Academic literature on the topic 'Krebs von den Lungen 6'

Disease progression (DP) in interstitial lung disease (ILD) is variable and difficult to predict. In previous reports, serum Krebs von den Lungen-6 (KL-6) was suggested to be useful in diagnosing and predicting survival in ILD. The aim of our study was to investigate the usefulness of serum KL-6 as a predictor of DP in ILD. Clinical data of 199 patients with ILD (idiopathic pulmonary fibrosis: 22.8%) were prospectively collected and serum KL-6 levels were measured. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, acute exacerbation, or death during follow-up. The median follow-up period was 11.1 months. The mean age of the subjects was 62.2 years, and 59.8% were male. DP occurred in 21.6% of patients. The progressed group showed lower FVC, lower diffusing capacity for carbon monoxide, lower the minimum oxygen saturation during the 6-minute walk test, higher fibrosis scores on high-resolution computed tomography, and higher KL-6 levels (826.3 vs. 629.0 U/mL; p < 0.001) than those of the non-progressed group. In receiver operating characteristic curve analysis, serum KL-6 levels were a significant predictor of DP in ILD (area under the curve = 0.629, p = 0.009, and the optimal cut-off level was 811 U/mL). In multivariable Cox analysis, high serum KL-6 levels (≥ 800 U/mL) were only independently associated with DP in ILD (HR 2.689, 95% CI 1.445–5.004, P = 0.002). Serum KL-6 levels might be useful to predict DP in patients with ILD.

Presepsin is an early indicator of infection, and Krebs von den Lungen 6 (KL-6) and Surfactant Protein A (SP-A) are related to the pathogenesis of pulmonary infection and fibrosis. This study aimed to establish reference intervals (RIs) of presepsin, KL-6, and SP-A levels and to evaluate the possible influence of neonatal and maternal factors on presepsin, KL-6, and SP-A levels in umbilical cord blood (UCB). Among a total of 613 UCB samples, the outliers were removed. The RIs for presepsin, KL-6, and SP-A levels were defined using non-parametric percentile methods according to the Clinical and Laboratory Standards Institute guidelines (EP28-A3C). These levels were analyzed according to neonatal and maternal factors: neonatal sex, gestational age (GA), birth weight (BW), Apgar score, delivery mode, the presence of premature rupture of membranes (PROM), gestational diabetes mellitus (GDM), and pre-eclampsia. Presepsin, KL-6, and SP-A levels showed non-parametric distributions and left-skewed histograms. The RIs of presepsin, KL-6, and SP-A levels were 64.9–428.3 pg/mL, 43.0–172.0 U/mL, and 2.1–36.1 ng/mL, respectively. Presepsin, KL-6, and SP-A levels did not show significant differences according to sex, GA, BW, Apgar score, delivery mode, PROM, GDM, and pre-eclampsia. The median level and 97.5th centile RI of KL-6 showed a slight increase with increased GA. We established RIs for presepsin, KL-6, and SP-A levels in large-scaled UCB samples. Further investigation would be needed to determine the clinical significance.

COVID-19 encompasses a broad spectrum of clinical conditions caused by SARS-CoV-2 infection. More severe cases experience acute respiratory and/or multiorgan failure. KL-6 is a glycoprotein expressed mainly from type II alveolar cells with pro-fibrotic properties. Serum KL-6 concentrations have been found in patients with COVID-19. However, the relevance of KL-6 in patients with severe and critical COVID-19 has not been fully elucidated. Methods: Retrospective data from consecutive severe to critical COVID-19 patients were collected at UOC Clinica Pnuemologica “Vanvitelli”, A.O. dei Colli, Naples, Italy. The study included patients with a positive rhinopharyngeal swab for SARS-CoV-2 RNA with severe or critical COVID-19. Results: Among 87 patients, 24 had poor outcomes. The median KL-6 value in survivors was significantly lower when compared with dead or intubated patients (530 U/mL versus 1069 U/mL p < 0.001). KL-6 was correlated with body mass index (BMI) (r: 0.279, p: 0.009), lung ultrasound score (LUS) (r: 0.429, p < 0.001), Chung Score (r: 0.390, p < 0.001). KL-6 was associated with the risk of death or oro-tracheal intubation (IOT) after adjusting for gender, BMI, Charlson Index, Chung Score, and PaO2/FIO2 (OR 1.003 95% CI 1.001–1.004, p < 0.001). Serum KL-6 value of 968 has a sensitivity of 79.2%, specificity of 87.1%, PPV 70.4%, NPV 91.5%, AUC: O.85 for risk of death or IOT. Conclusions: The presented research highlights the relevance of serum KL-6 in severe to critical COVID-19 patients in predicting the risk of death or IOT.

