Delphine Nguyen

Leukotriene B4 Contributes to Exhaled Breath Condensate and Sputum Neutrophil Chemotaxis in COPD

BACKGROUND Neutrophils have been implicated in the pathogenesis of COPD. Several chemoattractants for neutrophils have been measured in samples of exhaled breath condensate (EBC) and induced sputum (IS) from patients with COPD. The aims of this study were to compare EBC and IS supernatant neutrophil chemotactic activity (NCA) from ex-smoking subjects with COPD and healthy ex-smokers, and to assess the contribution of leukotriene B(4) (LTB(4)) to this activity. METHODS Thirty-four subjects with COPD were compared to 24 control subjects. EBC and IS chemotactic activity for neutrophils was assessed by using Boyden microchambers. The chemotactic index was used to evaluate cell migration. LTB(4) was measured by a specific enzyme immunoassay. The contribution of LTB(4) to EBC and sputum neutrophil chemotaxis was assessed by an LTB(4) receptor antagonist (U-75302; Cayman Chemical Company; Ann Arbor, MI). RESULTS EBC and IS samples from both COPD patients and healthy subjects displayed significant NCA, but this activity was raised in COPD patients compared to healthy subjects. The chemotactic activity contained in sputum, however, failed to correlate with that in EBC. In COPD patients, there was a significant correlation between EBC NCA and sputum neutrophil counts. LTB(4) levels were raised in EBC samples, but not in sputum samples, from COPD subjects compared to those from healthy subjects. LTB(4) receptor antagonist concentrations (2.5 x 10(-4) mol/L) reduced by 44.6% and by 44.4%, respectively, the chemotactic activity contained in the EBC and sputum samples. CONCLUSIONS EBC and IS from COPD patients have a raised NCA to which LTB(4) contributes.

18F-FDG PET imaging in assessing exudative pleural effusions.

Background This study evaluates the accuracy of [18F]fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging with semi-quantitative analysis for differentiating benign from malignant pleural exudates and for guiding the search for the primary tumour of pleural metastases. Methods Whole-body 18F-FDG PET was performed in 79 patients with exudative pleurisy. Standard uptake values were normalized for body weight, body surface area, lean body mass (SUVbw, SUVbsa, SUVlbm) with and without correction for blood glucose levels. Thoracoscopy was systematically performed to reveal pathological diagnosis. Results All SUVs were significantly higher in all malignant pleural diseases (n=51) than in benign (n=28) (P<0.001). Moreover SUVs were greater in the pleural metastases from pulmonary primaries (n=25) and in mesotheliomas (n=8) than in extrathoracic primaries (n=18) (P<0.01) with no significant difference between lung cancers and mesotheliomas. Receiver operating curve (ROC) analysis between benign and malignant lesions showed areas under the curves that ranged from 0.803 (SUVbsa g−1) to 0.863 (SUVbw). The cut-off value for SUVbw which gave the best accuracy (82.3%) was 2.2. When comparing thoracic with extrathoracic primaries the highest accuracy (80.4%) was found for a cut-off value of 2.6. Conclusion Semi-quantitative analysis of 18F-FDG PET imaging helps to differentiate malignant from benign pleural exudates and to distinguish between thoracic or extrathoracic primaries.

Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions.

STUDY OBJECTIVES We evaluate the accuracy of pleural interleukine-6 (IL-6), transforming growth factor-beta 1 (TGF-beta1), and vascular endothelial growth factor (VEGF) levels for differentiating benign from malignant pleural exudates. PATIENTS AND METHODS Levels of IL-6, TGF-beta1, and VEGF were measured by ELISA in 103 patients with non neutrophilic (<50%) exudative pleurisy including both benign and malignant effusions. Pleurisies were split into benign and malignant according to the pathological diagnosis. RESULTS Thirty-nine benign (seven infections; 32 inflammatory diseases) and 64 malignant (34 extrathoracic tumors; 25 lung cancers; five mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Pleural reticulo-monocyte count, protein Lights ratio and lactic dehydrogenase Lights ratio were significantly higher in malignant than in benign effusions (p<0.05, p<0.001 and p<0.001, respectively). The median (range) level of VEGF was significantly higher in malignant than in benign effusions (664.50 pg/ml [10-40,143] vs 349 pg/ml [10-8888]) (p<0.05). VEGF levels correlated with pleural LDH (r=0.41, p<0.0001), glucose (r=-0.30, p<0.01) and red cell count (r=0.57, p<0.0001). No significant difference was found between malignant and benign effusions with respect to IL-6 (26.8 ng/ml [1.8-421] vs 18.4 ng/ml [0.45-400], respectively) and TGF-beta1 (1079 pg/ml [18-6206] vs 1123 pg/ml [34-5447]) levels. ROC analysis between benign and malignant pleurisies for VEGF showed an area under the curve of 619 (p=0.03) with a value of 382 pg/ml as the best threshold for distinguishing benign from malignant effusions. CONCLUSIONS Malignant effusions may enhance the release of VEGF in pleural space and its measurement may help in the diagnosis of malignant effusion.

