RESUMEN
Background and Objectives: Procalcitonin (PCT) is a useful biomarker for the diagnosis of sepsis. Inflammatory markers are elevated in patients with Hodgkin lymphoma (HL), and yet ongoing infection rarely coexists at diagnosis. PCT levels might be helpful in differentiating bacterial from disease-related inflammation. Materials and Methods: We evaluated serum PCT levels and other inflammation markers in newly diagnosed HL patients. Values < 0.50 ng/mL were considered normal (0.10−0.50 ng/mL: detectable, <0.10 ng/mL: undetectable), while values ≥ 0.50 ng/L were considered elevated. Results: Among 137 patients, 55 had B symptoms (40%), 77/130 (59%) had elevated Erythrocyte Sedimentation Rate (ESR) and 116 (85%) had elevated C-Reactive Protein (CRP) (median 38.1 mg/L (range; 2.97−328)). PCT levels were normal in most patients (undetectable 94/137 (68.5%) and detectable 41/137(30%)) with median value < 0.10 ng/mL (range; <0.10−15.90). Elevated PCT was recorded in only two patients (1.5%). Patients with PCT < 0.10 ng/mL had significantly lower median CRP (25.75; range (2.97−203.0)) compared to patients with PCT ≥ 0.1 ng/mL (median CRP 92.50 mg/L; range (3.34−328.0)). Almost all patients (40/41, 97.6%) with detectable PCT had elevated CRP. Conclusions: This is the first study showing that the inflammation characterizing HL is not associated with PCT elevations, although CRP levels are elevated in 85% of the patients. Normal PCT levels may rule out the possibility of occult infection, thus preventing extensive evaluation, which may delay treatment initiation.
Asunto(s)
Enfermedad de Hodgkin , Polipéptido alfa Relacionado con Calcitonina , Humanos , Calcitonina , Proteína C-Reactiva/análisis , Enfermedad de Hodgkin/diagnóstico , Biomarcadores , InflamaciónRESUMEN
PURPOSE: In the present prospective multicentre observational study, we evaluated the potential role of blood eosinophils on the outcomes of patients hospitalized for COPD exacerbations. MATERIAL AND METHODS: Consecutive patients >40 years with a previous COPD diagnosis were recruited. Blood eosinophils were measured on admission prior to the initiation of treatment and were evaluated in three groups (<50, 50-149 and ≥150 cells/µL). Patients received standard care and were followed up for a year. RESULTS: A total of 388 patients were included (83.5% male, mean age 72 years). Patients with higher blood eosinophils had less dyspnoea (Borg scale), lower C-reactive protein (CRP) and higher PaO2/FiO2 (partial pressure for oxygen/fraction of inhaled oxygen), and were discharged earlier (median 11 vs. 9 vs. 5 days for patients with <50, 50-149 and ≥150 cells/µL, respectively). Patients with <50 cells/µL presented higher 30-day and 1-year mortality, whereas there were no differences in moderate/severe COPD exacerbations between the three groups. In a post hoc analysis, treatment with inhaled corticosteroids as per physicians' decision was associated with better exacerbation prevention during follow-up in patients with ≥150 cells/µL. CONCLUSIONS: Higher blood eosinophils were associated with better outcomes in hospitalized COPD patients, further supporting their use as a prognostic biomarker.
