Incidència i factors de risc associats a l'exacerbació, ingrés hospitalari i mortalitat de la malaltia pulmonar obstructiva crònica i determinació de les efectivitats de les vacunacions antigripal i antipneumocòccica 23V

INTRODUCCIÓ La MPOC és una patologia amb una elevada morbimortalitat. L’exacerbació és freqüent en la història natural de la malaltia i s’associa a una declinació irreversible de la capacitat pulmonar, a una pitjor qualitat de vida i a una disminució en la supervivència. L’objectiu de la tesi va ser estudiar la incidència i els factors de risc associats a l’exacerbació de la MPOC i determinar les efectivitats de les vacunacions antigripal i antipneumocòccica 23V. METODOLOGIA Es van realitzar quatre estudis observacionals: el primer va ser prospectiu i els tres següents retrospectius. El segon i el tercer estan fets en base a la mateixa població (2.501 malalts MPOC de la Regió Sanitària de Lleida). El primer en base a una mostra de 512 pacients diagnosticats de l’ABS Pla d’Urgell i el quart emprant una mostra de 1.323 de la mateixa ABS. Les variables depenents van ser la exacerbació, l’ingrés hospitalari i la mort. La resta de les variables recollides foren: demogràfiques, paràmetres espiromètrics, gravetat (GOLD), hàbit tabàquic, antecedent d’exacerbació, vacunacions (antigripal i antipneumocòccica 23V), comorbiditat associada (Charlson), BODEx, ansietat/sd depressiva (HAD), grau dispnea, qualitat de vida (EuroQOL 5D). A través de models de regressió logística s’han determinat les variables associades a l’exacerbació, a l’ingrés hospitalari i a la mortalitat global. Alhora, s’han dissenyat models score de predicció del risc. RESULTATS L’efectivitat de la vacunació antigripal per evitar l’ingrés per exacerbació va ser del 90,8% durant els 3 mesos de màxima activitat gripal; i per evitar la mortalitat global, del 33%. Tanmateix, la cobertura vacunal antigripal va ser del 55,3%, La incidència anual d’exacerbació de la MPOC va ser del 61,7%, la d’ingrés hospitalari anual per agudització del 10,8% i la de mortalitat global anual, del 4,2%. Es varen objectivar diferents factors associats sent els més rellevant l’antecedent d’agudització i el d’ingrés per exacerbació. CONCLUSIONS La cobertura de vacunació antigripal en la població és baixa. L’efectivitat de la vacunació antigripal és alta. L’antecedent d’exacerbació resultaria una variable clau a tenir en compte per part del metge i que discriminaria aquells pacients amb un risc major d’exacerbació.INTRODUCCIÓN La EPOC es una patología con una elevada morbimortalidad. La exacerbación es frecuente en la historia natural de la enfermedad y se asocia a una declinación irreversible de la capacidad pulmonar, a una peor calidad de vida y a una disminución en la supervivencia. El objetivo de la tesis fue estudiar la incidencia y los factores de riesgo asociados a la exacerbación de la EPOC y determinar las efectividades de las vacunaciones antigripal y antineumocócica 23V. METODOLOGÍA Se realizaron cuatro estudios observacionales: el primero fue prospectivo y los tres siguientes retrospectivos. El segundo y el tercero han utilizado la misma población (2.501 enfermos EPOC de la Región Sanitaria de Lleida). El primero está realizado en base a una muestra de 512 pacientes diagnosticados del ABS Pla d’Urgell y el cuarto utilizando una muestra de 1.323 pacientes de la misma ABS. Las variables dependientes fueron la exacerbación, el ingreso hospitalario y la muerte. Las demás variables recogidas fueron: demográficas, parámetros espirométricos, gravedad (GOLD), hábito tabáquico, antecedente de exacerbación, vacunaciones (antigripal y antineumocócica 23V), comorbilidad asociada (Charlson), Bodex, ansiedad/sd depresiva (HAD), grado de disnea, calidad de vida (EuroQOL 5D). A través de modelos de regresión logística se han determinado las variables asociadas a la exacerbación, al ingreso y a la mortalidad global. Al mismo tiempo se han diseñado modelos score de predicción del riesgo. RESULTADOS La efectividad de la vacunación antigripal para evitar el ingreso por exacerbación fue del 90,8% durante los 3 meses de máxima actividad gripal; y para evitar la mortalidad, del 33%. Sin embargo, la cobertura vacunal antigripal fue del 55,3%. La incidencia anual de exacerbación de la EPOC fue del 61,7%, la de ingreso hospitalario anual por exacerbación del 10,8% y la de mortalidad global anual del 4,2%. Se objetivaron diferentes factores asociados siendo los más relevantes el antecedente de agudización y el de ingreso por exacerbación. CONCLUSIONES La cobertura de vacunación antigripal en la población es baja. La efectividad de la vacunación es alta. El antecedente de exacerbación resultaría una variable clave a tener en cuenta y que discriminaría aquellos pacientes con un riesgo mayor de exacerbación.INTRODUCTION COPD is a disease with high morbidity and mortality. The exacerbation is common in the natural history of the disease, which is associated with an irreversible decline in lung capacity, a worse quality of life and a decrease in survival. The aim of the thesis was to study the incidence and risk factors associated with the exacerbation of COPD and to determine the effectiveness of flu vaccinations and antipneumococcal 23v. METHODS Four observational studies were conducted: the first was prospective and other three were retrospective. The second and third were carried out on the basis of the same population (2,501 COPD patients within the Lleida Health Care Region). The first was based on a sample of 512 patients diagnosed at the Pla d'Urgell Health Care Centre and the fourth using a sample of 1,323 at the same centre. The dependent variables were exacerbations, hospitalization and death. The remaining variables compiled were: demographics, spirometric parameters, severity (GOLD), smoking habit, a history of exacerbations, vaccination (flu and antipneumococcal 23v) associated comorbidity (Charlson) BODEx, anxiety/depressive ds (HAD), dyspnea level and quality of life (EuroQol 5D). Using logistic regression models we determined the variables associated with exacerbation, hospital admission and overall mortality. At the same time, models/score have been designed for predicting risk. RESULTS The effectiveness of flu vaccinations to prevent admission due to exacerbation was 90.8% during the three months of peak flu activity; and to prevent overall mortality, 33%. However, flu vaccination coverage was 55.3%, the annual incidence of COPD exacerbation was 61.7%, the annual hospitalization for deterioration was 10.8% and annual global mortality was 4.2%. We were able to interpret different factors associated with being the most important antecedent in the intensification and exacerbation of admission. CONCLUSIONS Flu vaccination coverage in the population is low. The effectiveness of the flu vaccine is high. The antecedent of exacerbation would be a key variable for the doctor to take into account, who would differentiate between patients with an increased risk of exacerbation

