This report describes methods for measuring nitric oxide production by the
lungs' lower alveolar airways ((V) over dot NO), defined as those alveoli a
nd bronchioles well perfused by the pulmonary circulation. Breath holding o
r vigorous rebreathing for 15-20 s minimizes removal of NO from the lower a
irways and results in a constant partial pressure of NO in the lower airway
s (PL). Then the amount of NO diffusing into the perfusing blood will be th
e pulmonary diffusing capacity for NO (DNO) multiplied by PL and by mass ba
lance equals (V) over dot NO, or (V) over dot NO = DNO(PL). To measure PL,
10 normal subjects breath held for 20 s followed by exhalation at a constan
t flow rate of 0.83 +/- 0.14 (SD) l/s or rebreathed at 59 +/- 15 l/min for
20 s while NO was continuously measured at the mouth. DNO was estimated to
equal five times the single-breath carbon monoxide diffusing capacity. By u
sing breath holding, PL equaled 2.9 +/- 0.8 mmHg x 10(-6) and (V) over dot
NO equaled 0.39 +/- 0.12 mu l/min. During rebreathing PL equaled 2.3 +/- 0.
6 mmHg x 10(-6) and (V) over dot NO equaled 0.29 +/- 0.11 mu l/min. Measure
ments of NO at the mouth during rapid, constant exhalation after breath hol
ding for 20 s or during rebreathing provide reproducible methods for measur
ing (V) over dot NO in humans.