In patients with chronic obstructive pulmonary disease (COPD), both high and low immunoglobulin G (IgG) serum levels are associated with a significant increase in 1-year mortality, according to findings published in the American Journal of Respiratory Critical Care Medicine. Investigators of the current study recently discovered that IgG deficiency is a significant risk factor for acute exacerbations from COPD (AECOPD) and related hospitalizations. Therefore, they set out to examine the associations between serum levels of IgG and 1-year mortality in patients with COPD.

A total of 621 patients had a mean (±SD) age of 66.9±11.6 years, 83.4% were white, 64.7% were men, and 55.7% were current smokers. Their mean postbronchodilator forced expiratory volume in 1 second (FEV1) was 52.6±23% predicted, and the overall 1-year rate of mortality was 17.7% (110/621). Similar serum IgG levels (expressed as median [interquartile range]) were found in patients hospitalized with AECOPD vs stable patients (10.9 [5.6] g/L vs 10.8 [4.8] g/L; P =.63). The lowest IgG level was 3.07 g/L and the highest was 33.97 g/L.

Considering the standard normative serum IgG range of 7 g/L to 16 g/L, investigators subdivided the patients and categorized 10.3% (64/621) of patients as having low serum IgG (hypogammaglobulinemia) and 16.1% (100/621) of patients as having high serum IgG (hypergammaglobulinemia). Across the groups, there were no significant differences in the prevalence of asthma history, cardiac comorbidities, or postbronchodilator FEV1.

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Within 1 year after enrollment, 31.3% of patients died in the hypogammaglobulinemia group, 22% died in the hypergammaglobulinemia group, and 14.9% died in the normal IgG group, with a mean time to death of 296 days (95% CI, 267-326) in the hypogammaglobulinemia group, 310 days (95% CI, 288-332) in the hypergammaglobulinemia group, and 332 days (95% CI, 324-341) in the normal group.

After Cox regression model was performed, adjusting for age, ethnicity, sex, and smoking status, patients with hypogammaglobulinemia were more than 2 times more likely to experience 1-year mortality than patients with normal serum IgG levels (adjusted hazard ratio [aHR], 2.3; 95% CI, 1.4-3.8; P =.001). Patients with hypergammaglobulinemia were slightly less than 2 times more likely to experience mortality than the normal serum IgG group (aHR, 1.8; 95% CI, 1.1-3.0; P =.01). The study investigators noted that serum IgG is not a perfect biomarker because the patient can mount an appropriate immune response despite reduced serum IgG levels. The study is also limited by the fact that specific IgG antibodies to microbes were not measured and the cause of hypogammaglobulinemia or hypergammaglobulinemia was not determined.

Although study investigators could not determine exact causes of death for patients included in the study, they proposed that those with hypogammaglobulinemia died primarily from AECOPD and recurrent respiratory tract infections. They concluded, “Our results raise the intriguing possibility [that] Ig replacement therapy may be effective in reducing AECOPD and, more importantly, improving short-term mortality in select COPD patients.”


Alotaibi NM, Leitao Filho FS, Mattman A, et al. Immunoglobulin G levels and mortality in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. Published online May 4, 2021. doi: 10.1164/rccm.202102-0382LE