Asunto(s)
Eosinófilos/metabolismo , Hospitalización/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Anciano , Proteína C-Reactiva/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Pronóstico , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapiaRESUMEN
BACKGROUND: In the last decade, the advent of thoracic endosonography has revolutionised the field of diagnostic bronchoscopy. METHODS: We conducted a single-centre prospective study in "Sotiria" Chest diseases hospital between January 2016 and December 2019. The study aimed to evaluate the efficacy and diagnostic value of combined EBUS/EUS-b in comparison with EBUS-TBNA and EUS-b FNA in different intrathoracic diseases. RESULTS: A total of 266 patients were enrolled (70.7% males, 85.7% smokers, mean age ± SD: 62.8 ± 11.8). Diagnosis and staging of suspected lung cancer (LC) were the main indications for EBUS/EUS-b in 56.7% of patients, followed by lymphadenopathy of unknown origin in 27%, lymphadenopathy in previous malignancy in 10.9%, and staging of proven LC in 5.3%. EUS-b FNA alone or combined with EBUS-TBNA was performed in 14.7% of patients. A total of 512 lymph nodes was sampled (481 through EBUS-TBNA and 31 through EUS-b FNA). EBUS/EUS-b led to a definitive diagnosis in 68.4% of the patients. Most cases (50.4%) were malignancies, while 18% represented benign diseases (83.3% sarcoidosis). Sensitivity of combined EBUS/EUS-b was higher in comparison with sensitivity of both procedures alone (100% vs 89.4% vs 88.9%). Accordingly, the overall sensitivity of EBUS/EUS-b for the detection of malignancy and sarcoidosis was 93% and 95.2%, respectively. No severe complications were observed. CONCLUSION: Thoracic endosonography is an efficient, safe, minimally invasive tool yielding high sensitivity and diagnostic accuracy in patients with suspected malignancy and mediastinal lymphadenopathy. Experienced pulmonologists in EBUS-TBNA should more routinely perform EUS-b FNA to avoid unnecessary surgical interventions.
Asunto(s)
Endosonografía , Neoplasias Pulmonares , Femenino , Grecia , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Systemic inflammation may be the common denominator between COPD and type 2 diabetes and may explain the correlation in both diseases' development and progress. The aim of this prospective observational study is to examine the prognostic value of glycated hemoglobin levels (HbA1c) and HbA1c-adjusted glycemic variables (glycemic gap, stress hyperglycemia ratio και modified stress hyperglycemia ratio) in an acute exacerbation of COPD (AECOPD) as well as in COPD disease's morbidity and mortality during the following year. We evaluated patients hospitalized only for COPD exacerbations. Levels of HbA1c and HbA1c-adjusted glycemic variables were recorded upon admission. The study outcomes included duration of hospital stay, need for mechanical ventilation and exacerbation outcome. All subjects were followed up for one year. A total of 156 patients were included in the study (74.4% men, age [mean ± SD] 72 ± 7 years). Patients (21.8%) had type 2 diabetes and 67.9% of patients were receiving ICS treatment. The median value of HbA1c was 5.9 (IQR: 5.4, 6.5). Necessity for mechanical ventilation was significantly higher for patients with lower values of HbA1c [median: 5.3 (IQR 5.02, 6.3) vs. 5.9 (IQR 5.5, 6.5), p = .038]. However, duration of hospitalization, death during hospitalization as well as the number of new exacerbation events, time to next exacerbation and mortality during the following year did not differ significantly. Moreover, none of the HbA1c-adjusted glycemic variables examined, demonstrated any statistical significance. In conclusion neither the preceding nor the present glycemic state exhibit a predictive value regarding short- or long-term outcomes of an AECOPD.
Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperglucemia , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Glucemia , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Femenino , Hemoglobina Glucada/análisis , Hospitalización , Humanos , MasculinoRESUMEN
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) remains a major burden with no clinically applicable biomarkers. AIM: To investigate the association of Red cell Distribution Width (RDW) values on admission with previous hospitalizations, need of non-invasive mechanical ventilation (NIMV) and long term oxygen therapy (LTOT) in patients with COPD. METHODS: Patients with AECOPD admitted to our department during 2018 were included in the study. RESULTS: One hundred sixty patients were enrolled (M/F 95/65, median age 71.00 years, mean FEV1± SD = 46.6 ± 28.9). Median RDW was significantly higher for patients in need of NIMV (14.8, 95% CI: 14.2 to 15.6) than patients not in need of NIMV (13.5, 95% CI: 13.2 to 13.8) (p < 0.001). Median RDW was significantly higher for patients in need of LTOT (14.2, 95% CI: 13.7 to 14.6) compared to patients not receiving LTOT (13.2, 95% CI: 12.5 to 13.6) (p = 0.001). Patients with hospitalization during the last 12 months had increased RDW values compared to patients with no hospitalizations [median RDW 14.3, (95% CI: 13.5 to 14.9) versus median RDW 13.5, (95% CI: 13.1 to 13.9)](p = 0.001). CONCLUSION: Patients with COPD in need of LTOT, NIMV or patients with previous hospitalizations presented with increased RDW values. Increased RDW values could serve as a negative prognostic marker in patients with COPD.
