Search Results (34)

The diagnosis and monitoring of eosinophilic esophagitis (EoE), a common pediatric pathology, typically involves invasive procedures such as an upper endoscopy with biopsies, imposing a significant burden on patients and healthcare systems. We aimed to assess miR-21-5p and miR-223-3p levels in pediatric EoE patients and evaluate their as potential non-invasive biomarkers of disease activity and response to treatments. We enrolled 13 children with EoE and 8 controls. Plasma and esophageal mucosa samples from patients were collected at diagnosis and after 8–10 weeks of therapy and compared with control samples. After microRNA(miRNA) extraction, the levels of miR-21-5p and miR-223-3p and their relevant target genes were analyzed. Bioinformatic analysis was used to identify the predicted target genes and pathways that are potentially relevant for disease pathophysiology. Plasma levels of miR-21-5p and miR-223-3p were significantly higher in EoE patients than in the controls, reflecting their levels in esophageal mucosa. The target genes of these miRNAs are involved in key signaling pathways (MAPK, Ras, and FoxO), relevant for EoE pathophysiology. Among these, STAT3 (Signal Transducer and Activator of Transcription 3) and PTEN (Phosphatase and Tensin Homolog), which are significantly downregulated in patient esophageal mucosa, are implicated in eosinophilic gastroenteropathies and autoimmune diseases. Following therapy (proton pump inhibitors and/or fluticasone propionate), plasma and tissue expression of both miRNAs significantly decreased and were no longer different from the controls. These microRNAs may serve as complementary non-invasive EoE markers and reduce the need for endoscopy/biopsies. Full article

Background/Objectives: Inhaler devices have been developed for the effective delivery of inhaled medications used in the treatment of pulmonary diseases. However, differing operating procedures across the devices can lead to user errors and reduce treatment efficacy, especially when patients use multiple devices simultaneously. To address this, we developed a novel dry powder inhaler (DPI), combining fluticasone propionate (FP), salmeterol xinafoate (SX), and tiotropium bromide (TB) into a single device designed for bioequivalent delivery compared to existing commercial products in an animal model. Methods: The micronized FP/SX/TB-loaded capsule was prepared by sieving, blending, and filling capsules. Capsule suitability of the drugs was investigated from the comparison of the stability of drugs within various capsule formulations to that of commercial products. The particle size of the drugs was adjusted using spiral air jet milling, and the ratio of lactose hydrate carriers was optimized by comparing the aerodynamic particle size distribution (APSD) with that of commercial products. To investigate the bioequivalence of micronized FP/SX/TB-loaded DPI to commercial products, the dissolution profile of FP/SX/TB particles and pharmacokinetics in rats were evaluated and compared to commercial products. Results: Capsules with hydroxypropyl methylcellulose (HPMC) without a gelling agent showed superior stability of the drugs compared to commercial products. The deposition pattern was influenced by the particle size of the drugs, and fine particle mass exhibited a significant correlation with the amount of fine carrier. Micronized FP/SX/TB-loaded DPI gave a similar APSD and dissolution profile compared to the commercial products and showed dose uniformity by the DPI device. Furthermore, micronized FP/SX/TB-loaded DPI exhibited bioequivalence to commercial products, as evidenced by no significant differences in pharmacokinetic parameters following intratracheal administration in rats. Conclusions: A novel triple-combination DPI containing FP/SX/TB was successfully developed, demonstrating comparable pharmacological performance to commercial products. Optimized FP/SX/TB-loaded DPI with HPMC capsule achieved bioequivalence in rat studies, suggesting its potential for improved patient compliance and therapeutic outcomes. This novel single-device DPI offers a promising alternative for triple therapy in pulmonary diseases. Full article

