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Introduction: Although some factors associated with asthma symptom deterioration and risk of exacerbation have been identified, these are not yet fully characterised. We conducted a clinical modelling and simulation study to understand baseline factors affecting symptom control, reliever use and exacerbation risk in patients with moderate–severe asthma during follow-up on regularly dosed inhaled corticosteroid (ICS) monotherapy, or ICS/long-acting beta2-agonist (LABA) combination therapy. Methods: Individual patient data from randomised clinical trials (undertaken between 2001 and 2019) were used to model the time course of symptoms (n = 7593), patterns of reliever medication use (n = 3768) and time-to-first exacerbation (n = 6763), considering patient-specific and extrinsic factors, including treatment. Model validation used standard graphical and statistical criteria. Change in symptom control scores (Asthma Control Questionnaire 5 [ACQ-5]), reduction in reliever use and annualised exacerbation rate were then simulated in patient cohorts with different baseline characteristics and treatment settings. Results: Being a smoker, having higher baseline ACQ-5 and body mass index affected symptom control scores, reliever use and exacerbation risk (p < 0.01). In addition, low forced expiratory volume in 1 s percent predicted, female sex, season and previous exacerbations were found to contribute to a further increase in exacerbation risk (p < 0.01), whereas long asthma history was associated with more frequent reliever use (p < 0.01). These effects were independent from the underlying maintenance therapy. In different scenarios, fluticasone furoate (FF)/vilanterol was associated with greater reductions in reliever use and exacerbation rates compared with FF or fluticasone propionate (FP) alone or budesonide/formoterol, independently from other factors (p < 0.01). Conclusions: This study provided further insight into the effects of individual baseline characteristics on treatment response and highlighted significant differences in the performance of ICS/LABA combination therapy on symptom control, reliever use and exacerbation risk. These factors should be incorporated into clinical practice as the basis for tailored management of patients with moderate–severe asthma. Plain Language Summary: In this study we quantified how individual baseline patient characteristics at the start of treatment influence the response to regular maintenance medication. Specifically, using computer modelling and simulations based on data from individual patients enrolled into clinical trials in moderate–severe asthma, we predicted how much reliever inhaler they need, how well they rate their asthma control, and how likely an asthma attack (exacerbation) is to occur within the next 12 months. Simulation scenarios were then implemented to evaluate opportunities to improve and personalise real-life management of patients in clinical practice. Considering symptom control level, reliever use and other patient-specific factors at the start of treatment, we assessed how well maintenance therapy with inhaled corticosteroids/bronchodilators contributes to symptom improvement and/or reduction in the risk of asthma attacks. These scenarios show that current smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. Moreover, this was linked to a higher risk of having an asthma attack and worse symptom control. This pattern appears to compensate in most cases for the effect of the same baseline factors on symptom control. Switching patients who are not responding well to initial treatment with the inhaled corticosteroid, fluticasone propionate, to fluticasone furoate/vilanterol resulted in a significantly greater reduction in reliever inhaler use and risk of asthma attack, compared with those switched to budesonide/formoterol. These findings highlight the importance of tailored choices for optimal management of patients with moderate–severe asthma. [ABSTRACT FROM AUTHOR]

Introduction: Once-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. Methods: 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. Results: 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. Conclusion: Once daily VI/FF pMDI was non-inferior to twice daily FOR/FP pMDI in patients with persistent asthma. [ABSTRACT FROM AUTHOR]

Purpose Umeclidinium plus vilanterol (UMEC/VI) is an inhaled long-acting muscarinic antagonist/long-acting beta2-agonist (LAMA/LABA), recently approved as once-daily maintenance therapy for chronic obstructive pulmonary disease (COPD). This meta-analysis aims to assess the efficacy and safety of UMEC/VI compared with fluticasone propionate plus salmeterol (FP/SAL). Methods A systematic search was conducted by a trained medical research librarian across MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese Biomedical Literature Database (CBM) for randomized controlled trials comparing UMEC/VI with FP/SAL in COPD patients. Two reviewers independently assessed the risk of bias and extracted data. The primary outcome was 0–24 h weighted mean (wm) forced expiratory volume in the first second (FEV1), trough FEV1. The secondary outcomes were other lung functions, symptoms, quality of life, and safety. Results Three studies with 2119 patients were included in the meta-analysis. UMEC/VI showed improvement in 0–24 h wm FEV1 (mean difference (MD) 0.08 L, 95% confidence interval (CI) 0.06 to 0.10, P  < 0.01, moderate quality) and trough FEV1 (MD 0.09 L, 95% CI 0.07 to 0.11, P  < 0.01, moderate quality) in comparison with FP/SAL. UMEC/VI statistically significantly improved all other lung functions compared with FP/SAL. However, there were no significant differences between UMEC/VI and FP/SAL in rescue-medication use, symptomatic endpoints, and health outcomes. UMEC/VI also demonstrated fewer drug-related adverse effects (risk ratio 0.47, 95% CI 0.27 to 0.82, P  = 0.01, low quality). Conclusions UMEC/VI, when compared with FP/SAL, demonstrated significant improvements in lung functions with fewer drug-related adverse effects. However, the conclusion was limited by the scarcity of studies and long-term trials. Key message What is already known on this topic Recent trials have demonstrated that umeclidinium/vilanterol boasts a favorable safety profile and delivers notable and sustained enhancements in lung function. However, there has been no definitive conclusion regarding the comparative efficacy of UMEC/VI versus FP/SAL. What this study adds This research not only evaluates the efficacy of UMEC/VI compared with FP/SAL on lung functions but also delves into its impact on symptomatic endpoints, health outcomes, and safety measures. How this study might affect research, practice or policy Given the potential advantages offered by UMEC/VI, we advocate for its utilization in COPD treatment and anticipate that forthcoming long-term trials will place emphasis on mortality and cardiovascular outcomes. Registration number CRD42021249409 [ABSTRACT FROM AUTHOR]

Salmeterol xinafoate (SAM) and fluticasone propionate (FLU) are one of the drug combinations used together in the treatment of lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). The aim of this study is to investigate the usability of novel dual molecular imprinted nanoparticles (poly(2-hydroxyethyl methacrylate-N-methacryloyl-(L)-alanine-N-methacryloyl-(L)-histidine) [p(HEMA-MAAL-MAH)], abbr. DMIPNPs) as a controlled drug release systems. In this study, SAM and FLU drugs were chosen as model drugs because they are used in the treatment of these diseases. DMIPNPs were prepared by surfactant-free emulsion polymerization method and characterized by scanning electron microscopy (SEM) and fourier transform infrared spectrometer (FTIR). In in vitro drug release experiments, drug release conditions were optimized. SAM and FLU release from DMIPNPs experiments were also performed in the simulated lung fluid (SLF). The amount of released SAM and FLU were found as 4.79 and 5.68 mg/g in the SLF medium at the end of 48 h, respectively. The release kinetics of SAM and FLU from DMIPNPs were calculated in the SLF medium. The release of SAM and FLU was determined to be compatible with the Higuchi release models. According to these results, these DMIPNPs, dual-template molecular imprinted nanoparticles with dual monomers, are promising materials that can be used in the controlled release of two different drugs. [ABSTRACT FROM AUTHOR]

