Airway surface mycosis in chronic TH2-associated airway disease

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Presentation transcript:

Airway surface mycosis in chronic TH2-associated airway disease Paul C. Porter, PhD, Dae Jun Lim, MD, PhD, Zahida Khan Maskatia, MD, Garbo Mak, MD, Chu-Lin Tsai, MD, MPH, PhD, Martin J. Citardi, MD, Samer Fakhri, MD, Joanne L. Shaw, PhD, Annette Fothergil, PhD, Farrah Kheradmand, MD, David B. Corry, MD, Amber Luong, MD, PhD Journal of Allergy and Clinical Immunology Volume 134, Issue 2, Pages 325-331.e9 (August 2014) DOI: 10.1016/j.jaci.2014.04.028 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Fungal recovery from sinus lavage is more likely in the context of TH2-associated airway disease. A-C, Percentage of patients yielding positive fungal cultures from sinus lavage comparing control patients to patients with CRSsNPs, patients with CRSwNPs, and patients with AFRS (Fig 1, A); control patients and nonasthmatic patients to patients with asthma (Fig 1, B); and patients with non–TH2-associated disease to patients with TH2-associated disease (Fig 1, C). *P < .05, **P < .01, and ***P < .001. D and E, Representative Sabouraud's plate fungal cultures of sinus lavage fluid from 2 subjects. F, Photomicrograph of unstained sinus lavage mucus from a representative patient with AFRS showing extensive hyphal network (400×). §Control is a subset of all patients without asthma. Journal of Allergy and Clinical Immunology 2014 134, 325-331.e9DOI: (10.1016/j.jaci.2014.04.028) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Fungus-specific IL-4 and IgE responses predict TH2-associated disease. Subjects with and without TH2-associated disease (TH2 and no TH2, respectively) were assessed for specific serum IgE (A) and IL-4 memory recall responses (B) from PBMCs against whole-cell antigens derived from the fungi A alternata, A fumigatus, and A niger, both individually and combined. For the combined analysis, the largest positive response obtained with any of the 3 fungal antigens was plotted. Values above dotted lines represent positive responses. C, ROC curve analyses for both IgE and IL-4 reactivity using optimal IgE and IL-4 cutoff values of 6 kIU/L and 50 cells/106 PBMCs, respectively. AUC, Area under the curve. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2014 134, 325-331.e9DOI: (10.1016/j.jaci.2014.04.028) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Fungus-specific PBMC IL-4 responses occur in the majority of patients with TH2-associated disease. A-C, PBMCs isolated from the indicated subject populations were cultured in media alone or supplemented with 5 mg of antigen derived from 9 fungi, and IL-4 secretion by ELISpot analysis was performed 24 hours later. A positive reaction to any antigen was more than 50 IL-4–secreting cells/106 PBMCs above media control. Patients with TH2-associated airway disease have either CRSwNPs or asthma or both. D, Maximal fungus-specific IL-4 ELISpot responses comparing subjects with TH2-associated and nonassociated disease. E, Distribution of the number of distinct fungi inducing positive IL-4 ELISpot responses in subjects with allergic airway disease. F, Percentage of patients with Th2–associated disease reacting to the indicated fungal allergens. **P < .01 and ***P < .001. §Control is a subset of all patients without asthma. Journal of Allergy and Clinical Immunology 2014 134, 325-331.e9DOI: (10.1016/j.jaci.2014.04.028) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Fungal-specific IL-4 responses are highly concordant with the species isolated. A-C, IL-4 ELISpot data were determined using antigens matched to fungi derived from the same patient and were otherwise collected as in Fig 3. *P < .05 and **P < .01. §Control is a subset of all patients without asthma. Journal of Allergy and Clinical Immunology 2014 134, 325-331.e9DOI: (10.1016/j.jaci.2014.04.028) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Fungal-specific IgE responses to A niger, A fumigatus, or A alternata are elevated in patients with AFRS and highly concordant with the species isolated. A-C, IgE positivity data analyses based on various patient groupings. D-F, IgE ELISA data limited to patients who grew A niger, A fumigatus, or A alternata from their airways. *P < .05. §Control is a subset of all patients without asthma. Journal of Allergy and Clinical Immunology 2014 134, 325-331.e9DOI: (10.1016/j.jaci.2014.04.028) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions