Seretide Research Articles

A Simulation Study of the Effect of Clinical Characteristics and Treatment Choice on Reliever Medication Use, Symptom Control and Exacerbation Risk in Moderate-Severe Asthma.

The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). Reduction in reliever medication use (puffs/24h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phaseIII/IV clinical studies. Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

Comparative Efficacy of Budesonide/Formoterol Versus Fluticasone/Salmeterol in Patients With Moderate-to-Severe Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Background/objective To compare the efficacy of budesonide/formoterol (BF) versus fluticasone/salmeterol (FS) in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). Methods The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for studies comparing BF versus FS in the treatment of COPD from inception to July 17, 2023. Outcomes, including exacerbations, hospitalizations, pneumonia, emergency department (ED) visits for COPD, length of hospitalization, and number of exacerbations, were compared using risk ratio (RR) with corresponding 95% confidence interval (CI) or weighted mean difference (WMD) with 95% CI. All statistical analyses were performed using Stata version 12.0. Results Ten studies comprising a total of 136,369 participants were included. Compared with those treated with FS, patients with COPD treated with BF experienced a reduced number of exacerbations (RR 0.91 [95% CI 0.83–1.00]; p = 0.040), hospitalizations (RR 0.77 [95% CI 0.67–0.88]; p < 0.001), and frequency of pneumonia (RR 0.77 [95% CI 0.64–0.92]; p = 0.05). However, no significant difference was observed between BF and FS in terms of ED visits for COPD (RR 0.87 [95% CI 0.69–1.10]; p = 0.243), length of hospitalization (WMD −0.18 [95% CI −0.62–0.27]; p = 0.437), and number of exacerbations (WMD −0.06 [95% CI −0.28–0.16]; p = 0.602). Notably, no significant heterogeneity was noted in length of hospitalization between the two groups, whereas clear heterogeneity was observed in other outcomes (I 2 > 50%, p < 0.05). Conclusion Compared with FS, BF therapy appears to be a more promising treatment strategy for patients with moderate-to-severe COPD; however, this should be verified in further high-quality studies.

Effect of Individual Patient Characteristics and Treatment Choices on Reliever Medication Use in Moderate-Severe Asthma: A Poisson Analysis of Randomised Clinical Trials.

Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50μg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5μg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.

Comparative effectiveness and safety of inhaled corticosteroid plus long-acting β2-agonist fixed-dose combinations vs. long-acting muscarinic antagonist in bronchiectasis

ABSTRACT Background This study aimed to evaluate the effectiveness and safety of fixed-dose combination (FDC) inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) in bronchiectasis. Research design and methods A retrospective cohort study analyzed electronic medical records of bronchiectasis patients initiating ICS/LABA FDC or LAMA between 2007 and 2021. All bronchiectasis diagnoses were made by radiologists using high-resolution computed tomography. Results Of the 1,736 patients, 1,281 took ICS/LABA FDC and 455 LAMA. Among the 694 propensity score matched patients, ICS/LABA FDC had comparable outcomes to LAMA, with HRs of 1.22 (95% CI 0.81–1.83) for hospitalized respiratory infection, 1.06 (95% CI 0.84–1.33) for acute exacerbation, and 1.06 (95% CI 0.66–1.02) for all-cause hospitalization. Beclomethasone/formoterol (BEC/FOR) or budesonide/formoterol (BUD/FOR) led to a lower risk of acute exacerbation compared to fluticasone/salmeterol (FLU/SAL) (BEC/FOR HR 0.59, 95% CI 0.43–0.81; BUD/FOR HR 0.68, 95% CI 0.50–0.93). BEC/FOR resulted in lower risks of hospitalized respiratory infection (HR 0.48, 95% 0.26–0.86) and all-cause hospitalization (HR 0.55, 95% 0.37–0.80) compared to FLU/SAL. Conclusion Our findings provide important evidence on the effectiveness and safety of ICS/LABA FDC compared with LAMA for bronchiectasis. BEC/FOR and BUD/FOR were associated with better outcomes than FLU/SAL.

Understanding the Clinical Implications of Individual Patient Characteristics and Treatment Choice on the Risk of Exacerbation in Asthma Patients with Moderate-Severe Symptoms.

