Squamous metaplasia is an indicator of acute exacerbation in patients with usual interstitial pneumonia / idiopathic pulmonary fibrosis

Yuri Tachibana; Masatake Hara; Mikiko Hashisako; Yasuhiko Yamano; Kensuke Kataoka; Yasuhiro Kondoh; Takeshi Johkoh; Shimpei Morimoto; Andrey Bychkov; Junya Fukuoka

doi:10.1016/j.resinv.2024.04.021

Squamous metaplasia is an indicator of acute exacerbation in patients with usual interstitial pneumonia / idiopathic pulmonary fibrosis

Respir Investig. 2024 May 8;62(4):631-637. doi: 10.1016/j.resinv.2024.04.021. Online ahead of print.

Authors

Affiliations

¹ Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashicho, Kamogawa-shi, Chiba, 2960041, Japan.
² Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan.
³ Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160, Nishioiwakecho, Seto-shi, Aichi, 4898642, Japan.
⁴ Department of Radiology, Kansai Rosai Hospital, 3-1-69, Inabaso, Amagasaki-shi, Hyogo, 6608511, Japan.
⁵ Clinical Research Center, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, Nagasaki-shi, 8528501, Japan.
⁶ Department of Pathology, Kameda Medical Center, 929, Higashicho, Kamogawa-shi, Chiba, 2960041, Japan.
⁷ Department of Pathology Informatics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4, Sakamoto, Nagasaki, Nagasaki-shi, 8528523, Japan; Department of Pathology, Kameda Medical Center, 929, Higashicho, Kamogawa-shi, Chiba, 2960041, Japan. Electronic address: fukuokaj@nagasaki-u.ac.jp.

PMID: 38723442
DOI: 10.1016/j.resinv.2024.04.021

Abstract

Background: Acute exacerbation (AE) is a potentially lethal event in patients with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF). However, to date, no pathological predictors of AE have been identified. This retrospective study aimed to elucidate the pathological features that could predict AE in patients with UIP.

Methods: We reviewed the pathological findings of 91 patients with UIP/IPF and correlated these findings with AE events. Thirteen histological variables related to acute lung injury were evaluated by three independent observers and classified as positive or negative. The patients' clinical data during follow-up were collected and reviewed for AE. A recursive partition using the Gini index for the prediction of AE was performed, with each pathological finding as a candidate for branching.

Results: Twenty patients (22%) developed AE during the median follow-up duration of 40 months. Thirty-eight patients died (15 due to AE and 23 for other reasons). The median time interval from surgical lung biopsy to AE onset was 497 (interquartile range: 901-1657) days. Histologically, squamous metaplasia was positively associated with AE (odds ratio: 4.7, P = 0.015) and worse event-free survival in patients with UIP (P = 0.04). Leaf scoring based on the Gini index for recursive partition, including five positive findings (squamous metaplasia, neutrophilic infiltration, septal widening, Kuhn's hyaline, and fibrin), showed a sensitivity of 90% with a specificity of 74.7% (area under curve: 0.89).

Conclusions: We found that squamous metaplasia is an important histopathological finding that predicts AE events and tends to unfavorable outcome in patients with UIP/IPF.

Keywords: Acute lung injury; Classification; Idiopathic pulmonary fibrosis; Pathology; Survival.