Asthma is a chronic lung disease characterized by airway inflammation, hyperresponsiveness, and narrowing, with a risk of life-threatening attacks. Most current treatments primarily consist of inhalable steroids, which are not without adverse effects. Recently, there has been growing interest in alternative approaches to asthma management. In this study, we investigated the anti-asthmatic effects of the non-steroidal compound CycloZ using acute and chronic mouse models of asthma. Allergic reactions were induced with house dust mite (HDM) extract, and CycloZ or fluticasone propionate (FP) was administered orally or intranasally, respectively. CycloZ significantly ameliorated the HDM-induced robust expression of Th2 cytokines in both models. CycloZ also decreased immune cell infiltration into the lungs and reduced IL-4 and IL-13 cytokine levels in bronchoalveolar lavage fluid (BALF). Moreover, CycloZ greatly attenuated the activation of the TLR-4 pathway, which is involved in HDM recognition and signaling. The beneficial effects of CycloZ were comparable to or even superior to the current steroid treatment, FP, suggesting that CycloZ could be a promising new option for asthma therapy. Full article

(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. Full article

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. Full article

Background: Macrophages and monocytes orchestrate inflammatory processes in the lungs. However, their role in the pathogenesis of chronic obstructive pulmonary disease (COPD), an inflammatory condition, is not well known. Here, we determined the characteristics of these cells in lungs of COPD patients and identified novel therapeutic targets. Methods: We analyzed the RNA sequencing (scRNA-seq) data of explanted human lung tissue from COPD (n = 18) and control (n = 28) lungs and found 16 transcriptionally distinct groups of macrophages and monocytes. We performed pathway and gene enrichment analyses to determine the characteristics of macrophages and monocytes from COPD (versus control) lungs and to identify the therapeutic targets, which were then validated using data from a randomized controlled trial of COPD patients (DISARM). Results: In the alveolar macrophages, 176 genes were differentially expressed (83 up- and 93 downregulated; P_adj < 0.05, |log₂FC| > 0.5) and were enriched in downstream biological processes predicted to cause poor lipid uptake and impaired cell activation, movement, and angiogenesis in COPD versus control lungs. Classical monocytes from COPD lungs harbored a differential gene set predicted to cause the activation, mobilization, and recruitment of cells and a hyperinflammatory response to influenza. In silico, the corticosteroid fluticasone propionate was one of the top compounds predicted to modulate the abnormal transcriptional profiles of these cells. In vivo, a fluticasone–salmeterol combination significantly modulated the gene expression profiles of bronchoalveolar lavage cells of COPD patients (p < 0.05). Conclusions: COPD lungs harbor transcriptionally distinct lung macrophages and monocytes, reflective of a dysfunctional and hyperinflammatory state. Inhaled corticosteroids and other compounds can modulate the transcriptomic profile of these cells in patients with COPD. Full article

Based on an indirect competitive method, a novel nano-Au/fluticasone propionate electrochemical immunosensor was successfully fabricated by combining the nanoscale effect, superior conductivity of nano-Au, stable Au−S chemical bond as well as strong interaction between glucocorticoid and the receptor, which was used to simultaneously detect eight kinds of glucocorticoids. The modified immunosensors’ electrochemical properties were explored by means of a cyclic voltammetry (CV) method and electrochemical impedance spectroscopy (EIS) measurements. Two factors (glucocorticoid receptor concentration, incubation time) were studied in order to obtain the optimal results. The immunosensor presents attractive electrochemical performance with a wide linear range (between 0.1 and 1500 ng⋅mL⁻¹) and low detection limit (between 0.057 and 0.357 ng⋅mL⁻¹), realizing the rapid multi-residue detection of a large class of glucocorticoids. Two glucocorticoids (hydrocortisone, triamcinolone) were detected in actual skincare samples, which obtained satisfactory detection results. Full article

