Current Issue : July - September Volume : 2012 Issue Number : 3 Articles : 8 Articles
The pathologic diagnosis of lung cancer historically has relied primarily on morphologic features of tumors in histologic sections.\r\nWith the emergence of new targeted therapies, the pathologist is called upon increasingly to provide not only accurate typing of\r\nlung cancers, but also to provide prognostic and predictive information, based on a growing number of ancillary tests, that may\r\nhave significant impact on patient management. This review provides an overview of ancillary tests currently used in the pathologic\r\ndiagnosis of lung cancer, with a focus on immunohistochemistry and molecular diagnostics....
Because pharmacologic treatment of patients with the established Acute Respiratory Distress Syndrome (ARDS) has not been successful, the emphasis on discovering biomarkers that predict ARDS development in at-risk individuals is being rekindled so that ways of preventing ARDS can be advanced and tested. However, the low incidence of ARDS in at-risk individuals, the variable time between becoming at risk and developing ARDS, and the varying incidence of ARDS following different predisposing conditions makes finding clinically-useful ARDS predicting biomarkers challenging. Ideally, biomarkers reflecting ARDS development will be obtainable non-invasively and repeatedly and provide sensitive, specific, accurate and real time results. Biomarkers will also likely need to mirror key events in the pathogenesis of ARDS and meaningfully reflect the effect of therapies on ARDS development. At the moment, analysis of potential biomarkers in breath samples offers an intriguing way of addressing these objectives. A number of ARDS implicated molecules (e.g. hydrogen peroxide, nitric oxide, lipid peroxidation byproducts, cytokeratins) are measurable in breath or breath condensates from ARDS patients. Moreover, powerful new approaches (e.g. proton transfer reaction mass spectrometry, carbon nanotubes analyses using aptamer based multiplexed proteomic technology and cavity-enhanced frequency comb spectroscopy) are emerging that may provide biomarkers that could generate insight regarding the responsible mechanisms for ARDS, monitor ARDS development, enable testing of new ARDS interventions, and guide treating and preventing ARDS....
Dysregulation of microRNAs (miRNAs), particularly their downregulation, has been widely shown to be associated with the\r\ndevelopment of lung cancer. Downregulation of miRNAs leads to the overactivation of their oncogene targets, while upregulation\r\nof some miRNAs leads to inhibition of important tumor suppressors. Research has implicated cigarette smoke in miRNA\r\ndysregulation, leading to carcinogenesis. Cigarette smoke may lead to genetic or epigenetic damage to miRNAs, many of which\r\nmap to fragile sites and some of which contain single nucleotide polymorphisms. Cigarette smoke may also cause dysregulation by\r\naffecting regulatory mechanisms controlling miRNA expression. Researchers have shown a correlation between smoke-exposureinduced\r\ndysregulation of miRNAs and age. Furthermore, dysregulation seems to be associated with intensity and duration\r\nof smoke exposure and duration of cessation. Longer exposure at a threshold level is needed for irreversibility of changes in\r\nexpression. Better understanding of miRNA dysregulation may allow for improved biomonitoring and treatment regimens for\r\nlung cancer....
Aims: Effectiveness of combination of pulmonary rehabilitation (PR) and neuromuscular electrical stimulation (NMPR) in severe chronic obstructive pulmonary disease (COPD) is well established. We verified the effects of NMPR compared with pulmonary rehabilitation and sham stimulation (SSPR) in patients with moderately impaired COPD.\r\n Methods: Quadriceps strength (sit-to-stand test: STST) and exercise capacity (6 minute walking test: 6MWT) were considered primary outcomes. Lung function, dyspnoea (modified Medical Research Council: mMRC) and quality of life (St. Georgeââ?¬â?¢s Respiratory Questionnaire: SGRQ) secondary outcomes.\r\n Results: 83 stable patients in stage II, moderate COPD (23 female; mean age, 61.7 Ã?± 9.1 years; FEV1 59.8 Ã?± 7.3% of predicted) were enrolled. Quadriceps strength was enhanced by SSPR (STST + 7Ã?±1.7 repetitions; p=0.001); NMPR further increased strength (+10Ã?±1.6 repetitions; p=0.001) with a significant difference (p=0.05) between the treatments. SSPR significantly increased exercise capacity (6MWD + 85.3Ã?±11.5 m; p=0.01); NMPR further increased the distance walked (6MWD +146.4Ã?±32.7 m; p=0.01) with a significant difference (p=0.05) between the treatments. None of the two treatments influenced lung function. Quality of life score (SGRQ ââ?¬â?? 8.3Ã?±2.1; p=0.01) and dyspnoea score (mMRC- 0.7Ã?±0.18; p=0.01) decreased after SSPR suggesting a positive effect. NMPR did not further improve the score.\r\n Conclusions: This study confirms that PR is able to ameliorate quadriceps strength, exercise capacity, quality of life and dyspnoea in moderately impaired COPD patients. NMPR may further improve quadriceps strength and exercise capacity with respect to PR alone....
