The inhalation of nebulized adenosine causes bronchoconstriction in asthmatics. In order to explore whether endogenously produced adenosine may contribute to the pathophysiologic aspects of asthma, we measured adenosine concentrations in bronchoalveolar lavage (BAL) fluid in seven subjects with asthma, eight asymptomatic cigarette smokers, and eight normal subjects. The mean concentration of adenosine in BAL fluid from the normal subjects was 0.72±0.16~ M. Subjects with asthma and cigarette smokers had significantly increased concentrations of adenosine in BAL fluid, 2.55±0.50 and 1.89±0.50~ M, respectively. Corrected for the dilution that occurs as a result of the lavage procedure, mean epithelial lining fluid adenosine concentrations were 60±13~ M in normal subjects, 193±58~ M in asthmatics, and 155±56~ M in smokers. Adenosine concentrations were positively correlated with the protein content of the lavage fluid (r= 0.79). Inhalation of nebulized adenosine in the subjects with asthma provoked a 20% reduction in lung function at concentrations 4-to 195-fold higher than was present in the epithelial lining fluid of the same individuals. The presence of increased BAL adenosine concentrations in asthmatics and in cigarette smokers suggests that adenosine may be a nonspecific marker for inflammation in the lung. The demonstration of physiologically relevant concentrations of adenosine in airway fluids of subjects with bronchial hyperreactivity to inhaled adenosine provides evidence for a role of endogenous adenosine in provoking bronchoconstriction in asthma.

Substantial evidence suggests that adenosine may playa role in the pathophysiology of asthma. Adenosine is known to cause bronchoconstriction when inhaled by subjects with asthma (1). Adenosine appears to promote bronchoconstriction in part by stimulating the release of mast-cell-derived mediators (2). Bronchoconstriction induced by adenosine occurs in association with the release of a high molecular weight neutrophil chemotactic factor into serum. This factor is believed to be ofmast cell origin since it is also released during IgE-mediated asthmatic reactions. Unequivocal proof of the cellular origin of this factor has not been established, however. Inhalation of the related adenine nucleotide, adenosine 5'monophosphate (AMP), by subjects with allergic rhinitis causes an increase in plasma histamine (3). Further evidence for the involvement of mast cells in adenosine-induced bronchoconstriction is the inhibition of bronchospasm by pretreatment with cromolyn sodium and terfenadine (4, 5). Theophylline is an adenosine receptor antagonist, and this property of the drug may be partly responsible for its therapeutic effects in asthma. Inhalation of aerosolized theophylline inhibits adenosine-induced bronchoconstriction (6). Theophylline also inhibits neutrophil chemotactic factor release associated with adenosine challenge in asthma (2). Enprofylline, a methylxanthine drug similar to theophylline, is also efficacious in the treatment of asthma even though it is not an adenosine antagonist (7). The therapeutic ac-