(1) Background: Sleep-disordered breathing and asthma are often interrelated. Children and adults with asthma are more susceptible to sleep apnea. Inhaled corticosteroids effectively reduce inflammation and prevent structural changes in the airways. Objective: to explore the existing literature to determine whether inhaled corticosteroids play a role in sleep-disordered breathing in patients with asthma. (2) Methods: We conducted a thorough search of the PubMed, Scopus, and Web of Science databases for English-language articles published up to 12 May 2024. We utilized the ROBINS-E tool to assess the risk of bias. (4) Conclusions: 136 articles were discerned upon conducting the literature search. A total of 13 articles underwent exhaustive full-text scrutiny, resulting in 6 being considered non-relevant. The remaining seven articles, assessed for eligibility, were incorporated into the final analysis. Five studies were identified in adults and two in children. In adult patients, inhaled corticosteroids, especially at high doses, appear to increase the risk of sleep apnea in a dose-dependent manner. Moreover, the properties of inhaled corticosteroids, such as particle size, may impact the risk of developing sleep apnea. In children, the severity of asthma is a key factor affecting the prevalence of sleep apnea, whereas inhaled corticosteroids appear to be a less significant risk factor compared to adults. All of the studies reviewed were classified as having a high risk of bias or some concerns regarding bias. Each study revealed at least one type of bias that raised notable concerns. This research highlights a complex interaction between the use of inhaled corticosteroids, the severity of asthma, and the onset of sleep apnea. Additional research is necessary to investigate these relationships further.

AIM: To investigate the effect of a new type of rhinodacryocystostomy combined with fluticasone propionate on patients with chronic dacryocystitis.METHODS: A total of 100 patients(100 eyes)with chronic dacryocystitis who admitted to our hospital between January 2021 and December 2022 were enrolled in the prospective study. The patients in the study were divided into a control group(n=50)and an observation group(n=50)based on their admission order and number. Patients in the control group were treated with novel rhinodacryocystostomy, while patients in the observation group were treated with a new type of rhinodacryocystostomy combined with fluticasone propionate. The preoperative and postoperative best corrected visual acuity(BCVA), quality of life score, and recurrence of chronic dacryocystitis were compared between the two groups of patients.RESULTS: All patients completed the postoperative 6 mo follow-up, and the total effective rate of patients in the observation group was better than that of patients in the control group(98% vs 84%, P=0.001). There was no significant difference in preoperative and postoperative BCVA between the two groups(P>0.05). Preoperatively, there was no significant difference in the quality of life scores between the two groups of patients(P>0.05); At 6 mo postoperatively, the quality of life scores of patients in the control group, including physical function, psychological function, social function, and material life status, were lower than those in the observation group(all P

The deposition, residence time, and dissolution profile of nasal suspensions containing corticosteroids play a key role in their in vivo efficacy after administration. However, the conventional methods available to characterize nasal products appear to be unsuitable to exhaustively cover these aspects. The work aims to investigate technological aspects of Ryaltris (mometasone furoate and olopatadine hydrochloride nasal spray) compared to other commercial anti-allergic nasal products, namely, Dymista (azelastine hydrochloride and fluticasone propionate), Nasonex (mometasone furoate), and Avamys (fluticasone furoate). Innovative characterization methods were combined with more traditional approaches to investigate the anti-allergic nasal sprays. These methods applied together allowed to differentiate between the different products and provided a clear picture of the nasal product behavior in terms of drug dissolution and deposition. In particular, the dissolution tests were performed exploiting the Respicell® apparatus, an innovative technique that allows for the investigation of inhalation products. Then, formulation viscosities were considered along with a formulation flow test on an inclined plane. Finally, the intranasal deposition profile of the commercial formulations was determined using a silicon nasal cast. The results highlight in vitro significant differences in terms of viscosity as well as dissolution rate of the nasal products, with Ryaltris showing a higher viscosity and lower flow compared to other products, which, along with a corticosteroid faster dissolution rate than Dymista, suggest a potential advantage in terms of clinical behavior. [ABSTRACT FROM AUTHOR]

Background: Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients. Objective: This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use. Methods: Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines. Results: In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients. Conclusion: These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma. [ABSTRACT FROM AUTHOR]

Introduction: 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). Methods: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months 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 phase III/IV clinical studies. Results: 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 3 months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24 h 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). Conclusions: 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. Plain Language Summary: In this study we looked at how different factors affect the response to asthma treatment in people with moderate to severe asthma who are taking regular medication. Specifically, we wanted to quantify how much asthma duration, differences in the degree of symptom control and lung function, as well as smoking habit, body weight, and sex influence how well someone responds to regular maintenance therapy. Using computer simulations based on models obtained from data in a large patient population with moderate–severe asthma, we explored scenarios that reflect real-life management of patients undergoing treatment with inhaled corticosteroids alone or in combination with long-acting beta agonists over a 12-month period. We looked at how much reliever inhaler they use, how well they rate their asthma control, and how often they have asthma attacks. By considering these results together, we evaluated how well the treatments work on ongoing symptoms and/or reduce the risk of future asthma attacks. Our simulations showed that smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. This was linked to a higher risk of having asthma attacks and worse symptom control. Switching those patients who do not respond well to their initial treatment with corticosteroid to combination therapy reduced how much reliever inhaler they need. Also, the effects of fluticasone propionate/salmeterol combination therapy were greater than budesonide/formoterol. In conclusion, our study found that certain patient characteristics can predict how well someone responds to asthma treatment. [ABSTRACT FROM AUTHOR]

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

The incidence of allergic rhinitis (AR) in Asia and the world is steadily rising. Patients experience incomplete symptom relief despite existing treatment options, which warrants the need for new therapeutic regimes. Azelastine hydrochloride/fluticasone propionate (MP-AzeFlu), a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate has been indicated in the treatment of AR. The current review discusses the effects of MP-AzeFlu versus conventional therapies in achieving superior clinical improvement with a very rapid onset of action (5 minutes). The superiority of MP-AzeFlu in offering complete symptom control with sustained relief in patients with AR compared to the existing therapeutic options is also discussed. MP-AzeFlu has been shown to improve the quality of life for patients with AR, thereby enhancing patient adherence to therapy and establishing its preference for the treatment of AR. Currently, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines recommend the use of a combination of intranasal corticosteroids and intranasal antihistamines as first-line treatment in patients with persistent AR with visual analog scores ≥ 5 or when prior treatment with single agents has been ineffective. Widely published data on the efficacy and safety of its prolonged use in adults and children have validated that effective treatment of AR can be achieved with MP-AzeFlu. [ABSTRACT FROM AUTHOR]

