Comparison of serum cardiac specific biomarker release after non-cardiac thoracic surgery.

BACKGROUND: The detection of postoperative myocardial infarction can be difficult in patients after lung surgery. The aim of this study was to verify the clinical significance of elevated Troponin I (cTnI), N-terminal pro-natriuretic peptide (NT-pro-BNP), lactate dehydrogenase (LDH), creatine kinase (CK), and CK-MB in the perioperative course. METHODS: Between 2007 and 2010, 64 patients (36 men, 28 women) were includeded in this prospective study and underwent thoracotomy and wedge lung resection (n = 20, group I), lobectomy/bilobectomy (n = 24, group II), and pneumonectomy (n = 20, group III). Peri-operative measurements were done for the serum markers: cTnI, NT-pro-BNP, LDH, CK, and CK-MB preoperatively and at 4 hours, 8 hours, and 24 hours postoperatively. Patients were followed over a 90-day period to evaluate postoperative cardiac mortality. RESULTS: No basal troponin I elevation (or CK-MB) was found prior to surgery. Elevation in concentrations of troponin I (> 0.32 ng/mL) occurring after the procedure were seen in 9 patients. However, there was neither association with 90-day survival, postoperative ECG changes, nor with elevated levels of the other cardiac serum markers. cTnI correlated significantly with intrapericardial procedures in 7 out of 20 patients (Spearman's rank correlation coefficient: 0.406; p < 0.0001). Additionally, of the 20 patients within the pneumonectomy group, 8 patients had postoperative elevated serum cTnI. The grouping of patients into groups I through III was significantly associated with cTnI elevation (Spearman's rank correlation coefficient: 0.455; p < 0.0001). CONCLUSIONS: Despite the excellent sensitivity of troponin I for detection of acute myocardial infarction the fact remains that troponin I elevations were common after intrapericardial procedures and pneumonectomies. Thus, to differentiate between cardiac ischemia provoked chest pain and wound pain related to thoracotomy remains most difficult. Patients with only marginally elevated cTnI concentrations after intrapericardial resections or pneumonectomy should remain in the intensive care unit and should be followed-up carefully by cardiologists.

Gene expression analysis of endobronchial epithelial lining fluid in the evaluation of indeterminate pulmonary nodules.

OBJECTIVE: Making a definitive preoperative diagnosis in patients with indeterminate pulmonary nodules is still a challenge. Gene expression profiling may be a useful adjunctive diagnostic utility in this regard. We investigated the feasibility of bronchoscopic microsampling to collect endobronchial epithelial lining fluid to obtain RNA as a starting point for gene expression profiling. METHODS: In 15 patients, epithelial lining fluid was collected in triplicate from subsegmental bronchi close to the pulmonary nodules and from contralateral lungs. Diagnosis was confirmed by transbronchial biopsy or surgery (non-small cell lung cancer, n = 11; benign or other lesions, n = 4). Total RNA was isolated from the samples and evaluated concerning quantity and quality. The complementary DNA was generated and analyzed by quantitative real-time polymerase chain reaction for potential lung cancer associated genes like matrix metalloprotinase (MMP9). RESULTS: Total RNA of adequate amount (>0.8 microg) and sufficient quality was obtained in 13 (86%) of the 15 patients. In patients with lung cancer, normalized MMP9 gene expression levels in endobronchial lining fluid samples collected close to the lesions were in median 12 times higher than levels in the matching contralateral samples. MMP9 expression levels were particularly high in endobronchial lining fluid samples collected from patients with squamous cell carcinoma but not elevated in the case of benign lesions. CONCLUSIONS: Our results show that quantitative gene expression analysis of endobronchial lining fluid collected by bronchoscopic microsampling is both feasible and reliable and may therefore be a useful additional diagnostic method in patients with indeterminate pulmonary nodules.

Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study.

RATIONALE: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears. OBJECTIVES: Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay. METHODS: Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELISpot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB. CONCLUSIONS: Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.

Correlation of soluble gp130 serum concentrations with arterial blood pressure.

OBJECTIVES: An increased blood pressure can elicit remodeling of the cardiovascular system. Experimental data have implicated gp130, a subunit of the receptor for interleukin-6 (IL-6)-related cytokines, in the regulation of proliferation and apoptosis of cardiomyocytes and vascular smooth muscle cells (VSMC). Here, we investigate whether serum soluble gp130 concentrations correlate with blood pressure in humans, whether gp130 expression in the aorta differs between hypertensive and control rats, and whether angiotensin II or endothelin regulate gp130 expression in human VSMC. METHODS: We measured serum concentrations of soluble gp130, IL-6, the soluble IL-6 receptor, and the intima-media thickness of the common carotid artery in stroke patients (n = 48) and in elderly controls (n = 48). Furthermore, soluble gp130 levels were measured in young controls (n = 200). Expression of gp130 in Wistar-Kyoto (n = 12), spontaneously hypertensive rats (n = 12), and human VSMC was detected by real-time reverse transcription-PCR and immunohistochemistry. RESULTS: Soluble gp130 serum concentrations correlated with blood pressure in stroke patients and in elderly and young controls and with the intima-media thickness of the common carotid artery in stroke patients. The hypothesis that elevated soluble gp130 derives from the vascular system was supported by the enhanced expression of gp130 in the aortic wall of spontaneously hypertensive rats. Furthermore, treatment of human VSMC with angiotensin II stimulated gp130 expression. CONCLUSION: Our data suggest that soluble gp130 serum concentrations are correlated with blood pressure and may reflect vascular remodeling in response to arterial hypertension.