Thromboxane A2 is a potent bronchial smooth muscle spasmogen in vitro, and it has been implicated in airway
inflammation and in the genesis of bronchial hyperresponsiveness in
asthma. We have examined the urinary excretion of a variety of products derived from
thromboxane A2 (
thromboxane B2, 2,3-
dinor, and 11-dehydro-
thromboxane B2) and
prostacyclin (6-oxo-PGF1 alpha and 2,3-dinor-6-oxo-PGF1 alpha) using gas chromatography-mass spectrometry in patients admitted acutely to hospital with severe
asthma and in atopic volunteers after bronchial
antigen challenge. Urinary excretion of all
thromboxane-derived products was markedly increased in a number of patients with severe acute
asthma compared with that in a nonsmoking control population, in some cases approaching those previously described in
myocardial infarction: TXB2, 31.6 +/- 12.0 versus 6.5 +/- 0.9; 2,3-dinor-TXB2, 79.0 +/- 19.2 versus 29.5 +/- 2.7; and
11-dehydro-TXB2, 234.3 +/- 65.3 versus 25.0 +/- 2.1 ng/mmol
creatinine (p less than 0.001). Urinary
prostacyclin-derived products were also significantly raised in acute
asthma. In contrast, after inhaled
allergen challenge in atopic volunteers, which caused significant bronchoconstriction, urinary excretion of
thromboxane-derived products was not significantly elevated: TXB2, 5.6 +/- 1.1 versus 5.7 +/- 1.0; 2,3-dinor-TXB2, 41.2 +/- 12.5 versus 28.5 +/- 6.9; and
11-dehydro-TXB2, 69.8 +/- 17.6 versus 39.7 +/- 11.2 ng/mmol
creatinine. In a separate experiment, less than 2% of exogenously administered TXB2 to the airway appeared as urinary
thromboxane-derived products, suggesting that production of greater than or equal to 1 microgram of TXA2 in vivo would be required to increase urinary
thromboxane excretion twofold.(ABSTRACT TRUNCATED AT 250 WORDS)