Systemic concentrations of asymmetric dimethylarginine (ADMA) in chronic obstructive pulmonary disease (COPD): state of the art.

Experimental evidence suggests that oxidative stress (OS) may increase the activity of arginine methylating enzymes that produce the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). In addition, it is well documented that OS can significantly decrease the synthesis and/or activity of ADMA degrading enzymes, thus causing ADMA accumulation in biological fluids. Recent reports have focused on circulating methylated arginine concentrations in chronic obstructive pulmonary disease, a disease characterized by a significant increase in OS. This review discusses the results of these studies and the opportunities for further research in this area.

Circulating serotonin levels in COPD patients: a pilot study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major and increasing global health problem. Serotonin is a neurotransmitter that participates in several pulmonary functions and it has been involved in oxidative stress, which plays essential roles in the pathogenesis of COPD. The current study aimed at establishing the levels of circulating serotonin in COPD, and investigating eventual relations between serotonin and oxidative stress markers. METHODS: Whole blood serotonin was assessed in 43 consecutive patients with stable COPD and in 43 age and sex-matched healthy controls. RESULTS: Serotonin blood levels were significantly higher in COPD patients than in controls (median 0.81 µmol/L, IQR: 0.61-4.02 vs 0.65 µmol/L, IQR: 0.53-1.39, p = 0.02). The univariate logistic regression analysis evidenced that serotonin levels are independently associated with presence of COPD (crude OR = 7.29, 95% CI: 1.296-41.05, p = 0.003) and such an association was confirmed also after adjusting for several confounders (OR 21.92, 95% CI 2.02-237.83; p = 0.011). CONCLUSIONS: Our study showed higher levels of circulating serotonin in COPD and an inverse correlation with the worsening of airway obstruction. Future studies are necessary to investigate the clinical utility of this finding.

Clinical and spirometric variables are better predictors of COPD exacerbations than routine blood biomarkers.

BACKGROUND: Understanding the risk factors for exacerbations of COPD may help provide a more personalised approach to exacerbation prevention. METHOD: Observational, prospective, international, multicentre study aimed at identifying risk factors for exacerbations of COPD. Clinical variables, lung function and CAT scores were collected at baseline. In addition, routine blood biomarkers were also obtained, and patients were followed for 12 months. RESULTS: A total of 326 patients were included. Of these, 155 (47.5%) presented at least one exacerbation. The median time to the first exacerbation was 147 days. Exacerbators had more respiratory symptoms, more impairment in FEV1(%), FVC(%) and a worse CAT score. Regarding biomarkers, only C-reactive protein was significantly higher in exacerbators (2.8 (standard deviation (SD):3.8) mg/dL vs. 1.9 (SD:2.6) mg/dL; p = 0.037). In multivariate analysis, only CAT scores, FEV1(%) and previous exacerbations were significantly associated with having an exacerbation during follow-up. In the equation of risk, patients with a CAT score ≥15, FEV1(%) <55% and at least one exacerbation the previous year had a probability of 76% of having an exacerbation during the next year, compared with 17% in patients who had none of the previous variables. No biomarkers showed a significant association in multivariate analysis. CONCLUSIONS: Less than half of the patients presented an exacerbation during the one-year follow-up. CAT scores, FEV1(%) and previous exacerbations were the only variables associated with increased risk of exacerbations. Routine biomarkers did not provide additional information to evaluate the risk of exacerbations.

Association Between Routine Blood Biomarkers and Clinical Phenotypes and Exacerbations in Chronic Obstructive Pulmonary Disease.

Introduction: Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations. Methods: Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤1 ambulatory exacerbation in the previous year) and exacerbators (≥2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators. Results: A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators. Conclusion: Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.

Bronchial mucoepidermoid carcinoma: A case report.

INTRODUCTION: Bronchial localization of Mucoepidermoid carcinoma (MEC) is rare. The precise nature of these neoplasms is not yet clear and little is known on the histogenesis and pathogenesis of the disease. Here we present a case of a bronchial MEC with a detailed pathological, immunohistochemical, and molecular analysis. PRESENTATION OF A CASE: A 46 years old Caucasian male patient was referred to our Unit for fever, non productive cough and dyspnea lasting for two months. The chest CT scan evidenced an 8-mm intraluminal lesion in the left main bronchus, in correspondence of the origin of the lingular segmental bronchus. Multiple biopsies were performed through bronchoscopy, and the diagnosis of a mucoepidermoid carcinoma of the lung was obtained. A left upper lobectomy was performed. The histopathological examination confirmed the preoperative diagnosis and stage (pT1N0M0). No further therapies were employed, given the stage of the disease. The patient is presently free of disease, approximately three years after surgery. DISCUSSION: The treatment of MECs is usually surgical by traditional or sleeve lobectomy, performed with an open or video-assisted technique, with the aim of an R0 resection. In this stage the prognosis is excellent. Conversely, high grade tumors seems to be particularly aggressive, even more than other NSCLC. CONCLUSIONS: Low grade type of Bronchial MEC, as our case, is often characterized by an optimal clinical management and prognosis. The lack of EGFR sensitizing mutations does not preclude the use of TKIs, which may be extremely useful in patients non responsive to other therapies.

Desmoplastic small round cell tumors of the pleura: a review of the clinical literature.

Desmoplastic small round cell tumor of the pleura is a rare malignancy, with only a few cases reported in the scientific literature. The aim of the present review is to discuss the demographic, pathological, clinical, and therapeutic features of this rare tumor. English-language articles published since 1989, when the first case of desmoplastic small round cell tumor of the pleura was described, were retrieved, and fifteen cases included in fourteen articles were revised. The mean age of the patients was 25.5 years, out of them 60% were males. Chest pain, pleural effusion, and dyspnea were the most common clinical manifestations, while chest roentgenogram and computed tomography were the imaging techniques most commonly used. Surgical biopsy was employed in 80% of the cases for diagnosis. A multidisciplinary approach consisting in a combination of surgery with chemotherapy and radiation therapy was adopted in most cases. Only two patients (13.3%) were alive at 3 years from diagnosis, reflecting the aggressiveness of the disease, and the poor outcomes of the treatments currently available. Desmoplastic small round cell tumors of the pleura are extremely aggressive and challenging to diagnose, because of their rarity and unspecific demographic, clinical, and radiological features. An in-depth knowledge of such features is necessary for the optimal management of patients with this rare malignancy.