Atopy, Asthma And The Nitrite-Nitrate-No Pathway Among Adults From The Egea Study

Abstract

– Epidemiological studies led to conflicting results regarding associations between the exhaled fraction of nitric oxide (FeNO), a Rationale biomarker of pulmonary inflammation, with atopy and asthma. Eosinophils, associated with both asthma and atopy and involved in the NO pathway, may partly drive these associations. Nitrate (NO -) and nitrite (NO -) represent other indicators of NO synthesis. The aim was 3 2 to study the associations between total NO -NO levels in plasma and in Exhaled Breath Condensate (EBC) with asthma and atopy in 2 3 adults from the Epidemiological case-control and family-based study on the Genetics and Environment of Asthma (EGEA). –Atopy was defined by a mean wheal diameter ≥3mm than the negative control to at least one of 12 aeroallergens (skin prick Methods tests, SPT). Subjects were classified according to the number of SPT (SPT+) as none, 1, 2, 3, 4 and >4. EBC was collected using RTubeTM. Total NO2-NO3 (converted nitrate plus nitrite, Griess reaction) was expressed as μM in plasma and as μmol/μg in EBC (NO -NO divided by 2 3 protein level). FeNO level was recorded in a subset of subjects (54%). GEE multivariate regression models taking into account familial resemblance of the subjects were performed in 1218 adults (43 years, 613 women, 41.9% with asthma). –Geometric means (95% CI) were 162 cells/mm (156-168) for eosinophils, 35.8 μM (34.7–37.0) in plasma and 1.64 μmol/μg Results 3 (1.54–1.75) in EBC for NO -NO , and 15.3 ppb (14.5-16.1) for FeNO. Overall, eosinophils was positively and significantly associated with 2 3 asthma (200 vs. 138 cells/mm , p<0.0001) and with atopy (172 vs. 141 cells/mm , p<0.0001) whatever the asthma status. No association 3 3 was found between plasma and EBC NO -NO levels with asthma and atopy. FeNO levels were positively and significantly associated with 2 3 asthma (17.4 vs. 13.5 ppb p<0.0001) and with atopy (19.3 vs. 14.7 ppb, p<0.0001) regardless the asthma status. Among subjects without asthma, EBC NO -NO level was positively associated with atopy (1.83 vs. 1.57 μmol/μg, p=0.09). 2 3 Among subjects without asthma, an overall increase in EBC NO -NO level was observed in relation to the number of SPT+ (see below). 2 3