The Response to Biologics is Better in Patients with Severe Asthma Than in Patients with Asthma–COPD Overlap Syndrome

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma-COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with >= 1 exacerbation and >= 1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of controlled patients (with no exacerbations, no need for corticosteroids and ACT >= 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients

Comparative effectiveness of Anti-IL5 and Anti-IgE biologic classes in patients with severe asthma eligible for both.

BACKGROUND: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. METHODS: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. RESULTS: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). CONCLUSIONS: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use

Characteristics and treatment regimens across ERS SHARP severe asthma registries

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals. This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases. Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg.m(-2) (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 mu g.day(-1) between those from Slovenia versus Poland when starting anti-interleukin (IL)5 antibody and from 772 to 1344 mu g.day(-1) in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively. The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries

Complicaciones del abordaje anterior en la patología de la columna cervical

Objetivo. Analizar las complicaciones de pacientes intervenidos mediante abordaje cervical anterior en la patología de la columna. Material y métodos. Estudio retrospectivo de una serie de 193 casos clínicos, entre Diciembre de 1989 y Diciembre de 2004, en el Hospital Germans Trias i Pujol de Badalona, donde se analizaron las complicaciones surgidas con el abordaje cervical anterior y su relación con las distintas técnicas aplicadas. Se analizaron variables sociodemográficas (edad, sexo), variables clínicas (sintomatología inicial, origen de la patología cervical, tipo de complicación, y tiempo de duración de la complicación) y quirúrgicas (número de niveles intervenidos, nivel intervenido, tipo de intervención realizada, tipo de injerto utilizado). A partir de los datos obtenidos se realizó un análisis estadístico con modelos de análisis multivariante, con la prueba de T-Student y con el test de Chi-cuadrado para analizar la relación entre las complicaciones y las distintas variables estudiadas. Resultados. De todos los individuos estudiados (193), hallamos complicaciones en 50 pacientes (25,91%). De ellas, la más frecuente fue la disfagia, presente en 15 pacientes. La mayoría de ellas se presentaron de forma transitoria (13 pacientes) y en muy pocas ocasiones de forma permanente (2 pacientes). El análisis estadístico mediante la prueba de la T de Student mostró que no existían diferencias estadísticamente significativas (p=0,431) entre las edades de los pacientes que habían presentado complicaciones frente a los que no, y tampoco se encontraron diferencias estadísticamente signi- ficativas, utilizado el test de la Chi-cuadrado, respecto el sexo (p=0,515), síntomas iniciales (p=0,923), origen de la patología (p=0,364), tipo de intervención realizada (p=0,295), y tipo de injerto utilizado (p=0,382,). Donde sí encontramos diferencias estadísticamente significativas fue en el número de niveles intervenidos (p=0,018) con una razón de las ventajas para el número de niveles (único/múltiple) de 2,221. Con el análisis multivariante siguiendo en modelo de regresión lineal considerando edad, sexo y número de niveles intervenidos, observamos que persistía el riesgo de complicaciones del número de espacios intervenidos, independientemente de la edad o el sexo, siendo los múltiples espacios un 117,3% más frecuente que la intervención de un único (OR 2,173; IC95% 1,104-4,279) Conclusiones. 1. La cirugía de la columna cervical por vía anterior, es una técnica simple, y un procedimiento quirúrgicamente seguro con un número bajo de complicaciones. 2. La disfagia es la complicación más frecuente, pero que se encuentra casi inherente al procedimiento y en la mayoría de ocasiones se resuelve sin tratamiento. 3. Han sido muchos los procedimientos utilizados para la fijación de la columna cervical, con más de 40 años de experiencia, y aún queda por definir cual es el mejor. Harían falta más estudios de carácter multicéntrico y de cohorte prospectiva para poder comparar resultados clínicos, radiológicos, y la presencia de complicaciones

Impact of acute exacerbations on platelet reactivity in chronic obstructive pulmonary disease patients

