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The most classic treatment recommended in the current chronic obstructive pulmonary disease (COPD) guidelines is glucocorticoid and β2 receptor agonist combination, such as salmeterol xinafoate and fluticasone propionate (Sal/Flu), causing many adverse reactions due to hormones. Magnesium isoglycyrrhizinate (MgIG) is an anti-inflammatory glycyrrhizic acid preparation for treating chronic inflammation, contributing to its structure is similar to steroidal anti-inflammatory drugs. In this study, we successfully established COPD rat model by endotracheal-atomized lipopolysaccharide exposure and cigarette smoke induction, as characterized by lung function decline. We discovered that salmeterol xinafoate/MgIG combination could alleviated lung inflammation infiltration, airway wall thickness (AWT) and the secretion of bronchial mucin MUC5AC of COPD rats more than salmeterol xinafoate, MgIG, or salmeterol xinafoate and fluticasone propionate treatment did, as well as reduced inflammatory cells (white blood cells, neutrophils and lymphocytes) accumulation in bronchoalveolar lavage fluid and decreased TNF-α, IL-6 and IL-1β production in the serum of COPD rats. Finally, we found that Moreover, the mechanism involved might be related to the suppression of JAK/STAT signaling pathway. Overall, our studies suggested that MgIG might be a potential alternative adjuvant drug for fluticasone propionate for the clinical treatment of patients with COPD. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary diseases (COPD) and asthma are fatal. The respiratory tract may be blocked, robbed of the adequate amounts of oxygen; hence, death ensues if a quick medical attention is not provided. The treatment available for the duo are inhaled corticosteroids (ICS). The ICS can work synergically with LABAS (long-acting β2-antagonists) and so many other medicines like bronchodilators. The drugs used for the treatment of asthma and COPD are metabolised once in the body system and at the same time exerting the therapeutic effect provided the concentration of the drug is within the therapeutic window. The CYP3A isoforms metabolise the ICS, in this case, salmeterol and fluticasone propionate (FP). Methods of administration are not limited to inhalation. Specific doses are prescribed accurately paying attention to factors like age, gender, race, and genetic makeup since these affect drug metabolisms. Generally, the ICS work by translocating glucocorticoid receptors to the nucleus from the cytosol. The mechanism is potentiated by the β-antagonists and this brings about an anti-inflammatory effect which is greater than either of the two drugs alone. Once this happens, it is not necessary to increase ICS dose. The ICS, in addition, cause more production of β-receptors by activating the β-receptor genes. This mode of action begets the LABAs' bronchodilator-effects. The challenge is that ICS are not limited only to "double" therapy. Analysing such therapies is daunting since coadministration interferes with pharmacology and pharmacokinetics of drugs. This work focuses on salmeterol/fluticasone propionate combination and aspects which has to do with administration, monitoring, metabolism, toxicity, and adverse effects. [ABSTRACT FROM AUTHOR]

• AZD5634 is a novel inhaled ENaC inhibitor for the treatment of cystic fibrosis. • Its safety, proof of mechanism and pharmacokinetics were assessed in two trials. • Absolute bioavailability post-inhalation of ∼3% indicated low systemic distribution. • AZD5634 inhibited ENaC in situ , but did not produce a therapeutic response. • AZD5634 was safe and well tolerated in both studies. Epithelial sodium channel (ENaC) inhibitors may offer clinical benefit in cystic fibrosis (CF); however, data are limited. We report the outcomes of a Phase I (NCT02679729) and a Phase Ib (NCT02950805) study of AZD5634, a novel inhaled ENaC inhibitor. A Phase I, first-in-human, single-blind, placebo-controlled, single ascending dose, sequential dose group study assessed the safety, tolerability, and pharmacokinetics of AZD5634 in healthy subjects (n=53) in part A following inhaled doses up to 1700 µg, and, in part B, following administration of single inhaled (1700 µg) and intravenous (65 µg) doses. A Phase Ib, randomized, double-blind, placebo-controlled, single-dose, 2-way cross-over study assessed the effects of a single dose (600 µg) of inhaled AZD5634 on mucociliary clearance (MCC), pharmacokinetics and safety and tolerability in patients with CF (n=11). Nasal potential difference (NPD) was assessed as an in situ target engagement exploratory biomarker. Absolute bioavailability of AZD5634 after inhalation was approximately 3%, indicating minimal distribution into the systemic circulation. Urinary excretion was a minor elimination pathway. Administration of inhaled AZD5634 did not improve MCC in CF patients, but AZD5634 inhibited ENaC in the nasal epithelium, as measured by NPD. AZD5634 was safe and well tolerated in both studies. AZD5634 showed favorable pharmacokinetics and safety in healthy subjects and patients with CF. However, despite achieving target engagement, proof of mechanism was not achieved after a single dose in patients with CF. Further evaluation into multiple dose studies is warranted to explore its therapeutic potential. [ABSTRACT FROM AUTHOR]

Background: In chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICSs) are recommended for use by patients with frequent exacerbations and blood eosinophilia. However, ICSs are often inappropriately prescribed and overused. COPD studies have reported an increased risk of tuberculosis among ICS users. This study aimed to compare the risk of tuberculosis according to the different ICS components. Methods: This study was conducted using a nationwide, population-based cohort. Patients newly diagnosed with COPD between 2005 and 2018, and treated with either fluticasone propionate or budesonide, were selected. The patients were followed up until the development of tuberculosis. Results: After propensity score matching, 16,514 fluticasone propionate and 16,514 budesonide users were identified. The incidence rate of tuberculosis per 100,000 person-years was 274.73 for fluticasone propionate and 214.18 for budesonide. The hazard ratio of tuberculosis in fluticasone propionate compared with budesonide was 1.28 (95% confidence interval 1.05–1.60). The risk of tuberculosis for fluticasone propionate increased with higher ICS cumulative doses: 1.01 (0.69–1.48), 1.16 (0.74–1.81), 1.25 (0.79–1.97), and 1.82 (1.27–2.62) from the lowest to highest quartiles, respectively. Conclusion: Fluticasone propionate is associated with a higher risk of tuberculosis than budesonide. ICS components can differently affect the risk of tuberculosis in patients with COPD. [ABSTRACT FROM AUTHOR]

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

[Display omitted] In this work we present the development of in situ gelling nanosuspension as advanced form for fluticasone propionate nasal delivery. Drug nanocrystals were prepared by wet milling technique. Incorporation of drug nanocrystals into polymeric in situ gelling system with pectin and sodium hyaluronate as constitutive polymers was fine-tuned attaining appropriate formulation surface tension, viscosity and gelling ability. Drug nanonisation improved the release profile and enhanced formulation mucoadhesive properties. QbD approach combining formulation and administration parameters resulted in optimised nasal deposition profile, with 51.8% of the dose deposited in the middle meatus, the critical region in the treatment of rhinosinusitis and nasal polyposis. Results obtained in biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient nasal corticosteroid delivery. [ABSTRACT FROM AUTHOR]

