Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and infective exacerbations, but lacks in-vitro models for studying host-pathogen interactions. This study established nasopharyngeal and bronchial organoids from healthy individuals and COPD patients, revealing goblet cell hyperplasia and reduced ciliary beat frequency in COPD organoids. Single-cell transcriptomics showed altered cellular differentiation. SARS-CoV-2 infection resulted in more productive replication in COPD bronchi. Viral and bacterial exposure triggered greater pro-inflammatory responses in COPD organoids. This organoid model recapitulates the in vivo lung microenvironment for studying host-pathogen interactions.

Louisa L. Y. Chan, Danielle E. Anderson, Hong Sheng Cheng, Fransiskus Xaverius Ivan, Si Chen, Adrian E. Z. Kang, Randy Foo, Akshamal M. Gamage, Pei Yee Tiew, Mariko Siyue Koh, Ken Cheah Hooi Lee, Kristy Nichols, Prabuddha S. Pathinayake, Yik Lung Chan, Tsin Wen Yeo, Brian G. Oliver, Peter A. B. Wark, Linbo Liu, Nguan Soon Tan, Lin-Fa Wang, Sanjay H. Chotirmall