Combined pulmonary fibrosis and emphysema (CPFE) is a recently defined syndrome, in which centrilobular and/or paraseptal\r\nemphysemas in upper lung zones coexist with pulmonary fibrosis in lower lobes in individuals. These patients have a characteristic\r\nlung function profile, with unexpected subnormal dynamic and static lung volumes, contrasting with a significant reduction of\r\ncarbon monoxide transfer (DLco) and exercise hypoxemia. Pulmonary hypertension is highly prevalent in CPFE and is the leading\r\ndeterminant of death. Tobacco smoking has been proposed as the main factor in its etiology, though the pathophysiology and\r\nits natural history remain to be determined. High-resolution computed axial tomography is the mandatory tool to confirm the\r\ndiagnosis. Currently, there is no consensus about its treatment since those published to date on this issue are limited to wellcharacterised\r\nseries of cases; hence, a better understanding of this entity may help in the development of future therapeutic\r\napproaches....
Background: Thoracic surgery mandates usually a one-lung ventilation (OLV) strategy with the collapse of the\r\noperated lung and ventilation of the non-operated lung. These procedures trigger a substantial inflammatory\r\nresponse. The aim of this study was to analyze the cytokine and chemokine reaction in both lungs, pleural space\r\nand blood in patients undergoing lung resection with OLV with special interest in the chemokine growthregulated\r\npeptide alpha (GROa) which is the human equivalent to the rat cytokine-induced neutrophil\r\nchemoattractant-1 (CINC-1).\r\nMethods: Broncho-alveolar lavage (BAL) fluid of both the collapsed, operated and the ventilated, non-operated\r\nlung, respectively, pleural space drainage fluid and blood was collected and the concentrations of interleukin (IL)-6,\r\nIL-1RA and GROa were determined with enzyme-linked immunosorbent assays in 15 patients.\r\nResults: Substantial inter-individual differences in the BAL fluid between patients in cytokine and chemokine levels\r\noccurred. In the pleural fluid and the blood these inter-individual differences were less pronounced. Both sides of the\r\nlung were affected and showed a significant increase in IL-6 and IL-1RA concentrations over time but not in GROa\r\nconcentrations. Except for IL-6, which increased more in the collapsed, operated lung, no difference between the\r\ncollapsed, operated and the ventilated, non-operated lung occurred. In the blood, IL-6 and IL-1RA increased early,\r\nalready at the end of surgery. GROa was not detectable. In the pleural fluid, both cytokine and chemokine\r\nconcentrations increased by day one. The increase was significantly higher in the pleural fluid compared to the blood.\r\nConclusion: The inflammatory response of cytokines affects both the collapsed, operated and the ventilated, nonoperated\r\nlungs. The difference in extent of response underlines the complexity of the inflammatory processes during\r\nOLV. In contrast to the cytokines, the chemokine GROa concentrations did not react in the BAL fluid or in the blood.\r\nThis indicates that GROa might not be useful as marker for the inflammatory reaction in complex surgical procedures....
Purpose: Incidentally discovered pulmonary nodules on computed tomography are common. Executing\r\nappropriate follow-up is challenging. The purpose of this study was to assess the impact of a standardized template\r\nof follow-up recommendations in radiology interpretation reports and an electronic messaging system on the rate of\r\nradiographic follow-up of indeterminate pulmonary nodules identified on computed tomography.\r\nMaterials and methods: This retrospective study examined rates of appropriate follow-up, as defined by the\r\nFleischner Society guidelines, of incidental pulmonary nodules over a seven-month period both before (17 patients;\r\nmean age 62.7 years) and after (72 patients, mean age 61.6 years) the commencement of the quality improvement\r\ninitiatives. Further analysis by risk group, patient and nodule characteristics, notification type and location of imaging\r\nrequest were performed.\r\nResults: There was a trend towards improved time-appropriate follow-up from 35.3% (6/17) to 56.9% (49/72)\r\n[p=0.18]. The largest change was noted in high-risk patients with an improvement from 11.1% (1/9) appropriate follow-\r\nup to 51.4% (18/35) [p=0.06] following the interventions. The largest improvement in on-time follow-up imaging was a\r\nreduction in premature imaging, which decreased from 17.6% (3/17) to 6.9% (5/72) [p=0.18]. Rates of on-time follow-\r\nup after the interventions were similar irrespective of patient age, nodule size or origin of initial imaging request.\r\nConclusions: Ensuring use of a rigorous approach to indeterminate pulmonary nodule reporting reporting that\r\nincludes standardized follow-up recommendations may improve rates of appropriate follow-up....
Background. Recurrent bacterial infections play a key role in the pathogenesis of bronchiectasis, but conventional microbiologic\r\nmethods may fail to identify pathogens in many cases. We characterized and compared the pulmonary bacterial communities\r\nof cystic fibrosis (CF) and non-CF bronchiectasis patients using a culture-independent molecular approach. Methods. Bacterial\r\n16S rRNA gene libraries were constructed from lung tissue of 10 non-CF bronchiectasis and 21 CF patients, followed by DNA\r\nsequencing of isolates from each library. Community characteristics were analyzed and compared between the two groups. Results.\r\nA wide range of bacterial diversity was detected in both groups, with between 1 and 21 bacterial taxa found in each patient.\r\nPseudomonas was the most common genus in both groups, comprising 49% of sequences detected and dominating numerically in\r\n13 patients. Although Pseudomonas appeared to be dominant more often in CF patients than in non-CF patients, analysis of entire\r\nbacterial communities did not identify significant differences between these two groups. Conclusions. Our data indicate significant\r\ndiversity in the pulmonary bacterial community of both CF and non-CF bronchiectasis patients and suggest that this community\r\nis similar in surgically resected lungs of CF and non-CF bronchiectasis patients....
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