Asunto(s)
Índices de Eritrocitos/fisiología , Eritrocitos/patología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Anciano , Biomarcadores , Estudios de Cohortes , Femenino , Humanos , Hipercapnia , Masculino , Ventilación no Invasiva , Pronóstico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Plasma drug concentrations, spectrum of antibacterial activity and minimum inhibitory concentration (MIC) had been widely considered as markers of the efficacy of antibiotics. Nonetheless, in several cases, antibiotics characterized by all these features were ineffective for the treatment of respiratory tract infections. A typical paradigm represented the case of patients with bronchiectasis who do not always benefit from antibiotics and thus experiencing increased sputum production, worse quality of life, more rapid forced expiratory volume in the first second (FEV1) decline, more frequent exacerbations and increased mortality rates, especially those with Pseudomonas aeruginosa (P. aeruginosa) chronic infection. Subsequently, penetrance of antibiotics in the epithelial lining fluid has gradually emerged as another key factor for the outcome of antibiotic treatment. Given that a plethora of antibiotics presented with poor or intermediate penetrance in the epithelial lining fluid, inhaled antibiotics targeting directly the site of infection emerged as a new option for patients with respiratory disorders including patients with bronchiectasis. This review article intends to summarize the current state of knowledge for the penetrance of antibiotics in the epithelial lining fluid and present results from clinical trials of inhaled antibiotics in patients with bronchiectasis of etiology other than cystic fibrosis.
Asunto(s)
Antibacterianos/administración & dosificación , Bronquiectasia/complicaciones , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Administración por Inhalación , Ensayos Clínicos como Asunto , Humanos , Pulmón/efectos de los fármacos , Penetrancia , Infecciones por Pseudomonas/tratamiento farmacológicoRESUMEN
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and asthma remain a major health burden. Adherence to inhaled therapy is critical in order to optimize treatment effectiveness. Properly designed questionnaires can assess patients' satisfaction with their inhaler devices. PATIENTS AND METHODS: A total of 766 patients with COPD, asthma or Asthma-COPD Overlap (ACO) were initially enrolled. During their first visit, patients were classified into three groups (Diskus™, Elpenhaler®, Turbuhaler®). Patients completed the FSI-10 questionnaire on Day 0 and Day 60. Test-retest reliability was evaluated. RESULTS: A total of 705 patients completed the study. FSI-10 questionnaire had good test-retest reliability (Total Intraclass Correlation Coefficient: 0.86). All dry powder inhaler (DPIs) yielded satisfactory results. Median score of FSI-10 questionnaire in first visit (FSI-10-I) was significantly higher for patients receiving Elpenhaler® (45, 95% CI: 44 to 46) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (42, 95% CI: 41 to 43) (pâ¯<â¯0.001). Accordingly, median score of FSI-10 questionnaire in the final visit (FSI-10-II) was significantly higher for patients receiving Elpenhaler® (46, 95% CI: 45 to 47) than patients receiving Diskus™ (42, 95% CI: 41 to 43) and Turbuhaler® (43, 95% CI: 42 to 44) (pâ¯<â¯0.001). CONCLUSION: FSI-10 questionnaire had good test-retest reliability and thus can be used in the follow-up of patients with COPD, asthma and ACO. All DPIs were highly acceptable among all study groups. Elpenhaler® achieved significantly higher ratings than Diskus™ and Turbuhaler® in FSI-10 score and presented higher preference among patients with obstructive lung diseases.
