Purpose of the Study
To study the effect of high-dose intravenous gammaglobulin (IVIG) in severe childhood asthma.
Thirty-one children (15 girls, 16 boys), 9 to 22 years of age (median, 14 years), with long-term severe asthma (forced expiratory volume in 1 second [FEV1] <70%), requiring more than 2 months of inhaled steroid (>800 μg/day of budesonide or beclomethasone) and at least 10 days of a systemic glucocorticoid in connection with an asthma exacerbation in the previous year, were included in the study.
The study was performed as a prospective, double-blind, placebo-controlled, multicenter study in Germany. They were randomized into 2 groups, one received 1 g/kg of IVIG and the other received an identical dose of intravenous albumin. Baseline twice daily symptom scores and peak-flow measurements and monthly lung function and bronchial hyperresponsiveness (BHR) to histamine measurements were made over a 2-month stabilization period and then repeated monthly during the 3-month treatment period and during a 1-month follow-up period.
There were no statistically significant differences between the two groups at baseline. Sixteen of the children (10 in active group, 6 in control group) were atopic by skin testing. The IVIG treated group had fewer days of upper respiratory infections versus the control group. There was a trend toward fewer symptoms in the treatment versus the control group, but this did not reach statistical significance. There was no statistical significance between the IVIG treated and control groups for BHR to histamine, lung function, peak expiratory flow rates including variability, blood eosinophil counts, total immunoglobulin E (IgE) level or inhaled steroid doses.
These results are quite different from the results reported by Landwehr et al (see below) who observed significant improvement with IVIG treatment in the 11 steroid dependent asthmatics that they studied. There are several differences between these studies. The group in this study was not steroid-dependent and was a less severe group compared with the Landwehr study. The Landwehr study evaluated 5 children and 6 adults (all treated with IVIG, no placebo-control) and this study looked included 31 children (16 on IVIG). This study did not address the steroid-sparing effect of IVIG, which was the primary focus of the Landwehr study. The dose of IVIG used in the Landwehr study was twice the dose of this study. Neither study found a change in BHR with IVIG treatment although histamine was used in this study and methacholine in the other.
This study further supports the need for more extensive placebo-controlled studies of IVIG treatment in severe asthma, including possible dose-response studies. From a cost-effective standpoint, it seems most reasonable to study this treatment in a more severely affected group (ie, oral steroid-dependent asthmatics).