The assessment of future risk has become an important feature in the management of patients with asthma. However, the contribution of patient-specific characteristics and treatment choices to the risk of exacerbation is poorly understood. Here we evaluated the effect of interindividual baseline differences on the risk of exacerbation and treatment performance in patients receiving regular maintenance doses of inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists (LABA) combination therapy. Exacerbations and changes to asthma symptoms 5-item Asthma Control Questionnaire (ACQ-5) were simulated over a 12-month period using a time-to-event and a longitudinal model developed from phaseIII/IV studies in patients with moderate-severe asthma (N = 16,282). Simulations were implemented to explore treatment performance across different scenarios, including randomised designs and real-world settings. Treatment options included regular dosing with ICS monotherapy [fluticasone propionate (FP)] and combination therapy [fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)]. Exacerbation rate was analysed using the log-rank test. The cumulative incidence of events was summarised stratified by treatment. Being a woman, smoker, having higher baseline ACQ-5 and body mass index (BMI) and lower forced expiratory volume in the first second (FEV1) are associated with increased exacerbation risk (p < 0.01). This risk is bigger in winter because of the seasonal variation effect. Across the different scenarios, the use of FP/SAL resulted in a 10% lower annual incidence of exacerbations relative to FP or regular dosing BUD/FOR, independently of baseline characteristics. Similar differences in the annual incidence of exacerbations were also observed between treatments in obese patients (BMI ≥ 25-35kg/m2) (p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. Individual baseline characteristics and treatment choices affect future risk. Achieving comparable levels of symptom control whilst on treatment does not imply comparable risk reduction, as shown by the lower exacerbation rates in FP/SAL vs. BUD/FOR-treated patients. These factors should be considered as a basis for personalised clinical management of patients with moderate-severe asthma.

Modelling ASthma TrEatment Responses (MASTER): Effect of individual patient characteristics on the risk of exacerbation in moderate or severe asthma: A time-to-event analysis of randomized clinical trials.

There is limited understanding of how clinical and demographic characteristics are associated with exacerbation risk in patients with moderate-to-severe asthma, and how these factors correlate with symptom control and treatment response. Here we assess the relationship between baseline characteristics and exacerbation risk during regular dosing with inhaled corticosteroids (ICS) monotherapy or in combination with long-acting beta2-agonists (ICS/LABA) in clinical trial patients with varying levels of symptom control, as assessed by the asthma control questionnaire (ACQ-5). A time-to-event model was developed using pooled patient data (N = 16 282) from nine clinical studies [Correction added on 26 July 2023, after first online publication: The N value in the preceding sentence has been corrected in this version.]. A parametric hazard function was used to describe the time-to-first exacerbation. Covariate analysis included the assessment of the effect of seasonal variation, clinical and demographic baseline characteristics on baseline hazard. Predictive performance was evaluated by standard graphical and statistical methods. An exponential hazard model best described the time-to-first exacerbation in moderate-to-severe asthma patients. Body mass index, smoking status, sex, ACQ-5, % predicted forced expiratory volume over 1 s (FEV1 p) and season were identified as statistically significant covariates affecting baseline hazard irrespective of ICS or ICS/LABA use. Fluticasone propionate/salmeterol (FP/SAL) combination therapy resulted in a significant reduction in the baseline hazard (30.8%) relative to FP monotherapy. Interindividual differences at baseline and seasonal variation affect the exacerbation risk independently from drug treatment. Moreover, it appears that even when a comparable level of symptom control is achieved in a group of patients, each individual may have a different exacerbation risk, depending on their baseline characteristics and time of the year. These findings highlight the importance of personalized interventions in moderate-to-severe asthma patients.

Ocular Surface, Intraocular Pressure, and Lens Condition in Bronchodilator and Steroid-Treated Patients with Chronic Pulmonary Disease

