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Circulating 1,3-Beta-D-Glucan is Associated with Lung Function, Respiratory Symptoms, and Mediators of Matrix
Matthew Gorgone1, Deepti Singhvi1, Seyed Mehdi Nouraie1
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
Introduction:
Factors beyond cigarette smoke likely contribute to chronic obstructive pulmonary disease (COPD) pathogenesis. Prior studies demonstrate fungal colonization of the respiratory tract and increased epithelial barrier permeability in COPD. We sought to determine whether 1,3-beta-d-glucan (BDG), a polysaccharide component of the fungal cell wall, is detectable in the plasma of individuals with COPD and associates with clinical outcomes and matrix degradation proteins.
Methods:
BDG was measured in the plasma of current and former smokers with COPD. High BDG was defined as a value greater than the 95th percentile of BDG in smokers without airflow obstruction. Pulmonary function, emphysema, and symptoms were compared between COPD participants with high versus low BDG. The relationship between plasma BDG, matrix metalloproteinases (MMP) 1, 7, and 9, and tissue inhibitor of matrix metalloproteinases (TIMP) 1, 2, and 4 was assessed adjusting for age, sex, and smoking status.
Results:
COPD participants with high BDG plasma levels (19.8%) had lower forced expiratory volume in 1 second to forced vital capacity ratios (median 31.9 versus 39.3, p=0.025), higher St George's Respiratory Questionnaire symptom scores (median 63.6 versus 57.4, p=0.016), and greater prevalence of sputum production (69.4% versus 52.0%) and exacerbations (69.4% versus 48%) compared to COPD participants with low BDG. BDG levels directly correlated with MMP1 (r=0.27, p<0.001) and TIMP1 (r=0.16, p=0.022) in unadjusted and adjusted analyses.
Conclusions:
Elevated plasma BDG levels correlate with worse lung function, greater respiratory morbidity, and circulating markers of matrix degradation in COPD. These findings suggest that targeting dysbiosis or enhancing epithelial barrier integrity may have disease-modifying effects in COPD.
Insights
Elevated fungal cell wall component 1,3-beta-d-glucan (BDG) in COPD patients’ plasma is linked to poorer lung function and increased respiratory symptoms. Targeting fungal dysbiosis may offer new COPD treatment strategies.
Area of Science:
- Pulmonary Medicine
- Microbiology
- Immunology
Background:
- Chronic obstructive pulmonary disease (COPD) pathogenesis involves factors beyond cigarette smoke, including fungal colonization and compromised epithelial barrier function.
- 1,3-beta-d-glucan (BDG), a fungal cell wall component, is investigated as a potential biomarker in COPD.
Purpose of the Study:
- To determine if BDG is detectable in the plasma of individuals with COPD.
- To assess the association of plasma BDG levels with clinical outcomes and matrix degradation proteins in COPD patients.
Main Methods:
- Plasma BDG levels were measured in current and former smokers with COPD.
- High BDG was defined as exceeding the 95th percentile of BDG in smokers without airflow obstruction.
- Pulmonary function, emphysema, symptoms, and the relationship between BDG, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) were analyzed.
Main Results:
- COPD participants with high plasma BDG exhibited significantly lower FEV1/FVC ratios, higher symptom scores, and increased prevalence of sputum production and exacerbations.
- Plasma BDG levels showed a direct correlation with MMP1 and TIMP1 in both unadjusted and adjusted analyses.
- Approximately 19.8% of COPD participants had high BDG plasma levels.
Conclusions:
- Elevated plasma BDG levels in COPD correlate with diminished lung function, increased respiratory morbidity, and elevated circulating matrix degradation markers.
- These findings suggest that targeting fungal dysbiosis or enhancing epithelial barrier integrity could represent novel disease-modifying therapeutic strategies for COPD.
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