44% of patients with acute exacerbations of COPD have hypogammaglobulinemia
Key takeaways:
- Included patients had exacerbations that required steroids or a hospitalization.
- More patients had an adequate response to tetanus/diphtheria vaccination vs. pneumococcal polyvalent vaccine-23.
SAN DIEGO — Immunoglobulin G hypogammaglobulinemia was found in 44.7% of patients with acute exacerbations of COPD receiving triple therapy, according to a presentation here.
This single-center, proof-of-concept study was presented at the 2025 American Academy of Allergy, Asthma and Immunology/World Allergy Organization Joint Congress.
“The study revealed that in patients with severe COPD who experience frequent steroid-requiring exacerbations despite being on triple therapy, over 40% had hypogammaglobulinemia, and the majority had a suboptimal response to vaccination against strep pneumoniae,” S. Shahzad Mustafa, MD, chief of allergy, immunology and rheumatology at Rochester Regional Health, told Healio.
Mustafa and colleagues assessed 38 patients (median age, 65 years; 32% men) with COPD receiving triple therapy who had at least two exacerbations that required steroids or a hospitalization within the past year to uncover how prevalent humoral immunodeficiency is in this population.
According to the abstract, three factors made up this study’s exclusion criteria: “known humoral dysfunction, ongoing immunoglobulin replacement therapy or chronic use of prednisone [greater than or equal to] 20 mg daily.”
Within the total cohort, researchers found immunoglobin G (IgG) hypogammaglobulinemia in 44.7% of patients (n = 17). The median IgG concentration in this set of patients was 730.5 mg/dL. Additionally, these patients had a median immunoglobulin M concentration of 80 mg/dL, and a median immunoglobulin A concentration of 203.5 mg/dL, according to the abstract.
In terms of vaccination response, researchers observed a greater proportion of patients with an adequate response to tetanus/diphtheria vaccination vs. pneumococcal polyvalent vaccine-23 (95% [n = 36] vs. 31.6% [n = 12]).
“These findings suggest these patients with severe COPD may have underlying antibody/humoral immunodeficiency predisposing them to infections that lead to exacerbations,” Mustafa told Healio. “These findings may also provide an alternative explanation of why therapy with macrolide antibiotics is effective in decreasing exacerbations, as it may be addressing the underlying immune deficiency.”
Mustafa also highlighted the role steroids play in the underlying antibody/humoral immunodeficiency in this patient population.
“It is important to note that these immune defects may be a result of frequent reliance on oral steroids, as steroid use is well known to lead to hypogammaglobinemia and potentially also decrease response to vaccination,” Mustafa said.
When analyzing cluster of differentiation (CD) counts, a similar proportion of patients had CD19 and CD4 counts deemed low (23.7% [n = 9] and 21% [n = 8]), according to the abstract. The median CD19 count was 122 cells/mm3, and the median CD4 count was 816 cells/mm3.
Lastly, researchers reported that a little over one-third of the study population (34.2%; n = 13) had specific antibody deficiency based on diagnostic criteria.
Looking ahead, Mustafa told Healio future studies will need to include more patients.
“This is a single-center proof-of-concept study with a small sample size,” Mustafa said. “Larger, multi-center studies are necessary to confirm these findings.
“Additionally, interventional studies are essential to evaluate how to best treat these patients with severe COPD and immunodeficiency,” Mustafa continued. “Our center is currently enrolling patients to study the effects of immunoglobulin replacement therapy on COPD exacerbations in this patient population (NCT 05764993).”
For more information:
S. Shahzad Mustafa, MD, can be reached at shahzad.mustafa@rochesterregional.org.