Body plethysmograph

Upper respiratory tract irritation can occur from inhalation of a medicinal gas, vapor, or aerosol. For assessing the potential of an inhalant to cause URT irritation, the mouse body plethysmographic technique (Alarie, 1966, 1981a, b) has proven to be extremely usefid. This technique operates on the principle that respiratory irritants stimulate the sensory nerve endings located at the surface of the respiratory tract from the nose to the alveolar region. The nerve endings in turn stimulate a variety of reflex responses (Alarie, 1973 Widdicombe, 1974) that result in characteristic changes in inspiratory and expiratory patterns and, most prominently, depression of respiratory rate. Both the potency of irritation and the concentration of... 

Many inhalation exposure techniques, such as the whole-body, nose-only, mouth-only, or head-only technique (Drew and Laskin, 1973 MacFarland, 1976 Leong et al., 1981 Phalen, 1984 Nelson, 1980), the intranasal exposure technique (Elliott and DeYoung, 1970 Smith et ah, 1981), the endotracheal nebulization technique (Leong et ah, 1985, 1988 Schreck et ah, 1986), and the body plethysmographic techniques (Alarie, 1966 Thome and Karol, 1989), have been developed for inhalation toxicity studies. Table 10.2 provides a summary of the advantages and disadvantages of each of the major inhalation exposure methodologies. 

Du Bois, A. B., S. Y. Botelho. and J. H. Comroe. A new method for measuring airway resistance in man using a body plethysmograph Values in normal subjects and in patients with respiratory disease. J. Gin. Invest. 35 327-335, 1956. 

Fig. 1. Buxco whole body plethysmograph for measuring lung function. The mouse is placed in a plexiglas chamber, where it is free to move. A port at the top of the chamber is connected to a nebulizer to allow administration of aerosolized chemicals. A transducer linked to an amplifier monitors the pressure changes within the chamber, which correspond to the animal s breathing rates and depths. These raw data are converted to a value called Penh, which is a measure of BHR. Readout consists of change in Penh over time. An increase in Penh indicates that the mouse is hyperresponsive.

Malek, D.E., and Y.Alarie. 1989. Ergometer within a whole-body plethysmograph to evaluate performance of guinea pigs under toxic atmospheres. Toxicol. Appl. Pharmacol. 101 (2) 340-355. 

Battenshy, J., Creasey, N.H., and Grace, T.J., A comparison and evaluation of the whole body plethysmograph and the guinea pig eye-hlink procedures for estimating the potency of sensory irritants, Technical Paper Number 301, dated 1981, Chemical Defence Establishment, Porton Down, Wiltshire, UK, 1981. 

It was hypothesized that airway tone may be affected by inhalation of NO. Dupuy et al. (1992) reported a reduction in bronchoconstriction with NO, studying open chest guinea pigs in a body plethysmograph during provocation with intravenous methacholine. A dose-dependent relaxation between 5 and 300 ppm NO was noted, with normalization of the reduced compliance at inhaled doses above 100 ppm NO. In the same model provocation with histamine, leukotriene D4, and neurokinin A was studied. Inhaled NO reverses bronchoconstriction induced by all of these inflammatory mediators (Dupuy et al., 1993a). Work with methylene blue and NO inhalation... 

Spirometry has its limitations, however. It can measure only ventilated volumes. It cannot measure lung capacities that contain the residual volume. Measurements of TLC, FRC, and RV have diagnostic value in defining lung overdistension or restrictive pulmonary disease the body plethysmograph can determine these absolute lung volumes. 

A third method for measuring lung volumes uses a device known as a body plethysmograph, also referred to as a body box. The body box is a large rigid-walled structure in which the patient is seated, after which the door is closed and sealed completely. In one variety, a small hole in the wall of the cabinet leads to a spirometer or flow sensor. Respiratory efforts within the box cause changes in volume to be recorded on this spirometer as chest wall movement displaces air within the box. In a second variety of body box, there is no hole in the wall of the box and respiratory efforts instead... 

The range of costs for pulmonary function equipment is from less than 300 for simple spirometers to 50,000 for hospital body plethysmographs. The cost must be appropriate for the use. In general, home-use devices are much less costly then hospital devices. Home devices are usually much simpler and may not be as accurate or reliable as hospital devices. The design engineer must know the maiket for a new device before investing inordinate amounts of time or before including too many options that lead to inappropriate purchase prices. 

Pulmonary Effects - Asthma - Three groups published last yesir on the pulmonary effects of marijuana. In one study > of nine, normal volunteers with previous marijuana smoking experience, airway resistance (measured in a body plethysmograph) fell 3S% and specific airway conductance increased kh% at a dose of yg/kg. This effect was accompanied by a 28% increase in heart rate. At a dose of 32 yg/kg, there was no increase in heart rate but there were significant changes in airway dynamics. 

---