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.