RESUMEN

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.

Asunto(s)

Agonistas de Receptores Adrenérgicos beta 2 , Beclometasona , Broncodilatadores , Combinación de Medicamentos , Fumarato de Formoterol , Glicopirrolato , Pulmón , Cumplimiento de la Medicación , Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Calidad de Vida , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Administración por Inhalación , Estudios Prospectivos , Anciano , Resultado del Tratamiento , Broncodilatadores/administración & dosificación , Glicopirrolato/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Pulmón/fisiopatología , Pulmón/efectos de los fármacos , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/efectos adversos , Beclometasona/administración & dosificación , Factores de Tiempo , Fumarato de Formoterol/administración & dosificación , Volumen Espiratorio Forzado , Índice de Severidad de la Enfermedad , Recuperación de la Función , Progresión de la Enfermedad , Glucocorticoides/administración & dosificación

RESUMEN

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.

Asunto(s)

Asma , Broncodilatadores , Espirometría , Humanos , Asma/tratamiento farmacológico , Asma/diagnóstico , Asma/fisiopatología , Niño , Femenino , Masculino , Adolescente , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Volumen Espiratorio Forzado/efectos de los fármacos , Biomarcadores

RESUMEN

BACKGROUND: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count - focusing on blood EOS count 100 to < 300 cells/mm3 - as a function of exacerbation history and COPD severity. METHODS: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12-24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses. RESULTS: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD. CONCLUSIONS: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations. TRIAL REGISTRATION: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).

Asunto(s)

Broncodilatadores , Budesonida , Eosinófilos , Fumarato de Formoterol , Glicopirrolato , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/sangre , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Glicopirrolato/administración & dosificación , Femenino , Anciano , Persona de Mediana Edad , Broncodilatadores/administración & dosificación , Budesonida/administración & dosificación , Eosinófilos/efectos de los fármacos , Fumarato de Formoterol/administración & dosificación , Método Doble Ciego , Progresión de la Enfermedad , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Administración por Inhalación , Resultado del Tratamiento , Antagonistas Muscarínicos/administración & dosificación , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología

RESUMEN

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

Asunto(s)

Asma , Antagonistas Muscarínicos , Oscilometría , Humanos , Femenino , Masculino , Persona de Mediana Edad , Antagonistas Muscarínicos/administración & dosificación , Asma/tratamiento farmacológico , Asma/fisiopatología , Asma/diagnóstico , Resultado del Tratamiento , Oscilometría/métodos , Adulto , Anciano , Combinación de Medicamentos , Quinuclidinas/administración & dosificación , Clorobencenos/administración & dosificación , Broncodilatadores/administración & dosificación , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico

RESUMEN

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.

Asunto(s)

Aerosoles , Inhaladores de Polvo Seco , Fluticasona , Lactosa , Tamaño de la Partícula , Polvos , Ácidos Esteáricos , Lactosa/química , Fluticasona/química , Fluticasona/administración & dosificación , Polvos/química , Ácidos Esteáricos/química , Excipientes/química , Reología , Composición de Medicamentos/métodos , Administración por Inhalación , Química Farmacéutica/métodos , Broncodilatadores/administración & dosificación , Broncodilatadores/química

RESUMEN

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.

Asunto(s)

Disnea , Inhibidores de Fosfodiesterasa 4 , Enfermedad Pulmonar Obstructiva Crónica , Índice de Severidad de la Enfermedad , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Disnea/tratamiento farmacológico , Disnea/fisiopatología , Anciano , Masculino , Femenino , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del Tratamiento , Adulto , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Inhibidores de Fosfodiesterasa 4/efectos adversos , Broncodilatadores/administración & dosificación , Inhibidores de Fosfodiesterasa 3/uso terapéutico , Inhibidores de Fosfodiesterasa 3/administración & dosificación , Inhibidores de Fosfodiesterasa 3/efectos adversos , Volumen Espiratorio Forzado , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Ensayos Clínicos Fase III como Asunto

Asunto(s)

Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Administración por Inhalación , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico

RESUMEN

INTRODUCTION: To date, there is limited evidence on the effects of bronchodilators on respiratory dynamics in chronic obstructive pulmonary disease (COPD). Dynamic chest radiography (DCR) is a novel radiographic modality that provides real-time, objective and quantifiable kinetic data, including changes in the lung area (Rs), tracheal diameter, diaphragmatic kinetics and pulmonary ventilation during respiration, at a lower radiation dose than that used by fluoroscopic or CT imaging. However, the therapeutic effect of dual bronchodilators on respiratory kinetics, such as chest wall dynamics and respiratory muscle function, has not yet been prospectively evaluated using DCR. AIM: This study aims to evaluate the effects of bronchodilator therapy on respiratory kinetics in patients with COPD using DCR. METHODS AND ANALYSIS: This is an open-label, prospective, single-centre, non-controlled, comparative study. A total of 35 patients with COPD, aged 40-85 years, with a forced expiratory volume in the first second of 30-80%, will be enrolled. After a 2-4 weeks washout period, patients will receive tiotropium/olodaterol therapy for 6 weeks. Treatment effects will be evaluated based on DCR findings, pulmonary function test results and patient-related outcomes obtained before and after treatment. The primary endpoint is the change in Rs after therapy. The secondary endpoints include differences in other DCR parameters (diaphragmatic kinetics, tracheal diameter change and maximum pixel value change rate), pulmonary function test results and patient-related outcomes between pre-therapy and post-therapy values. All adverse events will be reported. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the Ethics Committee of Chiba University Hospital. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCTs032210543.

Asunto(s)

Benzoxazinas , Broncodilatadores , Combinación de Medicamentos , Enfermedad Pulmonar Obstructiva Crónica , Bromuro de Tiotropio , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Bromuro de Tiotropio/administración & dosificación , Bromuro de Tiotropio/uso terapéutico , Estudios Prospectivos , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Anciano , Benzoxazinas/uso terapéutico , Benzoxazinas/administración & dosificación , Persona de Mediana Edad , Masculino , Anciano de 80 o más Años , Femenino , Adulto , Radiografía Torácica , Volumen Espiratorio Forzado/efectos de los fármacos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Pulmón/efectos de los fármacos

Asunto(s)

Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Broncodilatadores/uso terapéutico

RESUMEN

OBJECTIVE: To assess the clinical effect of Qingre Bawei capsules combined with budesonide in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: The retrospective study was conducted at the Baoding No.1 Central Hospital, China, and comprised data of patients with acute exacerbation of COPD admitted between June 1, 2020, and June 30, 2022. The patients were divided into two groups based on treatment methods. The group A had been treated with Qingre Bawei capsules in combination with budesonide, while the group B had been treated with budesonide alone. Both the groups had been treated for 2 consecutive weeks. The changes in blood gas indicators, inflammation indicators, and lung function indicators were compared between two groups of patients before and 24 hours after treatment. The time for clinical symptom disappearance and adverse reactions between the two groups of patients was also noted. RESULTS: Of the 120 patients, 60(50%) were in group A; 41(68.3%) males and 19(31.7%) females, with mean age 65.28±4.36 years (range: 47-78 years) and mean course of disease 31.22±4.75 hours (range: 6-65 hours). 60(50%) patients were in group B; 43(71.7%) males and 17(28.3%) females with mean age 65.31±4.31 years (range: 48-78 years) and mean course of disease 31.29±4.71 hours (range: 8-68 hours). The disappearance time of clinical symptoms in group A was better than group B (p<0.05). The levels of blood gas indicators, inflammation indicators, and lung function indicators in both groups significantly improved (p<0.05), but the degree of improvement in group A was better than group B (p<0.05); The total effective rate of group A was better than group B (p<0.05). None of the patients in either group experienced any significant adverse reaction. CONCLUSIONS: Qingre Bawei capsules combined with budesonide had a significantly better therapeutic effect on cases of acute exacerbation of chronic obstructive pulmonary disease compared to budesonide alone.

Asunto(s)

Budesonida , Medicamentos Herbarios Chinos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Budesonida/administración & dosificación , Budesonida/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Estudios Retrospectivos , Quimioterapia Combinada , Cápsulas , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Progresión de la Enfermedad , Resultado del Tratamiento , Glucocorticoides/administración & dosificación , Glucocorticoides/uso terapéutico , Volumen Espiratorio Forzado/efectos de los fármacos

