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

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

Authors

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.

Author Biographies

Emma M Stapleton, University of Iowa

Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Research Assistant Professor

*Co-corresponding author

Nervana Metwali, University of Iowa

College of Public Health, Department of Occupational and Environmental Health, Research Manager

Michael Shlossman, University of Iowa

Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Pulmonary Fellow

Linder Wendt, University of Iowa

Institute for Clinical and Translational Science

Alejandro A Pezzulo, University of Iowa

Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Associate Professor

Nabeel Y Hamzeh, University of Iowa

Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Professor

Alejandro P Comellas, University of Iowa

Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Clinical Professor

Peter S Thorne, University of Iowa

College of Public Health, Department of Occupational and Environmental Health, Professor

Alicia K Gerke, University of Iowa

Department of Internal Medicine, Division of Pulmonary, Critical Care and Occupational Medicine, Associate Professor

*Co-corresponding author

References

Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153-2165. doi:10.1056/NEJMra071714

Chen ES, Moller DR. Etiologies of Sarcoidosis. Clin Rev Allergy Immunol. 2015;49(1):6-18. doi:10.1007/s12016-015-8481-z

Müller-Quernheim J, Prasse A, Zissel G. Pathogenesis of sarcoidosis. Presse Medicale Paris Fr 1983. 2012;41(6 Pt 2):e275-287. doi:10.1016/j.lpm.2012.03.018

Judson MA. Environmental Risk Factors for Sarcoidosis. Front Immunol. 2020;11:1340. doi:10.3389/fimmu.2020.01340

Rossman MD, Thompson B, Frederick M, et al. HLA and environmental interactions in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG. 2008;25(2):125-132.

Beijer E, Kraaijvanger R, Roodenburg C, Grutters JC, Meek B, Veltkamp M. Simultaneous testing of immunological sensitization to multiple antigens in sarcoidosis reveals an association with inorganic antigens specifically related to a fibrotic phenotype. Clin Exp Immunol. 2021;203(1):115-124. doi:10.1111/cei.13519

Barnard J, Rose C, Newman L, et al. Job and industry classifications associated with sarcoidosis in A Case-Control Etiologic Study of Sarcoidosis (ACCESS). J Occup Environ Med. 2005;47(3):226-234. doi:10.1097/01.jom.0000155711.88781.91

Newman LS, Rose CS, Bresnitz EA, et al. A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med. 2004;170(12):1324-1330. doi:10.1164/rccm.200402-249OC

Kucera GP, Rybicki BA, Kirkey KL, et al. Occupational risk factors for sarcoidosis in African-American siblings. Chest. 2003;123(5):1527-1535. doi:10.1378/chest.123.5.1527

Laney AS, Cragin LA, Blevins LZ, et al. Sarcoidosis, asthma, and asthma-like symptoms among occupants of a historically water-damaged office building. Indoor Air. 2009;19(1):83-90. doi:10.1111/j.1600-0668.2008.00564.x

Huntley CC, Patel K, Mughal AZ, et al. Airborne occupational exposures associated with pulmonary sarcoidosis: a systematic review and meta-analysis. Occup Environ Med. 2023;80(10):580-589. doi:10.1136/oemed-2022-108632

Terčelj M, Salobir B, Harlander M, Rylander R. Fungal exposure in homes of patients with sarcoidosis - an environmental exposure study. Environ Health Glob Access Sci Source. 2011;10(1):8. doi:10.1186/1476-069X-10-8

Greaves SA, Ravindran A, Santos RG, et al. CD4+ T cells in the lungs of acute sarcoidosis patients recognize an Aspergillus nidulans epitope. J Exp Med. 2021;218(10):e20210785. doi:10.1084/jem.20210785

Douwes J, Thorne P, Pearce N, Heederik D. Bioaerosol health effects and exposure assessment: progress and prospects. Ann Occup Hyg. 2003;47(3):187-200. doi:10.1093/annhyg/meg032

Thorne PS. Environmental endotoxin exposure and asthma. J Allergy Clin Immunol. 2021;148(1):61-63. doi:10.1016/j.jaci.2021.05.004

Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;201(8):e26-e51. doi:10.1164/rccm.202002-0251ST

Wasfi YS, Rose CS, Murphy JR, et al. A new tool to assess sarcoidosis severity. Chest. 2006;129(5):1234-1245. doi:10.1378/chest.129.5.1234