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

Background: Many patients with allergic rhinitis (AR) have moderate-to-severe persistent AR. Meda Pharma's AzeFlu (MP-AzeFlu®) is an intranasal AR treatment comprising a novel formulation of azelastine hydrochloride and fluticasone propionate in a single device. Methods: This prospective observational study of 214 adults and adolescents in Austria with moderate-to-severe persistent AR assessed the effectiveness of MP-AzeFlu (one spray/nostril twice daily; daily doses: azelastine hydrochloride 548 μg; and fluticasone propionate 200 μg) for AR control in clinical practice using the visual analog scale. Symptom severity was reported on days 0, 1, 3, 7, 14, 21, 28, 35, and 42. Patient demographics, AR phenotype, allergen sensitization, symptomatology, AR treatments in the previous year, and the reason for the MP-AzeFlu prescription were recorded. Results: MP-AzeFlu treatment was associated with a rapid and statistically significant reduction in the visual analog scale score from baseline to each timepoint measured, including day 1 (all p < 0.0001). Mean (standard deviation) visual analog scale score was 53.5 mm (26.3) at baseline, 25.3 mm (21.0) on day 28, and 19.6 mm (17.4) on day 42, a mean overall reduction from baseline of 41.4 (23.9) mm for completers. Results were consistent irrespective of patient age, gender, severity, or traditional AR phenotype. Prior to MP-AzeFlu prescription, congestion was considered the most bothersome symptom. The majority of patients reported using at least two AR therapies in the past year, including oral antihistamines, intranasal corticosteroids, and intranasal antihistamines. Conclusions: Many patients in Austria live with uncontrolled persistent AR despite treatment. MP-AzeFlu provides effective and rapid control of persistent AR in a real-world Austrian setting. [ABSTRACT FROM AUTHOR]

This article discusses the use of sputum periostin as a biomarker for the treatment of severe asthma with anti-T2 biologics. Periostin is a protein secreted by airway epithelial cells and is regulated by IL-13. Previous studies have shown that serum periostin levels are elevated in patients with airway eosinophilia, but its usefulness as a biomarker for anti-IL-13 therapies is uncertain. The authors of this study found that sputum periostin levels correlated with sputum IL-13 and eosinophil levels, and treatment with benralizumab and dupilumab significantly reduced sputum periostin. However, baseline sputum periostin levels were not predictive of treatment response. The authors suggest that sputum periostin may be a useful marker for selecting patients for anti-IL-13 therapies, but further research is needed. [Extracted from the article]

Abstract Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines—fluticasone propionate (FP) and salmeterol xinafoate (SAL)—for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency– > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines—fluticasone propionate (FP) and salmeterol xinafoate (SAL)—for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency– > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma. [ABSTRACT FROM AUTHOR]

The introduction of inhaled corticosteroids (ICSs) changed over a few decades the treatment focus of mild-to-moderate asthma from bronchodilation to reduction in inflammation. This was achieved by inhaling a suitable corticosteroid (CS), giving a high, protracted airway concentration at a low total dose, thereby better combining efficacy and tolerance than oral therapy. Successful trials with the potent, lipophilic "skin" CS beclomethasone dipropionate (BDP) paved the way, suggesting that ICSs require a very low water solubility, prolonging their intraluminal dissolution within airways. The subsequent ICS development, with resulting clinical landmarks, is exemplified here with budesonide (BUD), showing that a similar efficacy/safety relationship is achievable by partly alternative mechanisms. BUD is much less lipophilic, giving it a 100-fold higher water solubility than BDP and later developed ICSs, leading to its more rapid intraluminal dissolution and faster airway and systemic uptake rates. In airway tissue, a BUD fraction is reversibly esterified to intracellular fatty acids, a lipophilic conjugate, which prolongs airway efficacy. Another mechanism is that the rapidly absorbed bulk fraction, via short plasma peaks, adds anti-inflammatory activity at the blood and bone marrow levels. Importantly, these plasma peaks are too short to provoke systemic adverse actions. Controlled clinical trials with BUD changed the use of ICS from a last resort to first-line treatment. Starting ICS treatment immediately after diagnosis ("early intervention") became a landmark for BUD. An established dose response made BUD suitable for the treatment of patients with all degrees of asthma severity. With the development of the budesonide/formoterol combination inhaler (BUD/FORM), BUD contributed to the widely used BUD/FORM maintenance and reliever therapy (MART). Recent studies demonstrated the value of BUD/FORM as a generally recommended as-needed therapy for asthma ("anti-inflammatory reliever", AIR). These abovementioned qualities have all influenced international asthma management and treatment guidelines. [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.

Abstract: Azelastine HCl and Fluticasone Propionate nasal spray drug product is commonly used to treat moderate to severe allergic rhinitis and rhino-conjunctivitis. To date, a simultaneous HPLC method for active sub-stances and impurities of this product has not been reported. Acetonitrile and buffer (Octane-1-Sulfonic Acid Sodium Salt and Potassium Dihydrogen Phosphate) were used as a mobile phase. The separation was achieved using Phenomenex Phenyl-hexyl (150 cm × 4.6 mm, 5 µm) column at 1 mL/min flow rate in gradient elution mode. The chromatograms were monitored at 240 nm. The validation parameters such as linearity, limit of quantification, limit of detection, accuracy, precision, robustness and specificity were investigated for the nasal spray. Overall, this study provides valuable insights into the development and validation of an efficient analytical method for assessing the quality and stability of a combination of Azelastine HCl and Fluticasone Propionate nasal spray.

Abstract Purpose This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children. Methods Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran’s Q test and I 2 statistics, followed by sensitivity analysis and publication bias evaluation. Results Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group. Conclusion Mon + Flu is effective and safe for the treatment of CVA in children.

