Matrix metaloproteinase-2 and -9 serum levels as potential markers of intraperitoneal adhesions.

OBJECTIVE: To assess the value of matrix metalloproteinases-2 (MMP-2) and -9 (MMP-9) as prognostic serum markers for intraperitoneal adhesions. BACKGROUND: Postoperative adhesions are associated with serious complications responsible for increased patient's morbidity. METHODS: Forty-eight rabbits were used and randomized into groups A, B, C, and D. Abdominal laparotomy and experimental adhesion formation model was carried out. In group A, 60 mL of N/S 0.9% were instilled intraperitoneally, in group B 60 mL of icodextrin 4% were instilled intraperitoneally, in group C 0.1 mL/kg of dimetindene maleate were administered intravenously, and in group D both agents were administered. Prior to euthanasia 0.5 mL of blood was obtained. The type, the surface area of adhesions, and serum concentration of MMPs were assessed. RESULTS: The mean surface area and Zuhlke classification of adhesions of groups B, C, and D has been proved to be significantly lower compared to group A. Serum MMP-2 levels were significantly higher in groups B and D than in group A, while group D was higher when compared to group C. Serum MMP-9 levels were significantly higher in group D compared to groups A, B, and C. Serum MMP-9 was the most accurate test to differentiate between animals with and without adhesions with a sensitivity of 81.8% and a specificity of 100% at a cut-off point of 21.5 (AUC = 0.934). CONCLUSIONS: The administration of icodextrin 4% and dimetindene maleate seems to prevent postoperative adhesion formation. Serum levels of MMP-2 and MMP-9 may serve as prognostic markers to identify postoperative adhesions.

Serum amyloid alpha in parapneumonic effusions.

STUDY OBJECTIVES: To assess serum amyloid alpha (SAA) pleural fluid levels in parapneumonic effusion (PPE) and to investigate SAA diagnostic performance in PPE diagnosis and outcome. METHODS: We studied prospectively 57 consecutive patients with PPE (empyema (EMP), complicated (CPE), and uncomplicated parapneumonic effusion (UPE)). SAA, CRP, TNF-α, IL-1ß, and IL-6 levels were evaluated in serum and pleural fluid at baseline. Patients were followed for 6-months to detect pleural thickening/loculations. RESULTS: Pleural SAA levels (mg/dL) median(IQR) were significantly higher in CPE compared to UPE (P < 0.04); CRP levels were higher in EMP and CPE compared to UPE (P < 0.01). There was no significant difference between IL-1ß, IL-6, TNF-α level in different PPE forms. No significant association between SAA levels and 6-month outcome was found. At 6-months, patients with no evidence of loculations/thickening had significantly higher pleural fluid pH, glucose levels (P = 0.03), lower LDH (P = 0.005), IL-1ß levels (P = 0.001) compared to patients who presented pleural loculations/thickening. CONCLUSIONS: SAA is increased in complicated PPE, and it might be useful as a biomarker for UPE and CPE diagnosis. SAA levels did not demonstrate considerable diagnostic performance in identifying patients who develop pleural thickening/loculations after a PPE.

Diagnostic accuracy of biomarkers of oxidative stress in parapneumonic pleural effusions.

