title: Exhaled Nitric Oxide in Systemic Sclerosis Lung Disease.
abstract: Background. Exhaled nitric oxide (eNO) is a potential biomarker to distinguish systemic sclerosis (SSc) associated pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). We evaluated the discriminative validity, feasibility, methods of eNO measurement, and magnitude of differences across lung diseases, disease-subsets (SSc, systemic lupus erythematosus), and healthy-controls.Methods. Consecutive subjects in the UHN Pulmonary Hypertension Programme were recruited. Exhaled nitric oxide was measured at 50 mL/s intervals using chemiluminescent detection. Alveolar and conducting airway NO were partitioned using a two-compartment model of axial diffusion (CMAD) and the trumpet model of axial diffusion (TMAD).Results. Sixty subjects were evaluated. Using the CMAD model, control subjects had lower median (IQR) alveolar NO than all PAH subjects (2.0 (1.5, 2.5) versus 3.14 ppb (2.3, 4.0),p= 0.008). SSc-ILD had significantly lower median conducting airway NO compared to controls (1009.5 versus 1342.1 ml⁎ppb/s,p= 0.04). SSc-PAH had increased median (IQR) alveolar NO compared to controls (3.3 (3.0, 5.7) versus 2.0 ppb (1.5, 2.5),p= 0.01). SSc-PAH conducting airway NO inversely correlated with DLCO (r-0.88 (95% CI -0.99, -0.26)).Conclusion. We have demonstrated feasibility, identified that CMAD modeling is preferred in SSc, and reported the magnitude of differences across cases and controls. Our data supports discriminative validity of eNO in SSc lung disease.
authors.affiliation: University Health Network Pulmonary Hypertension Programme, Toronto General Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Natalie K
authors.initials: NK
authors.lastname: Kozij
authors.affiliation: University Health Network Pulmonary Hypertension Programme, Toronto General Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: John T
authors.identifier: 0000-0002-2639-5958
authors.initials: JT
authors.lastname: Granton
authors.affiliation: Department of Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Silkoff
authors.affiliation: University Health Network Pulmonary Hypertension Programme, Toronto General Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Thenganatt
authors.affiliation: University Health Network Pulmonary Hypertension Programme, Toronto General Hospital, Toronto, ON, Canada.
authors.forename: Shobha
authors.initials: S
authors.lastname: Chakravorty
authors.affiliation: University Health Network Pulmonary Hypertension Programme, Toronto General Hospital, Toronto Scleroderma Program, Toronto Western Hospital, Mount Sinai Hospital, Department of Medicine, Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada.
authors.forename: Sindhu R
authors.identifier: 0000-0003-0591-2976
authors.initials: SR
authors.lastname: Johnson
mesh_terms: D000328:Adult; D001944:Breath Tests; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*
chemical_list: D020097:Natriuretic Peptide, Brain; D009569:Nitric Oxide