RESUMEN
RATIONALE: There are no accepted blood-based biomarkers in chronic obstructive pulmonary disease (COPD). Pulmonary and activation-regulated chemokine (PARC/CCL-18) is a lung-predominant inflammatory protein that is found in serum. OBJECTIVES: To determine whether PARC/CCL-18 levels are elevated and modifiable in COPD and to determine their relationship to clinical end points of hospitalization and mortality. METHODS: PARC/CCL-18 was measured in serum samples from individuals who participated in the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) and LHS (Lung Health Study) studies and a prednisolone intervention study. MEASUREMENTS AND MAIN RESULTS: Serum PARC/CCL-18 levels were higher in subjects with COPD than in smokers or lifetime nonsmokers without COPD (105 vs. 81 vs. 80 ng/ml, respectively; P < 0.0001). Elevated PARC/CCL-18 levels were associated with increased risk of cardiovascular hospitalization or mortality in the LHS cohort and with total mortality in the ECLIPSE cohort. CONCLUSIONS: Serum PARC/CCL-18 levels are elevated in COPD and track clinical outcomes. PARC/CCL-18, a lung-predominant chemokine, could be a useful blood biomarker in COPD.
Asunto(s)
Quimiocinas CC/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Antiinflamatorios/uso terapéutico , Biomarcadores/sangre , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prednisolona/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Factores de Riesgo , Fumar/sangreRESUMEN
Myeloperoxidase is a strong oxidant stored in primary granules of neutrophils with potent antibacterial and proatherogenic properties. Myeloperoxidase has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the relationship of myeloperoxidase to health outcomes in COPD is not well known. We measured serum myeloperoxidase levels from 4,677 subjects with mild to moderate airflow limitation in the Lung Health Study. Using a Cox proportional hazards model, we determined the relationship of serum myeloperoxidase concentration to the risk of all-cause and disease specific causes of mortality. We found that serum myeloperoxidase concentrations were significantly related to accelerated decline in forced expiratory volume in 1 second (FEV1) over 11 years of follow-up (p<0.0001), and this association persisted after adjustments for age, sex, race, baseline FEV1, and smoking status (pâ=â0.048). Serum myeloperoxidase concentrations were also associated with increased risk of cardiovascular mortality (pâ=â0.036). Individuals in the highest quintile of myeloperoxidase had a hazard ratio of cardiovascular mortality of 1.90 (95% confidence interval 1.00-3.58; pâ=â0.049) compared with those in the lowest quintile, which was particularly notable in patients who continued to smoke (adjusted p-value of 0.0396). However, serum myeloperoxidase concentration was not related to total mortality, respiratory mortality, or deaths from malignancies. In conclusion, increased serum myeloperoxidase levels are associated with rapid lung function decline and poor cardiovascular outcomes in COPD patients, which support the emerging role of myeloperoxidase in the pathogenesis of COPD progression and cardiovascular disease.
Asunto(s)
Peroxidasa/sangre , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Adulto , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/fisiopatologíaRESUMEN
BACKGROUND: COPD is a chronic inflammatory disorder with high risk of cardiovascular morbidity and mortality. Adiponectin is a hormone that has anti inflammatory, antidiabetic, and anti atherogenic activities. We investigated the relationship of serum adiponectin to health outcomes in COPD. METHODS: We measured adiponectin levels in serum samples from participants of the Lung Health Study, who were smokers with mild to moderate airflow limitation. We determined the relationship of serum adiponectin to hospitalization and mortality using a Cox proportional hazards model and to baseline lung function measurements and bronchial reactivity using multiple regression methods. RESULTS: Serum adiponectin concentrations were inversely related to hospitalizations and mortality from coronary heart disease (hazard ratio [HR], 0.73; 95% CI, 0.62-0.86) and to cardiovascular disease (HR, 0.83; 95% CI, 0.73-0.94) and positively related to deaths from respiratory causes (HR, 2.09; 95% CI, 1.41-3.11). However, serum adiponectin concentrations were not significantly related to total mortality (HR, 1.10; 95% CI, 0.93-1.29) or cancer-related mortality(HR, 1.11; 95% CI, 0.92-1.34). Serum adiponectin concentrations were significantly related to increased bronchial reactivity and an accelerated decline in lung function (both P , .0001). Smoking status had no material influence on serum adiponectin concentrations. CONCLUSIONS: Adiponectin is a complex serum biomarker in COPD that is associated with decreased risk of cardiovascular events but increased risk of respiratory mortality. Because serum adiponectin is not significantly influenced by smoking status, it is a very promising biomarker of cardiovascular outcomes in COPD.