Long-acting muscarinic antagonist and long-acting ß2-agonist combination for the treatment of maintenance therapy-naïve patients with chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Faster lung function impairment occurs earlier in the disease, particularly in mild-to-moderate COPD, highlighting the need for early and effective targeted interventions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report recommends initial pharmacologic treatment with a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) combination in group B (0 or 1 moderate exacerbation not leading to hospitalization, modified Medical Research Council score of ⩾2, and COPD Assessment Test™ score of ⩾10) and E (⩾2 moderate exacerbations or ⩾1 exacerbation leading to hospitalization and blood eosinophil count <300 cells/µL) patients. In randomized controlled trials (RCTs), LAMA/LABA combination therapy improved lung function, St. George's Respiratory Questionnaire (SGRQ) total score, and Transitional Dyspnea Index (TDI) focal score and reduced the use of rescue medications, exacerbation risk, and risk of first clinically important deterioration (CID), compared with LAMA or LABA monotherapy. However, there is limited evidence regarding the efficacy and safety of LAMA/LABA combination therapy versus LAMA or LABA monotherapy in maintenance therapy-naïve patients. This review discusses the rationale for the early initiation of LAMA/LABA combination therapy in maintenance therapy-naïve patients with COPD. In post hoc analyses of pooled data from RCTs, compared with LAMA or LABA monotherapy, LAMA/LABA combination therapy improved lung function and quality of life and reduced COPD symptoms, risk of first moderate/severe exacerbation, risk of first CID, and use of rescue medication, with no new safety signals. In a real-world study, patients initiating LAMA/LABA had significantly reduced risk of COPD-related inpatient admissions and rate of on-treatment COPD-related inpatient admissions over 12 months than those initiating LAMA. Consequently, LAMA/LABA combination therapy could be considered the treatment of choice in maintenance therapy-naïve patients with COPD, as recommended by the GOLD 2024 report.

Long-acting bronchodilator combination therapy for the treatment of maintenance therapy­naïve patients with chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease (COPD) is a common lung disease that makes it hard to breathe and is a leading cause of death and disability worldwide. This disease tends to worsen lung function from an early stage, especially in people who only have mild or moderate symptoms. To help stop the loss of lung function and maintain the quality of life for patients with COPD, two main types of long-lasting inhaler medications are used: one type focuses on relaxing the muscles around the airways, and the other type helps open the airways making it easier to breathe. Some medications combine these two types of action and are approved for long-term management of COPD. However, there is not much information on the effectiveness and safety of these combination medications in patients who have never taken long-lasting COPD medication before. Current health guidelines suggest starting these combination medications in patients who are likely to see their symptoms get worse quickly, and who do not have a high level of a specific type of white blood cell. In this review, we discuss the evidence for starting these combination treatments early in patients who have never used long-lasting COPD medications before. There is no strong evidence yet that shows starting treatment early benefits patients with newly diagnosed COPD. However, about 30% of patients in clinical trials designed to study the effectiveness of these combination medications, had never received any long-lasting treatment before. After-the-fact analyses of these patients showed that these combination medications could reduce symptoms such as breathlessness, improve lung function, enhance quality of life, lessen the need for emergency medications, and decrease the risk of severe symptom flare-ups. Overall, the evidence supports using these combination inhaler medications as the first choice of treatment for patients with moderate COPD symptoms who have not previously been treated with long-lasting inhalers.

Expiratory flow limitation development index (ELDI): a novel method of assessing respiratory mechanics in COPD.

BACKGROUND: Expiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI). METHODS: A retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance. RESULTS: The mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment. CONCLUSIONS: COPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.

Suboptimal Peak Inspiratory Flow in Patients Hospitalized for COPD Exacerbation: Prevalence and Predictive Factors.

