In the United States, an estimated 25 million people suffer from asthma, and despite optimal treatment, upward of 10% are left with severe disease. Due to chronic airway inflammation, bronchoconstriction, and airway remodeling, asthma causes airflow obstruction leading to debilitating exacerbations. The current mainstay of management is focused on allergen avoidance, while reducing inflammation and bronchoconstriction; however, few therapies are available to specifically target pathologic airway remodeling. One of the hallmark features of severe asthma is airway smooth muscle (ASM) hyperplasia and hypertrophy. Bronchial Thermoplasty (BT) is an approved endoscopic treatment for severe asthma that delivers radiofrequency energy to the airways with the goal of causing ASM destruction leading to decreased hyperresponsiveness. However, BT has not yet been adopted into routine practice due to limited studies investigating its efficacy, underlying mechanism of action, and absence of selection criteria to identify patients who are most likely to respond to treatment. Until recently, evaluation of the microstructures of the airway wall (ASM, epithelium, blood vessels, cartilage, glands) was limited by its reliance on tissue acquisition for pathologic assessment. Performed via an endoscopic approach, optical coherence tomography (OCT) is a recently developed technology capable of imaging the microstructures of the airway wall in vivo with near microscopic resolution, which was not previously possible. This novel technology offers the potential to negate the need for tissue acquisition for pathologic evaluation. Using this technology, OCT offers a minimally invasive method to address the gaps in our understanding of BT. We will use OCT to non-invasively investigate the longitudinal changes induced by BT on the airway wall in a canine model. In vivo visualization of ASM with OCT offers the potential to use ASM thickness as an optical biomarker for the prediction of treatment response to BT. However, prior to use on human subjects, OCT?s ability to characterize these changes must be validated. Thus, this study will use OCT to determine the acute and persistent structural (Aims 1&2) and functional (Aim 3) changes in the airway wall induced by BT in a canine model. The preclinical data generated from this study will be key in the translation of this technology to use in human subjects.

Public Health Relevance

Additional therapies are needed to target the pathologic airway modeling found in severe asthma. Bronchial Thermoplasty (BT), an approved therapy for severe asthma, is one of the only treatments that specifically act on remodeled airway smooth muscle, however, significant gaps in our understanding of BT exist. In this study, we aim to use optical coherence tomography, a non-invasive method of imaging the microstructures of the airway wall, to better understand and improve upon BT for the treatment of severe asthma.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Tigno, Xenia
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Johns Hopkins University
Schools of Medicine
United States
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