Link Between COPD Hospitalization Risk and Serum IgG Levels

Immunoglobulin G antibody molecule. Computer model of the secondary structure of immunoglobulin G (IgG). This is the most abundant immunoglobulin and is found in all body fluids. Each Y-shaped molecule has two arms (top) that can bind to specific antigens, for instance bacterial or viral proteins. In doing this they mark the antigen for destruction by phagocytes, white blood cells that ingest and destroy foreign bodies. Antibodies can also kill some pathogens directly, and can neutralise toxins.
The presence of hypogammaglobulinemia is associated with a higher risk for hospitalization in patients with COPD compared with patients without the condition.

The presence of hypogammaglobulinemia — that is, serum immunoglobulin G (IgG) levels <7.0 g/L — is associated with a higher risk for hospitalization in patients with chronic obstructive pulmonary disease (COPD) compared with patients without the condition, according to study results published in CHEST.

Researchers analyzed pooled data from 4 large clinical studies of COPD: Azithromycin for Prevention of Exacerbation of COPD (MACRO; Identifier: NCT00325897); Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; Identifier: NCT01061671); Long-Term Oxygen Treatment Trial (LOTT; Identifier: NCT00692198); and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE; Identifier: NCT01074515).

The investigators sought to establish the relationship between hypogammaglobulinemia and risk for hospitalization in patients with COPD. They measured serum IgG levels on baseline samples from the different COPD cohorts. A total of 2259 participants were considered for IgG analysis (MACRO n=976; STACOPE n=653; LOTT n=354; and CASCADE n=276). IgG concentrations were determined by immunonephelometry in the MACRO and STATCOPE cohorts or by mass spectrometry in the LOTT and CASCADE cohorts.

Overall, hypogammaglobulinemia was reported in 28.4% (n=641) of participants. Only 1.4% (n=32) of the patients had serum IgG levels <4.0 g/L. Compared with their counterparts with normal IgG levels, participants with COPD and hypogammaglobulinemia were older, more likely to be women and white, had a lower body mass index, had worse lung function (either forced expiratory volume in 1 second [FEV1] or forced vital capacity [FVC]), and often needed oxygen supplementation. Further, a greater proportion of patients with lower IgG levels required ≥1 steroid courses before entry into the study and had had hospital admissions for COPD in the previous year.

The median study follow-up was 1.02 years. Overall, 24.7% (n=558) of the participants required ≥1 hospitalization for COPD. A significantly higher proportion of participants with hypogammaglobulinemia vs those with normal IgG levels experienced ≥1 hospital admission for COPD (30.7% vs 22.3%, respectively; P <.001).

The pooled subdistribution hazard ratio (SHR), per meta-analysis, was 1.29 (95% CI, 1.06-1.56; P =.01). Moreover, of the 757 participants with a previous hospitalization for COPD, the pooled SHR increased to 1.58 (95% CI, 1.20-2.07; P <.01). The risk for COPD hospital admission, however, was similar between the IgG groups in patients with no prior hospitalizations for COPD (SHR, 1.15; 95% CI, 0.86-1.52; P =.34). Those with hypogammaglobulinemia also demonstrated significantly greater rates of COPD hospitalizations per person-year compared with those with normal IgG levels (0.48±2.01 vs 0.29±0.83, respectively; P <.001).

The investigators concluded that mechanistic studies are still warranted to better clarify how IgG and other immunoglobulins, in particular, IgA, may contribute to the local airway host defense. The possibility exists that in certain patients with COPD, IgG replacement therapy may be effective in decreasing the risk for COPD hospitalization. A well-designed trial to explore this hypothesis is needed.


Leitao Filho FS, Mattman A, Schellenberg R, et al. Serum IgG levels and risk of COPD hospitalization: a pooled meta-analysis [published online May 19, 2020]. CHEST. doi:10.1016/j.chest.2020.04.058