Quantitative assessment of airway remodelling and response to allergen in asthma

Abstract

Background and objective: In vivo evaluation of the microstructural differences between asthmatic and non-asthmatic airways and their functional consequences is relevant to understanding and, potentially, treating asthma. In this study, we use endobronchial optical coherence tomography to investigate how allergic airways with asthma differ from allergic non-asthmatic airways in baseline microstructure and in response to allergen challenge.

Methods: A total of 45 subjects completed the study, including 20 allergic, mildly asthmatic individuals, 22 non-asthmatic allergic controls and 3 healthy controls. A 3-cm airway segment in the right middle and right upper lobe were imaged in each subject immediately before and 24 h following segmental allergen challenge to the right middle lobe. Relationships between optical airway measurements (epithelial and mucosal thicknesses, mucosal buckling and mucus) and airway obstruction (FEV₁ /FVC (forced expiratory volume in 1 s/forced vital capacity) and FEV₁ % (FEV₁ as a percentage of predictive value)) were investigated.

Results: Significant increases at baseline and in response to allergen were observed for all four of our imaging metrics in the asthmatic airways compared to the non-asthmatic airways. Epithelial thickness and mucosal buckling exhibited a significant relationship to FEV₁ /FVC in the asthmatic group.

Conclusion: Simultaneous assessments of airway microstructure, buckling and mucus revealed both structural and functional differences between the mildly asthmatic and control groups, with airway buckling seeming to be the most relevant factor. The results of this study demonstrate that a comprehensive, microstructural approach to assessing the airways may be important in future asthma studies as well as in the monitoring and treatment of asthma.

Keywords: asthma; bronchoscopy and interventional techniques; radiology and other imaging; respiratory function test; respiratory structure and function.

Figure 1.

Structural airway features measured with OCT. (a) Mucosal thickness was measured from lumen to cartilage perichondrium, indicated with blue lines. (b) Epithelial thickness was measured from lumen to basement membrane, indicated with red lines. (c) Mucosal buckling was calculated as the percentage of frames in the dataset that exhibited buckling, indicated with arrows. (d) Mucus was automatically segmented and color-coded in yellow. Scale bars, 1 mm.

Figure 2.

Representative cross-sectional images comparing pre-challenge airway wall morphology (a-c) and mucus (d-f) for the three groups included in the study. Mucus was color-coded in yellow. (a,c) Allergic asthmatic, (b,e) allergic controls, and (c,f) healthy controls. (g-j) Airway morphology and mucus metrics measured pre-challenge for each of the three groups. (g) Mucosal thickness, (h) epithelial thickness, (i) percentage of frames exhibiting mucosal buckling, and (j) mucus contrast. AA, allergic asthmatic; AC, allergic control; HC, healthy control; A.U, arbitrary units. Scale bars, 1 mm. * p < 0.05, * p < 0.01, *** p < 0.001.

Figure 3.

Correlations between FEV₁/FVC and (a) mucosal thickness, (b) epithelial thickness, (c) mucosal buckling, and (d) mucus contrast, using baseline measurements for each. Values from both the AA (red dots) and AC (blue dots) group are included. Correlations are presented both AA and AC, separately. Trend line is included for AA only. A.U, arbitrary units.

Figure 4.

The four OCT metrics included in the study measured pre- and post- allergen (right middle lobe) and diluent (right upper lobe) for each of the three groups. (a) Mucosal thickness. (b) Epithelial thickness. (c) Mucosal buckling. (d) mucus contrast. AA, allergic asthmatic; AC, allergic control; HC, healthy control; A.U, arbitrary units. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 5.

Volumetric renderings of mucus in a right middle lobe airway segment of an allergic asthmatic study subject pre-challenge and 24 hours post-challenge. The airway wall was rendered in grayscale and the mucus false-colored in yellow. (a) Pre-allergen. (b) Post-allergen.