Search

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) 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.

Background: A combination of fluticasone propionate and formoterol fumarate (FLUT/FORM; flutiform®) in a single aerosol inhaler has been developed. This study investigated the efficacy and safety of the combination compared to its individual components administered concurrently (FLUT+FORM). Methods: Patients aged 12 years or over (N=210) with mild to moderate-severe persistent, reversible asthma were randomized in a 1:1 ratio to 12 weeks of twice daily treatment with one of two doses of FLUT/FORM or FLUT+FORM in an open-label, parallel group, multicentre study in Europe. Total daily doses were FLUT/FORM: 200/20μg or 500/20μg; FLUT+FORM: 200/24μg or 500/24μg. The primary objective was to show non-inferiority of FLUT/FORM compared to FLUT+FORM based on post-dose forced expiratory volume in 1 second (FEV1) on Day 84. Results: FLUT/FORM had comparable efficacy to FLUT+FORM in the treatment of asthma with mean FEV1 30 to 60 minutes post-dose on Day 84 of 2.6L in both groups (per protocol groups; least squares mean difference: -0.03 L; 95%CI: -0.148, 0.081; p=0.004). The lower limit of the 95% CI was above the pre-defined non-inferiority threshold of ≥-0.2L. Analysis of other pulmonary function tests, patient reported outcomes, rescue medication use, asthma exacerbations and quality of life questionnaires were also comparable. The safety profiles of the two study groups were similar overall. Conclusions: Fluticasone/formoterol combination therapy has comparable efficacy to its individual components administered concurrently. The safety and tolerability profile of fluticasone/formoterol combination therapy is similar to that of its individual components.

Мета роботи: удосконалення лікування легкої персистуючої бронхіальної астми на підставі розроблення диференційної програми протизапальної терапії. Зі 120 дітей сформовані 3 групи залежно від ефективної базисної терапії (антилейкотрієновий препарат, флутиказону пропіонат або їх комбінація), яка дозволила досягти контролю над захворюванням. Результати. Найбільш високі концентрації лейкотрієнів C4/D4/E4 у сироватці крові спостерігалися у дітей 3-ї групи, навіть після лікування вони залишалися вищими, ніж у дітей контрольної групи. При рівні лейкотрієнів від 500 до 1000 пг/мл шанси досягти контролю над бронхіальною астмою за допомогою антилейкотрієнового препарату у 5,9 раза вищі порівняно з інгаляційними глюкокортикостероїдами (95% довірчий інтервал 2,01–18,2). А коли рівень лейкотрієнів (C4/D4/E4) перевищував 1000 пг/мл, комбіноване лікування є ефективнішим, ніж терапія антилейкотрієновим препаратом (відношення шансів (OR) = 6,7; СІ95% 2,5–17,8) та флутиказону пропіонатом (OR = 83,3; СІ95% 9,9– 667,9).Висновки. Антилейкотрієновий препарат як монотерапія показаний дітям 6–7 років з легкою персистуючою бронхіальною астмою при сироваткових рівнях лейкотрієнів від 500 до 1000 пг/мл. При рівні лейкотрієнів нижче від 500 пг/мл доцільно призначати флутиказону пропіонат, вище від 1000 пг/мл — комбінацію антилейкотрієнового препарату та інгаляційного глюкокортикостероїду.

Objectives: Guidelines for asthma and chronic obstructive pulmonary disease (COPD) have undergone significant changes. Specifically, inhaled corticosteroids (ICSs) either alone or in combination with a long-acting beta2-agonist (LABA) are now first-line treatment for asthma, while long-acting muscarinic antagonists alone or in combination with LABAs are first-line treatment of COPD. Data on local availability, cost, and affordability of these medicines in The Gambia are unknown. Materials and Methods: We surveyed all registered pharmacists in Gambia and calculated affordability indices relative to the prevailing wage of the lowest government worker. Results: Eight out of 18 registered pharmacists responded to the survey. Respondents were responsible for stocking 19 out 26 registered pharmacies in the country, resulting in a response rate of 44%. Salbutamol inhalers were widely available, stocked by the central medical stores and 6 out of 8 surveyed pharmacists. Only one pharmacist reported stocking beclometasone 50 mcg, budesonide 100 mcg, and fluticasone propionate 125 mcg inhalers. Aminophylline was stocked by 4/8 pharmacists. The price of salbutamol 100 mcg inhaler was Gambian Dalasi (GMD) 200 (US$ 4, 4 days’ wages), while ipratropium bromide 20 mcg cost GMD 675 (US$ 14, 15 days’ wages). ICS maintenance inhalers at private pharmacies cost 15, 26, and 28 days’ wages for beclomethasone 50 mcg, fluticasone propionate 125 mcg, and budesonide 100 mcg, respectively. Combination of ICS/LABA inhaler was 26 days’ wages while tiotropium bromide 18 mcg affordability was 95 days’ wages. Conclusion: Guideline recommended medications for the management of asthma and COPD in The Gambia are unavailable, expensive, and unaffordable.

Eosinophilic esophagitis (EoE) is a chronic allergen-mediated disease of the esophagus. Pharmacologic treatment has largely relied on repurposing corticosteroids. Ciclesonide (CIC) is a corticosteroid for the treatment of asthma with biochemical properties that improve topical potency.To determine whether CIC decreased clinicopathological features of EoE.We performed a retrospective cohort study of patients with EoE treated with CIC at a pediatric hospital from 2010 to 2019. Data were extracted from the electronic health record. Patients who were prescribed CIC with pre- and post-CIC endoscopic and histological data available were included for analysis.A total of 281 patients were treated with CIC and 81 met criteria for inclusion. Use of CIC was associated with reduced symptoms including dysphagia (P.001), abdominal pain (P.001), vomiting (P = .01), heartburn (P = .02), and behavior changes (P = .02). Average composite endoscopic reference scores decreased from 2.54 to 1.37 (P.001), with improvement in exudates, edema, and furrows (all P.001). Peak eosinophil counts decreased from 48 to 23 eosinophils/hpf (P.001). Forty-three patients (53%) achieved remission (15 eosinophils/hpf). Esophageal Candida was reported in 1 patient. Fasting morning cortisol concentrations were low in 10 of 31 patients tested. Six of these 10 patients had abnormal adrenocorticotropic hormone stimulation testing, 5 of 6 diagnosed with adrenal insufficiency before transition to CIC and 3 of 6 with subsequent normalization of adrenal function on CIC therapy.Patients with EoE treated with CIC experienced significant reductions in clinicopathological features of EoE. CIC can be considered an alternative therapy in patients with known adrenal insufficiency or at risk of developing adrenal insufficiency.

Introduction. Poor medication adherence significantly increases the likelihood of complications, which leads to a decrease in quality of life (QoL) in patients and an increase in treatment costs.Goal. To study the adherence and effectiveness of treatment in COPD patients (group D) using a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate (FF/UMEC/VI).Material and methods. The study included 26 male patients with severe COPD with frequent exacerbations (group D). All patients were recommended therapy with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate (FF/UMEC/VI). Patients were monitored for 12 months, and the following endpoints were recorded: hospitalization due to exacerbation of COPD, progression of COPD (decrease in FEV1), and death of the patient. In addition, the dynamics of treatment adherence, the number of SAT test scores, and the level of depression on the Beck scale were evaluated.Results. After 6 months of taking a fixed triple combination of FF/UMEC/VI, there was an improvement in treatment adherence in the form of a 15.3% decrease in the proportion of non-committed patients with COPD and an increase in the proportion of patients committed to therapy by 7.7%; the average frequency of exacerbations significantly decreased, this dynamics remained by the 12th month of follow-up. After 12 months, patients with COPD showed a statistically significant decrease in the proportion of patients who were not committed to treatment and a statistically significant increase in the proportion of patients who were committed to treatment for COPD; there was a statistically significant decrease in the frequency of severe depression in COPD patients; there was a statistically significant decrease in the proportion of patients with severe and moderate COPD influence on the quality of life.Conclusion. The results of our study confirmed the view that adherence plays a significant role in the effectiveness of treatment of COPD patients, and the use of a fixed triple combination of FF/UMEC/VI helps to increase it.

