Animal models of the asthmatic state.

Abstract

Asthma is a common but poorly understood response of the lower respiratory tract of humans, which has and will require considerable investigative effort in order to define the basic mechanisms involved. Only limited studies can be done in asthmatic humans for safety reasons. Appropriate animal models are necessary to test hypoth­ eses of underlying mechanisms in this disease and to determine the significance of immunologic, pharmacologic, and cellular factors in human asthma. This discussion will include a brief review of the characteristics of asthma, the types of animal models that have evolved with comments on how tQese systems might relate to the human disease state, and, finally, summaries of some of the studies that have been carried out using these animal respiratory responses. Human asthma has been characterized clinically as recurrent wheezing dyspnea occurring in patients with bronchial hyperreactivity to a variety of stimuli. Physio­ logically asthma is characterized by reversible obstruction of the bronchi, such reversibility demonstrated most commonly by the administration of ,8-adrenergic agonists. An additional characteristic has been the clinical experimental observation that the hyperreactivity of the bronchi 'can be demonstrated by the administration of histamine, methyJcholine or, more recently, prostaglandin F2a (1). In minimal asthma there may be no pathologic changes observed in respiratory tissues but in asthma of long duration a thickened basement membrane and eosinophilia have been found at autopsy (2). Immunologically, one type of asthma is related to reaginic antibodies of the E class of immunoglobulins. This type of asthma may be associated with elevated serum concentrations of IgE (3) and the specific IgE antibodies may be demonstrated by in vivo skin tests or in vitro radioimmunoassay systems. Clinically, asthma is classified traditionally as either extrinsic or intrinsic. Extrin­ sic asthma is precipitated by inhalation of antigen, which reacts with IgE antibody fixed to mast cells in the lung with resultant mediator release. These mediators are 'Supported by USPHS Grants AI 11403 and AI 000 57 and the Ernest S. Bazley Grant.