Treatment persistence and exacerbations in patients with asthma initiating treatment with inhaled corticosteroids and beta-adrenergic agonists: retrospective cohort study.

OBJECTIVE: To determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma. DESIGN: Retrospective observational study conducted by review of electronic medical records (database: Fundación RediSS). SETTING: Retrospective cohort study. The follow-up period was 1 year. PARTICIPANTS: The study included patients aged ≥18 years who started treatment with ICS/LABA and met the inclusion/exclusion criteria. MAIN OUTCOMES AND MEASURES: The study groups were fluticasone propionate/salmeterol (FP/SAL), beclomethasone/formoterol (BDP/FORM), budesonide/formoterol (BUD/FORM), fluticasone furoate/vilanterol (FF/VI) and fluticasone propionate/formoterol (FP/FORM). The main measurements were persistence, medication possession ratio (MPR) and exacerbations. Statistical significance was established as p<0.05. RESULTS: In total, 3203 patients were recruited for the study. By groups, 31.1% FP/SAL, 28.6% BDP/FORM, 25.0% BUD/FORM, 8.2% FF/VI and 7.0% FP/FORM. The mean age was 52.2 years, 60.8% were female and 44.9% had persistent-moderate asthma. Treatment persistence was 61.7% (95% CI 60.0% to 63.4%) and by study group it was FP/SAL: 60.7%, BDP/FORM: 61.2%, BUD/FORM: 60.3%, FF/VI: 66.7% and FP/FORM: 67.6% (p=0.046). MPR by study group was FP/SAL: 74.3%, BDP/FORM: 73.8%, BUD/FORM: 74.6%, FF/VI: 79.4% and FP/FORM: 80.6% (p=0.028). The mortality rate was 2.9%. By treatment group, exacerbations were FP/SAL: 21.9% (95% CI 19.3% to 24.5%), BDP/FORM: 22.2% (95% CI 19.5% to 24.9%), BUD/FORM: 22.8% (95% CI 19.9% to 25.7%), FF/VI: 17.9% (95% CI 14.9% to 20.7%) and FP/FORM: 16.0% (95% CI 12.2% to 19.3%), p=0.036. CONCLUSIONS: Patients undergoing treatment with FP/FORM and FF/VI versus FP/SAL, BDP/FORM and BUD/FORM were associated with greater treatment adherence (persistence, MPR) and lower rates of exacerbations. However, further studies will be needed to strengthen the consistency of the results.

Papel de los polimorfismos de la GST (Glutation-S-transferasa) en la susceptibilidad genética a desarrollar asma bronquial en una población de asmáticos andaluces / The role of GST (Glutathione S-transferases) polymorphisms in the genetic susceptibility to develop bronchial asthma in a population of andalusian asthmatics

OBJETIVO: Analizar la presencia de variaciones genéticas en las enzimas de detoxificación GST (Glutation-S-transferasa), concretamente las enzimas GSTM1, GSTT1 y GSTP1.5, en pacientes con asma bronquial y la posible asociación con parámetros clínicos, funcionales e inflamatorios. METODOLOGÍA: Se incluyeron pacientes en seguimiento por asma bronquial junto a un grupo control de individuos no asmáticos. Se analizaron, junto al análisis genético, los parámetros clínicos, incluido ACT, grado de gravedad y grado de control, parámetros funcionales y de inflamación (FeNO-Fracción espirada de óxido nítrico). El estudio genético se realizó mediante extracción del ADN celular de sangre periférica y su posterior análisis por técnicas de biología molecular (PCR: reacción en cadena de la polimerasa y electroforesis en geles de agarosa) en el Instituto de Biomedicina de Sevilla (IBIS). RESULTADOS: Se estudiaron 256 asmáticos, y un grupo control de 40 pacientes. El mayor porcentaje de pacientes presentaban un asma moderada (53%), frente al 23% de asma leve y 24% de asma grave. Según el grado de control en el momento de la inclusión, presentaban buen control el 46% de la serie, mal control el 30% y un 24% de los pacientes estaban parcialmente controlados. En cuanto a la presencia de los polimorfismos: el polimorfismo GSTM1 presentaba genotipo positivo (sin delección) en el 34% de la serie, frente al 65,9% que presentaban genotipo nulo (deleccionadoausencia de la enzima de depuración); en el caso del polimorfismo GSTT1, el 75,6% presentaban genotipo positivo y 24,4% genotipo nulo. De las tres posibilidades polimórficas del GSTP1.5 (34% presentaban genotipo A/A; 48,8% genotipo A/G y 17,1% genotipo G/G). Encontramos un asociación estadísticamente significativa (p = 0,017) entre la presencia del alelo Ile/Ile (A/A) del polimorfismo GSTP1.5 y las mujeres asmáticas, así como con niveles más bajos de FeNO. CONCLUSIONES: no encontramos diferencias estadísticamente significativas entre la presencia de los polimorfismos GSTM1, GSTT1 con ninguno de los parámetros clínicos y funcionales analizados. En cuanto a la presencia del polimorfismo GSTP1.5, encontramos relación estadísticamente significativa con la presencia de asma bronquial en la población de mujeres, concretamente con la presencia del genotipo A/A homocigoto y que a su vez presentaba valores más bajos de FeNO

OBJECTIVE: to analyze the presence of genetic variations in the GST (glutathione S-transferase) detoxification enzymes, specifically the GSTM1, GSTT1 and GSTP1.5 enzymes, in patients with bronchial asthma and their possible association with clinical, functional and inflammatory parameters. METHODS: Patients undergoing follow-up for bronchial asthma were included along with a control group of non-asthmatic individuals. In addition to genetic analysis, the clinical parameters including ACT, degree of severity and degree of control, and functional and inflammation parameters (FeNO, fractional exhaled nitric oxide) were analyzed. The genetic study was done by extracting cellular DNA from peripheral blood which was then analyzed using molecular biology techniques (PCR: polymerase chain reaction and agarose gel electrophoresis) at the Instituto de Biomedicina de Sevilla (IBIS). RESULTS: 256 asthmatic patients and a control group of 40 patients were studied. The majority of patients presented with moderate asthma (53%), compared to 23% with mild asthma and 24% with severe asthma. According to degree of control upon inclusion, 46% of patients in the series had good control, 30% poor control, and 24% of patients were partially controlled. With regard to the presence of polymorphisms: the GSTM1 polymorphism showed a positive genotype (without deletion) in 34% of patients in the series, compared to 65.9% who showed a null genotype (deleted-absent purification enzyme); as for the GSTT1 polymorphism, 75.6% of patients showed a positive genotype and 24.4% a null genotype. Of the three polymorphic possibilities for GSTP1.5, 34% showed the AA genotype, 48.8% the AG genotype and 17.1% the GG genotype. We found a statistically significant association (p = 0.017) between the Ile/ Ile (AA) allele of the GSTP1.5 polymorphism and asthmatic women, as well as lower FeNO levels. CONCLUSIONS: We did not find statistically significant differences between the presence of the GSTM1 and GSTT1 polymorphisms and any of the analyzed clinical or functional parameters. With regard to the presence of the GSTP1.5 polymorphism, we found a statistically significant relationship with the presence of bronchial asthma in the female population, specifically with the presence of the homozygous AA genotype and the fact they also showed lower FeNO values