RESUMEN

OBJECTIVE: To compare the efficacy of inhaled salbutamol with salmeterol for the treatment of arterial hypoxaemia in anaesthetized horses. STUDY DESIGN: Prospective, randomized, clinical study. ANIMALS: A total of 108 client-owned horses (American Society of Anesthesiologists status I-V) anaesthetized for elective and emergency procedures. METHODS: Horses were premedicated with acepromazine [intramuscularly 0.1 mg kg-1 or intravenously (IV) 0.05 mg kg-1] and xylazine (0.6 mg kg-1 IV). Midazolam (0.06 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV) were combined to induce anaesthesia, and isoflurane in oxygen/air mixture (inspired oxygen fraction 0.7) was used for maintenance of anaesthesia. Mechanical ventilation was initiated without delay using the following ventilator settings: tidal volume 10 mL kg-1, respiratory rate 8 breaths minute-1, inspiratory-to-expiratory time ratio 1:2, no positive end-expiratory pressure. If arterial blood gas analysis revealed PaO2 < 100 mmHg (13.3 kPa), the administration of either inhaled salbutamol (2 µg kg-1) or salmeterol (0.5 µg kg-1) was randomly assigned Blood gas analysis was repeated 15 and 30 minutes after treatment. The intervention was considered successful when PaO2 after treatment ≥ 1.2 × PaO2 before treatment (i.e. ≥20% increase). PaO2 at 15 and 30 minutes was compared between groups using Mann-Whitney U test; p < 0.05 was considered significant. RESULTS: Of the 108 horses, 60 were administered salbutamol, 65% and 60% responded successfully at 15 and 30 minutes, increasing their initial PaO2 by 38% and 44%, respectively. The other 48 horses were administered salmeterol, 35% responded successfully at 15 and 30 minutes, increasing their initial PaO2 by 3% and 4%, respectively. PaO2 was significantly higher after salbutamol than after salmeterol at 15 and 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: Using the described protocol, inhaled salbutamol was more effective than salmeterol in improving PaO2 in anaesthetized horses with value < 100 mmHg (13.3 kPa).

Asunto(s)

Albuterol , Hipoxia , Xinafoato de Salmeterol , Animales , Caballos , Albuterol/administración & dosificación , Albuterol/uso terapéutico , Albuterol/análogos & derivados , Masculino , Femenino , Xinafoato de Salmeterol/administración & dosificación , Xinafoato de Salmeterol/uso terapéutico , Hipoxia/veterinaria , Administración por Inhalación , Enfermedades de los Caballos/tratamiento farmacológico , Estudios Prospectivos , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico

RESUMEN

Electronic inhalers provide information about patterns of routine inhaler use. During a 12-week study, 360 asthma patients using albuterol Digihaler generated 53,083 inhaler events that were retrospectively analyzed. A total of 41,528 (78%) of the recorded inhalation events were suitable for flow analysis (having a PIF ≥ 18 L/min and <120 L/min). Median PIF, inhalation volume, inhalation duration, and time to PIF for these events steadily decreased between the first and last 10 days of the study, by 5.1%, 12.6%, 15.9%, and 6.4%, respectively. Continuous short-acting beta2-agonist (SABA) overuse, defined as ≥2 SABA inhalations/week throughout the study period, was seen in 29% (n = 104) of patients. Of 260 patients with ≥1 instance of acute short-term SABA overuse, 55 (21%) had a confirmed exacerbation. Electronic recording of real-life inhaler use can capture valuable, objective information that could inform disease management and clinical decision-making.

Asunto(s)

Asma , Nebulizadores y Vaporizadores , Humanos , Asma/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Administración por Inhalación , Albuterol/administración & dosificación , Albuterol/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Anciano , Adulto Joven , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Adolescente

Asunto(s)

Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación

RESUMEN

Purpose: Triple therapy (long-acting muscarinic antagonist/long-acting ß2-agonist/inhaled corticosteroid) is recommended for patients with chronic obstructive pulmonary disease (COPD) who experience recurrent exacerbations. Multiple-inhaler triple therapy (MITT) is associated with poor adherence and persistence. This study assessed comparative adherence and persistence to single-inhaler triple therapy (SITT) versus MITT among patients with COPD in a real-world setting in Germany. Patients and Methods: This retrospective analysis using the WIG2 benchmark database identified patients with COPD newly initiating triple therapy with MITT or SITT (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or formoterol/beclomethasone/glycopyrronium bromide [FOR/BDP/GLY]) November 2017-June 2019. Eligible patients were ≥35 years with 1 year's continual insurance prior to triple therapy initiation and no previous record of triple therapy. Inverse probability of treatment weighting was used to balance baseline characteristics. Adherence was measured using proportion of days covered (PDC) at 6, 12, and 18 months post-treatment initiation; persistence (time until treatment discontinuation) was measured at 6, 12, and 18 months, with a gap of >30 days used to define non-persistence. Results: Of 5710 patients included in the analysis (mean age 66 years), 71.4% initiated MITT and 28.6% initiated SITT (FF/UMEC/VI: 41.4%; FOR/BDP/GLY: 58.6%). Mean PDC was higher among SITT versus MITT users at all time points; at each time point, mean PDC was highest among FF/UMEC/VI users. During the first 6 months following treatment initiation, higher adherence was exhibited by FF/UMEC/VI (29%) and FOR/BDP/GLY (19%) users versus MITT users. Over the entire observation period, FF/UMEC/VI users had the highest proportion of persistent patients; at 18 months, 16.5% of FF/UMEC/VI users were persistent versus 2.3% of MITT users. Conclusion: Patients initiating SITT in Germany had significantly higher adherence and persistence compared with patients initiating MITT over 6 to 18 months following treatment initiation. Among SITT, FF/UMEC/VI users had the highest proportion of adherence and persistence.

Asunto(s)

Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Combinación de Medicamentos , Cumplimiento de la Medicación , Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Alemania , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Administración por Inhalación , Antagonistas Muscarínicos/administración & dosificación , Broncodilatadores/administración & dosificación , Resultado del Tratamiento , Quinuclidinas/administración & dosificación , Factores de Tiempo , Bases de Datos Factuales , Clorobencenos/administración & dosificación , Clorobencenos/uso terapéutico , Reclamos Administrativos en el Cuidado de la Salud , Quimioterapia Combinada , Alcoholes Bencílicos/administración & dosificación , Alcoholes Bencílicos/uso terapéutico , Nebulizadores y Vaporizadores , Glicopirrolato/administración & dosificación , Pulmón/efectos de los fármacos , Pulmón/fisiopatología

Asunto(s)

Broncodilatadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos

RESUMEN

A 22-kg female in early childhood with a history of reactive airway disease presented to a paediatric emergency department with acute shortness of breath, tachypnoea and wheezing. Despite treatment with albuterol and corticosteroids, her bronchospasm persisted, prompting the administration of terbutaline. The patient received 220 mcg (10 mcg/kg) terbutaline intravenously, followed immediately by an inadvertent supratherapeutic intravenous dose of 10 000 mcg (454.5 mcg/kg). The patient's laboratory results obtained minutes after the medication error were notable for: potassium, 3.1 mmol/L, lactate, 2.6 mmol/L and troponin I, 0.30 ng/mL (normal <0.03 ng/mL). Over the next 48 hours, serial serum troponin values decreased. The patient was discharged home approximately 72 hours after the initial presentation and she remained well based on follow-up calls over the next several months. Given the timing and trend of troponin concentrations, we do not believe the terbutaline overdose to be responsible for the myocardial injury.

Asunto(s)

Sobredosis de Droga , Terbutalina , Humanos , Terbutalina/administración & dosificación , Femenino , Broncodilatadores/administración & dosificación , Administración Intravenosa , Troponina I/sangre , Preescolar

RESUMEN

INTRODUCTION: Symptom status and treatment changes among patients with chronic obstructive pulmonary disease (COPD) using inhaler treatment in real-world clinical settings are not well understood, particularly according to class of treatment. We investigated the proportion of symptomatic patients among those with COPD using inhaler treatment, based on COPD Assessment Test (CAT) scores in clinical practice, and changes in inhaler treatments and symptoms at 1-year follow-up. METHODS: This was a retrospective analysis of data from a multicenter, prospective cohort study conducted at medical institutions with respiratory specialists in Japan. The primary endpoint was the proportion of patients with CAT scores ≥ 10 or < 10 in each inhaler treatment group at registration. RESULTS: Of 414 patients in the full analysis set, 76 (18.4%), 261 (63.0%), and 77 (18.6%) were using long-acting muscarinic antagonist (LAMA), LAMA + long-acting ß2-agonist (LABA), and inhaled corticosteroids (ICS) + LABA, respectively, at registration. The proportions of patients with CAT scores ≥ 10 or < 10 per inhaler treatment group at registration, respectively, were 32.9% and 67.1% in the LAMA group, 55.0% and 45.0% in the LAMA + LABA group, and 50.0% and 50.0% in the ICS + LABA group. Most patients (> 75%) in each inhaler treatment group showed no change in inhaler treatment at 1 year, regardless of their CAT score at registration. Approximately 70-80% of patients with CAT scores ≥ 10 at registration still had CAT scores ≥ 10 at 1 year; 10-30% of patients with CAT scores < 10 at registration had CAT scores ≥ 10 at 1 year. CONCLUSION: In real-world Japanese clinical practice, a considerable proportion of patients have persistent symptoms (CAT score ≥ 10) despite using mono or dual inhaler treatment; > 75% of symptomatic patients with COPD using inhaler treatment did not undergo treatment escalation at 1-year follow-up and remained symptomatic. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05903989.

