Assessment of Induced Sputum Cellularity in COPD Patients Belonging to Two Different Classes of Air Pollution Exposure

IntroductionSeveral studies have previously demonstrated that long-term exposure to outdoor pollution present airway inflammation in term of an increase of sputum neutrophils.Aim and methodsThe aim of our study was to evaluate the level of airway inflammation by induced sputum in a group of 15 non-professionally exposed population of well-characterized COPD patients, residing in urban areas with high rate of outdoor pollution, compared to a control group of 13 individuals with COPD, living in rural areas with a low pollution rate. All participants underwent spirometry and sputum induction.ResultsA statistically significant increase in the percentage of neutrophil cell count was found among the residents in urban areas compared to those living in rural regions (89.1 vs 79.0, p < 0.05)ConclusionsIn conclusion, we showed that non-professionally exposed patients with COPD residing in highly-polluted urban areas had greater airway inflammation in terms of sputum neutrophils compared to a population with very similar characteristics, living in rural areas with lower outdoor pollution. The results of this pilot study may be relevant for the long term effect of environmental outdoor pollution in vulnerable patients like those with COPD.     

Montelukast,Leukotriene Inhibitor,Reduces LPS-Induced Acute Lung Inflammation and Human Neutrophil Activation

ObjectivesSome pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant, a cell centrally involved in acute respiratory distress syndrome (ARDS); a syndrome lacking effective treatment. Considering the beneficial effects of the leukotriene receptor inhibitor, montelukast, on other lung diseases, whether montelukast attenuates inflammation in a mouse model of ARDS, and whether it reduces LPS stimulated activation of human neutrophils was investigated.MethodsThirty-five C57Bl/6 mice were distributed into control (PBS) + 24 h, LPS + 24 h (10 μg/mouse), control + 48 h, LPS + 48 h, and LPS 48 h + Montelukast (10 mg/kg). In addition, human neutrophils were incubated with LPS (1 μg/mL) and treated with montelukast (10 μM).ResultsOral-tracheal administration of montelukast significantly attenuated total cells (P < .05), macrophages (P < .05), neutrophils (P < .01), lymphocytes (P < .001) and total protein levels in BAL (P < .05), as well as IL-6 (P < .05), CXCL1/KC (P < .05), IL-17 (P < .05) and TNF-α (P < .05). Furthermore, montelukast reduced neutrophils (P < .001), lymphocytes (P < .01) and macrophages (P < .01) in the lung parenchyma. In addition, montelukast restored BAL VEGF levels (P < .05). LTB4 receptor expression (P < .001) as well as NF-κB (P < .001), a downstream target of LPS, were also reduced in lung parenchymal leukocytes. Furthermore, montelukast reduced IL-8 (P < .001) production by LPS-treated human neutrophils.ConclusionIn conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils.     

Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

Valor pronóstico del recuento de leucocitos y plaquetas,en tumores testiculares de células germinales

IntroductionThe immune system plays an essential role in the organism's response to cancer. Several haematological markers can influence prognosis and survival of patients. The objective of this study is to determine their prognostic value in testicular germ cell tumours.Material and methodsRetrospective cohort study on 164 patients with germ cell tumours. Clinical, analytical, histological and evolutionary data were collected. The absolute neutrophil and absolute platelet counts, neutrophil-lymphocyte (NLR), platelet-lymphocyte and lymphocyte-monocyte ratios were estimated at diagnosis. The association that these markers can have with the classic prognostic factors, as well as their effect on prognosis and survival, have been analysed.Results17.7% had NLR >4 and 14.6% ANC >8000/μL. These patients presented higher percentages of residual disease and stage II-III tumours. Patients with elevated absolute neutrophil showed also higher percentages of progression and exitus.7.3% presented absolute platelet  >400000/μL. These patients obtained higher rates of residual disease, nonseminomatous and stage III tumours. 28.4% showed platelet-lymphocyte values >150. This data was associated to higher percentages of residual disease, progression, stage II and III tumours and seminomatous tumours.83.3% had an lymphocyte-monocyte  >3. These patients presented: higher tumour markers in normal range, decreased residual disease rates and higher percentages of stage I and II tumours.The mean survival time was shorter in patients with NLR >4 and absolute neutrophil  >8,000/μL.The ROC curves showed significance in the prediction of progression and values of lymphocyte-monocyte  >3, and prediction of survival and values NLR >4.ConclusionOur results indicate that the analysed haematological markers are associated with poor prognoses at diagnosis. Therefore, their use in daily clinical practice can be a valuable tool in the diagnosis and prognosis of patients with testicular germ cell tumours.     

Trivalent pneumococcal protein recombinant vaccine protects against lethal Streptococcus pneumoniae pneumonia and correlates with phagocytosis by neutrophils during early pathogenesis

ObjectiveDue to the fact that current polysaccharide-based pneumococcal vaccines have limited serotype coverage, protein-based vaccine candidates have been sought for over a decade to replace or complement current vaccines. We previously reported that a trivalent Pneumococcal Protein recombinant Vaccine (PPrV), showed protection against pneumonia and sepsis in an infant murine model. Here we investigated immunological correlates of protection of PPrV in the same model.MethodsC57BL/6J infant mice were intramuscularly vaccinated at age 1–3 weeks with 3 doses of PPrV, containing pneumococcal histidine triad protein D (PhtD), pneumococcal choline binding protein A (PcpA), and detoxified pneumolysin mutant PlyD1. 3–4 weeks after last vaccination, serum and lung antibody levels to PPrV components were measured, and mice were intranasally challenged with a lethal dose of Streptococcus pneumoniae (Spn) serotype 6A. Lung Spn bacterial burden, number of neutrophils and alveolar macrophages, phagocytosed Spn by granulocytes, and levels of cytokines and chemokines were determined at 6, 12, 24, and 48 h after challenge.ResultsPPrV vaccination conferred 83% protection against Spn challenge. Vaccinated mice had significantly elevated serum and lung antibody levels to three PPrV components. In the first stage of pathogenesis of Spn induced pneumonia (6–24 h after challenge), vaccinated mice had lower Spn bacterial lung burdens and more phagocytosed Spn in the granulocytes. PPrV vaccination led to lower levels of pro-inflammatory cytokines IL-6, IL-1β, and TFN-α, and other cytokines and chemokines (IL-12, IL-17, IFN-γ, MIP-1b, MIP-2 and KC, and G-CSF), presumably due to a lower lung bacterial burden.ConclusionTrivalent PPrV vaccination results in increased serum and lung antibody levels to the vaccine components, a reduction in Spn induced lethality, enhanced early clearance of Spn in lungs due to more rapid and thorough phagocytosis of Spn by neutrophils, and correspondingly a reduction in lung inflammation and tissue damage.