Introduction: Despite the importance of an adequate peak inspiratory flow (PIF) during inhaled therapy in patients with COPD, the available evidence in patients with severe exacerbations and their evolution after admission is limited. We conducted this study to evaluate the PIF during an exacerbation, its variability, and predictors of suboptimal PIF. Material and Methods: A prospective study that included patients admitted for COPD exacerbation. Clinical, demographic, and functional variables were recorded. Using the In-Check DIAL G16®, PIF without resistance (PIF-nr) and that obtained by simulating the resistance of the patients' usual inhalers (PIF) were determined within the first 48 hours of admission and prior to discharge; also assessed during a stable phase in a subgroup of patients. The results were compared and, through a multivariate study, the factors related to a suboptimal PIF were analyzed. Results: A total of 137 patients were included; 27% were women and the mean age was 69.4 ± 9.8 years. Moreover, 30.8% of the participants with dry powder inhalers had a suboptimal PIF at admission and it was independently associated with female sex (odds ratio [OR] = 8.635; 95% confidence interval [CI] [2.007, 37.152]; p < 0.01) and forced expiratory volume in the 1st second (FEV1) (OR = 0.997; 95% CI: [0.995, 0.999]; p = 0.04). At discharge, suboptimal PIF reduced to 17% (p < 0.01). PIF-nr increased from the time of admission to the stable phase. Conclusion: One third of COPD patients admitted with a severe exacerbation had a suboptimal PIF, being female sex and lower FEV1 independent predictors. PIF-nr improved progressively after the exacerbation.

Non-invasive positive pressure ventilation for acute asthma in children.

BACKGROUND: Asthma is one of the most common reasons for hospital admission among children, with significant economic burden and impact on quality of life. Non-invasive positive pressure ventilation (NPPV) is increasingly used in the care of children with acute asthma, although the evidence supporting it is weak, and clinical guidelines do not offer any recommendations on its routine use. However, NPPV might be an effective way to improve outcomes for some children with asthma. A previous review did not demonstrate a clear benefit, but was limited by few studies with small sample sizes. This is an update of the previous review. OBJECTIVES: To assess the benefits and harms of NPPV as an add-on therapy to usual care (e.g. bronchodilators and corticosteroids) in children (< 18 years) with acute asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, CENTRAL, MEDLINE, and Embase. We also conducted a search of ClinicalTrials.gov and the WHO ICTRP. We searched all databases from their inception to March 2023, with no restrictions on language of publication. SELECTION CRITERIA: We included randomised clinical trials (RCTs) assessing NPPV as add-on therapy to usual care versus usual care for children hospitalised for acute asthma exacerbations. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. MAIN RESULTS: We included three RCTs randomising 60 children with acute asthma to NPPV and 60 children to control. All included trials assessed the effects of bilevel positive airway pressure (BiPAP) for acute asthma in a paediatric intensive care unit (PICU) setting. None of the trials used continuous positive airway pressure (CPAP). The controls received standard care. The median age of children ranged from three to six years, and asthma severity ranged from moderate to severe. Our primary outcome measures were all-cause mortality, serious adverse events, and asthma symptom score. Secondary outcomes were non-serious adverse events, health-related quality of life, arterial blood gases and pH, pneumonia, cost, and PICU length of stay. None of the trials reported any deaths or serious adverse events (except one trial that reported intubation rate). Two trials reported asthma symptom score, each demonstrating reductions in asthma symptoms in the BiPAP group. In one trial, the asthma symptom score was (mean difference (MD) -2.50, 95% confidence interval (CI) -4.70 to -0.30, P = 0.03; 19 children) lower in the BiPAP group. In the other trial, a cross-over trial, BiPAP was associated with a lower mean asthma symptom score (MD -3.7; 16 children; very low certainty evidence) before cross-over, but investigators did not report a standard deviation, and it could not be estimated from the first phase of the trial before cross-over. The reduction in both trials was above our predefined minimal important difference. Overall, NPPV with standard care may reduce asthma symptom score compared to standard care alone, but the evidence is very uncertain. The only reported serious adverse event was intubation rate in one trial. The trial had an intubation rate of 40% and showed that BiPAP may result in a large reduction in intubation rate (risk ratio 0.47, 95% CI 0.23 to 0.95; 78 children), but the evidence is very uncertain. Post hoc analysis showed that BiPAP may result in a slight decrease in length of PICU stay (MD -0.87 day, 95% CI -1.52 to -0.22; 100 children), but the evidence is very uncertain. Meta-analysis or Trial Sequential Analysis was not possible because of insufficient reporting and different scoring systems. All three trials had high risk of bias with serious imprecision of results, leading to very low certainty of evidence. AUTHORS' CONCLUSIONS: The currently available evidence for NNPV is uncertain. NPPV may lead to an improvement in asthma symptom score, decreased intubation rate, and slightly shorter PICU stay; however, the evidence is of very low certainty. Larger RCTs with low risk of bias are warranted.