Clinico-epidemiological characteristics of men and women with a new diagnosis of chronic obstructive pulmonary disease: a database (SIDIAP) study

Background: The risk of developing Chronic Obstructive Pulmonary Disease (COPD), the associated comorbidities and response to bronchodilators might differ in men and women. The objective of this study was to determine the prevalence of COPD and the clinic-epidemiological characteristics of primary care patients with COPD according to gender. Methods: This is a cross-sectional study using electronic healthcare records Catalonia (Spain), during the 01/01/2012-31/12/2017 period. Patients from the SIDIAP database (System for the Development of Research in Primary Care) were included (5,800,000 patients registered in 279 primary care health centres). Clinic-demographic characteristics, comorbidities and blood tests results were collected for each patient. Adjusted OR (ORa) with logistic regression methods were used to determine variables associated with men and women. Results: From an initial sample of 800,899 people, 24,135 (3%) were considered COPD patients, and 22.9%were women. The most common risk factors in women were bronchiectasis (ORa = 20.5, SD = 19.5-21.6), age > 71 years (ORa = 18.8; SD = 17.3-20.5), cor pulmonale (ORa = 5.2; SD = 4.3-6.7) and lung cancer (ORa = 3.6, SD = 3.2-4.0). Men and women presented the same comorbidities, though the strength of association was different for each gender. Conclusions: Patients suffering high comorbidity rates. Comorbidities are similar in men and women, although the strength of association varies according to gender. Women are more susceptible to the harmful effects of smoking and present a higher proportion of bronchiectasis and OSAS. Keywords: Chronic obstructive pulmonary disease; Epidemiology; Prevalence

Alzheimer’s disease mutant mice exhibit reduced brain tissue stiffness compared to wild-type mice in both normoxia and following intermittent hypoxia mimicking sleep apnea

