Paul C Porter1, Dae Jun Lim2, Zahida Khan Maskatia1, Garbo Mak1, Chu-Lin Tsai3, Martin J Citardi4, Samer Fakhri4, Joanne L Shaw5, Annette Fothergil6, Farrah Kheradmand7, David B Corry8, Amber Luong9. 1. Department of Medicine, Baylor College of Medicine, Houston, Tex. 2. Department of Otolaryngology-Head and Neck Surgery, Konkuk University, Chungju Hospital, Chungbuk, Korea. 3. Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Tex. 4. Department of Otorhinolaryngolgy-Head and Neck Surgery, University of Texas Medical School at Houston, Houston, Tex. 5. Department of Otorhinolaryngolgy-Head and Neck Surgery, University of Texas Medical School at Houston, Houston, Tex; Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Medical School at Houston, Houston, Tex. 6. Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Tex. 7. Department of Medicine, Baylor College of Medicine, Houston, Tex; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex; Michael E. Debakey VA Center for Translational Research on Inflammatory Diseases, Houston, Tex. 8. Department of Medicine, Baylor College of Medicine, Houston, Tex; Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex; Michael E. Debakey VA Center for Translational Research on Inflammatory Diseases, Houston, Tex. Electronic address: dcorry@bcm.edu. 9. Department of Otorhinolaryngolgy-Head and Neck Surgery, University of Texas Medical School at Houston, Houston, Tex; Center for Immunology and Autoimmune Diseases, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Medical School at Houston, Houston, Tex. Electronic address: Amber.U.Luong@uth.tmc.edu.
Abstract
BACKGROUND: Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. OBJECTIVE: To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. METHODS: Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. RESULTS: Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). CONCLUSIONS: The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.
BACKGROUND: Environmental fungi have been linked to TH2 cell-related airway inflammation and the TH2-associated chronic airway diseases asthma, chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP), and allergic fungal rhinosinusitis (AFRS), but whether these organisms participate directly or indirectly in disease pathology remains unknown. OBJECTIVE: To determine the frequency of fungus isolation and fungus-specific immunity in patients with TH2-associated and non-TH2-associated airway disease. METHODS: Sinus lavage fluid and blood were collected from sinus surgery patients (n = 118) including patients with CRSwNP, patients with CRS without nasal polyps, patients with AFRS, and non-CRS/nonasthmatic control patients. Asthma status was determined from medical history. Sinus lavage fluids were cultured and directly examined for evidence of viable fungi. PBMCs were restimulated with fungal antigens in an enzyme-linked immunocell spot assay to determine total memory fungus-specific IL-4-secreting cells. These data were compared with fungus-specific IgE levels measured from plasma by ELISA. RESULTS:Filamentous fungi were significantly more commonly cultured in patients with TH2-associated airway disease (asthma, CRSwNP, or AFRS: n = 68) than in control patients with non-TH2-associated disease (n = 31): 74% vs 16%, respectively (P < .001). Both fungus-specific IL-4 enzyme-linked immunocell spot (n = 48) and specific IgE (n = 70) data correlated with TH2-associated diseases (sensitivity 73% and specificity 100% vs 50% and 77%, respectively). CONCLUSIONS: The frequent isolation of fungi growing directly within the airways accompanied by specific immunity to these organisms only in patients with TH2-associated chronic airway diseases suggests that fungi participate directly in the pathogenesis of these conditions. Efforts to eradicate airway fungi from the airways should be considered in selected patients.
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