Longitudinal changes in airway remodeling and air trapping in severe asthma

Abstract

Rationale and objectives: Previous cross-sectional studies have demonstrated that airway wall thickness and air trapping are greater in subjects with severe asthma than in those with mild-to-moderate asthma. However, a better understanding of how airway remodeling and lung density change over time is needed. This study aimed to evaluate predictors of airway wall remodeling and change in lung function and lung density over time in severe asthma.

Materials and methods: Phenotypic characterization and quantitative multidetector-row computed tomography (MDCT) of the chest were performed at baseline and ∼2.6 years later in 38 participants with asthma (severe n = 24 and mild-to-moderate n = 14) and nine normal controls from the Severe Asthma Research Program.

Results: Subjects with severe asthma had a significant decline in postbronchodilator forced expiratory volume in 1 second percent (FEV1%) predicted over time (P < .001). Airway wall thickness measured by MDCT was increased at multiple airway generations in severe asthma compared to mild-to-moderate asthma (wall area percent [WA%]: P < .05) and normals (P < .05) at baseline and year 2. Over time, there was an increase in WA% and wall thickness percent (WT%) in all subjects (P = .030 and .009, respectively) with no change in emphysema-like lung or air trapping. Baseline prebronchodilator FEV1% inversely correlated with WA% and WT% (both P < .05). In a multivariable regression model, baseline WA%, race, and health care utilization were predictors of subsequent airway remodeling.

Conclusions: Severe asthma subjects have a greater decline in lung function over time than normal subjects or those with mild-to-moderate asthma. MDCT provides a noninvasive measure of airway wall thickness that may predict subsequent airway remodeling.

Trial registration: ClinicalTrials.gov NCT01716494 NCT01760915.

Keywords: Severe asthma; airway remodeling; computed tomography.

Conflict of interest statement

Conflict of Interest Disclosure: All author's Universities have received grant monies from NIH to conduct the Severe Asthma Research Program (SARP). No additional potential conflicts exist with companies/organizations whose product or services pertinent to this article.

Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Change in FEV1% predicted post-bronchodilation by asthma severity between baseline and Year 2. *p = < 0.05 Severe asthma versus mild-to-moderate asthma

Figure 2

WA% versus airway generation at Baseline (A) and Year 2 (B). WA% was significantly greater at baseline in generations 3 and 5 in severe asthma versus normal patients and severe asthma versus mild-to-moderate asthma at baseline and at Year 2 in generation 3. Additionally, WA% increased between baseline and Year 2 at generation 3 across all groups. *p = †p = < 0.05 WA% in all subjects baseline versus Year 2

Figure 3

WT% versus generation at baseline (A) and Year 2 (B). WT% was significantly greater at baseline in severe asthma compared to normal patients at baseline. Additionally, WT% increased between baseline and Year 2 at generation 3, 4, and 6 across all groups. *p = †p = < 0.05 WT% in all subjects baseline versus Year 2