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Lung disorders

A new model and modulator of pulmonary oedema

Nature Reviews Drug Discovery volume 12, page 23 (2013)Cite this article

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Together, two complementary studies published in Science Translational Medicine have identified a new microdevice model — termed 'lung on a chip' — of pulmonary oedema, and identified a blocker of transient receptor potential cation channel vanilloid 4 (TRPV4) that inhibits pulmonary oedema in animal models.

In the study by Huh and colleagues, the authors built on previous work that had engineered the 'lung on a chip' device (which was shown to reconstitute the alveolar–capillary interface of the human lung and mechanically 'breathe') by investigating whether the device could mimic pulmonary oedema and be used to test pharmaceutical agents. To develop a drug toxicity-induced model, they perfused interleukin-2 (IL-2) — which can cause dose-limiting pulmonary oedema when given therapeutically — through the microvascular channel of the device. This caused leakage of liquid across the endothelial lining of the microvascular channel and into the previously air-filled alveolar compartment, which compromised oxygen transport. Moreover, this was exacerbated in the presence of breathing motions, showing that the device could mimic the clinical situation.

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ORIGINAL RESEARCH PAPERS

  1. Huh, D. et al. A human disease model of drug toxicity-induced pulmonary edema in a lung-on-a-chip microdevice. Sci. Transl. Med. 4, 159ra147 (2012)

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  2. Thorneloe, K. S. et al. An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. Sci. Transl. Med. 4, 159ra148 (2012)

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Authors
  1. Charlotte Harrison
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Harrison, C. A new model and modulator of pulmonary oedema. Nat Rev Drug Discov 12, 23 (2013). https://doi.org/10.1038/nrd3917

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