Asunto(s)

Corticoesteroides , Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas Muscarínicos , Medición de Resultados Informados por el Paciente , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Masculino , Femenino , Anciano , Japón , Antagonistas Muscarínicos/uso terapéutico , Antagonistas Muscarínicos/administración & dosificación , Persona de Mediana Edad , Estudios Retrospectivos , Administración por Inhalación , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Corticoesteroides/uso terapéutico , Corticoesteroides/administración & dosificación , Nebulizadores y Vaporizadores , Broncodilatadores/uso terapéutico , Broncodilatadores/administración & dosificación , Estudios Prospectivos , Quimioterapia Combinada , Resultado del Tratamiento

RESUMEN

BACKGROUND: The extrafine single inhaler triple therapy (efSITT) containing beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 µg has proved to be efficacious in patients with chronic obstructive pulmonary disease (COPD) in randomized control trials. OBJECTIVE: TRIWIN study evaluated the effectiveness of efSITT delivering beclomethasone dipropionate/formoterol fumarate/glycopyrronium 87/5/9 µg in COPD patients previously treated with multiple-inhaler triple therapy (MITT) in a real-world study in Greece. DESIGN: Prospective, multicenter, observational, non-interventional study was conducted over 24 weeks. METHODS: A total of 475 eligible patients had moderate-to-severe COPD, an indication for treatment with efSITT, and were symptomatic despite receiving MITT. COPD Assessment Test (CAT) score, pulmonary function parameters, use of rescue medication, and adherence to inhaler use were recorded at baseline (Visit 1), 3 (Visit 2), and 6 months (Visit 3) after treatment. RESULTS: Mean CAT score decreased from 21.4 points at Visit 1, to 16.6 at Visit 2 and 15.1 at Visit 3 (p < 0.001 for all pair comparisons). At Visit 3, 79.8% of patients reached a CAT improvement exceeding minimal clinically important difference (⩾2), compared to baseline. Mean forced expiratory volume in 1 s (%pred.) increased from 55.4% at Visit 1 to 63.5% at the end of study period (p < 0.001), while mean forced vital capacity (%pred.) increased from 71.1% at Visit 1, to 76.7% at Visit 3 (p < 0.001). The mean Test of Adherence to Inhalers score increased from 42.5 to 45.3 and 46.3 points, for the three visits, respectively (p < 0.001 comparing Visits 1/2 and Visits 1/3; p = 0.006 comparing Visits 2/3). The percentage of patients showing good adherence rose from 33.7% at baseline to 58.3% at Visit 3. The percentage of patients using rescue medication during the last month dropped from 16.2% to 7.4% at the end of study period (p < 0.001). Pulmonary function parameters also improved. CONCLUSION: The TRIWIN results suggest that extrafine beclomethasone dipropionate/formoterol fumarate/glycopyrronium is effective in improving health status, pulmonary function, and adherence and in reducing rescue medication use in COPD patients previously treated with MITT, in a real-world setting in Greece.

Asunto(s)

Beclometasona , Broncodilatadores , Combinación de Medicamentos , Fumarato de Formoterol , Glicopirrolato , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Masculino , Femenino , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Beclometasona/administración & dosificación , Beclometasona/efectos adversos , Administración por Inhalación , Fumarato de Formoterol/administración & dosificación , Resultado del Tratamiento , Broncodilatadores/administración & dosificación , Broncodilatadores/efectos adversos , Glicopirrolato/administración & dosificación , Glicopirrolato/efectos adversos , Grecia , Pulmón/fisiopatología , Pulmón/efectos de los fármacos , Índice de Severidad de la Enfermedad , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/efectos adversos , Factores de Tiempo , Volumen Espiratorio Forzado , Cumplimiento de la Medicación , Glucocorticoides/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/efectos adversos

