Open-lung biopsy identifies airway morphological changes in distal airways of patients with ARDS

Abstract

Introduction: Evidence of airway dysfunction has been reported in ARDS patients, and was associated with adverse outcomes (Morales et al. Critical Care 2011, 15:R4; Volta et al. Critical Care (2019) 23:395). Our objective was to assess whether open-lung biopsy OLB could identify morphological changes in distal airways in ARDS patients, and whether those changes were associated with ARDS severity and other clinical outcomes.

Methods: We retrospectively reviewed lung tissue from patients with ARDS (n=25) obtained with OLB, and compared data with control lung tissue sampled from lobectomies performed in patients with a solitary lung tumor and no evidence of other lung disease (n=15). Morphological changes in distal airways (<2mm diameter) were analyzed and quantified by a pathologist blinded to the clinical data. ARDS and control groups were subsequently compared (Mann-Whitney) and the association of morphological data with clinical data was evaluated using Pearson Rank Test.

Results: Airways of ARDS patients were characterized by increased epithelial denudation (22.6% of the total epithelium length ± 22% vs 3 ± 5%, mean ± SD, p=0.0003) and increased epithelial inflammation (semi-quantitative index on a 4-grade scale) with neutrophils [1 (0-2) vs 0 (0-0), p<0.0001] and lymphocytes [1 (1-1) vs 0 (0-1), p<0.0001]. Airway morphological changes were not correlated with mortality or duration of mechanical ventilation, while the inflammatory index was modestly associated with disease severity (PaO2/FiO2 ratio, r²=0.26, p=0.012).

Conclusion: OLB identified structural and inflammatory changes in distal airways of patients with ARDS, which correlate to a mild extent with disease severity.