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Introduction: The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. Objectives: We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-alpha), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO. Methods: This is a cross-sectional study of patients aged >= 40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity < 0.70 recruited from out-patient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking > 10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis. Results: In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p=0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p < 0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions. Conclusion: Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions., The authors are grateful to all the patients who participated in the study. A number of investigators contributed to the study logistics and they are listed in the Supplementary materials. The project was endorsed by the COPD and Asthma Research Board (PII de EPOC y asma) of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). The project was partially funded by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Economia y Competitividad (FIS 15/01263) through European Union FEDER funds and by unrestricted grant from Chiesi Espana S.A.U.

A chronic inflammatory state is a major characteristic of the aging process, and physical activity is proposed as a key component for healthy aging. Our aim was to evaluate the body composition, hypertension, lipid profile, and inflammatory status of older adults, and these factors' association with physical activity. A total of 116 elderly volunteers were categorized into terciles of quantitative metabolic equivalents of task (MET). Subjects in the first and third terciles were defined as sedentary and active subjects, respectively. Anthropometric and biochemical parameters, hemograms, and inflammatory markers were measured in plasma or peripheral mononuclear blood cells (PBMCs). The active groups exercised more than their sedentary counterparts. The practice of physical activity was accompanied by lower weight, fat mass, body mass index, and diastolic blood pressure when compared to a more sedentary life-style. Physical activity also lowered the haematocrit and total leukocyte, neutrophil, and lymphocyte counts. The practice of exercise induced a decrease in the IL-6 circulating levels and the TLR2 protein levels in PBMCs, while the expression of the anti-inflammatory IL-10 was activated in active subjects. The regular practice of physical activity exerts beneficial effects on body composition and the anti-inflammatory status of old people., This work was supported by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (Projects 11/01791 and 14/00636, Red Predimed-RETIC RD06/0045/1004, and CIBEROBN CB12/03/30038); Government of the Balearic Islands (grant numbers 35/2011 and AAEE26/2017), and European Union FEDER funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Journal Article; Research Support, Non-U.S. Gov't; CD66b is a member of the carcinoembryonic antigen family, which mediates the adhesion between neutrophils and to endothelial cells. Allergen-specific immunotherapy is widely used to treat allergic diseases, and the molecular mechanisms underlying this therapy are poorly understood. The present work was undertaken to analyze A) the in vitro effect of allergens and immunotherapy on cell-surface CD66b expression of neutrophils from patients with allergic asthma and rhinitis and B) the in vivo effect of immunotherapy on cell-surface CD66b expression of neutrophils from nasal lavage fluid during the spring season. Myeloperoxidase expression and activity was also analyzed in nasal lavage fluid as a general marker of neutrophil activation. RESULTS CD66b cell-surface expression is upregulated in vitro in response to allergens, and significantly reduced by immunotherapy (p

Journal Article; Research Support, Non-U.S. Gov't; The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G), DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis. Yes

This article is available from: http://www.biomedcentral.com/1471-2350/8/75, [Background] The etiology of Ulcerative Colitis (UC) and Crohn's Disease (CD), considered together as Inflammatory Bowel Diseases (IBD), involves environmental and genetic factors. Although some genes are already known, the genetics underlying these diseases is complex and new candidates are continuously emerging. The CD209 gene is located in a region linked previously to IBD and a CD209 functional polymorphism (rs4804803) has been associated to other inflammatory conditions. Our aim was to study the potential involvement of this CD209 variant in IBD susceptibility., [Methods] We performed a case-control study with 515 CD patients, 497 UC patients and 731 healthy controls, all of them white Spaniards. Samples were typed for the CD209 single nucleotide polymorphism (SNP) rs4804803 by TaqMan technology. Frequency comparisons were performed using χ2 tests., [Results] No association between CD209 and UC or CD was observed initially. However, stratification of UC patients by HLA-DR3 status, a strong protective allele, showed that carriage of the CD209_G allele could increase susceptibility in the subgroup of HLA-DR3-positive individuals (p = 0.03 OR = 1.77 95% CI 1.04–3.02, vs. controls)., [Conclusion] A functional variant in the CD209 gene, rs4804803, does not seem to be influencing Crohn's disease susceptibility. However, it could be involved in the etiology or pathology of Ulcerative Colitis in HLA-DR3-positive individuals but further studies are necessary., This work was supported by grants SAF2003-08522 and SAF2006-00398. Concepción Núñez and Alfonso Martínez have a FIS contract (CA06/0163 and CP04/00175, respectively) and Elena Urcelay works for the "Fundación para la Investigación Biomédica-Hospital Clínico San Carlos".

Journal Article; Research Support, Non-U.S. Gov't; BACKGROUND Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation. METHODS In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality. RESULTS A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P