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Objective: To explore the clinical value of Vitamin-D combined with budesonide/formoterol (BF) and theophylline sodium glycinate (TSG) sustained-release tablets in the treatment of patients with chronic obstructive pulmonary disease (COPD). Methods: Medical records of 114 patients with CODP, treated in Wenzhou Geriatric Hospital from October 2020 to February 2023, were retrospectively analyzed. Of them, 59 received treatment with Vitamin-D combined with BF and TSG sustained-release tablets (Group-A), and 55 patients received treatment with BF combined with TSG sustainedrelease tablets (Group-B). Lung function indicators, blood gas status, inflammatory factors, fractional exhaled nitric oxide (FeNO), and 25-hydroxyvitamin D [25(OH)D] levels before and after the treatment in both groups were collected. Results: After the treatment, lung function indicators, blood gas status, inflammatory factors, FeNO, and 25 (OH) D levels in both groups were significantly improved compared to pretreatment levels, and were significantly better in the Group-A compared to Group-B (P<0.05). Conclusions: The combination of Vitamin-D, BF, and TSG sustained-release tablets can effectively regulate the blood gas status of patients with COPD, improve lung function, regulate FeNO and 25 (OH) D, and effectively downregulate the levels of inflammatory factors, thus reducing the degree of inflammatory response. [ABSTRACT FROM AUTHOR]

To assess the impact of budesonide-formoterol on pulmonary ventilation function and prognosis in patients with mild-to-moderate acute exacerbations of bronchial asthma. A retrospective analysis was conducted on clinical data from 232 patients with acute exacerbations of bronchial asthma. These patients were divided into 2 groups based on their treatment: a control group (n=104) receiving budesonide dry powder inhalation and an observation group (n=107) receiving budesonide-formoterol dry powder inhalation. Clinical efficacy and safety indicators were compared. The results showed that the total treatment effectiveness rate in the observation group was significantly higher than that in the control group. Following treatment, the observation group exhibited significantly higher scores in the Asthma Quality of Life Questionnaire (AQLQ), as well as improved levels of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), compared to the control group. Moreover, levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein were significantly lower in the observation group. The incidence of adverse reactions between groups was comparable. Based on these findings, the application of budesonide-formoterol demonstrated significant effectiveness in patients with mild-to-moderate acute exacerbations of bronchial asthma. The combination therapy led to improved clinical outcomes, including enhanced pulmonary ventilation function and reduced inflammatory markers. Importantly, the safety profile of budesonideformoterol was comparable to that of budesonide monotherapy. These results highlight the potential benefits of using budesonide-formoterol as an alternative treatment option for patients experiencing acute exacerbations of mild-to-moderate bronchial asthma. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Currently, there is no effective therapy for takotsubo syndrome (stress‐induced cardiac injury in humans) in the clinics. It has previously been shown that β2‐adrenergic receptor (β2‐AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress‐induced cardiomyopathy.Stress‐induced cardiac injury was induced by immobilization of rats for 2, 6, and 24 hours.The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6 hours after the onset of stress and peaked at 24 hours. Apoptosis of cardiomyocytes significantly gained only after 24 hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase‐MB, syndecan‐1, and thrombomodulin after 24 hours of stress. Administration of β2‐AR agonist formoterol (50 μg/kg) four times during 24‐hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL‐positive cardiomyocytes, serum creatine kinase‐MB, syndecan‐1, and thrombomodulin levels.Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress‐induced cardiac injury can be mitigated by activation of the β2‐AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a life‐threatening vascular disease but effective drugs for treatment of AAA are still lacking. Recently, erythropoietin (EPO) is reported to induce AAA formation in apolipoprotein‐E knock out (ApoE−/−) mice but an effective antagonist is unknown. In this study, formoterol, a β2 adrenergic receptor (β2AR) agonist, is found to be a promising agent for inhibiting AAA. To test this hypothesis, ApoE−/− mice are treated with vehicle, EPO, and EPO plus low‐, medium‐, and high‐dose formoterol, respectively. The incidence of AAA is 0, 55%, 35%,10%, and 55% in these 5 groups, respectively. Mechanistically, senescence of vascular smooth muscle cell (VSMC) is increased by EPO while decreased by medium‐dose formoterol both in vivo and in vitro, manifested by the altered expression of senescence biomarkers including phosphorylation of H2AXserine139, senescence‐associated β‐galactosidase activity, and P21 protein level. In addition, expression of sirtuin 1 (SIRT1) in aorta is decreased in EPO‐induced AAA but remarkably elevated by medium‐dose formoterol. Knockdown of β2AR and blockage of cyclic adenosine monophosphate (cAMP) attenuate the inhibitory role of formoterol in EPO‐induced VSMC senescence. In summary, medium‐dose formoterol attenuates EPO‐induced AAA via β2AR/cAMP/SIRT1 pathways, which provides a promising medication for the treatment of AAA. [ABSTRACT FROM AUTHOR]