Left ventricular systolic function after inhalation of beta-2 agonists in healthy athletes.

Inhaled beta-2 adrenoceptor agonists (iß2A) are routinely used as bronchodilators in the treatment of asthma. However, their cardiac effects in athletes are scarcely examined. Thus, the aim of this study was to evaluate the effects of iß2A on left ventricular (LV) systolic function (SF) by echocardiography in healthy, non-asthmatic female and male endurance athletes. A randomized, double-blinded, placebo-controlled, balanced, 4-way complete block cross-over study was conducted. Twenty-four healthy athletes (12f/12m: 22.9 ± 2.7/24.4 ± 4.6 years) randomly completed 4 study arms (placebo; salbutamol; formoterol; formoterol + salbutamol). After inhalation of the study medication, the participants performed a 10-min time trial (TT) on a bicycle ergometer. After each TT an echocardiography was performed to determine LVSF. Blood samples were collected pre, post, 3 h and 24 h post TT. In females, total serum concentrations for salbutamol and formoterol were higher. LV ejection fraction (LVEF) and LV global longitudinal strain (LVendoGLS) showed a treatment effect for the whole study group (p < 0.0001) and a sex effect on LVEF (p = 0.0085). In women, there was a significant treatment effect for all medication arms (at least p ≤ 0.01) both on LVEF and LVendoGLS. In men only formoterol and formoterol + salbutamol displayed a treatment effect on LVEF (p = 0.0427, p = 0.0330; respectively), whereas on LVendoGLS only formoterol + salbutamol was significant (p = 0.0473). The iß2A significantly influenced LVSF after an acute bout of exercise in healthy endurance athletes. These effects were even more pronounced when combining both iß2A that supports a dose-dependent effect on cardiac function. Moreover, female athletes had higher serum concentrations of ß2 agonists and stronger effects on LVSF compared to male athletes. This is mainly explained by differences in body weight and related plasma volume and may indicate a potential risk when increasing dose above the tested concentrations. Trial registration: At the European Union Drug Regulating Authorities Clinical Trials (Eudra CT) with the number 201,500,559,819 (registered prospectively on 09/12/2015) and at the German register for clinical studies (DRKS number 00010574 registered retrospectively on 16/11/2021).

Effect of high-dose N-acetylcysteine on exacerbations and lung function in patients with mild-to-moderate COPD: a double-blind, parallel group, multicentre randomised clinical trial.

Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio <0.70 and an FEV1 ≥ 50% predicted value after bronchodilator use). The coprimary outcomes were the annual rate of total exacerbations and the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. COPD exacerbation was defined as the appearance or worsening of at least two major symptoms (cough, expectoration, purulent sputum, wheezing, or dyspnoea) persisting for at least 48 hours. Assessment of exacerbations was conducted every three months, and lung function was performed annually after enrolment. The difference between the N-acetylcysteine group and the placebo group in the annual rate of total exacerbation were not significant (0.65 vs. 0.72 per patient-year; relative risk [RR], 0.90; 95% confidence interval [CI], 0.80-1.02; P = 0.10). There was no significant difference in FEV1 before bronchodilator use at 24 months. Long-term treatment with high-dose N-acetylcysteine neither significantly reduced the annual rate of total exacerbations nor improved lung function in patients with mild-to-moderate COPD. Chinese Clinical Trial Registration: ChiCTR-IIR-17012604.

Current status and usefulness of therapeutic drug monitoring implementation of theophylline in elderly patients based on a nationwide database study and modeling approach.

