title: Increase of nitrosative stress in patients with eosinophilic pneumonia.
abstract: BACKGROUND
  Exhaled nitric oxide (NO) production is increased in asthma and reflects the degree of airway inflammation. The alveolar NO concentration (Calv) in interstitial pneumonia is reported to be increased. However, it remains unknown whether NO production is increased and nitrosative stress occurs in eosinophilic pneumonia (EP). We hypothesized that nitrosative stress markers including Calv, inducible type of NO synthase (iNOS), and 3-nitrotyrosine (3-NT), are upregulated in EP.
  
  
  METHODS
  Exhaled NO including fractional exhaled NO (FENO) and Calv was measured in ten healthy subjects, 13 patients with idiopathic pulmonary fibrosis (IPF), and 13 patients with EP. iNOS expression and 3-NT formation were assessed by immunocytochemistory in BALf cells. The exhaled NO, lung function, and systemic inflammatory markers of the EP patients were investigated after corticosteroid treatment for 4 weeks.
  
  
  RESULTS
  The Calv levels in the EP group (14.4 ± 2.0 ppb) were significantly higher than those in the healthy subjects (5.1 ± 0.6 ppb, p < 0.01) and the IPF groups (6.3 ± 0.6 ppb, p < 0.01) as well as the FENO and the corrected Calv levels (all p < 0.01). More iNOS and 3-NT positive cells were observed in the EP group compared to the healthy subject and IPF patient. The Calv levels had significant positive correlations with both iNOS (r = 0.858, p < 0.05) and 3-NT positive cells (r = 0.924, p < 0.01). Corticosteroid treatment significantly reduced both the FENO (p < 0.05) and the Calv levels (p < 0.01). The magnitude of reduction in the Calv levels had a significant positive correlation with the peripheral blood eosinophil counts (r = 0.802, p < 0.05).
  
  
  CONCLUSIONS
  These results suggested that excessive nitrosative stress occurred in EP and that Calv could be a marker of the disease activity.
authors.affiliation: Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Furukawa
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Koarai
authors.forename: Tsunahiko
authors.initials: T
authors.lastname: Hirano
authors.forename: Satoru
authors.initials: S
authors.lastname: Yanagisawa
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Minakata
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Akamatsu
authors.forename: Masae
authors.initials: M
authors.lastname: Kanda
authors.forename: Manabu
authors.initials: M
authors.lastname: Nishigai
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000704:Analysis of Variance; D001944:Breath Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016022:Case-Control Studies; D045853:Exhalation; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000097:blood; D007564:Japan; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism*; D011657:Pulmonary Eosinophilia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D012129:Respiratory Function Tests; D013312:Stress, Physiological / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000305:Adrenal Cortex Hormones; D018836:Inflammation Mediators; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II