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BACKGROUND: Asthma is one of the most common respiratory ailments worldwide. Despite broad understanding of the illness and of the available therapeutic options for it, patients with serious asthma suffer poor monitoring of their illness in 50% of cases. AIM: To assess the impact of the implementation of a mobile application (ESTOI) to control asthma in patients diagnosed with the illness, their adherence to treatment, and their perceived quality of life. METHODOLOGY: Randomized clinical trial with 52 weeks' follow-up of patients with asthma seen in a specialized hospital for their treatment in Spain. Some 108 included patients will be divided into two groups. The intervention group will undergo more exhaustive follow-up than normal, including access to the ESTOI application, which will have various categories of attention: control of symptoms, health recommendations, current treatment and personalized action plan, PEF record, nutritional plan, and chat access with a medical team. The asthma control questionnaire ACT is the main assessment variable. Other variables to be studied include an adherence test for the use of inhalers (TAI), the number of exacerbations, maximum exhalation flow, exhaled nitric oxide test, hospital anxiety and depression scale, asthma quality-of-life questionnaire, forced spirometry parameters (FVC, FEV1, and PBD), and analytic parameters (eosinophilia and IGE). The data will be collected during outpatient visits. TRIAL REGISTRATION: This trial has registered at ClinicalTrials.gov (Identifier: NCT06116292).
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Asma , Telemedicina , Humanos , Calidad de Vida , Asma/diagnóstico , Asma/tratamiento farmacológico , Nebulizadores y Vaporizadores , EspirometríaRESUMEN
The 55th SEPAR Congress was held in Pamplona from 2 to 4 of June 2022. Once again, it was the referral scientific meeting for specialists in pulmonology, thoracic surgery, nursing, physiotherapy, paediatric respiratory diseases and other disciplines involved in respiratory care. The Spanish Society of Pulmonology and Thoracic Surgery showed its national and international leadership in the management of respiratory diseases, which was reflected in a program with an excellent content and a high scientific level. In this review, we offer a summary of some notable aspects covered in six selected areas of interest: pulmonary vascular diseases, non-invasive mechanical ventilation and sleep disorders, asthma, chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), and interventional pulmonolgy and lung transplant.
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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.
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Antiasmáticos , Asma , Productos Biológicos , Humanos , Corticoesteroides/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Asma/inducido químicamente , Productos Biológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Estudios ProspectivosRESUMEN
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.
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OBJECTIVE: To develop a set of recommendations for the management of severe asthma during COVID-19 pandemic. METHODS: Eleven pneumologists and allergologists who were staff members of officially accredited asthma units in Catalonia (Spain) participated in a cross-section study based on three 2-hour virtual workshops (first: brainstorming, second: identification of impacts and challenges summarized in 10 topics, third: establishment of final recommendations by consensus). RESULTS: Impacts and challenges identified were improvement of referral protocols between different levels of care; assessment of the minimum number of function tests to be performed and promote the performance of spirometry in primary care; implementation of videoconferencing, mobile apps, telephone calls, or integral virtual platforms for the follow-up of patients, and definition of the model of care (face-to-face, telematics, mixed) according to the patient's individual needs; self-administration of biologics for domiciliary treatment; and empowerment of the role of nursing and hospital pharmacy in particular for follow-up and self-administration of biologics. The main recommendations included coordination between primary care and specialized care consultation, optimization of lung function testing, implementation of telemedicine, and the role of nursing and hospital pharmacy. CONCLUSION: The specific proposals in response to the effect of COVID-19 pandemic focused on four areas of interest (coordination between primary care and specialized care, optimization of lung function testing, implementation of telemedicine, and empowerment of the role of nursing and hospital pharmacy) may be generalized to other health care settings, and help to introduce new ways of caring asthma patients in the COVID-19 context.
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Asma , Productos Biológicos , COVID-19 , Telemedicina , Asma/diagnóstico , Asma/tratamiento farmacológico , Humanos , PandemiasRESUMEN
BACKGROUND: Sudan red or 1-[(2-methoxyphenyl)azo]-2-naphthol is a low molecular weight azoic agent widely used in industry, particularly in the production of hair dyes. The use of this product in the food industry is prohibited due to its potential carcinogenic effect, but no respiratory involvement has been reported to date. CASE PRESENTATION: We present the case of a 46-year-old female patient who had been working in a cosmetics packaging company for 20 years. The patient developed occupational asthma to a red azo dye known as Sudan red. The diagnosis was confirmed by specific bronchial provocation test. Induced sputum samples were obtained previously and in the 24 h following the procedure, with a rise in the percentage of eosinophils from 10 to 65%. CONCLUSIONS: This report describes the case of a patient who developed OA caused by exposure to an azoic dye called Sudan red. The clinical and analytical features suggest a type 2-related asthma; however, we are not yet able to confirm the specific pathophysiological mechanism. The extensive use of azo dyes in industry means that it is particularly important to describe their implications for health, which are probably underestimated at present.
