Mj. Hazucha et al., EFFECTS OF CYCLOOXYGENASE INHIBITION ON OZONE-INDUCED RESPIRATORY INFLAMMATION AND LUNG-FUNCTION CHANGES, European journal of applied physiology and occupational physiology, 73(1-2), 1996, pp. 17-27
Inhalation of O-3 causes airways neutrophilic inflammation accompanied
by other changes including increased levels of cyclo-oxygenase produc
ts of arachidonic acid in bronchoalveolar lavage fluid (BALF), Ozone (
O-3) exposure also causes decreased forced vital capacity (FVC) and fo
rced expiratory volume after 1 s (FEV(1)), associated with cough and s
ubsternal pain on inspiration, and small increases in specific airway
resistance (SRAW), The spirometric decrements are substantially blunte
d by pretreatment with indomethacin, Since the O-3-induced decrement i
n FVC is due to involuntary inhibition of inspiration, a role for stim
ulation of nociceptive respiratory tract afferents has been suggested
and cyclo-oxygenase products have been hypothesized to mediate this st
imulation. However, the relation (if any) between the O-3-induced neut
rophilic airways inflammation and decreased inspiratory capacity remai
ns unclear. We studied the effects of pharmacologic inhibition of O-3-
induced spirometric changes on the inflammatory changes, Each of ten h
ealthy men was exposed twice (5-week interval) to 0.4 ppm O-3 for 2 h,
including 1 h of intermittent exercise (ventilation 601 . min(-1)). O
ne-and-a-half hours prior to and mid-way during each exposure the subj
ect ingested 800 mg and 200 mg, respectively, of the non-steroidal ant
i-inflammatory drug ibuprofen (IBU), or placebo [PLA (sucrose)], in ra
ndomized, double-blind fashion, Spirometry and body plethysmography we
re performed prior to drug administration, and before and after O-3 ex
posure, Immediately following postexposure testing, fiberoptic broncho
scopy with bronchoalveolar lavage (BAL) was performed. Neither IBU nor
PLA administration changed pre-exposure lung function, O-3 exposure (
with PLA) caused a significant 17% mean decrement in FEV(1) (P < 0.01)
and a 56% increase in mean SRAW, Following IBU pretreatment, O-3 expo
sure induced a significantly lesser mean decrement in FEV(1) (7%) but
still a 50% increase in mean SRAW, IBU pretreatment significantly decr
eased post-O-3 BAL levels of prostaglandin E(2) (PGE(2)) by 60.4% (P <
0.05) and thromboxane B-2 (TxB(2)) by 25.5% (P < 0.05). Of the protei
ns, only interleukin-6 was significantly reduced (45%, P < 0.05) by IB
U as compared to PLA pretreatment. As expected, O-3 exposure produced
neutrophilia in BALF, There was, however, no effect of IBU on this fin
ding, None of the major cell types in the BALE differed significantly
between pretreatments, We found no association between post-exposure c
hanges of BALF components and pulmonary function decrements, We conclu
de that IBU causes significant inhibition of O-3-induced increases in
respiratory tract PGE(2) and TxB(2) levels concomitant with a blunting
of the spirometric response, This is consistent with the hypothesis t
hat the products of AA metabolism mediate inhibition of inspiration, H
owever, IBU did not alter the modest SRAW response to O-3 The neutroph
ilic component of the inflammatory response to O-3 was not significant
ly affected by IBU and does not appear to be directly related to the s
pirometric response.