Ana Montes-Worboys

Mechanisms of pleurodesis.

Pleurodesis aims to obliterate the pleural space by producing extensive adhesion of the visceral and parietal pleura, in order to control relapse of either pleural effusions (mostly malignant) or pneumothorax. A tight and complete apposition between the two pleural layers is a necessary condition to obtain a successful pleurodesis, but – besides this mechanical aspect – there are many biological mechanisms that appear to be common to most of the sclerosing agents currently used. Following intrapleural application of the sclerosing agent, diffuse inflammation, pleural coagulation-fibrinolysis imbalance (favoring the formation of fibrin adhesions), recruitment and subsequent proliferation of fibroblasts, and collagen production are findings in the pleural space. The pleural mesothelial lining is the primary target for the sclerosant and plays a pivotal role in the whole pleurodesis process, including the release of several mediators like interleukin-8, transforming growth factor-β and basic fibroblast growth factor. When the tumor burden is high, normal mesothelial cells are scarce, and consequently the response to the sclerosing agent is decreased, leading to failure of pleurodesis. Also, the type of tumor in the pleural cavity may also affect the outcome of pleurodesis (diffuse malignant mesothelioma and metastatic lung carcinomas have a poorer response). There is general agreement that talc obtains the best results, and there are also preliminary experimental studies suggesting that it can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of the malignant pleural effusion. There is concern about complications (possibly associated with talc but other agents as well) related to systemic inflammation and possible activation of the coagulation cascade. In order to prevent extrapleural talc dissemination, large-particle talc is recommended. Although it could – to some degree – interfere with the mechanisms leading to pleurodesis and a carefully balanced clinical decision has therefore to be made, prophylactic treatment with subcutaneous heparin is recommended during hospitalization (immediately before and after the pleurodesis procedure).

C-reactive protein and serum amyloid a overexpression in lung tissues of chronic obstructive pulmonary disease patients: a case-control study.

Background. Although researchers have consistently demonstrated systemic inflammation in chronic obstructive pulmonary disease (COPD), its origin is yet unknown. We aimed to compare the lung bronchial and parenchymal tissues as potential sources of major acute-phase reactants in COPD patients and resistant smokers. Methods. Consecutive patients undergoing elective surgery for suspected primary lung cancer were considered for the study. Patients were categorized as COPD or resistant smokers according to their spirometric results. Lung parenchyma and bronchus sections distant from the primary lesion were obtained. C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) gene expressions were evaluated by RT-PCR. Protein levels were evaluated in paraffin embedded lung tissues by immunohistochemistry and in serum samples by nephelometry. Results. Our study included 85 patients with COPD and 87 resistant smokers. In bronchial and parenchymal tissues, both CRP and SAA were overexpressed in COPD patients. In the bronchus, CRP, SAA1, SAA2, and SA4 gene expressions in COPD patients were 1.89-fold, 4.36-fold, 3.65-fold, and 3.9-fold the control values, respectively. In the parenchyma, CRP, SAA1, and SAA2 gene expressions were 2.41-, 1.97-, and 1.76-fold the control values, respectively. Immunohistochemistry showed an over-stained pattern of these markers on endovascular cells of COPD patients. There was no correlation with serum protein concentration. Conclusions. These results indicate an overexpression of CRP and SAA in both bronchial and parenchymal tissue in COPD, which differs between both locations, indicating tissue/cell type specificity. The endothelial cells might play a role in the production of theses markers.

Cyclooxygenase-2 polymorphisms confer susceptibility to sarcoidosis but are not related to prognosis.

BACKGROUND The aim of this multicenter study was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the cyclooxygenase-2 (COX2) gene and susceptibility to sarcoidosis, as well as the relation between these SNPs and the evolution of the disease. MATERIAL AND METHODS This multicenter investigation involved seven hospitals in Spain. We used a case-control design followed by a prospective follow-up study. Sarcoid patients were recruited from the participating institutions during outpatient routine visits. Age- and gender-matched control subjects were recruited mainly from among outpatients attending the participating hospitals. Four SNPs in the COX2 gene (COX2.5909 T > G, COX2.8473 T > C, COX2.926 G > C, and COX2.3050 G > C) were genotyped using fluorescent hybridization probes among 131 patients with sarcoidosis (63 males; mean age: 47 +/- 15 years) and 157 healthy controls (83 males; mean age: 50 +/- 16 years). We employed a binomial multiple logistic regression analysis to test the association between the selected SNPs and disease susceptibility. The clinical, functional and radiological prognosis of the sarcoidosis patients was determined after a mean follow-up of 37.4 +/- 30.4 months. RESULTS Carriers of the homozygous CC genotype of the COX2.8473 T > C polymorphism had a higher risk of sarcoidosis compared with TT carriers (OR: 3.08; 95% CI: 1.2-7.7; p = 0.035). 84% of patients achieved improvement or complete remission at follow-up. No association between the investigated SNPs and prognosis was seen. CONCLUSIONS Our data suggest that the homozygous CC genotype of the COX2.8473 T > C polymorphism may be associated with sarcoidosis susceptibility. No significant association with prognosis was detected.

Increased levels of soluble ICAM-1 in chronic obstructive pulmonary disease and resistant smokers are related to active smoking

AIM Serum ICAM-1 (sICAM-1) is known to be a smoking-associated inflammatory marker, but data in chronic obstructive pulmonary disease (COPD) are lacking. PATIENTS & METHODS A total of 142 COPD cases (48 active smokers) and 55 controls (41 active smokers) were consecutively enrolled in this cross-sectional study. The peripheral blood concentrations of sICAM-1, IL-8 (CXCL8), CRP and serum amyloid A (SAA) were determined by ELISA. RESULTS CRP and SAA (log-scale) were elevated in the patients with COPD compared with the control subjects (p = 0.005 for CRP and p = 0.024 for SAA). sICAM-1 was associated with active smoking when corrected for age, gender, the presence of COPD, inhaled corticosteroid use, BMI and forced expiratory volume in 1 s as covariates. CONCLUSION The present study confirms an association between sICAM-1 levels and active smoking in a group of COPD and non-COPD active smokers.

Expression of aquaporins in bronchial tissue and lung parenchyma of patients with chronic obstructive pulmonary disease

BackgroundAquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers.MethodsUsing a case–control design, we selected a group of 15 subjects with COPD and 15 resistant smokers (smokers without COPD) as a control, all of whom were undergoing lung resection surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry and reverse-transcription real-time polymerase chain reaction. Tissue expression of AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to 3 (maximum).ResultsThere were no significant differences in gene expression between COPD patients and resistant smokers both in the bronchial tissue and in the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene showed the opposite pattern, with a 7.75-fold higher expression in the bronchus of smokers with COPD compared with controls. AQP1 and AQP5 proteins were preferentially expressed in endothelial cells, showing a higher intensity for AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an extension of 3 among patients with COPD). Subtle interstitial disease was associated with type II pneumocyte hyperplasia and an increased expression of AQP1.ConclusionsThis study provides pilot observations on the differences in AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our findings suggest a potential role for AQP1 in the pathogenesis of COPD.

Residual thrombosis after a first episode of proximal deep venous thrombosis.

The aim of this study was to analyse the normalization rate of compression ultrasonography after a first episode of proximal deep venous thrombosis (DVT). Patients underwent compressive ultrasound (C-US) examinations during the 3–6 months following the first proximal DVT episode. Normalization rate of compressive ultrasound (C-US) during the follow-up period was 26.4% [95% confidence interval, 16.3–37.3]. Allelic variation in factor XIII gene (Val34Leu) significantly affected the improvement of popliteal residual thrombi (P = 0.019). We also observed a significant negative correlation between D-dimer levels at 3 months and improvement of popliteal residual thrombi (P = 0.016). There was a significant positive correlation between baseline lumen diameter of the femoral thrombi and IL-8 cytokine (P = 0.015). A significant difference was also found between 1 month-tumor necrosis factor (TNF)-&agr; levels and improvement of residual thrombi (P = 0.047). Our results show that normalization after a standard period of anticoagulation is not frequent and procoagulant and inflammatory biomarkers and also some genetic variations might be related to the resolution of thrombosis.

Stent‐induced tracheal stenosis can be predicted by IL‐8 expression in rabbits

Bare metal stents may cause complications like fibrous encapsulation, granulation and tracheal stenosis. We investigated the behaviour of three commercially available stents in vivo (rabbits) and in vitro (coculture of those stents with epithelial and fibroblast cell lines). Also, we investigated whether development of tracheal stenosis could be predicted by any biological marker.

Cyclooxygenase-2 -765G>C polymorphism is associated with C-reactive protein levels in resistant smokers but not in chronic obstructive pulmonary disease patients.

We sought to investigate whether the serum concentrations of several inflammatory biomarkers are related to the cyclooxygenase-2 (COX2) -765G>C polymorphism in chronic obstructive pulmonary disease (COPD) and a control group of non-COPD smokers. Serum inflammatory markers (CRP, SAA, CXCL8, and sICAM-1) were measured by ELISA in 144 patients with COPD and in 55 control subjects. Genomic DNA was extracted from peripheral blood leukocytes, and the COX2 -765G>C (rs20417) polymorphism was genotyped. After adjustment for age and active smoking, CRP and SAA concentrations were associated with the COX2 polymorphism in controls (p=0.041 and 0.014, respectively) but not in COPD patients. The CXCL8 and sICAM-1 concentrations were not associated with the COX2 polymorphism for either cases or controls. The results of the present study indicate that there is a relationship between the COX2 -765G>C polymorphism and the concentrations of CRP and SAA in non-COPD smokers and that this relationship does not exist in COPD patients.

Predictive factors and prognostic effect of telomere shortening in pulmonary fibrosis: Telomeric clinical implications in IPF

The abnormal shortening of telomeres is a mechanism linking ageing to idiopathic pulmonary fibrosis (IPF) that could be useful in the clinical setting. The objective of this study was to identify the IPF patients with higher risk for telomere shortening and to investigate the outcome implications.

Endobronchiale ultraschallgeführte transbronchiale Biopsie peripherer Lungenläsionen: Wie viele Proben sind notwendig?

Hintergrund: Obwohl bereits aufgezeigt wurde, dass eine durch endobronchialen Ultraschall (EBUS) geführte transbronchiale Biopsie (TBB) die diagnostische Ausbeute gegenüber herkömmlichen Bronchoskopietechniken erhöht, wurde der wichtige Aspekt der benötigten optimalen Anzahl an Biopsieproben bisher nicht gründlich untersucht. Studienziele: Untersuchung, ob die Anzahl der entnommenen Biopsieproben mit der diagnostischen Ausbeute einer EBUS-geführten TBB zusammenhing und - sofern dies der Fall ist - Bestimmung der optimalen Probenanzahl, die für eine maximale diagnostische Ausbeute bei peripheren Lungenläsionen erforderlich ist. Methoden: Die Krankenakten aus den Jahren 2008-2010 von Patienten, bei denen eine EBUS-geführte TBB zur Diagnose peripherer Lungenläsionen durchgeführt wurde, wurden retrospektiv ausgewertet. Ferner wurde der Zusammenhang zwischen klinischen und radiologischen Merkmalen (einschließlich der Anzahl der Biopsieproben) und der diagnostischen Ausbeute analysiert. Ergebnisse: Die Analyse umfasste insgesamt 384 Patienten. Die diagnostische Gesamtausbeute der EBUS-geführten TBB betrug 73%; der einzige Faktor, der die diagnostische Ausbeute beeinflusste, war die Position der Sonde. Bei Patienten, bei denen die EBUS-Sonde innerhalb der Läsion platziert wurde, ergab sich eine signifikant höhere Ausbeute (85%) als bei den Patienten, bei denen sich die Sonde in der Nähe bzw. außerhalb der Läsion befand (38%; p < 0,001). Bei der Bestimmung der Anzahl der Biopsieproben auf Grundlage ihrer Genauigkeit ergab sich kein signifikanter Faktor bei der Vorhersage der diagnostischen Ausbeute. Schlussfolgerungen: Die Position der Sonde ist ein unabhängiger Prädiktor der diagnostischen Ausbeute bei der EBUS-geführten TBB. In der alltäglichen Praxis sollte die optimale Anzahl an Biopsieproben von Fall zu Fall entschieden werden.