Exhaled NO in asthmatic children in unpolluted and urban environments

Abstract

Background: NO production (NOex) in the airway epithelium is increased in asthmatic patients and is potently inhibited by anti-inflammatory treatments. The study was designed to compare the: (i) levels of NOex in two groups of asthmatic children residing in different environments (one in a national park in the mountains and the other in a large city) and (ii) the influence of glucocorticoids on levels of NOex between the children and those without treatment. Methods: The measurements were performed during the same period in the two locations, 100 km apart. NOex was measured using a chemiluminescence analyzer in controls and two comparable groups of asthmatic children. The first group included 63 children (10±3 years) recruited from a specialized institution for asthmatic children, and the second group consisted of 46 asthmatic children (9±3 years) living in an urban area. A reference group of 17 healthy children residing in the same city was also studied. Measurements and results: The concentrations of NOex in children in the specialized institution were significantly lower (P<.001) than those in asthmatic children living in the city (5.1±2.4 vs. 13.8±9.3 ppb) and comparable to those in healthy controls (5.3±4.0 ppb). In the urban area, NOex levels increased when atmospheric pollution recorded on the previous day had increased. In contrast to that observed in the urban children, glucocorticoids had little influence on the levels of NOex in the children living in the specialized institution. Conclusions: Although these relationships need to be confirmed, our findings show that for the determination of NOex, specifying the quality of the environment, in particular, the purity of the air respired by asthmatic children, not only at the time of measurement but also over the previous days, is important.

Introduction

Patients with respiratory disorders, and more particularly asthmatics, exhale more NO than do healthy individuals Gustafsson et al., 1991, Alving et al., 1993, Kharitonov et al., 1994, Persson et al., 1994, Rutgers et al., 1998. Under normal physiological conditions, NO is produced from arginine by various isoforms of the NO synthase enzyme. Two isoforms are thought to be constitutive (cNOS) and calcium-dependant. One is found in endothelial cells of pulmonary veins and arteries as well as in epithelial cells, while the other is found in nonadrenergic noncholinergic inhibitory neurons Adnot et al., 1995, Asano et al., 1994. On the other hand, under immunological or inflammatory stimulation, NO is produced by an inducible NO synthase (iNOS) found in a variety of inflammatory and smooth muscle cells (Marletta, 1994). The rise in exhaled NO (NOex) is thought to reflect an increase in activity of iNOS induced by proinflammatory cytokines and endotoxins Adnot et al., 1995, Morris and Billar, 1994. Inhaled glucocorticoids exert a dose-dependent inhibition on these inflammatory processes and also reduce amounts of NOex (Kharitonov et al., 1996a). It has thus been suggested that NOex might provide a useful indicator of the response to anti-inflammatory treatment Kharitonov et al., 1996a, Barnes and Kharitonov, 1996.

Since asthma and atmospheric pollution are commonly associated, we compared over the same period, the levels of NOex in a group of healthy children with those of two groups of asthmatic children, one residing in the same city as the healthy controls and the other living in a specialized institution for asthmatic children in a national park 1000 m above sea level. In an attempt to evaluate the influence of air quality on levels of NOex by the asthmatic children in the urban environment, urban pollution was recorded. The mean daily levels of atmospheric NO and CO were used as markers of traffic density. We also examined the influence of glucocorticoid treatment in some children in the two groups of asthmatic children.