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. Full article

The efficacy of the fix-dose salmeterol/fluticasone propionate combination in chronic obstructive pulmonary disease (COPD) was only shown for the original product. This investigator-initiated study aimed to prove the efficacy and safety of Salflumix Easyhaler^®, a second-entry product (dry-powder inhaler) in a real-life setting. The efficacy of the therapy was assessed in 440 COPD outpatients (36.1% classified as C&D groups according to GOLD) using the COPD assessment test (CAT) and the modified Medical Research Council (mMRC). During 86 ± 30 days, the frequency of COPD with a big and very big impact on life (CAT > 20 pts); and high scores of dyspnea (mMRC ≥ 2) decreased from 60.7% and 57.5% at I visit to 15.2% and 22.6% at III visits, respectively (p < 0.001). There was a greater improvement in newly diagnosed patients than those who switched from other devices due to insufficient disease control or patient dissatisfaction with the used inhaler. Patients’ satisfaction was scored 3.2–3.5 in a 4 pts scale. Physicians scored the burden related to the use of Salflumix Easyhaler^® as very low. Adherence exceeded 90%. This study supports effectiveness, satisfaction, and convenience with the use of this new product in COPD, and shows that ICS-containing DPI therapy is still improperly prescribed for patients with a low risk of COPD exacerbation in real-life settings. Full article

Asthma is a chronic obstructive pulmonary disease, affecting approximately 300 million people worldwide. Current therapies have disadvantages such as side effects and high costs. Alternatively, herbal plants have been used for decades as focal medicine to cure asthma. The goal of this research was to make use of molinspiration and pkCSM in silico tools to determine the drug-likeness of nine phytochemicals (mangiferonic acid, withaferin A, stigmasterol, 6-shogaol, rosmarinic acid, glycyrrhizin, alphitolic acid, oleanic acid, and kalambroside A) present in nine distinct herbal plants. These phytochemicals have been reported to have anti-asthmatic properties. The currently available fluticasone propionate drug was used as the positive control. Molinspiration findings showed that except for glycyrrhizin and kamabroside A, all other phytochemicals obeyed Lipinski’s and Verber’s rules. Furthermore, all phytochemicals except for glycyrrhizin and kalambroside A exhibited considerable bioactivity for nuclear receptors (NRs) with bioactivity scores ranging from 0.20 to 0.96. The pkCSM results indicated that mangiferonic acid, withaferin A, 6-shogaol, and stigmasterol exhibit high intestinal absorption (>80%), high Caco-2 permeability (log Papp > 0.90 × 10⁻⁶ cm/s), high lethal dose (LD₅₀ = 2.081 to 3.201 mol/kg), non-mutagenicity, and non-hepatotoxicity. Furthermore, these phytochemicals were non-inhibitors of cytochrome P450 enzymes. In conclusion, mangiferonic acid abundantly available in Pericampylus glaucus is regarded as the best phytochemical that can be developed into a drug against asthma, since it has good bioavailability, considerable bioactivity towards NRs, and higher LD₅₀ than the control drug. However, further wet lab experiments are required to develop mangiferonic acid as a potent anti-asthmatic drug. Full article

Mesoporous Silica Nanoparticles (MSN) are porous inorganic materials that have been extensively used for drug delivery due to their special qualities, such as biocompatibility, biodegradability, and non-toxicity. MSN is a promising drug delivery system to enhance the efficacy and safety of drug administration in nasal diseases like chronic rhinitis (CR). In this study, we used the sol-gel technique for MSN synthesis and incorporate fluticasone propionate (FP) for intranasal drug administration for the treatment of chronic rhinitis (CR). In order to confirm the particle size, shape, drug release, and compatibility, various instruments were used. MSN was effectively prepared with average sizes ranging between 400 $\pm 34\mathrm{nm}$ (mean $\pm \mathrm{SD}$) as measured by dynamic light scattering (DLS), while zeta potential verified in all cases their positive charged surface. To investigate MSN features, the Fourier transform infrared spectrometer (FTIR), scanning electron microscopy (SEM), transmission electron microscope (TEM), thermal analysis, X-ray diffraction (XRD), and nitrogen adsorption/desorption measurement were used. The loaded compound was submitted to in vitro dissolution tests, and a remarkable dissolution rate improvement was observed compared to the crystalline drug in both pH conditions (1.2 and 7.4 pH). By using an MTT assay cell viability was assessed. The expression levels of the anti-inflammatory cytokines IL-4 and IL-5 were also measured using mRNA extraction from rat blood. Other characterizations like acute toxicity and hemolytic activity were also performed to confirm loaded MSN safety. Loaded MSN was incorporated in nasal spray prepared by using innovator excipients including poloxamer. After this, its nasal spray’s physical characteristics were also determined and compared with a commercial product (Ticovate). Full article

