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Abstract Asthma is a complex syndrome that can simply be defined as recurrent, reversible bronchospasm due to a trigger. NOS catalyzes the conversion of O2 and L-arginine to L-citrulline and NO. There are three isoforms of NOS: nNOS, eNOS, and iNOS. eNOS is involved in the regulation of bronchomotor tone, while iNOS plays an important role in inflammation, broncho-constriction and tissue damage. Cyclo-oxygenases enzymes catalyze the synthesis of prostaglandins from arachidonic acid. COX-1 is responsible for physiological roles including tissue protection. COX-2 by the contrast, is mainly involved in pathological processes including tissue injury. In our study, we explored the role of inducible NOS, endothelial NOS, COX-1 and COX-2, as markers in asthmatic children, and their relation to disease activity, severity and pulmonary function. 30 asthmatic children, and 15 healthy age and sex matched controls, were included in this study. The asthmatic children were divided into 3 groups : controlled, partly controlled and uncontrolled. All patients and controls were subjected to full history taking , clinical examination and chest x-rays. Full spirometric study was done including : FVC, FEV1 , FEV1 / FVC and FEF 25 % - 75% . Laboratory investigations were done including : complete blood picture for eosinophilia, serum IgE and induced sputum assessment for iNOS, eNOS, COX-1 and COX –2. In our study blood Eosinophil and serum IgE were progressively elevated in asthmatic patients subgroup I to III. The spirometric parameters of pulmonary function tests in asthmatic children were significantly reduced compared to controls. Our study revealed that FVC , FEV1, FEF25-75% were progressively reduced in asthmatic patients subgroups I to III. Estimation of sputum iNOS conc. showed that asthmatic patients had significantly higher levels for sputum iNOS as compared to controls and were progressively elevated in relation to worsening levels of asthma control. Our study revealed significant low levels of sputum eNOS in asthmatic children than controls, analysis of variance (ANOVA) showed that sputum eNOS enzymes were significantly different between the three patients subgroups, According to the least significant difference : there is a highly significant difference between group I and group III, while non significant differences between group II and group III or between group I and group II. Estimation of sputum COX-1 conc. showed that asthmatic patients had significantly lower levels of sputum COX-1 than controls and were progressively reduced in relation to worsening of asthma control. Our study revealed a significant high levels of COX-2 in asthmatic children sputum in comparison to controls and were progressively elevated in relation to worsening levels of asthma control. Our study revealed a significant positive correlations between sputum COX-1 and FVC, FEV1 & significant negative correlations between sputum COX-1 enzyme and blood Eosinophils percentage and serum IgE. Sputum COX-2 enzyme showed a significant positive correlation with blood Eosinophils percentages, serum IgE and sputum iNOS enzyme and a significant negative correlation with all spirometric parameters of pulmonary function tests , sputum COX-1 and eNOS enzymes. Sputum iNOS showed a significant positive correlation with blood Eosinophils percentages, IgE and negative correlations with FVC, FEV1, FEF25-75%, sputum COX-1 and eNOS enzymes. Our study revealed a significant positive correlation between sputum eNOS and FVC. We concluded that induced sputum iNOS, eNOS, COX-1 and COX-2 were not only linked to the presence of asthma or the severity of the attack but also to the worsening of pulmonary functions as evidenced by reduced spirometric measurements of FVC , FEV1 , and FEF25–75%. We also concluded that in asthmatic children the bronchoprotecting regulating constituitive isoforms (eNOS and COX-1) were significantly decreased, while the deleterious, bronchoconstricting inducible isoforms (iNOS and COX-2) were markedly increased, the most sensitive parameters for predicting severity and level of asthma control were: sputum COX-1 and sputum iNOS enzymes. It is most sensitive when sputum COX-1 enzyme level decreases below (209 u/ml) and sputum iNOS enzyme level increases above (6.8 u/ml). |