Background Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β2-agonists (LABAs) plus long-acting muscarinic antagonists (LAMAs) and LABAs plus inhaled corticosteroids (ICS) for COPD, uncertainty remains regarding their comparative effects. Research Question Can comparative effectiveness and safety of LABA plus LAMA (LABA/LAMA) and LABA plus ICS (LABA/ICS) FDCs vary by different individual components of the dual combinations in COPD? Study Design and Methods We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare the effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol plus glycopyrronium [IND/GLY] and vilanterol plus umeclidinium [VI/UMEC]) vs three commonly prescribed LABA/ICS FDCs (salmeterol plus fluticasone propionate [SAL/FP], formoterol fumarate plus budesonide [FF/BUD], and formoterol fumarate plus beclomethasone dipropionate [FF/BDP]) using the Taiwanese nationwide health care claims from 2014 through 2017. The primary effectiveness outcome was the annual moderate to severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were used to assess the effectiveness and safety outcomes, respectively. Results Patients with COPD initiating IND/GLY and VI/UMEC showed an 11% (incidence rate ratio [IRR], 0.89; 95% CI, 0.80-0.98) and 20% (IRR, 0.80; 95% CI, 0.71-0.90) reduced annual rate of moderate to severe exacerbations, respectively, than those initiating SAL/FP, but showed a similar rate as those initiating FF/BUD or FF/BDP. Both LABA/LAMA FDCs, compared with SAL/FP and VI/UMEC vs FF/BDP, were associated with a 27% (hazard ratio [HR], 0.73; 95% CI, 0.59-0.90) to 42% (HR, 0.58; 95% CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intraclass difference existed in rates of moderate to severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs, but not between LABA/LAMA FDCs. Interpretation Both LABA/LAMAs vs SAL/FP are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with FF/BDP or FF/BUD, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

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.

Introduction: Allergic rhinitis (AR) is a disease that affects ≤24% of people in Russia, significantly impairing quality of life (QoL). Intranasal corticosteroids, such as triamcinolone acetonide (TAA), are considered effective drugs for treatment. A post hoc analysis of data (phase III NASANIF trial) examined weekly QoL changes in patients receiving TAA for the treatment of perennial AR (PAR). Methods: NASANIF (NCT03317015) was a double-blind, parallel group, multicenter, prospective, noninferiority, phase III clinical trial. Patients with PAR were randomized (1:1) to receive TAA or fluticasone propionate (FP) for 4 weeks. Here, a post hoc analysis measures QoL using a shortened Rhinoconjunctivitis Quality of Life Questionnaire (miniRQLQ). Differences in miniRQLQ score were evaluated using a mixed linear model and descriptive statistics. A subgroup analysis was performed in patients with a previous diagnosis of allergic conjunctivitis. Results: Of 260 patients eligible for randomization, 128 each completed treatment with TAA or FP. Overall and individual domain scores progressively improved and were significantly different versus baseline at week 4 in both treatment groups: LS mean difference TAA: −30.92 (95% CI [−33.01 to −28.83]), p < 0.001, and FP: −31.13 (−33.23 to −29.04), p < 0.001. In both arms of the subgroup, there was a significant reduction in eye symptoms. There was no significant difference between the TAA and FP treatment groups in any analyses. Conclusions: TAA is effective in improving overall and individual domains of QoL in patients with PAR, over 4 weeks. Patients with a previous diagnosis of allergic conjunctivitis experienced significant improvements in QoL related to the resolution of these symptoms.

PURPOSE Relvar® (fluticasone furoate [FF]/vilanterol [VI]) is a once-daily inhaler with bronchodilator effect lasting 24 h. Our aim was to investigate the short- and long-term effects of FF/VI on exercise-induced asthma (EIA) in adolescents. METHODS Ninety-three adolescent asthmatics aged 12-18 years were referred for evaluation of EIA. Following a positive exercise challenge test (ECT), 22/44 were allocated to a single administration of salbutamol (400 μg) and 22/44 to FF/VI (92/22 μg) in a double-blind method. Thirty-five subjects were reassessed by repeat ECT 30-60 days of FF/VI. RESULTS Median FEV1 change post-ECT at baseline was -22.8% predicted (interquartile range [IQR] -26.1 and -18.0) for salbutamol and -21.0 (IQR -30.7 and -16.8) for FF/VI. Following bronchodilator, FEV1 improved similarly in both groups. Repeat ECT following 30-60 days of FF/VI resulted in negative ECT in 33/35 subjects; the median decrease in FEV1 of these 35 subjects was 22.6% predicted (IQR 29-18) before, and 4.6% predicted (IQR 8.7-2.5) after 30-60 days of FF/VI treatment (p

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.

Nicola A Hanania,1 Scott Caveney,2 Tedi Soule,2 Lee Tombs,3 Sally Lettis,4 Courtney Crim,5,6 David M Mannino,7 Hitesh Patel,2 Isabelle H Boucot4 1Airways Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA; 2US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC, USA; 3Precise Approach Ltd, Contingent Worker on Assignment at GlaxoSmithKline, Brentford, Middlesex, UK; 4Statistics, GlaxoSmithKline, Brentford, Middlesex, UK; 5R&D, GlaxoSmithKline, Research Triangle Park, NC, USA; 6Internal Medicine - Division of Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 7Department of Preventive Medicine and Environmental Health, University of Kentucky, College of Public Health, Lexington, KY, USACorrespondence: Nicola A HananiaAirways Clinical Research Center, Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USAEmail hanania@bcm.eduIntroduction: Concerns have been raised about the practical use and clinical benefits of medications and inhalers in older patients with chronic obstructive pulmonary disease (COPD). Here, we report analyses according to age from five clinical trials evaluating medications administered using the ELLIPTA dry-powder inhaler (DPI).Methods: Efficacy and safety according to age groups (< 65 and ≥ 65 years) were assessed using data from five clinical trials in patients ≥ 40 years of age with symptomatic COPD. There was a mix of pre-specified and post hoc analyses of two 24-week trials with fluticasone furoate (FF)/vilanterol (VI) 100/25 μg; one 24-week trial with umeclidinium (UMEC) 62.5 μg; and two 12-week trials with UMEC 62.5 μg + FF/VI 100/25 μg. The primary endpoint was trough forced expiratory volume in 1 second (FEV1) obtained 23 and 24 hours after dosing on the last day of the study.Results: A total of 2876 patients < 65 years of age and 2148 patients ≥ 65 years of age were enrolled across all studies of whom 1333 and 1111 patients, respectively, received treatment at the doses presented. Statistically significant and clinically meaningful treatment differences in improvement from baseline in mean trough FEV1 were reported for active comparators versus placebo at study end for both < 65 and ≥ 65 years subgroups (FF/VI vs placebo: 143 mL and 111 mL; UMEC vs placebo: 110 mL and 123 mL; UMEC + FF/VI vs placebo + FF/VI: 136 mL and 105 mL; p< 0.001 for all comparisons). The incidence of adverse events reported for active treatments was similar between age groups.Conclusion: These data provide evidence to support the use of FF/VI, UMEC, or UMEC + FF/VI, all delivered via the ELLIPTA DPI, to treat older (≥ 65 years) and younger (< 65 years) patients with COPD.Keywords: COPD, elderly, ELLIPTA dry-powder inhaler, fluticasone furoate/vilanterol, multiple-inhaler triple therapy, umeclidinium

Contact dermatitis is one the commonest dermatological condition which is managed by topical corticosteroids. Mid potent topical corticosteroids are commonly prescribed but there is no any comparative data between mometasone furoate and fluticasone propionate in the management of dermatitis.A real world retrospective study was conducted across India to compare the clinical assessment of mometasone 0.1% cream and fluticasone 0.005% cream in the management of contact dermatitis at 236 dermatology clinics.A data of 1106 patients were included in this analysis in which 598 were included in mometasone group while 508 in fluticasone group. At the end of 2 weeks, 216 patients (36.1%) in mometasone and 129 patients (25.4%) in fluticasone group achieved complete clearance of symptoms (pBoth, mometasone furoate and fluticasone propionate were effective and safe in treatment of eczema/dermatitis. But mometasone furoate had shown significantly better effectiveness as compared to fluticasone in all predisposing factors for the disease.

