Julia N.S. d'Hooghe

Emerging understanding of the mechanism of action of Bronchial Thermoplasty in asthma

ABSTRACT Bronchial Thermoplasty (BT) is an endoscopic treatment for moderate‐to‐severe asthma patients who are uncontrolled despite optimal medical therapy. Effectiveness of BT has been demonstrated in several randomized clinical trials. However, the asthma phenotype that benefits most of this treatment is unclear, partly because the mechanism of action is incompletely understood. BT was designed to reduce the amount of airway smooth muscle (ASM), but additional direct and indirect effects on airway pathophysiology are expected. This review will provide an overview of the different components of airway pathophysiology including remodeling, with the ASM as the key player. Current concepts in the understanding of BT clinical effectiveness with a focus on its impact on airway remodeling will be reviewed.

Optical coherence tomography and confocal laser endomicroscopy in pulmonary diseases

Purpose of review Current imaging techniques (X-ray, computed tomography scan, ultrasound) have limitations in the identification and quantification of pulmonary diseases, in particular, on highly detailed level. The purpose of this review is to provide an overview of the current knowledge of innovative light- and laser-based imaging techniques that might fill this gap. Recent findings Optical coherence tomography (OCT) and confocal laser endomicroscopy (CLE) are high-resolution imaging techniques, which, combined with bronchoscopy, provide ‘near histology’ detailed imaging of the airway wall, lung parenchyma, mediastinal lymph nodes, and pulmonary vasculature. This article reviews the technical background of OCT and CLE, summarizes study results, and discusses its potential clinical applications for various pulmonary diseases. Summary Although investigational at the moment, OCT and CLE are promising innovative high-resolution optical imaging techniques for the airway wall, lung parenchyma, mediastinal lymph nodes, and pulmonary vasculature. Clinical applications might contribute to improved disease identification and quantification, guidance for interventions/biopsies, and patient selection for treatments. Development of validated identification and quantification image-analysis systems is key for the future application of these imaging techniques in pulmonary medicine.

Optical coherence tomography for identification and quantification of human airway wall layers

Background High-resolution computed tomography has limitations in the assessment of airway wall layers and related remodeling in obstructive lung diseases. Near infrared-based optical coherence tomography (OCT) is a novel imaging technique that combined with bronchoscopy generates highly detailed images of the airway wall. The aim of this study is to 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 bronchoscopy including 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 and their corresponding areas were assessed by two independent observers. Airway wall layer areas (total wall area, mucosal layer area and submucosal muscular 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. A significant correlation was found between ex-vivo OCT imaging and histology, in-vivo OCT imaging and histology and ex-vivo OCT imaging and in-vivo OCT imaging for all measurements (p < 0.0001 all comparisons). A minimal bias was seen in Bland-Altman analysis. High inter-observer reproducibility with intra-class correlation coefficients all above 0.90 were detected. Conclusions OCT is an accurate and reproducible imaging technique for identification and quantification of airway wall layers and can be considered as a promising minimal-invasive imaging technique to identify and quantify airway remodeling in obstructive lung diseases.

Reduction of Airway Smooth Muscle Mass after Bronchial Thermoplasty: Are We There Yet?

technologies and future trends. Proteomics 2006;6:4716–4723. 10. Menni C, Kastenmüller G, Petersen AK, Bell JT, Psatha M, Tsai PC, Gieger C, Schulz H, Erte I, John S, et al. Metabolomic markers reveal novel pathways of ageing and early development in human populations. Int J Epidemiol 2013;42:1111–1119. 11. Moayyeri A, Hammond CJ, Valdes AM, Spector TD. Cohort Profile: TwinsUK and healthy ageing twin study. Int J Epidemiol 2013;42: 76–85. 12. Simpson GL, Ortwerth BJ. The non-oxidative degradation of ascorbic acid at physiological conditions. Biochim Biophys Acta 2000;1501:12–24. 13. Marchese ME, Kumar R, Colangelo LA, Avila PC, Jacobs DR Jr, Gross M, Sood A, Liu K, Cook-Mills JM. The vitamin E isoforms a-tocopherol and g-tocopherol have opposite associations with spirometric parameters: the CARDIA study. Respir Res 2014;15:31. 14. Zingg JM, Azzi A, Meydani M. Induction of VEGF expression by alphatocopherol and alpha-tocopheryl phosphate via PI3Kg/PKB and hTAP1/SEC14L2-mediated lipid exchange. J Cell Biochem 2015; 116:398–407. 15. Romieu I, Sienra-Monge JJ, Ramı́rez-Aguilar M, Téllez-Rojo MM, Moreno-Macı́as H, Reyes-Ruiz NI, del Rı́o-Navarro BE, Ruiz-Navarro MX, Hatch G, Slade R, et al. Antioxidant supplementation and lung functions among children with asthma exposed to high levels of air pollutants. Am J Respir Crit Care Med 2002;166:703–709.