Background: Evidence from patients and animal models suggests that obstructive sleep apnea (OSA) may increase the risk of Alzheimer’s disease (AD) and that AD is associated with reduced brain tissue stiffness. Aim: To investigate whether intermittent hypoxia (IH) alters brain cortex tissue stiffness in AD mutant mice exposed to IH mimicking OSA. Methods: Six-eight month old (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) AD mutant mice and wild-type (WT) littermates were subjected to IH (21% O2 40 s to 5% O2 20 s; 6 h/day) or normoxia for 8 weeks. After euthanasia, the stiffness (E) of 200-μm brain cortex slices was measured by atomic force microscopy. Results: Two-way ANOVA indicated significant cortical softening and weight increase in AD mice compared to WT littermates, but no significant effects of IH on cortical stiffness and weight were detected. In addition, reduced myelin was apparent in AD (vs. WT), but no significant differences emerged in the cortex extracellular matrix components laminin and glycosaminoglycans when comparing baseline AD and WT mice. Conclusion: AD mutant mice exhibit reduced brain tissue stiffness following both normoxia and IH mimicking sleep apnea, and such differences are commensurate with increased edema and demyelination in AD.This work was supported in part by Fundació Marató TV3 (20143231), the Spanish Ministry of Economy and Competitiveness—Instituto de Salud Carlos III (FIS-PI14/00004, FIS-PI14/00280) and SEPAR (139/2015). This work was partially funded by the CERCA Programme of Generalitat de Catalunya

Acetylsalicylic acid prevents intermittent hypoxia-induced vascular remodeling in a murine model of sleep apnea

Study objectives: Chronic intermittent hypoxia (CIH), a hallmark feature of obstructive sleep apnea (OSA), induces accelerated atherogenesis as well as aorta vascular remodeling. Although the cyclooxygenase (COX) pathway has been proposed to contribute to the cardiovascular consequences of OSA, the potential benefits of a widely employed COX-inhibitor such (acetylsalicylic acid, ASA) on CIH-induced vascular pathology are unknown. Therefore, we hypothesized that a common non-selective COX inhibitor such as ASA would attenuate the aortic remodeling induced by CIH in mice. Methods: 40 wild-type C57/BL6malemice were randomly allocated to CIH or normoxic exposures (N) and treated with daily doses of ASA or placebo for 6 weeks. At the end of the experiments, intima-media thickness (IMT), elastin disorganization (ED), elastin fragmentation (EF), length between fragmented fiber endpoints (LFF), aortic wall collagen abundance (AC) and mucoid deposition (MD) were assessed. Results: Compared to N, CIH promoted significant increases in IMT (52.58 ± 2.82μm vs. 46.07 ± 4.18μm, p < 0.003), ED (25.29 ± 14.60% vs. 4.74 ± 5.37%, p < 0.001), EF (5.80 ± 2.04 vs. 3.06 ± 0.58, p < 0.001), LFF (0.65 ± 0.34% vs. 0.14 ± 0.09%, p < 0.001), AC (3.43 ± 1.52% vs. 1.67 ± 0.67%, p < 0.001) and MD (3.40 ± 2.73 μm2 vs. 1.09 ± 0.72 μm2, p < 0.006). ASA treatment mitigated the CIH-induced alterations in IMT: 44.07 ± 2.73μm; ED: 10.57 ± 12.89%; EF: 4.63 ± 0.88; LFF: 0.25 ± 0.17% and AC: 0.90 ± 0.13% (p<0.05 for all comparisons). Conclusions: ASA prevents the CIH-induced aortic vascular remodeling, and should therefore be prospectively evaluated as adjuvant treatment in patients with OSA.This work was supported by the Spanish Respiratory Society (SEPAR), SOCAP, the Associació Lleidatana de Respiratori (ALLER), and the Spanish Fondo de Investigaciones Sanitarias (PI14/00486 and PI14-00004), Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”. DG is supported by National Institutes of Health grant HL130984

Central sleep apnoea is related to the severity and short-term prognosis of acute coronary syndrome

Objective To evaluate the relation of central sleep apnoea (CSA) to the severity and short-term prognosis of patients who experience acute coronary syndrome (ACS). Methods Observational study with cross-sectional and longitudinal analyses. Patients acutely admitted to participating hospitals because of ACS underwent respiratory polygraphy during the first 24 to 72 h. CSA was defined as an apnoea-hypopnoea index (AHI) >15 events·h-1 (>50% of central apnoeas). ACS severity (Killip class, ejection fraction, number of diseased vessels and peak plasma troponin) was evaluated at baseline, and short-term prognosis (length of hospitalization, complications and mortality) was evaluated at discharge.This work was supported by: ResMed Ltd. (Australia); Fondo de InvestigacioÂn Sanitaria (PI10/02763 and PI10/02745), Fondo Europeo de Desarrollo Regional (FEDER), Una manera de hacer Europa; the Spanish Respiratory Society (SEPAR); the Catalonian Cardiology Society, Esteve-Teijin (Spain); Oxigen Salud (Spain); and ALLER. This project has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no [609396]. Cofunded by Ministerio de EconomõÂa y Competitividad [COFUND2014-51501]