Airway responsiveness to inhaled antigen, histamine, and methacholine in inbred, ragweed-sensitized dogs

Abstract

We studied the responses to antigen in animals selected from a colony of inbred dogs sensitized to specific allergens to determine if they had characteristics similar to those of human asthmatics. They were immunized with ragweed and grass pollen extracts (10 micrograms in alum) immediately after routine vaccination with attenuated live virus (distemper and hepatitis) and killed bacteria (Leptospira) at 4, 8, and 12 wk of age. Subsequently, ragweed and grass injections were repeated every 2 months. Immunized dogs made specific IgE-antibodies in serum averaging 3 to 4 times that of control animals (no immunization with pollen or vaccine). They showed positive skin responses to the injection of ragweed pollen extract, whereas control dogs did not respond to ragweed pollen by quantitative skin test or inhalation challenge. In immunized dogs under barbiturate anesthesia, air-flow resistance of the total respiratory system increased from 0.60 +/- 0.07 (mean +/- SEM) before to 12.6 +/- 3.4 cm H2O/lps 5 min after the start of antigen aerosol; respiratory resistance remained increased for 20 min and was associated with 0 hypoxemia and increased arterial plasma histamine. In addition, airway responsiveness to both inhaled histamine and methacholine was greater in immunized dogs than in nonimmunized dogs of comparable age. Airway responses to each agonist were highly reproducible on repeated testing. These results indicate that physiologic responses to antigen by inbred, ragweed-sensitized dogs resemble human asthma closely and that these dogs appear suitable for a variety of experimental studies of asthma with respect to pathogenesis, diagnosis, prevention, and treatment.