OBJECTIVES: Theophylline is used in the treatment of chronic obstructive pulmonary disease but readily causes symptoms of intoxication and exhibits high risks in elderly patients. However, there have only been a few recent reports on the significance of therapeutic drug monitoring (TDM) implementation, especially in elderly patients. To examine the usefulness of theophylline TDM, we evaluated the current status of prescriptions containing theophylline and its side effects and assessed the influence of aging, sex, drug formulation, and concurrent drugs use on theophylline exposure using data from various nationwide databases and a pharmacokinetic modeling approach. METHODS: We utilized sampling data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Using the data of patients aged ≥80 years, we conducted an association analysis of theophylline and concurrent drugs. The transition in plasma theophylline concentration levels of elderly patients was estimated based on a previously reported physiological-based pharmacokinetic model. RESULTS: Altogether, 3973 patients using theophylline were registered in our dataset, and about 50% were over 70 years old and used theophylline. Therapeutic drug monitoring implementation was confirmed in only 1.13% of patients. The association analysis confirmed a frequent co-occurrence with allopurinol and famotidine, which increase theophylline exposure, in elderly patients aged ≥80 years. The physiologically based pharmacokinetic model indicated that theophylline trough concentrations were 1.65-fold higher in elderly patients aged 80 years compared to those aged 30 years and 1.35-fold higher in females compared to males. CONCLUSION: This study effectively combined information on the nationwide health care database and modeling approach, indicating the importance of proactive TDM and dose justification for female and elderly patients.

Association between illness perception and adherence to inhaler therapy in elderly Chinese patients with chronic obstructive pulmonary disease.

Background: Despite the fact that inhaled medications serve as the foundation of chronic obstructive pulmonary disease (COPD) treatment, patient adherence to inhaler therapy remains low, significantly impacting health outcomes in disease management. The Common Sense Model of Self-Regulation suggests that illness perception plays a crucial role in individual behavior. Nevertheless, the relationship between illness perception and inhaler adherence, as well as the underlying mechanisms, remains unclear in the elderly Chinese COPD population. Objective: This study aimed to explore the correlation between dimensions of illness perception and adherence to inhaler therapy in elderly Chinese patients with COPD. Methods: A cross-sectional study was conducted by recruiting 305 participants (mean age: 70.96 years; 69.8% male) using convenience sampling from a tertiary hospital in Anhui, China. The Chinese versions of the Test of Adherence to Inhalers (TAI) and Brief Illness Perception Questionnaire (B-IPQ) were used to evaluate adherence to inhalation and perception of their illness in patients with COPD. Binary logistic regression analyses were used to explore the relationship between inhaler adherence and illness perception in patients with COPD. Results: 84.3% of participants showed poor adherence, and the mean (standard deviation) B-IPQ total score was 44.87 (6.36). The results indicated an essential correlation between illness perception and inhaler adherence. Specifically, personal control (AOR = 2.149, p < 0.001), treatment control (AOR = 1.743, p < 0.001), comprehension (AOR = 5.739, p < 0.001) and emotions (AOR = 1.946, p < 0.001) within illness perception emerged as significant positive predictors for inhaler adherence among patients with COPD. Conclusion: This study suggests that clinical practitioners should monitor the illness perception of patients with COPD and develop targeted intervention measures to improve patient adherence to inhaler therapy.

Trends in COPD severe exacerbations, and all-cause and respiratory mortality, before and after implementation of newer long-acting bronchodilators in a large population-based cohort.

BACKGROUND: Little is known about the trends in morbidity and mortality at the population level that followed the introduction of newer once-daily long-acting bronchodilators for COPD. The purpose of the study was to evaluate whether the availability of new bronchodilators was associated with changes in the temporal trends in severe COPD exacerbations and mortality between 2007 and 2018 in the older population with COPD; and whether this association was homogeneous across sex and socioeconomic status classes. METHODS: We used an interrupted time-series and three segments multivariate autoregressive models to evaluate the adjusted changes in slopes (i.e., trend effect) in monthly severe exacerbation and mortality rates after 03/2013 and 02/2015 compared to the tiotropium period (04/2007 to 02/2013). Cohorts of individuals > 65 years with COPD were created from the nationally representative database of the Quebec Integrated Chronic Disease Surveillance System in the province of Quebec, Canada. Whether these trends were similar for men and women and across different socioeconomic status classes was also assessed. RESULTS: There were 130,750 hospitalizations for severe exacerbation and 104,460 deaths, including 24,457 (23.4%) respiratory-related deaths, over the study period (928,934 person-years). Significant changes in trends were seen after 03/2013 for all-cause mortality (-1.14%/month;95%CI -1.90% to -0.38%), which further decreased after 02/2015 (-1.78%/month;95%CI -2.70% to -0.38%). Decreases in respiratory-related mortality (-2.45%/month;95%CI -4.38% to -0.47%) and severe exacerbation (-1,90%/month;95%CI -3.04% to -0.75%) rates were only observed after 02/2015. These observations tended to be more pronounced in women than in men and in higher socioeconomic status groups (less deprived) than in lower socioeconomic status groups (more deprived). CONCLUSIONS: The arrival of newer bronchodilators was chronologically associated with reduced trends in severe exacerbation, all-cause and respiratory-related mortality rates among people with COPD > 65 years. Our findings document population benefits on key patient-relevant outcomes in the years following the introduction of newer once-daily long-acting bronchodilators and their combinations, which were likely multifactorial. Public health efforts should focus on closing the gap between lower and higher socioeconomic status groups.

