Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study

Introduction: The role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response.Methods: Observational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests.Results: The study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV1, FEV1/FVC and FENO, whereas they were FEV1/FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders.Conclusions: Our study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values. (AU)

Evaluation of the Diagnostic Accuracy of Non-Specific Bronchial Provocation Tests in the Diagnosis of Asthma: A Randomized Cross-Over Study.

INTRODUCTION: The role of bronchial provocation tests in the diagnosis of asthma remains to be fully explored. We aimed to evaluate methacholine and mannitol challenge testing, and explore the factors associated with this broncoprovocation response. METHODS: Observational, cross-over, randomized trial evaluating adult cases with suspected asthma, naïve to treatment, with normal pre-bronchodilator spirometry, and negative bronchodilator test. Patients were randomized to start with methacholine or mannitol. The diagnosis of bronchial asthma was confirmed if there was a good functional and clinical response to one month with twice daily formoterol/budesonide 9/320. The diagnostic profile and the concordance were calculated. Factors associated with a positive provocation test were entered into a multivariate binomial logistic regression analysis, and classification trees were created for both tests. RESULTS: The study included 108 cases (50.0% diagnosed with asthma and 51.9% cases starting with methacholine). The percentage of cases positive to methacholine and mannitol were 30.6% and 25.0% respectively. Kappa values were 0.40 (p<0.001). The diagnostic profile for methacholine was sensitivity 59.3% and specificity 98.1%, while for mannitol it was sensitivity 48.1% and specificity 98.1%. Variables associated with a positive methacholine response included sex, atopy, FEV1, FEV1/FVC and FENO, whereas they were FEV1/FVC and FENO for mannitol. A FENO value>26ppb, FEV1≤103.3% and female sex correctly classified 78.7% of methacholine responders. FENO value>26ppb was enough to correctly classify 81.5% of mannitol responders. CONCLUSIONS: Our study confirms the diagnostic profile of methacholine and mannitol challenge tests and describes the variable associated to their positivity with new proposed cutoff values.

Effectiveness of Switching to Benralizumab in Severe Refractory Eosinophilic Asthma.

Purpose: Benralizumab is a monoclonal antibody that targets the α subunit of the IL-5 receptor. Clinical trials have demonstrated the efficacy of this agent with respect to lung function and symptom control in patients with refractory eosinophilic asthma. However, few studies have evaluated the efficacy of benralizumab after switching previous treatment with other monoclonal antibodies. Patients and Methods: We performed a multicenter retrospective study under conditions of daily clinical practice. The study population comprised consecutively included patients with severe refractory eosinophilic asthma whose initial treatment with omalizumab or mepolizumab was switched to benralizumab. Patients were evaluated at 4 and 12 months after starting treatment with benralizumab. We analyzed asthma control, number of severe exacerbations, corticosteroid cycles, visits to the emergency department, and hospital admissions, as well as lung function. Similarly, we evaluated the response to treatment according to previously established criteria. Results: We evaluated 40 patients who switched from omalizumab (n=16) or mepolizumab (n=24) to benralizumab. The reasons for switching were lack of response in 30 cases, adverse effects in 9, and patient request in 1. Switching was followed by a significant decrease in the number of exacerbations, visits to the emergency department, and corticosteroid cycles, as well as improved ACT both at 4 and 12 months. However, no significant improvement in lung function was observed. Asthma control (including complete response and control) was achieved in 55% of patients (n=22) at 12 months. Specifically, a complete response was achieved in 30% of patients at 12 months (66.7% switching from omalizumab and 33.3% from mepolizumab). Conclusion: Patients diagnosed with severe refractory eosinophilic asthma who experience a partial response with omalizumab or mepolizumab could benefit from switching to benralizumab. This approach can reduce the number of exacerbations, visits to the emergency department, and corticosteroid cycles and improve control of asthma.

Enfermedades por micobacterias no tuberculosas en España: tratamiento y evolución / Non-Tuberculous Mycobacterial Diseases in Spain: Treatment and Evolution

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[Translated article] Non-Tuberculous Mycobacterial Diseases in Spain: Treatment and Evolution / Enfermedades por micobacterias no tuberculosas en España: tratamiento y evolución

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Preference for Easyhaler® Over Previous Dry Powder Inhalers in Asthma Patients: Results of the DPI PREFER Observational Study.

