RESUMEN
Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in clinical practice in adults with severe, refractory asthma.Methods: Prospective, single-center, open, observational study comprising patients with uncontrolled asthma (asthma control questionnaire (ACQ) >1.5) and/or frequent exacerbations despite treatment with at least high dose inhaled corticosteroids plus a second controller. Efficacy outcomes was change from baseline 4, 8, 12 and 24 months in FEV1, FVC and FEV1/FVC ratio, asthma control questionnaire (ACQ) score and asthma quality of life score (mini-AQLQ). Results are presented as median with interquartile ranges (IQR). The following were recorded as adverse events: Un-scheduled health care contacts, rescue courses of oral corticosteroid (OCS) and/or antibiotics for exacerbation for exacerbations/respiratory tract infections (RTI).Results: Six-teen patients were enrolled (nine males, median age 50 years; 14 followed for 24 months). Compared to baseline, an improvement in FEV1, FVC, FEV1/FVC ratio, mini-AQLQ and ACQ was observed, i.e.FEV1 (IQR) 1.98 L (1.65-2.45) vs. 2.45 L (2.09-2.93) (p = 0.006), FVC (IQR) 3.23 L (2.76-4.05) vs. 3.75 L (3.22-4.36) (p = 0.041), FEV1/FVC 0.60 (IQR: 0.55-0.70) vs. 0.66 (IQR: 0.63-0.71) (p = 0.016), mini-AQLQ 4.0 (IQR: 3.2-4.9) vs. 5.6 (IQR 4.5-6.5) (p = 0.008, and ACQ 2.9 (IQR: 2.1-3.7) versus 1.5 (IQR 1.0-2.4) (p = 0.004). On the other hand, an increase was observed in unscheduled visits (p = 0.005), as well as use of OCS and antibiotics (p = 0.009 and p = 0.003, respectively).Conclusion: BT in adults with severe asthma improved ACQ, mini-AQLQ and lung function, but resulted in an increased frequency of unscheduled doctor-visits and rescue courses of OCS and antibiotics.
Asunto(s)
Asma/cirugía , Termoplastia Bronquial/métodos , Corticoesteroides/uso terapéutico , Adulto , Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Termoplastia Bronquial/efectos adversos , Dinamarca , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estudios Prospectivos , Calidad de Vida , Pruebas de Función Respiratoria , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Interstitial lung disease (ILD) can be a severe extra-articular disease manifestation in Rheumatoid Arthritis (RA). A potential role of fibrocytes in RA associated ILD (RA-ILD) has not previously been described. We present a modified faster method for measuring circulating fibrocytes, without intracellular staining. The results are compared to the traditional culture method, where the number of monocytes that differentiate into mature fibrocytes in vitro are counted. The results are following compared to disease activity in patients with severe asthma, ILD, RA (without diagnosed ILD) and RA with verified ILD (RA-ILD). METHOD: CD45+ CD34+ CD11b+ (7-AAD- CD3- CD19- CD294-) cells were isolated by cell sorting and stained for pro-collagen type 1. Thirty-nine patients (10 RA, 9 ILD and 10 with severe asthma, 10 with RA-ILD) and 10 healthy controls (HC) were included. Current medication, disease activity, pulmonary function test and radiographic data were collected. Circulating fibrocytes were quantified by flow cytometry. Peripheral blood mononuclear cells were isolated and cultured for 5 days and the numbers of mature fibrocytes were counted. RESULTS: 90.2% (mean, SD = 1.5%) of the sorted cells were pro-collagen type 1 positive and thereby fulfilled the criteria for being circulating fibrocytes. The ILD and RA-ILD groups had increased levels of circulating fibrocytes compared to HC (p < 0.05). Levels of circulating fibrocytes correlated overall to number of monocytes that subsequently in vitro differentiated to mature fibrocytes (r = 0.81, p < 0.001). RA patients with pathologically reduced diffusion capacity for carbon monoxide adjusted for hemoglobin (DLCOc) in both the RA and in the combined RA + RA-ILD group, had significantly higher levels of both circulating and number of cultured mature fibrocytes (both p < 0.05). In both groups, the level of circulating fibrocytes and number of mature fibrocytes in culture also correlated to a reduction in DLCOc (r = -0.61 an r = -0.58 both p < 0.05). CONCLUSIONS: We presented a fast and valid method for measuring circulating fibrocytes using flow cytometry on lysed peripheral blood. Further, we showed for the first time, that the level of circulating fibrocytes correlated with the number of peripheral blood mononuclear cells, that differentiated into mature fibrocytes in vitro. Reduced DLCOc was correlated with high levels of circulating and mature fibrocytes in RA, which have not been reported previously. In such, this study suggests that fibrocytes may exhibit an important role in the pathogenesis of RA-ILD, which requires further clarification in future studies. TRIAL REGISTRATION: ClinicalTrials.gov : NCT02711657 , registered 13/3-2016, retrospectively registered.
Asunto(s)
Artritis Reumatoide/complicaciones , Diferenciación Celular , Separación Celular/métodos , Citometría de Flujo , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/patología , Monocitos/patología , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/patología , Asma/sangre , Asma/patología , Biomarcadores/sangre , Estudios de Casos y Controles , Células Cultivadas , Colágeno Tipo I/metabolismo , Estudios Transversales , Femenino , Humanos , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/fisiopatología , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Fenotipo , Valor Predictivo de las Pruebas , Procolágeno/metabolismo , Capacidad de Difusión Pulmonar , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
This review describes the current Danish guidelines for inhaled asthma treatment. Monotherapy with short-acting beta-agonists (SABA) taken when needed is no longer recommended in asthma therapy for adults due to safety concerns. The recommended first-line treatment is now inhaled corticosteroids (ICS) taken with formoterol or ICS taken with SABA. The choice of inhaler can have a significant impact on compliance and symptom control, and an individualized approach is therefore needed. Biological treatment may be an alternative to oral corticosteroids in selected patient groups.
Asunto(s)
Antiasmáticos , Asma , Medicina General , Administración por Inhalación , Corticoesteroides/uso terapéutico , Adulto , Antiasmáticos/efectos adversos , Asma/tratamiento farmacológico , Quimioterapia Combinada , Etanolaminas/uso terapéutico , Fumarato de Formoterol/uso terapéutico , HumanosRESUMEN
The evaluation and management of severe asthma patients require collection of comprehensive information, which is often a challenge in a busy outpatient clinic. The Danish Severe Asthma Register (DSAR) was designed as an electronic patient record form that captures operational clinical data and provides a clinical overview of the severe asthma patient. DSAR is a nationwide register; all patients in Denmark who are treated with biologics for severe asthma are included, and data are as a minimum entered at start of biological treatment, after four and 12 months of treatment, and hereafter annually. Currently, there are data from 621 treatment courses with biologics included in DSAR, with 71% of patients treated with anti-IL-5 drugs and 29% with an anti-IgE drug. Patients enter Patient Reported Outcome Measures electronically on tablets when they arrive in the outpatient clinic and their answers are immediately available to the clinician during the consultation. Nurses and doctors enter clinical data into DSAR during the consultation. DSAR offers immediate access to well-presented longitudinal overview and automatically creates a journal output that can be copy-pasted into the hospital's existing health record form. DSAR is also currently expanding with an app, to be used for monitoring of home-treatment. In addition to serving as an electronic patient record form, DSAR will also provide opportunities to monitor the real-life efficacy of biological treatment for severe asthma in Denmark, and it will be a valuable research platform that will aid in answering important research questions on severe asthma in the future.