Chronic obstructive pulmonary disease (COPD) treatment guidelines do not currently include recommendations for escalation directly from monotherapy to triple therapy. This 12-week, double-blind, double-dummy study randomized 800 symptomatic moderate-to-very-severe COPD patients receiving tiotropium (TIO) for ≥3 months to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 mcg via ELLIPTA (n = 400) or TIO 18 mcg via HandiHaler (n = 400) plus matched placebo. Study endpoints included change from baseline in trough forced expiratory volume in 1 s (FEV1) at Days 85 (primary), 28 and 84 (secondary), health status (St George’s Respiratory Questionnaire [SGRQ] and COPD Assessment Test [CAT]) and safety. FF/UMEC/VI significantly improved trough FEV1 at all timepoints (Day 85 treatment difference [95% CI] 95 mL [62–128]; P

Jennifer Cane,1,2 Laura Tregidgo,1 Samantha Thulborn,1,2 Donna Finch,3 Mona Bafadhel1,2 1Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 2Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK; 3Alchemab Therapeutics, Cambridge, UKCorrespondence: Jennifer Cane Email Jennifer.cane@ndm.ox.ac.ukBackground: Chronic obstructive pulmonary disease (COPD) and asthma have heterogeneous inflammation with inhaled corticosteroids (ICS) as a mainstay of treatment. There is increased prevalence of non-typeable Haemophilus influenzae (NTHi) persistence in airways of patients with neutrophilic airway inflammation, potentially due to suppressed host defence after corticosteroid treatment. Antimicrobial peptides (AMPs) have antimicrobial activity against pathogens and immunomodulatory effects. We investigated whether AMPs associate with NTHi presence in COPD and asthma, and whether ICS alter this.Methods: Secretory leukocyte protease inhibitor (SLPI), osteopontin, elafin and beta defensin-1 were measured in sputum supernatants from healthy donors (n=9), asthmatics (n=21) and patients with COPD (n=14). Elafin and beta defensin-1 were measured in a primary human bronchial epithelial cells (HBECs) from healthy and COPD donors infected with NTHi and pre-treated with fluticasone propionate (FP) and budesonide (BUD). Internalised NTHi was quantified by qPCR.Results: Sputum SLPI was negatively correlated with FEV1 (p< 0.001, r=− 0.610), FEV1% predicted (p< 0.001, r=− 0.583) and FEV1/FVC (p=0.001, r=− 0.528). Sputum beta defensin-1 was negatively associated with FEV1 (p< 0.001***r=− 0.594). SLPI and beta defensin-1 levels in sputum were higher in the healthy controls and COPD group compared to the asthma group (p=0.001 and p=0.014) and (p< 0.001 and p=0.007, respectively). ICS use was associated with higher sputum osteopontin compared to those with no ICS use. NTHi infection of COPD HBECs produced higher levels of beta defensin-1 compared to healthy donors (mean (SD) release: 45.1pg/mL (7.3) vs 21.2pg/mL (7.3) respectively, p=0.014). Elafin release from HBECs from COPD donors did not change following NTHi infection; however, elafin from healthy donors was significantly reduced (%mean reduction: 23.7%, 95% confidence intervals (CI) of reduction: 5.3– 38.4%, p< 0.01).Conclusion: Sputum SLPI and beta defensin-1 may be markers to identify those patients with declining lung function. ICS use was associated with higher sputum osteopontin compared to those with no ICS use.Keywords: antimicrobial peptide, non-typeable haemophilus influenzae, chronic obstructive pulmonary disease

Ravi Kalhan,1 David Slade,2 Riju Ray,2 Chad Moretz,3 Guillaume Germain,4 François Laliberté,4 Qin Shen,5 Mei Sheng Duh,6 Sean Dale MacKnight,4 Beth Hahn3 1Asthma and COPD Program, Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 2US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NC, USA; 3US Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 4Groupe d’Analyse, Ltée, Montréal, QC, Canada; 5US Value Evidence and Outcomes, GlaxoSmithKline, Collegeville, PA, USA; 6Analysis Group, Inc., Boston, MA, USACorrespondence: Beth HahnUS Value Evidence and Outcomes, GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC, 27709-3398, USATel +1 919-274-0660Email Beth.a.hahn@gsk.comBackground: Comorbidities in patients with chronic obstructive pulmonary disease (COPD) are associated with increased medical costs and risk of exacerbations. This study compared COPD-related medical costs and exacerbations in high-cost, high-comorbidity patients with COPD receiving initial maintenance treatment (IMT) with umeclidinium/vilanterol (UMEC/VI) versus fluticasone propionate/salmeterol (FP/SAL), budesonide/formoterol (B/F), or tiotropium (TIO).Methods: This retrospective, matched cohort study identified patients from Optum’s de-identified Clinformatics Data Mart database who initiated UMEC/VI, FP/SAL, B/F, or TIO between January 1, 2014 and December 31, 2018 (index date defined as date of the first fill). Eligibility criteria included age ≥ 40 years at index, ≥ 1 pre-index COPD diagnosis, no pre-index asthma diagnosis, 12 months of continuous insurance coverage pre-index, and high pre-index costs (≥ 80th percentile of IMT population) and comorbidities (Quan-Charlson comorbidity index ≥ 3). Propensity score matching was used to control for potential confounders. On-treatment COPD-related medical costs (primary endpoint) and exacerbations were evaluated.Results: Matched cohorts were well balanced on baseline characteristics (UMEC/VI vs FP/SAL: n=1194 each; UMEC/VI vs B/F: n=1441 each; UMEC/VI vs TIO: n=1277 each). Patients receiving UMEC/VI had significantly lower COPD-related medical costs versus FP/SAL (difference: $6587 per patient per year; P=0.048), and numerically lower costs versus B/F and TIO. Patients initiating UMEC/VI had significantly lower risk of COPD-related severe exacerbation versus FP/SAL (hazard ratio [95% CI]: 0.78 [0.62, 0.98]; P=0.032), B/F (0.77 [0.63, 0.95]; P=0.016), and TIO (0.79 [0.64, 0.98]; P=0.028). The rate of COPD-related severe exacerbations was significantly lower with UMEC/VI versus FP/SAL (rate ratio [95% CI]: 0.73 [0.59, 0.91]; P=0.008) and B/F (0.73 [0.59, 0.93]; P=0.012), and numerically lower versus TIO (0.83 [0.68, 1.04]; P=0.080).Conclusion: These findings suggest that high-cost, high-comorbidity patients with COPD receiving UMEC/VI compared with FP/SAL, B/F, and TIO as IMT may have lower medical costs and exacerbation risk.Keywords: COPD, LAMA/LABA, medical costs, comorbidities, severe exacerbations

Background: Wixela Inhub is a generic version of Advair Diskus recently approved by the U.S. Food and Drug Administration. The Inhub inhaler delivers fluticasone propionate (FP)/salmeterol in a dry powder formulation. The goals of our studies were to demonstrate that the Inhub inhaler can be used by representative end users and confirm the robustness of the Inhub inhaler. Methods: Study 1: A nondosing usability assessment, the device orientation study, confirmed that intended users (represented by patients diagnosed with asthma or chronic obstructive pulmonary disease [COPD] who were naive to dry powder inhalers and current Advair Diskus users) could use the Inhub inhaler safely and effectively. Subjects were provided with an Inhub inhaler in commercial packaging, including instructions for use, and were asked to undertake three dose simulations using the inhaler. Subjects were encouraged to interact with this new drug delivery device as they would at home. Subjects were not provided with training on the use of the device. Subjects were observed interacting with the Inhub inhaler, and those who currently use Diskus were also observed interacting with the Diskus to determine whether their mental model of the use of Diskus impacted their interaction with the Inhub device, this assessment was not a primary outcome of the study. Study 2: This is an open-label clinical study to confirm the robustness of the Inhub inhaler after at home patient use. Subjects diagnosed with asthma or COPD were provided Inhub inhaler training and subsequently self-administered 3 weeks of twice daily doses of Wixela Inhub 250 μg FP/50 μg salmeterol in the home environment. The Inhub inhalers were returned to the investigator after ∼3 weeks of outpatient use for in vitro tests on the drug remaining in each inhaler. Results: Study 1 enrolled 110 subjects, and all completed the study. Most subjects (100/110) held the Inhub inhaler in the correct orientation and of those who did not, 9 still achieved a peak inhalation flow rate of ≥30 L/min and a total inhaled volume of ≥1 L, thus meeting the requirements of the study success criteria. In Study 2, 111 pediatric, adult, and elderly subjects with asthma or COPD received the study drug. After ∼3 weeks of outpatient use of the Inhub inhaler by subjects, comprehensive in vitro testing demonstrated that the FP and salmeterol pharmaceutical performance in the Inhub inhaler was preserved. Conclusions: The majority of subjects demonstrated safe and effective use of the Inhub inhaler. In vitro testing and inspections confirmed the robustness of the Inhub inhaler after outpatient use. Clinical trial registration number: NCT02474017

