ten Hacken N H, van der Vaart H, van der Mark T W, Koëter G H, Postma D S
Department of Pulmonology, University Hospital Groningen, Groningen, The Netherlands.
Am J Respir Crit Care Med. 1998 Sep;158(3):902-7. doi: 10.1164/ajrccm.158.3.9712021.
Nitric oxide in exhaled air is thought to reflect airway inflammation. No data have been reported so far on circadian changes in NO in subjects with nocturnal asthma. To determine whether exhaled NO shows a circadian rhythm inverse to the circadian rhythm in airway obstruction in subjects with nocturnal asthma, we conducted a study involving six healthy controls, eight individuals without nocturnal asthma (4-h to 16-h variation in peak expiratory flow [PEF] <= 15%), and six individuals with nocturnal asthma (4-h to 16-h PEF variation > 15%). Smoking, use of corticosteroids, and recent respiratory infections were excluded. NO concentrations were measured at 12, 16, 20, and 24 h, and at 4, 8, and 12 h of the next day, using the single-breath method. At the same times, FEV1 and PEF were also measured. Mean NO concentrations were significantly higher in subjects with nocturnal asthma than in subjects without nocturnal asthma, and higher in both groups than in healthy controls at all time points. Mean exhaled NO levels over 24 h correlated with the 4-h to 16-h variation in PEF (r = 0.61, p < 0.01). Exhaled NO did not show a significant circadian variation in any of the three groups as assessed with cosinor analysis, in contrast to the FEV1 in both asthma groups (p < 0.05). At 4 h, mean +/- SD NO levels were higher than at 16 h in subjects with nocturnal asthma; at 50 +/- 20 ppb versus 42 +/- 15 ppb (p < 0.05); other measurements at all time points were similar. Differences in NO and FEV1 from 4 h to 16 h did not correlate with one another. We conclude that subjects with nocturnal asthma exhale NO at higher levels both at night and during the day, which may reflect more severe diurnal airway-wall inflammation. A circadian rhythm in exhaled NO was not observed. NO levels did not correspond to the circadian rhythm in airway obstruction. The small increase in NO at 4 h may indicate an aspect of inflammation, but it is not associated with increased nocturnal airway obstruction.
呼出气体中的一氧化氮被认为可反映气道炎症。目前尚无关于夜间哮喘患者一氧化氮昼夜变化的数据报道。为了确定夜间哮喘患者呼出的一氧化氮是否呈现出与气道阻塞昼夜节律相反的昼夜节律,我们开展了一项研究,纳入了6名健康对照者、8名无夜间哮喘的个体(呼气峰值流速[PEF]在4小时至16小时内的变化≤15%)以及6名夜间哮喘患者(4小时至16小时内的PEF变化>15%)。排除吸烟、使用皮质类固醇以及近期呼吸道感染情况。采用单次呼吸法在12、16、20和24小时以及次日的4、8和12小时测量一氧化氮浓度。同时,还测量了第一秒用力呼气容积(FEV1)和呼气峰值流速(PEF)。夜间哮喘患者的平均一氧化氮浓度显著高于无夜间哮喘的个体,且在所有时间点,两组患者的一氧化氮浓度均高于健康对照者。24小时内的平均呼出一氧化氮水平与4小时至16小时内的PEF变化相关(r = 0.61,p < 0.01)。与两个哮喘组的FEV1情况相反,经余弦分析评估,三组中任何一组的呼出一氧化氮均未显示出显著的昼夜变化(p < 0.05)。在4小时时,夜间哮喘患者的平均±标准差一氧化氮水平高于16小时时;分别为50±20 ppb和42±15 ppb(p < 0.05);其他所有时间点的测量结果相似。4小时至16小时内一氧化氮和FEV1的差异彼此不相关。我们得出结论,夜间哮喘患者在夜间和白天呼出的一氧化氮水平均较高,这可能反映出更严重的昼夜气道壁炎症。未观察到呼出一氧化氮的昼夜节律。一氧化氮水平与气道阻塞的昼夜节律不对应。4小时时一氧化氮的小幅升高可能表明炎症的一个方面,但它与夜间气道阻塞增加无关。