The Real-World Efficacy of Fixed Triple Inhalation Therapy in the Treatment of Moderate COPD Patients (RATIONALE Study).

Purpose: COPD affects more than 300 million people worldwide, requiring inhalation treatment. Novel triple formulations of ICS, LABAs and LAMAs are becoming the mainstay of treatment, however there is still a lack of clinical evidence for personalized therapy. Patients and Methods: RATIONALE was a non-interventional, prospective, 52 week study, assessing the effectiveness of beclometasone/formoterol/glycopyrronium-bromide (BDP/FF/G), in symptomatic COPD patients, with moderate airflow obstruction. The study included 4 visits, where data on demographic parameters, exacerbations, symptoms, quality of life (based on the EQ-5D-3L questionnaire) and lung function were collected. Data on adherence to treatment, based on prescriptions filled was collected from the database of the National Health Insurance Fund, with the patients' consent. The primary objective was the change of adherence to treatment during the study, compared to baseline. Results: Altogether 613 patients had been enrolled. Their average age was 64.56 years and 50.5% were female. The average CAT score was 20.86, and most patients had suffered minimum one exacerbation (82.2%). Average FEV1 was 59.6%. Most patients had some limitation in one or more dimensions of EQ-5D-3L, with an average visual analogue scale score (VAS) of 60.31. After 12 months of treatment, adherence improved significantly - proportion of patients in the highest adherence group increased from 29.8% to 69.7% (p<0.001). The average CAT score improved by 7.02 points (95% CI 5.82-8.21, p<0.001). There was a significant improvement in all dimensions of EQ-5D-3L, with an average increase of 17.91 (95% CI 16.51-19.31, p< 0.001) points in the VAS score. Exacerbation frequency also decreased significantly. Conclusion: Although limitations of observational studies are present, we observed that early introduction of fixed triple combination results in a marked improvement in adherence to treatment, symptom scores, exacerbation frequency and quality of life. The optimal choice of treatment is crucial for reaching the highest possible adherence.

Congenital Long QT Syndrome Unmasked by Albuterol in an Adolescent with Asthma.

BACKGROUND: Patients with congenital long QT syndrome (LQTS) are prone to ventricular dysrhythmia but may be initially asymptomatic with a normal QTc interval on resting electrocardiogram (ECG). Albuterol is listed as a medication that poses a "special risk" to patients with congenital LQTS, but its effects have been rarely described. We present a case of previously unknown, asymptomatic congenital LQTS unmasked by albuterol in an adolescent with asthma. CASE REPORT: A 12-year-old girl with a history of asthma presented to the emergency department (ED) with shortness of breath, wheezing, and tachycardia for 24 h, consistent with acute asthma exacerbation. She received two doses of her home albuterol inhaler 2 h prior to presentation. Initial ECG demonstrated a QTc of 619 ms. Her remaining history, clinical examination, and laboratory workup, including electrolytes, were unremarkable. She was observed with cardiac monitoring before being discharged from the ED in stable condition for next-day outpatient pediatric cardiology follow-up. Resting office ECGs revealed QTcs from 440-470 ms. Exercise stress test revealed QTc prolongation of 520 ms and 500 ms at minute-2 and minute-4 of recovery, respectively. Genetic testing revealed heterozygous pathogenic variants in KCNQ1, consistent with type 1 LQTS. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Albuterol may be a cause of marked QTc prolongation in ED patients with underlying congenital LQTS, which can be a diagnostic clue in previously unidentified patients. Extreme QTc prolongation also serves as an indication in the ED for Cardiology consultation, laboratory evaluation for electrolyte imbalances, and observation with cardiac monitoring.

