The following is a summary of “Towards an artificial human lung: modelling organ-like complexity to aid mechanistic understanding” published in the December 2022 issue of Respiratory by Humbert et al.

More than 5 million people lose their lives yearly due to respiratory disorders, placing a significant financial strain on healthcare systems worldwide. While murine models have proved invaluable for understanding human lung biology in vivo, important gaps remain due to fundamental differences in genetics, anatomy, physiology, and immunology. Thus, it is vital to design models that faithfully mimic the amazing complexity of human pulmonary architecture and biology to gain a thorough understanding of human lung physiology, development, homeostasis, and molecular dysregulation that may lead to illness. 

In an effort to close the gap between the native lung and its in vitro mimics, increasingly complex models have been developed thanks to recent advancements in micro-engineering technology and tissue engineering. The tremendous technical improvement in downstream analysis, together with cutting-edge culture techniques, has greatly improved the prediction capacity of human biology-based in vitro models by allowing the capture and quantification of complex signals. With improved integrated multi-omics readouts, the time it takes to go from in vitro experiments to medication development and clinical testing could be reduced. 

This article discusses the wide variety of disease states and prospective applications of state-of-the-art lung models, such as pre-clinical drug testing, that may be performed on these models. These models span from nasal to big airways to small airways to alveoli. Researchers investigate how optimizing in vitro human lung models to be physiologically appropriate may hasten the discovery of novel medicines with the potential to move quickly from the laboratory to the hospital bedside.