title: Airway contribution to alveolar nitric oxide in healthy subjects and stable asthma patients.
abstract: Alveolar nitric oxide (NO) concentration (Fa(NO)), increasingly considered in asthma, is currently interpreted as a reflection of NO production in the alveoli. Recent modeling studies showed that axial molecular diffusion brings NO molecules from the airways back into the alveolar compartment during exhalation (backdiffusion) and contributes to Fa(NO). Our objectives in this study were 1) to simulate the impact of backdiffusion on Fa(NO) and to estimate the alveolar concentration actually due to in situ production (Fa(NO,prod)); and 2) to determine actual alveolar production in stable asthma patients with a broad range of NO bronchial productions. A model incorporating convection and diffusion transport and NO sources was used to simulate Fa(NO) and exhaled NO concentration at 50 ml/s expired flow (Fe(NO)) for a range of alveolar and bronchial NO productions. Fa(NO) and Fe(NO) were measured in 10 healthy subjects (8 men; age 38 +/- 14 yr) and in 21 asthma patients with stable asthma [16 men; age 33 +/- 13 yr; forced expiratory volume during 1 s (FEV(1)) = 98.0 +/- 11.9%predicted]. The Asthma Control Questionnaire (Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Chest 115: 1265-1270, 1999) assessed asthma control. Simulations predict that, because of backdiffusion, Fa(NO) and Fe(NO) are linearly related. Experimental results confirm this relationship. Fa(NO,prod) may be derived by Fa(NO,prod) = (Fa(NO) - 0.08.Fe(NO))/0.92 (Eq. 1). Based on Eq. 1, Fa(NO,prod) is similar in asthma patients and in healthy subjects. In conclusion, the backdiffusion mechanism is an important determinant of NO alveolar concentration. In stable and unobstructed asthma patients, even with increased bronchial NO production, alveolar production is normal when appropriately corrected for backdiffusion.
authors.affiliation: Chest Dept., CUB Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Kerckx
authors.forename: Alain
authors.initials: A
authors.lastname: Michils
authors.forename: Alain
authors.initials: A
authors.lastname: Van Muylem
mesh_terms: D000328:Adult; D000465:Algorithms; D001249:Asthma / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism / Q000502:physiology; D004058:Diffusion; D005541:Forced Expiratory Volume / Q000502:physiology; D006371:Helium; D006801:Humans; D016014:Linear Models; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009569:Nitric Oxide / Q000378:metabolism*; D010100:Oxygen; D011650:Pulmonary Alveoli / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System
chemical_list: D006371:Helium; D009569:Nitric Oxide; C038949:heliox; D010100:Oxygen