Small airways response to bronchodilators as the marker of the uncontrolled asthma in children.

OBJECTIVE: Aim: To develop the criteria of small airways response to bronchodilators (by spirometry indices maximal expiratory flow (MEF50 and MEF25) as the markers of uncontrolled asthma course. PATIENTS AND METHODS: Materials and Methods: The study involved 92 participants (64 boys and 28 girls) aged 6 to 17 years (60 were less than 12 years old) with diagnosed asthma. Asthma control was assessed with the use of Asthma Control Test and Asthma Control Questionnaire. Spirometry and bronchodilator responsiveness testing were performed for all participants. RESULTS: Results: Mostly, the studied children had a normal level of forced expiratory volume in the first second (FEV1), even at unsatisfactory symptoms control. The indicators of the medium and small airways patency were significantly worse in uncontrolled asthma children even in normal FEV1. Among children, the lack of asthma control can be caused by small airways obstruction in up to 80% cases. Among children who need the high dose inhaled corticosteroids treatment 93.3% have uncontrolled asthma with small airways obstruction. We found out that MEF50 and MEF25 could be the signs of the reversibility of bronchial obstruction and uncontrolled asthma with high sensitivity and specificity. CONCLUSION: Conclusions: Indices MEF50 and MEF25 allow detecting the small airways obstruction and their reversibility as a mark of uncontrolled asthma (MEF25 has a higher diagnostic value). In case of MEF50 and/or MEF25 increasing for 22% or 25% accordingly in bronchodilator test in children, the asthma should be considered uncontrolled.

¿Cómo llega el paciente asmático al servicio de emergencias? Datos del estudio multicéntrico SABINA EMERGENCIAS / How Does the Asthmatic Patient Arrive at the Emergency Department? Data from the SABINA EMERGENCIAS Multicenter Study

Introducción: Los objetivos del control del asma son prevenir la aparición de síntomas y reducir el riesgo de exacerbaciones y mortalidad mediante educación médica, técnica inhalatoria, adherencia a medicación controladora e indicación de planes de acción (PA); pero los pacientes enfrentan exacerbaciones de diversa gravedad. Objetivos: El objetivo principal del estudio SABINA EMERGENCIAS fue describir la forma en que los pacientes concurren al servicio de emergencias (SE), considerando la frecuencia y uso de medicación de rescate. Objetivos secundarios: consultas al SE; uso de corticoides sistémicos (CS), agonistas beta-2 de acción corta (SABA) y tratamiento controlador; disponibilidad de PA. Material y Métodos: Estudio transversal, observacional, descriptivo, en cuatro hospitales del área metropolitana de Buenos Aires en adultos con asma. Resultados: n=323 (edad: 43,7±16,8 años; mujeres: 66,6%): 61,3% no eran seguidos por especialistas; 90,1% utilizaron SABA como rescate (mediana:10 inhalaciones; rango 0-100) la semana previa; 75,9% tuvieron ≥1 consulta al SE el año previo (mediana:2 [0-100]); 29,4% habían sido hospitalizados; 59,1% recibieron ≥1 ciclo de CS; mediana de consumo de SABA: 3 envases/año (0-23); 51,7% habían utilizado ≥3 envases; 30% no empleaban tratamiento de mantenimiento (23% usaba SABA); 75,9% no efectuaban terapia regular de mantenimiento; 77,1% no contaban con PA. Conclusión: Una reducida proporción de pacientes asmáticos que concurren al SE son seguidos por médicos especialistas, con alto consumo y elevada frecuencia de aplicación de SABA como rescate y baja adherencia al tratamiento de mantenimiento. Se remarca la necesidad de optimizar el manejo, con énfasis en la derivación al especialista, adherencia al tratamiento y prescripción de PA.

