Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis Jennifer K. Mulligan, PhD, Whitney Nagel,

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Presentation transcript:

Cigarette smoke exposure is associated with vitamin D3 deficiencies in patients with chronic rhinosinusitis Jennifer K. Mulligan, PhD, Whitney Nagel, BS, Brendan P. O'Connell, MD, Jennifer Wentzel, BS, Carl Atkinson, PhD, Rodney J. Schlosser, MD Journal of Allergy and Clinical Immunology Volume 134, Issue 2, Pages 342-349.e1 (August 2014) DOI: 10.1016/j.jaci.2014.01.039 Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Circulating and tissue levels of 25VD3 are reduced with CS exposure. A and B, CS exposure is associated with lower 25VD3 levels in plasma (Fig 1, A) and sinonasal tissues (Fig 1, B). Statistics shown are for the Mann-Whitney test between indicated diagnostic groups. C, Pearson correlation analysis with patient-matched plasma and sinonasal tissue 25VD3 levels. ○, White; ▴, African American; ♦, other. Journal of Allergy and Clinical Immunology 2014 134, 342-349.e1DOI: (10.1016/j.jaci.2014.01.039) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Sinonasal tissue expression of CYP27B1 and CS exposure. RT-PCR analysis of sinonasal mucosa for CYP27B1 was performed. *P < .05 versus smoke-naive, disease-matched subjects. #P < .05 versus the CRSsNP group. **P < .05 versus the control-CS or CRSsNP-CS groups. Control group, n = 5; CRSsNP group, n = 6; CRSwNP group, n = 6; Control-CS group, n = 5; CRSsNP-CS group, n = 8; CRSwNP-CS group, n = 10. Journal of Allergy and Clinical Immunology 2014 134, 342-349.e1DOI: (10.1016/j.jaci.2014.01.039) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 HSNEC VD3 conversion is impaired in patients with CRSwNP and by CSE. Data shown are means ± SEMs. A, Control HSNEC cultures treated with indicated 25VD3 dose plus 10% CSE. ˆP < .05 versus control or CSE-alone groups. $P < .001 versus the dose-matched, non–CS-treated group. N = 3 control patients. B, HSNECs treated with 4 × 104 pg/mL 25VD3 to determine disease-specific conversion and effect of CSE. *P < .05 versus the control group. **P < .05 versus each disease-matched, vehicle control subject. #P < .05 versus control + CSE or CRSsNP+ CSE. Control subjects and patients with CRSsNP, n = 3; patients with CRSwNP, n = 4. Journal of Allergy and Clinical Immunology 2014 134, 342-349.e1DOI: (10.1016/j.jaci.2014.01.039) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 CSE exposure downregulates HSNEC CYP27B1 expression. Intracellular staining and flow cytometric analysis of CYP27B1 expression 12 hours after treatment with media (control) or 10% CSE is shown. A, Representative histograms of isotype (blue dashed line), control-treated (red solid line), or CSE-treated (filled green area) groups. B, Mean ± SD CYP27B1 expression. N = 3 control subjects. Statistics shown are unpaired t tests. MFI, Mean fluorescence intensity. Journal of Allergy and Clinical Immunology 2014 134, 342-349.e1DOI: (10.1016/j.jaci.2014.01.039) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 1,25VD3 abrogates smoke-induced cytokine production by HSNECs. HSNECs were cultured with vehicle or 10% CSE in the presence or absence of 50 pg/mL 1,25VD3. Conditioned media were assessed for IL-6 (A), IL-8 (B), or CCL20 (C). Data shown are means ± SEMs (n = 3 control patients for each trial). *P < .01 versus the control group. #P < .008 versus 10% CSE treatment. Journal of Allergy and Clinical Immunology 2014 134, 342-349.e1DOI: (10.1016/j.jaci.2014.01.039) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Ex vivo analysis of sinus tissue explants by means of intracellular flow cytometry demonstrates general downregulation of CYP27B1 protein in all cells from sinus explants (A), as well as epithelial cell–specific CYP27B1 expression (B). Data shown are mean fluorescence intensity (MFI) ± SEM. *P < .05 versus control or CRSsNP. Control group, n = 6; CRSsNP group, n = 4; CRSwNP group, n = 4. Journal of Allergy and Clinical Immunology 2014 134, 342-349.e1DOI: (10.1016/j.jaci.2014.01.039) Copyright © 2014 American Academy of Allergy, Asthma & Immunology Terms and Conditions