Quantification of fluticasone propionate in human plasma by LC-MS/MS and its application in the pharmacokinetic study of nasal spray at clinical doses.

We developed a method for quantifying fluticasone propionate (FP) using general-purpose liquid chromatography-tandem mass spectrometry equipment to measure the plasma concentration of FP for the pharmacokinetic study of FP following the administration of a prescribed nasal spray dose (100 µg). Using ammonium acetate (0.01 M)-formic acid (pH 2.9; 499:1, v/v) and methanol as the mobile phase, 3 pg/mL of FP was quantified. The relative error and standard deviation of the lower limit of quantification were <3.1%. The intra- and interday assay reproducibility was <3.5%. After 15 min of administering 200 µg FP nasal spray as the first dose, the FP concentration detected in the plasma of the two participants was 3.99 and 3.69 pg/mL. Subsequent doses of 100 µg FP were administered twice daily. The area under the plasma concentration-time curve values after 8-10 days of repeated administration of 100 µg of FP were approximately 1.6-fold higher than those achieved following a single administration of 200 µg of FP, which confirmed drug accumulation. The bioavailability of nasal FP was estimated to be 2% and 4%. This knowledge might help in reducing anxiety among patients who avoid using FP nasal spray, fearing its adverse effects.

An efficacy and safety evaluation of montelukast + fluticasone propionate vs. fluticasone propionate in the treatment of cough variant asthma in children: a meta-analysis.

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

[Cushing's syndrome with inhaled corticosteroid: Drug interactions to avoid]. / Syndrome de Cushing sous fluticasone inhalée : interactions médicamenteuses à éviter.

Cushing's syndrome is an iatrogenic event occurring during co-administration of inhaled corticosteroids and potent inhibitors of P450 cytochromes. We report the clinical case of a 29-year-old woman with a past history of asthma treated with inhaled fluticasone propionate (FP), chronic pulmonary aspergillosis and allergic bronchopulmonary aspergillosis (ABPA) treated with itraconazole (ITZ), and Mycobacterium xenopi infection treated with moxifloxacin (MXF), ethambutol (EMB) and clarithromycin (CLR). Four months after initiation of antibiotic and antifungal medication, the patient contracted Cushing's syndrome. Its etiology consisted in interaction between FP, ITZ and CLR, which led to pronouncedly increased corticosteroid concentrations in circulating plasma cells. Following on the one hand cessation of FP and ITZ and on the other hand hydrocortisone supplementation, evolution was favorable. Several cases of iatrogenic Cushing's syndrome induced by co-administration of FP and potent CYP3A4 inhibitors have been reported in the literature. If possible, FP should be avoided in patients being treated with CYP3A4 inhibitors. Due to its differing physicochemical properties, beclometasone may be considered as the safest therapeutic alternative.

The assessment of effectiveness, tolerance, and patient satisfaction with the use of a new fixed-dose combination product, containing salmeterol and fluticasone propionate, Salflumix Easyhaler® in the treatment of asthma in the daily clinical practice.

BACKGROUND: The effectiveness of a fix-dose salmeterol/fluticasone combination therapy in asthma was previously shown for the original product. The study aim was to evaluate the clinical effectiveness and safety of a second entry DPI - dry powder inhaler (Salflumix Easyhaler) in patients with asthma in everyday clinical practice. PATIENTS AND METHODS: This multicenter Investigator-Initiated Study that enrolled 2,037 adult outpatients with asthma treated with Salflumix Easyhaler, was conducted by 220 pulmonologists across Poland. Asthma control was assessed during 3 visits with 6 ± 2 weeks intervals based on the Asthma Control Test (ACT). In addition, patient Satisfaction with Asthma Treatment Questionnaire (SATQ) and adherence and adverse events (AEs) were monitored. RESULTS: During the observation (86 ± 30 days) the percentage of patients with controlled asthma (ACT 20-25 pts) increased from 35.5% at the first visit to 86.5% at the third visit (p < 0.001). In the subgroup analysis, there were more patients not obtaining asthma control among patients that switched from the treatment with other devices than in naive ones. Global SATQ scores increased from 5.8 ± 0.7 to 6.2 ± 0.6 during the observation. Patients' satisfaction with the use of the Salflumix Easyhaler was high. Adherence exceeded 95%. Eight AEs were reported. CONCLUSIONS: Salflumix Easyhaler is highly effective and well-tolerated by naïve patients with asthma and those switching from another device. In general, patients show good compliance with medical product and are satisfied with the use of this new device, and not reporting difficulties and errors related to its' use. Their physicians' overall perception of Salflumix Easyhaler use is very positive.

