Application of Optical Coherence Tomography to Airway Structure in Sheep and in Human Asthma

Principal Investigator: William Calhoun, MD

Asthma, a chronic inflammatory disease of the human airway, is associated with peribronchial fibrosis and other structural changes collectively called remodeling. These structural changes have physiologic correlates of airway hyperresponsiveness, and, perhaps, presage progressive loss of lung function. The current state of the art for assessing airway remodeling requires bronchial biopsy, using forceps that sample a portion of the airway mucosa approximating 1mm3. A variety of biologic and technical sources of variability have hampered progress in the field. We propose to use optical coherence tomography [OCT] a novel methodology for assessing the histologic structure of mucosa, to assess airway mucosal structure in an animal (sheep) model, validate the methodology against formal histology, and refine the methods for application to human airways. The purpose of these experiments is to develop preliminary data sufficient to support a multidisciplinary collaborative (Calhoun and Motamedi) application for federal funding via the R21 mechanism.

Of note, there is no approved therapy at present that has been demonstrated to prevent airway remodeling, or to reduce its magnitude once established. This situation is in part due to the considerable difficulty in measuring airway remodeling in an objective, reproducible manner. Current ‘gold standard’ methods for measuring remodeling in human tissues include autopsy material, and bronchial biopsy. It would be a major advance in the assessment of the human airway if a technique could be applied repeatedly over time, which could be replicated many times during a bronchoscopy to provide better statistical inferences, and which was not associated with increased risk over that of bronchoscopy alone. This promise of Optical Coherence Tomography, a novel methodology for study of the airway structure, may offer a completely new strategy to assess long term consequences of asthma and its therapy.