Respiratory Tract

The chapter describes different aspects of the respiratory tract. In preclinical safety studies, pathologies of the respiratory system can be a result of an intercurrent disease or can be induced by systemically administered drugs. Intranasal or inhalation modes of therapy pose particular challenges in terms of the formulations and technologies required to administer a drug. A complex technology is developed to support the assessment of adverse effects of inhaled substances in rodent and nonrodent species, and the extrapolation of experimental findings to humans. The nasal chambers are the structures that are first to be subjected to the effects of inhaled substances, whether microorganisms or chemical substances. In rodents, the relatively small size of the nose and nasal sinuses facilitates a histological examination. Findings show that infectious agents cause inflammation in the nose and nasal sinuses, and this may be associated with inflammation in the conjunctiva, the middle ear, and the oral cavity. It has been observed that a particular response of the rodent nasal mucosa to some irritant substances, including pharmaceutical agents, is the formation of rounded eosinophilic inclusions in the cytoplasm of sustentacular cells of the olfactory epithelium, and to a lesser extent in respiratory and glandular epithelial cells.