreed to participate and signed an informed written consent after receiving all pertinent information. Participants were enrolled in a large Public Health Program for asthma control in Belo Horizonte, Brazil. The program is a partnership between UFMG and the Brazilian public health system (SUS, in the Portuguese acronym), which provides controller treatment according to The Global Strategy for Asthma Management and Prevention:7 ICS (beclomethasone dipropionate CFC with a spacer at daily doses of 100-200 mcg), inhaled bronchodilator SABA and OCS as needed (prednisone at 1-2 mg/kg). As part of the treatment, training for the children’s parents/guardians or carers and information on environmental control were also provided. Recurrent wheezing infants and children with persistent asthma who have been referred for ICS controller therapy trial were randomly recruited for a cross-sectional investigation of HPA axis integrity. Subjects who have previously received ICS or presented any other chronic disease that could interfere with adrenal function were not included. Morning cortisol level was assessed just before the beginning of ICS and 30, 60 and 90 days later. Following overnight fasting, blood samples were collected between 7:00 and 8:00 a.m., processed at the Hospital das Clínicas (HC) UFMG Laboratory Medical Service and evaluated using Immulite Siemens Medical Solutions Diagnostic chemiluminescent enzyme immunoassay, Los Angeles – USA, 2006. Lab work results were presented in mcg/dL (conversion factor: nmol/L = mcg/dL x 27.59). The participants’ basal serum cortisol levels were analyzed according to the manufacturer’s data. The manufacturer’s range is 5-25 mcg/dL, the detection limit (sensitivity) is > 0.2 mcg/dL and the working range is 1-50 mcg/dL. At each visit, all participants filled out a clinical data form. Statistical analysis Descriptive statistics were performed, and the data were presented as measures of central tendency and dispersion (median and mean±SD) for continuous variables and as proportions for categorical and quantitative variables. Chi-square or Fisher exact test were used to evaluate the association between categorical variables. To compare numeric variables between independent groups, Student’s t-test or Kruskal-Wallis test was used. A 95% confidence interval was calculated using the Fleiss quadratic method. The statistic (...truncated)