Simple Summary: Formoterol, an FDA-approved long-acting beta2-adrenergic receptor agonist, has shown potential benefits in various diseases, yet its effectiveness in Parkinson's disease (PD) is uncertain. The lack of a comprehensive understanding of formoterol's mechanism, particularly in mitochondrial remodeling, contributes to this uncertainty. PD involves mitochondrial dysfunction, leading to disruptions in energy production, heightened oxidative stress, and impaired mitochondrial dynamics and turnover. Understanding this link is vital for developing targeted therapies for PD. To explore this, this study used a cell model that mimics a specific genetic form of PD. This model displayed the above problems with mitochondria. The study found that after treating these cells with formoterol, there were positive effects. The medication enhanced the growth and survival of PD-associate mutant cells while protecting against stress. Crucially, it contributed to restoring normal mitochondrial function and machinery, promoting a rebalance in mitochondrial dynamics, including changes in morphology (fusion/fission), movement, and transport. This effect was achieved by influencing specific cell signals and proteins associated with mitochondrial health. This study underscores formoterol's pivotal role as a mitochondrial dynamic balance regulator, positioning it as a promising therapeutic candidate for PD. Formoterol, a β2-adrenergic receptor (β2AR) agonist, shows promise in various diseases, but its effectiveness in Parkinson's disease (PD) is debated, with unclear regulation of mitochondrial homeostasis. This study employed a cell model featuring mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) variants associated with familial parkinsonism, demonstrating mitochondrial dysfunction and dynamic imbalance, exploring the therapeutic effects and underlying mechanisms of formoterol. Results revealed that 24-h formoterol treatment enhanced cell proliferation, viability, and neuroprotection against oxidative stress. Mitochondrial function, encompassing DNA copy number, repatriation, and complex III-linked respiration, was comprehensively restored, along with the dynamic rebalance of fusion/fission events. Formoterol reduced extensive hypertubulation, in contrast to mitophagy, by significantly upregulating protein Drp-1, in contrast to fusion protein Mfn2, mitophagy-related protein Parkin. The upstream mechanism involved the restoration of ERK signaling and the inhibition of Akt overactivity, contingent on the activation of β2-adrenergic receptors. Formoterol additionally aided in segregating healthy mitochondria for distribution and transport, therefore normalizing mitochondrial arrangement in mutant cells. This study provides preliminary evidence that formoterol offers neuroprotection, acting as a mitochondrial dynamic balance regulator, making it a promising therapeutic candidate for PD. [ABSTRACT FROM AUTHOR]

When selecting inhaled therapies, it is important to consider both the active molecules and the device. Extrafine formulation beclomethasone dipropionate plus formoterol fumarate (BDP/FF) has been available for some years delivered via pressurized metered-dose inhaler (pMDI). More recently, a breath-activated, multi-dose dry-powder inhaler (DPI), the NEXThaler, has been approved. The current study aimed to demonstrate the non-inferiority of BDP/FF delivered via the DPI vs. via the pMDI, in Chinese adults with asthma. After a four-week run-in period, when all patients received BDP/FF pMDI 100/6 µg, two inhalations twice daily (BID), patients were randomized equally to BDP/FF pMDI or DPI, both 100/6 µg, two inhalations BID for 12 weeks. The primary objective was to demonstrate non-inferiority of BDP/FF DPI vs. BDP/FF pMDI in terms of average pre-dose morning peak expiratory flow (PEF) over the entire treatment period. Of 252 and 242 patients in the DPI and pMDI groups, respectively, 88.5% and 88.8% completed the study. The primary objective was met, with no statistically significant difference between the treatments in average pre-dose morning PEF, and with the lower limit of the 95% CI above the −15 L/min non-inferiority margin (adjusted mean difference: 5.25 L/min [95% CI: −0.56, 11.06]). Adverse events were reported by 48.4% and 49.6% patients in the DPI and pMDI groups, respectively, most mild or moderate. The NEXThaler DPI is a similarly effective device to the pMDI for the administration of BDP/FF in adults, so extending the options available for the management of asthma. [ABSTRACT FROM AUTHOR]

Background: The combination of an inhaled corticosteroid (ICS) and long-acting β-agonist (LABA) (ICS/LABA) has shown superiority in improving lung function (FEV1) compared with an ICS alone. The clinical effect of a ICS/LABA combination depends on the fine-particle fraction and the pulmonary deposition. Objective: We sought to compare the efficacy of 2 combinations of an ICS and LABA, namely, fluticasone propionate (FP) and formoterol (FORM) (FP/FORM) and fluticasone furoate (FF) and vilanterol (VI) (FF/VI), in asthmatic adolescents with chronic bronchial obstruction. Methods: FP/FORM (125 μg/5 μg, 2 doses twice daily via the k-haler [Mundipharma, Cambridge, UK]) and FF/VI (92 μg/22 μg, once daily via the Ellipta inhaler [GlaxoSmithKline]) were administered to adolescents aged 12 to 17 years who required regular antiasthmatic medication and had a ratio of FEV1 to forced vital capacity (FEV1/FVC) less than –1.65 SD in a 2-sequence, 16-week crossover trial. The primary efficacy end point was change in FEV1 compared with baseline. Secondary end points were FEV1/FVC ratio, maximal expiratory flow at 50% of the FVC, impulse oscillometry indices respiratory resistance at 5 Hz (R5), difference between R5 and respiratory resistance at 20 Hz (R20), area of reactance, and Asthma Control Test score. Results: Both ICS/LABA combinations resulted in a significant improvement in FEV1 and maximal expiratory flow at 50% of the FVC z scores without any significant difference between FP/FORM and FF/VI, with 40% of patients with either treatment achieving a normal prebronchodilator FEV1/FVC z score. Neither area of reactance nor difference between R5 and R20 improved significantly with either treatment. Conclusion: Both ICS/LABA combinations demonstrated significant improvements in FEV1 z score. More than one-third of the asthmatic adolescents with prolonged bronchial obstruction achieved a normal prebronchodilator FEV1/FVC ratio.

