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Airway surface mycosis in chronic TH2-associated airway disease - 01/08/14

Doi : 10.1016/j.jaci.2014.04.028 
Paul C. Porter, PhD a, Dae Jun Lim, MD, PhD b, Zahida Khan Maskatia, MD a, Garbo Mak, MD a, Chu-Lin Tsai, MD, MPH, PhD c, Martin J. Citardi, MD d, Samer Fakhri, MD d, Joanne L. Shaw, PhD d, e, Annette Fothergil, PhD f, Farrah Kheradmand, MD a, g, h, David B. Corry, MD a, g, h, , Amber Luong, MD, PhD d, e,
a Department of Medicine, Baylor College of Medicine, Houston, Tex 
g Department of Pathology and Immunology, Baylor College of Medicine, Houston, Tex 
b Department of Otolaryngology-Head and Neck Surgery, Konkuk University, Chungju Hospital, Chungbuk, Korea 
c Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Tex 
d Department of Otorhinolaryngolgy-Head and Neck Surgery, University of Texas Medical School at Houston, Houston, Tex 
e 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 
f Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Tex 
h Michael E. Debakey VA Center for Translational Research on Inflammatory Diseases, Houston, Tex 

Corresponding authors: David B. Corry, MD, Departments of Medicine and Pathology and Immunology, Baylor College of Medicine, BCM285, One Baylor Plaza, Houston, TX 77030.∗∗Amber Luong, MD, PhD, Department of Otorhinolaryngolgy – Head and Neck Surgery, University of Texas Medical School at Houston, 6431 Fannin St, MSB 5.036, Houston, TX 77030.

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.

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Key words : Allergic, airway, mycosis, fungal, asthma, chronic rhinosinusitis, TH2-associated airway disease

Abbreviations used : AFRS, CRS, CRSsNP, CRSwNP, ELISpot, ROC


Plan


 This study was supported by the Papadopoulos Family Fund for Allergic Disease Research from the Biology of Inflammation Center (to D.B.C.) and the National Institutes of Health (grant no. U19AI070973 to D.B.C. and F.K.).
 Disclosure of potential conflict of interest: P. C. Porter and Z. K. Maskatia have received research support from the National Institutes of Health (NIH). G. Mak has received research support from the Papadopoulos Family Fund for Allergic Disease Research (from the Biology of Inflammation Center) and from the National Institutes of Health (grant no. U19AI070973). M. J. Citardi has received consultancy fees from Polyganics and has received lecture fees from Arthrocare (sales force training) and Richie's Specialty Pharmacy (sales force training). A. Fothergil has received research support from Baylor College of Medicine (grant no. U19AI070973). A. Luong has received research support from Cadence Pharmaceuticals. The rest of the authors declare that they have no relevant conflicts of interest.


© 2014  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 134 - N° 2

P. 325 - août 2014 Retour au numéro
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