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Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment.
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Regulación de la Expresión Génica , Arteria Pulmonar/patología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Nucleótidos de Purina/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Transducción de Señal , Fumar/efectos adversosRESUMEN
BACKGROUND: Extracellular adenosine triphosphate (ATP) is up-regulated in the airways of patients with chronic obstructive pulmonary disease (COPD), resulting in increased inflammation, bronchoconstriction, and cough. Although extracellular ATP levels are tightly controlled by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; also known as CD39) in the lungs, the role of CD39 in the pathology of COPD is unknown. We hypothesized that alterations in the expression and activity of CD39 could be part of the mechanisms for initiating and perpetuating the disease. METHODS: We analyzed CD39 gene and protein expression as well as ATPase enzyme activity in lung tissue samples of patients with COPD (n = 17), non-obstructed smokers (NOS) (n = 16), and never smokers (NS) (n = 13). Morphometry studies were performed to analyze pulmonary vascular remodeling. RESULTS: There was significantly decreased CD39 gene expression in the lungs of the COPD group (1.17 [0.85-1.81]) compared with the NOS group (1.88 [1.35-4.41]) and NS group (3.32 [1.23-5.39]) (p = 0.037). This attenuation correlated with higher systemic inflammation and intimal thickening of muscular pulmonary arteries in the COPD group. Lung CD39 protein levels were also lower in the COPD group (0.34 [0.22-0.92]) compared with the NOS group (0.67 [0.32-1.06]) and NS group (0.95 [0.4-1.1) (p = 0.133). Immunohistochemistry showed that CD39 was downregulated in lung parenchyma, epithelial bronchial cells, and the endothelial cells of pulmonary muscular arteries in the COPD group. ATPase activity in human pulmonary structures was reduced in the lungs of patients with COPD. CONCLUSION: An attenuation of CD39 expression and activity is presented in lung tissue of stable COPD patients, which could lead to pulmonary ATP accumulation, favoring the development of pulmonary inflammation and emphysema. This may be a mechanism underlying the development of COPD.
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Adenosina Trifosfato/metabolismo , Apirasa/biosíntesis , Pulmón/metabolismo , Arteria Pulmonar/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Transducción de Señal/fisiología , Anciano , Apirasa/genética , Femenino , Expresión Génica , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Arteria Pulmonar/patología , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
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%±1.9% vs 68.8%±2.4%, p=0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%±3.1% vs 61.7%±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.
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Plaquetas/metabolismo , Activación Plaquetaria , Enfermedad Pulmonar Obstructiva Crónica/sangre , Anciano , Biomarcadores/sangre , Plaquetas/efectos de los fármacos , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Moléculas de Adhesión Celular/sangre , Progresión de la Enfermedad , Femenino , Humanos , Inflamación/sangre , Inflamación/complicaciones , Mediadores de Inflamación/sangre , Recuento de Leucocitos , Masculino , Proteínas de Microfilamentos/sangre , Persona de Mediana Edad , Fosfoproteínas/sangre , Activación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pruebas de Función Plaquetaria , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Factores de RiesgoRESUMEN
The respiratory Day Hospital (DH) is a care facility currently operating at various healthcare institutions. It monitors patients with severe chronic obstructive pulmonary disease (COPD) presenting repeated exacerbations with at least two hospital admissions per year. The main aim of the study was to evaluate the effectiveness of the DH program for controlling admissions for COPD exacerbations in this cohort of patients, and to identify clinical factors associated with hospitalizations and mortality. An observational prospective multicenter study was carried out at three hospitals. The sample comprised 150 consecutive patients (median age 70 [65-76] years, FEV1 33 [26-43]%, 97% males), included at the DH program. Over a one-year period, variables assessing effectiveness and use of healthcare resources were recorded. Factors associated with hospitalizations and mortality were identified. Patients made a median of 4[2-5] emergency visits due to COPD exacerbations with a median of 1[0-2] hospitalization(s)/year. Most of exacerbations (77%) were evaluated at the DH, but there were fewer hospitalizations from the DH than from the emergency department (21% vs. 81%, p < 0.001). In all, 29% of the patients had at least two admissions; these were the patients with the most severe disease. Age, readmission at 30-days and the presence of respiratory failure were the predictors of mortality. In conclusion, the DH program is an effective model for reducing hospitalizations in this cohort of patients. In all, 29% of the patients required two hospital admissions or more; these patients had more advanced disease and poorer prognosis, and would be most likely to benefit from additional care support.
