Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis

Emma M Stapleton; Nervana Metwali; Michael Shlossman; Linder Wendt; Alejandro A Pezzulo; Nabeel Y Hamzeh; Alejandro P Comellas; Peter S Thorne; Alicia K Gerke

doi:10.21203/rs.3.rs-5220174/v1

Background: Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis. Research Question: Does exposure to bioaerosol associate with worse lung disease in patients with pulmonary sarcoidosis? Study Design and Methods: Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation. Results: Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P <0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging ( P =0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV 1 ( P =0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis. Interpretation: In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.Background: Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis. Research Question: Does exposure to bioaerosol associate with worse lung disease in patients with pulmonary sarcoidosis? Study Design and Methods: Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation. Results: Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P <0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging ( P =0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV 1 ( P =0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis. Interpretation: In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.

Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis

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