OBJECTIVE: To study patient preference for and satisfaction with the Easyhaler® device and to assess ease of training and use of the inhaler in patients previously treated with a variety of dry powder inhalers (DPIs). METHODS: We designed a non-interventional, cross-sectional, single-visit observational study of adult patients with persistent asthma referred to specialized care who had previously been treated with DPI inhalers for at least 3 months. Once clinical baseline data had been checked, patients filled in questionnaires on asthma control (GINA 2019), Feeling of Satisfaction with the Inhaler (FSI-10), and adherence (TAI and Morisky-Green questionnaires). Thereafter, all patients were trained in the use of Easyhaler. We assessed ease of use and satisfaction (FSI-10) with Easyhaler, as well as inhaler device preferences. RESULTS: We recruited 502 patients (mean age, 50.2 ± 16.2 y; 63.1% female), of whom 485 were evaluable. In response to the main objective of the study, we compared the values of the self-completed adapted FSI-10, to measure satisfaction with the inhaler. A significantly higher score in each item of the questionnaire was recorded for Easyhaler. Overall, 38% of patients showed exclusive preference for Easyhaler (compared with 15% for the previous device) or were evenly matched in 46% of cases. CONCLUSION: In the present study, Easyhaler achieved better patient ratings in terms of preference and satisfaction than previously used DPI devices. In order to improve asthma adherence strategies, patient preferences and device choice should be taken into account.

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

Is the bronchodilator test an useful tool to measure asthma control?

INTRODUCTION: Asthma control includes the control of symptoms and future risk. We sought to evaluate the usefulness of the degree of spirometric reversibility of the forced expiratory volume in one second (FEV1) as the target parameter of control. METHODOLOGY: Patients with bronchial asthma were followed up for one year. The clinical, functional, inflammatory and control parameters of the asthma were collected. The area under the curve (AUC) was estimated to establish the cutoff point of the post-bronchodilator FEV1 reversibility in relation to non-control asthma. In the univariate analysis, the differences between groups were studied based on the degree of estimated reversibility. Factors with a significance <0.1 were included in the multivariate analysis by binary logistic regression. RESULTS: A total of 407 patients with a mean age of 38.1 ± 16.7 years were included. When the patients were grouped into controlled and non-controlled groups, compared with post-bronchodilator FEV1 reversibility, the cutoff point obtained for the non-controlled group was ≥10% (sensitivity: 65.8%, specificity: 48.4%, positive predictive value: 69.5%, and AUC: 0.619 [0.533-0.700], p < 0.01). In the year-long follow-up of this group (post-bronchodilator FEV1 ≥10), an increased use of relief medication was observed, along with a significantly progressive drop in post-bronchodilator FEV1 and post-bronchodilator FEV1/FVC (forced expiratory volume in one second/forced vital capacity). CONCLUSIONS: Spirometric reversibility can be useful in assessing control in asthmatic patients and can predict future risk parameters. The cutoff point related to the non-control of asthma found in our work was ≥10%.

Predictors of 10-year smoking abstinence in smokers abstinent for 1 year after treatment.

AIMS: To identify factors predicting long-term relapse to smoking in people attending smoking treatment services who have maintained at least 1 year abstinence. DESIGN: Observational, prospective study with multiple logistic regression used to model predictors of relapse between 1 and 10 years from cessation using variables measured pre-cessation. SETTING AND PARTICIPANTS: Among smokers receiving behavioural support for cessation in a clinic in Spain, in some cases with nicotine patches or bupropion, 366 had remained abstinent after 1 year of follow-up and were included into the study. MEASUREMENTS: Predictive measures (disease history, psychological disorder, age of starting smoking, years of smoking, cigarette dependence and smoking cessation treatment used) were obtained at the time of the quit attempt, and 'failure' (defined as reported smoking, loss to follow-up, died or an expired air carbon monoxide reading of > 5 parts per million) was assessed 10 years later. FINDINGS: At follow-up, abstinence status was confirmed in 50.5% (n = 185) of participants, while 21.0% (n = 77) reported that they had resumed smoking, and 28.5% (n = 104) were lost to follow-up (also counted as having resumed smoking). In the multiple regression model, the main factor that predicted relapse had a psychological disorder (odds ratio = 1.85, 95% confidence interval = 1.13-3.05; P < 0.02). CONCLUSIONS: Having a psychological disorder at the time of stopping smoking is a risk factor for relapse to smoking, even after more than 1 year of abstinence.

[Comparison of the Asthma Control Test (ACT) with lung function, levels of exhaled nitric oxide and control according to the Global Initiative for Asthma (GINA)]. / Relación del test de control del asma (ACT) con la función pulmonar, niveles de óxido nítrico exhalado y grados de control según la Iniciativa Global para el Asma (GINA).

