Study objective: Controlled human exposure studies have suggested that
the National Ambient Air Quality Standard for ozone (O-3) may not pro
vide 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 O-3 have not been identified,
recent work in our laboratory suggested that methacholine responsiven
ess might be an important determinant of susceptibility to O-3. Patien
ts and methods: To test the hypothesis that methacholine responsivenes
s is correlated with FEV(1) response after O-3 exposure, we conducted
methacholine challenge tests and O-3 (0.20 ppm) and filtered air expos
ures for 4 h with moderate exercise on 66 healthy individuals. Results
: Repeated measures analysis of variance demonstrated significant chan
ges in FEV(1) (-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 O-3
exposure that persisted after adjusting for responses to air. Baselin
e PC100 (the concentration of methacholine that caused a doubling of t
he baseline SRaw) was weakly associated with O-3-induced increases in
SRaw (F-1.54 = 2.85, p = 0.09), but not O-3-induced declines in FEV(1)
or FVC. There was a weak association (r = -0.29) between Os-induced r
esponses for SRaw and FEV(1). The FEV(1) responses for O-3 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 = -0.3), but not with chest discomfort or sputum production. Conclu
sions: Although we were unable to find support for our hypothesis, we
found, somewhat surprisingly, that respiratory symptoms were weakly as
sociated or unassociated with FEV(1) responses after O-3 exposure. Thi
s finding implies that individuals may experience adverse effects, ie,
respiratory symptoms, without large declines in lung function. Conver
sely, individuals may suffer large declines in lung function without p
rominent symptoms and, therefore, may remain in an unhealthy environme
nt despite evidence of toxicity.