Airway contribution to alveolar nitric oxide in healthy subjects and stable asthma patients

1 Biomedical Physics Laboratory, Université Libre de Bruxelles; and 2 Chest Department, Erasme University Hospital, Brussels, Belgium Submitted 27 September 2007 ; accepted in final form 16 January 2008 Alveolar nitric oxide (NO) concentration (F A 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 F A NO . Our objectives in this study were 1 ) to simulate the impact of backdiffusion on F A NO and to estimate the alveolar concentration actually due to in situ production (F A 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 F A NO and exhaled NO concentration at 50 ml/s expired flow (F E NO ) for a range of alveolar and bronchial NO productions. F A NO and F E 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, F A NO and F E NO are linearly related. Experimental results confirm this relationship. F A NO,prod may be derived by F A NO,prod = (F A NO – 0.08·F E NO )/0.92 ( Eq. 1 ). Based on Eq. 1 , F A 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. exhaled nitric oxide; alveolar nitric oxide; asthma; modeling Address for reprint requests and other correspondence: A. Van Muylem, Chest Dept., CUB Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium (e-mail: avmuylem{at}ulb.ac.be )