Associations in asthma between quantitative computed tomography and bronchial biopsy-derived airway remodelling

Rachid Berair, Ruth Hartley, Vijay Mistry, Ajay Sheshadri, Sumit Gupta, Amisha Singapuri, Sherif Gonem, Richard P Marshall, Ana R Sousa, Aarti Shikotra, Richard Kay, Andrew Wardlaw, Peter Bradding, Salman Siddiqui, Mario Castro, Christopher E Brightling, Rachid Berair, Ruth Hartley, Vijay Mistry, Ajay Sheshadri, Sumit Gupta, Amisha Singapuri, Sherif Gonem, Richard P Marshall, Ana R Sousa, Aarti Shikotra, Richard Kay, Andrew Wardlaw, Peter Bradding, Salman Siddiqui, Mario Castro, Christopher E Brightling

Abstract

Airway remodelling in asthma remains poorly understood. This study aimed to determine the association of airway remodelling measured on bronchial biopsies with 1) lung function impairment and 2) thoracic quantitative computed tomography (QCT)-derived morphometry and densitometry measures of proximal airway remodelling and air trapping.Subjects were recruited from a single centre. Bronchial biopsy remodelling features that were the strongest predictors of lung function impairment and QCT-derived proximal airway morphometry and air trapping markers were determined by stepwise multiple regression. The best predictor of air trapping was validated in an independent replication group.Airway smooth muscle % was the only predictor of post-bronchodilator forced expiratory volume in 1 s (FEV1) % pred, while both airway smooth muscle % and vascularity were predictors of FEV1/forced vital capacity. Epithelial thickness and airway smooth muscle % were predictors of mean segmental bronchial luminal area (R2=0.12; p=0.02 and R2=0.12; p=0.015), whereas epithelial thickness was the only predictor of wall area % (R2=0.13; p=0.018). Vascularity was the only significant predictor of air trapping (R2=0.24; p=0.001), which was validated in the replication group (R2=0.19; p=0.031).In asthma, airway smooth muscle content and vascularity were both associated with airflow obstruction. QCT-derived proximal airway morphometry was most strongly associated with epithelial thickness and airway smooth muscle content, whereas air trapping was related to vascularity.

Conflict of interest statement

Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com

Copyright ©ERS 2017.

Figures

Figure 1
Figure 1
a) Airway smooth muscle % and b) vascularity (mean Chalkley count) in subjects with and without persistent airflow limitation (post-bronchodilator [BD] FEV1 <80% and ≥80% predicted).
Figure 2
Figure 2
Scatterplots showing correlations of post-bronchodilator [BD] FEV1 and FEV1/FVC with a) and b) airway smooth muscle % and c) and d) vascularity.
Figure 3
Figure 3
Scatterplots showing correlations of epithelial thickness and airway smooth muscle % with a) and b) mean segmental bronchial luminal and c) and d) mean segmental wall area %.
Figure 4
Figure 4
Scatterplots showing correlations of vascularity and airway smooth muscle % with a) and b) MLD E/I and c) and d) VI-856 HU.
Figure 5
Figure 5
Validation of the association between vascularity and air-trapping in the replication group showing scatterplots of vascularity with a) MLD E/I and b) VI-856 HU.

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