We estimated the inhaled and deposited dose in humans using the International Commission on Radiological Protection (ICRP) and multiple-path particle dosimetry (MPPD) models following exposure to humidifier disinfectant containing polyhexamethylene guanidine (PHMG). The disinfectant has caused at least 1,810 deaths, with an odds ratio of lung injury of 47.3 (95% confidence interval: 6.1–369.7), because of its application in Korea. In this study, the Oxy product, which is regarded as the causative agent of most lung diseases, was sprayed into a cleanroom at normal (6.5 ppm in solution) and worst case (65 ppm in solution) dilutions; the airborne aerosol was monitored with direct reading instruments. Areas of deposition were divided into the head airway, tracheobronchial, and alveolar regions. Four dose scenarios were considered in this study: adults and children in both daily average and sleep conditions. Most PHMG aerosols were smaller than PM1 (96%). Number-based concentration analysis showed that <100 nm nanoparticles comprised 81% and 69% of the aerosol when the 6.5 and 65 ppm solutions were used, respectively. In all scenarios, the number-based deposited dose increased in the order of alveolar, tracheobronchial, and head airway regions; the mass-based deposited dose increased in the order of the head airway, alveolar, and tracheobronchial regions. The deposited dose per unit body weight was higher in children than in adults in terms of both number- and mass-based concentrations. When the humidifier was sprayed, the highest number-based concentration was found at a particle size of 15.4 nm; the highest deposition fraction or dose by PM1 was observed in the pulmonary and head airways in both models. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the potential of LPS (10–300 µg/rat) administered intratracheally (i.t.) to induce reproducible features of acute lung injury (ALI) and compared the pharmacological efficacy of anti-inflammatory glucocorticoids and antifibrotic drugs to reduce the disease. Additionally, we studied the time-dependent progression of ALI in this LPS rat model. Methods: We conducted (1) dose effect studies of LPS administered i.t. at 10, 30, 100, and 300 μg/rat on ALI at 4 h timepoint; (2) pharmacological interventions using i.t. fluticasone (100 and 300 μg/rat), i.t. pirfenidone (4,000 μg/rat), and peroral dexamethasone (1 mg/kg) at 4 h timepoint; (3) kinetic studies at 0, 2, 4, 6, 8, 10, and 24 h post-LPS challenge. Phenotype or pharmacological efficacy was assessed using predetermined ALI features such as pulmonary inflammation, edema, and inflammatory mediators. Results: All LPS doses induced a similar increase of inflammation, edema, and inflammatory mediators, e.g., IL6, IL1β, TNFα, and CINC-1. In pharmacological intervention studies, we showed fluticasone and dexamethasone ameliorated ALI by inhibiting inflammation (>60–80%), edema (>70–100%), and the increase of cytokines IL6, IL1β, and TNFα (≥70–90%). We also noticed some inhibition of CINC-1 (25–35%) and TIMP1 (57%) increase with fluticasone and dexamethasone. Conversely, pirfenidone failed to inhibit inflammation, edema, and mediators of inflammation. Last, in ALI kinetic studies, we observed progressive pulmonary inflammation and TIMP1 levels, which peaked at 6 h and remained elevated up to 24 h. Progressive pulmonary edema started between 2 and 4 h and was sustained at later timepoints. On average, levels of IL6 (peak at 6–8 h), IL1β (peak at 2–10 h), TNFα (peak at 2 h), CINC-1 (peak at 2–6 h), and TGFβ1 (peak at 8 h) were elevated between 2 and 10 h and declined toward 24 h post-LPS challenge. Conclusion: Our data show that 10 μg/rat LPS achieved a robust, profound, and reproducible experimental ALI phenotype. Glucocorticoids ameliorated key ALI features at the 4-h timepoint, but the antifibrotic pirfenidone failed. Progressive inflammation and sustained pulmonary edema were present up to 24 h, whereas levels of inflammatory mediators were dynamic during ALI progression. This study's data might be helpful in designing appropriate experiments to test the potential of new therapeutics to cure ALI. [ABSTRACT FROM AUTHOR]

• This systematic review and meta-analysis included 12 RCTs involving 9859 children with asthma to compare the efficacy and safety of two treatment regimens for step-up treatment. • FSC was more effective than FP in preventing asthma exacerbations and improving lung function indicators, especially when the dose of fluticasone was the same or the treatment duration exceeded 12 weeks. • The addition of salmeterol did not increase the risk of drug-related adverse events and other adverse events. • Both FSC and FP monotherapy are options for children with asthma who require step-up therapy, with FSC treatment being more beneficial for lowering asthma exacerbations and improving lung function, while FP monotherapy is suitable for patients with contraindications or intolerance to LABA. Asthma is a chronic respiratory disease that affects millions of children worldwide and can impair their quality of life and development. Inhaled glucocorticoids are the mainstay of asthma treatment, but some children require step-up therapy with additional drugs to achieve symptom control. Fluticasone propionate and salmeterol (FSC) has been shown to reduce asthma exacerbations and improve lung function in adults. However, the evidence for its efficacy and safety in children is limited. This study aims to provide a comprehensive basis for treatment selection by summarizing existing clinical randomized controlled trials (RCTs) on the efficacy of FSC compared to fluticasone propionate (FP) monotherapy in children with asthma who require step-up treatment. Five online databases and three clinical trial registration platforms were systematically searched. The effect size and corresponding 95% confidence interval (CI) were calculated based on the heterogeneity among the included studies. Twelve RCTs were identified and a total of 9, 859 patients were involved. The results of the meta-analysis revealed that the use of FSC was associated with a greater reduction in the incidence of asthma exacerbations than FP alone when the dose of FP was the same or when the duration of treatment exceeded 12 weeks. In addition, FSC resulted in a greater proportion of time with asthma-free and without the use of albuterol compared to FP alone when the duration of treatment exceeded 12 weeks. No significant differences were observed between FSC and FP alone in the incidence of drug-related adverse events and other adverse events. Both FSC and FP alone are viable options for the initial selection of step-up treatment in asthmatic children. While, FSC treatment demonstrates a greater likelihood of reducing asthma exacerbations which is particularly important for reducing the personnel, social and economic burden in children requiring step-up asthma treatment. [ABSTRACT FROM AUTHOR]

Target trial emulation is the process of mimicking target randomized trials using real-world data, where effective confounding control for unbiased treatment effect estimation remains a main challenge. Although various approaches have been proposed for this challenge, a systematic evaluation is still lacking. Here we emulated trials for thousands of medications from two large-scale real-world data warehouses, covering over 10 years of clinical records for over 170 million patients, aiming to identify new indications of approved drugs for Alzheimer's disease. We assessed different propensity score models under the inverse probability of treatment weighting framework and suggested a model selection strategy for improved baseline covariate balancing. We also found that the deep learning-based propensity score model did not necessarily outperform logistic regression-based methods in covariate balancing. Finally, we highlighted five top-ranked drugs (pantoprazole, gabapentin, atorvastatin, fluticasone, and omeprazole) originally intended for other indications with potential benefits for Alzheimer's patients. Target trial emulation (TTE) simulates randomized controlled trials using real world data (RWD). Here, authors show the effectiveness of different TTE strategies to identify drug candidates that could be potentially repurposed to Alzheimer's disease using two large scale RWD warehouses. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children. Methods: Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I2 statistics, followed by sensitivity analysis and publication bias evaluation. Results: Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The cough remission and disappearance times in the Mon + Flu group were significantly lower than those in the Flu group. FEV1% recovery in the Mon + Flu group was significantly better than that in the Flu group. Conclusion: Mon + Flu is effective and safe for the treatment of CVA in children. [ABSTRACT FROM AUTHOR]