AbstractIntroductionMethodsResultsConclusionOnce-daily inhalers have been shown to improve adherence leading to lesser discontinuation compared to twice- or thrice-daily inhalers in management of asthma. Combination of Vilanterol and Fluticasone Furoate (VI/FF) is approved for management of asthma and COPD and is available as a dry powder inhaler. Pressurized-Metered Dose Inhalers (pMDIs) offer ease-of-use and therapy alternatives for patients with low inspiratory flow. This study assessed the efficacy and safety of a new once-daily pMDI containing VI/FF in individuals diagnosed with persistent asthma.This phase 3, double-blind, randomized controlled study assessed the non-inferiority of VI/FF (12.5 mcg/50 mcg & 12.5 mcg/100 mcg; 2 puffs once-daily) over Formoterol Fumarate and Fluticasone Propionate (FOR/FP, 6 mcg/125 mcg & 6 mcg/250 mcg; 2 puffs twice-daily) in patients with persistent asthma. Primary outcome was change from baseline in trough FEV1 at the end of study (12 weeks). Adverse events and number of exacerbations were used to evaluate safety.A total of 330 patients were randomized into VI/FF (165) and FOR/FP (165). Trough FEV1 significantly improved in both the groups at week 12, with a mean difference (VI/FF minus FOR/FP) being 54.75 mL (95% CI, 8.42–101.08 mL, p = 0.02). The low dose VI/FF had similar efficacy to that of low dose FOR/FP and high dose VI/FF had similar efficacy to high dose FOR/FP. No serious adverse events were reported during the study.Once daily VI/FF pMDI was non-inferior to twice daily FOR/FP pMDI in patients with persistent asthma. [ABSTRACT FROM AUTHOR]

Backround Oxitropium bromide (OB) and formoterol fumarate dihydrate (FFD) are inhaler molecules that are widely used in the treatment of chronic lung diseases. Objective The goal of this work was to create a reversed phase–ultra performance liquid chromatography (RP-UPLC) technique for assay and identification of OB and FFD, as well as identification and estimate of its associated compounds in pressurized metered dose inhaler product (pMDI). Method Separation of oxitropium and formoterol peaks were enhanced on a C18 (50 × 2.1 mm × 1.7 μm) UPLC column with ethylene-bridged-hybrid technology, The mobile phase consists of buffer (0.07 M KH2PO4) and acetonitrile (80:20, v/v). The detector wavelength of 210 nm, flow rate of pump 0.6 mL/min, and oven temperature for column were set at 25°C. The injection volume was 10 μL. The method run time was 2 min. The mobile phase was used as the solvent. Results Retention times (RTs) were 0.5 min for OB and 1.0 min for FFD. The assay analysis was linear range for all analytes within the range for concentrations 0.03—14.8 µg/mL of OB, 0.01–0.88 µg/mL of FFD. LOD values and LOQ values 0.009 and 0.026 µg/mL for OB and 0.003 and 0.009 µg/mL for FFD, respectively. Recoveries were obtained at 96.3% for OB and 97.2% for FFD. Precisions values were (as RSD, %) ≤1.5%. Conclusions With the UPLC method developed and validated according to the current ICH guidelines, it is possible to simultaneously detect OB and FFD of assay analysis in pMDI products accurately, precisely and selectively, independent of the matrix effect. Highlights The present method is the first method in the literature based on the UPLC method for this purpose. The UPLC method is a time-saving method, it provides a faster and cheaper technique than the high performance liquid chromatography (HPLC) method. [ABSTRACT FROM AUTHOR]

Background: Although adherence to inhaled medication is critically important for treatment efficiency, around half of patients taking these drugs are non-adherent or make critical errors when using their delivery device. Segmental hair analysis might be a valuable tool for therapeutic monitoring because hair concentrations reflect exposure from month to month. The objective of the present proof-ofconcept study was to establish the feasibility of segmental hair analysis of inhaled budesonide and formoterol in asthma patients. Methods: We conducted a prospective, open-label, interventional study of adult patients being treated with budesonide/formoterol for controlled, moderate-tosevere asthma (CorticHair, NCT03691961). Asthma control, lung function, and medication adherence were recorded. Hair samples were taken 4 months after enrolment and cut into four 1 cm segments. Results: Samples were available from 21 patients (20 women; median age: 53; median budesonide dose: 600 µg/d). Budesonide and formoterol were detected in samples from 18 to 13 patients, respectively. The median hair concentrations were 6.25 pg/mg for budesonide and 0.9 pg/mg for formoterol. The intrapatient coefficient of variation between hair segments was 21% for budesonide and 40% for formoterol. Pearson's coefficients for the correlations between the hair concentration and the self-reported drug dose and the prescribed drug dose were respectively 0.42 (p = 0.08) and 0.29 (p = 0.25) for budesonide and 0.24 (p = 0.44) and 0.17 (p = 0.57) for formoterol. Conclusion: Segmental hair analysis of inhaled medications was feasible, with low intrapatient variability. This innovative, non-invasive means of assessing monthly drug exposure might help physicians to personalize drug regimens for patients with difficult-to-treat asthma. [ABSTRACT FROM AUTHOR]