Indacaterol/glycopyrronium/mometasone (Enerzair® Breezhaler®) is a fixed-dose combination of the long-acting β2 agonist (LABA) indacaterol, the long-acting muscarinic antagonist (LAMA) glycopyrronium and the inhaled corticosteroid (ICS) mometasone furoate (hereafter referred to as mometasone) delivered via a capsule-based dry-powder inhaler. It is approved in the EU for use as maintenance treatment in adult patients with inadequately controlled asthma who had experienced one or more exacerbations in the previous year. The approval also includes an optional digital companion (sensor and app) that provides data on the patient's use of the inhaler. In the 52-week IRIDIUM trial in patients with inadequately controlled asthma, indacaterol/glycopyrronium/mometasone improved lung function to a greater extent than LABA/ICS combinations (i.e. indacaterol/mometasone and fluticasone propionate/salmeterol), but superiority in Asthma Control Questionnaire 7 score was not shown. In the 24-week ARGON trial, indacaterol/glycopyrronium/mometasone via a single inhaler was non-inferior to fluticasone propionate/salmeterol + tiotropium via two inhalers with regard to Asthma Quality of Life Questionnaire score. Indacaterol/glycopyrronium/mometasone was generally well tolerated, and the most common adverse events were respiratory in nature. In conclusion, combination therapy with indacaterol/glycopyrronium/mometasone represents a valuable option for the maintenance treatment of asthma, with the convenience of once-daily administration via a single inhaler.

Martin Anderson,1 Kathryn Collison,2 M Bradley Drummond,3 Melanie Hamilton,4 Renu Jain,2 Neil Martin,5,6 Richard A Mularski,7 Mike Thomas,8 Chang-Qing Zhu,9 Gary T Ferguson10 1Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 2Respiratory Therapy Area, GSK, Research Triangle Park, NC, USA; 3Pulmonary and Critical Care Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4R&D, GSK, Ware, Hertfordshire, UK; 5Global Medical Affairs, GSK, Brentford, Middlesex, UK; 6Institute for Lung Health, University of Leicester, Leicester, Leicestershire, UK; 7Department of Pulmonary and Critical Care Medicine, Kaiser Permanente Northwest Center for Health Research, Portland, OR, USA; 8Primary Care Research, University of Southampton, Southampton, UK; 9Biostatistics, GSK, Stockley Park West, Uxbridge, Middlesex, UK; 10Pulmonary Research, Institute of Southeast Michigan, Farmington Hills, MI, USACorrespondence: Gary T FergusonPulmonary Research, Institute of Southeast Michigan, Farmington Hills, MI, USATel +1 248-478-6561Email garytferguson@msn.comBackground: The influence of peak inspiratory flow (PIF) on dose delivery from dry powder inhalers (DPIs) and association with treatment efficacy in patients with chronic obstructive pulmonary disease (COPD) has not been fully determined. In vitro studies have demonstrated adequate dose delivery through ELLIPTA DPI at PIF ≥ 30 L/min. This analysis of two clinical trials and a real-world population of COPD patients determined spirometric PIF distribution, and explored the relationship between PIF and outcomes in the trials.Methods: The replicate Phase IV, 12-week, randomized, double-blind 207608/207609 (NCT03478683/NCT03478696) trials evaluated fluticasone furoate/umeclidinium/vilanterol via ELLIPTA DPI versus budesonide/formoterol+tiotropium in COPD patients. This post hoc analysis assessed spirometric PIF distribution at screening and relationship between PIF and lung function outcomes in the pooled 207608/207609 population. Spirometric PIF distributions in a real-world population of COPD patients were evaluated by retrospective analysis of the Kaiser Permanente Northwest (KPNW) database to assess similarities between clinical trial and real-world populations.Results: A total of 1460 (207608/207609) and 3282 (KPNW) patients were included. There was considerable overlap between spirometric PIF distributions for both populations. Overall, 99.7% and 99.8% of the 207608/207609 and KPNW populations, respectively, reported spirometric PIF ≥ 50 L/min, estimated as equivalent to ELLIPTA PIFR ≥ 30 L/min. In the 207608/207609 combined analysis, there was no significant interaction between spirometric PIF and treatment for lung function endpoints, indicating treatment effect is independent of PIF.Conclusion: Nearly all COPD patients in the 207608/207609 and KPNW populations achieved spirometric PIF values estimated as equivalent to PIFR of ≥ 30 L/min through the ELLIPTA DPI. Lack of correlation between spirometric PIF at screening and treatment efficacy aligns with consistent dose performance from the ELLIPTA DPI across a wide range of PIFs, achieved by patients with COPD of all severities.Keywords: COPD, inhaled triple therapy, patient outcomes, real-world studies, peak inspiratory flow rate, DPI

Background In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. Research Question Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? Study Design and Methods IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 μg, FF/VI 100/25 μg, or UMEC/VI 62.5/25 μg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George’s Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. Results The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [−1 to 16]; P = .070; 65-74 years, 22% [14-29]; P Interpretation FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. Clinical Trial Registration ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855

Purpose Laryngotracheal stenosis describes various airflow compromising conditions leading to laryngeal and tracheal narrowing, including subglottic and tracheal stenosis. Direct laryngobronchoscopy is the diagnostic gold standard for laryngotracheal stenosis. This study aimed to explore the effect of inhaled fluticasone propionate as adjuvant medical therapy in patients with laryngotracheal stenosis after balloon dilation. Methods This prospective randomized controlled trial was conducted from April 2019 to April 2020. Fourteen adults (≥ 18 years) with laryngotracheal stenosis consented to participate. All patients underwent endoscopic balloon dilation. Seven patients were treated with inhaled fluticasone propionate, and seven acted as controls. Detailed documentation of operative findings and pre- and post-balloon dilation spirometry measurements were recorded. Basic demographic data and operative details, including information about the percentage of laryngotracheal stenosis, distance of laryngotracheal stenosis from the vocal cords, the stenotic segment vertical length, and the largest endotracheal tube used before and after dilation were noted. Results Spirometry measurements were obtained on 34 occasions (17 before and 17 after balloon dilation). The two groups were similar in spirometry values after treatment. Both groups had significantly improved on most spirometry values after balloon dilation. Conclusion We found that using inhaled steroids after balloon dilatation in patients with laryngotracheal stenosis had no benefit over non-user patients in spirometry parameters during the short postoperative follow-up. To confirm this outcome, we recommend a large-scale double-blind study with a longer follow-up period. Supplementary Information The online version contains supplementary material available at 10.1007/s00405-021-06622-x.

Objective: The aim of the study was to ascertain the effect of nasal polyposis on cardiac functions. Material and Methods: A prospective randomized interventional open-label endpoint-controlled study was conducted in an academic tertiary care hospital. Thirty-one patients with chronic rhinosinusitis with nasal polyposis were enrolled and administered fluticasone furoate nasal spray for 3 weeks before randomly segregation into surgical or medical group. The treatment continued for 3 months in both groups. The SNOT-22 (Sino-Nasal Outcome Test-22) score, polyp grade, and right ventricular and pulmonary arterial functions were recorded in both groups before and after 3 months of the intervention. Results: Both groups had significant improvement in SNOT-22 scores after 3 months of intervention. Both groups showed improvement in cardiac functions, but statistical significance was found only in subjects who underwent surgery. Conclusion: Nasal polyp affects cardiac functions, and this needs further evaluation and research through studies on large samples.

