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Communications to the Editor |

IV Immunoglobulin for Asthma? IV Immunoglobulin for Asthma? FREE TO VIEW

Miles Weinberger, MD
Author and Funding Information

Affiliations: University of Iowa College of Medicine, Iowa City, IA ,  National Jewish Medical and Research Center Denver, CO Correspondence to: Erwin W. Gelfand, MD, Chairman, Department of Pediatrics, National Jewish Medical and Research Center, 1400 Jackson St, Denver, CO; e-mail: gelfand@njc.org

Correspondence to: Miles Weinberger, MD, Director, Pediatric Allergy & Pulmonary Division, University of Iowa College of Medicine, 200 Hawkins Dr, Iowa City, IA 52242-1083; e-mail: miles-weinberger@uiowa.edu



Chest. 1999;116(1):267-268. doi:10.1378/chest.116.1.267-a
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To the Editor:

Landwehr et al (November 1998)1conclude that IV immunoglobulin (IVIg) “provides a potentially important adjunctive therapy in severe asthma, reducing oral steroid requirements and steroid side effects without deterioration of lung function.” They make this statement definitively and without apparent equivocation based on an open label study done without controls for a disease known to be highly variable in its clinical course. They identified the greatest benefit to be in adolescents, a population known to have a high rate of noncompliance with effective inhaled maintenance medications,2such as inhaled corticosteroids, without considering the potential influence of closer monitoring during a study on their adherence to other aspects of the medical regimen. No credible mechanism is proposed to explain the alleged benefit that IVIg has in patients with asthma other than the argument by analogy of its benefit for patients with other diseases quite unrelated to asthma. This series of 11 patients is a sequel to a previous open label study published in 19913 on the effect of IVIg on asthma. Although the results reported for these 11 cases are sufficient to argue for a controlled clinical trial, it appears premature and imprudent to state, as the authors do, that “this study extends and confirms the response of patients with severe, steroid-dependent asthma to IVIg therapy.” Since one of the authors of this manuscript also coauthored the previous report 8 years earlier, it is not apparent why a randomized placebo-controlled clinical trial, which the authors of the previous report suggested should be warranted,3 was not done in this case instead of repeating an open label period of treatment that continues to provide only a question, not an answer.

Landwehr, LP, Jeppson, JD, Katlan, MG, et al (1998) Benefits of high-dose IV immunoglobulin in patients with severe steroid-dependent asthma.Chest114,1349-1356. [CrossRef]
 
Kelloway, JS, Wyatt, RA, Adlis, SA Comparison of patients’ compliance with prescribed oral and inhaled asthma medications.Arch Intern Med1994;154,1349-1352. [CrossRef]
 
Mazer, BD, Gelfand, EW An open-label study of high-dose intravenous immunoglobulin in severe childhood asthma.J Allergy Clin Immunol1991;87,976-983. [CrossRef]
 

IV Immunoglobulin for Asthma?

To the Editor:

Dr. Weinberger has raised several important issues regarding our recent publication on the benefits of high-dose IV immunoglobulin (IVIg) in patients with severe steroid-dependent asthma (November 1998).1 He questions our use of definitive language, our conclusions based on a population with a high failure rate of compliance, our failure to propose a credible mechanism of action, and the absence of a randomized placebo-controlled clinical trial.

We believe that throughout the paper, we discuss in a nondefinitive manner the potential for IVIg therapy and the need for further studies that define the mechanism of action and the optimal treatment regimen. The issues raised about compliance are certainly valid. In the design of the study, we made vigorous attempts during the 2-month run-in to optimize therapy during regular visits. In addition, because these patients were regularly followed at the National Jewish Medical and Research Center, they were under close monitoring prior to the initiation of the study. During the study, the patients were only seen monthly. As to the mechanism of action, most investigators believe that IVIg exhibits potent anti-inflammatory effects, and one target is the inhibition of cytokine production. This has been documented in several publications including our own.24 A novel mechanism of action proposing that IVIg may affect steroid sensitivity has been reported.5The final issue questions why a randomized placebo-controlled trial has not been carried out. There is no doubt in any of our minds that such a trial is absolutely required. Some trials have been carried out in a double-blind fashion but at lower doses. Nonetheless, their findings support our conclusions.6 However, in light of the current limitations of IVIg availability and the reluctance of pharmaceutical companies to support such a trial at the recommended doses during the current crisis period, we have continued to examine all issues surrounding IVIg use in this small group of asthmatics by using a cross-over design. In this way, we believe that progress has been made and that patients have benefited. We have been cautious in our conclusions, and we do not consider any of our statements as “premature or imprudent.”

References
Landwehr, LP, Jeppson, JD, Katlan, MG, et al Benefits of high-dose IV immunoglobulin in patients with severe steroid-dependent asthma.Chest1998;114,1349-1356. [CrossRef]
 
Andersson, JP, Andersson, WG Human intravenous immunoglobulin modulates monokine production in vitro.Immunology1990;71,372-376
 
Amran, D, Renz, H, Lack, G, et al Suppression of cytokine dependent human T-cell proliferation by intravenous immunoglobulin.Clin Immunol Immunopathol1994;73,180-186. [CrossRef]
 
Modiano, JF, Amran, D, Lack, G, et al Post transcriptional regulation of T cell IL-2 production by human pooled immunoglobulin.Clin Immunol Immunopathol1994;83,75-88
 
Spahn, JD, Leung, DYM, Chan, MTS, et al Mechanisms of glucocorticoid reduction in asthmatics treated with intravenous immunoglobulin.J Allergy Clin Immunol1999;103,421-426. [CrossRef]
 
Salmun, LM, Barlan, I, Wolf, H, et al Intravenous immunoglobulin for the treatment of severe asthma [abstract]. J Allergy Clin Immunol. 1997;;99 ,.:S268
 

Figures

Tables

References

Landwehr, LP, Jeppson, JD, Katlan, MG, et al (1998) Benefits of high-dose IV immunoglobulin in patients with severe steroid-dependent asthma.Chest114,1349-1356. [CrossRef]
 
Kelloway, JS, Wyatt, RA, Adlis, SA Comparison of patients’ compliance with prescribed oral and inhaled asthma medications.Arch Intern Med1994;154,1349-1352. [CrossRef]
 
Mazer, BD, Gelfand, EW An open-label study of high-dose intravenous immunoglobulin in severe childhood asthma.J Allergy Clin Immunol1991;87,976-983. [CrossRef]
 
Landwehr, LP, Jeppson, JD, Katlan, MG, et al Benefits of high-dose IV immunoglobulin in patients with severe steroid-dependent asthma.Chest1998;114,1349-1356. [CrossRef]
 
Andersson, JP, Andersson, WG Human intravenous immunoglobulin modulates monokine production in vitro.Immunology1990;71,372-376
 
Amran, D, Renz, H, Lack, G, et al Suppression of cytokine dependent human T-cell proliferation by intravenous immunoglobulin.Clin Immunol Immunopathol1994;73,180-186. [CrossRef]
 
Modiano, JF, Amran, D, Lack, G, et al Post transcriptional regulation of T cell IL-2 production by human pooled immunoglobulin.Clin Immunol Immunopathol1994;83,75-88
 
Spahn, JD, Leung, DYM, Chan, MTS, et al Mechanisms of glucocorticoid reduction in asthmatics treated with intravenous immunoglobulin.J Allergy Clin Immunol1999;103,421-426. [CrossRef]
 
Salmun, LM, Barlan, I, Wolf, H, et al Intravenous immunoglobulin for the treatment of severe asthma [abstract]. J Allergy Clin Immunol. 1997;;99 ,.:S268
 
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