Osteonecrosis múltiple inducida por glucocorticoides / Multiple osteonecrosis induced bye glucocorticoids / Osteonecrose múltipla induzida por glicocorticóides

La osteonecrosis múltiple es una entidad poco frecuente que se define por el compromiso de al menos tres regiones diferentes. Es indispensable el abordaje multidisciplinario de los pacientes que la padecen tanto para el diagnóstico como el tratamiento oportuno. Presentamos el caso clínico de un paciente joven que presenta una osteonecrosis múltiple con compromiso de ambas caderas, hombros, rodillas, codo derecho y cuello de pie izquierdo. El principal factor de riesgo presente en nuestro caso es el consumo de glucocorticoides.

Multiple osteonecrosis is a rare entity that is defined by the involvement of at least three different regions. A multidisciplinary approach to patients who suffer from it is essential for both diagnosis and timely treatment. We present the clinical case of a young patient who presented multiple osteonecrosis with involvement of both hips, shoulders, knees, right elbow, and neck of the left foot. The main risk factor present in our case is the consumption of glucocorticoids.

A osteonecrose múltipla é uma entidade rara que se define pelo envolvimento de pelo menos três regiões diferentes. Uma abordagem multidisciplinar aos pacientes que sofrem com isso é essencial para o diagnóstico e tratamento oportuno. Apresentamos o caso clínico de um paciente jovem que apresenta osteonecrose múltipla envolvendo quadris, ombros, joelhos, cotovelo direito e pescoço do pé esquerdo. O principal fator de risco presente no nosso caso é o consumo de glicocorticóides.

Effects of Fluticasone Propionate on Klebsiella pneumoniae and Gram-Negative Bacteria Associated with Chronic Airway Disease.

Inhaled corticosteroids (ICS) are commonly prescribed first-line treatments for asthma and chronic obstructive pulmonary disease (COPD). Recent evidence has shown that ICS use is associated with changes in the airway microbiome, which may impact clinical outcomes such as potential increased risk for pneumonia in COPD. Although the immunomodulatory effects of corticosteroids are well appreciated, whether ICS could directly influence the behavior of respiratory tract bacteria has been unknown. In this pilot study we explored the effects of fluticasone proprionate, a commonly prescribed inhaled corticosteroid, on respiratory bacteria with an expanded focus on Klebsiella pneumoniae, a species previously implicated in fluticasone-associated pneumonia in COPD. We observed significant effects of fluticasone proprionate on growth responses of K. pneumoniae, as well as other bacterial species isolated from asthmatic patients. Fluticasone-exposed K. pneumoniae displayed altered expression of several bacterial genes and reduced the metabolic activity of bronchial epithelial cells and their expression of human ß-defensin 2. Targeted assays identified a fluticasone metabolite from fluticasone-exposed K. pneumoniae cells, suggesting this species may be capable of metabolizing fluticasone proprionate. Collectively, these observations support the hypothesis that specific members of the airway microbiota possess the functional repertoire to respond to or potentially utilize corticosteroids in their microenvironment. These findings lay a foundation for novel research directions into the potential direct effects of ICS, often prescribed long term to patients, on the broader airway microbial community and on the behavior of specific microbial species implicated in asthma and COPD outcomes. IMPORTANCE Inhaled corticosteroids are widely prescribed for many respiratory diseases, including asthma and COPD. While they benefit many patients, corticosteroids can also have negative effects. Some patients do not improve with treatment and even experience adverse side effects. Recent studies have shown that inhaled corticosteroids can change the make-up of bacteria in the human respiratory tract. However, whether these medications can directly impact the behavior of such bacteria has been unknown. Here, we explored the effects of fluticasone propionate, a commonly prescribed inhaled corticosteroid, on Klebsiella pneumoniae and other airway bacteria of interest, including primary species isolated from adult asthma patients. We provide evidence of growth responses to direct fluticasone exposure in culture and further examined fluticasone's effects on K. pneumoniae, including gene expression changes and effects of fluticasone-exposed bacteria on airway cells. These findings indicate that members of the human airway bacterial community possess the functional ability to respond to corticosteroids, which may have implications for the heterogeneity of treatment response observed clinically.

