Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans

Que LG, Stiles JV, Sundy JS, Foster WM. Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans. J Appl Physiol 111: 679-687, 2011. First published June 23, 2011; doi: 10.1152/japplphysiol.00337.2011.-Effect of laboratory exposure to O-3 (220 ppb) and filtered air (FA) on respiratory physiology were evaluated at two time points (acute and 1 day postexposure) in healthy cohort (n = 138, 18-35 yr, 40% women) comprised mainly of Caucasian (60%) and African American (33.3%) subjects. Randomized exposures had a crossover design and durations of 2.25 h that included rest and treadmill walking. Airway responsiveness (AHR) to methacholine (Mch) and permeability of respiratory epithelium (EI) to hydrophilic radiomarker (Tc-99m-DTPA, MW = 492), were measured at 1-day postexposure. O-3 significantly affected FEV1 and FVC indices acutely with mean decrements from pre-exposure values on the order of 7.7 to 8.8% and 1.8 to 2.3% at 1-day post. Acute FEV1 and FVC decreases were most robust in African American male subjects. At 1-day post, O3 induced significant changes in AHR (slope of Mch dose response curve) and EI (Tc-99m-DTPA clearance half-time). Based on conventional thresholds of response and dichotomous classification of subjects as responders and nonresponders, sensitivity to O3 was shown to be nonuniform. Acute decrements >= 15% in FEV1, a doubling of Mch slope, or >= 15% increase in EI developed in 20.3%, 23.1%, and 25.9%, respectively, of subjects evaluated. Results demonstrate a diffuse sensitivity to O-3 and physiological responses, either acutely (decreases in FEV1) or 1 day post (development of AHR or change in EI) occur differentially in healthy young adults. Random overlap among subjects classified as responsive for respective FEV1, AHR, and EI endpoints suggests these are separate and independent phenotypes of O-3 exposure.