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Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis
Journal article   Open access   Peer reviewed

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 and Alicia K Gerke
Sarcoidosis, vasculitis, and diffuse lung diseases, Vol.42(3), 16831
09/30/2025
DOI: 10.36141/svdld.v42i3.16831
PMCID: PMC12536839
PMID: 41026016
url
https://doi.org/10.36141/svdld.v42i3.16831View
Published (Version of record) Open Access

Abstract

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. The aim of this study was to assess whether exposure to bioaerosol associates with worse lung disease in patients with pulmonary sarcoidosis. 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. 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 FEV1 (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. 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.
sarcoidosis pulmonary fibrosis indoor air bioaerosol beta-(1,3)-D-glucan

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