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Background: The mechanism of action of Bronchial Thermoplasty (BT) and its related responder profile is unclear. Objective: Investigate if BT-induced airway smooth muscle mass (ASM) change correlates with FEV1. Methods: 16 severe asthma patients were analyzed. Before and after BT, pre- and post-bronchodilator FEV1 was measured and bronchial biopsies were taken and stained with ASM-specific desmin and ASM/myofibroblast/myoepithelial α-smooth muscle actin (α-SMA). Results: BT treatment reduced ASM mass significantly as assessed by both desmin (55%) and α-SMA analysis (40%)(Fig1A). Baseline pre-and post-bronchodilator FEV1 correlated negatively with desmin-determined baseline ASM mass (resp. R=-0.61;p=0.01 and R=-0.62;p=0.01). Furthermore desmin-determined ASM mass decrease correlated negatively with baseline pre- and post-bronchodilator FEV1 (resp. R=-0.61;p=0.01 and R=-0.54;p=0.03 Fig1B). Patients with FEV1 80%(n=10): 2.4%(0.4;6.3 IQR (p=0.01)Fig1C). This correlation was not found with α-SMA staining. Conclusions: The correlation between ASM and FEV1 seems to depend on the fully differentiated contractile ASM only. Patients with a FEV1< 80% show the most reduction of ASM mass after BT treatment. Whether this “obstructive” asthma phenotype qualifies as a responder criteria needs to be determined.

Background: Bronchial Thermoplasty (BT) is a bronchoscopic treatment for severe asthma during which airways are treated with radio-frequent energy and that aims to improve asthma control by reducing airway smooth muscle (ASM). Aim: Determine the effect of BT on ASM mass before and after BT and to compare this with the non-treated right middle lobe (RML) and delayed BT control group. Methods: After obtaining airway biopsies, 11 severe asthma patients were randomized to either direct BT or to 6 months delayed BT treatment (in this control group re-biopsies after 6 months of standard care were obtained). Airway biopsies were taken 6 months post-BT in all patients. ASM mass (% of total biopsy area) was measured by automatic digital image analysis on 2 desmin-stained sections per biopsy. Results: 6 months after BT mean (SD) ASM mass significantly decreased from 11.25 (4.8)% to 4.8 (2.2) % for pre-and post-BT respectively (p=0.007) (n=11, 44 sections). In the non-BT-treated RML, 6 months after BT, ASM mass was 7.3 (±6.2) % vs 10.3 (4.9) % pre BT (p=0.13) (n=9, 36 sections). In the control group, after 6 months of standard care, ASM mass was 10 (±6.1) % vs 7.15 (±4.3) % at the first measurement (p=0.63) (n=4, 16 sections). Conclusions: ASM mass significantly decreased 6 months following BT treatment. No significant change in ASM mass was found in controls or the untreated RML.

Background: Airway remodeling is a key feature in obstructive lung diseases. Near infrared-based optical coherence tomography (OCT) is a novel bronchoscopic imaging technique that generates highly-detailed images of the airway wall. Aim: Identify and quantify human airway wall layers both ex-vivo and in-vivo by OCT and correlate these to histology. Methods: Patients with lung cancer, prior to lobectomy, underwent in-vivo OCT imaging. Ex-vivo OCT imaging was performed in the resected lung lobe after needle insertion for matching with histology. Airway wall layer perimeters were assessed by two independent observers. Airway wall layer areas (total airway wall area, mucosal wall layer area and submucosal wall layer area) were calculated. Results: 13 airways of 5 patients were imaged by OCT. Histology was matched with 51 ex-vivo OCT images and 39 in-vivo OCT images. Significant correlation was found between ex-vivo OCT imaging and histology, in-vivo OCT imaging and histology and ex-vivo and in-vivo OCT imaging for all measurements (Fig 1). Minimal bias was seen in Bland-Altman plots. High inter-observer reproducibility with intra-class correlation coefficients all > 0.90 were detected. Conclusions: OCT is an accurate and reproducible imaging technique for identification and quantification of airway wall layers. Implications: OCT imaging might qualify as the imaging technique of choice to assess airway wall remodeling.