Should we exclude elderly patients with chronic obstructive pulmonary disease from a long-time ambulatory pulmonary rehabilitation programme?

OBJECTIVE To assess the outcomes of a 6-month comprehensive multidisciplinary outpatient pulmonary rehabilitation programme in patients with chronic obstructive pulmonary disease according to age. DESIGN Prospective cohort study. PATIENTS A total of 140 patients with chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) 3-4) admitted to our centre for pulmonary rehabilitation. METHODS Patients were divided into 3 groups: group A (< 65 years), group B (65-74 years) and group C (≥ 75 years). All the patients received an education and individualized training programme. Pulmonary rehabilitation efficacy was evaluated at 6 months of treatment and 12 months post-treatment. RESULTS A total of 116 patients completed the pulmonary rehabilitation programme: 59 in group A (85.5%), 40 in group B (80%) and 17 in group C (80.9%). All the parameters studied (number of sessions, 6-min walking distance, isometric quadriceps strength, health-related quality of life, maximal load, peak oxygen uptake, maximal inspiratory and expiratory pressures) were significantly improved in each of the groups at 3 and 6 months compared with baseline. Moreover, percentage changes from baseline at 6 months for all of the parameters studied were not significantly different between age-groups. CONCLUSION Pulmonary rehabilitation is efficient in elderly patients with severe and very severe chronic obstructive pulmonary disease, and their compliance with pulmonary rehabilitation was similar to that seen in younger groups. Therefore, elderly patients with chronic obstructive pulmonary disease should not be denied pulmonary rehabilitation.

Prognostic value of metabolic imaging in non-small cell lung cancers with neoplasic pleural effusion.

BackgroundThe intensity of the [18F]fluorodeoxyglucose (18F-FDG) uptake is an independent prognostic indicator in non-small cell lung cancer (NSCLC). We evaluate the relationship between the metabolic activity of the primary and the pleurisy in T4 NSCLC. Methods25 patients (16 males, nine females, mean age 63 years, performance status 1) with pathology-proven, T4 NSCLC and malignant pleurisy were included. All were treated by a platinum salt-based chemotherapy regimen. Positron emission tomography (18F-FDG-PET) was performed before treatment, according to a routine procedure. Regions of interest were placed over the primary and the pleural effusion on the transaxial slice showing the highest activity. The maximum pixel standard uptake values (SUVs) were calculated. Overall survival was determined by standard Kaplan–Meier survival analysis. All patients were followed up until death. ResultsThe median survival for the entire population was 83 days (7–988). The SUVs were higher in the primary than in the pleurisy (9.2±5.6 and 5.5±2.2, respectively). There was no correlation between primary and pleurisy SUVs (r=0.3, P>0.05). The metabolic activity of the primary tumor did not predict the outcome: the median survival was 77.5 days (range 7–988) and 87 days (19–454) in the groups with SUVs lower and higher than the median value (8.7), respectively (P>0.05). By contrast, the metabolic activity of the pleurisy was significantly correlated with the median survival, which was 196 days (40–988) when the SUVs were lower than the median value (5) and 74 days (7–170) when they were higher (P=0.0096). ConclusionAmong patients with T4 NSCLC, those with high metabolic activity in the pleural effusion have a dire prognosis, whereas the metabolic activity of the primary fails to predict the survival.