Background:The analysis of plasma cell-free DNA (cfDNA) is expected to provide useful biomarkers for early diagnosis of non-small-cell lung cancer (NSCLC). However, it remains unclear whether the intense release of cfDNA into the bloodstream of NSCLC patients results from malignancy or chronic inflammatory response. Consequently, the current diagnostic utility of plasma cfDNA quantification has not been thoroughly validated in subjects with chronic respiratory inflammation. Here we assess the effect of chronic respiratory inflammation on plasma cfDNA levels and evaluate the potential clinical value of this phenomenon as an early lung cancer diagnostic tool.Methods:We measured plasma cfDNA concentrations in 50 resectable NSCLC patients, 101 patients with chronic respiratory inflammation (chronic obstructive pulmonary disease, sarcoidosis, or asthma) and 40 healthy volunteers using real-time PCR.Results:We found significantly higher plasma cfDNA levels in NSCLC patients than in subjects with chronic respiratory inflammation and healthy individuals (P<0.0001). There were no significant differences in plasma cfDNA levels between patients with chronic respiratory inflammation and healthy volunteers. The cutoff point of >2.8 ng ml−1 provided 90% sensitivity and 80.5% specificity in discriminating NSCLC from healthy individuals (area under the curve (AUC)=0.90). The receiver-operating characteristics curve distinguishing NSCLC patients from subjects with chronic respiratory inflammation indicated 56% sensitivity and 91% specificity at the >5.25-ng ml−1 cutoff (AUC=0.76).Conclusions:We demonstrated that elevated plasma cfDNA levels in NSCLC resulted primarily from tumour development rather than inflammatory response, raising the potential clinical implications for lung cancer screening and early diagnosis. Further research is necessary to better characterise and identify factors and processes regulating cfDNA levels in the blood under normal and pathological conditions.

Patients with defective plasminogen activator inhibitor protein (PAI-1) or with PAI-1 deficiency can experience hemorrhage as a result of a hyperfibrinolysis. In these patients, a normal thrombus forms, but endogenous lysis is unchecked as tissue plasminogen activator is unopposed. Treatment includes anti-fibrinolytic agents, including oral tranexamic acid. Another treatment option is the administration of PAI-1, but this serpin rapidly inactivates itself. We have developed a mutant plasminogen activator inhibitor with a very long half life (VLHL PAI-1, t1/2>700 h). Here we investigate VLHL PAI-1 effects in the blood of PAI-1 deficient mice, as a model of human disease. Using a thrombelastograph, we found that blood clots of PAI-1 knockout mice were lysed much more quickly than wild type mice. Additionally, blood clots had less shear elastic modulus strength than clots of normal animals. VLHL PAI-1 treatment of PAI-1 deficient mice extended or prevented thrombus lysis and increased clot strength in a concentration dependent fashion. These two parameters determine the extent of thrombus growth and regression; thus, further testing is anticipated to confirm the effectiveness of plasminogen activator inhibitor with a very long half life in an in vivo model and we hope that this protein can be effective in human PAI-1 deficiency disorder.

The alpha-1 antitrypsin deficiency (AATD) targeted screening program, together with the National Registry, were established in Poland in 2010 soon after the AATD diagnostics became available. Between 2010 and 2014 a total of 2525 samples were collected from respiratory patients countrywide; 55 patients with severe AAT deficiency or rare mutations were identified and registered, including 36 PiZZ subjects (65%). The majority of AATD patients were diagnosed with COPD (40%) or emphysema (7%), but also with bronchial asthma (16%) and bronchiectasis (13%). Therefore, the registry has proved instrumental in setting-up the AATD-dedicated network of respiratory medical centres in Poland. Since augmentation therapy is not reimbursed in our country, the smoking cessation guidance, optimal pharmacotherapy of respiratory symptoms as well the early detection, and effective treatment of exacerbations is absolutely essential.

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IntroductIon It is estimated that in about 1% of all liver transplant candidates liver cirrhosis is caused by hereditary homozygous α 1 -antitrypsin (AAT) deficiency.objectIves The aim of the study was to evaluate the role of heterozygous AAT deficiency in the development of liver cirrhosis leading to liver transplantation. PAtIents And methodsIn the years 2009-2011, we conducted a prospective study of 304 consecutive patients (men, 57%) scheduled for orthotopic liver transplantation. AAT phenotyping and the clinical assessment of hepatic and cardiopulmonary functions were performed in all subjects.