A major issue of the pharmaceutical industry is the poor solubility, permeability, and bioavailability of most active ingredients. These properties also induce the accumulation of pharmaceuticals in groundwater, surface water, wastewater, soils and biota. Therefore, enhancing the solubility and bioavailability of pharmaceuticals could allow the prescription of lower doses, and could reduce environmental impact. Pharmaceutical solubility can be increased by pH modification, salt formation, ionization, complexation, and co-solvency. Here we report for the first time the use of cyclodextrin-based low-melting mixtures for the solubilization of four steroids: beclomethasone dipropionate, budesonide, fluticasone propionate and mometasone furoate. First, a low-melting mixture was prepared from sulfobutylether-β-cyclodextrin and levulinic acid, and characterized. Then, the shake flask method was used to determine the solubility of the drugs in this low-melting mixture. Results show a 4000-fold increase of the solubility of fluticasone propionate using the low-melting, cyclodextrin-based mixture versus water. This huge solubility enhancement could be explained by the formation of an inclusion complex with the cyclodextrin within the low-melting mixture. [ABSTRACT FROM AUTHOR]

The superior clinical effect of MP-AzeFlu compared to FP and AZE monotherapy may be related to greater up-regulation of anti-inflammatory GILZ gene expression and, to a lesser extent, MKP-1 and TTP. Keywords: azelastine; fluticasone; gene expression; GILZ; MKP-1; MP-AzeFlu; TTP EN azelastine fluticasone gene expression GILZ MKP-1 MP-AzeFlu TTP 788 791 4 06/01/22 20220601 NES 220601 Key Messages MP-AzeFlu has demonstrated efficacy in allergic rhinitis, and a superior effect compared with FP and AZE administered in monotherapy. Superior effect of MP-AzeFlu compared to monotherapy with fluticasone propionate or azelastine on GILZ, MKP-1 and TTP anti-inflammatory gene expression in healthy and inflamed upper airway mucosa. [Extracted from the article]

Topical corticosteroids are first-line medications in the treatment of an overwhelming number of both acute and chronic inflammatory noninfectious skin diseases. These drugs can be characterized as the drugs of choice in dermatological practice, which is determined by anti-inflammatory, immunosuppressive and antiproliferative effects of corticosteroids. Nevertheless, the use of these drugs in some cases may be limited by the potential risk of adverse side effects, which, in turn, determines a rather widespread corticophobia among patients, as well as among some doctors. In this regard, the current efforts of pharmaceutical companies are focused on the development of topical corticosteroids with the least number of side effects without loss of clinical efficacy. The synthetic carbothioate corticosteroid fluticasone propionate (FP) is a medium strength (class III) synthetic fluorinated corticosteroid for topical treatment of skin conditions. Its molecule has a high degree of lipophilicity, which allows it to be actively absorbed into the skin. The drug has a high affinity to glucocorticoid receptors against the background of the absence of mineralcorticoid activity. In addition, FP is relatively quickly subjected to enzymatic hydrolysis to inactive metabolites. This determines the high clinical efficacy of this drug with minimal risk of both local and systemic adverse events. It is available as cream and ointment with the same efficacy, but with different concentrations (0.05 or 0.005%) of the active substance. This article reviews the pharmacology and safety profile as well as the use of topical FP in clinical practice.

A recent article in the Journal of Antimicrobial Chemotherapy recommends using corticosteroids as adjuvant therapy for patients with community-acquired pneumonia (CAP). Corticosteroids can decrease the risk of complications and reduce hospital stays and antibiotic treatment duration for severe CAP cases. However, there is insufficient evidence to support the use of corticosteroids for mild cases or in patients without underlying lung disease. Further research is needed to determine the role of oral corticosteroids in different subpopulations of CAP patients. [Extracted from the article]

Introduction: Studies on the pathophysiology of chronic rhinosinusitis have shown an effect of IgE antibodies on the course of the disease, as well as the effectiveness of treatment. Steroid therapy remains the most prevailing method of CRS treatment. Aim: The aim of our study was to determine the clinical response to systemic and local steroid therapy in patients with CRSsNP depending on the total IgE antibody serum concentration. Material and methods: A total of 92 patients with CRSsNP took part in the study, where they were divided randomly into 2 groups. In group I, the patients received fluticasone propionate 800 mcg/day intranasally for 12 weeks. Patients in group II were treated with prednisone at a dose of 0.5 mg/kg/day, given orally, for 7 consecutive days and continued by another week with decreasing dosage. Both groups were evaluated prior to and following treatment using the TSS score of CRS clinical symptoms, the endoscopic Lund-Kennedy scale and the Lund-Mackay CT staging of chronic rhinosinusitis. Statistical analysis of the effectiveness of treatment was carried out in subgroups according to the total IgE serum concentrations obtained before treatment. Results: Both groups of patients achieved statistically significant improvement in the TSS evaluation, as well as in endoscopic and CT imaging findings. In patients with a total IgE serum concentration over 100 IU/ml systemic steroid therapy showed significantly greater effect on the relief of CRS symptoms in the TSS score than intranasal steroid therapy. Analogous differences in the effectiveness of both methods were not found in patients with a normal total IgE serum concentration (<100 IU/ml). Conclusions: A short course of systemic steroid therapy is more effective than local treatment in relieving of CRS symptoms in patients with CRSsNP with elevated serum concentration of IgE antibodies. Atopy may be considered a specific predictor of response to steroid therapy in the treatment of chronic rhinosinusitis. [ABSTRACT FROM AUTHOR]