Background: Even though doxorubicin (DOX) chemotherapy promotes intense muscle wasting, this drug is still widely used in clinical practice due to its remarkable efficiency in managing cancer. On the other hand, intense muscle loss during the oncological treatment is considered a bad prognosis for the disease's evolution and the patient's quality of life. In this sense, strategies that can counteract the muscle wasting induced by DOX are essential. In this study, we evaluated the effectiveness of formoterol (FOR), a β2-adrenoceptor agonist, in managing muscle wasting caused by DOX. Methods and results: To evaluate the effect of FOR on DOX-induced muscle wasting, mice were treated with DOX (2.5 mg/kg b.w., i.p. administration, twice a week), associated or not to FOR treatment (1 mg/kg b. w., s.c. administration, daily). Control mice received vehicle solution. A combination of FOR treatment with DOX protected against the loss of body weight (p<0.05), muscle mass (p<0.001), and grip force (p<0.001) promoted by chemotherapy. FOR also attenuated muscle wasting (p<0.01) in tumor-bearing mice on chemotherapy. The potential mechanism by which FOR prevented further DOX-induced muscle wasting occurred by regulating Akt/FoxO3a signaling and gene expression of atrogenes in skeletal muscle. Conclusions: Collectively, our results suggest that FOR can be used as a pharmacological strategy for managing muscle wasting induced by DOX. This study provides new insights into the potential therapeutic use of FOR to improve the overall wellbeing of cancer patients undergoing DOX chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract Abdominal aortic aneurysm (AAA) is a life‐threatening vascular disease but effective drugs for treatment of AAA are still lacking. Recently, erythropoietin (EPO) is reported to induce AAA formation in apolipoprotein‐E knock out (ApoE−/−) mice but an effective antagonist is unknown. In this study, formoterol, a β2 adrenergic receptor (β2AR) agonist, is found to be a promising agent for inhibiting AAA. To test this hypothesis, ApoE−/− mice are treated with vehicle, EPO, and EPO plus low‐, medium‐, and high‐dose formoterol, respectively. The incidence of AAA is 0, 55%, 35%,10%, and 55% in these 5 groups, respectively. Mechanistically, senescence of vascular smooth muscle cell (VSMC) is increased by EPO while decreased by medium‐dose formoterol both in vivo and in vitro, manifested by the altered expression of senescence biomarkers including phosphorylation of H2AXserine139, senescence‐associated β‐galactosidase activity, and P21 protein level. In addition, expression of sirtuin 1 (SIRT1) in aorta is decreased in EPO‐induced AAA but remarkably elevated by medium‐dose formoterol. Knockdown of β2AR and blockage of cyclic adenosine monophosphate (cAMP) attenuate the inhibitory role of formoterol in EPO‐induced VSMC senescence. In summary, medium‐dose formoterol attenuates EPO‐induced AAA via β2AR/cAMP/SIRT1 pathways, which provides a promising medication for the treatment of AAA.

Background: Exercise is an effective treatment for establishing and maintaining skeletal muscle health. The interconnected cascade of gene expression pathways related to myogenesis, mitochondrial homeostasis, and thyroid hormone metabolism are critical to skeletal muscle health. This in vitro study was conducted to investigate the effects of exercise mimetic (formoterol) stimulation on human skeletal muscle cell signaling during myogenesis, and to provide insight on potential targets for future studies exploring therapies for skeletal muscle atrophy. Human myoblasts were cultured and differentiated to evaluate the effects of exercise mimetic stimulation on gene expression during mid and late myogenesis. Results: We characterized the expression of 24 genes related to myogenesis, mitochondrial biogenesis, thyroid hormone metabolism, and cellular homeostasis and found that 21 genes were altered in response to formoterol, thus affecting related skeletal muscle pathways. Additionally, formoterol stimulation resulted in a myogenic program that appears to favor prolonged myoblast proliferation and delayed myotube maturation. Robust, yet distinctive effects of exercise mimetic stimulation on gene expression during mid-myogenesis and at terminal differentiation occurred. For instance, MYF5 increased in D6 FORM compared to other groups (p < 0.001) while MYOD and MYOG both decreased expression in the FORM groups compared to CON (p < 0.01). Secondly, mitochondrial biogenesis genes were stimulated following formoterol administration, namely PGC-1α, PGC-1β, and TFAM (p < 0.05). Uniquely in our study, thyroid hormone metabolism related genes were differentially expressed. For instance, DIO2 and DIO3 were both stimulated following formoterol administration (p < 0.05). Conclusions: The results of our study support the groundwork for establishing further experiments utilizing exercise signaling as a clinical treatment in models targeting dysfunctional skeletal muscle cell growth. [ABSTRACT FROM AUTHOR]

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (β2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population. [ABSTRACT FROM AUTHOR]

The implementation of nanotechnology in pulmonary delivery systems might result in better and more specific therapy. Therefore, a nano-sized drug carrier should be toxicologically inert and not induce adverse effects. We aimed to investigate the responses of a polymer nano drug carrier, a lysine poly-hydroxyethyl methacrylate nanoparticle (NP) [Lys-p(HEMA)], loaded with formoterol, both in vitro and in vivo in an ovalbumin (OVA) asthma model. The successfully synthesized nanodrug formulation showed an expectedly steady in vitro release profile. There was no sign of in vitro toxicity, and the 16HBE and THP-1 cell lines remained vital after exposure to the nanocarrier, both loaded and unloaded. In an experimental asthma model (Balb/c mice) of ovalbumin sensitization and challenge, the nanocarrier loaded and unloaded with formoterol was tested in a preventive strategy and compared to treatment with the drug in a normal formulation. The airway hyperresponsiveness (AHR) and pulmonary inflammation in the bronchoalveolar lavage (BAL), both cellular and biochemical, were assessed. The application of formoterol as a regular drug and the unloaded and formoterol-loaded NP in OVA-sensitized mice followed by a saline challenge was not different from the control group. Yet, both the NP formulation and the normal drug application led to a more deteriorated lung function and increased lung inflammation in the OVA-sensitized and -challenged mice, showing that the use of the p(HEMA) nanocarrier loaded with formoterol needs more extensive testing before it can be applied in clinical settings. [ABSTRACT FROM AUTHOR]