Asunto(s)
Antiasmáticos/administración & dosificación , Asma/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/instrumentación , Inhaladores de Polvo Seco/instrumentación , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Adulto , Anciano , Anciano de 80 o más Años , Inhaladores de Polvo Seco/estadística & datos numéricos , Diseño de Equipo , Femenino , Grecia , Humanos , Pulmón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
OBJECTIVES: The aim of the study was to assess the impact of social distancing interventions in Greece and to examine what would have happened if those interventions had not been implemented. STUDY DESIGN: A dynamic, discrete time, stochastic individual-based model was developed to simulate coronavirus disease 2019 (COVID-19) transmission. METHODS: The model was fitted to the observed trends in COVID-19 deaths and intensive care unit (ICU) bed use in Greece. RESULTS: If Greece had not implemented social distancing interventions, the healthcare system would have been overwhelmed between March 30 and April 4. The combined social distancing interventions and increase in ICU beds averted 4360 (95% credible interval: 3050, 5700) deaths and prevented the healthcare system from becoming overwhelmed. CONCLUSIONS: The quick and accurate interventions of the Greek government limited the burden of the COVID-19 outbreak.
Asunto(s)
Infecciones por Coronavirus/prevención & control , Brotes de Enfermedades/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Distancia Psicológica , Política Pública , Ocupación de Camas/estadística & datos numéricos , COVID-19 , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/transmisión , Atención a la Salud/organización & administración , Gobierno , Grecia/epidemiología , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricos , Modelos Teóricos , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Neumonía Viral/transmisiónAsunto(s)
Progresión de la Enfermedad , Recursos en Salud , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Recursos en Salud/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
Chronic obstructive pulmonary disease (COPD) is a major health problem worldwide, with co-morbidities contributing to the overall severity and mortality of the disease. The incidence and prevalence of cardiovascular disease among COPD patients are high. Both disorders often co-exist, mainly due to smoking, but they also share common underlying risk factors, such as aging and low-grade systemic inflammation. The therapeutic approach is based on agents, whose pharmacological properties are completely opposed. Beta2-agonists remain the cornerstone of COPD treatment due to their limited cardiac adverse effects. On the other hand, beta-blockers are administered in COPD patients with cardiovascular disease, but despite their proven cardiac benefits, they remain underused. There is still a trend among physicians over underprescription of these drugs in patients with heart failure and COPD due to bronchoconstriction. Therefore, cardioselective beta-blockers are preferred, and recent meta-analyses have shown reduced rates in mortality and exacerbations in COPD patients treated with beta-blockers.
Asunto(s)
Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Antagonistas Adrenérgicos beta/administración & dosificación , Enfermedades Cardiovasculares , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Comorbilidad/tendencias , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Salud Global , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factores de Riesgo , Tasa de Supervivencia/tendenciasRESUMEN
