Histologic factors associated with nintedanib efficacy in patients with idiopathic pulmonary fibrosis.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2021
Historique:
received: 06 11 2020
accepted: 22 12 2020
entrez: 7 1 2021
pubmed: 8 1 2021
medline: 11 5 2021
Statut: epublish

Résumé

Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib. This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment. The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range: [-25%--5%], vs. -3% [-7%-0%], P = 0.004) and reticular shadow (7% [3%-13%], vs. 0% [0%-5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval: [5.9-25.3], vs. event <50%, [12.1-Not available], P = 0.0009, and 6.1 months, [5.2-6.6] vs. 14.5 months [7.8-not available], P<0.0001). Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.

Sections du résumé

BACKGROUND
Histopathologic factors predictive of nintedanib efficacy in idiopathic pulmonary fibrosis have not been studied. We aimed to describe the characteristics, focusing on histopathology, of idiopathic pulmonary fibrosis patients who did and did not respond to nintedanib.
METHODS
This study retrospectively examined the clinicoradiopathologic features of 40 consecutive patients with surgical lung biopsy-confirmed idiopathic pulmonary fibrosis treated with nintedanib. Additionally, we compared the histopathologic scoring of 21 microscopic features between patients with functional or radiological progression and those with non-progression during 12 months of treatment.
RESULTS
The histopathologic evaluation showed edematous changes in the interlobular septum as the only histologic finding observed more frequently in patients with both functional and radiological progression than in those without (58% vs. 14%, P = 0.007 and 50% vs. 0%, P = 0.003, respectively). Regarding per-year change, patients with edematous changes in the interlobular septum showed greater progression in median changes in spared area (-12%, interquartile range: [-25%--5%], vs. -3% [-7%-0%], P = 0.004) and reticular shadow (7% [3%-13%], vs. 0% [0%-5%], P = 0.041) on computed tomography. Functional and radiological progression-free survival were shorter in patients with edematous changes in the interlobular septum than in those without (6.6 months, 95% confidence interval: [5.9-25.3], vs. event <50%, [12.1-Not available], P = 0.0009, and 6.1 months, [5.2-6.6] vs. 14.5 months [7.8-not available], P<0.0001).
CONCLUSIONS
Edematous changes in the interlobular septum may indicate poor nintedanib efficacy in idiopathic pulmonary fibrosis. Further studies are needed to validate these findings and address the mechanism behind ECIS.

Identifiants

pubmed: 33411718
doi: 10.1371/journal.pone.0245147
pii: PONE-D-20-34933
pmc: PMC7790243
doi:

Substances chimiques

Indoles 0
nintedanib G6HRD2P839

Types de publication

Clinical Trial Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0245147

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Masahiro Nemoto (M)

Department of Pulmonary Medicine, Kameda Medical Center, Kamogawa, Japan.
Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Yoshiaki Zaizen (Y)

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Kensuke Kataoka (K)

Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.

Kishio Kuroda (K)

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Kazuhiro Tabata (K)

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Andrey Bychkov (A)

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Pathology, Kameda Medical Center, Kamogawa, Japan.

Hiromitsu Sumikawa (H)

Department of Diagnostic Radiology, Sakai City Medical Center, Sakai, Japan.

Takeshi Johkoh (T)

Department of Radiology, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Japan.

Masahiro Aoshima (M)

Department of Pulmonary Medicine, Kameda Medical Center, Kamogawa, Japan.

Yasuhiro Kondoh (Y)

Department of Respiratory Medicine and Allergy, Tosei General Hospital, Seto, Japan.

Junya Fukuoka (J)

Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Pathology, Kameda Medical Center, Kamogawa, Japan.

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Classifications MeSH