CPZEN-45 is a novel compound with activity against drug-susceptible and drug-resistant tuberculosis (TB). The present study was undertaken to determine the best dose and dosing regimen of inhalable CPZEN-45 powders to use in efficacy studies with TB-infected guinea pigs. The disposition of CPZEN-45 after intravenous, subcutaneous (SC), and direct pulmonary administration (INS) was first determined to obtain their basal pharmacokinetic (PK) parameters. Then, the disposition of CPZEN-45 powders after passive inhalation using consecutive and sequential doses was evaluated. Plasma concentration versus time curves and PK parameters indicated that the absorption of CPZEN-45 after INS was faster than after SC administration (Ka = 12.94 ± 5.66 h−1 and 1.23 ± 0.55 h−1, respectively), had a longer half-life (2.06 ± 1.01 h versus 0.76 ± 0.22 h) and had higher bioavailability (67.78% and 47.73%, respectively). The plasma concentration versus time profiles and the lung tissue concentration at the end of the study period were not proportional to the dose size after one, two, and three consecutive passive inhalation doses. Three sequential passive inhalation doses maintained therapeutic concentration levels in plasma and lung tissue for a longer time than three consecutive doses (10 h vs. 3 h, respectively). Future studies to evaluate the efficacy of inhaled CPZEN-45 powders should employ sequential doses of the powder, with one nominal dose administered to animals three times per day. [ABSTRACT FROM AUTHOR]

Prallethrin ingestion and/or aspiration can manifest in a wide range of systemic effects. Evidence-based management of chemical pneumonitis following prallethrin aspiration does not exist yet. This case presents an unusual course of illness following prallethrin ingestion/aspiration that responded to antibiotics and steroid use. This is a previously well 22-month-old boy presented to the Emergency Department (ED) with a history of estimated 20 mL ingestion/aspiration of insecticide containing prallethrin 1.6% one hour earlier. The patient had bluish discoloration of his face, with eye tearing, drooling, and frothy secretions from his mouth. The patient was admitted for supportive care and observation. During his four days of admission, he progressively improved and returned to his previously healthy baseline. However, four hours after his discharge, he relapsed and was readmitted with an impression of superimposed pneumonia. During his second course of illness, the patient had worsening of his respiratory status requiring escalation of oxygen therapy and antibiotics. The patient received 21 days of intravenous (IV) antibiotics, and steroids, and was discharged on inhaled salbutamol and fluticasone. In conclusion, pyrethroid aspiration can lead to severe pneumonitis and secondary superimposed bacterial infection. [ABSTRACT FROM AUTHOR]

The aim of asthma treatment is to reduce airway inflammation by avoiding environmental triggers and using daily anti-inflammatory medications. This study aimed to compare the effects of fluticasone propionate (FP) and budesonide (Bud) on the clinical symptoms and control of asthma in children with moderate to severe asthma. In this open-label study, children with moderate to severe asthma were randomly selected to receive either FP 250 mcg or Bud 400 mcg for 3 months. Asthma control test scores were measured in both groups monthly. The clinical symptoms, drug adherence, and rescue medication were also evaluated. A total of 50 patients with ages between 4 and 7 years old were included in the study (25 cases received Bud and 25 cases received FP). Asthma control test scores, daily and nocturnal symptoms, and cough rates were significantly improved in both groups. The average asthma control scores for the fluticasone group were 21.68±3.32 in the second month and 24.84±2.67 in the third month, whereas the budesonide group had scores of 18.52±3.32 and 22.48±4.12 during the same periods. These variances were statistically significant. Additionally, the requirement for salbutamol use was notably reduced in the fluticasone group compared to the budesonide group throughout all three months. The efficacy of fluticasone propionate in decreasing the need for rescue medication and enhancing asthma control test scores was markedly superior to that of budesonide. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a common immunoglobulin (Ig) E-mediated disease. This study aimed to evaluate the gene expression levels of class 4 semaphorins and their receptors in AR patients before and after treatment with budesonide and fexofenadine (B/F) compared to fluticasone propionate and fexofenadine (FP/F). Methods: In this study, 29 AR patients (age 34.4 ± 1.2 years, 18 men and 11 women) were treated with B/F, and 24 AR patients (age 32.8 ± 1.9 years, 15 men and 9 women) were treated with FP/F for one month. Before and after treatment, peripheral blood samples were taken from patients. The expression levels of SEMA4A, SEMA4C, SEMA4D, Plexin-B2, and Plexin-D1 genes were measured using the qPCR method. In addition, the serum levels of IgE were measured using an enzyme-linked immunosorbent assay (ELISA). Results: The expression levels of SEMA4A (P = 0.011), 4C (P = 0.017), Plexin-B2 (P = 0.0005), and Plexin-D1 (P = 0.008) remarkably increased in AR patients treated with B/F. Our results show a significant reduction in the gene expression levels of SEMA4A (P = 0.002), 4C (P = 0.014), 4D (P = 0.003), Plexin-B2 (P = 0.033), and Plexin-D1 (P = 0.035) after treatment with FP/F. The serum levels of IgE increased in FP/F treated group (P = 0.017) and conversely decreased in the treated group with B/F (P = 0.019). Moreover, the percentages of eosinophils were reduced in both FP/F and B/F groups (P = 0.015 and P = 0.0001, respectively). Conclusion: In conclusion, concomitant use of fexofenadine and fluticasone propionate reduced SEMA4A, 4C, 4D, Plexin-B2, and Plexin-D1, while the SEMA4A, 4C, Plexin-B2, and Plexin-D1 gene expression levels were increased in the patient group treated with B/F.

