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

The concentration of nitric oxide (NO) in exhaled air is increased in patie nts with asthma, suggesting that measuring fractional exhaled NO concentrat ion (FENO) may be used to monitor asthmatic airway inflammation. However, i ncreased FENO is not specific for asthma, as other inflammatory lung diseas es may also increase FENO. To augment the specificity of FENO measurement, we tested a novel theoretical modelling of pulmonary NO dynamics that allow s the approximation of alveolar NO concentration and bronchial NO flux sepa rately by measuring FENO at several exhalation flow rates. We measured FENO at four exhalation flow rates in 10 steroid-naive asthmatics, 5 patients w ith extrinsic allergic alveolitis, and in 10 healthy controls. Both the ast hmatics and the patients with alveolitis had significantly higher FENO than the healthy controls. The increased NO concentration originated from the b ronchial level in the asthmatics and from the alveolar level in the patient s with alveolitis. In the second part of the study we assessed the repeatab ility 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 cmH(2)O in adults, 5-40 cmH( 2)O in children) during measurement had no effect on FENO. Smoking a cigare tte caused a small and transient but statistically significant increase in FENO at 1 and 5 min after smoking. In conclusion, FENO measurement is highl y repeatable with low day-to-day variation among healthy subjects. Our resu lts also suggest that the present novel method of measuring FENO at several exhalation flow rates can be used to approximate alveolar and bronchial co ntributions to FENO separately and thus increase the clinical value of this test.