title: Sulforaphane improves the bronchoprotective response in asthmatics through Nrf2-mediated gene pathways.
abstract: BACKGROUND
  It is widely recognized that deep inspiration (DI), either before methacholine (MCh) challenge (Bronchoprotection, BP) or after MCh challenge (Bronchodilation, BD) protects against this challenge in healthy individuals, but not in asthmatics. Sulforaphane, a dietary antioxidant and antiinflammatory phytochemical derived from broccoli, may affect the pulmonary bronchoconstrictor responses to MCh and the responses to DI in asthmatic patients.
  
  
  METHODS
  Forty-five moderate asthmatics were administered sulforaphane (100 μmol daily for 14 days), BP, BD, lung volumes by body-plethsmography, and airway morphology by computed tomography (CT) were measured pre- and post sulforaphane consumption.
  
  
  RESULTS
  Sulforaphane ameliorated the bronchoconstrictor effects of MCh on FEV1 significantly (on average by 21 %; p = 0.01) in 60 % of these asthmatics. Interestingly, in 20 % of the asthmatics, sulforaphane aggravated the bronchoconstrictor effects of MCh and in a similar number was without effect, documenting the great heterogeneity of the responsiveness of these individuals to sulforaphane. Moreover, in individuals in whom the FEV1 response to MCh challenge decreased after sulforaphane administration, i.e., sulforaphane was protective, the activities of Nrf2-regulated antioxidant and anti-inflammatory genes decreased. In contrast, individuals in whom sulforaphane treatment enhanced the FEV1 response to MCh, had increased expression of the activities of these genes. High resolution CT scans disclosed that in asthmatics sulforaphane treatment resulted in a significant reduction in specific airway resistance and also increased small airway luminal area and airway trapping modestly but significantly.
  
  
  CONCLUSIONS
  These findings suggest the potential value of blocking the bronchoconstrictor hyperresponsiveness in some types of asthmatics by phytochemicals such as sulforaphane.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rbrown@jhsph.edu.|Division of Pulmonary Medicine and Critical Care, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rbrown@jhsph.edu.|Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rbrown@jhsph.edu.|Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Room E7614, 615 N. Wolfe Street, Baltimore, MD, 21205, USA. rbrown@jhsph.edu.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Brown
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Room E7614, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
authors.forename: Curt
authors.initials: C
authors.lastname: Reynolds
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins University School of Public Health, Room E7614, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Brooker
authors.affiliation: Lewis B. and Dorothy Cullman Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Human Nutrition, Department of International Health, Johns Hopkins University School of Public Health, Baltimore, MD, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Talalay
authors.affiliation: Lewis B. and Dorothy Cullman Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.|Center for Human Nutrition, Department of International Health, Johns Hopkins University School of Public Health, Baltimore, MD, USA.
authors.forename: Jed W
authors.initials: JW
authors.lastname: Fahey
mesh_terms: D000328:Adult; D000403:Airway Resistance / Q000187:drug effects; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D001985:Bronchial Provocation Tests / Q000379:methods; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents / Q000008:administration & dosage; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000009:adverse effects; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008176:Lung Volume Measurements / Q000379:methods; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D011237:Predictive Value of Tests; D013454:Sulfoxides; D013997:Time Factors; D036542:Tomography, Spiral Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000975:Antioxidants; D016085:Bronchoconstrictor Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D013454:Sulfoxides; D016210:Methacholine Chloride; C016766:sulforaphane