Background: The InforMing the Pathway of COPD Treatment (IMPACT) trial demonstrated lower moderate/ severe exacerbation rates with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI or UMEC/VI in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Since IMPACT was a global study, post-hoc analyses were conducted by geographic region to investigate potential differences in overall findings. Methods: IMPACT was a 52-week, randomized, double-blind trial. Patients with symptomatic COPD and ≥1 moderate/severe exacerbation in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25µg, FF/VI 100/25µg, or UMEC/VI 62.5/25µg. Endpoints assessed in the overall, Western Europe and North America populations included on-treatment moderate/severe exacerbation (rates and time-to-first), trough forced expiratory volume in 1 second and St George’s Respiratory Questionnaire (SGRQ) total score. Safety was assessed. Results: Overall, 10,355 patients were enrolled, 3164 from Western Europe, 2639 from North America. FF/ UMEC/VI significantly reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/ VI in Western Europe (rate ratios 0.82 [95% CI 0.74-0.91], P

Background:Despite inhaled corticosteroid plus long-acting β2-agonist (ICS/LABA) therapy, 30–50% of patients with moderate or severe asthma remain inadequately controlled. We investigated the safety and efficacy of single-inhaler fluticasone furoate plus umeclidinium plus vilanterol (FF/UMEC/VI) compared with FF/VI. Methods:In this double-blind, randomised, parallel-group, phase 3A study (Clinical Study in Asthma Patients Receiving Triple Therapy in a Single Inhaler [CAPTAIN]), participants were recruited from 416 hospitals and primary care centres across 15 countries. Participants were eligible if they were aged 18 years or older, with inadequately controlled asthma (Asthma Control Questionnaire [ACQ]-6 score of ≥1·5) despite ICS/LABA, a documented health-care contact or a documented temporary change in asthma therapy for treatment of acute asthma symptoms in the year before screening, pre-bronchodilator FEV1between 30% and less than 85% of predicted normal value, and reversibility (defined as an increase in FEV1of ≥12% and ≥200 mL in the 20–60 min after four inhalations of albuterol or salbutamol) at screening. Participants were randomly assigned (1:1:1:1:1:1), via central based randomisation stratified by pre-study ICS dose at study entry, to once-daily FF/VI (100/25 μg or 200/25 μg) or FF/UMEC/VI (100/31·25/25 μg, 100/62·5/25 μg, 200/31·25/25 μg, or 200/62·5/25 μg) administered via Ellipta dry powder inhaler (Glaxo Operations UK, Hertfordshire, UK). Patients, investigators, and the funder were masked to treatment allocation. Endpoints assessed in the intention-to-treat population were change from baseline in clinic trough FEV1at week 24 (primary) and annualised moderate and/or severe asthma exacerbation rate (key secondary). Other secondary endpoints were change from baseline in clinic FEV1at 3 h post-dose, St George's Respiratory Questionnaire (SGRQ) total score, and ACQ-7 total score, all at week 24. Change from baseline in Evaluating Respiratory Symptoms in Asthma total score at weeks 21–24 was also a secondary endpoint but is not reported here. Exploratory analyses of biomarkers of type 2 airway inflammation on treatment response were also done. This study is registered withClinicalTrials.gov,NCT02924688, and is now complete. Findings:Between Dec 16, 2016, and Aug 31, 2018, 5185 patients were screened and 2439 were recruited and randomly assigned to FF/VI (100/25 μg n=407; 200/25 μg n=406) or FF/UMEC/VI (100/31·25/25 μg n=405; 100/62·5/25 μg n=406; 200/31·25/25 μg n=404; 200/62·5/25 μg n=408), with three patients randomly assigned in error and not included in analyses. In the intention-to-treat population, 922 (38%) patients were men, the mean age was 53·2 years (SD 13·1) and body-mass index was 29·4 (6·6). Baseline demographics were generally similar across all treatment groups. The least squares mean improvement in FEV1change from baseline for FF/UMEC/VI 100/62·5/25 μg versus FF/VI 100/25 μg was 110 mL (95% CI 66–153; pvsFF/VI 100/25 μg: 96 mL [52–139; pvs200/25 μg: 82 mL [39–125; p=0·0002]). These results were supported by the analysis of clinic FEV1at 3 h post-dose. Non-significant reductions in moderate and/or severe exacerbation rates were observed for FF/UMEC 62·5 μg/VI versus FF/VI (pooled analysis), with rates lower in FF 200 μg-containing versus FF 100 μg-containing treatment groups. All pooled treatment groups demonstrated mean improvements (decreases) in SGRQ total score at week 24 compared with baseline in excess of the minimal clinically important difference of 4 points; however, there were no differences between treatment groups. For mean change from baseline to week 24 in asthma control questionnaire-7 score, improvements (decreases) exceeding the minimal clinically important difference of 0·5 points were observed in all pooled treatment groups. Adding UMEC to FF/VI resulted in small, dose-related improvements compared with FF/VI (pooled analysis: FF/UMEC 31·25 μg/VI versus FF/VI, −0·06 (95% CI −0·12 to 0·01; p=0·094) FF/UMEC 62·5 μg/VI versus FF/VI, −0·09 (−0·16 to −0·02, p=0·0084). By contrast with adding UMEC, the effects of higher dose FF on clinic trough FEV1and annualised moderate and/or severe exacerbation rate were increased in patients with higher baseline blood eosinophil count and exhaled nitric oxide. Occurrence of adverse events was similar across treatment groups (patients with at least one event ranged from 210 [52%] to 258 [63%]), with the most commonly reported adverse events being nasopharyngitis (51 [13%]–63 [15%]), headache (19 [5%]–36 [9%]), and upper respiratory tract infection (13 [3%]–24 [6%]). The incidence of serious adverse events was similar across all groups (range 18 [4%]–25 [6%)). Three deaths occurred, of which one was considered to be related to study drug (pulmonary embolism in a patient in the FF/UMEC/VI 100/31·25/25 μg group). Interpretation:In patients with uncontrolled moderate or severe asthma on ICS/LABA, adding UMEC improved lung function but did not lead to a significant reduction in moderate and/or severe exacerbations. For such patients, single-inhaler FF/UMEC/VI is an effective treatment option with a favourable risk–benefit profile. Higher dose FF primarily reduced the rate of exacerbations, particularly in patients with raised biomarkers of type 2 airway inflammation. Further confirmatory studies into the differentiating effect of type 2 inflammatory biomarkers on treatment outcomes in asthma are required to build on these exploratory findings and further guide clinical practice.

Introduction. Eosinophilic esophagitis (EoE) represents chronic, a local immune-mediated disease with symptoms of esophageal dysfunction and histologically eosinophil-predominant inflammation and requires immediate endoscopy. Male gender is a strong risk factor. Case report. We presented a case of a 25-year-old young man with a history of allergic rhino-conjunctivitis, asthma, and intermittent severe feeding disturbance. The patient had begun sublingual immunotherapy therapy, containing specific soluble allergens for ambrosia. Six weeks after starting the ambrosia sublingual immunotherapy he developed burning epigastric pain, dysphagia, and odynophagia. Six days later, he was admitted to an emergency department due to choking on a solid of food. Esophageal histopathological findings were in favor of EoE. Sublingual immunotherapy was discontinued. He feels well now. Conclusion. The majority of cases of Eosinophilic esophagitis are diagnosed in spring or fall, 1-2 months following the peak of pollen season. Dysphagia, chest pain, food sticking, and bolus obstruction are the most common symptoms. Endoscopic findings are Schatzki ring, edema, exudates, furrows, and strictures. Six biopsies should be taken from areas with endoscopic mucosal abnormalities, and infiltration of eosinophils (more than 15 eosinophils/HRI) (HRI - high resolution imaging) is necessary for the diagnosis confirmation. Treatment options are proton pump inhibitors - oral dispersible tablets of budesonide or fluticasone propionate, an elimination diet. Sublingual immunotherapy should be discontinued. Family physicians should be aware of this complication in evaluating patients with dysphagia.

