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Published on: March 17, 2014
Effects of bacterial infection on airway antimicrobial peptides and proteins in COPD
Ganapathi Iyer Parameswaran1, Sanjay Sethi2, Timothy F Murphy3
1Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, NY; VA Western New York Healthcare System, Buffalo, NY.
Background:
Pathogenic bacteria colonize the airways of 30% to 40% of patients with COPD and cause approximately 50% of exacerbations. New strains of nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are associated with exacerbations. Antimicrobial protein/peptides (AMPs) play important roles in innate lung defense against pathogens. To our knowledge, the changes in AMP baseline levels in respiratory secretions during bacterial colonization and exacerbation have not been described. The objective of this study was to elucidate the effects of the acquisition of a new strain of pathogenic bacteria on the airway levels of AMPs in patients with COPD.
Methods:
One hundred fifty-three samples from 11 patients were selected from COPD sputum samples collected prospectively over 6 years. Samples were grouped as culture-negative (no pathogenic bacteria), colonization, and exacerbation due to new strains of NTHI and M catarrhalis. Levels of lysozyme, lactoferrin, LL-37, and secretory leukocyte protease inhibitor (SLPI) were measured by enzyme-linked immunosorbent assay and compared among groups by paired analysis.
Results:
Compared with baseline, sputum lysozyme levels were significantly lower during colonization and exacerbation by NTHI (P = .001 and P = .013, respectively) and M catarrhalis (P = .007 and P = .018, respectively); SLPI levels were lower with exacerbation due to NTHI and M catarrhalis (P = .002 and P = .004, respectively), and during colonization by M catarrhalis (P = 032). Lactoferrin levels did not change significantly; LL-37 levels were higher during exacerbation by NTHI and M catarrhalis (P = .001 and P = .018, respectively).
Conclusions:
Acquisition of NTHI and M catarrhalis is associated with significant changes in airway levels of AMPs, with larger changes in exacerbation. Airway AMP levels are likely to be important in pathogen clearance and clinical outcomes of infection in COPD.
Insights
Bacterial colonization and exacerbations in COPD patients significantly alter airway antimicrobial peptide (AMP) levels. Specific AMPs like lysozyme and SLPI decrease, while LL-37 increases during these events.
Area of Science:
- Pulmonary Medicine
- Infectious Disease
- Immunology
Background:
- Chronic Obstructive Pulmonary Disease (COPD) patients experience frequent airway infections.
- Nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis are key pathogens causing COPD exacerbations.
- Antimicrobial peptides (AMPs) are crucial for innate lung immunity, but their role during bacterial colonization and exacerbation in COPD is unclear.
Purpose of the Study:
- To investigate the impact of new bacterial strain acquisition on airway AMP levels in COPD patients.
- To quantify changes in specific AMPs (lysozyme, lactoferrin, LL-37, SLPI) during colonization and exacerbation.
Main Methods:
- Analysis of 153 sputum samples from 11 COPD patients over 6 years.
- Categorization of samples into culture-negative, colonization, and exacerbation groups.
- Quantification of lysozyme, lactoferrin, LL-37, and SLPI using ELISA.
Main Results:
- Sputum lysozyme levels decreased significantly during NTHI and M. catarrhalis colonization and exacerbation.
- Secretory leukocyte protease inhibitor (SLPI) levels were lower during exacerbation and M. catarrhalis colonization.
- LL-37 levels were elevated during exacerbation by both pathogens; lactoferrin levels showed no significant change.
Conclusions:
- Acquisition of NTHI and M. catarrhalis leads to significant alterations in airway AMP profiles in COPD.
- AMP level changes are more pronounced during exacerbations compared to colonization.
- Airway AMPs are likely critical for pathogen clearance and influencing clinical outcomes in COPD infections.
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