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous progressive lung condition characterized by long-term respiratory symptoms and airflow limitation. Appropriate bronchodilation is the cornerstone of COPD treatment, leading to better health status as well as benefits in prognosis and mortality. METHODS: In the current open, noninterventional, observational study, 716 patients diagnosed with COPD of variable severity were administered a fixed-dose combination (FDC) of fluticasone propionate and salmeterol (500 + 50 mcg) through the Elpenhaler® device. The patients' adherence to treatment (based on the MMAS-8 [8-item Morisky Medication Adherence Scale]) and health status (based on the CCQ [Clinical COPD Questionnaire]) were assessed at the beginning of the study and at the end of the 3-month follow-up period. RESULTS: The mean ± SD MMAS-8 score at 1 and 3 months was 6.12 ± 1.89 and 6.45 ± 1.80, respectively, indicating medium adherence overall; however, there was a statistically significant increase of 0.33 units in the MMAS-8 score at the end of the follow-up (paired t-test p < 0.0001), suggestive of an improvement in adherence throughout the study. Higher adherence was associated with better health status at baseline, which further improved by the end of the follow-up. Moreover, we observed a statistically significant decrease of 1.07 points (p < 0.0001) in the mean CCQ total score from the baseline (CCQ score = 2.2 ± 1.00) until the end of the study follow-up (CCQ score = 1.13 ± 0.67). Similar conclusions were also drawn in the mean domain scores regarding symptoms (score equal to 1.36 ± 0.72, decrease by 1.18) as well as functional and mental state (scores equal to 0.86 ± 0.73 and 1.20 ± 0.88, decrease by 1.04 and 1.00, respectively, p < 0.0001). Similarly, when patients were stratified into subgroups with and without comorbidities, the former group showed an increase of 7% in the patients with medium to high adherence during the course of the study. In the same patient subgroup, there was a notable decrease in CCQ score by 1.18 points (p < 0.0001) during the study. CONCLUSIONS: The administration of FDC of fluticasone propionate and salmeterol, (500 + 50 mcg) via the Elpenhaler® device for COPD, resulted in a well-maintained or slight increase in treatment adherence and a subsequent benefit in health status, which further persisted after 3 months of treatment.

Asunto(s)

Broncodilatadores , Combinación Fluticasona-Salmeterol , Estado de Salud , Cumplimiento de la Medicación , Enfermedad Pulmonar Obstructiva Crónica , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Administración por Inhalación , Albuterol/análogos & derivados , Albuterol/administración & dosificación , Albuterol/uso terapéutico , Broncodilatadores/administración & dosificación , Broncodilatadores/uso terapéutico , Combinación de Medicamentos , Combinación Fluticasona-Salmeterol/administración & dosificación , Combinación Fluticasona-Salmeterol/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Encuestas y Cuestionarios , Resultado del Tratamiento

RESUMEN

INTRODUCTION: In the management of chronic obstructive pulmonary disease (COPD), inhalation therapy plays a pivotal role. However, clinicians often face the dilemma of choosing between single and multiple inhaler therapies for their patients. This choice is critical because it can affect treatment efficacy, patient adherence, and overall disease management. AREAS COVERED: This article examines the advantages and factors to be taken into consideration when selecting between single and multiple inhaler therapies for COPD. EXPERT OPINION: Both single and multiple inhaler therapies must be considered in COPD management. While single inhaler therapy offers simplicity and convenience, multiple inhaler therapy provides greater flexibility and customization. Clinicians must carefully evaluate individual patient needs and preferences to determine the most appropriate inhaler therapy regimen. Through personalized treatment approaches and shared decision-making, clinicians can optimize COPD management and improve patient well-being. Nevertheless, further research is required to compare the effectiveness of single versus multiple inhaler strategies through rigorous clinical trials, free from industry bias, to determine the optimal inhaler strategy. Smart inhaler technology appears to have the potential to enhance adherence and personalized management, but the relative merits of smart inhalers in single inhaler regimens versus multiple inhaler regimens remain to be determined.

Asunto(s)

Broncodilatadores , Cumplimiento de la Medicación , Nebulizadores y Vaporizadores , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Administración por Inhalación , Broncodilatadores/administración & dosificación , Resultado del Tratamiento , Diseño de Equipo