Rhinitis is one of the most common diseases and this term is used as an umbrella diagnosis for patients with different clinical phenotypes of the disease (allergic, non-allergic, infectious, etc.). Recognizing the high socio-economic burden of the disease and complexities of choosing an optimal therapy, it is important to focus on interdisciplinary interactions, which are reflected in modern clinical guidelines created by experts from ARIA, EAACI, EPOS, as well as national and professional societies. Patients with rhinitis symptoms often self-medicate, use the advice of pharmacist, receive recommendations from general practitioners in outpatient practice, and very few patients get specialists (ENT or allergist-immunologist) advice; herefore, in many cases, optimal criteria for disease control (symptoms, quality of life, objective measurements) cannot be achieved. Currently international professional communities have developed innovative therapeutic approaches based on knowledge of the phenotypes/endotypes of rhinitis to achieve such a control. Physicians in both primary and specialized care are encouraged to use step therapy. This approach to treatment is based on the control of disease symptoms, and intranasal corticosteroids (InGCS) are considered to be the most effective anti-inflammatory drugs for long-term control of rhinitis, especially in moderate-severe/severe cases. This well-proven efficacy of InGCS and their advantages over other classes of drugs make them the first-line therapy in the treatment of allergic rhinitis (evidence level A), as well as the drugs of choice for non-allergic rhinitis and rhinosinusitis. This review discusses fluticasone propionate, one of the in-demand InGCS, which has been the cornerstone of the treatment of allergic rhinitis for many years.

Background: Various combinations of inhaled corticosteroid (ICS), long-acting muscarinic antagonist (LAMA), and long-acting beta-agonist (LABA) have been used as triple therapy for stable chronic obstructive pulmonary disease (COPD). Objective: Our study was conducted to answer whether there were significant differences among various combinations in efficacy, for reducing exacerbation or mortality, and in safety, for increasing cardiovascular events or pneumonia. Method: We searched parallel-group randomized controlled trials (RCTs) comparing ICS/LAMA/LABA with other inhaled drugs in patients with stable COPD for at least 12 weeks in PubMed, EMBASE, the Cochrane Library, and clinical trial registries from inception to December 31, 2019. We conducted a network meta-analysis with Bayesian statistics using a random-effects model with heterogeneous variance structure (PROSPERO, CRD42019126757). Results: Nine different combinations of ICS/LAMA/LABA were identified in 21 RCTs containing 29,892 patients with moderate to very severe COPD. We could not find any significant evidence suggesting a better treatment for reducing total exacerbations or all-cause mortality among ICS/LAMA/LABA combinations. There were also no significant differences in moderate to severe exacerbation, COPD-related mortality, or cardiovascular disease-related mortality among ICS/LAMA/LABA combinations, and the risk of major adverse cardiovascular events was not different. A significantly lower risk of pneumonia was found in fluticasone propionate (FP)/glycopyrrolate/salmeterol (SAL) than FP/tiotropium/SAL {median odds ratio [OR] (95% credible interval [CrI]) = 0 [0–0.72]} and FP/umeclidinium/SAL {median OR (95% Crl) = 0 [0–0.97]}. Conclusion: There were no significant differences in clinical outcomes, including acute exacerbation and all-cause mortality among various ICS/LAMA/LABA combinations in patients with moderate to very severe COPD.

Background: Rhinoconjunctivitis is a common health problem that plagues the lives of children and adolescents alike with a significant impairment of the quality of life. Purpose: Aim of this study was to investigate the effect of intranasal corticosteroid, fluticasone furoate, on the change of IOP in allergic rhinitis patients. Materials and Methods: This was a prospective observational study carried at the Ophthalmology outpatient department of a Government Medical College in West Bengal involving all consecutive patients attending ENT OPD for allergic rhinitis of age group 12 years and above and prescribed fluticasone furoate nasal spray. The IOP of patients were measured before and after start of steroid nasal spray and follow up was done at regular interval. One and half year and follow up was done on 1st, 2nd, 4th, 8th and 12th week respectively. Results: A total of 108 patients were selected for the study, out of which 100 remained till the end of all follow ups. The IOP for each eye was compared with baseline IOP values (RE: 16.02±2.29, LE: 16.04±2.20) and at the end of the study the P value for each follow up was calculated. The t test revealed that there was no significant change (increase/decrease) in IOP in any eye over the course of time. r values shows that there was a strong positive linear correlation of IOP between and within the eyes at different levels of assessment after the starting of the treatment. Even after age group adjustment, there was no statistical difference in IOP between the eyes among the various age groups. Conclusion: The study demonstrates no statistically significant increase in IOP after the administration of fluticasone furoate nasal spray. We believe, therefore, that fluticasone furoate administered for a short time for the treatment of nasal allergy, is safe in terms of its effect on IOP in the Indian population. Keywords: Allergic rhinoconjunctivitis, Fluticasone furoate, Intranasal steroids, Steroid induced glaucom

Chronic obstructive pulmonary disease (COPD) is becoming a leading cause of morbidity and mortality in China. In the IMPACT trial, fluticasone furoate[FF]/umeclidinium[UMEC]/vilanterol[VI] single-inhaler triple therapy demonstrated lower rates of moderate/severe exacerbations than dual therapy with FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations. This analysis investigates the China cohort and its consistency with the overall ITT population. 10,355 patients were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg for 52 weeks. Endpoints included: annual rates of exacerbations, time-to-first on-treatment moderate/severe exacerbation and change from baseline in trough forced expiratory volume in 1 s (FEV1) at Week-52. Clinical trial registration is NCT02164513 (CTT116855). 535 patients (5.2%) were from China. Annual on-treatment moderate/severe exacerbation rate was 0.81 with FF/UMEC/VI versus 0.96 with FF/VI (rate ratio: 0.84; 95% confidence interval [CI]: 0.64, 1.11; p = .227) and 0.80 with UMEC/VI (rate ratio: 1.02; 95% CI: 0.72, 1.44; p = .929). Hazard ratio for time-to-first moderate/severe exacerbation was 0.84 (95% CI: 0.63, 1.11; p = .218) for FF/UMEC/VI versus FF/VI and 0.89 (95% CI: 0.62, 1.27; p = .516) versus UMEC/VI. Significant improvements in mean change from baseline in trough FEV1 were observed for FF/UMEC/VI versus FF/VI (treatment difference 137 mL; 95% CI: 86, 188; p p = .050). Health status was improved with FF/UMEC/VI versus both dual therapies. Results were similar to the overall ITT population. No new safety signals were identified. Single-inhaler triple therapy with FF/UMEC/VI versus FF/VI or UMEC/VI reduced the rate and risk of exacerbations, and improved lung function and health status in the China cohort similar to the overall ITT population. No new safety signals were identified.

Purpose 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.

Purpose The purpose of this review is to discuss the development of Wixela™ Inhub™, a generic equivalent of Advair Diskus®, a fixed-dose combination of fluticasone propionate/salmeterol powder for oral inhalation for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. Summary We provide an overview of the Inhub device and the bioequivalence studies that have been conducted to date. Briefly, the in vitro performance, improvements in forced expiratory volume in 1 s, and the fluticasone propionate/salmeterol dose strengths for Wixela Inhub and Advair Diskus were comparable. Conclusion The bioequivalence demonstrated by the totality of clinical and in vitro data supports the use of Wixela Inhub and provides a treatment option for patients with asthma or COPD., Plain Language Summary The Wixela™ Inhub™ device has been developed as a generic equivalent of Advair Diskus®, and provides a combination treatment for patients with asthma whose symptoms are not controlled with inhaled corticosteroids alone and for those with chronic obstructive pulmonary disease (COPD) who are at a high risk for exacerbations. We provide information about the Inhub device and studies conducted to show how Inhub and Diskus are comparable products. Based on the similar results between the two devices, Inhub can be used as a treatment option for patients with asthma or COPD.

