title: Inducible nitric oxide synthase expression is increased in the alveolar compartment of asthmatic patients.
abstract: BACKGROUND
  Increased exhaled nitric oxide (NO) levels in asthma are suggested to be through inducible NO synthase (iNOS). The aim of this study was to investigate the expression of iNOS in bronchoalveolar lavage (BAL) cells and tissue from central and peripheral airways and compare it with the exhaled bronchial and alveolar NO levels in patients with asthma vs a control group.
  
  
  METHODS
  Thirty-two patients with asthma (defined as controlled or uncontrolled according to Asthma Control Test score cut-off: 20) and eight healthy controls were included. Exhaled NO was measured, and alveolar concentration and bronchial flux were calculated. iNOS was measured in central and peripheral lung biopsies, as well as BAL cells. Bronchoalveolar lavage macrophages were stimulated in vitro, and iNOS expression and NO production were investigated.
  
  
  RESULTS
  Expression of iNOS was increased in central airway tissue and the alveolar compartment in uncontrolled as compared to controlled asthmatics and healthy controls. There were no differences, however, in iNOS mRNA levels in total BAL cells in uncontrolled as compared to controlled asthma. Bronchoalveolar lavage cell mRNA levels of iNOS or iNOS expression in central and alveolar tissue did not relate to alveolar NO, nor to bronchial flux of NO. In vitro stimulation with leukotriene D4increased iNOS mRNA levels and NO production in cultured BAL macrophages.
  
  
  CONCLUSIONS
  The levels of both bronchial and alveolar iNOS are increased in uncontrolled as compared to controlled asthma. However, levels of iNOS in BAL macrophages were not reflected by alveolar NO. Both central and distal iNOS levels may reflect responsiveness to steroid treatment.
authors.affiliation: Respiratory Medicine and Allergology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Tufvesson
authors.affiliation: National Heart & Lung Institute, Imperial College, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Andersson
authors.affiliation: Respiratory Medicine and Allergology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Weidner
authors.affiliation: Airway inflammation, Department of Experimental Medical Science, Lund University, Lund, Sweden.
authors.forename: J S
authors.initials: JS
authors.lastname: Erjefält
authors.affiliation: Respiratory Medicine and Allergology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Bjermer
mesh_terms: D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012129:Respiratory Function Tests; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II
keywords: asthma; exhaled nitric oxide; inducible nitric oxide synthase