Introduction: Inhaled corticosteroid/long-acting β2-adrenoceptor agonist/long-acting muscarinic antagonist (ICS/LABA/LAMA) fixed-dose combination (FDC) is currently recommended as controller option at asthma Step 4 and as preferred treatment at asthma Step 5, but no research investigated the potential drawbacks of this therapeutic option in a large asthmatic population. Thus, the aim of this study was to quantify the potential drawbacks of triple FDC therapy in asthma. Methods: A pairwise meta-analysis was performed according to PRISMA-P guidelines to assess the risk of overall serious adverse events (SAEs), cardiovascular SAEs, and pneumonia reported as SAE in asthmatic patients treated with ICS/LABA/LAMA FDC vs ICS/LABA FDC. A pooled analysis was performed to calculate the frequency of SAEs. Results: Data from 7204 asthmatic patients were extracted from the CAPTAIN, IRIDIUM, TRIMARAN, and TRIGGER studies. Triple FDC vs ICS/LABA FDC did not increase the risk of total SAEs (RR 0.99 95% CI 0.83– 1.18) and cardiac SAEs (RR 0.74 95% CI 0.39– 1.40), whereas the sensitivity analysis performed to resolve heterogeneity resulted in increased risk of vascular SAEs (RR 3.23 95% CI 1.05– 9.90, P< 0.05). The level of ICS dose did not modulate the risk of pneumonia, in any case pneumonia was the most frequent SAE (0.57%). These results were not affected by significant risk of bias. Conclusion: Triple FDC is a safe pharmacological therapy in severe asthmatic patients; it is characterized by a favourable safety profile and few potential drawbacks, namely, the increased risk of vascular SAEs, that certainly are worthy of future investigations. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroid (ICS)-containing therapies are the mainstay of pharmacological management of asthma. They can be administered alone or in combination with a long-acting bronchodilator, depending on asthma severity, and may also be supplemented with short-acting bronchodilators for as-needed rescue medication. Adherence to asthma therapies is generally poor and characterized by underuse of ICS therapies and over-reliance on short-acting bronchodilators, which leads to poor clinical outcomes. This article reviews efficacy versus systemic activity profiles for various dosing regimens of budesonide (BUD) and fluticasone propionate (FP). We performed a structured literature review of BUD and FP regular daily dosing, and BUD/formoterol (FOR) as-needed dosing, to explore the relationship between various dosing patterns of ICS regimens and the risk–benefit profile in terms of the extent of bronchoprotection and cortisol suppression. In addition, we explored how adherence could potentially affect the risk–benefit profile, in patients with mild, moderate, and moderate-to-severe asthma. With a specific focus on BUD or FP-containing treatments, we found that regular daily ICS and ICS/long-acting β2-agonist (LABA) dosing had a greater degree of bronchoprotection than as-needed BUD/FOR dosing or BUD/FOR maintenance and reliever therapy (MART) dosing, and still maintained low systemic activity. We also found that the benefits of regular daily ICS dosing regimens were diminished when adherence was low (50%); the shorter duration of bronchoprotection observed was similar to that seen with typical as-needed BUD/FOR usage. These findings have implications for aiding clinicians with selecting the most suitable treatment option for asthma management, and subsequent implications for the advice clinicians give their patients. Plain Language Summary: Inhaled corticosteroid (ICS)-containing therapies can be administered in a variety of ways depending on a patient's asthma severity. Patients with mild asthma tend to experience symptom relief with as-needed or regular daily use of an ICS alone, whereas patients with more severe asthma may require regular daily use of an ICS plus a long-acting β2-agonist (LABA) to experience sufficient asthma control. However, failure to correctly adhere to ICS-containing therapies or an over-reliance on short-acting bronchodilators for symptom relief hinders optimal asthma management, thus negatively affecting overall patient health and wellbeing. Understanding how different dosing regimens affect the degree of bronchoprotection (efficacy) and cortisol suppression (systemic activity) of ICS treatments would benefit physicians by helping them to prescribe the most appropriate treatment for their patient's asthma. We performed a structured literature review of two ICS molecules—budesonide (BUD) (alone and combined with formoterol [FOR]) and fluticasone propionate (FP)—to explore the relationship between various ICS dosing regimens, and then used these findings to construct models for ICS risk–benefit profiles. Our models factored in different ICS dosing regimens—as-needed, regular daily dosing, and maintenance and reliever therapy (MART)—and various degrees of treatment adherence. We found that regular daily ICS and ICS/LABA dosing provided better bronchoprotection than as-needed BUD/FOR dosing or BUD/FOR MART dosing, but this benefit was diminished with low adherence. Regular daily dosing maintained low cortisol suppression, which indicated a fairly low risk of negative side effects. Our findings have subsequent implications for optimizing treatment in patients with asthma. [ABSTRACT FROM AUTHOR]

Fractional exhaled nitric oxide (FeNO) from the lower airways and nasal nitric oxide (nNO) from the upper airways are biomarkers of eosinophilic airway inflammation and are used to assess responses to corticosteroid treatment. To examine the influence of inhaled fluticasone propionate/salmeterol (FP/SAL) or fluticasone propionate (FP) treatment on the concentration of FeNO and nNO, the percentage of eosinophils, lung function, and asthma control test (ACT) scores among children with asthma, allergic rhinitis, and combined allergic rhinitis and asthma. A total of 95 steroid-naïve pediatric subjects with asthma (n = 29), asthma and allergic rhinitis (n = 30), and allergic rhinitis (n = 36) participated in this study. Initially, patients had a physical exam, baseline FeNO and nNO measurement, spirometry, blood sampling, skin tests, and an ACT questionnaire. After assessment of the baseline values, inhaled FP/SAL (100/50 µg) was administered twice daily for 4 weeks in patients with asthma; intranasal FP (100 µg) was added twice daily in cases of allergic rhinitis. Two weeks after treatment, spirometry, FeNO and nNO measurements, blood sampling, and the ACT questionnaire were repeated. A 4-week low dose combination treatment with FP/SAL in asthmatic participants or FP alone in allergic rhinitis patients is effective in reducing FeNO (p < 0.001) and/or nNO (p < 0.001) levels and reducing the percent of eosinophils in peripheral blood. Moreover, we observed improvement in lung function and an increase in ACT scores among pediatric patients. We conclude that measurements of FeNO and nNO are helpful for assessing the effectiveness of treatment with corticosteroids, especially due to the fact that these measurements are inexpensive, fast, painless, and easier to perform than spirometry, which can be a benefit for younger children. [ABSTRACT FROM AUTHOR]

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)–dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2–driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS. Ameliorating asthma: Many individuals with mild or moderate asthma benefit from treatment with inhaled corticosteroids. However, patients with severe asthma often do not benefit from inhaled corticosteroid treatment. Here, Guidi and colleagues investigated the mechanism behind these poor responses. The authors found that patients with severe asthma had increased corticosteroid-driven fibroblast growth factor (FGF) expression. In mice, FGF exposure increased hyaluronan production and neutrophil infiltration into the lungs, worsening allergic responses. This could be reversed by treating mice with pan-FGF receptor inhibitors, suggesting that a combination of corticosteroids and FGF inhibition may be a therapeutic option for those with severe asthma. [ABSTRACT FROM AUTHOR]

Type 2-high severe asthma is described as a distinct endotype with Th2 inflammation, high eosinophil lung infiltration, impaired lung function, and reduced corticosteroid sensitivity. While the inflammatory milieu is similar to mild asthma, patients with type 2-high severe asthma likely have underlying mechanisms that sustain asthma pathophysiology despite corticosteroid treatments. Acute and chronic allergen models induce robust type 2 inflammatory responses, however differences in corticosteroid sensitivity remains poorly understood. In the present study, we sensitized and challenged mice with ovalbumin (OVA; acute model) or mixed allergens (MA; chronic model). Corticosteroid sensitivity was assessed by administering vehicle, 1, or 3 mg/kg fluticasone propionate (FP) and examining key asthmatic features such as airway inflammation, remodeling, hyperresponsiveness, and antioxidant capacity. Both acute and chronic allergen exposure exhibited enhanced AHR, immune cell infiltration, airway inflammation, and remodeling, but corticosteroids were unable to fully alleviate inflammation, AHR, and airway smooth muscle mass in MA-challenged mice. While there were no differences in antioxidant capacity, persistent IL-4+ Th2 cell population suggests the MA model induces type 2 inflammation that is insensitive to corticosteroids. Our data indicate that chronic allergen exposure is associated with more persistent type 2 immune responses and corticosteroid insensitivity. Understanding differences between acute and chronic allergen models could unlock underlying mechanisms related to type 2-high severe asthma. [ABSTRACT FROM AUTHOR]

