A Novel Non-invasive Approach for Measuring Upper Airway Collapsibility in Mice

Introduction: Invasive procedures were previously developed for measuring pharyngeal collapsibility in rodents during expiration, when declining neuromuscular activity makes the airway unstable. We developed a non-invasive approach for streamlining collapsibility measurements by characterizing responses in physiologic markers of dynamic expiratory airflow obstruction to negative nasal pressure challenges. Methods: Anesthetized mice were instrumented to monitor upper airway pressure-flow relationships with head-out plethysmography while nasal pressure was ramped down from ~ +5 to -20 cm H₂O over several breaths. Inspiratory and expiratory flow, volume, and timing characteristics were assessed breath-wise. Pcrit was estimated at transitions in expiratory amplitude and timing parameters, and compared to gold standard P_CRIT measurements when nasal and tracheal pressures diverged during expiration. Predictions equations were constructed in a development data set (n = 8) and applied prospectively to a validation data set (n = 16) to estimate gold standard P_CRIT. Results: The development data demonstrated that abrupt reversals in expiratory duration and tidal volume during nasal pressure ramps predicted gold standard P_CRIT measurements. After applying regression equations from the development to a validation dataset, we found that a combination of expiratory amplitude and timing parameters proved to be robust predictors of gold standard P_CRIT with minimal bias and narrow confidence intervals. Conclusions: Markers of expiratory airflow obstruction can be used to model upper airway collapsibility, and can provide sensitive measures of changes in airway collapsibility in rodents. This approach streamlines repeated non-invasive P_CRIT measurements, and facilitates studies examining the impact of genetic, environmental, and pharmacologic factors on upper airway control.