BACKGROUND: The imbalance between oxidants and antioxidants is referred to as oxidative stress and has been associated with various respiratory disorders. The aim of this study was the assessment of 8-isoprostane (8-iso-PGF(2α)) and Cu/Zn superoxide dismutase (Cu/Zn SOD) in exudative pleural effusions in order to examine the diagnostic accuracy of these markers in the differentiation between complicated and uncomplicated parapneumonic effusions. METHODS: The study included 214 consecutive patients with pleural effusions [68 parapneumonic (31 uncomplicated parapneumonic, 20 complicated parapneumonic, 17 empyemas), 24 tuberculous, 88 malignant and 34 transudates]. 8-Isoprostane and Cu/Zn SOD were determined by ELISA in pleural fluid and serum. RESULTS: Parapneumonic effusions were characterized by higher pleural fluid 8-isoprostane levels compared to transudative, malignant and tuberculous effusions. Pleural fluid Cu/Zn SOD levels were lower in transudates, while serum levels were higher in transudative compared to all exudative pleural effusions. Both pleural fluid 8-isoprostane and Cu/Zn SOD were higher in complicated parapneumonic effusions and empyemas compared to uncomplicated parapneumonic effusions. Pleural fluid 8-isoprostane was the most accurate test to differentiate between complicated and uncomplicated parapneumonic pleural effusions with a sensitivity of 100% and a specificity of 58·1% at a cut-off point of 35·1 (AUC = 0·848). CONCLUSIONS: Pleural fluid 8-isoprostane and Cu/Zn SOD may provide useful information for the differentiation between uncomplicated and complicated parapneumonic effusions and empyemas.

Adiposity and low-grade systemic inflammation modulate matrix metalloproteinase-9 levels in Greek children with sleep apnea.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) plasma levels correlate with C-reactive protein (CRP) concentrations and they are both increased in adults with obstructive sleep apnea (OSA). No studies have evaluated MMP-9 levels in children with sleep apnea and CRP is not consistently elevated in pediatric OSA. The aim of this investigation was to evaluate the association of severity of OSA, adiposity, and CRP with MMP-9 plasma levels in Greek children. METHODS: Consecutive children with snoring who underwent polysomnography and were found to have OSA (obstructive apnea-hypopnea index-OAHI > or = 1 episode/hr) were recruited. Subjects without OSA (OAHI < 1 episode/hr) were included for comparison. Morning plasma MMP-9 and CRP were measured. RESULTS: Twenty-nine children with moderate-to-severe OSA (age 5.4 +/- 1.5 years; OAHI 13.9 +/- 13.0 episodes/hr), 55 participants with mild OSA (6.4 +/- 2.6 years; OAHI 2.4 +/- 1.1 episodes/hr) and 22 subjects without OSA (6.8 +/- 2.6 years; OAHI 0.6 +/- 0.2 episodes/hr) were studied. Children with moderate-to-severe OSA were similar to those with mild OSA or without OSA regarding ln-transformed MMP-9 values (5.87 +/- 0.60 vs. 5.84 +/- 0.55 vs. 5.80 +/- 0.46; P > 0.05) and CRP concentrations (0.22 +/- 0.29 mg/dl vs. 0.21 +/- 0.36 vs. 0.13 +/- 0.16 mg/dl; P > 0.05). In multiple linear regression, body mass index (P = 0.027) and CRP levels (P = 0.008), but not OAHI or SpO(2) nadir (P > 0.05), were significantly related to MMP-9 values. CONCLUSIONS: Adiposity and systemic inflammation unrelated to OSA severity, modulate MMP-9 levels in Greek children.

Matrix metalloproteinase levels in the differentiation of parapneumonic pleural effusions.

BACKGROUND: Matrix metalloproteinases (MMPs) have been implicated in the escalation of fibrosis and remodeling which are central to the subsequent progression of a parapneumonic pleural effusion to empyema. OBJECTIVES: The aim of this study was the assessment of MMP-2, MMP-8 and MMP-9 in parapneumonic pleural effusions in order to examine their value in the differentiation between uncomplicated and complicated parapneumonic effusions. METHODS: The study included 208 consecutive patients with pleural effusions [60 parapneumonic (27 uncomplicated parapneumonic, 17 complicated parapneumonic, 16 empyemas), 24 tuberculous, 89 malignant and 35 transudates]. Concentrations of pleural fluid and serum MMP-2, MMP-8 and MMP-9 were determined by immunoassay. RESULTS: Pleural fluid MMP-8 and MMP-9 levels were higher in complicated parapneumonic effusions or empyema than in uncomplicated effusions, while their serum levels were higher in complicated parapneumonic effusions. MMP-2 levels were higher in uncomplicated than in complicated parapneumonic effusions or empyema. Pleural fluid MMP-2/MMP-9 ratio was the best marker to differentiate complicated from uncomplicated parapneumonic effusions, with a sensitivity of 94.1% and a specificity of 77.8% at a cut-off point of 1.32 (AUC = 0.887). CONCLUSIONS: Pleural fluid MMP-2, MMP-8 and MMP-9 may provide useful information for differentiating between uncomplicated and complicated parapneumonic effusions.

