Kerckx Yannick, Michils Alain, Van Muylem Alain
Chest Dept., CUB Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.
J Appl Physiol (1985). 2008 Apr;104(4):918-24. doi: 10.1152/japplphysiol.01032.2007. Epub 2008 Jan 24.
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.
肺泡一氧化氮（NO）浓度（Fa(NO)）在哮喘研究中越来越受到关注，目前被认为是肺泡中NO生成的反映。最近的模型研究表明，在呼气过程中，轴向分子扩散会将气道中的NO分子带回肺泡腔（反向扩散），并对Fa(NO)产生影响。本研究的目的是：1）模拟反向扩散对Fa(NO)的影响，并估算实际由原位生成导致的肺泡浓度（Fa(NO,prod)）；2）确定不同NO支气管生成水平的稳定哮喘患者的实际肺泡生成量。使用一个包含对流、扩散传输和NO源的模型，模拟了一系列肺泡和支气管NO生成情况下，呼气流量为50 ml/s时的Fa(NO)和呼出NO浓度（Fe(NO)）。对10名健康受试者（8名男性；年龄38±14岁）和21名稳定哮喘患者[16名男性；年龄33±13岁；第1秒用力呼气量（FEV(1)）=预测值的98.0±11.9%]进行了Fa(NO)和Fe(NO)测量。采用哮喘控制问卷（Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Chest 115: 1265 - 1270, 1999）评估哮喘控制情况。模拟结果预测，由于反向扩散，Fa(NO)和Fe(NO)呈线性相关。实验结果证实了这种关系。Fa(NO,prod)可通过Fa(NO,prod) = (Fa(NO) - 0.08.Fe(NO))/0.92（公式1）得出。根据公式1，哮喘患者和健康受试者中的Fa(NO,prod)相似。总之，反向扩散机制是NO肺泡浓度的重要决定因素。在稳定且无气道阻塞的哮喘患者中，即使支气管NO生成增加，经反向扩散适当校正后，肺泡生成量仍正常。
