Lung adenocarcinoma and chronic obstructive pulmonary disease (COPD) are pulmonary diseases that share common aetiological factors (tobacco smoking) and probable dysregulated pathways. MicroRNAs (miRNAs) play an essential role in regulating numerous physiological and pathological processes. The purpose of this study was to assess global miRNA expression patterns in patients with COPD and/or adenocarcinoma to elucidate distinct regulatory networks involved in the pathogenesis of these two smoking-related diseases.Expression of 381 miRNAs was quantified by TaqMan Human MicroRNA A Array v2.0 in bronchoalveolar lavage fluid samples from 87 patients classified into four groups: COPD, adenocarcinoma, adenocarcinoma with COPD, and control (neither COPD nor adenocarcinoma). 11 differentially expressed miRNAs were randomly selected for validation in an independent cohort of 40 patients.Distinct miRNA expression profiles were identified and validated for each pathological group, involving 66 differentially expressed miRNAs. Four miRNA clusters (the mir-17-92 cluster and its paralogues, mir-106a-363 and mir-106b-25; and the miR-192-194 cluster) were upregulated in patients with adenocarcinoma and one miRNA cluster (miR-132-212) was upregulated in patients with COPD.These results contribute to unravelling miRNA-controlled networks involved in the pathogenesis of adenocarcinoma and COPD, and provide new tools of potential use as biomarkers for diagnosis and/or therapeutic purposes. @ERSpublications MicroRNA expression profiles in bronchoalveolar lavage fluid enable discrimination of adenocarcinoma from COPD
It was hypothesised that monitoring neutrophil and D-dimer (DD) levels into the pleural fluid, after talc instillation, could predict the outcome of pleurodesis.The current authors investigated a total of 168 patients with malignant pleural effusion, who were treated with talc poudrage. According to the outcome the patients were categorised into one of two groups, either successful or failed pleurodesis. In all cases, pleural fluid neutrophils and DDS were determined on serial measurements at 0, 3, 24 and 48 h after the procedure. The time course of these parameters was assessed in both groups and the time point at which they could better predict the outcome was further explored.Neutrophils rose rapidly after talc poudrage in both groups, reaching a plateau at 24 h, although in successful pleurodesis this response was significantly higher. DD dropped markedly at 24 h in the group with the successful outcome, but it did not show significant changes in the other group. A cut-off value of 61% for neutrophils and 61 mg?L -1 for the DD at 24 h yielded the best prognosis for successful pleurodesis. The current authors conclude that serial measurements of neutrophil and D-dimer values into the pleural fluid after talc poudrage could be used as predictors of the outcome of pleurodesis.
Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.
Ultrasound techniques will stay as valuable tools for pleural effusions. Biomarkers in pleural fluid do not currently provide an acceptable yield for MPE. In subjects with past history of asbestos exposure, some serum or plasma markers (soluble mesothelin, fibulin) might help in selecting cases for close follow-up, to detect mesothelioma early. Needle pleural biopsy is justified only if used with image-techniques (ultrasound or CT) guidance, and thoracoscopy is better for both diagnosis and immediate palliative treatment (pleurodesis). Animal models of MPE and 'spheroids' are promising for research involving both pathophysiology and therapy. Considering the possibility of direct pleural delivery of nanotechnology-developed compounds-fit to both diagnosis and therapy purposes ('theranostics')-MPE and mesothelioma in particular are likely to benefit sooner than later from this exciting perspective.
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