Radiographic Phenotypes Affect the Risk of Inhaled Corticosteroid-Associated Pneumonia in Patients with COPD.

Purpose: Few studies have reported the association between the radiographic characteristics and the development of pneumonia in patients with chronic obstructive pulmonary disease (COPD) treated with inhaled corticosteroids (ICSs). Our study aimed to assess the effect of radiographic phenotypes on the risk of pneumonia in patients treated with ICSs. Patients and Methods: This study retrospectively analysed all patients with COPD treated with ICSs in a subset of the Korea Chronic Obstructive Pulmonary Disorders Subgroup Study registry between January 2017 and December 2019. The association between radiographic phenotypes including the presence and severity of emphysema, airway wall thickening, or bronchiectasis on chest computed tomography were determined visually/qualitatively and the risk of pneumonia was analyzed using the Cox regression model. Results: Among the 90 patients with COPD treated with ICSs, 41 experienced pneumonia more than once during the median follow-up of 29 (interquartile range, 8-35) months. In univariate Cox regression analysis, older age, longer use of ICSs, use of fluticasone propionate or metered dose inhaler, and severe exacerbation events increased the risk of pneumonia. In multivariate analysis, the presence of emphysema (adjusted hazard ratio [aHR]=3.73, P=0.033), severity measured using the visual sum score (mild-to-moderate, aHR=8.58, P=0.016; severe, aHR=3.58, P=0.042), Goddard sum score (mild-to-moderate, aHR=3.31, P=0.058; severe, aHR=5.38, P=0.014), and the upper lobe distribution of emphysema (aHR=3.76, P=0.032) were associated with a higher risk of pneumonia. Subtypes of centrilobular and panlobular emphysema had a higher risk of pneumonia compared with paraseptal emphysema (aHR=3.98, P=0.033; HR=3.91, P=0.041 vs HR=2.74, P=0.304). The presence of bronchiectasis (aHR=2.41, P=0.02) and emphysema/bronchiectasis overlap phenotype (aHR=2.19, P=0.053) on chest CT was a risk factor for pneumonia in this population. However, severity of bronchiectasis and the presence or severity of bronchial wall thickening according to the visual sum score were not associated with the risk of pneumonia. Conclusion: Among patients with COPD treated with ICSs, radiographic phenotypes including the presence of emphysema, bronchiectasis or emphysema/bronchiectasis overlap phenotype, severity with emphysema, subtypes of centrilobular or panlobular emphysema, and upper lobe distribution of emphysema may help predict the risk of pneumonia.

Inhaled Corticosteroids and Mycobacterial Infection in Patients with Chronic Airway Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND: Inhaled corticosteroids (ICSs) have been widely used in chronic airway diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. However, whether ICS use causes mycobacterial infection is uncertain. Some conclusions of published studies were inconsistent. OBJECTIVE: We aimed to investigate the association between the use of ICSs and mycobacterial infections in patients with chronic airway diseases. METHODS: This review was registered on PROSPERO (CRD42021284607). We focused on examining the association between ICS use and mycobacterial infection (nontuberculous mycobacterial [NTM] infection as well as tuberculosis [TB]). We searched PubMed (MEDLINE), Sciencenet, Cochrane, and EMBASE databases for studies up to 2021 to retrieve articles. The enrollment conditions included gender, enrollment diagnosis and ICS use in chronic airway disease patients, and so on. Preclinical studies, review articles, editorials, reviews, conference abstracts, and book chapters were excluded. Methodologically, the study was assessed using the Newcastle Ottawa Scale, and Rev-man5 was used for statistical analysis. RESULTS: Ten studies (including 4 NTM and 6 TB articles) with 517,556 patients met the inclusion criteria and were included in this meta-analysis. From the NTM pooled analyses, ICS use was associated with increased odds of NTM infection in patients with chronic airway diseases (odds ratio [OR] = 3.93, 95% confidence interval [CI] 2.12-7.27), subgroup analysis showed that high-dose ICS use (OR = 2.27, 95% CI 2.08-2.48) and fluticasone use (OR = 2.42, 95% CI 2.23-2.63) were associated with increased odds of NTM infection risk in patients with chronic respiratory diseases. The TB pooled analyses showed a significant association between ICS use and risk of TB infection in patients with chronic respiratory diseases (OR = 2.01, 95% CI 1.23-3.29). Subgroup analysis showed that in chronic respiratory diseases, ICS use increased odds of TB infection in high-dose ICS use (OR = 1.70, 95% CI 1.56-1.86) and in COPD patients (OR = 1.45, 95% CI 1.29-1.63). CONCLUSION: Our meta-analysis indicated that ICS use may increase the odds of mycobacterial infection in chronic respiratory disease patients, and this conclusion is more applicable to patients with high dose of ICS or fluticasone in NTM infection subgroups. In addition, high-dose ICS use may have higher risk of TB infection in patients with chronic respiratory diseases, especially COPD. Therefore, we should be vigilant about the application of ICS use in chronic respiratory diseases to avoid infection.

