Nitric oxide (NO) can be derived from constitutive nitric oxide synthase (NOS), which is involved in physiologic regulation of airway function, or from inducible nitric oxide synthase (iNOS), which is involved in inflammatory disease of the airways and in host defense against infection. It is iNOS that is active in asthmatic airways. The purpose of this study was to determine if exhaled nitric oxide (eNO) levels in children varied according to their asthmatic and atopic states.
Between 1993 and 1995, questionnaires were sent to parents or guardians of 3290 children in the Wythenshawe Community Asthma Project (WYCAP) regarding respiratory symptoms and asthma-related conditions. The parents of 2434 children completed the questionnaire. A stratified weighted random sample of respondents attending one of the general practices was personally invited to participate in the study. Children were not excluded if they had a previous diagnosis of asthma or were receiving treatment for asthma. The clinical assessment included a full medical history and physical examination, an exercise challenge, spirometry with reversibility to a β2-agent, 1-week electronic peak flow daily record, and skin prick testing to house dust mite, grass pollen, cockroach, dog, and cat. Both the eNO and nasal nitric oxide (nNO) levels were measured. Three independent consultant pediatricians were supplied with all the information from the clinical assessment except for the NO findings. After reviewing the results, the pediatricians were asked to rate the subjects into four categories that reflected the probability that each child had asthma: >90% (probable asthma), 50% to 90% (possible asthma), 10% to 50% (asthma unlikely), or <10% (nonasthmatic).
Atopic, probable asthmatic children had higher geometric mean eNO (12.5 ppb) than did nonatopic probable asthmatics (3.2 ppb), the atopic nonasthmatics (3.8 ppb), and the nonatopic nonasthmatics (3.4 ppb) (P < .05). Atopic children with positive exercise test results had higher geometric mean eNO levels than the other groups.
Elevated levels of eNO were observed in atopic asthmatic children compared with nonatopic asthmatic children. Nonatopic asthmatics had levels of eNO similar to those of nonasthmatics whether atopic or not. A positive exercise test result also showed a higher eNO level compared with those with negative exercise test results, but the important co-factor was the atopic status with the highest values being observed in atopic asthmatics.
This is an interesting observation that has tremendous potential as a noninvasive marker of inflammation in childhood asthma. The results suggest that asthma and atopy as co-factors determine the magnitude of eNO production. What is missing here is knowing more about the clinical status of the patient and what medications they may have received, to determine the relationship of airway inflammation to eNO. It is not clear why atopy makes such a big difference in the asthmatic group. Further studies are needed comparing atopic and nonatopic asthmatics with a similar degree of asthma severity.