Uniformity in air trapping distribution is associated with the severity of airway hyper-responsiveness in asthma.

Abstract

Severe airway hyper-responsiveness is associated with poor outcomes in asthma. Spatial heterogeneities in airway closures and subsequent air trapping (AT) during bronchoconstriction have been poorly assessed in asthma. We assessed the spatial distribution of AT by acquiring expiratory lung CT at each dose of a methacholine challenge in 31 women with asthma. A statistical method based on k-nearest-neighbors (knn) informed about between AT-area distance toward uniformity at the peak of bronchoconstriction (PC20). Fractal dimensions of binarized low attenuation areas were also computed at each methacholine dose. Whereas AT progressed with methacholine concentration and peaked at PC20, the clustering of knn curves identified two patterns of AT-spatial distribution. The first cluster (23 patients) presented heterogeneous patterns of AT assessed at the PC20, eventually fitting with segmental or lobar distribution. Conversely, the second cluster (8 patients) had spatial distribution close to uniformity, suggestive of an even progression of airway closure throughout the whole airway tree. This last cluster had lower PC20 concentrations (153 µg [83-392] vs 693 µg [370-980], p = 0.01), lower baseline FEV1 values (0.72 [0.65-0.77] vs 0.82 [0.74-0.88]% predicted, p < 0.05) and lower recovery of airflow after albuterol, a short-acting beta2-agonist (SABA) (0.66 [0.63-0.69] vs 0.76 [0.67-0.86]% predicted, p = 0.04). Expiratory-to-inspiratory ratio of the fractal dimension progressed with the methacholine concentration, peaked at the PC20, and remained significantly higher throughout the challenge in the uniform cluster. Unevenly distributed spatial progression of AT with methacholine might represent a protective mechanism against excessive bronchoconstriction. Patients at risk of uniform AT might be identified by either low PC20 concentrations and limited SABA recovery. Question How does regional heterogeneity of air trapping affect asthmatic patients? Findings Acquisition of expiratory CT at each dose of a methacholine challenge allowed for assessing k-nearest-neighbors and fractal dimensions informing about spatial uniformity of air trapping. Clinical relevance Low methacholine concentrations, low baseline FEV1 and limited FEV1 recovery post bronchodilator are indicative of uniformly distributed air trapping, deserving clinical attention.