title: Pulmonary function, bronchial reactivity, and epithelial permeability are response phenotypes to ozone and develop differentially in healthy humans.
abstract: Effect of laboratory exposure to O₃ (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 ((99m)Tc-DTPA, MW = 492), were measured at 1-day postexposure. O₃ 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 O₃ 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 O₃ exposure.
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Loretta G
authors.initials: LG
authors.lastname: Que
authors.forename: Jane V
authors.initials: JV
authors.lastname: Stiles
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.forename: W Michael
authors.initials: WM
authors.lastname: Foster
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D001980:Bronchi / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced* / Q000503:physiopathology; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents; D018592:Cross-Over Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D019570:Inhalation Exposure; D016014:Linear Models; D008168:Lung / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D009657:North Carolina; D010126:Ozone / Q000008:administration & dosage / Q000009:adverse effects*; D010539:Permeability; D010641:Phenotype; D019275:Radiopharmaceuticals; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D012737:Sex Factors; D016284:Technetium Tc 99m Pentetate; D013997:Time Factors; D014797:Vital Capacity / Q000187:drug effects; D044465:White People; D055815:Young Adult
chemical_list: D016085:Bronchoconstrictor Agents; D019275:Radiopharmaceuticals; D016210:Methacholine Chloride; D010126:Ozone; D016284:Technetium Tc 99m Pentetate