Landwehr LP, Jeppson JD, Katlan MG, et alChest.114199813491356To determine the efficacy of intravenous gammaglobulin (IVIG) in severe asthma to reduce steroid requirements.Eleven severe steroid-dependent asthmatics (5 adolescents, mean age 14 years; 6 adults, mean age 38.5 years) were studied at National Jewish Medical Center in Denver, Colorado. Subjects were excluded if they had cystic fibrosis, chronic bronchitis, acute sinusitis, immunodeficiency, or other chronic diseases besides asthma.Steroid dependency was defined as requiring ≥0.25 mg/kg/day for a minimum of 2 months before entry into the study and subjects must have had at least one exacerbation of their asthma during the previous 3 months requiring an additional short course of high-dose oral steroids. All subjects had been taking daily or alternate day oral steroids for several years. All subjects received optimal asthma therapy including high-dose inhaled steroids and short- and long-acting β-agonists. Subjects underwent a 2-month observation period before starting IVIG during which aggressive attempts were made to wean their steroids. The subjects then underwent a 6-month treatment period during which they received in addition to optimal asthma treatment, 2 g/kg/28 days of IVIG. They were then followed for an additional 30 days until the study end. Pre- and postbronchodilator pulmonary function testing and bone densitometry was performed the month before the treatment period and at the end of the study. Twice daily peak expiratory flow rates (PEFRs) were obtained and diurnal variability was calculated. Symptom score diaries were kept twice daily by subjects or family members and medication usage was monitored throughout. Bronchial hyperresponsiveness was determined by methacholine challenge at baseline, at midpoint of the treatment phase, and at the study end.Monthly treatment with high-dose IVIG resulted in a substantial decrease in oral steroid requirements in all subjects with an average pre-IVIG treatment daily steroid dose of 31.6 ± 5.1 mg to an average daily dose of 5.5 ± 0.2 mg at the end of the 6-month treatment, an 82% overall mean reduction in oral steroid dose. There was no significant difference in the dosage difference between adolescent and adult subjects, although the initial taper was more rapid in the adolescents. All parameters of pulmonary function showed overall improvement, including 3 adolescents who had forced expiratory volume in 1 second (FEV1) levels in normal range (>80% of predicted) at study completion. There was, however, no difference in methacholine reactivity despite improvements in overall clinical improvement, pulmonary function, PEFR measurements, and symptom scores. Bone mineral density improved in 9 of 10 subjects studied.A significant steroid-sparing effect of high-dose IVIG was found in both groups, without an adverse effect on pulmonary function. Previous studies have shown symptom reemergence upon IVIG cessation, although this study only reported follow-up for 1 month posttreatment. The authors suggest that the lack of change in methacholine hyperresponsiveness may indicate that IVIG reduces inflammation and symptoms without affecting airway smooth muscle responsiveness, but further studies are needed to investigate this possibility. The mechanism of action of IVIG in asthma is unknown, but possible mechanisms include effects on cytokine production, improved host defense, and other immunomodulatory effects.Given the significant side effects of long-term oral steroid use, alternative antiinflammatory agents for the treatment of severe asthma have been sought for years with disappointing results (eg, methotrexate, gold, troleandomycin). The results of this study as well as a similar study by the same group in younger children (Mazer,J Allergy Clin Immunol. 1991) are encouraging. However, a large scale longer term placebo-controlled study is needed to truly determine the efficacy of this product in severe steroid-dependent asthmatics. In addition, cost-benefit and risk-benefit analysis needs to be determined, given the high cost of such treatment and the fact that previous viral contaminations have occurred.