Radiological abnormalities following bronchial thermoplasty: is the pathophysiology understood?

Radiological abnormalities after BT seems related to the severity of endobronchial mucosal injury after BT http://ow.ly/ZGeA30gLZa3 We read with great interest the paper by Debray et al. [1] reporting on early radiological lung abnormalities on computed tomography (CT) of the chest after bronchial thermoplasty (BT). The described findings in 13 patients are in line with our observations in 12 patients with severe asthma treated with BT in the TASMA trial (www.clinicaltrials.gov identifier number NCT02225392). Transient radiological abnormalities were seen after all 36 BT procedures, predominantly consisting of peribronchial consolidations with ground-glass opacities (figure 1a and c), partial occlusions/filling of bronchial lumen and atelectasis. Furthermore, we also observed a residual bronchial dilatation in a single case [2].

Reduction of airway smooth muscle mass in airway biopsies following bronchial thermoplasty; the TASMA randomized controlled trial

BACKGROUND Bronchial thermoplasty (BT) is a novel bronchoscopic treatment for severe asthma that is based on radiofrequent energy delivery to ∼3-10mm airways and aims to reduce airway smooth muscle (ASM). The TASMA study is the first randomised controlled trial that investigates the change in ASM after BT. AIM To determine the change in ASM mass in airway biopsies before and after BT and to compare this with a control group and the non-treated right middle lobe (RML). METHODS 6 severe asthma patients were randomized- after obtaining airway biopsies (pre-BT)- to either direct BT treatment (immediate group) or to 6 months waiting followed by re – airway biopsies and BT treatment (delayed group). From all patients, airway biopsies were taken 6 months post-BT. For each biopsy the ASM mass in percentage of the total biopsy area was measured automatically on 2 desmin-stained sections. RESULTS 6 months after BT mean ASM mass percentage significantly decreased (ASM mass % 11.6±5.5 vs 6±1.2 for pre-and post-BT respectively; p=0.029 (n=6, 23 biopsies)). In the delayed group (ASM mass % 7.6±5.2 vs 11±6.6 for pre-BT and delayed group respectively; P=0.473 (n=3, 12 biopsies)) and in the non-treated RML (ASM mass % 10.9±5.9 vs 10±7 for pre-BT and RML respectively; P=0.820 (n=5, 15 biopsies) no significant differences were detected when compared to pre-BT ASM mass %. CONCLUSIONS ASM mass percentage significantly decreases following BT treatment. ASM mass stays the same over time and in the untreated RML. IMPLICATIONS ASM mass might qualify as a biomarker for Bronchial Thermoplasty response.

Acute radiological abnormalities after bronchial thermoplasty (BT)

Background: BT is a novel treatment for severe asthma based on radiofrequent energy delivery to the airways. Although BT application is rapidly increasing worldwide, systematic radiological assessment immediately after BT has not been reported. Methods: Prospective, observational study of radiological abnormalities after BT. Chest X-rays taken Results: All 11 chest X-rays showed radiology abnormalities; subtotal lobar atelectasis (n=1), peribronchial opacities (n=4), peribronchial opacities and segmental atelectasis (n=5), peribronchial opacities, subtotal and segmental atelectasis (n=1). In 2 patients chest CT was performed Conclusions: BT frequently causes immediate, but transient radiology abnormalities. : Subtotal atelectasis of the right upper lobe, lingular peribronchial opacities and partial atelectasis of the anterior segments of the left upper lobe after BT of both upper lobes.