Fig. 3
From: Use of a pulmosphere model to evaluate drug antifibrotic responses in interstitial lung diseases
Differential pulmosphere invasiveness in patients with ILD following exposure to nintedanib and pirfenidone. A Representative image of an invasive pulmosphere compared to pulmosphere treated with nintedanib and pirfenidone. Scale bars: 100 μm. B, C Paired scatter plots depicting change in ZOI% of untreated (black) versus nintedanib (red) ILD pulmospheres, and untreated (white) versus pirfenidone (grey) treated ILD pulmospheres. Untreated (95% CI 465.1, 516.9 ± 119.9) vs nintedanib (95% CI 165.4,218.6, 192 ± 61.5, ****P value < 0.0001 by Wilcoxon test). Untreated (95% CI 471.4, 581.2 ± 126.9) vs pirfenidone (95% CI 444.5, 580.1, 512.3 ± 156.7, P value ns by Wilcoxon test). D Measurement of fold change of zone of invasion (ZOI) was calculated as the ratio of ZOI% with treatment to ZOI% without treatment in vitro with antifibrotic drug. E Median values of ZOI > 1 represent pulmospheres nonresponsive to the treatment, and median values of ZOI < 1 represent pulmospheres responsive to drug treatment. For each patient tested, 5 pulmospheres were seeded without either test drug; 5 pulmospheres were seeded with nintedanib (1 μM); and 5 pulmospheres were seeded with pirfenidone (100 μM). ZOI fold change values were obtained from the ratio of ZOI% with treatment to ZOI% without treatment of pulmospheres in vitro with antifibrotic drug for each patient. F Dot and whisker plot for ILD patient pulmospheres treated with nintedanib (red circles) and pirfenidone (black squares). Whiskers show maximum to minimum values. G Dot and whisker plot for CTD-ILD patient pulmospheres treated with pirfenidone (black squares). Dot and whisker plot depicting response to nintedanib (H) and pirfenidone (I) among ILD pulmospheres grouped into progressors (red circle), non-progressors (blue inverted triangle), and undetermined (no follow up data, black squares)