Partitioning of Alveolar and Conducting Airway Nitric Oxide in Scleroderma Lung Disease

We partitioned exhaled nitric oxide (NO) into alveolar concentration (CA) and conducting airway flux (JNO(air,max)) in scleroderma (SSc) lung disease and hypothesized that CA would be elevated. Twenty patients with SSc, 15 with interstitial lung disease (SSc-ILD) alone, and 5 with pulmonary hypertension (SSc-PH) were compared with 20 control subjects. CA and JNO(air,max) were derived from the slope and y intercept, respectively, of the NO output versus expiratory flow rate ((V).exh) relationship obtained by measuring exhaled NO (FE(NO)) at multiple (V).exh values of 50-200 ml/second. There were no significant differences in FE(NO) at any (V).exh between the SSc group and control subjects. JNO(air,max) was reduced (0.6 +/- 0.1 versus 1.2 +/- 0.2 nl of NO per second; p = 0.01), whereas CA was increased (4.7 +/- 0.5 versus 1.8 +/- 0.2 ppb; p < 0.001) in the SSc group compared with control subjects. No differences were noted between SSc-ILD and SSc-PH. There was a negative correlation between CA and DL(CO) among the patients with SSc (R = -0.66, p = 0.002). We conclude that CA is increased whereas JNO(air,max) is decreased in SSc-ILD and SSc-PH. A reduced diffusing capacity of NO from the alveolar space into the blood could explain the observed increase in CA.