Background: In asthma, persistent airflow limitation (PAL) is associated with poorer control, lung function decline and exacerbations. Using post‐hoc analyses we evaluated: the relationship between post‐salbutamol PAL at screening, airflow limitation (AL) during 52 weeks treatment with extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) versus BDP/FF and the risk of moderate/severe asthma exacerbations. Methods: TRIMARAN and TRIGGER were double‐blind studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium‐dose ICS; TRIGGER high‐dose) in adults with uncontrolled asthma. Patients were subgrouped according to post‐salbutamol PAL status at screening, and AL over the 52‐week treatment period. Results: Most patients with post‐salbutamol PAL at screening had AL at all on‐treatment visits (TRIMARAN 62.8%; TRIGGER 66.8%). A significantly higher proportion of patients had normalised airflow on ≥1 follow‐up visit when receiving BDP/FF/G than BDP/FF (TRIMARAN 44.1 vs. 33.1% [p = 0.003]; TRIGGER 40.1 vs. 26.0% [p < 0.001]). In patients with post‐salbutamol PAL at screening and normalised AL at ≥1 follow‐up visit, exacerbation rates were 15% (p = 0.105) and 19% (p = 0.039) lower in TRIMARAN and TRIGGER versus those with AL on all visits. There was a trend to lower exacerbation rates in patients receiving BDP/FF/G than BDP/FF, particularly in patients in whom AL was normalised. Conclusion: In these analyses, AL in asthma was associated with an increased exacerbation incidence. Inhaled triple therapy with extrafine BDP/FF/G was more likely to normalise airflow, and was associated with a trend to a lower exacerbation rate than BDP/FF, particularly in the subgroup of patients in whom treatment was associated with airflow normalisation. ClinicalTrials.gov: TRIMARAN, NCT02676076; TRIGGER, NCT02676089. [ABSTRACT FROM AUTHOR]

Summary: Background: Recent evidence has suggested that oral antihistamines could have a beneficial role in atopic dermatitis (AD) because of their anti‐inflammatory action. Aim: To evaluate the effectiveness of adding an oral second‐generation, nonsedating, H1‐receptor antihistamine (fexofenadine) to topical treatment in AD. Methods: In this prospective randomized study, 50 patients with a diagnosis of mild to moderate AD were recruited and randomized into two groups: Group A was given appropriate topical treatment (topical tacrolimus 0.03–0.1% ointment once daily along with topical fluticasone propionate 0.05% cream once daily, as well as paraffin‐based emollients) combined with oral fexofenadine, while Group B was given appropriate topical treatment only. Both groups received the respective treatments for 8 weeks. Results: There was no significant difference between the two groups in terms of the SCORing Atopic Dermatitis and the 5‐dimensions Itch Scale at any of the time points (Weeks 2, 4 and 8). However, in the fexofenadine group, the level of serum interleukin (IL)‐31 decreased significantly from baseline to Week 8 of treatment. Conclusions: Although we could not conclusively confirm the clinical efficacy of adding oral fexofenadine to topical treatment in AD, serological evaluation indicates that fexofenadine treatment can lead to significant lowering of serum IL‐31 levels in patients with AD. [ABSTRACT FROM AUTHOR]

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One of the key challenges in developing a dry powder inhaler (DPI) of an inhalable potent fixed-dose combination (FDC) is the ability of the formulation to generate an effective and reproducible aerosol able to reach the lower parts of the lungs. Herein, a one-step approach is presented to expedite the synthesis of nanoaggregates made from a biocompatible and biodegradable polyamide based on L-lysine amino acid employing market-leading active pharmaceutical ingredients (fluticasone propionate (FP) and salmeterol xinafoate (SAL)) for the management of asthma. The nanoaggregates were synthesized using interfacial polycondensation that produced nanocapsules with an average particle size of 226.7 ± 35.3 nm and zeta potential of −30.6 ± 4.2 mV. Differential scanning calorimetric analysis and x-ray diffraction, as well as scanning electron microscopy of the produced FDC, revealed the ability of the produced nanocapsules to encapsulate the two actives and display the best aerodynamic performance. The FDC nanocapsules displayed 88.5% and 98.5% of the emitted dose for FP and SAL, respectively. The fine particle fraction of the nominated dose was superior to the marketed product (Seretide Diskus®, Brentford, United Kingdom). The in-vitro release study showed an extended drug release profile. Our findings suggest that nanoaggregates using polyamides based on L-lysine and interfacial polycondensation can serve as a good platform for pulmonary drug delivery of FDC systems. [ABSTRACT FROM AUTHOR]

This study aimed to quantitatively compare the efficacy of fluticasone furoate (FF) and fluticasone propionate (FP) in adolescents and adults with asthma. We searched the PubMed and EMBASE databases for placebo‐controlled trials that met the inclusion criteria. Pharmacodynamic models were established to describe the time–course of the primary outcome (trough forced expiratory volume in the first second [FEV1]). Secondary outcomes (asthma symptoms, quality of life and exacerbations) were also compared via a meta‐analysis. A total of 14 articles were included in the analysis, involving 6640 subjects. The efficacy plateau of the two drugs could be reached in 2 weeks. The changes from the baseline in trough FEV1 (95% CI) at week 2 of FF at 200 and 100 μg/day were 0.168 L (0.064–0.199) and 0.127 L (0.048–0.163), respectively. The changes from the baseline in trough FEV1 (95% CI) at week 2 of FP at 1000, 500, 250 and 100 μg/day were 0.133 L (0.049–0.171), 0.127 L (0.043–0.163), 0.117 L (0.039–0.150) and 0.093 L (0.032–0.129), respectively. The efficacy of FP had reached a plateau at the maximum evaluated dose (1000 μg/day), while a plateau effect was not seen at the maximum evaluated dose of FF (200 μg/day). In terms of secondary outcomes, the relative effects of the two drugs relative to the placebo were similar and did not show obvious dose–effect relationships. In this study, the time–course and dose–effect characteristics of FP, FF and placebo were quantitatively evaluated, providing necessary quantitative information for asthma‐related guidelines. [ABSTRACT FROM AUTHOR]

Background: The combination of the antihistamine azelastine (AZE) with the corticosteroid fluticasone propionate (FP) in a single spray, has been reported to be significantly more effective at reducing allergic rhinitis (AR) symptoms than treatment with either corticosteroid or antihistamine monotherapy. However, the biological basis for enhanced symptom relief is not known. This study aimed to compare gene expression profiles (760 immune genes, performed with the NanoString nCounter) from peripheral blood and nasal brushing/lavage lysate samples in response to nasal spray treatment. Methods: Moderate/severe persistent dust mite AR sufferers received either AZE (125 μg/spray) nasal spray (n = 16), FP (50 μg/spray) nasal spray (n = 14) or combination spray AZE/FP (125 μg AZE and 50 μg FP/spray) (n = 14) for 7 days, twice daily. Self‐reported symptom questionnaires were completed daily for the study duration. Gene expression analysis (760 immune genes) was performed with the NanoString nCounter on purified RNA from peripheral blood and nasal brushing/lavage lysate samples. Results: In nasal samples, 206 genes were significantly differentially expressed following FP treatment; 182 genes downregulated (−2.57 to −0.45 Log2 fold change [FC]), 24 genes upregulated (0.49–1.40 Log2 FC). In response to AZE/FP, only 16 genes were significantly differentially expressed; 10 genes downregulated (−1.53 to −0.58 Log2 FC), six genes upregulated (1.07–1.62 Log2 FC). Following AZE treatment only five genes were significantly differentially expressed; one gene downregulated (−1.68 Log2 FC), four genes upregulated (0.59–1.19 Log2 FC). Immune gene changes in peripheral blood samples following treatment were minimal. AR symptoms improved under all treatments, but improvements were less pronounced following AZE treatment. Conclusion: AZE/FP, FP, and AZE had diverse effects on immune gene expression profiles in nasal mucosa samples. The moderate number of genes modulated by AZE/FP indicates alternative pathways in reducing AR symptoms whilst avoiding extensive local immune suppression. Key Highlights: Antihistamine, steroid and combination nasal sprays elicit distinct gene expression profiles in nasal mucosa samples.Modest mucosal gene expression changes were noted for combination therapy compared with a steroid‐only formulation. [ABSTRACT FROM AUTHOR]

