Clinical phenotyping in sarcoidosis management.

Sarcoidosis is a heterogeneous granulomatous disease. Biological markers and clinical features could allow specific phenotypes to be associated with different prognosis, severity and treatment responses. This retrospective multicentre study aims to analyse the clinical and immunological features of sarcoidosis and to identify a routine non-invasive biomarker useful in clinical practice. MATERIALS AND METHODS: 129 Caucasian patients with sarcoidosis (median age IQR, 56 (47-62)) were enrolled retrospectively in the study. Medical history, routine laboratory findings, lung function results and radiological features from the last examination of October 2019 - February 2020 were gathered from the patients' clinical records. RESULTS: Regardless their clinical status at disease onset, at the last clinical examination we didn't observe any differences in terms of therapeutic management between symptomatic and asymptomatic patients. Stratifying sarcoidosis population according to therapeutic management, the N/L ratio was higher in the treated group than in the non-treated group (p=0.0034). Receiver operating curve (ROC) analysis distinguished these two groups according to N/L ratio with an area under the curve (AUC) of 65.3% and a best cut-off value of 2.21. Peripheral N/L ratio was significantly higher in radiological stages 2-4 than in stages 0-1 (p=0.0090) distinguishing these two groups with an AUC of 64% and a best cut-off value of 2.13. DISCUSSION: In our multicentric cohort study similar periodic follow-up can be suggested for symptomatic and asymptomatic sarcoidosis patients at onset. In the heterogeneous context of this disease, N/L ratio proved to be a useful and simple routine laboratory biomarker related to disease activity and need for treatment.

Utility of serological biomarker' panels for diagnostic accuracy of interstitial lung diseases.

Interstitial lung diseases (ILD) are a heterogeneous group of illnesses of known and unknown aetiology. Differential diagnosis among the three disorders is often challenging. Specific biomarkers with good sensitivity and specificity are therefore needed to predict clinical outcome and guide clinical decisions. The aim of this study was to investigate inflammatory/fibrotic biomarkers, to determine whether single mediators or panels of mediators could be useful to stratify patients into three distinct domains: sarcoidosis, idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis (cHP). A total of 163 ILD patients monitored at Siena Referral Centre for Sarcoidosis and other Interstitial Lung Diseases were enrolled in the study. Clinical data, pulmonary function tests and biochemical analytes were retrospectively collected. SAA levels were detected by ELISA kit and Krebs von den Lungen 6 (KL-6) were measured by CLEIA method, for sarcoidosis, cHP and IPF patients. Multiple comparison analysis showed significant differences in C reactive protein (CRP), white blood cell count (WBC) and creatinine levels between the three groups. In the logistic regression model, KL-6, CRP and WBC showed areas under curves (AUC) 0.86, for sarcoidosis diagnosis. The logistic regression model KL-6 and SAA showed the best performance with an AUC 0.81 for discriminating IPF than cHP and sarcoidosis. For differential diagnosis of IPF and cHP, KL-6 and SAA were considered in the logistic regression model, showed an AUC 0.79. The combination of serum biomarkers proposed here offers insights into the pathobiology of ILDs. These panels of bioindicators will improve diagnostic accuracy and will be useful in the clinical management of ILDs.

Serum KL-6 concentrations as a novel biomarker of severe COVID-19.

Severe acute respiratory syndrome coronavirus 2-induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen-6 (KL-6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL-6 in patients with coronavirus disease (COVID-19) to verify its potential as a prognostic biomarker of severity. Twenty-two patients (median age [interquartile range] 63 [59-68] years, 16 males) with COVID-19 were enrolled prospectively. Patients were divided into mild-moderate and severe groups, according to respiratory impairment and clinical management. KL-6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut-off value was 119 cells/µL. KL-6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL-6 serum levels and the best cut-off value was 406.5 U/mL. NK cell analysis and assay of KL-6 in serum can help identify severe COVID-19 patients. Increased KL-6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL-6 measurement to evaluate COVID-19 patients' prognosis.