Opposing Effects of Nasal Epithelial NAD(P)H Dehydrogenase Quinine 1 and Heme Oxygenase 1 Expression on Upper and Lower Airway Symptoms in Adolescents with Asthma

Details

• Personal Author:
  Biswal S ; Breysse P ; Diette G ; Matsui EC ; Noel S ; Ong MJC ; Saams J
• Description:
  To the Editor: Oxidative stress plays an important role in asthma. Nuclear factor (erythroid-derived 2)-like 2 (NRF2), a basic leucine zipper transcription factor, appears to be critical in this context because it regulates the expression of important antioxidant genes. As such, small molecule activators, such as sulforaphane, are being pursued as therapeutic agents in asthma. NRF2 target genes, including NAD(P)H dehydrogenase quinine 1 (NQO1) and heme oxygenase 1 (HO-1), are routinely assessed as markers of NRF2 activity in both laboratory and clinical settings with an underlying assumption that greater expression of these NRF2 target genes is a marker of a more robust antioxidant response, which should protect against airway inflammation and asthma symptoms. To test the hypothesis that greater HO-1 and NQO1 gene expression is associated with less airway inflammation, better lung function, and fewer asthma symptoms, we examined relationships between expression of these NRF2 target genes and clinical features of asthma in nonsmoking Baltimore City adolescents (14-17 years; n = 22) with moderate to severe asthma. Study participants were predominantly black (85%) and male (55%). Eighty-two percent had public health insurance. Ninety percent of participants had at least 1 positive skin test. NQO1 and HO-1 mRNA levels in nasal epithelium were inversely correlated (Spearman's correlation [rs] = -0.43; P = .04; Fig 1, A). Higher NQO1 expression was associated with more days of exercise-related symptoms (rs = 0.44; P = .04) and slowed activity because of asthma (rs = 0.57; P = .006; Fig 1, D and E). NQO1 expression was not associated with days of asthma symptoms (rs = -0.24; P = .27). In contrast, higher HO-1 expression was associated with fewer days of slowed activity because of asthma (rs = -0.45; P = .03; Fig 1, C) and asthma symptoms (rs = -0.43; P = .05). Higher HO-1 expression was also associated with fewer days of exercise-induced symptoms (rs = -0.27; P = .21; Fig 1, B), but this finding was not statistically significant. NQO1 expression was positively correlated with days of cough without a cold (rs = 0.48; P = .03), whereas HO-1 expression was negatively correlated with this symptom variable (rs = -0.56; P = .01). NQO1 expression was also higher among subjects with rhinoconjunctivitis (see this article's Fig E1 in the Online Repository at www.jacionline.org), resulting in greater odds of rhinoconjunctivitis symptoms (odds ratio [95% CI], 1.32 [1.02-1.70]), whereas higher HO-1 expression was associated with lower nonsignificant odds of rhinoconjunctivitis symptoms (odds ratio [95% CI], 0.36 [0.12-1.08]). Overall, higher NQO1 expression was positively associated with upper and lower respiratory symptoms, whereas higher HO-1 expression was inversely associated upper and lower respiratory symptoms. [Description provided by NIOSH]
• Subjects:
  Adolescent Asthma Asthma, Occupational Biomarkers Genetics Nose Occupational Health Respiratory System Safety Sense Organs
• Keywords:
  Adolescents Gene Expression Genes Nasal Cavity Oxidative Stress Respiratory Function
• ISSN:
  0091-6749
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  128
• Issue:
  2
• NIOSHTIC Number:
  nn:20062702
• Citation:
  J Allergy Clin Immunol 2011 Aug; 128(2):422-424.e3
• Email:
  sbiswal@jhsph.edu
• Federal Fiscal Year:
  2011
• Performing Organization:
  Johns Hopkins University
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  Journal of Allergy and Clinical Immunology
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d5a286a70e3c97d6917bf25bad1dcb8b33e282b583bc4fcce8e176a602e3167b4afe21a5102fe0c47e1d50d6758a932f7763412c9bddb362533d846b93ae7f34
• Download URL:
  https://stacks.cdc.gov/view/cdc/225898/cdc_225898_DS1.pdf
• File Type:
  [PDF - 395.37 KB ]