Fluticasone propionate as a potential treatment for COVID-19.

Outpatient treatment options for mild to moderate COVID-19 are severely limited. While many therapeutic options have been proposed, very few have demonstrated the appropriate safety and efficacy to warrant approval by national or international regulatory bodies. Monoclonal antibodies have been shown to decrease hospitalization in high-risk patients, but use remains limited due to challenges associated with both production and administration, and other treatment options are urgently needed. The anti-inflammatory drug fluticasone propionate has recently emerged as a potential outpatient treatment option, especially for those with newly diagnosed disease. This manuscript reviews what is known about fluticasone and looks ahead to examine how the drug may be used in the future to address the COVID-19 pandemic.

Effect of acupuncture therapy combined with fluticasone propionate in the treatment of persistent allergic rhinitis: study protocol for a randomized controlled trial.

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.

Clinical Response and Cost-Savings Associated With Generic Fluticasone Propionate/Salmeterol Multidose, Dry-Powder Inhaler in Asthma Patients Managed in an Ambulatory Care Practice Setting.

BACKGROUND: Fluticasone propionate/salmeterol multidose, dry powder inhaler (MDPI) was the first and only authorized generic inhaled corticosteroid/long-acting beta agonist (ICS/LABA) combination inhaler at the time of this study. This offers the potential for significant prescription cost-savings for both patients and accountable care organizations. The objective of the study was to demonstrate patients' clinical response to generic fluticasone propionate/salmeterol MDPI when switched from one of its brand name competitors. METHODS: The study was approved by the Institutional Review Board at MCPHS University. This was a prospective chart review of a large, multi-center ambulatory care organization in the Greater Boston area. Patients 12 years of age or older who were switched from a brand-name ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI were included in the study. The primary endpoint was worsened asthma control requiring a change in therapy, oral corticosteroid therapy, or hospitalization at or before 12 weeks after the inhaler was switched. RESULTS: In total, 203 patients met inclusion criteria. Of those 203 patients, 35 had a change in therapy due to worsened asthma control (17.2% of patients, 95% CI 12.0% to 22.4%) within 12 weeks. Total projected yearly prescription cost-savings for patients who were switched and remained on the generic inhaler was $581,628. CONCLUSION: Eighty-three percent of patients maintained appropriate asthma control after switching from a brand ICS/LABA inhaler to the generic fluticasone/salmeterol MDPI for 12 weeks. Switching to the generic inhaler resulted in significant prescription cost-savings for the accountable care organization.

Evaluation of the ocular safety associated with the exhalation delivery system with fluticasone.

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.Clinical trials NCT01622569 and NCT01624662, www.clinicaltrials.gov.

Comparison of Risk of Pneumonia Caused by Fluticasone Propionate versus Budesonide in Chronic Obstructive Pulmonary Disease: A Nationwide Retrospective Cohort Study.

