Exhaled Nitric Oxide in epidemiological and experimental studies

Abstract

The overall purpose with this thesis has been to contribute to the assessment of theutility of exhaled nitric oxide (eNO) in epidemiological studies. The specific aims have been toinvestigate whether eNO increases after occupational exposure to high peaks of ozone, or afterexperimental exposure to ozone in ambient concentrations. The aim has also been to seewhether occupational exposure to ozone increases the risk of asthma or rhinitis. A furtherintention has been to examine the association between atopy and exhaled NO. The influence ofintake of nitrate-rich food on exhaled NO was also studied.Two cross-sectional studies of bleachery workers were carried out, where in the first 56bleachery workers and 39 controls were examined and in the second, performed three yearslater, 228 bleachery workers and 63 controls. All were examined with measurements of exhalednitric oxide (eNO), lungfunction, questionnaires and blood samples. How atopy andsensitization were related to eNO and respiratory symptoms among the non-smoking subjectswas also studied. Furthermore eNO was measured after experimental exposure to ozone where11 healthy volunteers were randomly exposed to 200 ppb ozone or filtered air for two hours.eNO was measured before and directly afterwards, as well as six and 24 hours later. The effectof intake of a meal rich in nitrate on the concentration of nitrate in plasma and eNO, wasexamined in 16 healthy volunteers, who had been on a low nitrate diet for three days.There was no difference in eNO between bleachery workers and controls in either of the twostudies. Within the exposed group, those who had reported ozone exposure followed byrespiratory symptoms ( gassings ) had elevated levels of eNO (58.8 vs. 90.0 nL/min, p=0.019).The same was found in the second study, although only four or more gassings were associatedwith increased eNO (0 gassing: 15.7 ppb, 1-3 gassings: 14.1 ppb and >3 gassings 19.2 ppb,p=0.037). In the second study there were significantly increasing prevalences of rhinitis, adultonsetasthma and current asthma symptoms with increasing frequency of gassings. The atopicsubjects without asthma and rhinitis had eNO levels within the range of non-atopic subjects.Among the atopic subjects reporting symptoms of asthma or rhinitis, only those sensitized toperennial allergen had elevated NO levels. No significant changes of eNO were found afterexperimental exposure to ozone, when adjusting for changes of eNO after filtered air. eNO andplasma nitrate levels were increasing significantly up to two hours after the nitrate-rich meal,with a median increase of 47% (range 7-89%). The increase of eNO and plasma nitrate wascorrelated (rs=0.57, p=0.03).To conclude: gassings from ozone seem to be associated with increased prevalence of adultonset asthma, current asthma symptoms and rhinitis. eNO appears to be a marker for airwayinflammation after repeated occupational exposure to ozone, but not after experimentalexposure to ozone in ambient concentrations. Sensitization to perennial allergens and reportedsymptoms of asthma or rhinitis were found to be associated with higher levels of eNO. Intakeof nitrate- rich food may increase the levels of eNO, and should be restricted or noted beforemeasuring eNO.