The proximal and distal portions of the lungs may respond differently to antigen challenge and bronchodilator treatment. This difference may contribute to differences in actual and perceived efficacy of therapies. In this study we used the forced oscillation technique (FOT) to measure impedance in the pulmonary system and discern the effects of antigen challenge on proximal (large airway) and distal (small airway and lung parenchyma) portions of the lung. In addition we treated the animals with two i.m. injections of either a saline control or dexamethasone (0.5 mg/kg) 18 and 1 hour(s) before the antigen challenge. The FOT technique was used to measure indices of proximal airway status, Newtonian airway resistance (R(N)), and distal airway status, including tissue damping (G) and tissue elastance (H). Challenging the animals with Ascaris Suum antigen caused a significant increase in both the proximal and distal lung measures. Pretreatment with dexamethasone significantly reduced the peak increase in R(N) but not G or H. In addition, the area under the curve (AUC) of the FOT response over 60 minutes was significantly reduced for the R(N) but again, G and H were not significantly reduced. These data indicate that, using the FOT, we can dissociate the response of proximal and distal airways to an antigen challenge. Moreover, steroid pre-treatment can reduce the bronchoconstrictor response to inhaled antigen but this effect is primarily via effects on the proximal airways with little effect on the distal airways and parenchymal component of pulmonary impedance. These data may help to provide a mechanism for evaluation of novel therapies for small airway dysfunction.

We evaluated an inductance plethysmography (IP) system in 3 allergic cynomolgus monkeys for measurement of breathing and phase angle (Φ) as a surrogate for airway resistance. Initial studies in anesthetized, intubated animals compared a standard pneumotachograph measure of ventilation with IP to estimate the accuracy of the measurement. Data showed excellent agreement between IP and the standard approach. 24 hours of baseline unanesthetized breathing was then recorded. After 24 hours, monkeys were re‐anesthetized, exposed to an aerosolized ascaris suum antigen and immediately returned to their cages. A subsequent 24 hours of recording provided data from each animal during and following a bronchoconstrictor response. Data indicate that ventilatory pattern is distinctly altered for a period of at least 60 minutes post challenge at which point breathing recovers to normal values. These data agree with our AUC measures in anesthetized animals after antigen exposure. The Φ for each breath was also calculated. During bronchoconstriction, a distinct different angle was measurable. Upon recovery, Φ returned to normal and remained stable, regardless breathing pattern. We conclude that this system is a useful tool to measure breathing in unencumbered, conscious animals for a long period and may be useful in evaluating bronchoconstrictor events.

We used the forced oscillation technique (FOT) to measure impedance in the pulmonary system and the effects of antigen challenge on the proximal and distal lung. In addition, we treated animals with two oral doses of placebo or betamethasone (1 mg/kg) 18 and 2 hours prior to antigen challenge. FOT provides indices of proximal (Newtonian airway resistance RN) and distal airway status (tissue damping (G) and elastance (H)). Ascaris suum antigen challenge caused a significant increase in RN, G and H. Pretreatment with betamethasone significantly reduced the peak increase in RN and the area under the curve of the FOT response over 60 minutes. G and H responses were unaffected by steroid treatment. These data indicate that, using the FOT, we can dissociate the response of proximal and distal airways to an antigen challenge. Moreover, steroid pre‐treatment can reduce the bronchoconstrictor response to inhaled antigen but this effect is primarily via effects on proximal airways with little effect on the distal airways and parenchymal component of pulmonary impedance. These data may help to explain the apparent disconnect between the empirical and subjective measures of efficacy for some asthma treatments.