Aim: to determine the efficacy and safety of clobetasol propionate compared with fluticasone propionate in the form of ointment for the treatment of psoriasis patients. Materials and methods. A total of 65 psoriasis patients were included in the study, 40 healthy individuals were included in the control group, all aged 14 to 65. Psoriasis patients were divided into 2 therapeutic groups: I – received topical treatment with fluticasone propionate; II – with clobetasol propionate. The severity of psoriasis was assessed by BSA and PASI index. Assessment of itching severity was carried out by a ten-point visual analogue scale. The quality of life was assessed according to the Ukrainian version of DLQI questionnaire. Results. PASI index averaged 16.50 ± 0.65 points, and BSA index was 9.30 ± 0.94 % in the examined patients before the treatment. On average, the DLQI index in patients with psoriasis before the treatment was 13.80 ± 0.27 points. PASI index was lower in psoriasis patients treated with clobetasol propionate compared with the therapeutic group I patients. The ΔPASI indicator (%) at the end of the treatment was significantly lower in patients from the I therapeutic group, compared with the group of patients who used clobetasol propionate for treatment of psoriasis. Patients who used clobetasol propionate had lower scores for pruritus and excoriation at the end of the treatment compared with patients from the I therapeutic group. The DLQI index at the end of the treatment was significantly higher in the I therapeutic group compared with its values in patients who used clobetasol propionate in the complex treatment. Conclusions. The use of topical corticosteroid clobetasol propionate in the form of ointment is the effective treatment for psoriasis, which causes a rapid regression of psoriatic rashes, a decrease in PASI and BSA indices, a decrease in pruritus and its objective signs, and indirectly improves the quality of life.

Background: Wixela™ Inhub™ is a fluticasone propionate/salmeterol dry powder inhaler developed as a generic equivalent of Advair Diskus® for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Wixela Inhub and Advair Diskus are comparable in terms of functionality, user interface, and device resistance. The primary objectives of the studies were to evaluate in vitro dose delivery with Wixela Inhub compared with Advair Diskus at relevant flow rates and to explore inhalation profiles generated by patients with asthma or COPD. Methods: In vitro studies: Emitted dose (ED) and individual dose aerodynamic particle size distribution (APSD) were measured at flow rates ranging from 30 to 90 L min-1. Patient inhalation study: Inhalation profile recording was conducted three times in each patient (40 children with asthma, 14 adults with asthma, and 14 adults with severe-to-very-severe COPD) with an empty Inhub in an open-label study. The primary endpoint was peak inhaled flow rate (PIFR). An additional endpoint was peak pressure drop. Results: In vitro studies: ED and APSD delivered from Wixela Inhub showed low flow dependency across the patient-relevant flow-rate range. Wixela Inhub gave in vitro performance comparable with Advair Diskus for all strengths and flow rates. Patient inhalation study: For Inhub, mean PIFR was lowest for children with asthma ages 4 to 7 years (50.6 L min-1) and highest for adults with asthma (74.8 L min-1). For adults with severe-to-very-severe COPD, mean PIFR was 69.5 L min-1 with Inhub. The PIFRs observed with Diskus were higher than those with Inhub, consistent with slightly higher resistance measured in vitro. The difference in resistance did not impact demonstration of bioequivalence and does not impact substitutability of the product. Peak pressure drop values were comparable between Diskus and Inhub. Conclusions: Comparable in vitro performance of Wixela Inhub to Advair Diskus confirmed that Wixela Inhub is a generic equivalent to Advair Diskus across all patient groups.

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.

Rationale: In the IMPACT (Informing the Pathway of Chronic Obstructive Pulmonary Disease Treatment) trial, fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) significantly reduced exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations. Objectives: To understand whether inhaled corticosteroid (ICS) withdrawal affected IMPACT results, given direct transition from prior maintenance medication to study medication at randomization. Methods: Exacerbations and change from baseline in trough FEV1 and St. George’s Respiratory Questionnaire results were analyzed by prior ICS use. Exacerbations were also analyzed while excluding data from the first 30 days. Measurements and Main Results: FF/UMEC/VI significantly reduced the annual moderate/severe exacerbation rate compared with UMEC/VI in prior ICS users (29% reduction; P

Background: Nasal polyps (NPs) are inflammatory outgrowths of paranasal sinus mucosa that occur in one to four percent of the population and most commonly cause congestion, obstruction, or hyposmia. Intranasal corticosteroids, along with short courses of oral corticosteroids, are most often recommended for symptomatic nasal polyposis, prior to consideration of surgical intervention. We present the first reported case of spontaneous nasal polypectomy, occurring after use of fluticasone propionate (XHANCE®) and zileuton (Xyflo®). Methods: A 43-year-old Asian-Indian male with history of allergic rhinitis, asthma, and nasal polyposis had been prescribed subcutaneous immunotherapy for five years without effectiveness before another polypectomy was scheduled. After the polyps resurfaced, the patient was prescribed prednisone and underwent another polypectomy. He later presented with persistent NPs and congestion, as well as diffuse lymphadenopathy and pruritic eyes and ears. Fluticasone Propionate was continued as maintenance therapy and Zileuton was prescribed in place of Montelukast (Singulair®). Results: After several weeks of the new treatment regimen, the patient reported polyp irritation and movement, as well as influenza-like symptoms. Epistaxis soon occurred, followed by a spontaneous polypectomy. Three more polyps were expelled with bloody discharge. The patient reported resolved hyposmia and reduced symptoms thereafter. The treatment regimen was continued without change or further episodes of epistaxis and polypectomy. Conclusion: Few case reports in the literature describe polyp autoamputation. We report the first instance of spontaneous nasal polypectomy in the literature, induced by Fluticasone Propionate and Zileuton.

Background Intranasal corticosteroids are the most efficacious anti-inflammatory medications for allergic rhinitis (AR). However, the efficacy and safety of intranasal corticosteroids in children have not yet been subject to specific research in China. The aim of this study was to investigate the efficacy and safety of fluticasone furoate nasal spray (FFNS) in a Chinese pediatric population. Methods In this phase 4 randomized, double-blind, placebo-controlled, multicenter study, pediatric AR patients aged 2–12 years were randomized 1:1:1, receiving either FFNS 55 µg or 110 µg or placebo. Electronic diary cards were completed to record symptoms, rescue medication use, and treatment compliance. Anterior rhinoscopy and overall response to therapy were evaluated and recorded. Results Patients treated with FFNS at either dose experienced a significantly greater reduction in daily reflective total nasal symptom score compared with placebo. This was maintained in a younger subset of patients (2–6 years). Drug-related adverse events occurred in Conclusions This study demonstrates favorable efficacy and safety profiles for FFNS 55 µg or 110 µg in Chinese pediatric populations (2–12 years), supporting its use in clinical treatment for AR children, including younger children aged 2–6 years. Impact The aim of this study was to investigate the efficacy and safety of intranasal fluticasone furoate in Chinese pediatric allergic rhinitis. This research not only addresses the deficiency in efficacy and safety data for intranasal corticosteroids in very young patients (aged 2–6 years) worldwide but also demonstrates that fluticasone furoate nasal spray shows a favorable benefit/risk profile at different dose levels. Our data will be of interest to the broad readership of Pediatric Research and will positively contribute to the dialog regarding the treatment of allergic rhinitis in children aged 2–6 years.

Omar S Usmani,1 Nicola Scichilone,2 Benjamin Mignot,3 Dennis Belmans,3 Cedric Van Holsbeke,3 Jan De Backer,3 Roberta De Maria,4 Erika Cuoghi,4 Eva Topole,4 George Georges4 1Airway Disease Section, National Heart and Lung Institute, Imperial College, London, UK; 2PROMISE Department of Medicine, University of Palermo, Palermo, Italy; 3FLUIDDA, Kontich, Belgium; 4Chiesi Farmaceutici, SpA, Parma, ItalyCorrespondence: George GeorgesChiesi USA Inc., 175 Regency Woods Place, Ste. 600, Cary, NC 27518, USATel +1 (919) 678 6611 x1536Email george.georges@chiesi.comIntroduction: There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and non-extrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs.Materials and Methods: Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients’ high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition.Results: HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were < 1, indicating greater peripheral than central deposition (0.48± 0.13, 0.48± 0.13 and 0.49± 0.13 for BDP, FF and GB, respectively; 1.96± 0.84, 0.97± 0.34 and 1.20± 0.48 for FluF, VI and UMEC, respectively).Conclusions: Peripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB.Keywords: tomography, X-ray computed, metered dose inhalers, dry powder inhalers, inhaled corticosteroid, long-acting beta2 agonist, long-acting muscarinic antagonist

