Abstract

Extended exhaled nitric oxide (eNO) analysis can distinguish proximal and distal airway contributions to FeNO. Thus, it has the potential to detect effects of different environmental influences, allergic phenotypes, and genetic variants on proximal and distal airways. However, its feasibility in field surveys has not been demonstrated, and models for estimating compartmental NO contributions have not been standardized. In this study we verified that extended NO tests can be performed by children in schools, and assessed different analytical models to estimate bronchial flux and alveolar NO concentration. We tested students at a middle school, using EcoMedics NO analyzers with ambient NO scrubbers, at flows of 50 (conventional), 30, 100, and 300 ml/sec, with 2-3 trials at each flow. Data from 65 children were analyzed by two linear and four nonlinear published models, plus a new empirical nonlinear model. Bronchial NO flux estimates from different models differed in magnitude but were strongly correlated (r >or= 0.95), and increased in subjects with allergic asthma. Alveolar concentration estimates differed among models and did not consistently show the same effects of allergy or asthma. A novel index of nonlinear behavior of NO output versus flow was significantly related to asthma status, and not strongly correlated with bronchial flux or alveolar concentration. Field-based extended NO testing of children can yield useful information about NO in different regions of the respiratory tract that is not obtainable from conventional FeNO. Extended NO analysis holds promise for investigating environmental and genetic determinants of regional airway inflammatory states.

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