The present study hypothesises that the selective brain β2 receptor activation through β2-adrenoreceptor agonist (β2ARA), Formoterol (FMT), suppresses SNCA gene expression, a pathological hallmark of Parkinson's disease (PD) in brain. Further, it is also hypothesized that brain targeted delivery of Formoterol via polysorbate-80 surface modified solid lipid nanoparticles of Formoterol (FMT-SLNs-PS80) can improve its stability, therapeutic efficacy and avoid/reduce peripheral off-target side effects. FMT-SLNs-PS80 was prepared by solvent injection method, the formulation was optimized by using Box–Behnken design and characterized by measuring drug content, entrapment efficacy, particle size, zeta potentials and poly dispersibility. The FMT-SLNs-PS80, significantly decreases the SNCA expression, mitochondrial membrane damage and rotenone induced changes in oxidative (SOD, CAT, GSH and ROS) stress markers in SH-SY5Y cell lines. The ex vivo permeation study of the formulation using everted chicken ileum exhibited a steady state flux. The pharmacokinetic and tissue distribution studies of the formulation in rats showed a significant improvement in the kinetic parameters when compared to naïve FMT, further the formulation also improved the brain bioavailability of FMT. The anti-Parkinson's efficacy studies of the formulation in mice showed a significant neuroprotection against rotenone-induced changes in behavioural and biochemical parameters. Further, the histopathological analysis of mice brain confirms a significant neuroprotective benefit. The present study successfully establishes the brain targeted delivery and anti-Parkinson's therapeutic efficacy of FMT-SLNs-PS80. [ABSTRACT FROM AUTHOR]

Lung cancer frequently affects patients with Chronic Obstructive Pulmonary Disease (COPD). Cigarette smoke (CS) fosters cancer progression by increasing oxidative stress and by modulating epithelial-mesenchymal transition (EMT) processes in cancer cells. Formoterol (FO), a long-acting β2-agonist widely used for the treatment of COPD, exerts antioxidant activities. This study explored in a lung adenocarcinoma cell line (A549) whether FO counteracted the effects of cigarette smoke extract (CSE) relative to oxidative stress, inflammation, EMT processes, and cell migration and proliferation. A549 was stimulated with CSE and FO, ROS were evaluated by flow-cytometry and by nanostructured electrochemical sensor, EMT markers were evaluated by flow-cytometry and Real-Time PCR, IL-8 was evaluated by ELISA, cell migration was assessed by scratch and phalloidin test, and cell proliferation was assessed by clonogenic assay. CSE significantly increased the production of ROS, IL-8 release, cell migration and proliferation, and SNAIL1 expression but significantly decreased E-cadherin expression. FO reverted all these phenomena in CSE-stimulated A549 cells. The present study provides intriguing evidence that FO may exert anti-cancer effects by reverting oxidative stress, inflammation, and EMT markers induced by CS. These findings must be validated in future clinical studies to support FO as a valuable add-on treatment for lung cancer management. [ABSTRACT FROM AUTHOR]

The choice of bronchodilators for responsiveness testing (BRT) is a clinical decision according to ATS/ERS. Since January 2019 we use budesonide/formoterol for BRT in asthma at our center in Argentina. The aim was to compare budesonide/formoterol with salbutamol for BRT in stable asthmatic patients that were followed up in a short-acting beta2 agonist (SABA)-free asthma center. From the Hospital database, we found for the same patient at least one BRT using salbutamol 200 µg and another with budesonide/formoterol 320/9 µg. We found similar BRT between salbutamol and budesonide/formoterol in 101 asthmatic individuals (26 males) aged 38.14 ± 16.1 yrs (mean ± Standard deviation). The absolute response was 0.18 ± 0.21 L in FEV1 after salbutamol and 0.20 ± 0.22 L in FEV1 after budesonide/formoterol. Afterwards, we showed 202 patients tested with budesonide/formoterol; the mean absolute response was 0.21 ± 0.22 L in FEV1. There were no unexpected safety findings. In asthmatic patients, we demonstrated similar efficacy between Budesonide/formoterol and salbutamol for BRT. [ABSTRACT FROM AUTHOR]

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Objective: To explore the effects of budesonide glycopyrronium bromide and budesonide formoterol on pulmonary function and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) during remission. Methods: A total of 300 patients with COPD during remission in the hospital were enrolled and randomly divided into group A (n=150) and group B (n=150) between January 2020 and December 2022. The group A was given budesonide glycopyrronium bromide, while group B was given budesonide formoterol for inhalation therapy. After 3 months of continuous treatment, curative effect and medication safety, changes of pulmonary function, blood gas level, exercise tolerance, quality of life and inflammatory indexes were compared between the two groups. Results: After 3 months of continuous treatment, total response rate of treatment in group A was higher than that in control group (96.00% vs 90.00%, P<0.05). After treatment, forced expiratory volume in 1 second (FEV₁), FEV₁/forced vital capacity, FEV, as percentage of predicted value, partial pressure of oxygen and 6 min walking distance in both groups were increased, which were higher in group A than group B (P<0.05), while residual volume/total lung capacity, partial pressure of carbon dioxide, interleukin-17, matrix metalloproteinase-9 and score of St. George's Respiratory Questionnaire were decreased, which were lower in group A than group B (P<0.05). There were no serious adverse reactions in either group during treatment (P>0.05). Conclusion: Compared with budesonide formoterol, budesonide glycopyrronium bromide has better curative effect, which can effectively reduce airway inflammation injury, improve pulmonary function, blood gas level, exercise tolerance and quality of life in patients with COPD during remission. [ABSTRACT FROM AUTHOR]

