1 Nitroglycerin (GTN), often used in conditions of cardiovascular ischaemia, acts through the liberation of nitric oxide (NO) and the local concentration of NO in the tissue is responsible for any biological eect. However, little is known about the way in which the concentration of NO from GTN and other NO-donors is in¯uenced by low oxygen tension in the target tissues. 2 To evaluate the impact of changes in oxygen tension in the metabolism of NO-donors we measured exhaled NO in anaesthetized rabbits in vivo and expired NO and perfusate nitrite (NO 2 7 ) in buer-perfused lungs in situ. The impact of acute hypoxia on NO formation from GTN, isosorbide-5-mononitrate (ISMN), dissolved authentic NO, NO 2 7 and NO generated from endogenous NO-synthase (NOS) was studied in either model. 3 Acute hypoxia drastically increased exhaled NO concentrations from all NO-donors studied, both in vivo and in the perfused lung. During similar conditions endogenous NO generation from NOS was strongly inhibited. The eects were most pronounced at less than 3% inspired oxygen. 4 The mechanisms for the increased NO-formation during hypoxia seems to dier between GTNand NO 2 7 -derived NO. The former phenomenon is likely due to diminished breakdown of NO. 5 In conclusion, hypoxic conditions preserve very high local NO concentrations generated from organic nitrates in vivo and we suggest that this might bene®t preferential vasodilation in ischaemic tissue regions. Our ®ndings point out the necessity to consider the in¯uence of oxygen tension when studying the action of NO-donors.

Measurement of leukotriene E 4 (LTE 4 ) in urine is a noninvasive method for assessing changes in the rate of total body cysteinyl leukotriene production. Eosinophil protein X (EPX) has been used to assess eosinophil activity and monitor inflammation in bronchial asthma. The aim of the study was to look for differences in urinary LTE 4 and EPX concentrations between children with stable atopic asthma and healthy controls and to compare asthmatic children with different disease severity. In addition the relationship was evaluated between urinary LTE 4 amd EPX levels and lung function.LTE 4 was also measured (enzyme immunoassay) together with EPX (radioimmunoassay) in urine and lung function tests were carried out in children with mild asthma (steroid-naive) (n=49), moderate to severe asthma (using inhaled steroids) (n=31) and healthy control subjects (n=28).Urinary leukotriene E 4 (LTE 4 ) was significantly higher in children with asthma than in controls (median [25±75 percentile] 238.5 (126.5±375.7) SD 191.8 versus 189 (51±253.2) SD 131.7 pg . mg -1 creatinine; p=0.021). Urinary EPX was also significantly increased in asthmatic children compared with controls (85.5 [64±131.5] SD 76.2 versus 48.5 [43.2±90] 112.1 mg . mmol -1 creatinine; p=0.006). There were no differences in urinary LTE 4 and EPX between the group of mild and the group of moderate to severe asthmatic children. There were significant associations between the urinary LTE 4 and intrathoracic gas volume (ITGV), residual volume (RV), forced expiratory volume in one second (FEV1), forced expiratory capacity (FVC) and maximum expiratory flow rate at 25% of vital capacity (MEF25).Urinary EPX was only correlated with maximum expiratory flow rate at 75% of vital capacity (MEF75). Thus measurement of urinary LTE 4 may predict the degree of airflow obstruction in asthmatic children. Urinary LTE 4 and EPX are useful markers of airway inflammation and can be helpful in guiding asthma management. There was no correlation between LTE 4 and EPX levels. Eur Respir J 2000; 16: 588±592.

Exhaled nitric oxide can be detected in exhaled air and is readily measured by chemiluminescence. It is thought to be involved in both the regulation of ciliary motility and host defence. Recently, upper airway NO has been found to be reduced in a small number of children with primary ciliary dyskinesia (PCD) and its measurement has been recommended as a diagnostic test for this condition.The aim of this study was to compare the levels of NO in the upper and lower airways in a larger number of children with proven PCD with those found in healthy children. Exhaled NO was measured in the upper airway by direct nasal sampling during a breath-hold and in the lower airway as the end-tidal plateau level, using a chemiluminescence NO analyser.Upper airway NO levels were significantly lower in PCD (n=21) than in the healthy children (n=60) (meanSD, 97193, 664298 parts per billion (ppb), respectively, p<0.0001). In PCD, the lower airway NO levels were also reduced (2.171.18, 5.94 3.49 ppb, respectively, p<0.0001). The levels were not associated with steroid use and did not correlate with lung function.Although there was some overlap between normal children and those with primary ciliary dyskinesia with regard to lower airway NO, nasal NO discriminated between the two groups in all but one child in each group. Measurement of nasal NO therefore may be a useful screening test for primary ciliary dyskinesia.

Children with bronchial asthma have significantly higher levels of orally exhaled nitric oxide than healthy controls.