Schanberg LE, Anthony KK, Gil KM, Lefebvre JC, Kredich DW, Macharoni LM. Family pain history predicts child health status in children with chronic rheumatic disease. Pediatrics. 2001;108(3):E47. doi:10.1542/peds.108.3.e47

Cox CE, Donohue JF, Brown CD, Kataria YP, Judson MA. The Sarcoidosis Health Questionnaire: a new measure of health-related quality of life. Am J Respir Crit Care Med. 2003;168(3):323-329. doi:10.1164/rccm.200211-1343OC

Kilburg-Basnyat B, Metwali N, Thorne PS. Effect of deployment time on endotoxin and allergen exposure assessment using electrostatic dust collectors. Ann Occup Hyg. 2015;59(1):104-115. doi:10.1093/annhyg/meu063

Aketagawa J, Tanaka S, Tamura H, Shibata Y, Saitô H. Activation of limulus coagulation factor G by several (1-->3)-beta-D-glucans: comparison of the potency of glucans with identical degree of polymerization but different conformations. J Biochem (Tokyo). 1993;113(6):683-686. doi:10.1093/oxfordjournals.jbchem.a124103

Kilburg-Basnyat B, Metwali N, Thorne PS. Performance of electrostatic dust collectors (EDCs) for endotoxin assessment in homes: Effect of mailing, placement, heating, and electrostatic charge. J Occup Environ Hyg. 2016;13(2):85-93. doi:10.1080/15459624.2015.1078468

Hoppe Parr KA, Hađina S, Kilburg-Basnyat B, et al. Modification of sample processing for the Limulus amebocyte lysate assay enhances detection of inflammogenic endotoxin in intact bacteria and organic dust. Innate Immun. 2017;23(3):307-318. doi:10.1177/1753425917694084

Kwon JH, Choi O, Kim J. First Report of Kalanchoe Leaf Scorch Caused by Stemphylium xanthosomatis in Korea. Plant Dis. 2012;96(2):292. doi:10.1094/PDIS-05-11-0403

Metwali N, Stapleton EM, Hadina S, Thorne PS. (1→3)-β-D-Glucan Derivatives with Unique Structural Properties Differentially Affect Murine Lung Inflammation and Histology. Immunology; 2023. doi:10.1101/2023.10.18.562993

Rankin J, Kobayashi M, Barbee RA, Dickie HA. AGRICULTURAL DUSTS AND DIFFUSE PULMONARY FIBROSIS. Arch Environ Health. 1965;10:278-282. doi:10.1080/00039896.1965.10663996

Cesta MF, Ryman-Rasmussen JP, Wallace DG, et al. Bacterial lipopolysaccharide enhances PDGF signaling and pulmonary fibrosis in rats exposed to carbon nanotubes. Am J Respir Cell Mol Biol. 2010;43(2):142-151. doi:10.1165/rcmb.2009-0113OC

Terčelj M, Stopinšek S, Ihan A, et al. In vitro and in vivo reactivity to fungal cell wall agents in sarcoidosis. Clin Exp Immunol. 2011;166(1):87-93. doi:10.1111/j.1365-2249.2011.04456.x

Miyara M, Amoura Z, Parizot C, et al. The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 2006;203(2):359-370. doi:10.1084/jem.20050648

Witte K, Witte E, Sabat R, Wolk K. IL-28A, IL-28B, and IL-29: promising cytokines with type I interferon-like properties. Cytokine Growth Factor Rev. 2010;21(4):237-251. doi:10.1016/j.cytogfr.2010.04.002

Lazear HM, Schoggins JW, Diamond MS. Shared and Distinct Functions of Type I and Type III Interferons. Immunity. 2019;50(4):907-923. doi:10.1016/j.immuni.2019.03.025

Egli A, Santer DM, O’Shea D, et al. IL-28B is a key regulator of B- and T-cell vaccine responses against influenza. PLoS Pathog. 2014;10(12):e1004556. doi:10.1371/journal.ppat.1004556

Moller DR. Cells and cytokines involved in the pathogenesis of sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis Off J WASOG. 1999;16(1):24-31.

