Influence of Omalizumab Therapy on Airway Remodeling Assessed with High-Resolution Computed Tomography (HRCT) in Severe Allergic Asthma Patients

Abstract

Introduction: Airway remodeling is an important factor in persistent obstruction in severe asthma. High resolution computed tomography (HRCT) is an effective method of detecting changes in airway structure. Our aim was to use HRCT to assess changes in airway remodeling in patients with severe allergic asthma who are treated with omalizumab. Material and methods: In 12 patients with severe allergic asthma, HRCT was performed before and after treatment with omalizumab. In selected bronchial airways, parameters were calculated: bronchial wall area (BA), also corrected for body surface area (BSA); percentage of wall area (WA%); and the ratio of luminal area to total bronchial area (Ai/Ao). Clinical response to treatment was assessed using an asthma control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ), and number of exacerbations per year. Assessment included spirometry and blood eosinophilia. Results: Treatment resulted in significant improvement in ACQ (p = 0.035) and AQLQ (p = 0.001). We observed significant reduction in exacerbations per year (p = 0.002) and reduction of daily systemic steroid dose (p = 0.032). FEV 1 and peripheral blood eospinophilia did not change (p = 0.846 and p = 0.221). Airway dimensions (Ai/Ao) of particular bronchi were consistent with the mean of the parameters calculated for all bronchi measured. Although we observed a significant decrease in WA (p = 0.002) and WA/BSA (p = 0.002), WA% and Ai/Ao did not improve (p = 0.39 and p = 0.49). We found no correlations between changes in airways and changes in spirometry or clinical parameters. Conclusion: Despite clinical effectiveness of omalizumab, its effect on airway remodeling may be limited.

Status and prospects: personalized treatment and biomarker for airway remodeling in asthma

“…Moreover, imaging examinations, especially CT, are also considered a useful way to assess airway remodeling in human asthma subjects. However, all of these techniques are limited by practicality and ethicality (28).…”

“…A wealth of clinical trials regarding monoclonal antibodies suggested that a variety of IL-5 monoclonal antibodies (e.g., mepolizumab and reslizumab) can facilitate airway remodeling in asthma, including reducing the expression of ECM protein in the RBM, thereby partially restricting airway remodeling (48). For patients with long-term asthma with persistent airway obstruction, however, the current biologics have limited effects (28,(88)(89)(90). Though largescale clinical trials have suggested that the new monoclonal antibodies against IL-4/IL-13, [e.g., dupilumab and tralokinumab (91,92)] can effectively reduce the onset of asthma and improve FEV1, their exact effects on airway remodeling require further research.…”

Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

“…Several studies have reported that bronchial wall thickness was improved by ICSs or omalizumab treatment in adult patients with severe asthma. 23 – 25 Airway wall thickness on CT images includes not only irreversible tissue structural changes, but also reversible airway mucosal changes caused by swelling or the infiltration of inflammatory cells. 26 This reversible mucous membrane thickness in the airways can be reduced by the initiation of an ICS or omalizumab to suppress airway inflammation, resulting in improved airway wall thickness in CT images.…”

Novel Lung Growth Strategy with Biological Therapy Targeting Airway Remodeling in Childhood Bronchial Asthma

“…Three studies using biopsied bronchial tissue before and after omalizumab treatment in adult patients with severe asthma showed a significant reduction in bronchial reticular basement membrane thickness, airway smooth muscles, and fibronectin deposition [ 134 , 135 , 136 ]. Furthermore, three studies using CT airway analysis gave similar assessments, reporting that omalizumab treatment in adult patients with severe asthma significantly reduced airway wall thickness and area [ 137 , 138 , 139 ]. The improving effect on airway remodeling has been confirmed not only with omalizumab, but also with other biological drugs.…”