Novel effects of PGF(₂α) on airway function in asthmatic subjects

The effects of inhaled prostaglandin F(₂α) (PGF(₂α)) have been examined in eight subjects with asthma. Incremental PGF(₂α) aerosol concentrations, ranging from 1 to 5,000 μg/ml, were administered at 15-min intervals. Plethysmographic specific airway conductance (sGaw), forced expiratory volume at 1 s (FEV₁) and maximum expiratory flow at 50% vital capacity breathing air (V̇max50% air) and 80% He-20% O₂ (V̇max50% He-O₂) were measured after each dose and compared with saline control values. We observed unexpected triphasic dose-response characteristics, i.e., an initial decline in physiological variables at low concentrations (1-100 μg/ml), followed by improvement at intermediate concentrations (100-1,000 μg/ml) and a subsequent steep decline at high concentrations (1,000-5,000 μg/ml). Improvement in FEV₁ and V̇max50% air between 100 and 1,000 μg/ml was associated with sGaw increases above control levels in six subjects and a significant fall in density-dependent index (V̇max50% He-O₂/V̇max50% air) when compared with values before challenge and at low concentrations. Inhaled atropine (5 mg) improved pre-challenge lung function but had no effect on PGF(₂α) dose-response characteristics. Intermediate PGF(₂α) concentrations given as a single dose consistently induced greater FEV₁ reductions than the same concentration during graded dose challenges. Our findings are consistent with the demonstration of in vivo airway tachyphylaxis and indicate that airway effects of PGF(₂α) are far more complex than previously reported. Moreover, these novel effects suggest that, in addition to its well-known bronchoconstrictor effects, PGF(₂α) directly or indirectly causes airway relaxation, predominantly in large airways.