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

The purpose of this study was to evaluate the clinical effect of inhaled glucocorticoids on asthmatic children by high resolution CT (HRCT). 118 children with asthma were divided into observation group (n=63) and control group (n=55). The control group was given routine treatment, the observation group was given fluticasone propionate aerosol or Budesonide aerosol on the basis of the control group, the therapeutic effects of the two groups were observed, the thickness of segmental and sub segmental bronchial wall/airway outer diameter (T/D) and the percentage of airway wall area in total airway area (WA) were measured by HRCT. The therapeutic effect of the observation group was better than that of the control group (P<0.05). T/D and WA in the observation group were significantly lower than those in the control group (P<0.05). Compared with ineffective patients, effective patients had lower T/D and WA after treatment (P<0.05). The area under ROC curve of T/D and WA was 0.859 and 0.826, respectively, P<0.05. Inhaled glucocorticoids have a good effect on children with asthma, and HRCT quantitative parameters have a certain value in predicting the therapeutic effect. [ABSTRACT FROM AUTHOR]

Ranny van Weissenbruch,1 Ludger Klimek,2 Gabriella Gálffy,3 Melanie Emmeluth,4 Arkady Koltun,5 Ferdinand Kopietz,4 Duc Tung Nguyen,6 Hans Christian Kuhl,4 Wolfgang Pohl,7 Glenis K Scadding,8 David Price,9,10 Joaquim Mullol11 1Department of ENT Head and Neck Surgery, Wilhelmina Ziekenhuis, Assen, the Netherlands; 2Department of Otorhinolaryngology and Head and Neck Plastic Surgery, Zentrum für Rhinologie und Allergologie, Wiesbaden, Germany; 3Pulmonology Hospital, Torokbalint, Hungary; 4Global Medical Affairs, MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany; 5Mylan, Inc., Canonsburg, PA, USA; 6GBK Clinical Affairs, MEDA Pharma GmbH & Co. KG (A Mylan Company), Bad Homburg, Germany; 7Department of Respiratory and Pulmonary Diseases, Karl Landsteiner Gesellschaft, Institute of Clinical and Experimental Pneumology, Vienna, Austria; 8Roy National Throat Nose and Ear Hospital, London, UK; 9Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 10Observational and Pragmatic Research Institute, Singapore, Singapore; 11Rhinology Unit & Smell Clinic, ENT Department, Hospital Clinic Barcelona IDIBAPS University of Barcelona, CIBERES, Barcelona, Catalonia, SpainCorrespondence: Ranny van WeissenbruchWilhelmina Ziekenhuis, Europaweg-Zuid 1, Assen 9401 RK, the NetherlandsTel +31 592 325229Fax +31 592 325226Email r.van.weissenbruch@wza.nlPurpose: Patients with poorly controlled allergic rhinitis (AR) experience nasal symptoms, sleep disturbances, activity impairment, and decreased quality-of-life (QoL). MP-AzeFlu is safe and effective for moderate-to-severe seasonal and perennial AR, but its impact on QoL requires investigation in the real-world, especially among phenotypes of immunoglobulin (Ig)E-mediated AR. This subanalysis of an observational study evaluated response to MP-AzeFlu via assessment of sleep quality and trouble with daily activities.Patients and Methods: This multicenter, prospective, non-interventional, real-life study included a convenience sample of patients with a history of moderate-to-severe AR presenting with acute AR symptoms (visual analog scale [VAS] ≥ 50 mm). Over approximately 14 days of treatment with MP-AzeFlu (137 μg azelastine HCL and 50 μg fluticasone propionate administered via single 0.137-mL spray in each nostril twice daily), changes in sleep quality and trouble with daily work, school, social, and outdoor activities were evaluated using a VAS for the entire study population and for four subgroups based on IgE response phenotype. VAS scores ranged from “not at all troubled” (0 mm) to “extremely troubled” (100 mm).Results: Following MP-AzeFlu treatment, mean VAS scores for sleep quality impairment and work or school impairment decreased from 55.2 mm at baseline to 22.1 mm and 57.6 mm at baseline to 23.0 mm, respectively, after ∼ 14 days. Similar results were observed for mean VAS scores for impairment of social activity (55.1 mm to 22.4 mm) and impairment of outdoor activity (64.4 mm to 25.0 mm). For all VAS scores, results were similar across populations, regardless of phenotype of IgE-mediated disease, comorbidity, age, and sex.Conclusion: MP-AzeFlu relieves symptoms and improves patient-reported QoL, illustrated by better sleep quality and less impairment of work, school, social, and outdoor activities after 14 days. The QoL benefits of MP-AzeFlu were consistent regardless of the phenotype of IgE-mediated disease.Registration: Clinical Trial Registration (CTR) Number: EUPAS23075. Trial Register Date: March 12, 2018. First patient visit; Last patient visit: February 2018; April 2019.Keywords: azelastine hydrochloride, daily activities, fluticasone propionate, sleep

Introduction: Allergic rhinitis (AR) is a disease which affects >24% of the population in Russia. Triamcinolone acetonide (TAA) is a corticosteroid used for treating AR. This post hoc analysis assesses the efficacy of intranasal TAA in improving perennial AR (PAR) symptom scores over 4 weeks. Methods: NASANIF (NCT03317015) was a double-blind, parallel-group, multicenter, prospective, non-inferiority, phase III clinical trial in which patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) over 4 weeks. Our post hoc analysis evaluates weekly change in PAR symptoms using the reflective Total Nasal Symptom Score (rTNSS), overall and for individual symptoms (sneezing, nasal itching, rhinorrhoea, and nasal obstruction). Proportion of patients and time to achieve a ≥50 or ≥75% reduction in rTNSS were assessed. For rTNSS endpoints, a linear mixed-model methodology was used; for time-to-event endpoints, cumulative incidence functions were estimated using the Kaplan-Meier method, in the per-protocol population. Results: Of 260 patients, 128 each completed the study and were randomized to receive TAA or FP. From baseline to week 4, the changes in total rTNSS were −7.78 (95% CI: −8.1701 to −7.3967; p < 0.001) and −7.52 (−7.9053 to −7.1320; p < 0.001) for TAA and FP, respectively. Individual symptoms improved significantly from baseline. The proportion of patients achieving ≥50 and ≥75% reductions in total rTNSS was 88.0 and 67.2%, respectively in the TAA group. No significant differences were observed between the TAA and FP in any analyses. Conclusions: TAA produced effective and prolonged improvement of PAR symptoms over a 4-week treatment period. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory response. Persistent allergic rhinitis (PAR) is a subtype of AR, but the treatment of PAR is still a problem. Acupuncture is used as an alternative therapy for AR in clinical practice. The aim of this study is to evaluate the effectiveness of acupuncture therapy combined with fluticasone propionate nasal spray in comparison to fluticasone propionate nasal spray alone in the relief of symptoms for PAR.Methods: This study is a multicenter, single-blind, randomized controlled trial. A total of 260 eligible patients will be randomly assigned into the treatment group or the control group. The treatment group will receive the nasal fluticasone propionate combined with acupuncture, and the control group will receive fluticasone propionate nasal spray alone for 6 weeks. The primary outcome is the change in the Reflective Total Nasal Symptom Score (rTNSS) from baseline to the end of treatment, and the Total Non Nasal Symptom Score (TNNSS), reflective total ocular symptom score (rTOSS), Rhinitis Quality of Life Questionnaire (RQLQ), use of antiallergic drugs, and the Rhinitis Control Assessment Test (RCAT) are used as secondary outcomes. The participants will be followed up for another 24 weeks after treatment.Discussion: This clinical trial will be able to provide high level evidence on the acupuncture therapy combined with fluticasone propionate nasal spray in the treatment of PAR.Trial Registration: ISRCTN Registry, ID: ISRCTN44040506 . Registered on 22 July 2020. [ABSTRACT FROM AUTHOR]

