RESUMEN
Rationale: Androgens are potentially beneficial in asthma, but AR (androgen receptor) has not been studied in human airways.Objectives: To measure whether AR and its ligands are associated with human asthma outcomes.Methods: We compared the effects of AR expression on lung function, symptom scores, and fractional exhaled nitric oxide (FeNO) in adults enrolled in SARP (Severe Asthma Research Program). The impact of sex and of androgens on asthma outcomes was also evaluated in the SARP with validation studies in the Cleveland Clinic Health System and the NHANES (U.S. National Health and Nutrition Examination Survey).Measurements and Main Results: In SARP (n = 128), AR gene expression from bronchoscopic epithelial brushings was positively associated with both FEV1/FVC ratio (R2 = 0.135, P = 0.0002) and the total Asthma Quality of Life Questionnaire score (R2 = 0.056, P = 0.016) and was negatively associated with FeNO (R2 = 0.178, P = 9.8 × 10-6) and NOS2 (nitric oxide synthase gene) expression (R2 = 0.281, P = 1.2 × 10-10). In SARP (n = 1,659), the Cleveland Clinic Health System (n = 32,527), and the NHANES (n = 2,629), women had more asthma exacerbations and emergency department visits than men. The levels of the AR ligand precursor dehydroepiandrosterone sulfate correlated positively with the FEV1 in both women and men.Conclusions: Higher bronchial AR expression and higher androgen levels are associated with better lung function, fewer symptoms, and a lower FeNO in human asthma. The role of androgens should be considered in asthma management.
Asunto(s)
Asma/genética , Sulfato de Deshidroepiandrosterona/sangre , ARN Mensajero/metabolismo , Receptores Androgénicos/genética , Mucosa Respiratoria/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/sangre , Asma/fisiopatología , Pruebas Respiratorias , Broncoscopía , Femenino , Volumen Espiratorio Forzado , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Calidad de Vida , Factores Sexuales , Capacidad Vital , Adulto JovenRESUMEN
BACKGROUND: Right ventricular (RV) dysfunction and pulmonary hypertension (PH) are commonly unrecognized in the emergency department (ED), but are associated with poor outcomes. Prior research has found a 30% prevalence of isolated RV dysfunction in ED patients after non-significant computed tomographic pulmonary angiography (CTPA). We aimed to prospectively define the prevalence of RV dysfunction and/or PH in short of breath ED patients, and assess outcomes. METHODS: Prospective observational study of patients with a non-significant CTPA. Isolated RV dysfunction and/or PH was defined as normal left ventricular function plus RV dilation, moderate to severe tricuspid regurgitation or RV systolic pressure>40mmHg on comprehensive echocardiography. RESULTS: Of 83 patients, 20 (24%, 95% [confidence interval] CI: 16-34%) had isolated RV dysfunction and/or PH. These patients had 40% ED recidivism and 30% hospital readmission at 30-days. When compared to patients with normal echocardiographic function, they had significantly longer intensive care unit and hospital length of stays. CONCLUSIONS: In a prospective cohort of ED patients, we found a high prevalence of isolated RV dysfunction and/or PH after a non-significant CTPA. These patients had high rates of recidivism and hospital readmission. This data supports a continued need for ED based screening and specialty referral.