Metabolic differences between bronchial epithelium from healthy individuals and patients with asthma and the effect of bronchial thermoplasty

Background: Asthma is a heterogeneous disease with differences in onset, severity, and inflammation. Bronchial epithelial cells (BECs) contribute to asthma pathophysiology. Objective: We determined whether transcriptomes of BECs reflect heterogeneity in inflammation and severity in asthma, and whether this was affected in BECs from patients with severe asthma after their regeneration by bronchial thermoplasty. Methods: RNA sequencing was performed on BECs obtained by bronchoscopy from healthy controls (n = 16), patients with mild asthma (n = 17), patients with moderate asthma (n = 5), and patients with severe asthma (n = 17), as well as on BECs from treated and untreated airways of the latter (also 6 months after bronchial thermoplasty) (n = 23). Lipidome and metabolome analyses were performed on cultured BECs from healthy controls (n = 7); patients with severe asthma (n = 9); and, for comparison, patients with chronic obstructive pulmonary disease (n = 7). Results: Transcriptome analysis of BECs from patients showed a reduced expression of oxidative phosphorylation (OXPHOS) genes, most profoundly in patients with severe asthma but less profoundly and more heterogeneously in patients with mild asthma. Genes related to fatty acid metabolism were significantly upregulated in asthma. Lipidomics revealed enhanced levels of lipid species (phosphatidylcholines, lysophosphatidylcholines. and bis(monoacylglycerol)phosphate), whereas levels of OXPHOS metabolites were reduced in BECs from patients with severe asthma. BECs from patients with mild asthma characterized by hyperresponsive production of mediators implicated in neutrophilic inflammation had decreased expression of OXPHOS genes compared with that in BECs from patients with mild asthma with normoresponsive production. BECs obtained after thermoplasty had significantly increased expression of OXPHOS genes and decreased expression of fatty acid metabolism genes compared with BECs obtained from untreated airways. Conclusion: BECs in patients with asthma are metabolically different from those in healthy individuals. These differences are linked with inflammation and asthma severity, and they can be reversed by bronchial thermoplasty

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

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. 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. 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. 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 disease

<i>Ex-vivo</i> OCT cross-sectional image and corresponding histology image of human airway.

<p>(A) Clean histology cross section of human airway of the segmental LLL, stained with desmin. (B) cross section images of histology, stained with desmin, with manually traced perimeters; P_L: lumen perimeter, P_muc: mucosal perimeter, P_submusc: submucosal muscular perimeter. (C) Corresponding cross section of OCT of <i>ex-vivo</i> airway to histology airway image A. (D) cross section images of OCT and with manually traced perimeters; P_L: lumen perimeter, P_muc: mucosal perimeter, P_submusc: submucosal muscular perimeter and OCT probe in situ.</p

Patient characteristics undergoing OCT and lobectomy.

<p>Patient characteristics undergoing OCT and lobectomy.</p

E<i>x-vivo</i> OCT cross-sectional image visualizing the different layers of the human airway wall and corresponding histology image.

<p>(A) Histology cross section, stained with H&E. (B) Higher magnification view of the square of histology image A, visualizing the different layers of the airway wall of the segmental LLL. (C) Histology cross section, stained with desmin. (D) Higher magnification view of the square of histology image C, visualizing the submucosal muscular layer of the airway wall. (E) Corresponding cross section of OCT of <i>ex-vivo</i> airway to histology airway image A and C. (F) Higher magnification view of the square of OCT image E, visualizing the corresponding layers of the airway wall.</p

Linear regression analysis and Bland-Altman plots for histology and OCT <i>ex-vivo</i> airway wall area measurements (n = 51).

<p>(A) A_L lumen area in mm². (B) A_muc mucosal area in mm². (C) A_submusc submucosal muscular area in mm². (D) WA_t total airway wall area in mm². (E) WA_muc mucosal wall area in mm². (F) WA_submusc submucosal muscular wall area in mm².</p