Background: This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β2-agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function. Methods: Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siVaw) and resistance (siRaw) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siVaw and siRaw changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siVaw and siRaw at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV1) and COPD Assessment Test (CAT) were also assessed. Results: There were no significant changes in pre-dose siVaw or siRaw at TLC from baseline to V3, although at FRC there was a significant decrease in mean siRaw in the distal airways (− 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siVaw and siRaw (siVaw: 39.8% and 62.6%; siRaw: − 51.1% and − 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siVaw: 77.9%; siRaw: − 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV1 was 62.2 mL (p = 0.0690), and in CAT total score was − 3.30 (p < 0.0001). Conclusions: In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021 [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. While two approved fixed-dose inhaled corticosteroid/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) triple therapies reduce all-cause mortality (ACM) versus dual LAMA/LABA therapy in patients with COPD, head-to-head studies have not compared the effects of these therapies on ACM. We compared ACM in adults with moderate-to-very severe COPD receiving budesonide/glycopyrrolate/formoterol fumarate (BGF) in ETHOS versus fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in IMPACT using a matching-adjusted indirect comparison (MAIC). A systematic literature review identified two studies (ETHOS [NCT02465567]; IMPACT [NCT02164513]) of ≥52 weeks reporting ACM as an efficacy endpoint in patients receiving triple therapy. As ETHOS and IMPACT lack a common comparator, an unanchored MAIC compared ACM between licensed doses of BGF (320/18/9.6 μg) from ETHOS and FF/UMEC/VI (100/62.5/25 μg) from IMPACT in patients with moderate-to-very severe COPD. Using on- and off-treatment data from the final retrieved datasets of the intention-to-treat populations, BGF data were adjusted according to aggregate FF/UMEC/VI data using 11 baseline covariates; a supplementary unadjusted indirect treatment comparison was also conducted. P-values for these post-hoc analyses are not adjusted for Type I error. ACM over 52 weeks was statistically significantly reduced by 39% for BGF versus FF/UMEC/VI in the MAIC (hazard ratio [HR] [95% CI]: 0.61 [0.38, 0.95], p = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], p = 0.019). In this MAIC, which adjusted for population heterogeneity between ETHOS and IMPACT, ACM was significantly reduced with BGF versus FF/UMEC/VI in patients with moderate-to-very severe COPD. Chronic obstructive pulmonary disease (known as COPD) is a leading cause of death worldwide, being responsible for over 3 million deaths in 2019. People living with COPD are more likely to die. Importantly, a sudden worsening of COPD symptoms (known as an exacerbation) is associated with a higher chance of death from heart-related and breathing-related problems. Therefore, reducing risk of death is an important treatment goal for COPD. Of the three medications approved for treating COPD that combine three drugs in a single-inhaler device, there are two—referred to generically as budesonide/glycopyrrolate/formoterol fumarate (BGF) and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)—that can reduce the risk of death in people living with COPD compared with treatments that combine two drugs. However, no studies have directly compared the risk of death in people living with COPD treated with these medicines. We compared the risk of death in people living with moderate-to-very severe COPD who received either BGF during a clinical trial called ETHOS or FF/UMEC/VI during a clinical trial called IMPACT. To make this comparison, we used a method called "matching-adjusted indirect comparison", which used specific features (such as sex, breathing difficulty, and whether they were current smokers) to match patients from the two studies to ensure similar groups were examined. Our analysis showed a 39% decrease in the chance of death in patients who received BGF compared with patients who received FF/UMEC/VI. This finding may be important for doctors to improve patient health and reduce the risk of death in people living with COPD. [ABSTRACT FROM AUTHOR]

Background: Although adherence to inhaled medication is critically important for treatment efficiency, around half of patients taking these drugs are non-adherent or make critical errors when using their delivery device. Segmental hair analysis might be a valuable tool for therapeutic monitoring because hair concentrations reflect exposure from month to month. The objective of the present proof-of-concept study was to establish the feasibility of segmental hair analysis of inhaled budesonide and formoterol in asthma patients.Methods: We conducted a prospective, open-label, interventional study of adult patients being treated with budesonide/formoterol for controlled, moderate-to-severe asthma (CorticHair, NCT03691961). Asthma control, lung function, and medication adherence were recorded. Hair samples were taken 4 months after enrolment and cut into four 1 cm segments.Results: Samples were available from 21 patients (20 women; median age: 53; median budesonide dose: 600 μg/d). Budesonide and formoterol were detected in samples from 18 to 13 patients, respectively. The median hair concentrations were 6.25 pg/mg for budesonide and 0.9 pg/mg for formoterol. The intrapatient coefficient of variation between hair segments was 21% for budesonide and 40% for formoterol. Pearson’s coefficients for the correlations between the hair concentration and the self-reported drug dose and the prescribed drug dose were respectively 0.42 (p = 0.08) and 0.29 (p = 0.25) for budesonide and 0.24 (p = 0.44) and 0.17 (p = 0.57) for formoterol.Conclusion: Segmental hair analysis of inhaled medications was feasible, with low intrapatient variability. This innovative, non-invasive means of assessing monthly drug exposure might help physicians to personalize drug regimens for patients with difficult-to-treat asthma.