INTRODUCTION: Inhaled corticosteroids (ICSs) play an important role in lowering the risk of acute exacerbation of chronic obstructive pulmonary disease (COPD). However, ICSs are known to increase the risk of pneumonia. Moreover, previous studies have shown that the incidence rate of pneumonia varies depending on the type of ICS. In this study, the risk of pneumonia according to the type of ICS was investigated in a population-based cohort. METHODS: A retrospective cohort study was conducted using claims data of the entire population from the Korean National Health Insurance Service. Patients who were newly diagnosed with COPD and prescribed fluticasone propionate or budesonide were enrolled as study subjects. Cumulative doses of ICSs were classified into categorical variables to analyze the risk of pneumonia within identical ICS doses. RESULTS: A total of 47,473 subjects were identified and allocated as 14,518 fluticasone propionate and 14,518 budesonide users through 1:1 propensity score matching. Fluticasone propionate users were more likely to develop pneumonia than budesonide users (14.22% vs 10.66%, p<0.0001). The incidence rate per 100,000 person-years was 2,914.77 for fluticasone propionate users and 2,102.90 for budesonide users. The hazard ratio (HR) of pneumonia in fluticasone propionate compared to budesonide was 1.34 (95% CI 1.26-1.43, p<0.0001). The risk of pneumonia for fluticasone propionate compared to budesonide increased with higher ICS cumulative doses: 1.06 (0.93-1.21), 1.41 (1.19-1.66), 1.41 (1.23-1.63), and 1.49 (1.33-1.66) from the lowest to highest quartiles, respectively. CONCLUSION: ICS types and doses need to be carefully considered during treatment with ICSs in patients with COPD.

Drug interactions in HIV-infected children undergoing treatment with antiretrovirals. / Interacciones farmacológicas en niños con infección por VIH en tratamiento con antirretrovirales.

INTRODUCTION: Drug interactions are undesirable events observed in clinical practice. In patients with HIV infection on antiretroviral therapy (ART), it is particularly important to bear in mind that many drugs com monly used in pediatrics can cause such interactions. OBJECTIVE: to report a case of drug interaction between an antiretroviral drug (lopinavir/ritonavir) and inhaled corticosteroid in a child with HIV infection, and to review more frequent drug interactions in children on ART. CLINICAL CASE: 5-year- old male with history of stage N1 vertical transmitted HIV infection (1994 CDC classification), on ART from 8 months of age with zidovudine, lamivudine, and lopinavir/ritonavir, with successful virological and immunological outcome. Due to symptoms of allergic rhinitis (congestion, itchy nose, and nocturnal snoring) treatment with intranasal fluticasone was started. After 1 month of treatment, he developed cushingoid facies, weight gain, mixed dyslipidemia, insulin resistance, morning basal cortisol levels < 1 µg/dL, and Adrenocorticotropic hormone (ACTH) < 2 pg/ml, presenting ACTH stimulation test compatible with central adrenal insufficiency, attributed to a drug interaction with lopinavir/ritonavir due to known interaction. He started hydrocortisone replacement treatment, recovering hypothalamic-pituitary-adrenal axis function after 18 months. CONCLUSION: Knowledge of this and other drug interactions between ART and drugs commonly used in pediatrics is essential for the comprehensive management of patients with HIV infection, especially in the prevention of unwanted adverse effects.

Prescribing intranasal steroids in HIV-positive patients: systematic review of the literature.

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing's syndrome. METHOD: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted. RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019. CONCLUSION: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.

MP-AzeFlu in Moderate-to-Severe Allergic Rhinitis: A Literature Review.

Allergic rhinitis (AR) is prevalent, and many patients present with moderate-to-severe symptomatic disease. The majority of patients are not satisfied with their AR treatment, despite the use of concurrent medications. These gaps underscore the need for treatment with more effective options for moderate-to-severe AR. The authors' objective was to review systematically the efficacy and safety of MP-AzeFlu for the treatment of AR. The primary outcomes studied were nasal, ocular, and total symptoms. Other outcomes included time to onset and of AR control, quality of life, and safety. Searches of PubMed and Cochrane databases were conducted on May 14, 2020, with no date restrictions, to identify publications reporting data on MP-AzeFlu. Clinical studies of any phase were included. Studies were excluded if they were not in English, were review articles, did not discuss the safety and efficacy of MP-AzeFlu for AR symptoms. Treatment of AR with MP-AzeFlu results in effective, sustained relief of nasal and ocular symptoms, and faster onset and time to control compared with intranasal azelastine or fluticasone propionate. Long-term use of MP-AzeFlu was safe, with benefits in children, adults, and adults aged ≥65 years. Other treatment options, including fluticasone propionate and azelastine alone or the combination of intranasal corticosteroids and oral antihistamine, do not provide the same level of efficacy as MP-AzeFlu in terms of rapid and sustained relief of the entire AR symptom complex. Furthermore, MP-AzeFlu significantly improves patient quality of life. MP-AzeFlu is a currently available combination that may satisfy all these patient needs and expectations.

Comparison of the effect of fluticasone combined with salmeterol and fluticasone alone in the treatment of pediatric asthma.

INTRODUCTION: A systematic review and meta-analysis was performed to investigate the effect of fluticasone + salmeterol and fluticasone alone in the treatment of pediatric asthma. EVIDENCE ACQUISITION: Studies meeting specific selection criteria were selected from online databases, including Pubmed, Embase, and the Cochrane Library. The quality of randomized controlled trials was assessed using the Cochrane Library. Weighted mean difference (WMD) and 95% CI were used to evaluate the effect size of continuous variables, while rate ratio (RR) and 95% CI were used for dichotomous variables. EVIDENCE SYNTHESIS: A total of 11 studies, including 8272 pediatric asthma patients, were included in this meta-analysis. Among these, 4133 patients were in the salmeterol + fluticasone group. The changes in forced expiratory volume in 1 second in children with asthma in the salmeterol + fluticasone and fluticasone alone groups were significantly different (fixed effects model, WMD=3.26, 95% CI: 1.52-5.00, P=0.0002). Asthma exacerbation between two groups were significantly different (fixed effects model, RR=0.85, 95% CI: 0.73-0.98, Z=2.18, P=0.03). There was no difference in the incidence of adverse events between salmeterol + fluticasone and fluticasone alone in the treatment of pediatric asthma (P>0.05). When the control group was treated with double dose fluticasone, the difference of changes in FEV1 and asthma exacerbation in children with asthma between the two groups was not significant. CONCLUSIONS: The efficacy of salmeterol + fluticasone is better than fluticasone alone, and the efficacy of salmeterol + fluticasone is equal to doubling the dose of fluticasone in the treatment of pediatric asthma.

Comparative nasal airflow with loratadine-pseudoephedrine and fluticasone nasal spray for allergic rhinitis.

BACKGROUND: Although it is known that oral antihistamine-pseudoephedrine combination tablets have a faster onset than intranasal corticosteroid sprays in the treatment of allergic rhinitis after the first dose, the magnitude of change has not been measured in a comparative manner. Furthermore, the sensation of sprayed liquid in the nose may lead patients to mistakenly believe that intranasal steroid sprays work instantly. OBJECTIVE: To evaluate, numerically, nasal airflow changes provided by a single dose of loratadine-pseudoephedrine tablet (LP) and fluticasone propionate nasal spray (FP) in participants experiencing allergic rhinitis symptoms, including nasal congestion. METHODS: This single-center, double-blinded, placebo-controlled, crossover study evaluated objective nasal airflow changes in patients with a documented sensitivity to ragweed pollen. Participants were randomized to receive 1 of 4 treatment sequences, and their peak nasal inspiratory flow (PNIF) was measured in a span of 4 hours after pollen exposure in an environmental exposure unit. RESULTS: Average change in PNIF was 31% with LP in the course of the study, significantly greater than with placebo and FP (12% and 15%, respectively; P < .001). Nevertheless, FP did not produce a significant change compared with its placebo. At hour one post-dose, LP had a clinically significant 31% increase in PNIF, whereas FP only yielded an 8.6% increase (P < .001). Measurable nasal airflow improvements are associated with the opening of nasal passages, allowing congested patients to breathe more freely. CONCLUSION: A single dose of LP quickly and significantly (P < .001) improved nasal airflow after ragweed pollen challenge in an environmental exposure unit. Comparatively, FP did not display this same benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03443843.

Regular treatment with formoterol and an inhaled corticosteroid versus regular treatment with salmeterol and an inhaled corticosteroid for chronic asthma: serious adverse events.

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta2-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta2-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments. OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid. SEARCH METHODS: We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021. SELECTION CRITERIA: We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect. MAIN RESULTS: Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence). AUTHORS' CONCLUSIONS: Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.