Objectives: The aim of this study was to investigate the ocular surface, intraocular pressure, and lens condition in bronchodilator- and steroid-treated chronic pulmonary disease patients. Methods: In this cross-sectional clinical study, 101 patients with chronic pulmonary disease were treated with an inhaler and/or nebulized therapy for bronchodilatation. The patients were evaluated in 2 groups namely chronic obstructive pulmonary disease and asthma. We investigated the effects of patient demographic characteristics, smoking, and medications on the presence of dry eye disease (DED), intraocular pressure, and cataract. Results: Patients had a mean age of 66.4 ± 11.9 years, and 46.5% (n = 47) were female. A unit increase in the length of inhaled corticosteroids (ICS) and long-acting β-agonists (LABA) combination use was associated with a 1.02-fold increase in cataract risk (OR: 1.02, CI: 1.01–1.04, p = 0.016), and current smokers had 10.8 times as many cataracts (OR: 10.79, CI: 1.70–68.30, p = 0.011). Patients who used a nebulized corticosteroid had a 9.15 times higher risk of developing dry eyes than those who did not (OR: 9.15, CI: 2.34–35.75, p = 0.001). In patients using ICS-LABA, in comparison to formoterol beclomethasone, salmeterol fluticasone was found to increase the risk 7.49-fold for DED (OR: 7.49, CI: 1.48–35.75, p = 0.015). Conclusions: Nebulizer delivery of steroids is associated with dry eyes and cataracts. Smoking, aging, and long-term inhaled steroid use have all been linked to an increased risk of cataracts. Longitudinal and larger sample size studies are needed to explore cause-effect relationships.

Breath-actuated INhalation TheRapy: survey of phySicians’ PErCepTion (INTROSPECT) in Nepal

Objective Breath-actuated inhalers (BAIs) are gaining attention in the management of obstructive airway diseases (OADs). In Nepal, a BAI containing fluticasone propionate/salmeterol (FPS) has been available for a year. This survey is aimed at determining the perception and experience of physicians in Nepal concerning BAIs. Methods A cross-sectional, questionnaire-based survey was conducted. A total of 141 physicians participated and filled the survey. Results Most physicians felt that the right device should be easy to teach, learn and remember. They considered coordination and multiple steps as the primary challenges with pressurized metered-dose inhalers and dry powder inhalers, respectively. Most of them agreed that BAIs could address these challenges. BAIs were not only preferred by most of the physicians for asthma and chronic obstructive pulmonary disease but were also the preferred choice in newly diagnosed patients. Physicians believed that if current patients were shifted to BAIs, it could improve inhalation technique (88%) and compliance/adherence (81%). Almost all of them (92–97%) agreed that teaching the breathing technique and the cleaning process was easier and faster in BAIs. BAIs were considered easy and simple to use. Also, BAI’s dose-counter helps patients to increase adherence to inhalation therapy. Conclusions In this INTROSPECT survey, physicians in Nepal believed that BAIs could address the key challenges faced with using pMDIs and DPIs in asthma and COPD patients.

Effectiveness and Treatment Compliance of Salmeterol-Fluticasone Easyhaler® Among Patients with Asthma, COPD, or Asthma-COPD Overlap Syndrome: Real-World Study Findings.

For inhalation therapies to be effective, it is crucial that patients manage inhaler use correctly in their everyday life and achieve treatment compliance. We investigated the effectiveness of the salmeterol-fluticasone propionate Easyhaler® (SF EH) device-metered dry powder inhaler in a real-world setting in Hungary among adult patients with asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap syndrome (ACO). A prospective, open-label, multicenter, noninterventional, investigator-sponsored study was conducted in outpatient pneumonology centers. Eligible patients were aged ≥ 18years with either a new diagnosis of asthma, COPD, or ACO, or whose disease was not controlled with preexisting medication. Data were collected at baseline and 12 + 4weeks, including the asthma control test (ACT), COPD assessment test (CAT), spirometry parameters [including forced expiratory volume for 1s (FEV1)], and physician- and patient-reported outcomes. Five hundred sixteen patients were recruited from 103 centers: 376 with asthma; 104 with COPD; and 36 with ACO. At week 12, there were significant improvements from baseline in both mean ACT score in patients with asthma (14.4 ± 4.2 versus 21.4 ± 2.8; P < 0.001) and mean CAT score in patients with COPD (24.0 ± 6.1 versus 16.0 ± 5.8; P < 0.001). Significant improvement was observed when the switch from the most frequently used previous inhalers was analyzed separately. Mean FEV1 improved from 76.0% ± 17.2 to 84.7% ± 16.1 (P < 0.001) and from 53.8% ± 15.0 to 59.9% ± 15.0 (P < 0.001) in patients with asthma or COPD, respectively. The study demonstrated improved physician-rated overall treatment compliance and patient preference for the SF EH over 3months use compared with previous inhaler treatment, with patients effectively adopting the SF EH into everyday life. Treatment with SF EH significantly improved patients' lung function parameters and disease control.

Study on the Effect of Self-Made Lifei Dingchuan Decoction Combined with Western Medicine on Cough Variant Asthma.

Aims To observe the clinical efficacy of self-made Lifei Dingchuan decoction combined with western medicine in the treatment of cough variant asthma (phlegm-heat accumulation in the lung syndrome). Materials and Methods The clinical data of 90 patients with cough variant asthma who were hospitalized in the Department of Respiratory Medicine of our hospital from January 2020 to April 2022 were selected as the research objects, and they were equally divided into the observation group and the reference group according to different treatment methods, 45 cases in each group. The group was treated with traditional montelukast sodium chewable tablet and salmeterol fluticasone mixed powder inhalation, and the observation group was treated with self-made Lifei Dingchuan decoction on the basis of the control group, saturation, pH, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, length of stay, and hospitalization costs. Results After the patients underwent self-made Lifei Dingchuan decoction, there were significant differences between the observation group and the reference group in terms of heart rate, respiratory rate, blood oxygen saturation, pH value, arterial blood oxygen partial pressure, carbon dioxide partial pressure, and within the group. There was a statistical difference (P < 0.05). The adverse reactions in patients with cough variant asthma after treatment showed that the red throat, shortness of breath, chest tightness, and dry mouth in the observation group were significantly different from those in the control group (P < 0.05). After investigation, follow-up, and statistics, the hospitalization time, hospitalization cost, asthma exacerbation control time, effective rate, and recurrence rate were compared between the two groups, and the differences between the two groups were statistically significant (P < 0.05). Conclusion The study on the clinical efficacy and low hospitalization cost of the self-prepared lung and asthma-restorative soup in patients with cough variant asthma significantly improved the patients' arterial oxygen saturation, acid-base value, arterial partial pressure of oxygen, and partial pressure of carbon dioxide and effectively controlled the heart rate and respiratory rate with high safety, which is worth further promotion.

Treatment persistence and exacerbations in patients with asthma initiating treatment with inhaled corticosteroids and beta-adrenergic agonists: retrospective cohort study

ObjectiveTo determine treatment persistence and exacerbations in patients initiating inhaler treatment with fixed-dose combinations of inhaled corticosteroids/long-acting beta-2-adrenergic agonists (ICS/LABA) for the treatment of asthma.DesignRetrospective observational study conducted by review...

Effectiveness of Indacaterol-Glycopyrronium in preventing COPD exacerbations in comparison to Salmeterol-Fluticasone

COPD exacerbations are complex events usually associated with increased airway inflammation, increased mucus production and marked gas trapping. These changes contribute to increased dyspnoea that is the key symptom of an exacerbation. Inhaled long acting bronchodilators not only control symptoms but also prevent exacerbations of chronic obstructive pulmonary disease (COPD). The purpose of the study was to compare the efficacy between Indacaterol-Glycopyrronium and salmeterol fluticasone (SFC) in preventing COPD exacerbations during 24 weeks of treatment. This randomised active-controlled trial was conducted at Department of Respiratory Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka involving 200 patients with COPD exacerbations. Patients were randomly divided into two groups; &amp; treated with Indacaterol- Glycopyrronium 110/50 ug o.d. &amp; Salmeterol-Fluticasone (50/500 ug b.i.d.) (SFC) respectively; &amp; follow-up was done after 12 and 24 weeks. The FEV1 was significantly higher at 12 and 24 weeks in the Indacateol- Glycopyrronium group compared with SFC. Statistically significant improvements in peak FVC was observed in Indacaterol- Glycopyrronium when compared to SFC at week 12 and week 24. Our study result showed that Indacaterol-Glycopyrronium was superior to Salmeterol-Fluticasone in terms of prevention and optimal management of COPD exacerbation. BSMMU J 2021; 14(3): 43-49

Clinical Interpretation of Efficacy Outcomes in Pharmacological Studies on Triple Fixed-Dose Combination Therapy for Uncontrolled Asthma: Assessment of IRIDIUM and ARGON Studies.

The IRIDIUM and ARGON studies provided positive findings concerning the benefits of the once-daily triple mometasone furoate/indacaterol/glycopyrronium (MF/IND/GLY) fixed-dose combination (FDC) for the treatment of uncontrolled asthma, at the least by a strict statistical point of view. In the IRIDIUM study patients received medium-dose (MD) or high-dose (HD) MF/IND/GLY or MF/IND oncex daily or HD fluticasone/salmeterol (FLU/SAL) twice daily; in the ARGON study patients received MD or HD MF/IND/GLY once daily or HD FLU/SAL twice daily + tiotropium (TIO) once daily. Since a detailed interpretation of clinical results has not yet been performed, we provided the clinical interpretation of efficacy outcomes resulting from the IRIDIUM and ARGON studies according to the currently available minimal clinically important difference (MCID) thresholds. The triple MF/IND/GLY FDC elicited beneficial clinically relevant effects compared to active comparators in asthmatic patients, according to the levels of ICS doses, by generally achieving and overcoming the MCID. The level of clinical benefit was usually greater in patients treated with HD-MF/IND/GLY compared to those treated with MD-MF/IND/GLY. Overall, HD-MF/IND/GLY induced greater clinically relevant benefits even when compared to HD-FLU/SAL + TIO. Considering that a balanced triple MF/IND/GLY FDC with MD ICS resulted as effective as HD-MF/IND in preventing moderate or severe exacerbations, thus triple ICS/LABA/LAMA FDCs with MD ICS should be considered for the treatment not only of uncontrolled asthma but also for those patients suffering from less severe forms of disease with airflow limitation as well as a possible as-needed therapeutic option.

Fractional Exhaled Nitric Oxide Guided-Therapy in Chronic Obstructive Pulmonary Disease: A Stratified, Randomized, Controlled Trial

IntroductionChronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation represents a distinct phenotype that might respond to treatment with inhaled corticosteroids. Fractional exhaled nitric oxide (FENO) might predict eosinophilic inflammation and guide treatment option. We hypothesized that COPD patients with different baseline levels of FENO might have differentiated response to treatment with salmeterol/fluticasone (SFC) or tiotropium (TIO). MethodsThis open-label, randomized-controlled trial enrolled treatment-naïve COPD patients who were stratified into high- (≥23.5ppb) and low-FENO group, followed by 12-week treatment with SFC or TIO. A linear mixed model with repeated measures was applied to analyze the changes in FENO (primary outcome), COPD assessment test (CAT) score, FEV1, and parameters in induced sputum and blood after treatment. Results134 patients were divided into 4 subgroups: low-FENO/SFC (n=30), low-FENO/TIO (n=29), high-FENO/SFC (n=37), and high-FENO/TIO (n=38). At baseline, FENO 23.5ppb clearly differentiated between eosinophilic and non-eosinophilic inflammation groups based on the eosinophils in induced sputum and blood. FENO significantly correlated with sputum and blood eosinophils at baseline. High-FENO/SFC (vs. high-FENO/TIO) subgroup had significant reduction in FENO and sputum inflammation profiles (including eosinophils, macrophages, matrix metalloproteinase-9, and interlukin-8) after treatment. These differences were not replicated between low-FENO/SFC and low-FENO/TIO subgroups. The improvement in CAT and FEV1 after treatment was indiscriminate between SFC and TIO in the low- and high-FENO groups. ConclusionHigh baseline FENO can serve as an indicator of eosinophilic airway inflammation in COPD patients who may respond favorably to treatment with inhaled corticosteroids/long-acting β2-agonists. Trial registration numberClinicalTrials.gov Identifier: NCT02546349.

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

昔萘酸沙美特罗是目前治疗哮喘夜间发作和哮喘维持治疗的理想药物之一,它在临床上以外消旋体形式给药。昔萘酸沙美特罗的两个对映体在药理活性和毒理作用等方面差异较大,建立昔萘酸沙美特罗对映体的手性分离分析方法对提高手性药物质量、保证临床用药安全有效具有重要意义。该文以L(+)-酒石酸-硼酸络合酸为手性选择剂,建立了测定沙美特罗替卡松粉吸入剂中昔萘酸沙美特罗对映体含量的非水毛细管电泳法。实验考察了L(+)-酒石酸浓度、硼酸浓度和表观pH(apparent pH, pH* )对手性分离效果的影响。优化的缓冲溶液为:含120.0 mmol/L L(+)-酒石酸和120.0 mmol/L硼酸的甲醇溶液,pH* 为0.93;其他实验条件为:未涂层弹性熔融石英毛细管(内径50.0 μm,总长度64.5 cm,有效长度55.5 cm),重力进样17.5 cm×10.0 s,检测波长225 nm,室温,工作电压20.0 kV。在优化的实验条件下,昔萘酸沙美特罗的两个对映体在18.0 min内获得了2.18的分离度;在27.5~800.0 mg/L质量浓度范围内,与峰面积呈现良好的线性关系,相关系数(r)大于0.9990;检出限和定量限分别为7.5和25.0 mg/L;加标回收率为98.1%~101.9%,相对标准偏差为1.2%~1.9%。随机购买市面上出售的沙美特罗替卡松粉吸入剂,对其昔萘酸沙美特罗对映体的含量进行了分析检测。结果显示,昔萘酸沙美特罗对映体1和对映体2的标示量百分含量均为98.7%, RSD分别为2.5%和2.7%。该方法操作简便易行,结果准确可靠,消耗低,可用于市售沙美特罗替卡松粉吸入剂中昔萘酸沙美特罗对映体的含量测定。

Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis.

Background:Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.Methods:A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.Results:Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57–9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24–1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39–3.21; I2 = 72%; P < 0.001) compared with MFC.Conclusions:SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.PROSPERO registration number:CRD42019133156.

Magnesium isoglycyrrhizinate inhibits airway inflammation in rats with chronic obstructive pulmonary disease

BackgroundChronic obstructive pulmonary disease (COPD) is a kind of chronic lung diseases with the characteristics of airway remodeling and airflow obstruction. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating hepatitis. However, whether MgIG can treat other diseases and its action mechanism is still obscure. In this study, we evaluated the anti-inflammatory effect of MgIG in rats with COPD and investigated the underlying mechanisms.MethodsRat model of COPD was constructed by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction. Rats were randomly divided into 5 groups: control group, COPD model group, salmeterol fluticasone comparator group, low dose of MgIG group, and high dose of MgIG group. Except for normal control group, the other four groups received sensitization treatment by cigarette smoking and endotracheal-atomization of endotoxin lipopolysaccharide to construct COPD rats model. After model established successfully, the COPD rats in each group received corresponding dose of endotracheal-atomized normal saline, salmeterol fluticasone, and MgIG every day prior to exposure of cigarette smoke from days 30 to 45. Normal control group were treated with normal saline. Finally, All rats were euthanatized. Pulmonary function was measured. Cells in bronchoalveolar lavage fluid were classified, inflammatory factors IL-6 and TNF-α were determined, histopathological analysis was performed by HE staining, and expression of NLRP3 and cleaved caspase-1 in the lung tissue was also determined by Western blotting.ResultsIt showed that MgIG treatment (0.40 or 0.80 mg/kg/day) could recover the weight and the clinical symptoms of rats with COPD, accompanied with lung inflammation infiltration reduction, airway wall attenuation, bronchial mucus secretion reduction. Additionally, MgIG administration reduced inflammatory cells (white blood cells, neutrophils, lymphocytes and monocytes) accumulation in bronchoalveolar lavage fluid and decreased IL-6 and TNF-α production in the serum of COPD rats. Furthermore, MgIG treatment also reduced the expression level of NLRP3 and cleaved caspase-1.ConclusionIt indicate that MgIG might be an alternative for COPD treatment, and its mechanism of action might be related to the suppression of NLRP3 inflammasome.

In Vitro Performance of the Wixela Inhub Inhaler Using Severe Chronic Obstructive Pulmonary Disease Patient Inhalation Profiles.

Background: Wixela Inhub (trademarks of Viatris, Inc.) is a dry powder inhaler (DPI) that delivers a fixed-dose combination of fluticasone propionate and salmeterol and is approved as a generic equivalent to Advair Diskus (trademarks of GlaxoSmithKline plc) for the treatment of asthma and chronic obstructive pulmonary disease (COPD). The dosing performance of DPIs is dependent on the patient's inspiratory capability, which may be impacted in disease populations such as those with severe COPD. The objective of this study was to evaluate the in vitro dose delivery of fluticasone propionate and salmeterol from the Inhub inhaler with in vivo inhalation profiles of severe COPD patients, using two types of breathing simulator with different modes of operation. Materials and Methods: Two breathing simulators (Si-Plan and Copley BRS3100) were used with United States Pharmacopoeia (USP) <601> apparatus 5 (Next Generation Impactor and accessories) to measure the total emitted dose and fine particle mass of fluticasone propionate and salmeterol for Wixela Inhub (250/50 mcg) using 13 severe COPD patient inhalation profiles. Results: Wixela Inhub demonstrated low flow dependency across the range of COPD patient profiles tested (peak inspiratory flow rate 60.8-84.9 L minute-1), when assessed by total emitted dose and fine particle mass. The results were similar to literature results reported for fluticasone propionate from the Diskus inhaler, tested using a proprietary breathing simulator and Andersen Cascade Impactor. Comparison between the breathing simulators showed no significant difference in fluticasone propionate results, but a small difference was observed between the breathing simulators for salmeterol total emitted dose and fine particle mass. Conclusions: This study demonstrates that severe COPD patients are likely to achieve a consistent inhaled dose from Wixela Inhub, with low flow dependency observed within this patient population. In addition, both breathing simulators, which differ significantly in design, produced similar results for fluticasone propionate, but yielded slightly (but statistically significant) different results for salmeterol.

Synthesis and characterization of double molecular imprinted nanoparticles and investigation to adsorption of respiratory drugs

ABSTRACT In this study, novel double molecular imprinted nanoparticles (DMIP nanoparticles) with multi-functional monomers were prepared for adsorption of salmeterol xinafoate (SAM) and fluticasone propionate (FLU) drugs. For this purpose, SAM and FLU imprinted poly (2-hydroxyethyl methacrylate-N-methacryloyl-(L)-alanine-N-methacryloyl-(L)-histidine) [p(HEMA-MAAL-MAH)] nanoparticles were synthesized by surfactant-free emulsion polymerization method. After the characterization, adsorption conditions were optimized, and the adsorption kinetics parameters were also calculated. In the selectivity experiments, budesonide (BS) and formoterol fumarate (FF) drugs were used as competitive drugs. These novel development DMIP nanoparticles have the potential for use in many different areas, for purposes such as drug release, separation, and purification.

Once-daily, single-inhaler indacaterol/mometasone versus twice-daily salmeterol/fluticasone in Asian patients with inadequately controlled asthma: post hoc pooled analysis from PALLADIUM and IRIDIUM studies

Objective PALLADIUM and IRIDIUM studies demonstrated efficacy and safety of indacaterol/mometasone (IND/MF) versus salmeterol/fluticasone (SAL/FLU). This post hoc analysis of pooled data from PALLADIUM and IRIDIUM studies evaluated efficacy and safety of IND/MF versus SAL/FLU in Asian patients with inadequately controlled asthma. Methods Both studies were Phase III, 52-week, randomized, double-blind, active-controlled that included patients with predicted pre-bronchodilator FEV1 (PALLADIUM, ≥50%–<85%; IRIDIUM, <80%), ACQ-7 score ≥1.5. Patients treated with IND/MF high- (150/320 μg) or medium-dose (150/160 μg) or SAL/FLU high-dose (50/500 μg) were included. Lung function, asthma control, and asthma exacerbations were evaluated. Results In total, 323 patients (IND/MF high-dose, n = 107; IND/MF medium-dose, n = 106, SAL/FLU high-dose, n = 110) were included. IND/MF high-dose showed improvement in trough FEV1 versus SAL/FLU high-dose at Weeks 26 (Δ, 42 mL; 95% CI, −35 to 120 mL), and 52 (Δ, 41 mL; 95% CI, −37 to 120 mL). IND/MF high-dose exhibited numerically greater improvement in ACQ-7 score versus SAL/FLU high-dose at Weeks 26 (Δ, −0.215; 95% CI, −0.385 to −0.044) and 52 (Δ, −0.176; 95% CI, −0.348 to −0.005). Improvements in trough FEV1 and ACQ-7 score were comparable between IND/MF medium-dose and SAL/FLU high-dose. IND/MF high- and medium-dose showed reductions in moderate or severe (45%; 30%), severe (39%; 41%), and all (9%; 25%) exacerbations, respectively, versus SAL/FLU high-dose over 52 weeks. All treatments were well tolerated. Conclusions Once-daily, single-inhaler IND/MF high-dose improved lung function with better asthma control, reduced asthma exacerbations with comparable safety versus twice-daily SAL/FLU high-dose. IND/MF medium-dose showed comparable outcomes to SAL/FLU high-dose at a reduced steroid dose.