ABSTRACT. An update to the Global Initiative for Asthma (GINA) report released this May includes new scientific information on bronchial asthma. This overview presents the main changes in the latest version of the report. The key changes include the clarification of terminology regarding drugs for the treatment of asthma, including the meaning of the terms “maintenance treatment” and “controller medication”; inclusion of a combination of an inhaled corticosteroid and a short-acting β-agonist in the asthma treatment algorithm for adults and adolescents; update of the treatment algorithm for children aged 6-11 years and clarification of the treatment algorithm for children aged ≤5 years; addition of environmental considerations for inhaler choice; updated advice on definition of mild asthma and guidance on managing severe asthma; new practical guide to management of asthma exacerbations; addition of a small section on the use of imaging studies in the asthma diagnosis. GINA calls on international respiratory societies to collaborate with colleagues, patients and medical institutions to promote the development and implementation of effective asthma management programs in all resource countries. Providing access to effective and well-studied drugs, as well as treatment of asthma according to modern step-by-step GINA algorithms, can reduce the burden of asthma on the planet.

AIM: To evaluate the efficacy and safety of complex basic therapy for chronic heart failure (CHF) of ischemic origin in combination with chronic obstructive pulmonary disease (COPD) with the inclusion of prolonged bronchodilators. MATERIALS AND METHODS: The study included 67 patients (50 men and 17 women) with CHF IIIII functional class (FC) with left ventricular ejection fraction (LVEF) of 45% in combination with moderate-to-severe COPD (GOLD). The patients were divided into three groups: group 1 (n=30) received formoterol as part of therapy, group 2 (n=19) received aclidinium, and group 3 (n=18) received a fixed combination of aclidinum and formoterol. The basic therapy for CHF included nebivolol, losartan, eplerenone, diuretics, low-dose glucocorticosteroids, nitrates, and cardiac glycosides (if necessary). The clinical condition of patients, intracardiac hemodynamics, was indicated using echocardiography, a 6-min walking test (6MWT), bifunctional 24-h monitoring of blood pressure and heart rate, and spirometry. Quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire, St. Georges Respiratory Questionnaire, and Modified Medical Research Council dyspnea scale. RESULTS: After 6 months of therapy, the clinical and instrumental parameters and quality of life improved in all groups. At the end of the observation period, the average FC of CHF and dyspnea severity decreased by 17.5, 18.2, 20.1 20.5, 24.2, and 28.1%, respectively. The increase in exercise tolerance was 22.1, 22.6, and 29.2%. An improvement in intracardiac hemodynamics was noted. The LVEF increased by 17.1, 20.5, and 24.6%, and the myocardial mass index decreased by 8.7, 14.2, and 17.4%. The total peripheral vascular resistance, degree of pulmonary hypertension, and duration and frequency of painless myocardial ischemia significantly decreased. The best results were obtained in group 3 using nebivolol, reninangiotensinaldosterone system antagonists, and a combination of long-acting bronchodilators. Therapy was well tolerated by all study groups, with no serious adverse side effects. CONCLUSION: The inclusion of nebivolol and losartan in basic therapy, while taking long-acting bronchodilators, improves the clinical and functional states of patients and quality of life, and slows down disease progression. When used in a fixed combination, the use of aclidinium and formoterol improves spirometry to a greater extent.

Tobacco smoking directly affects the airway, where it triggers a very strong local inflammatory response. To determine the predictors of improvement or worsening of asthma control in asthmatic smokers. Observational, prospective, multicenter, single cohort study, carried out in the outpatient pulmonology departments with a follow-up period of 6 months. The treatment was adjusted according to the indications of standard clinical practice. 196 patients were included, with a mean age of 54.64 years.39% of the patients were active smokers. Interpreting an Asthma Control Questionnaire (ACQ) score of ≤ 0.75 as asthma control, this was achieved in 30.2% of the cases. Patients with greater adherence were more likely to improve their asthma symptoms (p < 0.05), defined as a decrease in ACQ of 0.5 points or more at the final visit, while taking concomitant medication was a negative risk factor for improvement (p < 0.001). An eosinophil value >300 was a predictor for achieving control (p < 0.01). Patients treated with fluticasone propionate/formoterol versus those receiving budesonide/formoterol or beclomethasone/formoterol had a lower ACQ score (p < 0.01 and p < 0.01, respectively). Asthmatic patients with active tobacco exposure and a higher number of anti-asthma medications are more likely to have poorer control. Correct adherence to treatment is the main intervention to be performed to achieve the control. An eosinophil count greater than 300 was the main predictor for achieving control. Fluticasone propionate/formoterol FP/FORM was associated with a greater likelihood of improving ACQ score. [ABSTRACT FROM AUTHOR]

Purpose: To study the effectiveness of formoterol fumarate tablets when used in combination with interventional bronchoscopy for central airway tumor. Methods: A total of 154 central airway tumor patients on admission in Second Affiliated Hospital of Zunyi Medical University, Zunyi, China (August 2020 - December 2022) were assigned to benign group (BG, n = 70) and malignant group (MG, n = 84), based on the nature of tumor lesion. The patients were administered formoterol fumarate tablets as well as interventional bronchoscopy. Clinical efficacy, lung function indices such as forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio, blood gas indices (pH, partial pressure of oxygen (PaO2) and partial pressure of carbon dioxide (PaCO2)), scores on shortness of breath, and survival rate, were determined and compared between the two groups. Results: The overall effectiveness in BG (97.14 %) was significantly higher than that in MG (84.52 %). There were higher post-treatment values of FEV1, FVC and FEV1/FVC; higher values of pH and PaO2, lower PaCO2, and lower scores on shortness of breath in BG and MG, relative to pre-treatment levels (p < 0.05). Follow-up showed no recurrence in patients with benign tumor, and clinical efficacy was satisfactory. The 2-year survival rate of patients with malignant tumor was 51.19 %. Conclusion: The combination of formoterol fumarate tablets and interventional bronchoscopy produces significant curative effect on benign and malignant tumor in central airway. It improves lung function, blood gas indices and survival rate, and mitigates shortness of breath. Therefore, this treatment strategy has a high potential for use in clinical practice. [ABSTRACT FROM AUTHOR]

