Lutz-Bernhard Jehn

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2)-infection is associated with an extremely variable disease course. When interstitial pneumonia (IP) occurs, it can lead to acute respiratory distress syndrome and death. Serum Krebs von den Lungen-6 (KL-6) is an established marker of IP, but its role as a marker of SARS-CoV-2 pneumonia is debated. This bicentric study included 157 patients with SARS-CoV-2 pneumonia. The WHO Ordinal Scale for Clinical Improvement (0–10 points) was used to classify the clinical course. Serum samples were collected at admission, and on days 3 and 7 of hospitalization. KL-6 was measured by using automated chemiluminescence immunoassay. A total of 68 patients developed a severe SARS-CoV-2 pneumonia, 135 of them required oxygen, and 15 died during hospitalization. The patients requiring non-invasive ventilation, invasive ventilation, or extracorporeal membrane oxygenation had significantly higher serum KL-6 levels at admission. The serum KL-6 levels were tendentially higher in patients who died than in those who survived. Logistic regression identified serum KL-6 at a cut-off of 335 U/mL at admission as a significant predictor of severe SARS-CoV-2 pneumonia outcome. Serum KL-6 seems to be a candidate biomarker for the clinical routine to stratify patients with SARS-CoV-2 pneumonia for the risk of a severe disease outcome or death.

Introduction: PAP is due to accumulation of phospholipids and lipoproteins in the alveoli. WLL is still the treatment of choice. Light microscopy examination of WLL fluid reveals a moderate to high lymphocytosis but lymphocyte subpopulations have not been further characterized at yet. Aims: To investigate T lymphocyte subsets in WLL fluid from patients with PAP. Methods: From the first recovered fluid portion during WLL, samples of 50 mL each were collected and analyzed fresh. Pancoll density-gradient centrifugation was performed to separate mononuclear (MN) cells. MACS^® enrichment was used to separate T lymphocytes from remaining MN cells and acellular particles after adding anti-CD3 microbeads to the MN cell layer. Flow cytometry for T cell immunophenotyping was performed by using a 9-color antibody panel and a FACSAria^™ Fusion cytometer (Becton Dickinson, Germany). Zombie UV^™ fluorescent dye was used to assess cell viability. T lymphocyte counts were expressed as proportion of CD3⁺ viable lymphocyte counts. Results: WLL fluid from 3 consecutive PAP patients (2 M, 1 F, age 44±12) who underwent therapeutic WLL was analyzed. The mean T lymphocyte count was 87±1%. CD4⁺ T cells were the dominant T cell subset across all samples (73±7%), followed by CD8⁺ cytotoxic T cells (19±7%). Th17.1 cells were the most frequent Th cell subset (33±14%), followed by Th1 cells (29±2%), Tregs (17±6%), Th17 cells (4±2%), and Th2 cells (0.7±0.2%). Conclusions: Our study identified different T lymphocyte subsets, mostly related to autoimmunity, in WLL fluid obtained from PAP patients. Flow cytometry may be used to unravel pathogenetic mechanisms of this rare disease.

The development of a progressive phenotype of interstitial lung disease (ILD) is still unpredictable. Whereas tools to predict mortality in ILD exist, scores to predict disease progression are missing. The aim of this study was to investigate whether baseline serum KL-6 as an established marker to assess disease activity in ILD, alone or in combination with clinical variables, could improve stratification of ILD patients according to progression risk at any time. Consecutive patients with fibrotic ILD, followed at our institution between 2008 and 2015, were investigated. Disease progression was defined as relative decline of ≥10% in forced vital capacity (FVC) or ≥15% in diffusing capacity of the lung for carbon monoxide (DLco)% from baseline at any time. Serum KL-6 was measured using an automated immunoassay (Fujirebio Europe, Gent, Belgium). A stepwise logistic regression was performed to select variables to be included in the score. A total of 205 patients (49% idiopathic pulmonary fibrosis (IPF), 51% fibrotic nonspecific interstitial pneumonia (NSIP)) were included, of them 113 (55%) developed disease progression during follow up. Male gender (G) and serum KL-6 strata (K) were significant predictors of progression at regression analysis and were included in the GK score. A threshold of 2 GK score points was best for discriminating patients at high risk versus low risk to develop disease progression at any time. Serum KL-6 concentration, alone or combined in a simple score with gender, allows an effective stratification of ILD patients for risk of disease progression at any time.

Introduction: ICIs are emerging treatment options for several types of cancer. IP occurs under ICI treatment with variable incidence and different clinical, radiologic and pathologic features. BALF cytology is an established diagnostic tool in IP. Objectives: To investigate BALF findings in patients with suspected ICI-associated IP (ICI-IP). Methods: Based on medical history, clinical and HRCT findings, consecutive patients with suspected ICI-IP underwent bronchoscopy with BAL. BALF cytology was performed to confirm diagnosis. In patients with a BALF lymphocytosis >13%, immunocytochemistry staining for lymphocyte subpopulations was performed. Results: 24 patients (54% male, 46% female, age 54±12 years) with ICI-IP, 75% of whom had melanoma, 17% NSCLC, 4% SCLC, and 4% breast cancer, were included. Two-thirds of patients received anti-PD-1/PD-L1 monoclonal antibody (mAb) monotherapy, while one-third of patients was treated with anti-PD-1/anti-CTLA-4 mAb combination therapy. The most frequent HRCT pattern was sarcoidosis-like (45%), followed by organizing pneumonia (38%) and NSIP/ground glass opacities (GGO) (17%). Mean lymphocyte count was 44±24% with T-cells being the most frequent lymphocyte subpopulation (89±3%). Patients with sarcoidosis-like pattern had the highest T-lymphocyte count vs those with other patterns (91±2 vs 86±2%, p=0.017). A tendency for CD4/CD8 ratio was seen (2,4±0,6 vs 1,5±0,7, p=0.06). Conclusions: BALF lymphocytosis with predominance of T-cells seems to be the most prevalent BALF differential cell count pattern in ICI-IP. BALF cytology is a promising tool to confirm diagnosis of ICI-IP.