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. Left untreated, EoE progresses to fibrous remodeling and stricture formation that impairs quality of life. Therefore, EoE requires either repeated treatments or maintenance therapy. Current guidelines recommend swallowed topical corticosteroids (STCs), proton-pump inhibitors (PPIs), or dietary intervention as initial options to induce and maintain long-term disease remission. Impractical exclusive elemental diets and suboptimal allergy testing-directed food avoidance paved the way for empirical elimination diets. These are moderately effective and highly reproducible in inducing EoE remission and allow for identification of specific food triggers. Step-up strategies, including two- and four-food rather than six-food elimination diets, should be considered as initial approaches for dietary treatment in patients of all ages, as they reduce the need for endoscopic procedures, shorten diagnostic processing time, and avoid unnecessary restrictions. Formulations of STC originally designed for asthma therapy are suboptimal for EoE treatment, with new effervescent orodispersible tablets and viscose formulations designed to coat the esophageal mucosa providing increased effectiveness at reduced doses. The anti-inflammatory effects of PPI in EoE are independent from gastric acid secretion inhibition; despite evidence from observational research, PPIs are the most commonly prescribed first-line therapy for EoE due to their accessibility, low cost, and safety profile. Double doses of PPI only induce remission in half of EoE patients, irrespective of the drug used or patients' age. Inflammatory rather than stricturing EoE phenotype and treatment duration up to 12 weeks increase chances of achieving EoE remission. Most responders effectively maintain long-term remission with standard PPI doses. Finally, endoscopic dilation should be considered in patients with reduced esophageal caliber or persistent dysphagia despite histological remission. This article provides a state-of-the-art review and updated discussion of current therapies and newly developed options for EoE. [ABSTRACT FROM AUTHOR]

Common inflammatory conditions of the airways, such as chronic rhinitis, nasal polyposis, seasonal and chronic allergic rhinitis can greatly affect a patient's health and quality of life. For each of these disorders, intranasal corticosteroids are suggested as a component of the therapy regimen because they can assist to lessen symptoms by reducing inflammation. In this randomized controlled trial, 30 people with rhinitis were enrolled to evaluate a new nano formulation of fluticasone propionate nano-nasal spray (FP-NNS) with commercially available nasal spray called FP-NS for the treatment of allergic rhinitis (15 to 60 years). 50 mcg dosages of FP-NNS were administered to patients in the morning and evening. This regimen was administered as a nasal spray for a 4-week effectiveness and safety phase. Analysis of variance was used to evaluate each efficacy endpoint. More of our clinical studies have shown that FP-NNS reduces inflammatory indicators in adults and children. [ABSTRACT FROM AUTHOR]

To compare the efficacy of single-breath continuous positive airway pressure manoeuvre (CPAP-M) with inhaled salbutamol, and a combination of both. Randomized, clinical study. A total of 62 client-owned horses (American Society of Anesthesiologists status III–V) anaesthetized for laparotomy. Horses were premedicated with intravenous (IV) xylazine (0.4–0.6 mg kg–1), anaesthesia was induced with midazolam (0.06 mg kg–1 IV) and ketamine (2.2 mg kg–1 IV) and maintained with isoflurane in oxygen using volume-controlled ventilation without positive end-expiratory pressure. If PaO 2 was < 100 mmHg (13.3 kPa), either a CPAP-M (50 cmH 2 O for 45 seconds) or salbutamol (0.002 mg kg–1) was administered. The intervention was considered successful if PaO 2 reached 100 mmHg (13.3 kPa). If PaO 2 remained < 100 mmHg (13.3 kPa), treatments were switched. PaO 2 /F i O 2 ratio and estimated shunt fraction (F-shunt) were derived from data obtained from arterial blood gas measurements. Dynamic compliance (C dyn) was calculated from variables recorded at the moment of arterial blood analysis. Fisher's exact tests compared success rates between treatments, and linear models were performed to test whether the treatment modified the values of the measurements; p < 0.05. Salbutamol was the first intervention in 28 horses and was effective in 22 horses. CPAP-M was the first intervention in 34 horses and was effective in 26 horses. CPAP-M after salbutamol was performed in six horses, with four responders, and salbutamol after CPAP-M was administered to eight horses, with one responder. Salbutamol, but not CPAP-M, significantly decreased F-shunt. Both salbutamol and CPAP-M significantly increased C dyn. Salbutamol and CPAP-M were comparably effective in improving oxygenation and C dyn in anaesthetized horses with PaO 2 < 100 mmHg (13.3 kPa). Whether combining both treatments might be beneficial needs to be confirmed on a larger number of horses. [ABSTRACT FROM AUTHOR]

