Mapping airway smooth muscle remodelling in vivo using polarization-sensitive optical coherence tomography

Introduction/Aim: <br/>More than a century after being identified as a chief culprit in excessive bronchoconstriction in asthma, airway smooth muscle (ASM) remodelling still plays no part in diagnosis or treatment plans, mainly due to a lack of screening methods. This study assessed the feasibility of polarization-sensitive optical coherence tomography (PS-OCT) to map the distribution of ASM remodelling in vivo and identify possible structural phenotypes.<br/><br/>Methods: <br/>We developed PS-OCT for minimally invasive measurement of ASM during bronchoscopy, sampling an area equivalent to 500 biopsies per subject. Normalised ASM mass (ASM area/lumen perimeter2) was measured in 154 airways from 20 adults (9F/11M) with/without (7/13) ‘doctor-diagnosed’ asthma (ACQ6 1.43±1.05).<br/><br/>Results: <br/>Distribution of remodelling (ASM mass above normal) was mapped in under 10 min using PS-OCT, from airways as small as 1 mm diameter up to the trachea. ASM mass (area/perimeter2) was increased in subjects with asthma (median 0.0072 (0.0064 – 0.0089 IQR)) compared to a control group (0.0039 (0.0032 – 0.0040), p=0.017). ASM remodelling was also more prevalent in subjects with asthma (44 (24 – 53)% of airways examined) than in control subjects (0 (0 – 11)%, p=0.018). Heterogeneity (coefficient of variation) of the ASM mass was substantial (~50%) but was not different between asthma and control groups. ASM mass and its heterogeneity were not associated with spirometry (FEV1 % predicted, FEV1/FVC). Distinct phenotypes of ASM remodelling were detectable in subjects with asthma: large airways only (17%), small airways only (17%), small and large airways (33%), or none (33%). In control subjects only the unremodelled phenotype was observed. <br/><br/>Conclusion: <br/>Bronchoscopic-guided PS-OCT is an effective diagnostic technique to measure ASM thickness and was used to demonstrate an increase in the extent and prevalence of ASM remodelling in asthma. PS-OCT can be used to identify ASM remodelling phenotypes and investigate the effects of pharmaceuticals on ASM structure in clinical trials.