Introduction
Asthma is a chronic airway inflammatory disease characterized by recurrent episodes of wheezing which have been associated with bronchoconstriction1, 2. Chronic airway inflammation has been a critical driver of airway remodeling, characterized by luminal narrowing and airway wall thickening that are mainly responsible for the significantly increased airway resistance and airflow limitation3-5. Importantly, airway remodeling was thought to mainly occur in large and middle-sized airways in asthma6, 7. Few studies, however, have systematically compared the structural abnormalities from medium-sized to small airways in asthmatic patients with different disease severity. Clinically, inhalation of bronchodilators rapidly improves lung function and ameliorates respiratory symptoms (particularly wheezing) in asthma, but how and where the bronchodilator effects take place have not been thoroughly elucidated with an objective measurement. Exploration of the structural abnormalities of asthmatic airways and bronchodilator responses might help unravel the pathophysiology of, and highlight therapeutic targets for, asthma.
Both computed tomography (CT) and histology have limited ability to measure small airway morphology because of the technical constraints (e.g. low resolution with a limited value in detecting small airways beyond the 6th generation bronchi, and unavailability of obtaining biopsy specimens). Endobronchial optical coherence tomography (EB-OCT), accessible to distal airways up to the 10th generation of bronchi, is a validated real-time imaging technique that generates high-resolution transverse and longitudinal images of the airway architecture in vivo , which have a high concordance with CT and histologic measurements8, 9. By using EB-OCT, we have recently revealed that small airways, refer to the airways with an inner diameter of less than 2 mm, are mainly located at the 7thgeneration or more distal bronchi10, and that more advanced stages of COPD were characterized by a greater magnitude of abnormality in airway architecture (i.e. tapering airway caliber and greater airway wall thickness). More importantly, EB-OCT has confirmed the presence of airway remodeling in early-stage COPD11.
We hypothesized that more prominent airway structural abnormalities correlated with greater asthma severity, and that changes in medium-sized airways caliber correlated with the improvement in lung function. Based on EB-OCT measurement, we sought to investigate airway remodeling in asthmatic patients with different disease severity, and elucidate the bronchodilator responses of different airway generations after inhalation of salbutamol.