Azelastine HCl and fluticasone propionate nasal spray drug product is commonly used to treat moderate to severe allergic rhinitis and rhino-conjunctivitis. To date, a simultaneous HPLC method for active substances and impurities of these products has not been reported. Acetonitrile and buffer (octane-1-sulfonic acid sodium salt and potassium dihydrogen phosphate) were used as a mobile phase. Separation was achieved using Phenomenex Phenyl-hexyl (150 cm × 4.6 mm, 5 µm) column at 1 mL/min flow rate in gradient elution mode. The chromatograms were monitored at 240 nm. Validation parameters such as linearity, limit of quantification, limit of detection, accuracy, precision, robustness, and specificity were investigated for the nasal spray. Overall, this study provides valuable insights into the development and validation of an efficient analytical method for assessing the quality and stability of a combination of azelastine HCl and fluticasone propionate nasal spray. [ABSTRACT FROM AUTHOR]

Spray freeze-drying has emerged as a valid alternative to traditional spray drying to produce therapeutic dry microparticles. In particular, the spherical shape and high porosity of spray freeze-dried microparticles make them suitable for pulmonary drug delivery through dry powder inhalers. However, an appropriate particle size and fine particle fraction are required to guarantee lung deposition. This study used ultrasonic spray freeze-drying to generate dry microparticles composed of mannitol either alone or added with the bronchodilator salbutamol sulphate. The influence of the solid concentration and the feed flow rate on the particle size, morphology, surface area, porosity, and crystallinity was investigated. Growing particle size was observed, increasing the concentration and feed flow rate. Similarly, the addition of the drug led to a larger particle size and surface area. The in vitro simulation of drug deposition highlighted the dependence of the aerodynamic properties on the solid concentration and feed flow rate. Due to the lower density and particle geometric size, the highest fine particle fraction (26%) and smallest mass median aerodynamic diameter (4.4 μm) were reached at the lowest solid concentration and feed flow rate. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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 phase III/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. Results: 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 ≥ 25–35 kg/m2) (p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. Conclusions: 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. Plain Language Summary: The goal of this project was to demonstrate that individual baseline characteristics can affect the risk of exacerbation as well as the overall treatment response in patients receiving regular maintenance doses of inhaled corticosteroids, given as monotherapy or in combination with long-acting beta-agonists. Using computer simulations based on a drug–disease model previously developed from a large pool of patients with moderate–severe asthma symptoms (N = 16,282), we describe how demographic and clinical baseline patient characteristics at the time of treatment start correlate with the risk of exacerbation. Our results indicate that poor symptom control, limited lung function, obesity, smoking and sex are associated with significant increase in the incidence of asthma attacks. Such an effect is augmented in winter because of the contribution of seasonal variation. This analysis also allowed us to assess how different treatments modify or reduce the annual incidence of moderate to severe attacks. In addition, simulated scenarios showed that combination therapy with fluticasone propionate/salmeterol results in 10% fewer asthma attacks relative to budesonide/formoterol combination therapy. Such a difference may be associated with corticosteroid-specific properties, which vary between inhaled corticosteroids. Consequently, even though comparable level of immediate relief and symptom control may be achieved whilst on treatment, these effects do not imply the same long-term reduction in the risk of exacerbation. These factors should be considered as a basis for personalised clinical management of patients with moderate–severe asthma. [ABSTRACT FROM AUTHOR]

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]

Dry powder inhalers, comprising an active pharmaceutical ingredient (API) and carrier excipients, are often used in the delivery of pulmonary drugs. The stability of the API particle size within a formulation blend is a critical attribute for aerodynamic performance but can be challenging to measure. The presence of excipients, typically at concentrations much higher than API, makes measurement by laser diffraction very difficult. This work introduces a novel laser diffraction approach that takes advantage of solubility differences between the API and excipients. The method allows insight into the understanding of drug loading effects on API particle stability of the drug product. Lower drug load formulations show better particle size stability compared with high drug load formulations, likely due to reduced cohesive interactions. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is a symptomatic condition of the nose, caused by an IgE-mediated inflammation of the nasal membranes. Allergic rhinitis is further split into two categories, based on the duration of symptoms: intermittent (IAR) or persistent (PER) disease. Oral or topical antihistamines and topical nasal steroids are the most popular and efficient treatments for allergic rhinitis. Methods: The present prospective comparative study was done between December 2021 to November 2022, with 64 subjects of PER divided into groups A and B. Group A patients received Fluticasone propionate (50 mcg) combined with Azelastine (140 mcg) nasal spray, whereas Group B patients received standalone Fluticasone propionate (50 mcg) nasal spray. Results: In both groups, the difference in mean TSS between the beginning and end of the 4-week study period was statistically significant (p for both < 0.05). After 4 weeks of treatment, Group A had a TSS of 2.02 ± 0.83 and Group B was at 3.80 ± 1.49; the difference between them was statistically significant (p < 0.05). Conclusions: According to results obtained from the current study, while both fluticasone propionate with azelastine nasal spray and standalone fluticasone propionate nasal spray are widely used for control of symptoms in PER, the former offers better results with significant reduction of symptoms when compared to the latter. [ABSTRACT FROM AUTHOR]

Introduction: The objective of the present study was to evaluate the efficacy and safety of MP-AzeFlu nasal spray in comparison to commercially available azelastine hydrochloride and fluticasone propionate sprays in Chinese patients with moderate-to-severe allergic rhinitis (AR). Methods: We conducted a 14-day multicenter, randomized, double-blind, active controlled prospective clinical study in adult and adolescent patients with AR, who had moderate-to-severe symptoms. The primary efficacy endpoint was the change from baseline in combined 12-h reflective total nasal symptom score (rTNSS) (morning [AM] + afternoon [PM]). The safety profile of the study medications was assessed through the recording, reporting, and analysis of baseline medical conditions, adverse events (AEs), vital signs, and focused nasal examination. Three hundred patients per treatment group were randomized, which led to a total sample size estimation of 900 patients. Results: MP-AzeFlu group showed significantly higher symptom reduction for the entire 2-week treatment period in rTNSS when compared with the AZE group (LS mean difference: − 1.96; 95% CI: − 2.53, − 1.39; p < 0.0001), or the FLU group (LS mean difference: − 0.98; 95% CI: − 1.55, − 0.41; p = 0.0007). The results of adult RQLQ showed improvement in QoL in all treatment groups. Except for dysgeusia (bitter taste) that was reported by more patients (13 [4.3%]) in the MP-AzeFlu group, the incidence of all other TEAEs in the MP-AzeFlu group was comparable or even lower than in other treatment groups. Conclusions: MP-AzeFlu, when administered as one spray per nostril twice daily for 14 days, alleviated AR symptoms in Chinese patients with moderate-to-severe AR. Trial Registration: Clinicaltrials.gov; NCT03599791, Registered June 29, 2018, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03599791. [ABSTRACT FROM AUTHOR]

