In vivo real-time imaging of airway dynamics during bronchial challenge test

Asthmatic patients exhibit airway hyper-responsiveness, which induces bronchoconstriction and results in a ventilation defect. The bronchial challenge test using methacholine is a useful way to measure airway hyper-responsiveness with airway constriction. Anatomical optical coherence tomography has been used to image airway hyper-responsiveness of medium sized bronchus with the aid of an endoscopic probe. Recently, a thoracic window was reported that allows direct visualization of terminal airway such as alveolus. A multi-scale integrated airway dynamics was assessed in this study. We imaged in vivo changes in the right intermedius bronchus and alveolar structure during the bronchial challenge test using two optical coherence tomography systems and correlated the changes with airway resistance.

Rabbits intubated with a non-cuffed endotracheal tube on a ventilator sequentially inhaled normal saline and methacholine (2 or 5 μg/ml). The airway resistance was measured by mechanical ventilation and airway structures were monitored by a commercial endoscopic optical coherence tomography system (1,310 nm) and a house-made table-top spectral-domain optical coherence tomography system (850 nm).

We demonstrated an early decrease in the size of the right intermedius bronchus and alveoli in accordance with increased airway resistance after methacholine inhalation. OCT image after inhalation of 2 μg/ml methacholine showed some segmental narrowing of the right intermedius bronchus and the image after inhalation of 5 μg/ml methacholine showed even greater segmental narrowing. The cross-sectional areas were 7.2 ± 3.3 mm2 (normal saline), 3.7 ± 2.1 mm2 (2 μg/ml methacholine), and 2.4 ± 1.1 mm2 (5 μg/ml methacholine), respectively (P = 0.04). Most of the alveolar space was collapsed under elevated airway resistance with methacholine inhalation. The averaged areas per alveolus at the end of inspiration were 0.0244 ±0.0142 mm2 (normal saline), 0.0046 ±0.0026 mm2 (2 μg/ml methacholine), and 0.0048 ±0.0028 mm2 (5 μg/ml methacholine), respectively (P = 0.03). Methacholine induced a dose-dependent increase in airway resistance (1.1 ± 0.3 cm H2O sec/ml for 2 μg/ml methacholine, 1.5 ± 0.5 cm H2O sec/ml for 5 μg/ml methacholine) (P = 0.03). These results were obtained from normal rabbits during the bronchial challenge test with a non-cuffed endotracheal tube on a ventilator. With this setup increased airway resistance possibly resulted in larger leakage around the endotracheal tube, decreased inhaled volumes, and, in turn, alveolar collapse.

We performed a feasibility study of in vivo visualization of real-time airway dynamics. To our best knowledge, this is the first report of real-time integrated airway dynamics including the right intermedius bronchus and alveoli during a bronchial challenge test. OCT showed bronchial constriction and alveolar collapse with a higher methacholine dose. OCT images correlated with the measured airway resistance. Therefore, OCT could be a potential diagnostic device for airway hyper-responsiveness and airway remodeling.