Increased bronchial nitric oxide production in patients with asthma measured with a novel method of different exhalation flow rates

Abstract

The concentration of nitric oxide (NO) in exhaled air is increased in patients with asthma, suggesting that measuring fractional exhaled NO concentration (FENO) may be used to monitor asthmatic airway inflammation. However, increased FENO is not specific for asthma, as other inflammatory lung diseases may also increase FENO. To augment the specificity of FENO measurement, we tested a novel theoretical modelling of pulmonary NO dynamics that allows the approximation of alveolar NO concentration and bronchial NO flux separately by measuring FENO at several exhalation flow rates. We measured FENO at four exhalation flow rates in 10 steroid-naive asthmatics, 5 patients with extrinsic allergic alveolitis, and in 10 healthy controls. Both the asthmatics and the patients with alveolitis had significantly higher FENO than the healthy controls. The increased NO concentration originated from the bronchial level in the asthmatics and from the alveolar level in the patients with alveolitis. In the second part of the study we assessed the repeatability of FENO test, within-day and day-to-day (during two weeks) variation in FENO, and the effects of mouth pressure and cigarette smoking on FENO in healthy volunteers. Repeatability of 10 subsequent measurements was high (coefficient of variation (CV) 4.6% ± 0.4%), and no diurnal variation was found. The day-to-day variation during a 2-week period gave a CV of 10.6% ± 1.0%. The magnitude of mouth pressure (5-20 cmH2O in adults, 5-40 cmH2O in children) during measurement had no effect on FENO. Smoking a cigarette caused a small and transient but statistically significant increase in FENO at 1 and 5 min after smoking. In conclusion, FENO measurement is highly repeatable with low day-to-day variation among healthy subjects. Our results also suggest that the present novel method of measuring FENO at several exhalation flow rates can be used to approximate alveolar and bronchial contributions to FENO separately and thus increase the clinical value of this test.