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J Appl Physiol (January 24, 2008). doi:10.1152/japplphysiol.01032.2007
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Submitted on September 27, 2007
Accepted on January 16, 2008

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

Yannick Kerckx1, Alain Michils2, and Alain Van Muylem2*

1 Biomedical Physics Laboratory, Universite Libre de Bruxelles, Brussels, Belgium
2 Chest Department, Erasme University Hospital, Brussels, Belgium

* To whom correspondence should be addressed. E-mail: avmuylem{at}ulb.ac.be.

Rationale: Alveolar nitric oxide concentration (FANO), increasingly considered in asthma, is currently interpreted as a reflection of nitric oxide (NO) production in the alveoli. Recent modelling studies showed that axial molecular diffusion brings NO molecules from the airways back into the alveolar compartment during exhalation ("back-diffusion") and contributes to FANO. Objective: 1) to simulate the impact of back-diffusion on FANO and to estimate the alveolar concentration actually due to in-situ production (FANOprod). 2) To determine actual alveolar production in stable asthma patients with a broad range of NO bronchial productions. Methods: 1) A model incorporating convection and diffusion transport and NO sources was used to simulate FANO and exhaled NO concentration at 50 ml.s-1 expired flow (FENO) for a range of alveolar and bronchial NO productions. 2) FANO and FENO were measured in 10 healthy subjects (8 males; age: 38 ± 14 years) and in 21 asthma patients with stable asthma (16 males; age: 33 ± 13 years, FEV1 : 98.0 ± 11.9%pred ). The Asthma Control Questionnaire of Juniper assessed asthma control. Results: Simulations predict that, due to back-diffusion, FANO and FENO are linearly related. Experimental results confirm this relationship. FANOprod may be derived by FANOprod = (FANO-0.08·FENO)/0.92 (Equation 1). Based on (1), FANOprod is similar in asthma patients and in healthy subjects. Conclusion: The back-diffusion 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 back-diffusion.




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How accurately should we estimate the anatomical source of exhaled nitric oxide?
J Appl Physiol, April 1, 2008; 104(4): 909 - 911.
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