New developments in lung function measurements in rodents.

There are invasive and noninvasive pulmonary function tests available which are sensitive in detecting bronchoconstriction in rodents. Noninvasively measured midexpiratory flow (EF50) has been shown to be an appropriate parameter to monitor bronchoconstriction in a large number of animals, e.g. for screening purposes. Recently, a novel technique for repetitive lung function measurements in orotracheally intubated, spontaneously breathing mice has been established. Bronchoconstriction is assessed by the "gold standard" parameters airway resistance and dynamic compliance in response to aerosolized methacholine or allergens in anesthetized mice. This measurement technique has been combined with an inhalation technique which has been optimized to allow simultaneous lung function measurement in intubated animals and to obtain high aerosol concentrations. A feedback dose control system has been developed to administer a defined and constant aerosol dose to each individual animal. Using this system a prominent early allergic response and late airway hyperresponsiveness could be demonstrated in intubated mice challenged with Aspergillus fumigatus allergen. We conclude: The noninvasive EF50 method seems particularly appropriate for measurements of respiratory function in large numbers of conscious mice in assembly line fashion. The invasive technology--newly established for the mouse--is more sensitive and specific since true airway resistance and dynamic compliance are determined and allows now the adequate detection of an early allergic response in the mouse and also repetitive measurements e.g. to assess the airway hyperresponsiveness in the same animal or for monitoring purposes in chronic models.