High‐performance thin‐layer chromatography has the capacity to run many samples simultaneously and reduced solvent usage. It offers a number of advantages that can save both time and money. The simultaneous quantification of fluticasone propionate and olopatadine hydrochloride in nasal spray has been developed and validated using a specific, precise, accurate, and economical high‐performance thin‐layer chromatography technique. Methanol:water:glacial acetic acid (8:2:0.05, v/v/v) was used as the mobile phase during the separation, which took place on a stationary phase of pre‐coated silica gel aluminum plate 60 F254. At 232 nm, separated components were densitometrically measured. The method was validated for linearity and range, precision, reproducibility, specificity, accuracy, the limit of detection, and the limit of quantification as per the International Council for Harmonization Q2(R1) guideline. Fluticasone propionate and olopatadine hydrochloride regression coefficients (R2) were found to be 0.9996 and 0.9991, accordingly. Fluticasone propionate and olopatadine hydrochloride percentage recoveries were measured to be 101.6 ± 0.69 and 99.62 ± 0.54, respectively. The analytical findings demonstrate that the proposed approach could be used to quantify Fluticasone propionate and olopatadine hydrochloride simultaneously in Pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Simple Summary: Coughing is common in dogs with tracheal collapse (TC). Inhaled corticosteroids are the standard of care in humans, but their use in dogs is less widespread than oral corticosteroids. This study compared the efficacy, adherence, and tolerance to treatment of inhaled versus oral corticosteroids in 30 dogs with cough and TC, randomized to each treatment. Responses were monitored in the hospital (enrolment and weeks 2 and 4) and at home (weeks 1 to 4) using a semiquantitative clinical scale based on four key clinical parameters (respiratory distress, cough episodes, cough frequency, tracheal sensitivity). Both treatments provided comparable clinical improvements, with significantly greater improvements at the end in the fluticasone group. Adherence and tolerance were equivalent, but thirst and the frequency of urination increased in those taking prednisone. In conclusion, inhaled fluticasone is effective in controlling cough in dogs with TC without side effects, which encourages its use to be extended compared to prednisone. Coughing is common in dogs with tracheal collapse (TC). The use of inhaled corticosteroids is less widespread than oral ones. This study aims to compare the effects of oral and inhaled corticosteroids in dogs with cough and TC. Thirty dogs were prospectively included and randomized to the prednisone oral group (OG, 14) or fluticasone inhaled group (IG, 16). A clinical score (CS) based on four clinical parameters (respiratory distress, cough episodes, cough frequency, tracheal sensitivity) was monitored at the hospital (enrolment and weeks 2 and 4). Water intake, urination habits, and adherence and tolerance to treatments were monitored weekly. Significant improvements in clinical parameters were identified in both groups throughout the study. Between-group (OG–IG) comparisons revealed no significant differences, indicating equivalent improvement. At the study's endpoint, the IG dogs had a significantly lower CS (5.69 ± 0.79) than OG dogs (6.43 ± 1.02, p < 0.05). Adherence and tolerance were comparable. From weeks 2 to 4, OG dogs were significantly thirstier and urinated more frequently than IG dogs. In conclusion, fluticasone provided good tolerability and efficacy in controlling cough in dogs with TC, and they showed a lower incidence of signs of hypercortisolism compared to prednisone. These data encourage the use of inhaled fluticasone in dogs with cough and TC. [ABSTRACT FROM AUTHOR]

With the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS). The FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell. From 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs. Gustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology. III. [ABSTRACT FROM AUTHOR]

Asthma is a steady fiery aviation route ailment with a excessive commonness, round 10% in youngsters and 5% in grown-ups in Western nations. Asthma is a noteworthy purpose for inability and well being asset use, and diminishes personal delight. To restriction bronchial asthma intensifications, remedy ought to be balanced stepwise, determined with the aid of the patient's bronchial asthma manage level. Breathed in corticosteroids (ICS) are the foundation of support treatment for asthma. Numerous examinations have demonstrated ICS to enhance manifestations and reduce asthma-related bleakness and mortality, however regardless of this, a excessive variety of patients being handled with the aid of rules stay hard to control with successive intensifications and continuing symptoms. [ABSTRACT FROM AUTHOR]

Background: Azelastine HCl (AZ) and fluticasone propionate (FL) nasal spray drug product is commonly used in the treatment of allergic rhinitis worldwide. To date, the impurity profiling of this product has not been reported. Objective: The present study aimed to develop and validate a novel RP-HPLC stability-indicating analytical method for the estimation of impurities from AZ and FL nasal spray drug product. Methods: A mixture of octane sulfonic acid sodium salt and trifluroacetic acid is used as a mobile phase A. Acetonitrile is used as a mobile phase B. Good separation was achieved on Baker bond phenyl hexyl, 250 4.6, 5 mm column at 1 mL/min flow rate in gradient elution mode. The chromatograms were monitored at 239 nm. Results: The LOD and LOQ were found to be 0.006 and 0.019 μg/mL for AZ and 0.010 and 0.030 μg/mL for FL, respectively. The correlation coefficient for all the known impurities and principal analytes was 0.999 from LOQ level to 150% of standard concentration. The recovery for all the known impurities was found to be between 90 and 110%. In the stress study, 15% degradation was observed in basic conditions and 8.7% in acidic conditions. No significant degradation was observed in thermal and oxidative conditions. Conclusion: An impurity profiling method for AZ and FL combination nasal spray product was successfully developed, validated, and demonstrated to be accurate, precise, specific, robust, and stability-indicating. The method can be routinely used for impurity testing of commercial batches in QC laboratories in the pharmaceutical industry. Highlights: No impurity study has been reported for this combination product until now. [ABSTRACT FROM AUTHOR]

Prolonged exposure to environmental respirable toxicants can lead to the development and worsening of severe respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD) and fibrosis. The limited number of FDA-approved inhaled drugs for these serious lung conditions has led to a shift from in vivo towards the use of alternative in vitro human-relevant models to better predict the toxicity of inhaled particles in preclinical research. While there are several inhalation exposure models for the upper airways, the fragile and dynamic nature of the alveolar microenvironment has limited the development of reproducible exposure models for the distal lung. Here, we present a mechanistic approach using a new generation of exposure systems, the Cloud α AX12. This novel in vitro inhalation tool consists of a cloud-based exposure chamber (VITROCELL) that integrates the breathing AXLung-on-chip system (AlveoliX). The ultrathin and porous membrane of the AX12 plate was used to create a complex multicellular model that enables key physiological culture conditions: the air-liquid interface (ALI) and the three-dimensional cyclic stretch (CS). Human-relevant cellular models were established for a) the distal alveolarcapillary interface using primary cell-derived immortalized alveolar epithelial cells (AXiAECs), macrophages (THP-1) and endothelial (HLMVEC) cells, and b) the upperairways using Calu3 cells. Primary human alveolar epithelial cells (AXhAEpCs) were used to validate the toxicity results obtained from the immortalized cell lines. To mimic in vivo relevant aerosol exposures with the Cloud α AX12, three different models were established using: a) titanium dioxide (TiO2) and zinc oxide nanoparticles b) polyhexamethylene guanidine a toxic chemical and c) an antiinflammatory inhaled corticosteroid, fluticasone propionate (FL). Our results suggest an important synergistic effect on the air-blood barrier sensitivity, cytotoxicity and inflammation, when air-liquid interface and cyclic stretch culture conditions are combined. To the best of our knowledge, this is the first time that an in vitro inhalation exposure system for the distal lung has been described with a breathing lung-on-chip technology. The Cloud α AX12 model thus represents a state-of-the-art pre-clinical tool to study inhalation toxicity risks, drug safety and efficacy. [ABSTRACT FROM AUTHOR]

