Summary Background Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment. Methods In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5–18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 µg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 µg) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329. Results 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)—555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37–61), the frequency of exacerbations was lower in the daily (28%, 18–40, p=0·03), combined (31%, 21–43, p=0·07), and rescue (35%, 24–47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14–43) in the placebo group, compared with 5·6% (1·6–14) in the combined (p=0·012), 2·8% (0–10) in the daily (p=0·009), and 8·5% (2–15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis. Interpretation Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled...

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.

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Background Inhaled corticosteroids (ICSs) are recommended as first-line therapy for children with mild persistent asthma; however, specific patient characteristics may modify the treatment response. Objective Identify demographic, clinical, and atopic characteristics that may modify the ICS treatment response among children enrolled in the Treating Children to Prevent Exacerbations of Asthma (TREXA) trial. Methods Children age 6-18 years with mild persistent asthma were randomized to 44 weeks of combined, daily, rescue, or placebo treatment. Daily treatment consisted of 40 mcg of beclomethasone twice daily. Rescue treatment consisted of 40 mcg beclomethasone accompanying each symptom-driven albuterol actuation. Combined treatment consisted of both. Outcomes included time to first exacerbation and proportion of asthma control days. Fourteen baseline characteristics were selected for interaction testing based on their clinical relevance. Results Two-hundred-eighty-eight children were randomized. Seventy-five percent were white and 55% were male. As measured by time to first exacerbation, 4 characteristics identified children who received greater benefit from treatment: non-Hispanic ethnicity, positive aeroallergen skin test, serum immunoglobulin E level ≥350 K/μL, and history of oral corticosteroid use in the year prior to enrollment. As measured by asthma control days, 4 characteristics identified children who received greater benefit from treatment: male sex, positive aeroallergen skin test, serum immunoglobulin E level ≥350 K/μL, and incomplete run-in asthma control. Conclusions Children with mild persistent asthma who have markers of atopic asthma or who have greater asthma burden may obtain greater benefit from beclomethasone therapy. Additional study is needed to confirm whether these markers can guide individualized therapy.

Over the last two decades, the prevalence of peanut and tree nut allergy has increased throughout the western world. Adverse reactions to these foods account for over 50% of all deaths resulting from food-related anaphylaxis. Until recently, evidence suggested that all peanut and tree nut allergy were permanent. It is now known that about 20% and 10%, respectively, of young patients outgrow peanut and tree nut allergies. Achieving tolerance is associated with increasing circulating T regulatory cells and reduced production of allergen-specific IgE. Reliable predictors of resolution are not yet available. A direct correlation between skin test weal size and allergen-specific IgE, at the time of diagnosis and likelihood of resolution, has been reported. Resolution of peanut or tree nut allergy cannot be determined conclusively by either allergen-specific IgE analysis or by skin prick testing. Oral food challenge is the gold standard for determining resolution of food allergy. Food challenges should only be undertaken in a clinical setting fully equipped to deal with a potential severe adverse reaction. Approximately 8% of patients who outgrow peanut allergy may suffer a recurrence, but recurrent tree nut allergy has not been reported to date. Infrequent ingestion of peanut may be related to the re-emergence of allergy. Induction of tolerance through oral immunotherapy or sublingual immunotherapy is now being actively studied, but remains experimental. Studies have reported short-term desensitization to peanut, but ongoing follow-up will determine whether tolerance is achieved long term.