title: Assessment of small-airways disease using alveolar nitric oxide and impulse oscillometry in asthma and COPD.
abstract: The contribution of the alveolar compartment to exhaled nitric oxide (alveolar nitric oxide or CA(NO)) can be calculated as a surrogate of distal inflammation. This value should be corrected for nitric oxide produced in the conducting airways which "back-diffuses" into the alveolar compartment (Corrected CA(NO)). Impulse oscillometry (IOS) (Nava et al., Am J Respir Crit Care Med 168:1432-1437, 2003) is used to derive values for peripheral airways resistance. Twenty-four healthy volunteers, 21 severe asthmatics, 15 mild-to-moderate asthmatics, and 24 COPD patients were assessed with spirometry, impulse oscillometry, and fractionated exhaled nitric oxide. Compared to healthy volunteers, FE(NO) was higher in mild-to-moderate and severe asthmatics: geometric mean fold ratios of 1.91 (P = 0.02) and 2.74 (P < 0.001), respectively. However, there was no difference for mild-to-moderate versus severe asthma. Ratios for CA(NO) were not different for severe asthma versus COPD, but both were elevated compared to that of healthy volunteers [2.64 (P < 0.001) and 3.07 (P < 0.001), respectively] and mild-to-moderate asthma [1.95 (P = 0.04) and 2.28 (P < 0.01)]. However, after correction for axial diffusion, Corrected CA(NO) was increased in COPD compared to severe asthma (geometric mean fold ratio 1.28, P = 0.04), mild-to-moderate asthma (1.34, P < 0.01), and healthy volunteers (1.28, P = 0.02), and there was no difference between other groups. R5 and RF were reduced in healthy volunteers versus mild-to-moderate asthma (P = 0.011 and P < 0.001 respectively), severe asthma (P = 0.002 and P < 0.001), and COPD (P < 0.001 and P < 0.001). Peripheral resistance (R5-R20) was not different for healthy versus mild-to-moderate asthma but was higher in severe asthma (P < 0.001) and COPD (P < 0.001). Correlations were observed between R5-R20 versus FEF(25-75) (r = 0.71, P < 0.01), CA(NO) (r = 0.44, P < 0.01), and Corrected CA(NO) (r = 0.24, P < 0.01). CA(NO) and IOS provide additional information to traditional measures of spirometry and tidal nitric oxide. Previous data reporting elevated alveolar nitric oxide in severe asthma may reflect back-diffusion of nitric oxide from the conducting airways into the alveolar compartment. Corrected CA(NO) and IOS may prove to be useful noninvasive measurements of small-airways disease.
authors.affiliation: Asthma & Allergy Research Group, Centre for Cardiovascular & Lung Biology, Division of Medical Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee DD1 9SY, UK. p.a.williamson@dundee.ac.uk
authors.forename: Peter A
authors.initials: PA
authors.lastname: Williamson
authors.forename: Karine
authors.initials: K
authors.lastname: Clearie
authors.forename: Daniel
authors.initials: D
authors.lastname: Menzies
authors.forename: Sriram
authors.initials: S
authors.lastname: Vaidyanathan
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D009991:Oscillometry / Q000379:methods*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism*; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D013147:Spirometry
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide