Giant lung cavity due to three different pathogens in a patient receiving inhaled salmeterol plus fluticasone propionate for asthma.

INTRODUCTION: High-dose and long-term use of inhaled corticosteroids may cause systemic and local side effects such as opportunistic infections. Here we report a patient with asthma who developed a giant cavity in the lung while using inhaled salmeterol plus fluticasone propionate. CASE STUDY: A 57-year-old female patient presented with a three-week history of cough, hemoptysis, and dyspnea. She had a diagnosis of asthma for 4 years and was using an inhaled salmeterol plus fluticasone treatment intermittently for 2 years. A giant cavity was detected in the patient's chest X-ray. As a result of further investigations, three different microorganisms were isolated from the samples of sputum, bronchial lavage and lung biopsy. RESULTS: Staphylococcus aureus was the first microorganism that was isolated from the sputum and the bronchial lavage. Afterwards, Candida albicans was detected in both the bronchial lavage fluid and the histologic examination of the tissue samples obtained by percutaneous lung biopsy. Appropriate antibiotics and antifungals were prescribed. Moderate clinical and radiological response to the treatment was obtained. During the outpatient follow-up, Mycobacterium tuberculosis growth which was sensitive to all of the major anti-tuberculosis drugs was reported in the mycobacterial culture, and the patient was started on anti-tuberculosis treatment. CONCLUSION: Tuberculosis and other opportunistic infections are a potential consequences of inhaled corticosteroids. Clinicians overseeing such patients need to be vigilant about the need for timely investigations about tuberculosis before and during prescribing medications containing inhaled corticosteroids.

The assessment of effectiveness, tolerance, and patient satisfaction with the use of a new fixed-dose combination product, containing salmeterol and fluticasone propionate, Salflumix Easyhaler® in the treatment of asthma in the daily clinical practice.

BACKGROUND: The effectiveness of a fix-dose salmeterol/fluticasone combination therapy in asthma was previously shown for the original product. The study aim was to evaluate the clinical effectiveness and safety of a second entry DPI - dry powder inhaler (Salflumix Easyhaler) in patients with asthma in everyday clinical practice. PATIENTS AND METHODS: This multicenter Investigator-Initiated Study that enrolled 2,037 adult outpatients with asthma treated with Salflumix Easyhaler, was conducted by 220 pulmonologists across Poland. Asthma control was assessed during 3 visits with 6 ± 2 weeks intervals based on the Asthma Control Test (ACT). In addition, patient Satisfaction with Asthma Treatment Questionnaire (SATQ) and adherence and adverse events (AEs) were monitored. RESULTS: During the observation (86 ± 30 days) the percentage of patients with controlled asthma (ACT 20-25 pts) increased from 35.5% at the first visit to 86.5% at the third visit (p < 0.001). In the subgroup analysis, there were more patients not obtaining asthma control among patients that switched from the treatment with other devices than in naive ones. Global SATQ scores increased from 5.8 ± 0.7 to 6.2 ± 0.6 during the observation. Patients' satisfaction with the use of the Salflumix Easyhaler was high. Adherence exceeded 95%. Eight AEs were reported. CONCLUSIONS: Salflumix Easyhaler is highly effective and well-tolerated by naïve patients with asthma and those switching from another device. In general, patients show good compliance with medical product and are satisfied with the use of this new device, and not reporting difficulties and errors related to its' use. Their physicians' overall perception of Salflumix Easyhaler use is very positive.

Effectiveness and safety of salmeterol/fluticasone fixed-dose combination delivered through Synchrobreathe® in patients with asthma: the real-world EVOLVE study.

BACKGROUND: Inhalation therapy with corticosteroids and long-acting ß2-agonists has been the mainstay of asthma management. However, choosing the correct inhaler technique is essential to effectively deliver the medication to the lungs to attain good asthma control. OBJECTIVE: This study aimed to evaluate asthma control and device usability with salmeterol/fluticasone fixed-dose combination (FDC) administered through Synchrobreathe®, a breath-actuated inhaler (BAI), in Indian patients with persistent asthma (EVOLVE study). DESIGN: The present study was a prospective, open-label, non-comparative, multi-center, observational study. METHODS: The study enrolled 490 patients with documented diagnoses of asthma who were treatment-naive or uncontrolled due to poor inhaler technique associated with a previous device. The primary endpoint was a change from baseline in the Asthma Control Questionnaire-6 (ACQ-6) score at week 12. RESULTS: Mean ACQ-6 score reduced from 2.2 ± 1.07 (baseline) to 0.4 ± 0.49 (mean change: -1.9 ± 1.12, p < 0.0001) at week 12 in the intention-to-treat (ITT) population, and minimal clinically important difference of 0.5 was observed from week 4 onwards. Peak expiratory flow rate improved by 82.5 ± 75.74 ml/min (p < 0.0001) at week 12 in the ITT population. The proportion of well-controlled responders increased from 39.9% (week 4) to 77.1% (week 12). Most (91%) patients preferred the Synchrobreathe® and rated it very high for usability, portability, patient confidence, and satisfaction. Salmeterol/fluticasone FDC administered through Synchrobreathe® was well tolerated. CONCLUSION: Treatment with salmeterol/fluticasone FDC administered through Synchrobreathe® for 12 weeks persistently improved asthma control and lung function and was well tolerated. Most patients were satisfied with it and preferred Synchrobreathe® BAI over their previous device. REGISTRATION: The study was registered with the Clinical Trial Registry of India (CTRI/2018/12/016629).

Respiratory questionnaire-based analysis of awareness of COPD in a large multicenter rural population-based study in India.

Background: Chronic obstructive pulmonary disease (COPD) is a more prevalent chronic lung disease with a significant health burden, and the majority of these cases receive inadequate treatment. Methods: Prospective, observational, interview (questionnaire) based complete workup COPD study, screened 12,000 cases with chronic respiratory symptoms with cough, sputum production, and shortness of breath. A total of 6000 COPD cases were enrolled after the spirometry test. COPD cases were assessed as disease knowledge and methods of treatment offered by applying questionnaires to patients and treating physicians. Results: In the present study, 3% of study cases were aware of their COPD illness, 54% were not having knowledge about the disease, and 43% cases were not accepting the COPD diagnosis (p < 0.0001). A total of 58% of cases received inhalation treatment as levosalbutamol monotherapy in 31% cases, levosalbutamol plus beclometasone in 18% cases, and formoterol plus budesonide or salmeterol plus fluticasone only in 9% of COPD cases (p < 0.0001). Total 42% cases received oral treatment as theophylline in 16% cases, salbutamol in 7% cases, oral steroids in 19% cases (p < 0.0001). Conclusion: "Doctor-patient-drug trio" discordance clubbed as "difficult doctor, difficult patient, and difficult treatment" is a very crucial issue observed during diagnosis and management of COPD in peripheral settings in India.

[Pharmacoeconomics analysis of using a fixed combination of budesonide/formoterol in patients with asthma in the health care system of the Russian Federation].

AIM: To evaluate the budgetary impact of using budesonide + formoterol (Symbicort Turbuhaler) as maintenance therapy in real clinical practice compared with standard therapy for asthma of varying severity: for mild asthma with on-demand salbutamol; for moderate and severe asthma with the drug salmeterol + fluticasone and salbutamol on demand. MATERIALS AND METHODS: A static mathematical model was built to assess the impact on the budget when introducing the drug budesonide + formoterol (Symbicort Turbuhaler) in the treatment of asthma into clinical practice from the point of view of the state. Demographic data was taken from the official data of the Federal State Statistics Service. Direct medical costs included the cost of medicines, the cost of hospitalization of patients associated with the development of asthma exacerbations, and the cost of scheduled outpatient visits. Indirect costs considered the loss of GDP due to hospitalization of patients against the background of asthma exacerbations. A one-way sensitivity analysis was performed to confirm the robustness of the study results. RESULTS: Assessment of direct costs in the treatment of mild, moderate and severe asthma showed that a gradual increase in the proportion of patients receiving the drug budesonide + formoterol (Symbicort Turbuhaler) over the years to 5.5, 7.7 and 9.7% accordingly, led to an increase in the cost of pharmacotherapy over 3 years by 1.7 billion rubles, while direct non-drug costs associated with the treatment of complications that developed during the treatment of asthma decreased by 8.3 billion rubles. Thus, the reduction in total direct costs amounted to RUB 6.7 billion. At the same time, indirect costs decreased by 6.0 billion rubles. The total reduction in all costs (direct and indirect) when switching patients to budesonide + formoterol (Symbicort Turbuhaler) amounted to 12.5 billion rubles. In addition, the use of the drug budesonide + formoterol (Symbicort Turbuhaler) resulted in a decrease in the number of exacerbations: in the first year by 3137, in the second by 4393 and in the third by 5534 cases. A total of 13 064 asthma exacerbations were prevented over 3 years. CONCLUSION: Increasing the proportion of patients with asthma of varying severity receiving therapy with budesonide + formoterol (Symbicort Turbuhaler) will reduce the financial burden on both the healthcare system and the budgetary system.

[Determination of the enantiomers of salmeterol xinafoate in salmeterol fluticasone powder inhalant by chiral nonaqueous capillary electrophoresis].

Salmeterol xinafoate (SalX) is one of the ideal drugs used for the treatment of nocturnal asthma attacks and daily maintenance. The molecular structure of SalX contains a chiral carbon atom, and thus, SalX has two enantiomers, viz. (R)-SalX and (S)-SalX. It is clinically administered in the racemic form. Related studies have shown that the two enantiomers of SalX are quite different in pharmacology, toxicology, and other aspects. Therefore, it is of great significance to establish an analytical method for the chiral separation and determination of the SalX enantiomers to guarantee their quality and ensure their safety and effectiveness in clinical use. In this study, a chiral nonaqueous capillary electrophoresis (NACE) method, using a L(+)-tartaric acid-boric acid complex as the chiral selector, was established to determine the enantiomers of SalX in salmeterol fluticasone powder inhalant. The L(+)-tartaric acid-boric acid complex was synthesized in situ by the reaction of L(+)-tartaric acid and boric acid in methanol solution. The ion pair principle was considered the enantioseparation mechanism, and the non-aqueous system was found to be more favorable for ion pair formation, which is useful for chiral recognition. Chiral separation is based on the reversible formation of diastereomeric ion pairs between the negatively charged L(+)-tartaric acid-boric acid complex and the positively charged salmeterol enantiomers. Due to the difference in ion-pair binding ability between different enantiomers, the apparent electrophoretic mobilities of different enantiomers were also different, resulting in chiral separation in NACE. To achieve good resolution, the effects of L(+)-tartaric acid concentration, boric acid concentration, and apparent pH (pH* ) on the chiral separation were investigated. The optimized buffer solution (pH* 0.93) contained 120.0 mmol/L L(+)-tartaric acid and 120.0 mmol/L boric acid in methanol. Other experimental conditions were as follows: uncoated fused-silica capillary with an I. D. of 50.0 µm, a total length (Ltot) of 64.5 cm, and an effective length (Leff) of 55.5 cm, along with gravity injection of 17.5 cm×10.0 s, detection wavelength of 225 nm, room temperature, and operating voltage of 20.0 kV. Under these experimental conditions, the two enantiomers of SalX achieved a resolution of 2.18 within 18.0 min. Both enantiomers showed a good linear relationship of the peak area in the concentration range of 27.5-800.0 mg/L, the correlation coefficient (r) being greater than 0.9990. The detection limit (S/N=3) and quantitative limit (S/N=10) were 7.5 mg/L and 25.0 mg/L, respectively; the standard recovery was 98.1%-101.9%, with relative standard deviations (RSDs) of 1.2%-1.9%. The intra- and inter-day precisions were examined, and the RSDs of the peak area and migration time were found to be below 4.9% and 1.9%, respectively, indicating good repeatability (inter-day) and reproducibility (inter-day) of the method. The established chiral NACE method was used to determine the two SalX enantiomers in a random salmeterol fluticasone powder inhalant purchased from a local market. The results showed that the percentage of labeled quantities was 98.7% for both enantiomer 1 and enantiomer 2, with RSDs of 2.5% and 2.7%, respectively. Thus, this method is simple, feasible, accurate, and inexpensive, and can be applied for the determination of SalX enantiomers in commercially available salmeterol fluticasone powder inhalants.

A non-interventional switch study in adult patients with asthma or COPD on clinical effectiveness of salmeterol/fluticasone Easyhaler® in routine clinical practice.

BACKGROUND: Selection of the most appropriate device for a switch from one inhaler to an equivalent product is known to have a major impact on clinical outcomes in patients with asthma or chronic obstructive pulmonary disease (COPD). Salmeterol/fluticasone propionate (S/F) Easyhaler® has been demonstrated to be therapeutically equivalent with a reference product. However, no data on real-life effectiveness are currently available for patients switching to S/F Easyhaler from another S/F inhaler. METHODS: The aim of this prospective, open, multicenter, non-interventional study was to assess clinical effectiveness of propionate S/F Easyhaler in adult asthma and COPD patients switched from another inhaler. The primary endpoints were Asthma Control Test (ACT) and COPD Assessment Test (CAT). Secondary endpoints included assessments of patient satisfaction and preference and physician/nurse perception on S/F Easyhaler use. The study included three visits during a 12-week follow-up. RESULTS: A total of 211 patients (160 with asthma; 51 with COPD) were included in the analyses. In patients with asthma, there was a statistically significant increase in the mean ACT score at week 12 (20.2 ± 3.9) compared with the baseline (18.6 ± 4.1), with a mean increase of 1.6 (±3.5) points (p < 0.0001). In patients with COPD, CAT score persisted from baseline (19.9 ± 8.6) to week 12 (19.6 ± 7.0). Patients were significantly more satisfied with Easyhaler and most patients preferred Easyhaler over their previous inhaler. The physicians/nurses reported that it was 'very easy' to teach the use of Easyhaler and the training took less than 5 minutes in most cases. CONCLUSION: The results from this prospective real-life clinical study indicate better or at least similar treatment control of asthma and COPD after switching to S/F Easyhaler from another S/F inhaler. This study also shows that S/F Easyhaler was favored by the patients and that it is easy to teach, learn and use in a real-life setting.The reviews of this paper are available via the supplemental material section.

Consistent Dosing Through the Salmeterol-Fluticasone Propionate Easyhaler for the Management of Asthma and Chronic Obstructive Pulmonary Disease: Robustness Analysis Across the Easyhaler Lifetime.

Background: Easyhaler (registered trademark by Orion Corporation) is a multidose dry powder inhaler (DPI) for the treatment of asthma and chronic obstructive pulmonary disease (COPD), designed to be simple and easy to use. Salmeterol-fluticasone propionate (S-F) Easyhaler (50/250 and 50/500 µg per dose), available in several European countries, provides combined inhaled corticosteroid and long-acting beta agonist therapy for the management of asthma and COPD. A requirement of the European Committee for Medical Products for Human Use guidelines is to demonstrate product performance under conditions that mimic real-life patient use. Therefore, our aims were to assess the robustness of the S-F Easyhaler by assessing the delivered dose (DD) and fine particle dose (FPD) throughout the inhaler lifespan and under simulated environmental stress conditions. Methods: This was a noncomparative exploratory in vitro study. Two batches and six to nine inhalers per batch from both dose strengths were used to assess drug delivery performance over the inhaler lifespan (doses 1-60). For determining the impact of simulated environmental stress (tests for exposure of dropping, vibration, moisture, and freeze-thawing) on DD and FPD, one batch and three inhalers per batch from both dose strengths were used per test, respectively. Aerodynamic particle size distribution was evaluated during the simulated dropping and vibration tests. Results: DD and FPD from both dose strengths of S-F Easyhaler performance remained consistent through the inhaler lifespan and simulated environmental stress did not affect its performance. Similar DD and FPD values were observed with or without dropping, vibration, exposure to moisture, and freeze-thawing, and no inhaler breakages occurred during the simulated tests. Conclusions: The in vitro performance of S-F Easyhaler at both dose strengths suggests that reliable dosing and robustness can be achieved under real-life stress conditions; S-F Easyhaler is a durable DPI for the management of asthma and COPD.

Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON).

BACKGROUND: The efficacy and safety of once-daily (o.d.) fixed-dose combination of indacaterol (IND), glycopyrronium (GLY) and mometasone furoate (MF) via Breezhaler® versus concurrent administration of salmeterol/fluticasone (SAL/FLU) twice-daily (b.i.d.) via Accuhaler®+Tiotropium (TIO) o.d. via Respimat® was evaluated in patients with uncontrolled asthma. METHODS: Patients (aged ≥18 years), symptomatic (Asthma Control Questionnaire [ACQ]-7 ≥1.5) despite treatment with long-acting ß2-agonist/inhaled corticosteroid medium- or high-dose, received IND/GLY/MF high- (150/50/160 µg) or medium-dose (150/50/80 µg) o.d. or SAL/FLU high-dose (50/500 µg) b.i.d.+Tio 5 µg o.d. for 24 weeks. The primary objective was to confirm the non-inferiority of either dose of IND/GLY/MF to SAL/FLU high dose + TIO in terms of Asthma Quality of Life Questionnaire (AQLQ). Additional endpoints: ACQ-7, lung function, health status (St George's Respiratory Questionnaire [SGRQ]), exacerbations, and safety after 24 weeks. RESULTS: IND/GLY/MF high- and medium-dose met the primary endpoint, confirming non-inferiority to SAL/FLU high dose + TIO for AQLQ (least square mean treatment difference [Δ]: 0.073 and -0.038, respectively; both p < 0.001). IND/GLY/MF high-dose improved ACQ-7 (Δ: -0.124; p = 0.004), trough FEV1 (Δ: 96 mL; p < 0.001), peak expiratory flow (morning [Δ: 9.56 L/min; p = 0.005], evening [Δ: 9.15 L/min; p = 0.006]) and SGRQ (Δ: -2.00; p = 0.04) versus SAL/FLU high dose + TIO. Improvements in these endpoints were comparable for IND/GLY/MF medium-dose and SAL/FLU high dose + TIO. Adverse events were generally comparable across treatments. CONCLUSIONS: IND/GLY/MF high- and medium-dose o.d. via a single inhaler were non-inferior to SAL/FLU high-dose b.i.d. + TIO o.d. via two inhalers for AQLQ. IND/GLY/MF high-dose o.d. improved lung function, asthma control and health status versus SAL/FLU high dose + TIO, while IND/GLY/MF medium-dose had comparable efficacy but at a corresponding lower steroid dose.

In Vitro Flow Rate Dependency of Delivered Dose and Fine Particle Dose of Salmeterol/Fluticasone Propionate Easyhaler and Seretide Diskus with Patient Flow Rates Collected in a Randomized Controlled Trial.

BACKGROUND: The Easyhaler® device-metered dry powder inhaler containing Salmeterol and Fluticasone propionate (S/F) has been developed for the treatment of patients with asthma and chronic obstructive pulmonary disease (COPD). We report two studies which evaluated the in vitro flow rate dependence of delivered dose (DD) and fine particle dose (FPD) of S/F Easyhaler versus Seretide Diskus®. METHODS: A randomized controlled trial (RCT) assessed inspiratory flow parameters of S/F Easyhaler and Seretide Diskus in subgroups of patients with asthma (children, adolescents and adults, and elderly) and in COPD patients. The 10th, 50th, and 90th percentile airflow rates were determined and utilized in vitro, to evaluate flow rate dependence of DD and FPD. Flow rate dependence was evaluated relative to the result obtained at the 50th percentile and any values deviating from 100% indicated flow rate dependence. The volumetric flow rate dependence (Q) index derived from FPD at 10th and 90th percentile airflows was also evaluated. RESULTS: Overall, 227 patients were enrolled and randomized; 216 completed the RCT. In total, 55.5% of patients were female, and the mean age was 46.3 years. Clinically relevant airflow rates (46, 68, and 85 L/min for S/F Easyhaler and 44, 71, and 96 L/min for Seretide Diskus) were carried forward into the in vitro study, which demonstrated similar flow rate dependence of DD and FPD for S/F Easyhaler compared with Seretide Diskus; all values were within ±15% limits across the 10th, 50th, and 90th percentile airflow rates. Q index results suggested that both S/F Easyhaler and Seretide Diskus are medium airflow-dependent products. CONCLUSIONS: Similar in vitro flow rate dependence of DD and FPD was demonstrated for S/F Easyhaler compared with Seretide Diskus, across a range of clinically relevant airflow rates, collected from patients with asthma and COPD.

Therapeutic effect of salmeterol-fluticasone aerosol on mild to moderate chronic obstructive pulmonary disease / 中国基层医药

Objective@#To analyze the clinical efficacy of salmeterol-fluticasone aerosol in the treatment of mild to moderate chronic obstructive pulmonary disease (COPD).@*Methods@#From February 2017 to February 2018, 68 patients with mild to moderate COPD treated in the General Hospital of Shanxi Tongmei Group were selected in the study.The patients were divided into control group (34 cases) and observation group (34 cases) by random number table method.The control group was treated with salbutamol aerosol inhalation, while the observation group was treated with salmeterol and fluticasone aerosol inhalation.Both two groups were treated for 12 weeks.The clinical efficacy, improvement of pulmonary function, 6-minute walking distance, oxygen saturation and heart rate were compared between the two groups.@*Results@#The total effective rate of the observation group was 97.06% (33/34), which was significantly higher than that of the control group [73.53%(25/34)] (χ2=7.503, P<0.05). Before treatment, FEV1%, FEV1/FVC (percentage of forced expiratory volume in 1 second forced vital capacity), FEV1 (1 second hard breathing volume), blood oxygen saturation, heart rate and 6 min walking distance had no statistically significant differences between the two groups (all P>0.05). After treatment, the FEV1, FEV1/FVC, FEV1% in the observation group were (65.48±4.06)%, (74.66±8.12)%, (1.99±0.55) L, respectively, which were significantly higher than those in the control group [(63.55±6.14)%, (70.85±7.56)%, (1.71±0.52)L] (t=2.321, 2.002, 2.157, all P<0.05). The oxygen saturation, heart rate and 6-minute walking distance in the observation group were (92.27±1.83)%, (80.55±4.08)times/min and (263.35±28.73)m, respectively, which in the control group were (88.52±2.06)%, (91.43±5.16)times/min and (231.95±22.69)m, respectively, and there were statistically significant differences between the two groups (t=7.936, 9.644, 5.001, all P<0.05).@*Conclusion@#Salmeterol and fluticasone aerosol inhalation has good clinical efficacy in the treatment of mild to moderate COPD, and can significantly improve the lung function of patients.

Eficacia de la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar de personas mayores con Enfermedad Pulmonar Obstructiva Crónica: revisión sistemática de literatura / Effectiveness of budesonide/formoterol compared to fluticasone / salmeterol in improving the lung capacity of older people with Chronic Obstructive Pulmonary Disease: systematic literature review / Eficiência da budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar de idosos com Doença Pulmonar Obstrutiva Crônica: revisão sistemática da literatura

Introducción. La Enfermedad Pulmonar Obstructiva Crónica (EPOC) es una patología no transmisible, caracterizada por una limitación de flujo de aire en las vías respiratorias debido a una respuesta inmunológica anormal frente a partículas. Objetivo. Conocer la eficacia que tiene la budesonida/formoterol comparado con la fluticasona/salmeterol en la mejoría de la capacidad pulmonar en personas mayores de 40 años con Enfermedad Pulmonar Obstructiva Crónica. Materiales y métodos. Se realizó una revisión sistemática de documentos producidos entre el año 2000 y 2018 en distintas bases de datos, donde se incluyeron ensayos clínicos. Se identificaron cuatro artículos para el análisis final. Resultados. Durante la evaluación comparativa de budesonida con formoterol, los artículos muestran un total de 709 personas evaluadas, con un promedio de edad de 53,5 años. El 65,4 % eran varones, el 21 % manifestaba no haber consumido tabaco, todos con diagnóstico de Enfermedad Pulmonar Obstructiva Crónica moderada-severa, según la escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Los estudios determinaron que al administrar budesonida/formoterol de 400/12 mcg y 320/9 mcg, los pacientes tuvieron una leve mejoría en el Volumen Espiratorio Forzado del primer segundo (VEF1). Solo dos pacientes presentaron efectos adversos. No obstante, para los resultados mencionados anteriormente no se encontró diferencias significativas. Conclusiones. El uso de budesonida/formoterol es eficaz al mejorar la capacidad ventilatoria pulmonar, disminuye el número de exacerbaciones anuales y genera un adecuado control de los síntomas, sin embargo, es igual de efectivo a la fluticasona/salmeterol.

Introduction. Chronic Obstructive Pulmonary Disease (COPD) is a not transmissible disease, characterized by a limitation of airflow in the respiratory tract, due to an abnormal immune response to particles. Objective. This article aims to show that the application of budesonide / formoterol improves lung capacity in people over 40 years with Chronic Obstructive Pulmonary Disease. Materials and methods. A systematic review was conducted in the period between 2000 and 2018 in different databases where clinical trials were included. Four articles were identified for the final analysis. Results. During the comparative evaluation of budesonide with formoterol, a total of 709 people were evaluated, with an average age of 53.5 years, 65.4% were male, 21% reported not having used tobacco, all with a diagnosis of moderate-severe Chronic Obstructive Pulmonary Disease according to the GOLD scale (Global Initiative For Chronic Obstrutive Lung Disease). The studies determined that when budesonide / formoterol of 400/12 mcg and 320/9 mcg was administered, the patients had a slight improvement in the Forced Expiratory Volume of the first second (FEV1). Only two patients presented adverse effects. However, for the results mentioned above no significant differences were found. Conclusions. The use of budesonide / formoterol is effective in improving pulmonary ventilatory capacity, decreases the number of annual exacerbations and generates adequate control of symptoms, however, it is equally effective in fluticasone / salmeterol.

Introdução. A Doença Pulmonar Obstrutiva Crônica (DPOC) é uma patologia não transmissível, caraterizada por uma limitação do fluxo de ar nas vias aéreas devido a uma resposta imune anormal contra partículas. Objetivo. Conhecer a eficiência que apresenta a budesonida/formoterol comparado com fluticasona/salmeterol na melhora da capacidade pulmonar em pessoas com mais de 40 anos com Doença Pulmonar Obstrutiva Crônica. Materiais e métodos. Foi realizada uma revisão sistemática dos documentos produzidos entre 2000 e 2018 em diferentes bancos de dados, onde foram incluídos ensaios clínicos. Quatro artigos foram identificados para a análise final. Resultados. Durante a avaliação comparativa de budesonida com formoterol, os artículos mostram um total de 709 pessoas avaliadas, com uma idade média de 53,5 anos. O 65,4 % eram do sexo masculino, o 21 % disseram que não usavam tabaco, todos diagnosticados com Doença Pulmonar Obstrutiva Crônica moderada a grave, de acordo com a escala GOLD (Global Initiative For Chronic Obstrutive Lung Disease). Os estudos determinaram que administrar budesonida/formoterol de 400/12 mcg e 320/9 mcg, os pacientes apresentaram uma leve melhora no Volume Expiratório Forçado no primeiro segundo (VEF1). Apenas dois pacientes tiveram efeitos adversos. No entanto, não foram encontradas diferenças significativas para os resultados mencionados acima. Conclusões. O uso de budesonida/formoterol é eficaz na melhora da capacidade ventilatória pulmonar, diminui o numero de exacerbações anuais e gera controle adequado dos sintomas, no entanto, é igualmente eficaz para a fluticasona/salmeterol.

Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 µg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 µg twice daily in moderate-to-very severe COPD patients from the FLAME study. METHODS: CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St. George's Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID-) at Week 12. RESULTS: IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID- patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID- patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID- patients. CONCLUSIONS: IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year. TRIAL REGISTRATION: Clinicaltrials.gov NCT01782326 .

Exacerbation heterogeneity in COPD: subgroup analyses from the FLAME study.

BACKGROUND: The FLAME study compared once-daily indacaterol/glycopyrronium (IND/GLY) 110/50 µg with twice-daily salmeterol/fluticasone (SFC) 50/500 µg in symptomatic patients with moderate to very severe COPD and a history of exacerbations in the previous year. METHODS: This prespecified and post hoc subgroup analysis evaluated treatment efficacy on 1) moderate/severe exacerbations according to prior exacerbation history and treatment, and 2) types of exacerbations according to health care resource utilization (HCRU) during 1-year follow-up. RESULTS: IND/GLY reduced the rate of moderate/severe exacerbations versus SFC in patients with a history of 1 exacerbation (rate ratio [RR]: 0.83, 95% CI: 0.75-0.93), ≥2 exacerbations (RR: 0.85, 95% CI: 0.70-1.03) and ≥2 exacerbations or ≥1 hospitalization in the previous year (RR: 0.86, 95% CI: 0.74-1.00). Prolonged time-to-first exacerbation was observed in all the groups according to exacerbation history. Moderate/severe exacerbations decreased with IND/GLY versus SFC, independent of previous treatment. IND/GLY significantly reduced rates of moderate/severe exacerbations treated with antibiotics (RR: 0.79, 95% CI: 0.67-0.93) and systemic corticosteroids and antibiotics (RR: 0.80, 95% CI: 0.70-0.91); rates of exacerbations treated with systemic corticosteroids alone were comparable (RR: 0.99, 95% CI: 0.80-1.22). CONCLUSION: Overall, IND/GLY demonstrated consistent beneficial effects versus SFC on moderate/severe exacerbations, independent of prior exacerbation history or treatment. The efficacy of IND/GLY on exacerbation prevention was superior to SFC for exacerbations treated with antibiotics with/without systemic corticosteroids and was similar for exacerbations treated with systemic corticosteroids alone.

Cost-effectiveness of indacaterol/glycopyrronium in comparison with salmeterol/fluticasone combination for patients with moderate-to-severe chronic obstructive pulmonary disease: a LANTERN population analysis from Singapore.

INTRODUCTION: In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting. METHODS: A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis. RESULTS: Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC. CONCLUSION: IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.

Efficacy and Safety of Salmeterol/fluticasone Combined with Montelukast versus Salmeterol/fluticasone in the Treatment of Cough Variant Asthma: A Meta-analysis / 中国药房

OBJECTIVE: To evaluate the efficacy and safety of salmeterol/fluticasone combined with montelukast versus salmeterol/fluticasone in the treatment of cough variant asthma, and to provide reference for evidence-based reference in clinic.METHODS: Retrieved from Cochrane library, PubMed, Chinese Journal Full-text Database, VIP and Wanfang database, randomized controlled trials (RCTs) about therapeutic efficacy (total response rate, marked improvement rate, cough disappearance time, 6-12 months recurrence rate) and safety (the incidence of ADR) of salmeterol/fluticasone combined with montelukast (trial group) vs. salmeterol/fluticasone (control group) in the treatment of cough variant asthma were included. Meta-analysis was performed by using Rev Man 5. 3 software after data extraction and quality evaluation with Cochrane system evaluation manual 5. 1. 0. RESULTS: Totally 10 RCTs were included, involving 976 patients. Results of Meta-analysis showed the total response rate [RR=1. 22, 95％CI(1. 16, 1. 29), P<0. 001] and marked improvement rate [RR= 1. 38,95％CI(1. 22,1. 56),P<0. 001] of trial group were significantly higher than those of control group; the cough disappearance time was significantly shorter than control group [MD= - 3. 07, 95％ CI (- 3. 54, -2. 59),P<0. 001],and 6-12 months recurrence rate was significantly lower than control group [RR=0. 24, 95％CI(0. 11, 0. 54), P<0. 001], with statistical significance. There was no statistical significance in the incidence of ADR between 2 groups [RR=1. 58, 95％ CI (0. 99, 2. 51), P=0. 05]. CONCLUSIONS: The salmeterol/fluticasone combined with montelukast is better than of salmeterol/fluticasone in the treatment of cough variant asthma, but great importance should be attached to the occurrence of adverse events when using drug combination.

Effects of salmeterol fluticasone inhalation on pulmonary function and inflammatory cytokines in patients with acute exacerbation of chronic obstructive pulmonary disease / 中国基层医药

