Animal Models of Chronic Obstructive Pulmonary Disease: Some Critical Remarks

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Abstract
A variety of animal models of chronic obstructive pulmonary disease (COPD) are available, comprising elastase instillation or inhalation of noxious agents and genetic models like mouse mutants, gene-targeted and transgenic mice. The present review discusses some critical aspects which should be taken into account when evaluating these animal models of human COPD. Critical aspects related to the human disease itself: (1) diagnosis is largely symptom based, and symptoms cannot be mimicked in animals; (2) COPD is not a well-defined entity, but comprises patients with variable contribution of chronic bronchitis, mucus hypersecretion and emphysema, and (3) various factors contribute to the development of COPD, indicating that different pathways may converge into a single endpoint. Critical aspects related to the animals used: (1) species-, strain- and gender-related differences in lung structure and function preclude mimicking some features of the human disease; (2) genetic models frequently present with air space enlargement as a result of the disturbance of early postnatal alveolization (conditionally controlled transgenic animals are recommended); (3) inhalation models frequently use young animals during lung growth, which may preclude distinguishing effects owing to growth retardation or to loss of existing alveolar walls; (4) inhalation of noxious agents may result in reduction of food intake and loss of body weight, which itself may result in emphysema, and (5) the presence of emphysema cannot be concluded based on measurement of air space enlargement alone, but should include the determination of total alveolar surface area.