Associations between haemophilus influenzae and levels of sputum antimicrobial peptides in COPD

Abstract

Background: Non-typeable Haemophilus influenzae (NTHi) is frequently isolated from the COPD airways. Antimicrobial peptides (AMPs) may play a role in modifying responses to inflammation and microorganisms, a topic yet sparsely investigated.

Aims: Explore sputum levels of two AMPs (hCAP18/LL-37 and SLPI) and inflammatory markers (IP-10, IL-8 and IL-6) in response to NTHi colonization in COPD.

Methods: Induced sputum samples were collected in stable COPD patients (n=426), 40-76 yrs, participating in the 3-year Bergen COPD Cohort Study. NTHi colonization was identified by sputum culture, and samples without potential airway pathogens defined culture-negativity. Samples were analyzed for AMP levels (enzyme-linked immunosorbent assay) and inflammatory markers (bead-based immunoassay). Non-parametric tests served for univariate comparisons, and linear regression models with log transformed dependent variable (hCAP18/LL-37) to assess the possible impact of NTHi status. Coefficients were expressed as geometric mean (GM) ratios with 95% confidence intervals (CI).

Results: NTHi-positive patients (n=50) compared to culture negative (n=124) had similar baseline characteristics (FEV₁, sex, age, and smoking habits), increased sputum hCAP18/LL-37, IL-8 levels, and a higher neutrophil count in univariate comparison. SLPI, IL-6, and IP-10 levels did not differ between groups. Adjusted estimates showed a more than two-fold higher hCAP18/LL-37 levels in NTHi-positive patients (GM ratio 2.45, CI: 1.41-4.22).

Conclusion: NTHi status, hCAP18/LL-37 release and neutrophilic inflammation are closely linked. Combined, these changes may sustain inflammation and further derange airway host defense mechanisms in COPD.