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Atención Ambulatoria/métodos , Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Aguda , Anciano , Atención a la Salud/métodos , Atención a la Salud/organización & administración , Progresión de la Enfermedad , Femenino , Recursos en Salud/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital , Estudios Prospectivos , España/epidemiologíaRESUMEN
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.
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Quimiocinas CC/metabolismo , Arteria Pulmonar/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Anciano , Quimiocinas CC/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Expresión Génica , Humanos , Pulmón/metabolismo , Pulmón/patología , Masculino , Persona de Mediana Edad , Arteria Pulmonar/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Fumar/metabolismo , Arterias Torácicas/metabolismo , Arterias Torácicas/fisiopatología , Remodelación VascularRESUMEN
BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a frequent condition in chronic obstructive pulmonary disease (COPD). Tenascin-C (Tn-C) and matrix metalloproteinase-9 (MMP-9) are extracellular matrix proteins associated with myocardial fibrosis and wall remodeling because of inflammation. OBJECTIVE: To determine whether the circulating levels of inflammatory markers, Tn-C and MMP-9 are associated with LVDD in COPD patients. METHODS: Forty-two severe stable COPD patients (64 ± 8 years, 88% male, FEV1% 38 ± 5.7) and a control group (n = 11) were included. Pulmonary function tests and a Doppler echocardiography were performed on COPD patients. Baseline serum levels of C-reactive protein (CRP), leukocytes, fibrinogen, interleukins (IL) 6 and 8, Tn-C and MMP-9 were analyzed in all participants. RESULTS: COPD patients were classified in two groups: LVDD (n = 35) and non-LVDD (n = 7). Serum levels of IL-6 and CRP were higher in the LVDD group compared to the non-LVDD group [median(IQR)] [3.46 pg/mL (2.36-4.74) vs 1.87 pg/mL (1.10-3.28), P = 0.045] and [6.0 mg/L (3.0-13.0) vs 1.0 mg/L (1.0-2.3), P = 0.001], respectively. The same trend was observed in the analysis adjusted by age and BMI, being significant for CRP (P = 0.04). Circulating IL-6 was associated with the type of LVDD, being higher in the type-II (P = 0.046). Obese patients with COPD-LVDD showed a higher level of inflammatory markers (P = 0.021). Tn-C were significantly higher in patients with LVDD type-II compared to type-I [1422 ng/mL (826-1948) vs 781 ng/mL (640-1139), P = 0.015], without differences in MMP-9. CONCLUSIONS: Severe COPD patients with LVDD showed a different inflammatory pattern, suggesting a link between low-grade inflammation and the presence of LVDD. In COPD, high levels of Tn-C are related to LVDD type-II.
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Metaloproteinasa 9 de la Matriz/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Tenascina/metabolismo , Disfunción Ventricular Izquierda/sangre , Anciano , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Estudios Transversales , Ecocardiografía Doppler/métodos , Femenino , Humanos , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Obesidad/sangre , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Pruebas de Función Respiratoria/métodos , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/fisiopatología , Prueba de Paso/métodosRESUMEN
Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.
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Infecciones Bacterianas , Inflamación/inmunología , Enfermedad Pulmonar Obstructiva Crónica , Prevención Secundaria/métodos , Virosis , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/inmunología , Infecciones Bacterianas/prevención & control , Toma de Decisiones Clínicas , Ensayos Clínicos como Asunto , Manejo de la Enfermedad , Progresión de la Enfermedad , Humanos , Guías de Práctica Clínica como Asunto , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Factores de Riesgo , Índice de Severidad de la Enfermedad , Brote de los Síntomas , Virosis/complicaciones , Virosis/prevención & controlRESUMEN
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes. METHODS: All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio. RESULTS: In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008). CONCLUSIONS: Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.
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Enfermedad Pulmonar Obstructiva Crónica/patología , Remodelación Vascular , Anciano , Aorta/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Pulmonar/patología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Túnica Íntima/patología , Calcificación Vascular/patologíaRESUMEN
PURPOSE: Fibronectin (Fn) and tenascin-C (TnC) are two extracellular matrix proteins associated with remodeling changes. Fn and TnC gene and protein expression in lung tissue, including their predominant location in bronchial and pulmonary artery structures, have not yet been fully evaluated. The aim of the present study was to assess: (1) gene expression of Fn and TnC in lung samples from chronic obstructive pulmonary disease (COPD) and non-COPD subjects; and (2) protein content and location of Fn and TnC in both groups. METHODS: Consecutive subjects requiring lung resection due to lung cancer surgery were included. Lung specimens were examined for gene expression by quantitative real-time PCR (values expressed as fold change ratio). The analysis of their protein content and location was performed by western blot and immunohistochemical studies, respectively. Patients were divided into two cohorts according to COPD status. RESULTS: A total of 41 patients (20 with COPD and 21 without COPD) were included. An enhanced Fn gene expression was observed in the COPD group compared to the non-COPD group (4.73 ± 0.54 vs. 2.65 ± 0.57; P = 0.012), whereas no differences in gene TnC expression were observed (2.91 ± 0.44 vs. 2.60 ± 0.48; P = 0.633). No differences in lung protein content and location were found between groups. Immunohistochemical evaluation showed a predominantly vascular and bronchial location of Fn and TnC in both groups. CONCLUSIONS: An enhanced lung gene expression of Fn was observed in COPD subjects compared to non-COPD subjects. No differences were found in Fn protein expression or in TnC gene or protein expression among groups.
