A METABOLIC BASIS FOR SEVERE INTRACTABLE ASTHMA

Abstract

We have previously reported that severe asthmatics after receiving catecholamines have decreased urinary cyclic AMP as compared to normals. To better define this abnormality, which suggests B-adrenergic blockade, 15 severe asthmatic children were studied prospectively. Whereas, normals had a mean 3.2±0.4 Nm/min/1.73M2 increment in 2 hour urinary cyclic AMP, asthmatics had a mean 1.6±0.3 Nm/min/1.73M2 increment after 6 μg/Kg of epinephrine. After 12 μg/Kg epinephrine the asthmatics had a mean 2.2±0.4 Nm/min/1.73M2 increment in 2 hour urinary cyclic AMP: individually, 7 asthmatics had no increased urinary cyclic AMP excretion with double the epinephrine; whereas, 8 patients had 1.0 to 5.2 Nm/min/1.73M2 increment after 12 μg/Kg epinephrine. Clinical evaluation the past 18 months demonstrated that 6 of 7 asthmatics who had no increase in urinary cyclic AMP to 12 μg/Kg epinephrine persisted with severe intractable asthma. However, 5 of 8 asthmatics who demonstrated with the dose response test an increase in urinary cyclic AMP had clinical improvement: their asthma is intermittent and less severe. These data support the hypothesis that severe asthmatic patients have a defect in formation of cyclic AMP after B-adrenergic stimulation. Also, lack of a dose response to epinephrine has delineated a unique group of asthmatics.