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Intermittent Inhaled Corticosteroids in Infants With Episodic Wheezing Did Not Decrease Rate of Progression to Asthma


  • In infants with wheezing and coughing, does the acute use of inhaled steroids control during symptomatic time periods result in decreased progression to asthma later in childhood?

Clinical Bottom Lines

  1. Early intervention in infants with intermittent inhaled corticosteroid therapy had no effect on the progression from episodic to persistent wheezing in young children.1
  2. Intermittent inhaled corticosteroid therapy in infants with wheezing had no short-term effect on acute symptomatic relief.

Summary of Key Evidence

  1. Randomized, double blind, placebo controlled trial.1
  2. Number of patients enrolled at one month of age = 411, number of patients undergoing randomization at mean age of 10.7 months of age (when first episode of wheezing occurred) = 301, number of patients actually receiving treatment = 294.
  3. Excluded for severe congenital anomaly, gest age < 36 weeks, need for mechanical ventilation, and airway infection prior to enrollment.
  4. “Wheezing” defined as any symptom severely affecting child’s breathing, manifested as noisy breathing (wheezing, whistling), breathlessness, SOB, or persistent coughing; “episode” defined as wheezing on three consecutive days.
  5. Budesonide 400mcg daily vs placebo to be given by MDI with spacer at the start of a wheezing episode for total of two weeks.
  6. Terbutaline used as needed for rescue medication; otherwise, no other asthma medications.
  7. Patients were monitored and treated if episodes occurred during the first three years of life.
  8. Discontinued participation if persistent wheezing, defined as five “episodes” within six months, daily symptoms for four weeks, or acute severe symptoms resulting in hospitalization.
  9. Primary outcomes: proportions of symptom-free days, days free of need for rescue medication, and number of episodes were similar in the two groups.
  10. Secondary outcomes: percentage of patients discontinued from study due to persistent wheezing, time to study discontinuation, and time between the first and second wheezing episodes were similar between the two groups.

Additional Comments

  • Frequency of episodes was 3.1 per child per year in budesonide group and 2.7 per child per year in the placebo group
  • The respiratory symptoms were similar between the two groups, lasting on average 10 days
  • Each patient screened for respiratory viruses with each episode. The immediate treatment effect not affected by viral status
  • Height and bone mineral density at three years were unaffected by treatment
  • Recent randomized, double blind, controlled study and associated commentary confirmed results of this study.2


  1. Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. Intermittent inhaled corticosteroids in infants with episodic wheezing.  N Engl J Med 2006;354:1998-2005.
  2. Murray CS, Woodcock A, Langley SJ, Morris J, Custovic A; IFWIN study team. Secondary prevention of asthma by the use of iInhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study.  Lancet. 2006;368:754-62.

CAT Author: David Jeong, MD

CAT Appraisers: John Frohna, MD, MPH

Date appraised: February 21, 2007

Last updated July 2, 2007
Department of Pediatrics and Communicable Diseases
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