INTRODUCTION: Bronchiectasis is a heterogeneous entity, taking into account clinical characteristics, inflammatory response, effectiveness of treatment and frequency of exacerbations. In stable state non-cystic fibrosis (non-CF) bronchiectasis, little is known about non-invasive techniques used for evaluating airway inflammation in obstructive airway diseases. OBJECTIVES: We sought to evaluate the associations between induced sputum and clinical/radiologic characteristics, and the differences between biomarkers expressing Th1 and Th2 response in patients with non-CF bronchiectasis and to compare our findings with a previously studied population of patients with asthma and COPD. METHODS: We evaluated prospectively collected data from subjects with bronchiectasis. Comparisons were made between clinical, radiographic and physiologic characteristics, as well as induced sputum markers using appropriate statistical tools. We compared the levels of sputum markers with those of a previously studied cohort of asthma and COPD patients. RESULTS: We enrolled 40 subjects (21men, mean age 63.5yrs) with bronchiectasis. Fifteen subjects (37.5%) had a neutrophilic phenotype, 7 (17.5%) had an eosinophilic phenotype, 3 (12.5%) had a mixed neutrophilic-eosinophilic phenotype and 15 (37.5%) had a paucigranulocytic phenotype. Subjects with sputum neutrophilia had more severe bronchiectasis in HRCT and higher levels of IL-8 in sputum, whereas subjects with eosinophilia had higher levels of FeNO, greater bronchodilator reversibility and higher sputum IL-13. Sputum IL-8 levels were higher in subjects exhibiting frequent exacerbations and correlated with neutrophils in sputum (r=0.799), the extent of bronchiectasis in HRCT (r=0.765) and post-bronchodilator FEV1 (r=-0.416). Sputum IL-13 levels correlated with sputum eosinophils (r=0.656) and bronchodilator reversibility (r=0.441). Neutrophilic bronchiectasis exhibited comparable IL-8 levels to COPD, whereas eosinophilic bronchiectasis showed significantly lower IL-13 levels compared to asthma. CONCLUSIONS: Sputum cell counts and IL-8 and IL-13 correlate with distinct clinical and functional measurements of disease severity and therefore may have a role for non-invasively assessing inflammation in non-cystic fibrosis bronchiectasis.
Asunto(s)
Bronquiectasia/complicaciones , Fibrosis Quística/complicaciones , Inflamación/complicaciones , Bronquiectasia/microbiología , Bronquiectasia/fisiopatología , Recuento de Células , Fibrosis Quística/microbiología , Fibrosis Quística/fisiopatología , Demografía , Femenino , Humanos , Inflamación/microbiología , Inflamación/fisiopatología , Interleucina-13/metabolismo , Interleucina-8/metabolismo , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Fenotipo , Pseudomonas aeruginosa/fisiología , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Esputo/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Activin A is a pleiotropic cytokine holding a fundamental role in inflammation and tissue remodelling. Follistatin can modulate the bioactivity of activin. We aimed to measure activin A and follistatin in sputum supernatants and bronchoalveolar lavage (BAL) of asthmatic patients and to determine the possible associations with severity as well as with inflammatory and remodelling indices. METHODS: A total of 58 asthmatic patients (33 with severe refractory asthma (SRA)) and 10 healthy controls underwent sputum induction for % cells, activin A, follistatin, eosinophilic cationic protein (ECP), transforming growth factor beta 1 (TGF-ß1), IL-13 and IL-8 measurements. In 22 asthmatic patients, BAL and bronchial biopsies were also performed for the assessment of the above-mentioned variables, measurement of remodelling indices and immunostaining for different activin A receptors. RESULTS: Sputum activin A (pg/mL) was higher in patients with SRA (median (interquartile ranges): 76 (33-185)) compared to mild-to-moderate asthma (44 (18-84); P = 0.005), whereas follistatin did not differ between the two groups. BAL activin A (pg/mL) was higher in patients with SRA compared to those with mild-to-moderate disease. A significant association was observed between activin A and TGF-ß1, eosinophils in sputum and/or in BAL, while reticular basement membrane (RBM) thickness was significantly associated with BAL activin levels only. No difference in immunostaining for activin receptor type IB was observed between patients with SRA and those with mild-to-moderate asthma. CONCLUSION: Sputum and BAL levels of activin A are higher in SRA. The association of activin A with TGF-ß1, eosinophils and RBM thickness may indicate a role of this cytokine in the inflammatory and remodelling process in SRA.
