Extract
We thank the authors for highlighting the innovation of our study [1] using micro-computed tomography (micro-CT) imaging to match tissue pathology with its gene transcriptome to understand the pathobiology of small airway disease in end-stage COPD. We agree with the authors that post-transplant, explanted COPD lungs do represent the end stages of the disease, however, such lung samples provide the only opportunity to assess the entire lung structure and the heterogeneity of small airways disease and emphysema across lung height without the presence of cancer. As the authors note, we have previously shown that destruction of the last generation of small conducting airways, the terminal bronchioles precedes emphysematous tissue destruction in end-stage COPD [2]. But more recently, this work has been validated using formalin-fixed-paraffin embedded (FFPE) samples from patients with mild and moderate COPD, which demonstrated over 41% of their terminal bronchioles are destroyed prior to the detection of emphysema on clinical CT or microscopically on microCT [3]. These data highlight that loss of terminal bronchioles occurs early in the disease process and understanding the pathobiology of terminal bronchiole reduction has the potential to develop new therapeutics for COPD.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of Interest: Angelico Mendy's contribution is funded in part by NIEHS grant P30ES006096. Outside the submitted work, Angelico Mendy has no further disclosures.
- Received August 2, 2022.
- Accepted September 26, 2022.
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