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BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases


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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Interstitial lung diseases


High-resolution CT scan


Bronchoalveolar lavage


Cluster of differentiation


Hypersensitivity pneumonitis


Krebs von den Lungen-6




Natural killer


Natural killer T-like


Receiver operating characteristic


Area under the curve

r :

Rho coefficient

p :

Probability value


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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.


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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d’Alessandro, M., Carleo, A., Cameli, P. et al. BAL biomarkers’ panel for differential diagnosis of interstitial lung diseases. Clin Exp Med (2020).

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