Asunto(s)
Activinas/metabolismo , Asma/metabolismo , Bronquios/patología , Líquido del Lavado Bronquioalveolar/química , Folistatina/metabolismo , Esputo/metabolismo , Adulto , Anciano , Remodelación de las Vías Aéreas (Respiratorias) , Asma/patología , Asma/fisiopatología , Membrana Basal/patología , Líquido del Lavado Bronquioalveolar/citología , Estudios de Casos y Controles , Citocinas/metabolismo , Eosinófilos , Femenino , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Esputo/citología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Sputum and blood eosinophils are proposed as candidate biomarkers for the identification of chronic obstructive pulmonary disease (COPD) patients at risk for exacerbation and treatment response. In this study, we evaluated the associations of eosinophils with the presence of emphysema in COPD patients. Induced sputum and blood eosinophil measurements were performed in consecutive COPD patients. Patients underwent lung function testing and high resolution computed tomography (HRCT) of the chest and the presence of emphysema was quantified. Patients with emphysematous lesions in ≥15% of the pulmonary parenchyma were considered having significant emphysema. Ninety-eight patients were included in the study. Patients with significant emphysema had lower blood eosinophil counts compared to patients without emphysema [median (IQR) 34.6 (0.0, 63.0) vs. 169.0 (110.0, 260.0) cells/µL, p < 0.001]; similar results were observed for the percentage (%) of blood eosinophils, but no difference was observed for sputum eosinophils. The differences were evident in frequent and non-frequent exacerbators and irrespective of the use of inhaled corticosteroids (ICS). Patients with significant emphysema in HRCT present lower levels of blood eosinophils and these differences were present irrespective of the frequent exacerbator history or the use of ICS. Blood eosinophils may not represent a clinically relevant biomarker in the presence of emphysema.
Asunto(s)
Eosinófilos/citología , Enfisema Pulmonar/inmunología , Anciano , Estudios Transversales , Eosinófilos/inmunología , Femenino , Volumen Espiratorio Forzado , Humanos , Recuento de Leucocitos , Masculino , Flujo Espiratorio Medio Máximo , Persona de Mediana Edad , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/fisiopatología , Índice de Severidad de la Enfermedad , Esputo/citología , Tomografía Computarizada por Rayos X , Capacidad VitalRESUMEN
BACKGROUND: Angiopoietin-1 (Ang-1) is an essential mediator of angiogenesis by establishing vascular integrity, whereas angiopoietin-2 (Ang-2) acts as its natural inhibitor. OBJECTIVE: We aimed to determine the levels of angiopoietins in sputum supernatants of patients with optimally treated asthma and to investigate whether smoking represents a significant covariate on the above possible processes. METHODS: Eighty-seven patients with asthma (42 smokers) and 28 healthy subjects (14 smokers) were studied. All subjects underwent lung function tests, bronchial hyper-responsiveness assessment and sputum induction for cell count identification and measurement of Ang-1, Ang-2, vascular endothelial growth factor, TGF-ß1, MMP-2, IL-13, Eosinophilic cationic protein and IL-8 in supernatants. Airway vascular permeability (AVP) index was also assessed. RESULTS: Ang-1 (ng/mL) levels were significantly higher in patients with asthma compared to normal subjects. Smoking significantly increased Ang-1 levels [median, interquartile ranges 24 (13-37) in smoking asthmatics vs 10 (7-14) in nonsmoking asthmatics vs 5·3 (3·7-6·5) and 4·6 (3·8-5·7) in healthy smokers and nonsmokers, respectively, P < 0·001]. Similar results were observed for Ang-2 (pg/mL) [168 (132-203) vs 124 (82-152) vs 94 (78-113) vs 100 (96-108), respectively, P < 0·001]. Regression analysis in the whole study population showed a significant negative association for Ang-1, with AVP index, and MMP-2. Smoking was a significant covariate for both Ang-1 and Ang-2 in asthmatic patients. CONCLUSIONS: Ang-1 and Ang-2 levels are upregulated in patients with optimally treated asthma. Our data support a possible role for smoking in the angiogenetic process in asthma.
