title: Methacholine responsiveness is not associated with O3-induced decreases in FEV1.
abstract: OBJECTIVE
  Controlled human exposure studies have suggested that the National Ambient Air Quality Standard for ozone (O3) may not provide a margin of safety to protect the most susceptible members of the population from adverse health effects. Although the subgroups of the population that are most susceptible to O3 have not been identified, recent work in our laboratory suggested that methacholine responsiveness might be an important determinant of susceptibility to O3.
  
  
  METHODS
  To test the hypothesis that methacholine responsiveness is correlated with FEV1 response after O3 exposure, we conducted methacholine challenge tests and O3 (0.20 ppm) and filtered air exposures for 4 h with moderate exercise on 66 healthy individuals.
  
  
  RESULTS
  Repeated measures analysis of variance demonstrated significant changes in FEV1 (-0.82 +/- 0.63 L), FVC (-0.69 +/- 0.48 L), and specific airway resistance (SRaw) (+1.5 +/- 1.1 L x cm H2O/L/s) across the O3 exposure that persisted after adjusting for responses to air. Baseline PC100 (the concentration of methacholine that caused a doubling of the baseline SRaw) was weakly associated with O3-induced increases in SRaw (F1.54 = 2.85, p = 0.09), but not O3-induced declines in FEV1 or FVC. There was a weak association (r = -0.29) between O3-induced responses for SRaw and FEV1. The FEV1 responses for O3 were weakly associated with the symptoms of cough (r = -0.37), wheeze (r = -0.29), chest pain on deep inspiration (r = -0.31), and shortness of breath (r = -0.37), but not with chest discomfort or sputum production.
  
  
  CONCLUSIONS
  Although we were unable to find support for our hypothesis, we found, somewhat surprisingly, that respiratory symptoms were weakly associated or unassociated with FEV1 responses after O3 exposure. This finding implies that individuals may experience adverse effects, ie, respiratory symptoms, without large declines in lung function. Conversely, individuals may suffer large declines in lung function without prominent symptoms and, therefore, may remain in an unhealthy environment despite evidence of toxicity.
authors.affiliation: Lung Biology Center, San Francisco General Hospital, CA.
authors.forename: R M
authors.initials: RM
authors.lastname: Aris
authors.forename: I
authors.initials: I
authors.lastname: Tager
authors.forename: D
authors.initials: D
authors.lastname: Christian
authors.forename: T
authors.initials: T
authors.lastname: Kelly
authors.forename: J R
authors.initials: JR
authors.lastname: Balmes
mesh_terms: D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D010126:Ozone / Q000494:pharmacology*; D011446:Prospective Studies
chemical_list: D016210:Methacholine Chloride; D010126:Ozone