Reply

Abstract

Cowan et al1Cowan J. Mulpuru S. Alvarez G. Corrales-Medina V. Cameron D.W. Chronic obstructive pulmonary disease exacerbation frequency and serum IgG levels.J Allergy Clin Immunol. 2018; 141: 830-831PubMed Google Scholar bring up a number of important points regarding our findings2Leitao Filho F.S. Won Ra S. Mattman A. Schellenberg R.S. Fishbane N. Criner G.J. et al.Serum IgG and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease.J Allergy Clin Immunol. 2017; 140: 1164-1167.e6Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar and the potential use of immunoglobulin replacement therapy (IGRT) for patients with chronic obstructive pulmonary disease (COPD). First, we agree that the measurements of total IgG levels in our study could have been influenced by other factors, such as long-term therapy with inhaled corticosteroids or a recent course of systemic corticosteroids. To reduce this possibility, in our analysis, we adjusted for these variables and serum IgG levels were still significantly associated with reduced risk of exacerbations. Although we cannot fully discount the possibility of residual confounding by these and other variables, we believe based on this and other analyses3McCullagh B.N. Comellas A.P. Ballas Z.K. Newell Jr., J.D. Zimmerman M.B. Azar A.E. Antibody deficiency in patients with frequent exacerbations of chronic obstructive pulmonary disease (COPD).PLoS One. 2017; 12: e0172437Crossref PubMed Scopus (38) Google Scholar, 4Cowan J. Gaudet L. Mulpuru S. Corrales-Medina V. Hawken S. Cameron C. et al.A retrospective longitudinal within-subject risk interval analysis of immunoglobulin treatment for recurrent acute exacerbation of chronic obstructive pulmonary disease.PLoS One. 2015; 10: e0142205Crossref PubMed Scopus (31) Google Scholar that reduced circulating IgG levels predispose patients with COPD to exacerbations. Second, we agree with Cowan et al that rigorously designed therapeutic trials are needed to determine whether IGRT would significantly reduce severe exacerbations in COPD. Although it is uncertain whether all or only some patients with COPD should be entered in such trials, based on a priori biology, it is unlikely that all patients with COPD would derive clinical benefit from IGRT. In addition, it is not clear what the best strategy would be for selecting patients with COPD for IGRT. Should we select patients with COPD with a relatively low serum total IgG concentration (eg, patients in the lowest 5th percentile)? Or, should we consider patients with COPD presenting with recurrent exacerbations, regardless of their total IgG levels? In our study, we observed that patients in the lowest quartile of total IgG levels, which included all subjects with hypogammaglobulinemia (total IgG levels < 7.0 g/L), demonstrated the highest risk for developing an acute exacerbation of COPD. Given the costs (>$40,000 per year5Beaute J. Levy P. Millet V. Debre M. Dudoit Y. Le Mignot L. et al.Economic evaluation of immunoglobulin replacement in patients with primary antibody deficiencies.Clin Exp Immunol. 2010; 160: 240-245Crossref PubMed Scopus (60) Google Scholar) related to this therapy, we believe that it is reasonable to target such trials in patients with reduced serum IgG levels (serum IgG levels below the lower limit of normal), who have frequent exacerbations (more than 2 per year) or experience repeated emergency visits or hospitalizations (more than 1 per year). In our laboratory the lower limit of normal of the assay is 7.0 g/L. Thus, we believe that this is a reasonable cutoff, though a formal health economics assessment would be required to fine-tune this parameter. We thank the COPD Clinical Research Network for conducting both the MACRO and STATCOPE trials and for providing us access to all available samples in both cohorts. F.S.L.F. gratefully acknowledges postdoctoral support from CNPq-Brazil and the Canadian Institutes of Health Research Integrated and Mentored Pulmonary and Cardiovascular Training program (CIHR IMPACT). S.W.R. acknowledges support from the Ulsan University Hospital (Biomedical Research Center Promotion Fund, 10-03). Chronic obstructive pulmonary disease exacerbation frequency and serum IgG levelsJournal of Allergy and Clinical ImmunologyVol. 141Issue 2PreviewWe compliment Leitao Filho et al1 for their recent publication titled “Serum immunoglobulin G and risk of exacerbations and hospitalizations in chronic obstructive pulmonary disease.” Leitao Filho et al1 make a novel contribution to the understanding of the relationship between baseline serum IgG levels and the frequent chronic obstructive pulmonary disease (COPD) exacerbator phenotype. Full-Text PDF