Introduction: The objectives of asthma control are to prevent the onset of symptoms and reduce the risk of exacerbations and mortality through medical education, inhaler technique, adherence to controller medication and indication of action plans (AP); but patients experience exacerbations of varying severity. Objective: The main objective of the SABINA EMERGENCIAS study was to describe how patients attend the emergency department (ED), considering the frequency and use of rescue medication. Secondary objectives: ED visits; use of systemic corticosteroids (SC), short-acting beta-2 agonists (SABA) and controller therapy; availability of AP. Methods: Cross-sectional, observational, descriptive study in 4 hospitals in the metropolitan area of Buenos Aires in adults with asthma. Results: n=323 (age:43.7±16.8 years; women:66.6%): 61.3% were not followed by specialists; 90.1% used SABA as rescue medication (median:10 puffs; range 0-100) the previous week; 75.9% had ≥1 visit to the ES the previous year (median: 2 [0-100]); 29.4% had been hospitalized; 59.1% received ≥1 cycle of CS; median SABA consumption: 3 cannisters/year (0-23); 51.7% had used ≥3 cannisters; 30% did not use maintenance therapy (23% used SABA); 75.9% did not perform regular maintenance therapy; 77.1% did not have an AP. Conclusion: A small proportion of asthmatic patients attending the ES are followed by specialist physicians, with high consumption and high frequency of SABA application as rescue medication and low adherence to maintenance treatment. The need to optimize management is highlighted, with emphasis on referral to specialists, adherence to treatment and prescription of APs.

Greenhouse Gas Emissions and Costs of Inhaler Devices in the US.

This study assesses mean emissions and costs and estimated total yearly emissions and costs for US-branded inhalers prescribed to Medicare Part D and Medicaid beneficiaries.

Effect of ensifentrine on dyspnea in patients with moderate-to-severe chronic obstructive pulmonary disease: pooled analysis of the ENHANCE trials.

BACKGROUND: Dyspnea is a critical component of chronic obstructive pulmonary disease (COPD). We report the effect of ensifentrine, a novel PDE3/PDE4 inhibitor, on dyspnea using pooled data from the Phase 3 ENHANCE-1/2 trials. METHODS: The pooled population (ensifentrine, n = 975; placebo, n = 574) included patients aged 40-80 years with post-bronchodilator FEV1/FVC <0.7, FEV1 30-70% predicted, mMRC Dyspnea Scale score ≥2, and a smoking history ≥10 pack-years. Patients taking dual LAMA/LABA or LAMA/LABA/ICS triple therapy were excluded. Dyspnea measures included the Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms (E-RS), and rescue medication use. RESULTS: After 24 weeks, ensifentrine significantly improved TDI scores (least-squares mean difference, 0.97; 95% CI, 0.64, 1.30; p < 0.001) and across all TDI subdomains. Ensifentrine-treated patients were more likely to be TDI responders at week 24 (p < 0.001), which was consistent across clinically relevant subgroups. Ensifentrine-treated patients had improved E-RS breathlessness subdomain scores (p = 0.053) and reduced rescue medication use (p = 0.002). CONCLUSION: Ensifentrine produced clinically meaningful improvements in multiple dyspnea measures in patients with symptomatic, moderate-to-severe COPD. A limitation of this study was the exclusion of patients taking dual LAMA/LABA and LAMA/LABA/ICS triple therapy. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.

Synergistic effect of magnesium stearate and fine lactose in improving aerosolization performance of fluticasone propionate in dry powder formulation.

Magnesium stearate (MgSt) and lactose fines are often used as ternary components in carrier-based dry powder inhalers (DPIs) to improve fine particle fraction (FPF), but whether they act synergistically to improve aerosolization performance of DPI formulations is currently less studied. In addition, the applicability of utilizing powder rheological parameters to predict the FPF needs to be further verified. Thus, in this study, using fluticasone propionate (FP) as a model drug, effect of lactose fines addition in 0.5% MgSt containing DPI formulations on their powder and aerodynamic properties was explored. Influence of MgSt and fines mixing order on the DPIs performance was also investigated. The results showed that addition of lactose fines (1-10%) in 0.5% MgSt containing formulations could further improve flowability and enhance adhesion of the mixtures, and they could act synergistically to improve FPF. Moreover, the presence of 0.5% MgSt can greatly reduce the amount of lactose fines required to achieve the comparable FPF. The mixing order can affect distribution of MgSt on the carrier surface, with higher FPF noted when MgSt was mixed with carrier first, followed by lactose fines. A good linear relationship between powder rheological parameters such as basic flowability energy (BFE), Permeability and FPF was disclosed. In conclusion, in FP based DPIs, MgSt and lactose fines act synergistically to enhance FPF by tuning powder characteristics. Good flowability (27.39%) and strong adhesion (72.61%) contributed to the enhanced drug deposition in the lung.