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Fibronectinas/análisis , Fibronectinas/genética , Pulmón/química , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Tenascina/análisis , Tenascina/genética , Anciano , Remodelación de las Vías Aéreas (Respiratorias) , Western Blotting , Estudios de Casos y Controles , Femenino , Regulación de la Expresión Génica , Humanos , Inmunohistoquímica , Pulmón/fisiopatología , Pulmón/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Roflumilast is used in severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. However, limited information is available on its impact in a "real-life" population that may be receiving triple therapy. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of roflumilast in COPD patients already receiving triple therapy (long-acting ß-agonist/inhaled corticosteroids and long-acting muscarinic antagonist). METHODS: Prospective registry that included COPD patients who were prescribed roflumilast added to triple therapy. The yearly rate of all COPD exacerbations before and after roflumilast and side effects related to the drug were registered. RESULTS: Among 55 patients prescribed 500 mg of roflumilast. Only 50.9% (n = 28) completed 1 year of therapy (roflumilast group). A reduction of all exacerbations with roflumilast was observed (2.75 ± 0.29 vs. 3.57 ± 0.26; P = 0.022), with a particular benefit in patients with ≥4 exacerbations prior to initiating therapy (3.55 ± 0.51 vs. 5.00 ± 0.30; P = 0.034). Side effects (mainly gastrointestinal) and treatment discontinuation occurred in 69.1% and 49.1% of the overall population, respectively. CONCLUSIONS: Roflumilast, when added to triple therapy, reduces exacerbations in a "real-life" population of severe COPD patients with frequent exacerbations. However, side effects are more common and lead more frequently to discontinuation of therapy than has been reported in trials.
Asunto(s)
Aminopiridinas/uso terapéutico , Benzamidas/uso terapéutico , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Agonistas Adrenérgicos beta/administración & dosificación , Agonistas Adrenérgicos beta/efectos adversos , Agonistas Adrenérgicos beta/uso terapéutico , Anciano , Aminopiridinas/administración & dosificación , Aminopiridinas/efectos adversos , Benzamidas/administración & dosificación , Benzamidas/efectos adversos , Ciclopropanos/administración & dosificación , Ciclopropanos/efectos adversos , Ciclopropanos/uso terapéutico , Quimioterapia Combinada , Femenino , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/efectos adversos , Antagonistas Muscarínicos/uso terapéutico , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Sistema de Registros , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: A subclinical left ventricle diastolic dysfunction (LVDD) has been described in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To evaluate the prevalence of LVDD in stable severe COPD patients, to analyze its relationship with exercise capacity and to look for its possible causes (lung hyperinflation, ventricular interdependence or inflammatory mechanisms). METHODS: We evaluated 106 consecutive outpatients with severe COPD (FEV1 between 30-50%). Thirty-three (31%) were excluded because of previous heart disease. A pulmonary function test, a 6-minute walking test (6MWT), a Doppler echocardiography test, including diastolic dysfunction parameters, and an analysis of arterial blood gases, NT-proBNP and serum inflammatory markers (CRP, leucocytes), were performed in all patients. RESULTS: The prevalence of LVDD in severe stable COPD patients was 90% (80% type I, n=57, and 10% type II, n=7). A significant association between a lower E/A ratio (higher LVDD type I) and a lower exercise tolerance (6-minute walked distance (6MWD)) was found (r=0.29, p<0.05). The fully adjusted multivariable linear regression model demonstrated that a lower E/A ratio, a DLCO in the quartile 4(th) and a higher tobacco consumption were associated with a lower 6MWD (76, 57 and 0.7 metres, respectively, p<0.05). A significant correlation between E/A ratio and PaO2 was observed (r=0.26, p<0.05), but not with static lung hyperinflation, inflammation or right ventricle overload parameters. CONCLUSION: In stable severe COPD patients, the prevalence of LVDD is high and this condition might contribute in their lower exercise tolerance. Hypoxemia could have a concomitant role in their pathogenesis.