Nitrative stress in refractory asthma

J Allergy Clin Immunol. 2008 Feb;121(2):355-60. doi: 10.1016/j.jaci.2007.11.009. Epub 2007 Dec 26.


Background: Most asthma is mild and moderate and can be well controlled by low-dose inhaled steroid with or without bronchodilators. However, 5% to 10% of patients with asthma have more troublesome disease despite using such medication. Recent reports showed that nitrative stress induced tissue remodeling in vitro, which is associated with a component of refractoriness in asthma. However, there is no report that nitrative stress is involved in refractory asthma.

Objective: The aim of this study is to evaluate whether patients with refractory asthma have more nitrative stress.

Methods: Ten healthy subjects, 10 patients with well-controlled asthma, and 8 patients with refractory asthma took part in the current study. Exhaled nitric oxide, xanthine oxidase activity in the supernatant of the sputum, immunostaining for the inducible type of nitric oxide synthase, and 3-nitrotyrosine in induced sputum from the subjects were assessed.

Results: All nitrative markers including exhaled nitric oxide (P < .01), immunopositivities for inducible nitric oxide synthase (P < .01), xanthine oxidase activities (P < .01), and 3-nitrotyrosine (P < .01) in sputum from the refractory asthma group were enhanced compared with the well-controlled group. All these nitrative markers in the sputum had a significant negative correlation with the %FEV(1) values (P < .01).

Conclusion: These results suggested that patients with refractory asthma have more nitrative stress in their airways compared with patients with well-controlled asthma.

MeSH terms

  • Adult
  • Aged
  • Asthma / drug therapy
  • Asthma / metabolism
  • Asthma / physiopathology*
  • Biomarkers / metabolism
  • Bronchodilator Agents / therapeutic use
  • Drug Resistance
  • Exhalation
  • Female
  • Forced Expiratory Volume
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism*
  • Sputum / metabolism*
  • Staining and Labeling
  • Steroids / therapeutic use
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism
  • Vital Capacity
  • Xanthine Oxidase / metabolism*


  • Biomarkers
  • Bronchodilator Agents
  • Steroids
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase Type II
  • Xanthine Oxidase