Mariana Mu&ntilde;oz-Esquerre,1 Jos&eacute; Luis Ferreiro,2 Daniel Huertas,1,3 Ana Lucrecia Marcano,2 Marta L&oacute;pez-S&aacute;nchez,1 Gerard Roura,2 Joan Antoni G&oacute;mez-Hospital,2 Jordi Dorca,1 Angel Cequier,2 Salud Santos1,3 1Department of Pulmonary Medicine, Bellvitge University Hospital, IDIBELL, University of Barcelona, L&rsquo;Hospitalet de Llobregat, 2Heart Diseases Institute, Bellvitge University Hospital, IDIBELL, University of Barcelona, L&rsquo;Hospitalet de Llobregat, 3Biomedical Research Networking Centre Consortium Respiratory Diseases, CIBERES, Barcelona, Spain Background: A higher risk of atherothrombotic cardiovascular events, which are platelet-driven processes, has been described during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the relevance of platelet reactivity during AECOPD and whether this is affected by antiplatelet agents are not fully elucidated to date. This study aimed to evaluate whether platelet reactivity is augmented during an exacerbation in COPD patients with and without antiplatelet therapy and its association with systemic inflammatory parameters.Materials and methods: Prospective, observational, ex vivo investigation was conducted in consecutive patients suffering an exacerbation of COPD. Platelet reactivity was assessed during AECOPD and at stable state. Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay expressed as P2Y12 reactivity index (PRI), 2) multiple electrode aggregometry and 3) optical aggregometry. Systemic inflammatory parameters such as leukocyte count, interleukin-6 and fibrinogen were also assessed.Results: Higher platelet reactivity was observed during AECOPD compared to stability measured by vasodilator-stimulated phosphoprotein (PRI: 75.2%&plusmn;1.9% vs 68.8%&plusmn;2.4%, p=0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%&plusmn;3.1% vs 61.7%&plusmn;7.5%, p=0.071). Consistent findings were observed with all other platelet function tests. Patients with greater enhancement of inflammatory markers during AECOPD were more likely to present a higher increase in platelet reactivity.Conclusion: Platelet reactivity is increased during AECOPD, which may contribute to the augmented cardiovascular risk of these patients. Additionally, the increase in platelet reactivity might be associated with an increment in inflammatory markers during exacerbations. Keywords: airflow limitation, inflammation, platelet aggregation, antiplatelets agents, thrombosi

Integrating morphological and genetic data at different spatial scales in a cosmopolitan marine turtle species: Challenges for management and conservation

Patterns of genetic structure in highly mobile marine vertebrates may be accompanied by phenotypic variation. Most studies in marine turtles focused on population genetic structure have been performed at rookeries. We studied whether genetic and morphological variation of the endangered green turtle (Chelonia mydas) is consistent geographically, focusing on foraging grounds. An association between population genetic structure and body shape variation at broad (inter-lineage) and fine (foraging grounds) scales was predicted and analysed using mitochondrial DNA and geometric morphometrics. Although genetic and phenotypic differentiation patterns were congruent between lineages, no fine-scale association was found, suggesting adaptive divergence. Connectivity among Pacific foraging grounds found here suggests that temperatures of ocean surface currents may influence the genetic structure of C. mydas on a broad scale. Our results suggest that vicariance, dispersal, life-history traits and ecological conditions operating in foraging grounds have shaped the intraspecific morphology and genetic diversity of this species. Considering a range of geographic and temporal scales is useful when management strategies are required for cosmopolitan species. Integrating morphological and genetic tools at different spatial scales, conservation management is proposed based on protection of neutral and adaptive diversity. This approach opens new questions and challenges, especially regarding conservation genetics in cosmopolitan species.Financial support for this study was provided by the National Commission for Scientific and Technological Research of Chile (CONICYT), Núcleo Milenio de Ecología y Manejo Sustentable de Islas Oceánicas (ESMOI), National Oceanic and Atmospheric Administration (NOAA), RUFFORD Small Grant, IDEA WILD, Chilean Government Environmental Protection Fund (FPA), the Vice-Rectory of Research of the University of Costa Rica through the Integral Network of Marine Turtles in the Eastern Pacific (RITMA), The Leatherback Trust, Veritas University, Surfari del Mar, Centro de Rescate de Especies Marinas Amenazadas (CREMA), Turner Foundation, National Fish and Wildlife Foundation, DEFRA Darwin Initiative, Sea Life Trust and the Institute of Natural and Mathematical Sciences, Massey University. Data collection and sampling in Fiji were performed within a project that received funding under award NA17NMF4540081 from NOAA Fisheries PIRO

Data from: Vascular disease in COPD: systemic and pulmonary expression of PARC (Pulmonary and Activation-Regulated Chemokine)

Introduction. The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects. Methods. To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal arteries and serum samples from COPD patients, non-obstructed smokers (NOS) and never-smokers (NS). Results. A total of 57 subjects were included in the analysis (23 COPD, 18 NOS and 16 NS). In the comparisons between groups, a significantly increased lung protein expression of PARC was observed in the COPD group compared to the NOS group (1.96±0.22 vs. 1.29±0.27, P-adjusted=0.038). PARC was located predominantly in the smooth muscle cells of the remodeled pulmonary muscular arteries and the macrophage-rich area of the alveolar parenchyma. No differences were detected in PARC gene expression analyses. The protein content of PARC in the intercostal arteries were similar between groups, though little remodeling was observed in these arteries. Circulating levels of PARC were numerically higher in patients with COPD compared to NOS and NS. Conclusion. The results of the present study suggest an increased lung protein expression of PARC in COPD subjects. This protein was mainly localized in the smooth muscle cells of the pulmonary muscular arteries and was associated with the severity of intimal thickening, indicating its possible role in this remodeling process