INTRODUCTION: The current goal of asthma treatment is to achieve and maintain control. This study aimed to explore the relationship between the ACT (Asthma Control Test) questionnaire and the levels of control according to GINA (Global Initiative for Asthma) to establish the cut-off points for the ACT and evaluate its relationship with lung function and fractionated exhaled nitric oxide level (FeNO). PATIENTS AND METHODS: A multi-centre prospective study including 441 patients followed up in an outpatient Chest Clinic. A clinical protocol was followed, and FeNO, spirometry and ACT performed. Disease was classified according to levels of control using GINA. The study analysed sensitivity, specificity and area under the curve (ROC), and the ACT cut-off points. We studied the differences between the functional parameters and FeNO between levels of control. RESULTS: For controlled asthma the cut-off obtained was ACT> or =21 (area under the curve 0.791) and for uncontrolled < or =18 (AUC 0.774). We found significant differences in FeNO levels and pulmonary function among ACT> or =21 and ACT< or =18, although only 26.3% of patients with ACT< or =18 had a FEV1 <80% and 40% higher FeNO (> or =35 ppb). We found a correlation between baseline FEV1 and ACT (r=0.19, P<0.01) and between ACT and FeNO (r=-0.16, P<0.01). CONCLUSIONS: The cut-off points would be, for controlled asthma ACT> or =21, partly controlled asthma ACT=19-20 and uncontrolled asthma ACT< or =18. A more complete assessment would require including monitoring operating parameters and FeNO.

Relación del test de control del asma (ACT) con la función pulmonar, niveles de óxido nítrico exhalado y grados de control según la Iniciativa Global para el Asma (GINA) / Comparison of the Asthma Control Test (ACT) with Lung Function, Levels of Exhaled Nitric Oxide and Control According to the Global Initiative for Asthma (GINA)

Introducción. El objetivo actual en el tratamiento del asma es conseguir y mantener el control. Este estudio tiene como objetivos estudiar la relación entre el cuestionario ACT (Asthma Control Test) y los niveles de control según Global Initiative for Asthma para establecer los puntos de corte del ACT y evaluar su relación con la función pulmonar y la Fracción exhalada de óxido nítrico (FeNO). Pacientes y métodos. Estudio prospectivo multicéntrico con inclusión de 441 pacientes seguidos en consultas externas de neumología. Se realizó protocolo clínico, FeNO, espirometría forzada y ACT. Se clasificó la enfermedad según los niveles de control de la Global Initiative for Asthma. Se realizó estudio de sensiblidad, especificidad y área bajo la curva (ROC), estimándose los puntos de corte de ACT. Se estudiaron las diferencias entre los parámetros funcionales y FeNO entre los niveles de control. Resultados. Para el asma controlada el punto de corte obtenido fue ACT≥21 (área bajo la curva 0,791) y para el no controlada fue ≤18 (área bajo la curva 0,774). Encontramos diferencias significativas en niveles de FeNO y función pulmonar entre ACT≥21 y ACT≤18, aunque solo el 26,3% de pacientes con ACT≤18 presentaron un FEV1<80% y el 40% FeNO elevado (≥35 ppb). Encontramos correlación entre FEV1 basal y ACT (r=0,19, p<0,01), así como entre ACT y FeNO (r=−0,16, p<0,01). Conclusiones. Los puntos de corte para el asma controlada serían ACT≥21, para el asma parcialmente controlada ACT=19–20 y para el asma no controlada ACT≤18. Una valoración más completa del control requeriría incluir parámetros funcionales y FeNO.(AU)

Introduction. The current goal of asthma treatment is to achieve and maintain control. This study aimed to explore the relationship between the ACT (Asthma Control Test) questionnaire and the levels of control according to GINA (Global Initiative for Asthma) to establish the cut-off points for the ACT and evaluate its relationship with lung function and fractionated exhaled nitric oxide level (FeNO). Patients and methods. A multi-centre prospective study including 441 patients followed up in an outpatient Chest Clinic. A clinical protocol was followed, and FeNO, spirometry and ACT performed. Disease was classified according to levels of control using GINA. The study analysed sensitivity, specificity and area under the curve (ROC), and the ACT cut-off points. We studied the differences between the functional parameters and FeNO between levels of control. Results. For controlled asthma the cut-off obtained was ACT≥21 (area under the curve 0.791) and for uncontrolled ≤18 (AUC 0.774). We found significant differences in FeNO levels and pulmonary function among ACT≥21 and ACT≤18, although only 26.3% of patients with ACT≤18 had a FEV1 <80% and 40% higher FeNO (≥35 ppb). We found a correlation between baseline FEV1 and ACT (r=0.19, P<0.01) and between ACT and FeNO (r=−0.16, P<0.01). Conclusions. The cut-off points would be, for controlled asthma ACT≥21, partly controlled asthma ACT=19–20 and uncontrolled asthma ACT≤18. A more complete assessment would require including monitoring operating parameters and FeNO. (AU)