Michael J. Kraemer

Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid–dependent, persistent asthma

BACKGROUND Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers. OBJECTIVE We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children. METHODS This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients. RESULTS Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P </=.026), reducing use of breakthrough medication (P </=.032), and improving morning peak expiratory flow (P </=.030). The number of dropouts because of worsening asthma was also significantly fewer in the budesonide groups (P </=.015). There were no differences between doses of budesonide. Adverse events and basal and adrenocorticotrophic hormone-stimulated cortisol responses were not different between budesonide and placebo groups. CONCLUSION Budesonide inhalation suspension, 0.25 mg, 0.50 mg, and 1.0 mg twice daily, is an effective and safe treatment for young children with inhaled steroid-dependent, persistent asthma.

In vitro studies of the hyper-IgE disorders: Suppression of spontaneous IgE synthesis by allogeneic suppressor T lymphocytes

Abstract We evaluated seven hyper-IgE patients and five nonatopic controls to determine whether in vitro IgE synthesis was under T-cell control. Cultures of B lymphocytes with or without various T-cell subsets were assayed for in vitro de novo IgE synthesis. Hyper-IgE B cells but not B cells from normal controls spontaneously synthesized IgE. Hyper-IgE B cells cultured with autologous T cells showed slight suppression of IgE synthesis (average 13.4%); greater suppression occurred in cocultures with allogeneic T cells from normal controls (average 48.7%). Similar suppression was observed in cocultures with allogeneic T cells obtained from another hyper-IgE patient. The allogeneic suppression of IgE synthesis was ablated by removing the suppressor T-cell (OKT8+) subset. These studies show that (i) B cells from hyper-IgE patients actively synthesize large amounts of IgE in vitro; (ii) this can be suppressed by adding normal or hyper-IgE allogeneic T cells (OKT8+); and (iii) the observed suppression may reflect solely an in vitro allogeneic effect and not biologic regulatory mechanisms.