Asunto(s)
Angiopoyetina 1/metabolismo , Angiopoyetina 2/metabolismo , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Fumar/efectos adversos , Adulto , Asma/fisiopatología , Estudios de Casos y Controles , Volumen Espiratorio Forzado/fisiología , Humanos , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Persona de Mediana Edad , Neovascularización Patológica/patología , Fumar/fisiopatología , Esputo/química , Capacidad Vital/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVE: Angiopoietin-2 (Ang-2) is an important mediator of angiogenesis and has been implicated in many inflammatory diseases. COPD is characterized by systemic inflammation, which is enhanced during exacerbations and may be assessed by measuring serum C-reactive protein (CRP). The aim of the study was to evaluate serum CRP and Ang-2 levels on the first (D1) and seventh day (D7) of hospitalization due to a COPD exacerbation and to examine possible associations of CRP and Ang-2 levels and kinetics with the length of hospital stay and outcome. METHODS: We conducted a prospective study and evaluated 90 patients admitted to the hospital with a diagnosis of an acute exacerbation of COPD. A venous blood sample was obtained from all patients on D1 and D7 of hospitalization, for the measurement of Ang-2 and CRP. RESULTS: Serum Ang-2 levels were significantly higher on D1 compared to D7 during the course of COPD exacerbation (p < 0.001). Serum CRP levels were also significantly higher on D1 compared to D7 (p < 0.001). Serum Ang-2 presented a significant positive correlation with CRP levels both on D1 and D7 (r = 0.315 and r = 0.228, respectively). Patients with unfavorable outcome had significantly higher Ang-2 levels both on D1 (p = 0.04) and D7 (p = 0.01). CONCLUSIONS: Serum Ang-2 levels are elevated at the onset of COPD exacerbations and are positively associated with CRP levels. Ang-2 levels decrease during the course of COPD exacerbations in patients with favorable outcome. Serum Ang-2 may serve as a biomarker that could predict the outcome of a COPD exacerbation.
Asunto(s)
Angiopoyetina 2/sangre , Proteína C-Reactiva/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Anciano , Biomarcadores/sangre , Biomarcadores/metabolismo , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Índice de Severidad de la Enfermedad , EspirometríaRESUMEN
COPD is a major healthcare problem and cause of mortality worldwide. COPD patients at increased mortality risk are those who are more symptomatic, have lower lung function and lower diffusing capacity of the lung for carbon monoxide, decreased exercise capacity, belong to the emphysematous phenotype and those who have concomitant bronchiectasis. Mortality risk seems to be greater in patients who experience COPD exacerbations and in those who suffer from concomitant cardiovascular and/or metabolic diseases. To predict the risk of death in COPD patients, several composite scores have been created using different parameters. In previous years, large studies (also called mega-trials) have evaluated the efficacy of different therapies on COPD mortality, but until recently only nonpharmaceutical interventions have proven to be effective. However, recent studies on fixed combinations of triple therapy (long-acting ß-agonists, long-acting muscarinic antagonists and inhaled corticosteroids) have provided encouraging results, showing for the first time a reduction in mortality compared to dual therapies. The aim of the present review is to summarise available data regarding mortality risk in COPD patients and to describe pharmacological therapies that have shown effectiveness in reducing mortality.
RESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous progressive lung condition characterized by long-term respiratory symptoms and airflow limitation. Appropriate bronchodilation is the cornerstone of COPD treatment, leading to better health status as well as benefits in prognosis and mortality. METHODS: In the current open, noninterventional, observational study, 716 patients diagnosed with COPD of variable severity were administered a fixed-dose combination (FDC) of fluticasone propionate and salmeterol (500 + 50 mcg) through the Elpenhaler® device. The patients' adherence to treatment (based on the MMAS-8 [8-item Morisky Medication Adherence Scale]) and health status (based on the CCQ [Clinical COPD Questionnaire]) were assessed at the beginning of the study and at the end of the 3-month follow-up period. RESULTS: The mean ± SD MMAS-8 score at 1 and 3 months was 6.12 ± 1.89 and 6.45 ± 1.80, respectively, indicating medium adherence overall; however, there was a statistically significant increase of 0.33 units in the MMAS-8 score at the end of the follow-up (paired t-test p < 0.0001), suggestive of an improvement in adherence throughout the study. Higher adherence was associated with better health status at baseline, which further improved by the end of the follow-up. Moreover, we observed a statistically significant decrease of 1.07 points (p < 0.0001) in the mean CCQ total score from the baseline (CCQ score = 2.2 ± 1.00) until the end of the study follow-up (CCQ score = 1.13 ± 0.67). Similar conclusions were also drawn in the mean domain scores regarding symptoms (score equal to 1.36 ± 0.72, decrease by 1.18) as well as functional and mental state (scores equal to 0.86 ± 0.73 and 1.20 ± 0.88, decrease by 1.04 and 1.00, respectively, p < 0.0001). Similarly, when patients were stratified into subgroups with and without comorbidities, the former group showed an increase of 7% in the patients with medium to high adherence during the course of the study. In the same patient subgroup, there was a notable decrease in CCQ score by 1.18 points (p < 0.0001) during the study. CONCLUSIONS: The administration of FDC of fluticasone propionate and salmeterol, (500 + 50 mcg) via the Elpenhaler® device for COPD, resulted in a well-maintained or slight increase in treatment adherence and a subsequent benefit in health status, which further persisted after 3 months of treatment.
Asunto(s)
Broncodilatadores , Combinación Fluticasona-Salmeterol , Estado de Salud , Cumplimiento de la Medicación , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Administración por Inhalación , Albuterol/análogos & derivados , Albuterol/administración & dosificación , Albuterol/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Combinación de Medicamentos , Combinación Fluticasona-Salmeterol/administración & dosificación , Combinación Fluticasona-Salmeterol/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by progressive airflow obstruction, influenced by genetic and environmental factors. Eosinophils have been implicated in COPD pathogenesis, prompting the categorization into eosinophilic and non-eosinophilic endotypes. This study explores the association between eosinophilic inflammation and mRNA expression of ELAVL1, ZfP36, and HNRNPD genes, which encode HuR, TTP and AUF-1 proteins, respectively. Additionally, it investigates the expression of IL-9 and IL-33 in COPD patients with distinct eosinophilic profiles. Understanding these molecular associations could offer insights into COPD heterogeneity and provide potential therapeutic targets. Methods: We investigated 50 COPD patients, of whom 21 had eosinophilic inflammation and 29 had non-eosinophilic inflammation. Epidemiological data, comorbidities, and pulmonary function tests were recorded. Peripheral blood mononuclear cells were isolated for mRNA analysis of ELAVL1, ZfP36, and HNRNPD genes and serum cytokines (IL-9, IL-33) were measured using ELISA kits. Results: The study comprised 50 participants, with 66% being male and a mean age of 68 years (SD: 8.9 years). Analysis of ELAVL1 gene expression revealed a 0.45-fold increase in non-eosinophilic and a 3.93-fold increase in eosinophilic inflammation (p = 0.11). For the ZfP36 gene, expression was 6.19-fold higher in non-eosinophilic and 119.4-fold higher in eosinophilic groups (p = 0.07). Similarly, HNRNPD gene expression was 0.23-fold higher in non-eosinophilic and 0.72-fold higher in eosinophilic inflammation (p = 0.06). Furthermore, serum levels of IL-9 showed no statistically significant difference between the eosinophilic and non-eosinophilic group (58.03 pg/mL vs. 52.55 pg/mL, p = 0.98). Additionally, there was no significant difference in IL-33 serum levels between COPD patients with eosinophilic inflammation and those with non-eosinophilic inflammation (39.61 pg/mL vs. 37.94 pg/mL, p = 0.72). Conclusions: The data suggest a notable trend, lacking statistical significance, towards higher mRNA expression for the ZfP36 and HNRNPD genes for COPD patients with eosinophilic inflammation compared to those with non-eosinophilic inflammation.