천식 환자에서 흡입용 스테로이드 장기 사용의 시상하부-뇌하수체-부신축 억제 효과 = AARD : ORIGINAL ARTICLE ; Suppressive effects of long-term treatment with inhaled steroids on hypothalamic-pituitary-adrenal axis in asthma

다국어 초록 (Multilingual Abstract)

Purpose: Long-term treatment with inhaled steroids (ICS), especially fluticasone that developed lately, may suppress the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the relationship between ICS use and HPA axis suppression in asthmatics under ICS treatment for average 4.5 years. Methods: The medical records of 129 adult asthmatics who received ICS treatment for 6 months or more and underwent a corticotropin stimulation test from January 2005 to August 2013 were retrospectively reviewed. Results: The patients received ICS only (n=87) were found to have an abnormal response to the corticotropin test in as high as 32.2%, and those received ICS in combination with oral steroids (n=42) had a significantly higher prevalence of the response (71.4%, P<0.001). Abnormal responses to corticotropin occurred depending on ICS daily doses (low, n=8, 12.5%; medium, n=19, 36.8%; high, n=102, 49.0%; X2=4.384, P=0.036). Among the subjects received ICS only, nasal steroid doses (P=0.016) but not ICS doses (P=0.159) were significantly higher in those with abnormal responses than the others. Among all the subjects, oral steroid use (odds ratio [OR], 4.27; 95% confidence interval [CI], 2.35-11.80; P<0.001) and nasal steroid dose (OR, 1.02; 95% CI, 1.00-1.04; P=0.015) were significant risk factors for HPA axis suppression. Conclusion: One-third of asthmatics under long-term treatment with ICS showed a suppression of the HPA axis in a dose-dependent manner. Oral or nasal steroid use may be a risk factor for the suppression. However, since our results may have been overestimated due to subject selection bias, further prospective case-control studies are warranted.

참고문헌 (Reference)

1 Yip CE, "The role of morning basal serum cortisol in assessment of hypothalamic pituitary-adrenal axis" 36 : E216-E222, 2013

2 The Global Initiative for Asthma, "The Global Initiative for Asthma. Global strategy for asthma management and prevention 2012(update)[Internet]. [cited 2014 Jan 22]. Available from"

3 Lipworth BJ, "Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis" 159 : 941-955, 1999

4 Todd GR, "Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom" 87 : 457-461, 2002

5 Pauwels RA, "Safety and efficacy of fluticasone and beclomethasone in moderate to severe asthma. Belgian Multicenter Study Group" 157 (157): 827-832, 1998

6 Webster JI, "Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products" 181 : 207-221, 2004

7 Guilbert TW, "Role of infection in the development and exacerbation of asthma" 4 : 71-83, 2010

8 Heller MK, "Reversal of adrenal suppression with ciclesonide" 47 : 337-339, 2010

9 Crapo RO, "Reference spirometric values using techniques and equipment that meet ATS recommendations" 123 : 659-664, 1981

10 The Korean Society of Allergology, "National guideline for the diagnosis and management of allergic rhinitis" 19 : 809-885, 1999

11 Schwartz RH, "Moderate dose inhaled corticosteroid-induced symptomatic adrenal suppression: case report and review of the literature" 51 : 1184-1190, 2012

12 Wolthers OD, "Measures of hypothalamic-pituitary-adrenal function in patients with asthma treated with inhaled glucocorticoids: clinical and research implications" 36 : 477-486, 1999

13 Dickstein G, "Low-dose and high-dose adrenocorticotropin testing: indications and shortcomings" 15 : 244-249, 2008

14 Adams RJ, "Intranasal steroids and the risk of emergency department visits for asthma" 109 : 636-642, 2002

15 Masoli M, "Inhaled fluticasone propionate and adrenal effects in adult asthma: systematic review and meta-analysis" 28 : 960-967, 2006

16 Han ER, "Inhaled corticosteroid-related tooth problems in asthmatics" 46 : 160-164, 2009

17 Wlodarczyk JH, "Impact of inhaled corticosteroids on cortisol suppression in adults with asthma: a quantitative review" 100 : 23-30, 2008

18 Zollner EW, "Hypothalamic-pituitary-adrenal axis suppression in asthmatic school children" 130 : e1512-e1519, 2012

19 Zollner EW, "Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled corticosteroids: part 1. Which test should be used?" 18 : 401-409, 2007

20 National Heart, Lung, and Blood Institute, "Expert panel report 3: Guidelines for the diagnosis and management of asthma full report 2007" National Institute of Health 2007

21 Lee YC, "Effect of inhaled steroids on the cortisol concentration by different dosage or delivery method" 42 : 888-899, 1995

22 Lipworth BJ, "Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma" 94 : 465-472, 2005

23 Waalkens HJ, "Cessation of long-term treatment with inhaled corticosteroid (budesonide) in children with asthma results in deterioration. The Dutch CNSLD Study Group" 148 : 1252-1257, 1993

24 Bousquet J, "Allergic rhinitis and its impact on asthma" 108 (108): 147-334, 2001

25 Ahmet A, "Adrenal suppression: a practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy" 7 : 13-, 2011

26 Sim D, "Adrenal suppression from high-dose inhaled fluticasone propionate in children with asthma" 21 : 633-636, 2003

27 Neary N, "Adrenal insufficiency: etiology, diagnosis and treatment" 17 : 217-223, 2010

28 Oelkers W, "Adrenal insufficiency" 335 : 1206-1212, 1996

29 Charmandari E, "Adrenal insufficiency" 383 : 2152-2167, 2014