Animal models of occupational asthma

Abstract

A An ni im ma al l m mo od de el ls s o of f o oc cc cu up pa at ti io on na al l a as st th hm ma a M.H. KarolAnimal models of occupational asthma. M.H. Karol. ERS Journals Ltd 1994. ABSTRACT: Occupational asthma is characterized by variable airflow obstruction occurring in the workplace. The presence of airways inflammation and hyperreactivity provides further evidence for the disease. Since its pathogenic mechanism(s) are unknown, animal models have been developed to investigate the various disease processes, as well as to enable study of environmental and genetic factors which may contribute to disease development.Numerous parameters can be measured in animal systems, including specific and total immunoglobulin E (IgE), pulmonary eosinophilia, diaphragm contractions and airflow muscle hypertrophy. It is recognized that no single factor is sufficient to lead to a conclusion of occupational asthma, but rather that a selected combination of parameters is most fitting. Animal species selected for study have included: mice, rats, guinea-pigs, rabbits, sheep, horses and nonhuman primates. A guinea-pig system has been utilized for more than 90 yrs and has contributed to the basic understanding of physiological and immunological processes involved in allergic respiratory sensitization. The benefits as well as the disadvantages to be derived from each of the animal systems have been enumerated in this review.Certain caveats must be recognized in using animal systems. Attention must always be given to identifying differences which exist between animal and human systems, including morphological, physiological and immunological factors. The extent of bronchus-associated lymphoid tissue (BALT) differs greatly among animal species and probably plays a major role in development of allergic responsiveness in animals. In using animal systems, it must be appreciated that animals are only surrogates. Results from such studies must be compared with information obtained from clinical evaluation in order to avoid faulty extrapolations. Prudent employment of animal models is expected to advance the recognition, treatment and prevention of occupationally-based asthma.

Airway isocyanate-adducts in asthma induced by exposure to hexamethylene diisocyanate

“…Isocyanate asthma has been difficult to diagnose and control, in part because the mechanisms by which isocyanates cause asthma and the determinants of exposure have not been well defined ( 2 -4 ) . Most of the prior clinical and animal investigations have involved methylene diphenyl diisocyanate (MDI) and toluene diisocyanate (TDI), rather than hexamethylene diisocyanate (HDI), which is increasingly being used in place of TDI (4)(5)(6)(7)(8)(9)(10). To our knowledge, none of the diisocyanates have previously been identified or localized in the human respiratory tract.…”

Target organs and systems: methodologies to assess immune system function.

“…Animal models have been developed to better understand the pathogenesis of the disorder and to compare potencies of test agents, largely proteins. As reviewed by the author (22), a variety of species has been utilized including mice, rats, guinea pigs, rabbits, dogs, sheep, horses, and nonhuman primates. Differences among the models indude animal species utilized, route of administration of the agent, protocol for induction and elicitation of responses, type of response measured, and judgment of a significant response.…”

“…Models of respiratory sensitization by LMW agents include the guinea pig, mouse and rat models, and the mouse IgE model (22). Guinea Pig Model Guinea pigs have been the species of choice for predictive models of respiratory hypersensitivity.…”

Gene therapy strategies for asthma

“…28 Studies so far published reveal two types of abnormalities of the GR in sterlavage fluid. 31 To this end, numerous animal species have however been utilized in the development of models of oid-resistant asthma: a decrease in the affinity for the hormone 24,25 and a diminution in the numbers of recepasthma including mice, rats, guinea-pigs, hamsters, rabbits, dogs, horses, sheep, pigs and monkeys. 31 tors which bind with high affinity to the DNA 26 and this could be explained by an increase in AP-1 (activator proIn fact, of all the models which have been proposed as being potentially useful for the study of the pathophysioltein-1)/GR complexes.…”