Sarcoidosis is a multi-system granulomatous disease of unknown etiology characterized by the infiltration of various organs by non-necrotizing granulomas. Disease morbidity is strictly related to the mechanisms that govern granulomatous inflammation, including the release of pro-inflammatory cytokines (mainly IFNγ, IL-2 and TNFα) by immune cells. An important and debated role in sarcoidosis diagnosis is played by serum biomarkers such as angiotensin-converting enzyme (ACE), lysozyme (LSZ), chitotriosidase (CTO) and Krebs von den lungen-6 (KL-6). Neurosarcoidosis is namely the involvement of central and/or peripheral nervous system by sarcoid granulomas. Symptomatic nervous system involvement is reported in 3-16% of patients with sarcoidosis, but post-mortem studies report higher prevalence. Moreover, neurosarcoidosis can present isolated (with no other organ involvement) in about 10% of cases and neurologic manifestations can be the presenting syndrome of sarcoidosis in more than 50% of cases. Finally, neurosarcoidosis can virtually involve every part of CNS and PNS or skeletal muscle with polymorphic clinical presentations. Three main sets of diagnostic criteria have been proposed in the literature to define neurosarcoidosis, all attributing the highest grade of diagnostic certainty to cases with CNS or PNS/muscle pathology demonstrating sarcoid granulomas. Moreover, brain and spinal cord MRI and cerebrospinal fluid (CSF) analysis are the main diagnostic tools taken into account by the aforementioned criteria, but the specificity of their finding is often poor. Therefore, CNS and neuromuscular presentations of sarcoidosis represent a diagnostic challenge for neurologists. Thanks to the cooperation with the Sarcoidosis Regional Referral Center, managed by Respiratory Diseases and Lung Transplantation Unit of the University Hospital of Siena, we were able to evaluate and follow a large number of sarcoidosis patients with suspected or confirmed neurologic involvement. Therefore, we decided to critically analyze the data derived from consultant activity and to perform focused clinico-pathologic studies, in order to gain more insight on the disease and its complications, and to propose new diagnostic tools. Specifically, our study was developed in three main parts: (i) A retrospective cohort study on a population of CNS neurosarcoidosis patients, performed with the aims of identifying recurrent or peculiar clinical patterns and evaluating the possible use of established diagnostic criteria in clinical practice; (ii) A controlled study on serum and CSF biomarkers of CNS neurosarcoidosis including KL-6 (a mucin-like glycoprotein secreted by type II pneumocytes, increased in serum and BAL of patients with ILD and sarcoidosis), which was never systematically investigated in this localization of the disease; (iii) A retrospective/prospective cohort study on sarcoidosis patients undergoing muscular biopsy, in order to define every clinico-pathological presentation and investigate, for the first time, the role of TNFα in sarcoid myopathy. (i). From the retrospective review of the charts from Sarcoidosis Regional Referral Center we identified 22 patients who fulfilled criteria for possible neurosarcoidosis or higher in at least one of the proposed diagnostic criteria. Neurologic symptoms were the presenting feature of sarcoidosis in 59,1% of patients and pathological confirmation of sarcoidosis was available in 17 of them (in one patient it was obtained in CNS biopsy, allowing diagnosis of defined neurosarcoidosis). Lesions involved brain parenchyma, meninges, spinal cord, cranial nerves, hypothalamus/hypophysis and intracranial arteries, and 8 patients had multiple localizations. Most useful investigations for the diagnosis were MRI (positive in 20 patients and showing post-contrast enhancement in 16) and CSF analysis (showing inflammatory findings in 11 out of 13 patients), while classic serum biomarkers such as ACE and lysozyme were increased only in a small proportion of patients; instead, serum chitotriosidase (CTO) was significantly increased in the majority of the tested patients. (ii). From this cohort, we retrospectively enrolled patients for whom samples of serum and CSF had been simultaneously collected and stored at -20°C and were available for further analysis. We enrolled 9 patients with a chronic inflammatory disease, namely multiple sclerosis (MS), and 9 patients with a chronic neurodegenerative disease, namely amyotrophic lateral sclerosis (ALS), as control groups. Serum samples from 9 healthy controls were also collected for KL-6 assay. The four groups were matched for sex and age. Measurable CSF concentrations of KL-6 were detected in 7/9 NS patients but in no ALS or MS patients. In NS patients, CSF concentrations of KL-6 were directly correlated with CSF albumin index, albumin, IgG and total protein concentrations. As KL-6 is a high molecular weight (200 kDa) protein produced outside the central nervous system, it is unable to diffuse in CSF when blood-brain barrier is intact. Instead, when the barrier is damaged as in NS, KL-6 could cross it. This interpretation is confirmed by the direct correlation between KL-6 concentration in CSF and albumin index. Our finding of KL-6 in CSF of NS patients but not in ALS and MS patients suggests that this protein may discriminate this specific phenotype of sarcoidosis with 81,2% sensitivity and 100% specificity. (iii). Regarding skeletal muscle involvement, we performed a retrospective/prospective cohort study, enrolling 29 sarcoidosis patient who underwent muscular biopsy due to suspect muscular involvement. General myopathic changes, with different degrees of inflammation, were detected in almost all patients, while granulomas were detected only in 4/29 patients. Inflammatory changes ranged from massive endomysial infiltrates to minimal perivasal deposits. Upregulation of tissue immunity markers was observed. Electron microscopy confirmed endothelial involvement in most cases. Associated neurogenic changes were also detected in a subgroup. Our findings support the hypothesis of symptomatic muscle involvement in sarcoidosis besides granulomatous sarcoid myositis. Local and circulating cytokines result crucial in Th1 inflammatory response of sarcoidosis and increased circulating TNFα is considered a possible cause of sarcoidosis associated small fiber neuropathy. Therefore, in order to investigate the pathophysiology of non-granulomatous sarcoid related myositic changes and of the common muscle pain complaint in these patients, we investigated by immunocytochemical localization tissue expression of TNFα and its receptors (TNFR1-2) in 9 patients from our cohort and in healthy controls. An endothelial increase and sarcolemmal/sarcoplasmic deposition of TNFα/TNFR1-2 was detected in all cases, with or without granulomas, including samples with minimal pathological or immunohistologic changes. Our findings suggest that TNFα/TNFR1-2 may represent a sensitive diagnostic marker, especially in milder presentations of sarcoid myopathy, and underline the relevance of capillary endothelium as the first site of the pathological process.