Objective To investigate the effect of salmeterol fluticasone inhalation on pulmonary function and inflammatory cytokines in patients with acute exacerbation of chronic obstructive pulmonary disease ( COPD ) . Methods 110 patients with acute exacerbation of asthma combined with COPD were selected and divided into observation group (55 cases) and control group (55 cases) by the random number table .The control group was given conventional treatment ,while the observation group was given salmeterol fluticasone inhalation therapy on the basis of routine treatment .The pulmonary function ,inflammatory cytokines and curative effects were compared between the two groups.Results After treatment,the FVC,FEV1,FEV1/FVC of the observation group were (2.64 ±0.45) L, (1.98 ±0.46)L and (80.42 ±6.43)％,which were significantly better than those of the control group (t=2.89, 2.59,6.27,all P<0.05),the improvement of lung function was more obvious than that of the control group (P<0.05).After treatment,the levels of TNF-α,IL-8,IL-10 and IL-17 in sputum of the observation group were (30.03 ±6.78)μg/L,(59.96 ±7.73)μg/L,(29.89 ±4.11)μg/L and (92.37 ±9.79)μg/L,respectively,which were significantly lower than those of the control group (t=7.54,6.16,7.04,12.31,all P<0.05).After treatment, the levels of TNF -α, IL -8, IL-10 and IL -17 in peripheral blood of the observation group were ( 14.08 ± 5.36)μg/L,(26.32 ±4.03)μg/L,(30.32 ±5.04)μg/L and (173.82 ±18.19)μg/L,respectively,which were significantly lower than those of the control group (t =4.26,7.95,11.25.5.31,all P<0.05).The decrease of inflammatory cytokines in sputum and peripheral blood of the observation group was more significant than that of the control group (P<0.05).The effective rate of the observation group was 94.55％,which was significantly higher than 81.82％of the control group (P<0.05).Conclusion Salmeterol fluticasone inhalation can improve patients'pulmonary function,decrease the level of inflammatory cytokines in sputum and peripheral blood ,which is worthy of clinical application and spread .

Cost-effectiveness of indacaterol/glycopyrronium in comparison with salmeterol/fluticasone combination for patients with moderate-to-severe chronic obstructive pulmonary disease: a LANTERN population analysis from Singapore

<p><b>INTRODUCTION</b>In light of the growing evidence base for better clinical results with the use of the dual bronchodilator indacaterol/glycopyrronium (IND/GLY) over inhaled corticosteroid-containing salmeterol/fluticasone combination (SFC), this study aimed to evaluate the cost-effectiveness of IND/GLY over SFC in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) who are at low risk of exacerbations, in the Singapore healthcare setting.</p><p><b>METHODS</b>A previously published patient-level simulation model was adapted for use in Singapore by applying local unit costs. The model was populated with clinical data from the LANTERN and ECLIPSE studies. Both costs and health outcomes were predicted for the lifetime horizon from a payer's perspective and were discounted at 3% per annum. Costs were expressed in 2015 USD exchange rates. Uncertainty was assessed through probabilistic sensitivity analysis.</p><p><b>RESULTS</b>Compared to SFC, use of IND/GLY increased mean life expectancy by 0.316 years and mean quality-adjusted life years (QALYs) by 0.246 years, and decreased mean total treatment costs (drug costs and management of associated events) by USD 1,474 over the entire lifetime horizon. IND/GLY was considered to be 100% cost-effective at a threshold of 1 × gross domestic product per capita. The cost-effectiveness acceptability curve showed that IND/GLY was 100% cost-effective at a willingness-to-pay threshold of USD 0 (additional cost) when compared to SFC.</p><p><b>CONCLUSION</b>IND/GLY was estimated to be highly cost-effective compared to SFC in patients with moderate-to-severe COPD who are not at high risk of exacerbations in the Singapore healthcare setting.</p>

Clinical Observation of Tiotropium Bromide Combined with Salmeterol Fluticasone Aerosol in the Treat-ment of Elderly Severe COPD / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of tiotropium bromide combined with Salmeterol flutica-sone aerosol in the treatment of severe COPD in elderly patients. METHODS:A total of 90 elderly patients with severe COPD se-lected from May 2013 to May 2015 in our hospital as research objects were divided into control group and observation group ac-cording to random number table,with 45 cases in each group. Control group was given Salmeterol xinafonate and fluticasone propi-onate aerosol 1 press/time,bid;observation group was additionally given Tiotropium bromide powder for inhalation 18 μg,qd,on the basis of control group. Both groups were treated for 8 weeks. The short-term clinical efficacy,dyspnea score,pulmonary venti-lation function indexes [FVC,EFV1,EFV1%],blood gas analysis indexes [p(O2),p(CO2)] and QLI score before and after treat-ment were observed in 2 groups. The re-hospitalization time and the occurrence of ADR were compared between 2 groups. RE-SULTS:The total response rate of short-term treatment in observation group was 97.78%,which was significantly higher than 80.00% of control group,with statistical significance (P0.05). After treatment,dyspnea scores and p(CO2) of 2 groups were decreased significantly,while pulmonary ventilation function indexes,p??????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????????(O2)and QLI scores were increased significantly;the observation group was significantly better than the control group,with statis-tical significance(P<0.05). The re-hospitalization time of observation group was significantly less than that of control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups(P<0.05). CON-CLUSIONS:Tiotropium bromide assisted with Salmeterol fluticasone aerosol show significant therapeutic efficacy for elderly se-vere COPD,and effectively relieve dyspnea symptom,improve pulmonary ventilation function and quality of daily life,reduce the re-hospitalization risk and do not increase the incidence of ADR.