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

Rationale Airway smooth muscle (ASM) remodelling is a central feature of asthma pathology but cannot currently be measured in vivo with adequate coverage, limiting the development of targeted therapies. Objectives Trial bronchoscopic polarization-sensitive optical coherence tomography (PS-OCT) to assess ASM remodelling and its distribution in vivo throughout the lungs in individuals with and without asthma. Methods Participants with (n=7) and without (n=13) doctor-diagnosed asthma undergoing bronchoscopy were recruited to obtain PS-OCT imaging data during the procedure. ASM area in large and small airways was measured and normalized for airway size (lumen perimeter). ASM remodelling was defined as ASM mass (ASM area/perimeter ² ) >1.96 sd above a histological reference control group. Measurements and Main Results PS-OCT quantified ASM mass was greater in participants with asthma (median 0.0072, Q1–Q3 0.0064–0.0089) compared with a control group (0.0039, 0.0035–0.0049), (p=0.012). ASM remodelling was also more prevalent in the asthma group (44% of airways examined, 24–53%) than in the control group (0%, 0–4%) (p=0.007). ASM mass was heterogeneously distributed within airways, lungs and the sample population. Phenotypes of ASM remodelling (based on location in small or large airways) were apparent in the asthma group, compared with the control group where participants were all classified as non-remodelled. Conclusions PS-OCT is a minimally-invasive, accurate, efficient and effective modality to measure ASM mass. Visualizing and quantifying ASM in patients with asthma provides an opportunity to make ASM remodelling a treatable trait and may facilitate the development of novel therapeutics for the treatment of asthma.