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.

Wojciech J. Piotrowski et al., Diagnosis and treatment of idiopathic pulmonary fibrosis 43 www.journals.viamedica.pl

The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls.

The association between venous thromboembolism (VTE) and sarcoidosis has been reported recently, nevertheless the true incidence of co-incident sarcoidosis and VTE is unknown. Sarcoidosis as a chronic disease of immune dysregulation might be associated with an increased risk of VTE. The mechanisms responsible for VTE development are not clear and may be influenced by several factors: activity of inflammation, clinical characteristics of sarcoidosis and comorbidities. Pulmonary embolism (PE) as a potentially fatal condition should be considered in all of the patients with sarcoidosis in whom worsening of the respiratory status is diagnosed. A high plasma D-dimers (DD) level may be suggestive of VTE, nevertheless elevated plasma DD should be interpreted with caution, in the context of the active inflammatory process. If sarcoidosis appears to be one of risk factors for VTE development, further investigations are needed to define the pro-thrombotic phenotype of this disease.

MTX as a single agent in the treatment of sarcoidosis has proved to be a safe and effective steroid alternative. Selected patients with chronic pulmonary sarcoidosis experience definite PFT improvements after MTX treatment. There is need to search for predictors of MTX treatment effectiveness.