Increased KL-6 levels in moderate to severe COVID-19 infection.

peer reviewed[en] BACKGROUND: The global coronavirus disease 2019 (COVID-19) has presented significant challenges and created concerns worldwide. Besides, patients who have experienced a SARS-CoV-2 infection could present post-viral complications that can ultimately lead to pulmonary fibrosis. Serum levels of Krebs von den Lungen 6 (KL-6), high molecular weight human MUC1 mucin, are increased in the most patients with various interstitial lung damage. Since its production is raised during epithelial damages, KL-6 could be a helpful non-invasive marker to monitor COVID-19 infection and predict post-infection sequelae. METHODS: We retrospectively evaluated KL-6 levels of 222 COVID-19 infected patients and 70 healthy control. Serum KL-6, fibrinogen, lactate dehydrogenase (LDH), platelet-lymphocytes ratio (PLR) levels and other biological parameters were analyzed. This retrospective study also characterized the relationships between serum KL-6 levels and pulmonary function variables. RESULTS: Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects (470 U/ml vs 254 U/ml, P 453.5 U/ml was associated with COVID-19 (AUC = 0.8415, P < 0.0001). KL-6 level was positively correlated with other indicators of disease severity such as fibrinogen level (r = 0.1475, P = 0.0287), LDH level (r = 0,31, P = 0,004) and PLR level (r = 0.23, P = 0.0005). However, KL-6 levels were not correlated with pulmonary function tests (r = 0.04, P = 0.69). CONCLUSIONS: KL-6 expression was correlated with several disease severity indicators. However, the association between mortality and long-term follow-up outcomes needs further investigation. More extensive trials are required to prove that KL-6 could be a marker of disease severity in COVID-19 infection

Diagnosis of Idiopathic Pulmonary Fibrosis in High-Resolution Computed Tomography Scans Using a Combination of Handcrafted Radiomics and Deep Learning

peer reviewedPurpose: To develop handcrafted radiomics (HCR) and deep learning (DL) based automated diagnostic tools that can differentiate between idiopathic pulmonary fibrosis (IPF) and non-IPF interstitial lung diseases (ILDs) in patients using high-resolution computed tomography (HRCT) scans. Material and Methods: In this retrospective study, 474 HRCT scans were included (mean age, 64.10 years ± 9.57 [SD]). Five-fold cross-validation was performed on 365 HRCT scans. Furthermore, an external dataset comprising 109 patients was used as a test set. An HCR model, a DL model, and an ensemble of HCR and DL model were developed. A virtual in-silico trial was conducted with two radiologists and one pulmonologist on the same external test set for performance comparison. The performance was compared using DeLong method and McNemar test. Shapley Additive exPlanations (SHAP) plots and Grad-CAM heatmaps were used for the post-hoc interpretability of HCR and DL models, respectively. Results: In five-fold cross-validation, the HCR model, DL model, and the ensemble of HCR and DL models achieved accuracies of 76.2 ± 6.8, 77.9 ± 4.6, and 85.2 ± 2.7%, respectively. For the diagnosis of IPF and non-IPF ILDs on the external test set, the HCR, DL, and the ensemble of HCR and DL models achieved accuracies of 76.1, 77.9, and 85.3%, respectively. The ensemble model outperformed the diagnostic performance of clinicians who achieved a mean accuracy of 66.3 ± 6.7% (p &lt; 0.05) during the in-silico trial. The area under the receiver operating characteristic curve (AUC) for the ensemble model on the test set was 0.917 which was significantly higher than the HCR model (0.817, p = 0.02) and the DL model (0.823, p = 0.005). The agreement between HCR and DL models was 61.4%, and the accuracy and specificity for the predictions when both the models agree were 93 and 97%, respectively. SHAP analysis showed the texture features as the most important features for IPF diagnosis and Grad-CAM showed that the model focused on the clinically relevant part of the image. Conclusion: Deep learning and HCR models can complement each other and serve as useful clinical aids for the diagnosis of IPF and non-IPF ILDs

Heterogeneity in the use of biologics for severe asthma in Europe: a SHARP ERS study

International audienceIntroduction Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown. Materials and methods The ERS SHARP clinical research collaboration conducted a 3-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on 7 endpoints: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics, and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies. Results Availability of biologics varied between countries, with 17/28 countries having all 5 existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, FEV 1 was used in 46%. Blood eosinophils were an inclusion criterion in all countries for IL5- and IL4/IL13- targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191/263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity. Conclusion Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation

Heterogeneity in the use of biologics for severe asthma in Europe: a SHARP ERS study

Introduction Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown. Materials and methods The European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies. Results Availability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity. Conclusion Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation