title: Reduced sinonasal levels of 1α-hydroxylase are associated with worse quality of life in chronic rhinosinusitis with nasal polyps.
abstract: BACKGROUND
  Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have deficiencies in circulating and sinonasal levels of the inactive form of vitamin D3, 25-hydroxycholecalciferol (25VD3). Moreover, CRSwNP patients have reduced epithelial cell-specific expression of 1α-hydroxylase; the enzyme responsible for the conversion of 25VD3 to its metabolically active form, 1α,25-dihydroxyvitamin D3 (1,25VD3). The objective of this work was to determine the impact of sinonasal 1α-hydroxylase levels combined from all cellular sources on subjective disease severity and to identify variables influencing its expression.
  
  
  METHODS
  Blood and sinus tissue explants were collected at the time of surgery from control, chronic rhinosinusitis without nasal polyps (CRSsNP), CRSwNP, and allergic fungal rhinosinusitis (AFRS) patients. 1α-Hydroxylase was measured by immunostaining with flow cytometric analysis. Subjective disease severity was measured by the 22-item Sino-Nasal Outcomes Test (SNOT-22). 1,25VD3 and 25VD3 were measured by enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  Patients with CRSwNP or AFRS have reduced 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Circulating 1,25VD3 levels were the same among all groups. No differences in sinonasal 1α-hydroxylase or 1,25VD3 were found between CRSwNP and AFRS. Gender, age, race, atopy, and systemic 25VD3 had no impact on sinonasal 1α-hydroxylase levels in any group. However, CRSwNP patients with asthma had higher 1α-hydroxylase than those without asthma. Total 1α-hydroxylase levels inversely correlated with SNOT-22 in CRSwNP, but not CRSsNP.
  
  
  CONCLUSIONS
  Patients with CRSwNP and AFRS both have reduced sinonasal 1α-hydroxylase and 1,25VD3 compared to controls or CRSsNP. Reductions in intracellular 1α-hydroxylase combined from all sinonasal cell types were associated with more severe subjective disease severity in CRSwNP.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.|Ralph H. Johnson VA Medical Center, Charleston, SC.
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Schlosser
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.
authors.forename: William W
authors.initials: WW
authors.lastname: Carroll
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Soler
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.
authors.forename: Whitney N
authors.initials: WN
authors.lastname: Pasquini
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC.|Ralph H. Johnson VA Medical Center, Charleston, SC.|Department of Pediatrics, Medical University of South Carolina, Charleston, SC.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Mulligan
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications* / Q000378:metabolism; D010256:Paranasal Sinuses / Q000378:metabolism*; D011788:Quality of Life; D012220:Rhinitis / Q000150:complications / Q000378:metabolism*; D012720:Severity of Illness Index; D012852:Sinusitis / Q000150:complications / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
keywords: 1-alpha-hydroxylase; allergic fungal rhinosinusitis; nasal polyp; sinusitis; vitamin D