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Diagnostic and prognostic biomarkers for progressive fibrosing interstitial lung disease

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  • Mayuko Watase
  • Takao Mochimaru
  • Honomi Kawase
  • Hiroyuki Shinohara
  • Shinobu Sagawa
  • Toshiki Ikeda
  • Shota Yagi
  • Hiroyuki Yamamura
  • Emiko Matsuyama
  • Masanori Kaji
  • Momoko Kurihara
  • Midori Sato
  • Kohei Horiuchi
  • Risa Watanabe
  • Shigenari Nukaga
  • Kaoru Irisa
  • Ryosuke Satomi
  • Yoshitaka Oyamada

Abstract

No biomarkers have been identified in bronchoalveolar lavage fluid (BALF) for predicting fibrosis progression or prognosis in progressive fibrosing interstitial lung disease (PF-ILD). We investigated BALF biomarkers for PF-ILD diagnosis and prognosis assessment. Overall, 120 patients with interstitial pneumonia who could be diagnosed with PF-ILD or non PF-ILD were enrolled in this retrospective study. PF-ILD was diagnosed according to Cottin’s definition. All patients underwent bronchoscopy and BALF collection. We evaluated blood and BALF parameters, high-resolution computed tomography (HRCT) patterns, and spirometry data to identify factors influencing PF-ILD diagnosis and prognosis. On univariate logistic analysis, age, sex, the BALF white blood cell fraction (neutrophil, lymphocyte, eosinophil, and neutrophil-to-lymphocyte ratio), BALF flow cytometric analysis (CD8), and an idiopathic pulmonary fibrosis/usual interstitial pneumonia pattern on HRCT were correlated with PF-ILD diagnosis. Multivariate logistic regression analysis revealed that sex (male), age (cut-off 62 years, area under the curve [AUC] 0.67; sensitivity 0.80; specificity 0.47), white blood cell fraction in BALF (NLR, neutrophil, and lymphocyte), and CD8 in BALF (cut-off 34.2; AUC 0.66; sensitivity, 0.74; specificity, 0.62) were independent diagnostic predictors for PF-ILD. In BALF, the NLR (cut-off 8.70, AUC 0.62; sensitivity 0.62; specificity 0.70), neutrophil count (cut-off 3.0, AUC 0.59; sensitivity 0.57; specificity 0.63), and lymphocyte count (cut-off 42.0, AUC 0.63; sensitivity 0.77; specificity 0.53) were independent diagnostic predictors. In PF-ILD patients (n = 77), lactate dehydrogenase (cut-off 275, AUC 0.69; sensitivity 0.57; specificity 0.78), Krebs von den Lungen-6 (cut-off 1,140, AUC 0.74; sensitivity 0.71; specificity 0.76), baseline forced vital capacity (FVC) (cut-off 1.75 L, AUC 0.71; sensitivity, 0.93; specificity, 0.46), and BALF neutrophil ratio (cut-off 6.0, AUC 0.72; sensitivity 0.79; specificity 0.80) correlated with death within 3 years. The BALF cellular ratio, particularly the neutrophil ratio, correlated with the diagnosis and prognosis of PF-ILD. These findings may be useful in the management of patients with interstitial pneumonia.

Suggested Citation

  • Mayuko Watase & Takao Mochimaru & Honomi Kawase & Hiroyuki Shinohara & Shinobu Sagawa & Toshiki Ikeda & Shota Yagi & Hiroyuki Yamamura & Emiko Matsuyama & Masanori Kaji & Momoko Kurihara & Midori Sato, 2023. "Diagnostic and prognostic biomarkers for progressive fibrosing interstitial lung disease," PLOS ONE, Public Library of Science, vol. 18(3), pages 1-12, March.
  • Handle: RePEc:plo:pone00:0283288
    DOI: 10.1371/journal.pone.0283288
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    1. Mouhamad Nasser & Sophie Larrieu & Loic Boussel & Salim Si-Mohamed & Fabienne Bazin & Sébastien Marque & Jacques Massol & Françoise Thivolet-Bejui & Lara Chalabreysse & Delphine Maucort-Boulch & Eric , 2021. "Estimates of epidemiology, mortality and disease burden associated with progressive fibrosing interstitial lung disease in France (the PROGRESS study)," Post-Print hal-03260533, HAL.
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