Chad Moretz,1 Beth Hahn,1 John White,2 Alyssa Goolsby Hunter,2 Breanna Essoi,2 Caitlin Elliott,2 Riju Ray3 1US Value Evidence & Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Optum, Eden Prairie, MN, USA; 3US Medical Affairs, GlaxoSmithKline, Research Triangle Park, NCCorrespondence: Beth HahnGSK, 5 Moore Drive, Research Triangle Park, Durham, NC, USATel +1 919 274 0660Email beth.a.hahn@gsk.comBackground: Long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) provide greater improvements in lung function and symptoms than inhaled corticosteroid (ICS)/LABA in patients with chronic obstructive pulmonary disease (COPD). This study evaluated symptom burden and Global Initiative for Obstructive Lung Disease (GOLD) categorization among patients who recently initiated umeclidinium/vilanterol (UMEC/VI; LAMA/LABA) or fluticasone propionate/salmeterol (FP/SAL; ICS/LABA) single-inhaler dual therapy.Methods: COPD-diagnosed Medicare Advantage enrollees aged ≥ 65 years were identified from the Optum Research Database (ORD). Eligible patients had ≥ 1 pharmacy claim for UMEC/VI or FP/SAL in the 6-month period before sample identification, with no evidence of triple therapy (ICS/LAMA/LABA), asthma, or lung cancer. Symptom burden was assessed via cross-sectional surveys using the COPD Assessment Test (CAT) and modified Medical Research Council (mMRC) dyspnea scale. Patients were classified into GOLD categories using patient-reported symptoms and claims-based exacerbation history. Treatment groups were balanced on potential confounders using inverse probability of treatment weighting (IPTW). CAT and mMRC scores were analyzed with generalized linear regression models using IPTW propensity scores.Results: The final analytic sample included 789 respondents (UMEC/VI: N=392; FP/SAL: N=397). Approximately 66% patients were classified as GOLD B when assessing symptoms with CAT and mMRC together, or CAT alone; more patients were classified as GOLD A (∼ 40%) than GOLD B (∼ 36%) using mMRC alone. Proportions of patients in each GOLD group were similar between treatment cohorts. Post-IPTW multivariable modeling showed similar symptom burden between treatment groups.Conclusion: After controlling for baseline characteristics, symptom burden was similar between patients receiving UMEC/VI or FP/SAL. GOLD classification using mMRC produced more conservative results compared with CAT, potentially underestimating patient symptoms. Many patients receiving FP/SAL were classified as GOLD A or B, despite GOLD recommending non-ICS-containing therapy in these patients. These findings support the need for routine assessment of symptoms in patients with COPD.Keywords: COPD, fluticasone propionate/salmeterol, umeclidinium/vilanterol, CAT, mMRC, GOLD group

Treating twenty-five cases of chronic resistant otitis externa with fluticasone propionate (Flixonase®): a case series Utilising Flixonase® in treatment of chronic otitis externaKey points:Chronic cases of otitis externa, resistant to conventional treatments are notoriously difficult to treat, with resolution in these cases challenging.Guidelines suggest the use of corticosteroid in chronic otitis externa, however, there is no specific advice on which corticosteroid to utilise.Our case-series demonstrates the potential benefit of fluticasone propionate in patients who have previously failed a multitude of conventional management options.Despite the limitations of our study, our experience highlights a gap in the literature and suggest fluticasone propionate as an exciting and potentially important tool in the arsenal of the otolaryngologist.

Systemic corticosteroids are considered to be the standard treatment for allergic bronchopulmonary aspergillosis (ABPA). However, there is controversy regarding use of inhaled corticosteroid (ICS) therapy for ABPA. Here we report a case of ABPA that was successfully treated with inhaled fluticasone furoate/vilanterol (FF/VI) and oral voriconazole (VRCZ). The patient was a 62-year-old Japanese man with bronchiectasis and diabetes mellitus who presented with fever, cough, and purulent sputum. Computed tomography scans of the chest showed consolidation in the left upper and lower lobes. Laboratory investigations revealed an abnormal increase in the number of eosinophils (3,340/mm3) and elevated levels of C-reactive protein (3.04 mg/dL) and serum immunoglobulin E (IgE) (763 U/mL). Eight days after admission, he experienced a sudden attack of asthma. Aspergillus-precipitating antibodies were positive and Aspergillus fumigatus was detected in sputum culture. These results were consistent with a diagnosis of ABPA, and he was started on inhaled FF/VI and oral VRCZ. Systemic corticosteroids were not used because of the patient's history of diabetes mellitus and left atrial thrombus. His symptoms and consolidation improved significantly after treatment. He has not experienced an exacerbation for more than 3 years. In mild cases of ABPA in which total IgE is relatively low, inhaled FF/VI in combination with oral VRCZ can be considered as an alternative treatment to systemic corticosteroids in patients with ABPA.

Allergic rhinitis has been on the rise because of urbanization and major population shift in addition to changes in the particulate matter in the atmosphere. Intranasal corticosteroid sprays are recommended as first-line prescription treatment in all cases of allergic rhinitis. The propensity of co-existing non-apparent lower airway hyper-responsiveness is also on the rise and must be evaluated. The aim of this study is to compare the symptomatic improvement, changes in nasal eosinophilia and asymptomatic airway hyper responsiveness before and after short term treatment with steroid nasal spray. Fifty patients meeting the inclusion criteria for allergic rhinitis with no symptoms of asthma underwent pulmonary function tests and assessment of symptoms before and after one-month treatment with inhalational steroid nasal spray (Fluticasone Furoate), in the standard adult dosage. Based on TNSS (Total nasal symptom score) and TOSS (Total ocular symptom score), all 50 patients showed significant improvement after treatment. Among 20 patients with > 50 eosinophils per high power field, 80% had 0–10 eosinophils per high power field on nasal smear after treatment. Among 40 patients with mild large airway obstruction, 37 showed significant improvement in FEV1 data. Also FEV1/FVC data showed significant improvement. Significant improvement (FEF25–75 > 50%) was also noticed in small airway disease after treatment among the 5 patients. The study showed that lower airway hyper responsiveness coexists with allergic rhinitis and treating allergic rhinitis with just steroid nasal spray assists in reducing the former, supporting the concept of Unified Airway Disease (UAD).

The present study was conducted to evaluate the efficacy of topical therapy in patients with allergic rhinitis by fluticasone propionate as well as corticosteroid propionate in conjunction with fluticasone propionate alone. The study aims to evaluate the efficacy of topical treatment on people with Allergic Rhinits (AR). The medicines propionate fluticasone and antihistamine corticosteroids and propionate fluticasone alone were administered to patients with allergic rhinitis. AR was tested. A comparison of the effectiveness of topical treatment with Azelastine of fluticasone propionate and Fluticasone to suppress Allergic Rhinitis symptoms was assessed. Significant disruptions in the quality of living, health as well as function are linked with potentially severe allergic rhinitis. The most prevalent form of recurrent rhinitis is allergic rhinitis, impacting between 10 and 20% of the world population. Statistics show that there is an exponential increase in this condition. The common signs of human rhinorrhea, sneezing, coughing, respiratory inflammation, vomiting and weeping of skin, palatal scratching and ear coughing are considerably higher(* P=.001). The average symptom value (84,14 per cent) was significantly minimised during the test by Fluticasone propionate nasal spray. The intensity of complication decreased substantially by the administration of fluticasone propionate + azelastine hydrochloride nasal spray often functions (91.16 per cent). A mixture of Fluticasone propionate and Azelastine hydrochloride is better than Fluticasone propionate nasal spray to relieve the reactions of Allergic Rhinitis.

Background : MP- AzeFlu (azelastine/fluticasone propionate in one spray) is the most effective allergic rhinitis (AR) treatment available. Its effect on asthma control in co- morbid patients is unknown. We examined whether MP- AzeFlu altered asthma control in patients with AR and asthma. Method : This pre- post historical cohort study, carried out using the Optimum Patient Care Database, included patients aged ≥12 years from UK general practice with active asthma in the year before MP- AzeFlu initiation. Active asthma was defined as a recorded diagnosis, with ≥ 1 prescription for reliever or controller inhaler in the year prior to and including the initiation date. The primary endpoint was change in number of acute respiratory events (i.e. an exacerbation or an antibiotic course for a respiratory event) between baseline and outcome years. