title: High alveolar concentration of nitric oxide is associated with alveolitis in scleroderma.
abstract: Alveolar concentration of nitric oxide (C(A)NO) is a non invasive prognostic marker of systemic sclerosis (SSc) lung disease. There is, however, as yet no direct evidence showing concomitant increase of C(A)NO and the presence of inflammatory cells in alveoli. We have therefore measured C(A)NO and performed broncho-alveolar lavage (BAL) in SSc patients. Exhaled NO was measured, by the means of two different models, the two-compartment model (2CM) and the trumpet model with axial diffusion (TMAD), in 22 SSc patients and compared with 15 healthy controls. BAL was performed in all SSc patients. Alveolitis was defined as lymphocytes >14%, polymorphonuclears >4%, or eosinophils >3% on cell count in BAL fluid. Comparisons of C(A)NO levels were made between SSc patients with, and without, alveolitis. Levels of C(A)NO were significantly higher in SSc patients as compared with controls (p<0.001). Median C(A)NO was significantly higher in SSc patients with alveolitis as compared with SSc patients without alveolitis (8.4ppb; 1st and 3rd interquartile range: 6.0-10.5 vs 3.3ppb; 2.2-3.5; p=0.004 for 2CM and 5.4ppb; 3.2-9.2 vs 3.2ppb; 1.4-3.3, p=0.02 for TMAD), while bronchial airway output of NO (J'awNO, p=0.19), and fractional exhaled NO (F(E)NO, p=0.12) were comparable. C(A)NO was consistently high in SSc patients with alveolitis irrespective of the methods chosen (TMAD or 2CM). Our findings showed that increased C(A)NO was associated with alveolitis in patients with SSc. We submit that C(A)NO could be used as a reliable non-invasive surrogate biomarker of alveolitis in scleroderma lung disease.
authors.affiliation: University Paris VI, Department of Internal Medicine, Saint Antoine Hospital, 184 rue du Faubourg Saint Antoine, 75571 Paris Cedex 12, France.
authors.forename: Kiet Phong
authors.initials: KP
authors.lastname: Tiev
authors.forename: Thong
authors.initials: T
authors.lastname: Hua-Huy
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rivière
authors.forename: Nhat-Nam
authors.initials: NN
authors.lastname: Le-Dong
authors.forename: Michel
authors.initials: M
authors.lastname: Febvre
authors.forename: Jean
authors.initials: J
authors.lastname: Cabane
authors.forename: Anh Tuan
authors.initials: AT
authors.lastname: Dinh-Xuan
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000032:analysis* / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D009569:Nitric Oxide