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:10.36141/svdld.vi.16831

Authors

Emma M Stapleton Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA. https://orcid.org/0000-0003-4565-094X
Nervana Metwali Department of Occupational & Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0003-4314-0700
Michael Shlossman Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA
Linder Wendt Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0003-1832-0486
Alejandro A Pezzulo Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0001-7544-5109
Nabeel Y Hamzeh Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0001-7296-8975
Alejandro P Comellas Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0003-1521-7520
Peter S Thorne Department of Occupational & Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0002-5045-0929
Alicia K Gerke Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, University of Iowa, Iowa City, IA, USA https://orcid.org/0000-0002-8333-3403

Keywords:

Sarcoidosis, pulmonary fibrosis, indoor air, bioaerosol, β-(1,3)-D-glucan.

Abstract

Background and aim: 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.

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 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.

Conclusions: 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.

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