Residual pleural thickening is related to vascular endothelial growth factor levels in parapneumonic pleural effusions.

BACKGROUND: Many patients with pneumonia develop pleural effusions. Pleural fluid vascular endothelial growth factor (VEGF) levels are known to be elevated in complicated parapneumonic effusion and seem to play a major role in the fibrotic process in the pleura. OBJECTIVES: To test whether VEGF levels in pleural effusions of infectious origin correlate with the residual pleural thickening. METHODS: VEGF levels were measured in the pleural fluid of 45 patients with pleural effusion of infectious origin. Patients were reassessed 3 months after hospital discharge and residual pleural thickening (RPT) was recorded using a simple chest radiograph. RESULTS: Pleural fluid VEGF was higher in empyemas compared to simple parapneumonic and complicated parapneumonic effusions. RPT was higher in patients with empyemas compared to simple parapneumonic effusions. Patients with RPT >2 mm had higher pleural fluid LDH and pleural fluid to serum LDH ratio, lower glucose and pH and higher VEGF levels. However, patients with RPT ≥10 mm differed only in pleural fluid VEGF levels. Pleural fluid VEGF levels correlated to RPT and to pleural fluid pH. VEGF presented moderate performance for the prediction of RPT 3 months after hospital discharge. Its performance was comparable to that of pleural fluid glucose and pH for the development of a radiologically significant RPT >2 mm, whereas it was the only statistically significant predictor of a clinically significant RPT ≥10 mm. CONCLUSION: VEGF levels are elevated in complicated parapneumonic effusions and empyemas compared to simple parapneumonic effusions and are a significant predictor for the development of clinically significant RPT.

Matrix metalloproteinases in respiratory diseases: from pathogenesis to potential clinical implications.

Matrix metalloproteinases (MMPs) are zinc-endopeptidases responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The turnover and remodeling of ECM must be tightly regulated since excessive or inappropriate expression of MMPs may contribute to the pathogenesis of tissue destructive processes associated with lung inflammation and disease. Despite the fact that our knowledge in the field of MMP biology is rapidly expanding, the role of MMPs in the pathogenesis of lung diseases is still not clear. The aim of the present review is to present the basic principles of MMP biology and, subsequently, to focus on the clinical and experimental evidence related to MMP activity in various lung disorders, including lung cancer, pleural effusions, chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome and interstitial lung diseases.

Acute phase markers for the differentiation of infectious and malignant pleural effusions.

Acute-phase markers, such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), have been studied in inflammatory and malignant disorders. We examined the diagnostic value of these markers for the differentiation among parapneumonic, tuberculous and malignant effusions. We studied 124 patients with pleural effusions, classified as exudates [total (n=97), parapneumonic (n=15), tuberculous (n=25), malignant (n=57)] and transudates due to congestive heart failure (n=27). CRP, IL-6 and TNF-alpha were measured in pleural fluid and serum. Pleural fluid CRP was higher in parapneumonic compared to tuberculous and malignant effusions, providing 100% sensitivity for a cut-off point of 5.3mg/dL. IL-6 was higher in both parapneumonic and tuberculous compared to malignant effusions. TNF-alpha was higher in tuberculous compared to malignant effusions, providing 96.0% sensitivity, and 93.0% specificity for a cut-off point of 88.1 pg/mL. Pleural fluid CRP levels were lower than serum in all groups, probably reflecting systemic inflammation, whereas IL-6 and TNF-alpha were higher in pleural fluid indicating local production. Our data suggest that these markers may provide useful information for the differentiation of infectious and malignant effusions in clinical practice. However, further studies are needed for the validation of these findings in usual clinical circumstances.