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BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases

Abstract

Bronchoalveolar lavage (BAL) is a useful procedure for differential diagnosis of interstitial lung diseases (ILDs) and for identification of granulomatous lung diseases. We investigated a panel of biomarkers from BAL fluid of ILD patients to evaluate their utility in differentiating ILDs. Bronchoscopy with BAL was performed in 100 consecutive patients with suspected ILD (41 sarcoidosis, 11 cHP and 24 other ILDs); the 24 patients negative for ILD diagnosis were included as control group. BAL phenotypes and cell profiles (CD4+/CD8+ ratio, NK and CD103+ cell counts, chitotriosidase and KL-6 levels in BAL) were determined by flow cytometry. A decision-tree statistical algorithm was applied. Sarcoidosis was discriminated by a higher BAL CD4+/CD8+ ratio (p = 5.8E−05), a lower BAL CD103+CD4+ count (p = 5.0E−02) and lower BAL NK percentages (p = 8.8E−03) than the other groups. BAL KL-6 concentrations were higher in sarcoidosis than in other ILDs (p = 1.5E−02) and were directly correlated with CD4+/CD8+ ratio. We used decision-tree statistical analysis to combine our biomarkers into two diagnostic algorithms for differential diagnosis of ILDs. A panel of BAL biomarkers for diagnosis of ILDs is proposed; CD4+/CD8+ ratio, KL-6 concentrations, and NK and CD103+CD4+ cell percentages in BAL could improve the identification and differential diagnosis of sarcoidosis.

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Abbreviations

ILDs:

Interstitial lung diseases

HRCT:

High-resolution CT scan

BAL:

Bronchoalveolar lavage

CD-:

Cluster of differentiation

HP:

Hypersensitivity pneumonitis

KL-6:

Krebs von den Lungen-6

CTO:

Chitotriosidase

NK:

Natural killer

NKT-like:

Natural killer T-like

ROC:

Receiver operating characteristic

AUC:

Area under the curve

r :

Rho coefficient

p :

Probability value

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Acknowledgements

The authors acknowledged BD-Biosciences for gating strategy support, FUJIREBIO for assistance with the KL-6 assay, and our patients associations Amici Contro la Sarcoidosi, Profondi Respiri and Un Soffio di speranza “Il sogno di Emanuela” ONLUS for their constant help.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Correspondence to Miriana d’Alessandro.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (include name of committee + reference number) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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The original version of this article was revised: First and last names of the authors were interchanged.

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d’Alessandro, M., Carleo, A., Cameli, P. et al. BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases. Clin Exp Med (2020). https://doi.org/10.1007/s10238-020-00608-5

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Keywords

  • Bronchoalveolar lavage
  • KL-6
  • CD4+/CD8+ ratio
  • CD103, NK cells
  • Sarcoidosis
  • Interstitial lung diseases