Airway Remodeling and Bronchodilator Responses in Asthma Accessed by Endobronchial Optical Coherence Tomography

Abstract

Background: Asthma is characterized by chronic airway inflammation and remodeling. Understanding airway structural changes and the bronchodilator responses may help unravel targets for intervention. However, structural abnormalities of asthmatic airways with different disease severity and the major anatomical site of bronchodilator responses have not been well elucidated. Methods: We recruited 104 asthmatic patients (when clinically stable) and 31 non-smoking control subjects to compare the airway inner area (Ai) and airway wall area percentage (Aw%) with endobronchial optical coherence tomography. We also enrolled 32 patients with moderate-to-severe asthma to dynamically access the airway morphological changes after salbutamol inhalation. Findings: More prominent airway structural abnormalities correlated with greater asthma severity, evidenced by the decreased Ai and greater Aw% in medium-sized and small airways. Patients with mild asthma yielded comparable Ai but greater Aw% than control subjects. A longer disease duration correlated with lower Ai and greater Aw% from the 3rd to 6th generation of bronchi. Salbutamol inhalation led to a rapid dilatation of both medium-sized and small airways, the lung function improvement correlated significantly with the increase in Ai of the medium-sized, but not small, airways at 15 min. Interpretation: Luminal narrowing and airway wall thickening of the medium-sized and small airways are present in mild asthma and reflect asthma severity, lending support to the use of anti-imflammatory intervention in mild asthma. The medium-sized airways are the crucial site of the bronchodilator responses, providing the scientific rationale for future development of more effective delivery of inhaled medications for asthma. Funding Statement: National Natural Science Foundation of China (No.81770017), National Natural Science Foundation of China (No.81900032), Pearl River S&T Nova Program of Guangzhou No. 201710010097 and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017 Declaration of Interests: Prof. Li declared that he had received the National Natural Science Foundation of China (No.81770017). Dr Su declared that he had received the National Natural Science Foundation of China (No.81900032). Prof. Guan declared that he had received Pearl River S&T Nova Program of Guangzhou No. 201710010097, and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme 2017. All other authors declared no potential conflict of interest. None of the funding sources had any role on the study Ethics Approval Statement: This study was approved by the Ethics Committee of The First Affiliated Hospital of Guangzhou Medical University (Medical Ethics [Year 2014] No. 51 and [Year 2019] No. K09). All subjects gave written informed consent.