The following is a summary of “Reply to: Broadening concepts of core pathobiology in various aspects of COPD development” published in the December 2022 issue of Respiratory by Xu et al.

Researchers would like to extend their gratitude to E.H. Walters and his colleagues for drawing attention to the novel approach that their research  took in matching tissue pathology with its gene transcriptome using micro-computed tomography (micro-CT) imaging. This allowed us to better understand the pathobiology of small airway disease in end-stage Chronic obstructive pulmonary disease (COPD). 

Investigators concur with the authors that post-transplant, explanted COPD lungs do indeed represent the end stages of the disease. On the other hand, such lung samples provide the only opportunity to evaluate the entire lung structure as well as the heterogeneity of small airway disease and emphysema across lung height in the absence of cancer. According to the authors, they have previously demonstrated that the loss of the terminal bronchioles, which are the last generation of small conducting airways, comes before the degradation of emphysematous tissue in end-stage COPD. 

More recently, this work has been validated using formalin-fixed-paraffin embedded (FFPE) samples from patients with mild and moderate COPD. The results of this validation showed that over 41% of the terminal bronchioles of these patients are destroyed prior to the detection of emphysema on clinical CT or microscopically on micro-CT . Understanding the pathobiology of terminal bronchiole decrease has the potential to lead to the development of new treatments for COPD. The findings presented here underline the fact that the loss of terminal bronchioles occurs early on in the progression of the illness.