Specifically, 69.8%, 67.7%, and 69.0% of patients prescribed adjustable-dose BUD/FORM maintenance, fixed-dose BUD/FORM maintenance, and intermittent BUD/FORM, respectively, did not claim SABA during follow-up (Table 1). Adjustable-dose BUD/FORM maintenance: physician-indicated temporary titration of BUD/FORM maintenance therapy to a maximum daily dose in the event of deteriorating asthma control plus an as-needed SABA reliever. [Extracted from the article]

The adrenergic beta-2 agonists formoterol and salbutamol are used for the treatment of asthma and COPD but are also misused in sports competitions. Therefore, they are included in WADA regulations. Both drugs are mainly excreted in urine after administration via inhalation. A four-armed, double-blind cross-over clinical trial was conducted involving endurance-trained participants (12 females and 12 males). Inhalation dosages of 36 μg formoterol, 1200 μg salbutamol, a combination of both, or a placebo were administered before exercise. Serum and urine were collected after exercise and 3 and 24 h after administration. Here, we show the successful quantitation of formoterol, salbutamol, and its phase II metabolite salbutamol-4′-O-sulfate in all urine and serum samples using ultra-high performance liquid chromatography–tandem mass spectrometry. In the serum analysis, results of up to 14.2 pg/mL formoterol, 10.0 ng/mL salbutamol, and 21.4 ng/mL salbutamol-4′-O-sulfate (calculated as salbutamol equivalent) were found. In urine, maximum concentrations (after deglucuronidation) were 17.2 ng/mL formoterol, 948.5 ng/mL salbutamol, and 2738.5 ng/mL salbutamol-4′-O-sulfate. Sex-specific differences in serum concentrations as well as in urinary excretion were observed. The results pronounce the importance of the implementation and elucidation of phase II metabolites to quantitation methods in antidoping. [ABSTRACT FROM AUTHOR]

Today, respiratory diseases are one of the most common problems in animals and humans. One of the methods to control respiratory diseases is the use of bronchodilator drugs such as salbutamol and formoterol. The aim of the present study was to compare the effect of salbutamol and formoterol on electrocardiogram, blood pressure, potassium and glucose changes in dogs. For this purpose, fifteen male adult dogs were used. After a health check, animals were divided into three groups: control, salbutamol and formoterol. Treatment groups were inhaled daily with a single dose of one puff twice daily (morning and night) for 7 days. Finally, 4 hours after the last administration, electrocardiogram, blood pressure and arterial oxygen saturation were measured. Then, blood samples were taken from cephalic vein (5 ml) to measure blood potassium and glucose levels. Results showed that Administration of salbutamol caused a significant decrease in systolic and diastolic blood pressure, while formoterol caused a significant increase in blood pressure. Salbutamol and formoterol significantly increased heart rate. Blood potassium level as well as RR interval in electrocardiogram were significantly reduced in the groups treated with both drugs compared with the control group. The group treated with salbutamol showed a significant increase in blood glucose compared with the control group. According to the results, administration of salbutamol and formoterol reduced potassium unlike glucose. Salbutamol also was more effective than formotrol on cardiac effects and arrhythmogenic potential. Therefore, the administration of salbutamol and formoterol in cardiac or diabetic patients should be treated with caution and control. [ABSTRACT FROM AUTHOR]

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The article discusses the use of inhaled corticosteroid (ICS)-formoterol maintenance and reliever therapy (MART) in the treatment of moderate to severe asthma. The authors conducted a survey of individual ICS-formoterol prescriptions from selected pharmacies in New Zealand and found that the co-prescription of short-acting beta-agonists (SABA) with ICS-formoterol MART was low, occurring in only 16% of scripts. This suggests that patients can be appropriately reassured by their prescribing practitioners and that the transition to ICS-formoterol MART can be achieved with lesser degrees of SABA co-prescribing. The study also observed early adoption of ICS-formoterol reliever alone regimen with minimal SABA co-prescribing. [Extracted from the article]

Formoterol, a β2-adrenergic receptor (β2AR) agonist, shows promise in various diseases, but its effectiveness in Parkinson’s disease (PD) is debated, with unclear regulation of mitochondrial homeostasis. This study employed a cell model featuring mitochondrial ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) variants associated with familial parkinsonism, demonstrating mitochondrial dysfunction and dynamic imbalance, exploring the therapeutic effects and underlying mechanisms of formoterol. Results revealed that 24-h formoterol treatment enhanced cell proliferation, viability, and neuroprotection against oxidative stress. Mitochondrial function, encompassing DNA copy number, repatriation, and complex III-linked respiration, was comprehensively restored, along with the dynamic rebalance of fusion/fission events. Formoterol reduced extensive hypertubulation, in contrast to mitophagy, by significantly upregulating protein Drp-1, in contrast to fusion protein Mfn2, mitophagy-related protein Parkin. The upstream mechanism involved the restoration of ERK signaling and the inhibition of Akt overactivity, contingent on the activation of β2-adrenergic receptors. Formoterol additionally aided in segregating healthy mitochondria for distribution and transport, therefore normalizing mitochondrial arrangement in mutant cells. This study provides preliminary evidence that formoterol offers neuroprotection, acting as a mitochondrial dynamic balance regulator, making it a promising therapeutic candidate for PD.