Background: Intranasal corticosteroids (INCS) are the cornerstone of treatment for chronic rhinosinusitis. Although INCS are generally considered safe and effective, there is a concern that chronic use may lead to ocular adverse effects. Objective: To assess ocular safety of the exhalation delivery system with fluticasone propionate (EDS-FLU) in patients with chronic rhinosinusitis with nasal polyps. Methods: Ocular safety data were collected during two randomized, double-blind, placebo controlled studies with open-label extensions. Ophthalmologists performed tonometry, slit-lamp, and visual acuity examinations to assess intraocular pressure (IOP) and the presence of cataracts. Ocular examinations were conducted before double-blind treatment, at the end of the 16-week double-blind phase, and at the end of the 8-week open-label phase. The results of pooled data from patients who received EDS-FLU 186 µg (n = 160), EDS-FLU 372 µg (n = 161), and EDS-placebo (n = 161) twice daily are reported here. Results: At the end of the double-blind phase, six patients developed elevated average IOP > 21 mm Hg: two patients (1.2%) in the EDS-placebo group, three patients (1.9%) in the EDS-FLU 186 µg group, and one patient (0.6%) in the EDS-FLU 372 µg group. In addition, 6 of 482 patients developed cataracts: 3 patients in the EDS-placebo group, 2 patients in the EDS-FLU 186 µg group, and 1 patient in the EDS-FLU 372 µg group. At the end of the open-label phase, two additional patients showed IOP > 21 mm Hg and two additional patients developed cataracts. Conclusion: No increased risk of elevated IOP was detected with EDS-FLU; the rate of cataract development was similar to EDS-placebo and to that reported with other INCS. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the bronchoprotective and benefit/risk profiles of various inhaled corticosteroid (ICS) dosing regimens in mild asthma. Methods: A pharmacokinetic/pharmacodynamic model was developed and validated describing the relationship between ICS dose and time-course for airway bronchoprotection, [provocative concentration of adenosine monophosphate (AMP) causing ≥ 20% decline in forced expiratory volume in 1 s (FEV1) (AMP PC20)], for fluticasone furoate (FF), fluticasone propionate (FP) and budesonide (BUD). For regular ICS maintenance therapy (100% and 50% adherence) and infrequent or as-needed use (dosing 3–4 times per week), treatment effectiveness was expressed as percent time during 28 days when bronchoprotection exceeded either the threshold for a treatment-related bronchoprotective effect (AMP PC20 ≥ 0.25 doubling dose) or the threshold for a clinically significant bronchoprotective effect (AMP PC20 ≥ 1.0 doubling dose). This value was divided by the total ICS dose administered expressed in prednisolone equivalents to give a therapeutic index (TI). Results: The model-predicted time course of ICS-induced bronchoprotection with regular daily maintenance dosing and 100% adherence showed that all ICS at the highest recommended doses for mild asthma exceeded the threshold for clinically significant bronchoprotective effect for all or most of the 28-day dosing period, mean (90% CI); 100% (96.1–100), 99.9% (8.0–100) and 100% (58.2–100) with TI values of 16.9, 6.6 and 5.4 for FF 100 µg OD, FP 200 µg BID and BUD 200 µg BID, respectively. For simulated poor adherence (50%) to regular daily maintenance therapy, corresponding mean (90% CI) values were; 75.7% (39.4–89.1), 52.3% (0.7–69.2) and 51.3% (28.6–58.3) with TI values of 25.7, 6.9 and 5.6. For simulated infrequent/as needed use the corresponding values were; 77.0% (37.6–87.0), 25.5% (0.0–38.0) and 26.2% (14.3–31.5) with TI values of 26.1, 6.7 and 5.7. For all regimen/scenarios, FF had the most sustained efficacy and favourable TI followed by FP and BUD. Conclusions: At doses recommended for mild asthma, all ICS regimens provide sustained bronchoprotective efficacy when dosed regularly with high adherence. With poor adherence or use 3–4 times per week (infrequent/as needed), longer-acting ICS molecules will more likely provide sustained protection and a better TI versus shorter duration of action molecules (FF > FP ≥ BUD). These data highlight the benefits of using ICS as regular daily maintenance dosing in mild asthma and the potential risks of under-treatment with ICS (which may occur with ICS/formoterol as-needed approach in mild persistent asthma) associated with reduced levels of bronchoprotection. [ABSTRACT FROM AUTHOR]

Background: COPD is characterised by progressive lung function decline. Leveraging prior work demonstrating bronchial airway COPD-associated gene expression alterations, we sought to determine if there are alterations associated with differences in the rate of FEV1 decline.Methods: We examined gene expression among ever smokers with and without COPD who at baseline had bronchial brushings profiled by Affymetrix microarrays and had longitudinal lung function measurements (n=134; mean follow-up=6.38±2.48 years). Gene expression profiles associated with the rate of FEV1 decline were identified by linear modelling.Results: Expression differences in 171 genes were associated with rate of FEV1 decline (false discovery rate <0.05). The FEV1 decline signature was replicated in an independent dataset of bronchial biopsies from patients with COPD (n=46; p=0.018; mean follow-up=6.76±1.32 years). Genes elevated in individuals with more rapid FEV1 decline are significantly enriched among the genes altered by modulation of XBP1 in two independent datasets (Gene Set Enrichment Analysis (GSEA) p<0.05) and are enriched in mucin-related genes (GSEA p<0.05).Conclusion: We have identified and replicated an airway gene expression signature associated with the rate of FEV1 decline. Aspects of this signature are related to increased expression of XBP1-regulated genes, a transcription factor involved in the unfolded protein response, and genes related to mucin production. Collectively, these data suggest that molecular processes related to the rate of FEV1 decline can be detected in airway epithelium, identify a possible indicator of FEV1 decline and make it possible to detect, in an early phase, ever smokers with and without COPD most at risk of rapid FEV1 decline. [ABSTRACT FROM AUTHOR]

Evidence-based management of bronchial asthma and wheezing in children and adults recommends the employment of inhaled corticosteroids (ICSs). Difficulty in using some inhalation devices for ICS delivery, such as pressurized metered-dose and dry-powder inhalers, is common among young children and in the elderly, and for that reason, they are replaced with nebulizers. We reviewed comparative studies that evaluated funisolide with other ICSs currently available on the market, including beclomethasone dipropionate, fluticasone propionate, and budesonide. Moreover, we assessed the physicochemical properties of these ICSs in determining drug fate in the lung. Data indicate that the flunisolide output in respirable particles by any type of pneumatic nebulizer (traditional, open breath or breath-enhanced) is superior to the output of other ICSs. This is principally attributed to the higher water solubility of flunisolide. Furthermore, in vivo simulation studies demonstrate that the intersubject variability of the inhaled dose among asthmatic children was much greater for suspensions of fluticasone propionate and beclomethasone dipropionate than for those of flunisolide. The physicochemical properties and pharmacokinetic profile of flunisolide favor its employment in nebulization. [ABSTRACT FROM AUTHOR]

This study aimed to systematically investigate if any of the available drugs in the electronic health record (EHR) can be repurposed as potential treatment for coronavirus disease 2019 (COVID‐19). Based on a retrospective cohort analysis of EHR data, drug‐wide association studies (DrugWAS) were performed on 9,748 patients with COVID‐19 at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID‐19 disease outcomes. Patient exposure to a drug between 3‐months prior to the pandemic and the COVID‐19 diagnosis was chosen as the exposure of interest. All‐cause of death was selected as the primary outcome. Hospitalization, admission to the intensive care unit, and need for mechanical ventilation were identified as secondary outcomes. Overall, 17 drugs were significantly associated with decreased COVID‐19 severity. Previous exposure to two types of 13‐valent pneumococcal conjugate vaccines, PCV13 (odds ratio (OR), 0.31, 95% confidence interval (CI), 0.12–0.81 and OR, 0.33, 95% CI, 0.15–0.73), diphtheria toxoid and tetanus toxoid vaccine (OR, 0.38, 95% CI, 0.15–0.93) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID‐19 outcomes: acellular pertussis vaccine, 23‐valent pneumococcal polysaccharide vaccine (PPSV23), flaxseed extract, ethinyl estradiol, estradiol, turmeric extract, ubidecarenone, azelastine, pseudoephedrine, dextromethorphan, omega‐3 fatty acids, fluticasone, and ibuprofen. In conclusion, this cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID‐19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs. [ABSTRACT FROM AUTHOR]

The article highlights the urgent problem of modern medicine - allergic diseases. Over the past decades, there has been a significant increase in the prevalence of this pathology, the share of which in the general structure of the incidence of the population remains high to this day. The statistics are staggering. According to various sources, various manifestations of allergies affect from 10% to 40% of the world’s population. According to conservative estimates, more than 500 million people in the world. According to epidemiological studies, the amount of atopy is growing by 5-6% every year. The disease has a huge impact on the quality of life of the patient. Needless to say, an allergic disease can be accompanied by complications, including life-threatening. The big financial burden on the budget of our country is the economic costs of combating allergies and its complications. Therefore, the treatment of this nasology is one of the key issues both in the global and in Russian healthcare.Intranasal (topical) corticosteroids (IKS) are the drug of choice in the treatment of patients diagnosed with allergic rhinitis (AR). However, ICS are widely used in clinical practice and in the treatment of other diseases of the nose and paranasal sinuses. Depending on the nature of the pathological process, the duration of the drug can vary widely: from two weeks to several months or years. The purpose of this work is to systematize relevant publications and analyze possible uses for this group of drugs. The article reflects the issues of epidemiology, etiopathogenesis of allergic rhinitis. Consistently considered modern methods of treatment, in particular the use of (ICS) in therapy regimens. The results of international multicenter randomized controlled clinical trials are presented, the purpose of which was to determine and evaluate the efficacy and tolerability of ICS, in particular fluticasone propionate. It is concluded that fluticasone propionate is a modern and effective agent for the pathogenetic treatment of patients with not only allergic but also non-allergic rhinitis and can be recommended in the modern treatment regimen for both allergic and non-allergic rhinitis.

