Invasive and noninvasive lung function measurements in rodents

Precise and repeatable measurements of pulmonary function in intact mice or rats are becoming increasingly important for experimental investigations on various respiratory disorders like asthma and for pharmacological, safety-pharmacological or toxicological testing of drugs or chemicals. This review provides a short overview of typical in-vivo measurement techniques, discusses their advantages and disadvantages and presents two of these methods in detail: the noninvasive head-out body plethysmography and an invasive but repeatable body-plethysmography in orotracheally intubated rodents. It will be demonstrated that these methods are able to monitor bronchoconstriction in safety-pharmacological tests or in asthma models showing early allergic response or late airway hyperresponsiveness in response to inhaled allergens and demonstrate drug effects on pulmonary endpoints. The changes in the respective parameters such as tidal midexpiratory flow (EF(50)) or lung resistance in typical bronchoconstriction models have been measured in the same animals and compared for validation purposes. It is concluded that both invasive and noninvasive pulmonary function tests are capable of detecting allergen-specific as well as non-allergic bronchoconstriction in intact mice or rats. The invasive determination of resistance is superior in sensitivity, whereas the noninvasive EF(50) method is particularly appropriate for quick and repeatable screening of respiratory function in large numbers of mice and rats or if the conscious animal has to be tested (e.g. safety pharmacology). The use of both techniques in a large number of studies in the last years have demonstrated that they provide useful and necessary information on pulmonary mechanics in studies of respiratory disorders including experimental models of asthma, in investigations of pulmonary pharmacology, safety pharmacology and toxicology in mice and rats.