EXHALED NITRIC-OXIDE (NO) IS REDUCED SHORTLY AFTER BRONCHOCONSTRICTION TO DIRECT AND INDIRECT STIMULI IN ASTHMA

Exhaled NO is increased in patients with asthma and may reflect diseas e severity. We examined whether the level of exhaled NO is related to the degree of airway obstruction induced by direct and indirect stimul i in asthma. Therefore, we measured exhaled NO levels before and durin g recovery from histamine and hypertonic saline (HS) challenge (Protoc ol 1) or histamine, adenosine 5'-monophosphate (AMP), and isotonic sal ine (IS) challenge (Protocol 2) in 11 and in nine patients with mild t o moderate asthma, respectively. The challenges were randomized with a 2-d interval. Exhaled NO and FEV1 were measured before and at 4, 10, 20, and 30 min after each challenge. NO was measured during a slow VC maneuver with a constant expiratory flow of (0.05 x FVC)/s against a r esistance of 1 to 2 cm H2O. Baseline exhaled NO levels were not signif icantly different between study days in Protocol 1 (mean +/- SD: 4.8 /- 1.8 ppb [histamine] versus 5.4 +/- 2.1 ppb [HS], p = 0.4) or in Pro tocol 2 (7.9 +/- 4.7 ppb [histamine], 8.3 +/- 5.2 ppb [AMP], and 7.2 /- 3.7 ppb [IS], p = 0.7). A significant reduction in exhaled NO was o bserved directly after HS (mean +/- SEM: 39.2 +/- 3.9 %fall) and AMP c hallenge (32.3 +/- 7.3 %fall) (MANOVA, p < 0.001), respectively, where as exhaled NO levels tended to decrease after histamine challenge. Iso tonic saline challenge did not induce changes in exhaled NO (p = 0.7). There was a positive correlation between %fall in FEV1 and the %fall in exhaled NO after histamine, HS, and AMP challenge as indicated by t he mean slope of the within-subject regression lines (p less than or e qual to 0.04). We conclude that acute bronchoconstriction, as induced by direct and indirect stimuli, is associated with a reduction in exha led NO levels in asthmatic subjects. This suggests that airway caliber should be taken into account when monitoring exhaled NO in asthma.