Simultaneous measurement of nitric oxide production by conducting and alveolar airways of humans

Human airways produce nitric oxide (NO), and exhaled NO increases as expira tory flow rates fall. We show that mixing during exhalation between the NO produced by the lower, alveolar airways ((V) over dot (LNO)) and the upper conducting airways ((V) over dot (UNO)) explains this phenomenon and permit s measurement of (V) over dot (LNO), (V) over dot (UNO) and the NO diffusin g capacity of the conducting airways (D-UNO) After breath holding for 10-15 s the partial pressure of alveolar NO (PA) becomes constant, and during a subsequent exhalation at a constant expiratory flow rate the alveoli will d eliver a stable amount of NO to the conducting airways. The conducting airw ays secrete NO into the lumen ((V) over dot (UNO)), which mixes with PA dur ing exhalation, resulting in the observed expiratory concentration of NO (P E). At fast exhalations, PA makes a large contribution to PE, and, at slow exhalations, NO from the conducting airways predominates. Simple equations describing this mixing, combined with measurements of PE at several differe nt expiratory flow rates, permit calculation of PA, (V) over dot (UNO), and DUNO. (V) over dot (LNO) is the product of PA and the alveolar airway diff usion capacity for NO. In seven normal subjects, PA = 1.6 +/- 0.7 x 10(-6) (SD) Torr, (V) over dot (LNO) = 0.19 +/- 0.07 mu l/min, (V) over dot (UNO) = 0.08 +/- 0.05 mu l/min, and DUNO = 0.4 +/- 0.4 ml.min(-1).Torr(-1). These quantitative measurements of (V) over dot (LNO) and (V) over dot (UNO) are suitable for exploring alterations in NO production at these sites by dise ases and physiological stresses.