Currently, there is a wide introduction of inhaled glucocorticosteroids (InGCS) into otorhinolaryngological practice, which is explained by their local impact and low bioavailability, as well as proven high therapeutic effectiveness in various forms of rhinosinusitis (RS), adenoiditis and allergic rhinitis (AR). The feasibility of using InGCS enshrined in international consensus documents. Thus, this group of drugs is recommended for use in acute postviral and bacterial MS, chronic MS, polypous chronic rhinosinusitis, and in the postoperative period when intervening in the nasal cavity and in the paranasal sinuses.Recently, due to the deterioration of the environmental situation in the world and in connection with the improvement of the diagnosis of sensitization, the number of patients suffering from AR has increased. InGCS are included in the complex of treatment of moderate and severe course of intermittent and persistent AR.The effectiveness of InGCS in non-allergic eosinophilic rhinitis has been proved. In the complex therapy of adenoids and chronic adenoiditis, InGCS is also used with a high degree of efficiency, which allows such patients to avoid invasive treatment methods, including adenotomy.Particularly severe course of RS and adenoids is observed in patients with allergies. In this situation, the feasibility of using InGCS has been proven.One of the most effective and safe drugs in this group is fluticasone propionate (FP) - Flixonase, especially if the patient is sensitized to inhaled allergens. The advantages and possible side effects of FP are described.The authors cite the results of their own research, which used FP in the complex treatment of children with nasal breathing difficulties caused by adenoids and various forms of AR. As a result of 3 months of treatment and follow-up, 95.2% of patients recovered nasal breathing and no need for surgical removal of adenoids.The authors consider the feasibility and effectiveness of using inhaled glucocorticosteroids in the treatment of major diseases of the ENT organs, such as various forms of rhinosinusitis (RS), allergic and non-allergic rhinitis, and adenoiditis. It is emphasized that this group of drugs has an evidence base and is included in the main concession documents on otorhinolaryngology. Their advantages, pharmacotherapy and possible side effects are noted. The advantages of the drug fluticasone propionate (Flixonase), the relevance and advantages of its use are highlighted. The paper presents the authors own observations in the treatment of patients with nasal polypous chronic RS with this drug.

Background: Treatment of childhood lichen planus (LP) is challenging owing to high rate of relapses. Moreover, majority of treatment options for LP have been extrapolated from studies done in adults. Topical corticosteroid remains the first line of treatment in localized classic form of LP, but till date, no consensus exists regarding standardized therapy in children. Hence, we conducted this study to evaluate the efficacy of mid-potent topical steroid fluticasone propionate 0.005% in childhood LP. Aims and Objectives: The aim of this study was to evaluate the therapeutic efficacy of fluticasone propionate ointment 0.005% in childhood LP. Materials and Methods: Thirty-one patients (6 months to 18 years of age) with clinical and histopathologically confirmed diagnosis of LP were subjected to routine baseline severity assessment, patient/parent assessment, pretreatment photographic record of the fixed anatomical site under treatment, and then received topical mid-potent steroid therapy (fluticasone propionate ointment 0.005%) twice daily and cetirizine dihydrochloride in predefined doses for 8 weeks. Follow-up was done at the end of 2 weeks, 4 weeks, 6 weeks, and 8 weeks. After 8 weeks, a proportion of patients achieving clinical improvement and side effects were assessed. Observation and Results: The difference between pre- and posttreatment induration was not statistically significant (P = 0.336). The mean number of lesions before the start of treatment was 50.29, which reduced to 14.77 (P = 0.000) after treatment, and the mean of patients' itching score before treatment was 6.74 ± 1.6, which reduced to 2.61 ± 2.3 (P = 0.000) following treatment, which was statistically significant. Clinical improvement was seen in 67.7%, whereas 32.3% showed no improvement over a period of 8 weeks. Conclusion: Mid-potency steroid fluticasone propionate ointment twice daily is an effective therapeutic agent for localized childhood LP, with minimal side effects.

Objective: EP-104IAR is a novel, sustained-release, intra-articular (IA) formulation of the corticosteroid fluticasone propionate (FP), in development for the treatment of osteoarthritis (OA) pain. This study evaluated the safety, pharmacokinetics (PK) and efficacy of a single dose of EP-104IAR in patients with OA of the knee. Design: This was a multi-center, randomized, double-blind, placebo-controlled trial performed at 3 sites in Canada. Subjects with moderate to severe pain received either a single dose of the investigational product EP-104IAR (15 ​mg) or placebo (vehicle) and were evaluated for up to 42 weeks. The primary outcome measures were safety and PK. The study was not powered to assess efficacy, however patient reported outcome measures were analyzed to evaluate pain and symptom relief. Results: Thirty-two subjects were randomized (21 women, 11 men, mean age: 64.8 years). EP-104IAR was well tolerated. Average serum cortisol levels showed no clinically significant deviations compared to placebo and remained within the normal range of cortisol variation. Plasma PK concentrations were within acceptable safety margins, compared to marketed FP products. Synovial fluid FP levels were approximately 2 orders of magnitude higher and at efficacious concentrations for most subjects. Efficacy evaluations indicated that EP-104IAR provided an immediate improvement of OA symptoms and these effects persisted for 8–12 weeks consistently across all measures. Conclusions: This study provides evidence that 15 ​mg of EP-104IAR is well tolerated and has the potential for efficacy in OA patients. These data support further examination of EP-104IAR in larger clinical studies.

T helper-9 (Th9) is a new T cell subset involved in allergic rhinitis (AR) pathogenesis. Fexofenadine and fluticasone propionate are the first effective line of AR treatment. This study aimed to evaluate the effect of fexofenadine and fluticasone propionate on the gene expression levels of Interferon regulatory factor 4 (IRF4), B cell-activating transcription factor-like (BATF), and SPI1 gene-encoded protein (PU.1), essential transcription factors for Th9 cell differentiation, in AR patients. Twenty-six AR patients (aged 32.8 ± 9.1 years, 13 men and 13 women) were treated with fexofenadine and fluticasone propionate for one month. Expression levels of PU.1, IRF4, and BATF genes were measured using Real-Time PCR. Our results showed that after one month of treatment, the expression level of IRF4 and BATF genes decreased significantly (P < 0.001, P < 0.01, respectively), while PU.1 gene expression was not remarkably different. Overall, our results showed that after one month of treatment with fexofenadine and fluticasone propionate, the expression levels of IRF4 and BATF genes in AR patients decreased, which may be due to this treatment regimen. However, the exact mechanism of action of fexofenadine and fluticasone propionate needs further study.

(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.

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., (© 2024. The Author(s).)