No evidence shows that one intranasal corticosteroid (INCS) is better than another for treating moderate-to-severe allergic rhinitis (AR). This network meta-analysis assessed the comparative efficacy and acceptability of licensed dose aqueous INCSs. PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane Central Register of Controlled Trials were searched until 31 March 2022. Eligible studies included randomized controlled trials comparing INCSs with placebo or other types of INCSs in patients with moderate-to-severe allergic rhinitis. Two reviewers independently screened and extracted data following the Preferred Reporting Items in Systematic Reviews and Meta-analysis guideline. A random-effects model was used for data pooling. Continuous outcomes were expressed as standardized mean difference (SMD). The primary outcomes were the efficacy in improving total nasal symptom score (TNSS) and treatment acceptability (the study dropout). We included 26 studies, 13 with 5,134 seasonal AR patients and 13 with 4,393 perennial AR patients. Most placebo-controlled studies had a moderate quality of evidence. In seasonal AR, mometasone furoate (MF) was ranked the highest efficacy, followed by fluticasone furoate (FF), ciclesonide (CIC), fluticasone propionate and triamcinolone acetonide (TAA) (SMD -0.47, 95% CI: -0.63 to -0.31; -0.46, 95% CI: -0.59 to -0.33; -0.44, 95% CI: -0.75 to -0.13; -0.42, 95% CI: -0.67 to -0.17 and -0.41, 95% CI: -0.81 to -0.00), In perennial AR, budesonide was ranked the highest efficacy, followed by FF, TAA, CIC, and MF (SMD -0.43, 95% CI: -0.75 to -0.11; -0.36, 95% CI: -0.53 to -0.19; -0.32, 95% CI: -0.54 to -0.10; -0.29, 95% CI: -0.48 to -0.11; and -0.28, 95% CI: -0.55 to -0.01). The acceptability of all included INCSs was not inferior to the placebo. According to our indirect comparison, some INCSs have superior efficacy to others with moderate quality of evidence in most placebo-controlled studies for treating moderate-to-severe AR. [ABSTRACT FROM AUTHOR]

Objective was to evaluate the pharmacokinetic parameters of MP-AzeFlu compared with the commercially available mono-components. Methods: Both studies were a randomized, open-label, three-period, six-sequence, single-dose cross-over trial (William's design) conducted at Beijing Hospital (Beijing, China) in September and October of 2019 in 30 healthy adult male and female volunteers. The natural log transformed parameters: AUC0-tlast, AUC0-∞ and Cmax were analyzed. Results: The comparison of PK parameters between MP-AzeFlu and Aze (commercially available) showed that the LS mean ratios (90% CI) values for, AUC0–tlast, AUC 0–∞ and Cmax were 100.29% (94.31– 106.66%), 100.76% (94.60– 107.32%) and 93.14% (81.47– 106.48%). The comparison of PK parameters between MP-AzeFlu and Flu (commercially available) for the bioavailability evaluation showed that the LS mean ratios (90% CI) values for, AUC0–tlast, AUC 0–∞ and Cmax were 83.48% (69.81– 99.82%), 100.19% (87.34– 114.94%) and 81.91% (68.50– 97.95%). Conclusion: The study results confirm that neither the FLU or the AZE component in the combination product (MP-AzeFlu), nor the existing qualitative and quantitative differences in the formulation between the currently marketed AZE and FLU mono-product, display significant potential to impact the systemic exposure of AZE or FLU in Chinese subjects. [ABSTRACT FROM AUTHOR]

Introduction: Adenoidectomy is currently considered the treatment of choice for relief of the nasal airway obstruction due to adenoid hypertrophy. Evidence suggests that topical nasal steroid sprays can cause a reduction in adenoid size. We aim to compare the effectiveness of fluticasone propionate, mometasone furoate (MF) and saline nasal sprays in relieving the signs and symptoms of adenoid hypertrophy and in reducing the size of the adenoids. Materials and Methods: We conducted a randomized comparative study on 60 patients divided into three groups A, B, C (20 each). Group A patients treated with fluticasone propionate nasal spray (400 μg/day), Group B patients treated with MF nasal spray (100 μg/day), and Group C patients treated with saline spray (0.65% w/v in purified water which is made isotonic and buffered). Treatment was given up to 12 weeks with follow-up at 4, 8, and 12 weeks and at each follow-up visit assessment was done. Final data were analyzed using SPSS software version 21 and numerical variables associated with different groups were analyzed and analysis of variance test was used. Results: Diagnostic nasal endoscopy and X-ray grades at day 1 among the study groups were not statistically significant, whereas, at 12 weeks results among fluticasone and mometasone groups were significantly better (P < 0.001) as compared to the saline group. There was a significant improvement in the symptoms under all the categories with the use of fluticasone and mometasone. Conclusion: In our study, both fluticasone propionate and MF were able to effectively reduce symptoms and signs of adenoid hypertrophy as well as help in reducing the size of the enlarged adenoid. Both these drugs were well tolerated by the patients.

llergic rhinitis (AR) is increasing at an alarming rate in Ukraine. The clinical picture of AR in modern conditions is changing towards more severe and mixed forms. Allergic rhinitis, especially moderate to-severe, has a negative impact on patient quality of life, productivity, direct, and indirect costs. Achieving adequate symptom control is essential for successful AR management, and relies mostly on pharmacotherapy. Most patients use multiple medications to control symptoms faster and better, but symptoms may persist. With the advent of new combination therapies, such as the intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (MP-AzeFlu) like Dymista®, most AR symptoms can be treated effectively. MP-AzeFlu acts synergistically and blocks two important pathophysiological pathways involved in the early- and late-phase reactions of the disease, providing rapid relief from all AR-associated symptoms. A total of 13 experts from Ukraine, Germany, and India participated in the development of this consensus statement. The lead author drafted the questions pertaining to diagnosis, management, treatment adherence, and real-life evidence of AR in Ukraine, and was agreed with the co-authors and expert panel. This consensus is obtained through guiding statements and recommendations based on literature evidences (recent research outcomes, randomized, and comparative studies), clinical practices and personal experience of using MP-AzeFlu in AR by allergist/ immunologists/ otolaryngologists from Ukraine. This consensus statement aimed to assist practitioners in selecting the appropriate treatment strategies, facilitate optimum use of MP-AzeFlu and provide symptomatic relief for patients with AR in the in Ukraine