Daily or Intermittent Budesonide in Preschool Children with Recurrent Wheezing

Abstract

BACKGROUND Daily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy. METHODS We studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy. RESULTS The daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen. CONCLUSIONS A daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year.

Classification and pharmacological treatment of preschool wheezing: changes since 2008

“…Two randomised trials compared the effect on day-to-day symptoms and exacerbation frequency of daily low-dose and intermittent high-dose nebulised ICS [24,25]. Interval symptoms decreased more with continuous low-dose treatment in one study [25] but there was no difference in the number and severity of exacerbations in either study [24,25]. Both studies used nebulised treatment, which is more cumbersome and less effective than a metered-dose inhaler (MDI)/spacer combination [26].…”

Inhaled Corticosteroids in Lung Diseases

“…Although the combination BUD with the long-acting b 2 agonist (LABA) formoterol in a single inhaler has been approved in Europe and other countries for maintenance and reliever therapy, it has not been approved for this use in the United States, and recently concerns have been expressed that patients receiving this therapy are not well controlled and may have inadequately treated airways inflammation (30). The use of intermittent ICS therapy for preschool children with viral-induced wheezing is of particular interest (36)(37)(38). Two recent trials suggest that intermittent high-dose use is as effective as continuous low-dose therapy and placebo in infants and young children (37,38).…”

“…The use of intermittent ICS therapy for preschool children with viral-induced wheezing is of particular interest (36)(37)(38). Two recent trials suggest that intermittent high-dose use is as effective as continuous low-dose therapy and placebo in infants and young children (37,38). However, the children in the latter trial who received very-high-dose FP (1.5 mg/d via MDI plus VHC) experienced systemic effects of weight and growth retardation (38), whereas the children who received high-dose BUD (2.0 mg/d via jet nebulization) did not (37).…”

Mortality in Asthma-Chronic Obstructive Pulmonary Disease Overlap in the United States

“…463 In young children with recurrent viral-induced wheezing, regular LTRA improves some asthma outcomes compared with placebo, but does not reduce the frequency of hospitalizations, courses of prednisone, or number of symptom-free days (Evidence A). 464 For pre-school children with frequent viral-induced wheezing and with interval asthma symptoms, as-needed (prn) 465 or episodic ICS 466 may be considered but a trial of regular ICS should be undertaken first.…”