title: Exhaled breath condensate eicosanoid levels associate with asthma and its severity.
abstract: BACKGROUND
  The relationship between anti-inflammatory lipoxins and proinflammatory leukotrienes might be important in the pathobiology and severity of asthma.
  
  
  OBJECTIVE
  We sought to investigate whether exhaled breath condensate (EBC) lipoxin and leukotriene measurements can noninvasively characterize the asthmatic diathesis and its severity.
  
  
  METHODS
  We measured lipoxin A4 (LXA4) and leukotriene B4 (LTB4) levels in EBC collected from patients with asthma of different severities and from healthy control subjects.
  
  
  RESULTS
  EBC LXA4 and LTB4 levels are increased in asthmatic patients compared with those seen in healthy control subjects (LXA4: 31.40 vs 2.41 pg/mL EBC, respectively [P < .001]; LTB4: 45.62 vs 3.82 pg/mL EBC, respectively [P < .001]). Although levels of both eicosanoids are increased in asthmatic patients, the LXA4/LTB4 ratio decreases with increasing asthma severity. It is 41% lower in patients with severe versus moderate asthma (0.52 vs 0.88, P = .034). EBC LXA4 levels correlate with the degree of airflow obstruction measured by using FEV1 (r = 0.28, P = .018). An LXA4 cutoff value of 7 pg/mL EBC provides 90% sensitivity and 92% specificity for the diagnosis of asthma (area under the curve, 0.96; P < .001). An LTB4 cutoff value of 11 pg/mL EBC provides 100% sensitivity and 100% specificity for the diagnosis of asthma (area under the curve, 1; P < .001).
  
  
  CONCLUSIONS
  Proresolving and proinflammatory eicosanoids are generated in the airways of all asthmatic patients. The proportion of proresolving compounds decreases with asthma severity. These findings support the role for EBC eicosanoid measurements in the noninvasive diagnosis of asthma and suggest that proresolving eicosanoid pathways are dysregulated in patients with severe asthma.
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: skazani@partners.org.
authors.forename: Shamsah
authors.initials: S
authors.lastname: Kazani
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Anna
authors.initials: A
authors.lastname: Planaguma
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Emiko
authors.initials: E
authors.lastname: Ono
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bonini
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zahid
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Gautham
authors.initials: G
authors.lastname: Marigowda
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wechsler
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Levy
authors.affiliation: Pulmonary and Critical Care Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000175:diagnosis* / Q000378:metabolism; D001944:Breath Tests; D045853:Exhalation; D005260:Female; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D044045:Lipoxins; C040527:lipoxin A4; D007975:Leukotriene B4
keywords: Asthma; BAL; Bronchoalveolar lavage; CysLT; Cysteinyl leukotriene; EBC; Exhaled breath condensate; Feno; Fraction of exhaled nitric oxide; ICS; Inhaled corticosteroid; LTB(4); LXA(4); Leukotriene B(4); Lipoxin A(4); biomarkers; breath tests; eicosanoids; leukotriene B(4); lipoxin A(4)