Wolk K, Witte K, Witte E, et al. Maturing dendritic cells are an important source of IL-29 and IL-20 that may cooperatively increase the innate immunity of keratinocytes. J Leukoc Biol. 2008;83(5):1181-1193. doi:10.1189/jlb.0807525

Kohan M, Puxeddu I, Reich R, Levi-Schaffer F, Berkman N. Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts. Ann Allergy Asthma Immunol Off Publ Am Coll Allergy Asthma Immunol. 2010;104(1):66-72. doi:10.1016/j.anai.2009.11.003

Collison AM, Sokulsky LA, Sherrill JD, et al. TNF-related apoptosis-inducing ligand (TRAIL) regulates midline-1, thymic stromal lymphopoietin, inflammation, and remodeling in experimental eosinophilic esophagitis. J Allergy Clin Immunol. 2015;136(4):971-982. doi:10.1016/j.jaci.2015.03.031

Clayton F, Peterson K. Eosinophilic Esophagitis: Pathophysiology and Definition. Gastrointest Endosc Clin N Am. 2018;28(1):1-14. doi:10.1016/j.giec.2017.07.011

Ushach I, Zlotnik A. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol. 2016;100(3):481-489. doi:10.1189/jlb.3RU0316-144R

Rodriguez RM, Suarez-Alvarez B, Lavín JL, et al. Signal Integration and Transcriptional Regulation of the Inflammatory Response Mediated by the GM-/M-CSF Signaling Axis in Human Monocytes. Cell Rep. 2019;29(4):860-872.e5. doi:10.1016/j.celrep.2019.09.035

Hofer TP, Zawada AM, Frankenberger M, et al. slan-defined subsets of CD16-positive monocytes: impact of granulomatous inflammation and M-CSF receptor mutation. Blood. 2015;126(24):2601-2610. doi:10.1182/blood-2015-06-651331

Nazaroff WW. The particles around us. Indoor Air. 2018;28(2):215-217. doi:10.1111/ina.12444

Liu H, Zhang X, Zhang H, et al. Effect of air pollution on the total bacteria and pathogenic bacteria in different sizes of particulate matter. Environ Pollut Barking Essex 1987. 2018;233:483-493. doi:10.1016/j.envpol.2017.10.070

Buma R, Maeda T, Kamei M, Kourai H. Pathogenic bacteria carried by companion animals and their susceptibility to antibacterial agents. Biocontrol Sci. 2006;11(1):1-9. doi:10.4265/bio.11.1

Kim KH, Kabir E, Jahan SA. Airborne bioaerosols and their impact on human health. J Environ Sci China. 2018;67:23-35. doi:10.1016/j.jes.2017.08.027

LeBouf R, Yesse L, Rossner A. Seasonal and diurnal variability in airborne mold from an indoor residential environment in northern New York. J Air Waste Manag Assoc 1995. 2008;58(5):684-692. doi:10.3155/1047-3289.58.5.684

Crawford C, Reponen T, Lee T, et al. Temporal and spatial variation of indoor and outdoor airborne fungal spores, pollen, and (1→3)-β-d-glucan. Aerobiologia. 2009;25(3):147-158. doi:10.1007/s10453-009-9120-z

Banoei MM, Iupe I, Bazaz RD, et al. Metabolomic and metallomic profile differences between Veterans and Civilians with Pulmonary Sarcoidosis. Sci Rep. 2019;9(1):19584. doi:10.1038/s41598-019-56174-8

Parker GJ, Ong CH, Manges RB, et al. A Novel Method of Collecting and Chemically Characterizing Milligram Quantities of Indoor Airborne Particulate Matter. Aerosol Air Qual Res. 2019;19(11):2387-2395. doi:10.4209/aaqr.2019.04.0182

Stapleton EM, Simmering JE, Manges RB, et al. Continuous in-home PM2.5 concentrations of smokers with and without a history of respiratory exacerbations in Iowa, during and after an air purifier intervention. J Expo Sci Environ Epidemiol. 2020;30(5):778-784. doi:10.1038/s41370-020-0235-1

How to Cite

1.
Stapleton EM, Metwali N, Shlossman M, Wendt L, Pezzulo AA, Hamzeh NY, et al. Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis [Internet]. [cited 2025 May 20];42(4):16831. Available from: https://mattioli1885journals.com/index.php/sarcoidosis/article/view/16831

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Review

How to Cite

1.
Stapleton EM, Metwali N, Shlossman M, Wendt L, Pezzulo AA, Hamzeh NY, et al. Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis [Internet]. [cited 2025 May 20];42(4):16831. Available from: https://mattioli1885journals.com/index.php/sarcoidosis/article/view/16831