Beclomethasone diproprionate reduced airway inflammation without adrenal suppression in young children with cystic fibrosis: a pilot study

Pediatr Pulmonol. 2001 Oct;32(4):293-302. doi: 10.1002/ppul.1122.

Abstract

Inhaled corticosteroids are commonly used in cystic fibrosis (CF), but there are few studies evaluating their safety in young children. We, therefore, prospectively administered beclomethasone diproprionate (BDP) to 12 clinically stable young children with CF to examine the safety of this therapy with respect to adrenal suppression and airway infection. To determine potential mechanisms of corticosteroid action in CF, we also examined airway markers of inflammation before and after inhaled steroid treatment. BDP 210 microg twice a day was given via spacer for 2 months. Twelve-hour serum and urine cortisols and response to low-dose synthetic ACTH cortisol stimulation were assessed. Bronchoalveolar lavage fluid (BALF) was examined pre- and posttreatment with BDP by quantitative bacteriology and indices of airway inflammation, including levels of total neutrophils, neutrophil elastase-alpha-1 antiprotease complexes (NEAP), CA 19-9 mucin-associated antigen, interleukin-8 (IL-8), and macrophage IL-8 mRNA. Following 2 months of treatment, serum and urine cortisol levels were unchanged. Response to low-dose ACTH cortisol stimulation was not significantly decreased at 30 min. Posttreatment BALF bacterial density was not statistically different from pretreatment; however, one patient who was initially culture negative became culture-positive with Hemophilus influenzae. BALF total neutrophil counts, corrected for epithelial lining fluid dilution, were decreased to approximately one third of pretreatment values (P = 0.03). NEAP and CA 19-9 mucin-associated antigen demonstrated similar decreases. BALF IL-8 levels and macrophage IL-8 mRNA levels were not statistically changed. These findings suggest that treatment with BDP 420 microg per day for 2 months in young children with CF does not affect urine and blood cortisol, causes no decrease in adrenal reserve, and does not result in a clinically significant increase in airway infection. In addition, the fall in bronchoalveolar lavage fluid inflammatory markers following BDP suggests possible modulation of neutrophil influx into the CF airway and provides justification for further studies of inhaled corticosteroids in CF.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Glands / drug effects*
  • Adrenal Glands / physiology
  • Airway Resistance / drug effects
  • Analysis of Variance
  • Anti-Inflammatory Agents / administration & dosage*
  • Beclomethasone / administration & dosage*
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoscopy
  • Child
  • Child, Preschool
  • Cystic Fibrosis / diagnosis
  • Cystic Fibrosis / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation Mediators / analysis*
  • Interleukin-8 / analysis*
  • Male
  • Nebulizers and Vaporizers
  • Pilot Projects
  • Probability
  • Prospective Studies
  • RNA, Messenger / analysis*
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Inflammation Mediators
  • Interleukin-8
  • RNA, Messenger
  • Beclomethasone