In the present study, the blends of CS and Vanillin–CS derivative (VACS) were utilized for the preparation of printable inks for their application in three-dimensional (3D) printing procedures. Despite the synergic interaction between the blends, the addition of ι-carrageenan (iCR) as a thickening agent was mandatory. Their viscosity analysis was conducted for the evaluation of the optimum CS/VACS ratio. The shear thinning behavior along with the effect of the temperature on viscosity values were evident. Further characterization of the 3D-printed structures was conducted. The effect of the CS/VACS ratio was established through swelling and contact angle measurements. An increasing amount of VACS resulted in lower swelling ability along with higher hydrophobicity. Fluticasone propionate (FLU), a crystalline synthetic corticosteroid, was loaded into the CS/VACS samples. The drug was loaded in its amorphous state, and consequently, its in vitro release was significantly enhanced. An initial burst release, followed by a sustained release profile, was observed. Full article

The goal of this study was to develop an add-on device for dry powder inhalers (Accuhaler) via 3D printing to improve drug administration efficiency in patients with limited inspiratory capacity, including young children, the elderly, and those with chronic obstructive pulmonary disease. With salmeterol xinafoate and fluticasone propionate as model active pharmaceutical ingredients (API), the emitted API doses were used to assess the effectiveness of the add-on device. The APIs were quantified by an HPLC assay validated for specificity, range, linearity, accuracy, and precision. The motor power of the add-on device could be regulated to moderate fan speed and the air flow in the assembled device. When 50–100% of the fan motor power of the add-on device was used, the emitted dose from the attached dry powder inhaler (DPI) was increased. A computational fluid dynamics application was used to simulate the air and particle flow in the DPI with the add-on device in order to elucidate the operating mechanism. The use of the add-on device combined with a sufficient inhalation flow rate resulted in a larger pressure drop and airflow velocity at the blister pocket. As these characteristics are associated with powder fluidization, entrainment, and particle re-suspension, this innovative add-on device might be utilized to enhance the DPI emitted drug dose for patients with low inspiratory rates and to facilitate the provision of adequate drug doses to achieve the treatment outcomes. Full article

Inhaled corticosteroids (ICS) use is associated with an increased risk of Pseudomonas aeruginosa (PA) infection in patients with COPD. We aimed to evaluate the effects of ICS on alveolar macrophages in response to PA in COPD patients with and without baseline ICS treatment (COPD and COPD + ICS, respectively) as well as smoker and nonsmoker controls. To do so, cells were infected with PA and cotreated with budesonide (BUD) or fluticasone propionate (FLU). The analysis of NF-κB and c-jun activity revealed a significant increase in both factors in response to PA cotreated with BUD/FLU in smokers but not in COPD or COPD + ICS patients when compared with PA infection alone. The expression of Toll-like receptor 2 (TLR2) and the transcription factor c-jun were induced upon PA infection in nonsmokers only. Moreover, in the smoker and COPD groups, there was a significant increase in TLR2 and a decrease in c-jun expression when treated with BUD/FLU after PA infection, which were not observed in COPD + ICS patients. Therefore, the chronic use of ICS seemingly makes the macrophages tolerant to BUD/FLU stimulation compared with those from patients not treated with ICS, promoting an impaired recognition of PA and activity of alveolar macrophages in terms of altered expression of TLR2 and cytokine production, which could explain the increased risk of PA infection in COPD patients under ICS treatment. Full article

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. Full article