Numerous published papers are investigating the utility of biomarkers in Idiopathic Pulmonary Fibrosis (IPF) diagnosis, treatment, and outcome prediction. This chapter will summarize our current knowledge about biomarkers associated with alveolar epithelial cell damage and dysfunction (Krebs von den Lungen, surfactant proteins, the mucin MUC5B, CA 15-3, CA 125, CA 19-9, defensins, Clara cell protein (CC16), telomere shortening), biomarkers associated with fibrogenesis, fibroproliferation and extracellular matrix (ECM) remodeling (MMPs and their inhibitors, osteopontin, periostin, insulin-like growth factors, fibulin-1, heat shock protein 47, lysyl oxidase-like 2, circulating fibroblasts, extracellular matrix neoepitopes) and biomarkers related to immune dysfunction and inflammation (C-C chemokine ligand-18, C-C chemokine 2, YKL-40, C-X-C motif chemokine 13, S100A4, S100A8/9, S100A12, autoantibodies to heat shock protein 72, toll-like receptor 3, soluble receptor for advanced glycosylated end products, endothelial damage (vascular endothelial growth factor, interleukin 8, endothelin 1). The future directions in incorporating IPF biomarkers into clinical practice will be reviewed.

Introdução: A pneumocystis jirovecii (PDC) é a causa mais prevalente de doença pulmonar oportunista em imunodeprimidos pelo HIV. Devido ao seu tropismo e especificidade para o pulmão humano, ela resulta em pneumonia intersticial grave, com hipoxemia e insuficiência respiratória progressiva. É derivada de um fungo “atípico” por não conter ergosterol na membrana celular, não sendo susceptível à ação da maioria dos antifúngicos, como é o caso da anfotericina B. A probabilidade de PPC está significativamente aumentada quando a contagem de CD4 cai abaixo de 200 células/µL ou é menor que 20% dos linfócitos circulantes. Porém quando se trata do diagnostico, ele depende da obtenção de espécimes respiratórios obtidos de forma invasiva e da visualização do microrganismo mediante técnicas complexas, tornando-se necessário explorar novas abordagens. Objetivo: Abordar possíveis métodos diagnósticos práticos e menos invasivos para detecção da patologia. Metodologia: Realizou-se uma revisão de literatura das bases de dados PubMed e Google Scholar utilizando os descritores: pneumocystis jirovecii, microbiota pulmonar e marcadores diagnósticos de PPC. Foram selecionados artigos publicados a partir de 2008 para base deste estudo. Resultados: O diagnóstico de certeza da patologia depende da identificação do fungo em secreções ou em tecido pulmonar. Devido a pobreza de escarro espontâneo, duas técnicas são realizadas: a indução de escarro e o lavado broncoalveolar. A biópsia transbrônquica e a biópsia por toracotomia são as alternativas secundárias. Para uma abordagem mais rápida e pratica, estuda-se a utilização de amostras biológicas, como a pesquisa de IgA anti-P. jirovecii em saliva. Parece ser promissora, já que os títulos médios de anticorpos IgA detectados na saliva de doentes com infeção foi superior ao detectado nos doentes sem infeção. Outros estudos sugerem que Krebs von den Lungen-6 (KL-6), e S-adenosilmetionina (SAM), poderão ser utilizados como indicadores sensíveis para o diagnóstico da PPC no futuro. Conclusão: Diante de uma suspeita de PPC, o médico se encontra com 2 alternativas: iniciar tratamento de forma empírica ou proceder com uma investigação diagnóstica. Assim, estudos abrangendo métodos mais práticos e rápidos de diagnostico seriam um avanço considerável para os danos causados por métodos invasivos a um paciente que já se encontra imunossuprimido.