Evaluation of Different Doses in Inhaled Therapy: A Comprehensive Analysis.

BACKGROUND: Currently, there is a considerable degree of confusion over the dosage of inhaled medications. Here, we carried out a review of all the doses used for the devices used in inhalation therapy. METHODS: We first performed a systematic search of the different inhalation devices included on the July 2023 Spanish Ministry of Health Billing List. We then consulted the Spanish Agency for Medicines and Health Products to find the updated official label and to obtain the information on the exact composition. RESULTS: We identified 90 unique products, of which 22 were long-acting bronchodilators (and combinations thereof) and 68 were products containing inhaled corticosteroids (ICS). Overall, 10 products with bronchodilators and 40 with ICS were marketed with the metered dose, while 11 with bronchodilators and 28 with ICS were marketed with the delivered dose. In addition, in some bronchodilators, the drug was referred to as a type of salt, whereas in others the information referred to the drug itself. CONCLUSIONS: Our data show that for each inhaled drug there may be up to four different doses and that the marketed name may refer to any of these. Clinicians must be aware of these different dosages when prescribing inhaled medications.

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.

Effectiveness of Text Message Reminders on Adherence to Inhaled Therapy in Patients With Asthma: Prospective Multicenter Randomized Clinical Trial.

BACKGROUND: Poor adherence to inhaled medication in asthma patients is of great concern. It is one of the main reasons for inadequate asthma control. OBJECTIVE: The goal of the research was to determine if motivational messages using short message service (SMS, or text) improved adherence to inhaled medication in patients with asthma. METHODS: A prospective multicenter randomized parallel-group clinical trial was conducted in 10 asthma clinics in Spain. Adherence was assessed with electronic monitors (Smartinhaler, Adherium Ltd) connected to inhalers. Patients in the SMS group received psychologist-developed motivational messages every 3 days for 6 months. RESULTS: There were 53 patients in the SMS group and 88 patients in the control group. After 6 months, mean electronic adherence was 70% (SD 17%) in the intervention group and 69% (SD 17%) in the control group (P=.82). Significant differences between the study groups in morning and evening adherence to inhaled therapy, asthma control, exhaled nitric oxide levels, or improvement of lung functions were not observed. CONCLUSIONS: Motivational messages were not useful to improve adherence to inhaled asthma medication compared with usual care.

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

Algorithm for the management of asthma in pregnant women: a protocol to optimize processes in healthcare.

INTRODUCTION: Asthma is the most common chronic disease in pregnant women. Its evolution during pregnancy could improve, stay the same or worsen, especially in cases where there is a loss of clinical control. This can lead to maternal and fetal hypoxia with serious adverse perinatal outcomes. Areas covered: This article reviews physiological modifications in pregnancy, effects of pregnancy on asthma, and possible consequences on fetus development. Furthermore, it reviews evidence on assessment and both pharmacological and non-pharmacological management of asthma in pregnant and breastfeeding women as well as in acute exacerbations. Electronic databases, such as PUBMED, were searched for terms pregnan* or perinat* or obstet* and breastfeeding or asthma or wheeze, as well as a book published by the present authors. Expert commentary: A patient-centered multidisciplinary approach, where the respiratory specialists have a key role in assessing and achieving control, as well as the education interventions for self-monitoring and adherence are at least as important as adequate pharmacological treatment.

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.

Small particle-size talc is associated with poor outcome and increased inflammation in thoracoscopic pleurodesis.

RATIONALE: Talc is very effective for pleurodesis, but there is concern about complications, especially acute respiratory distress syndrome. OBJECTIVES: It was the aim of this study to investigate if talc with a high concentration of small particles induces greater production of cytokines, and if pleural tumor burden has any influence on the local production and spillover of cytokines to the systemic circulation and eventual complications. METHODS: We investigated 227 consecutive patients with malignant effusion submitted to talc pleurodesis. One hundred and three patients received 'small-particle talc' (ST; containing about 50% particles <10 µm) and 124 received 'large-particle talc' (with <20% particles <10 µm). Serial samples of both pleural fluid and blood were taken before and 3, 24, 48 and 72 h after thoracoscopy. Also, mesothelial cells were stimulated with both types of talc in vitro. MEASUREMENTS AND RESULTS: Interleukin-8, tumor necrosis factor-α, vascular endothelial growth factor, basic fibroblast growth factor and thrombin-antithrombin complex were measured in all samples. Early death (<7 days after talc) occurred in 8 of 103 patients in the ST and in 1 of 124 in the 'large-particle talc' group (p = 0.007). Patients who received ST had significantly higher proinflammatory cytokines in pleural fluid and serum after talc application, and also in supernatants of the in vitro study. Pleural tumor burden correlated positively with proinflammatory cytokines in serum, suggesting that advanced tumor states induce stronger systemic reactions after talc application. CONCLUSIONS: ST provokes a strong inflammatory reaction in both pleural space and serum, which is associated with a higher rate of early deaths observed in patients receiving it.

[Blood uric acid levels in patients with sleep-disordered breathing]. / Valores de ácido úrico en sangre en pacientes con trastornos respiratorios del sueño.

OBJECTIVE: Recurrent hypoxia associated with sleep apnea-hypopnea syndrome (SAHS) leads to an increase in the degradation of adenosine triphosphatase to xanthine and, secondarily, to an increase in uric acid concentrations. The aim of the present study was to determine whether there is a correlation between uric acid levels in peripheral blood and sleep-disordered breathing, independently of known confounding factors. PATIENTS AND METHODS: We carried out a retrospective cross-sectional study of 1135 patients evaluated for suspected SAHS. For all patients, a medical history was taken using a standardized protocol. In addition, biochemical analysis of venous blood and an overnight sleep study (with either conventional polysomnography or home monitoring) were carried out. RESULTS: The mean (SD) concentration of uric acid was 6.31 (1.5) mg/dL, and 36% of patients had concentrations above established normal values for their sex. We found a significant correlation between uric acid levels and some sleep study parameters (number of respiratory events, number of desaturations, or the cumulative percentage of time with oxygen saturation less than 90%). Those patients with more respiratory events (apnea-hypopnea index or respiratory event index >or= 30) had higher uric acid levels than those with mild or no SAHS. However, this difference was not apparent in the univariate analysis of variance, in which body mass index and cholesterol and triglyceride levels were considered confounding factors. CONCLUSIONS: Uric acid levels are positively correlated with the number of obstructive respiratory episodes and oxygen desaturations during sleep, but this correlation seems to be influenced by other factors, such as obesity.

A case of valproate-associated hepatotoxicity treated with L-carnitine.

Valproate is a major broad-spectrum anti-epileptic drug that is effective against many different types of epileptic seizures and that is usually well tolerated. Nevertheless, serious side effects can occur, including hepatotoxicity. This side effect is rare but often fatal, and it has been hypothesized that long-term valproate therapy may induce a carnitine deficiency and cause non-specific symptoms of hepatotoxicity and hyperammonemia. These factors suggest that L-carnitine supplementation may play a role in preventing hepatotoxicity. We report a case of valproate-induced acute liver injury with a favorable evolution after L-carnitine therapy.