Reproducibility of NOexp using standardized methods was good both in healthy subjects and in asthmatic patients. However, in asthmatics the short-term variation of NOexp was over two times as high as in healthy subjects. The level of NOexp was elevated, except in asthma, also in patients with asthmatic respiratory symptoms who did not fulfill the functional criteria of asthma.

Exhaled nitric oxide (NOexp) is an indicator of inflammation in the airways. Reference values obtained from healthy adults or information on long-term variation of NOexp are not yet available. The aims of this pilot study were to collect values of NOexp from a selected group of healthy adults and to assess their long-term variation. We studied 26 healthy subjects (age 21-48, 16 male, 10 female) with normal findings in flow-volume spirometry, pulmonary diffusing capacity, relative amount of blood eosinophils, chest X-ray and ECG at rest. NOexp was determined according to the European Respiratory Society guidelines during slow expiration against an airflow resistance. The measurements were repeated after 7 (n = 13) and 23 days (n = 17). The mean value of NOexp (n = 26) was 6.9 ng g-1 (95% confidence interval, 6.0-7.9 ng g-1). The upper limit of intra-individual variation (+2 SD) was 11.9 ng g-1 and the lower limit (-2 SD) 1.9 ng g-1, respectively. The mean (SD) value of NO production (NO output) was 39.1 pmol s-1 (20 pmol s-1). We found no correlation between NOexp and age (r = -0.06, P = 0.78) and no association of NOexp with the gender (male vs. female, P = 0.40). The intraindividual coefficient of variation (CoV) was 15.8% of NOexp and 20.7% of NO output within the interval of 7 days. CoV was 16.8% of NOexp and 18% of NO output within the interval 23 days. The results suggest that NOexp values over 12 ng g-1 are abnormally high in healthy subjects. According to the results the change of NOexp by 30-35% or more within the interval of 1-3 weeks would be abnormal.

Background: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks. Methods: Twenty six asthmatic patients aged 21-59 years were selected for this randomised, double blind, parallel group study. The effect of 250 µg inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV 1 ) by 15% (PD 15 FEV 1 ) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD 15 FEV 1 were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves. Results: The increase in PD 15 FEV 1 from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD 15 FEV 1 was 1.85-2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment. Conclusions: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 µg. The effect tapered within 2 weeks of cessation of treatment.

This study was conducted to evaluate how bronchial responsiveness to direct and indirect stimuli relate to nitric oxide producing airway inflammation, and whether the relationship differs between atopic and nonatopic patients with various degrees of bronchial hyperresponsiveness and airway inflammation in a group of otherwise homogenous young men. We studied 181 consecutive non-smoking steroid-naive young male conscripts referred to military hospital because of respiratory symptoms suggesting asthma. Skin prick tests, spirometry, measurement of exhaled nitric oxide (FENO), and standardized airway challenges with histamine and exercise were performed. 128 patients were atopic. FENO was significantly higher in the atopic group, median 21.2 ppb, compared to 10.2 ppb in the nonatopic group. Still, 36% of all nonatopic patients had elevated FENO. Bronchial responsiveness to histamine (HIB) was similar in the two groups, but exercise-induced bronchoconstriction (EIB) was stronger in atopics (P < 0.01). FENO associated significantly with atopy (P < 0.001), severity of EIB (P < 0.001) and HIB (P = 0.006) in multiple linear regression model. In separate regression models for atopic and nonatopic patients FENO associated with severity of EIB and HIB in atopic patients only. The results were similar when patients with confirmed diagnosis of asthma were analyzed separately. Our results indicate that FENO significantly associates with EIB and HIB in atopic, but not in nonatopic steroid-naïve patients with asthmatic symptoms. The finding suggests that in such atopic patients degree of airway hyperresponsiveness may reflect severity of airway inflammation. However, in nonatopic patients with similar symptoms other mechanisms of airway hyperresponsiveness may be more important.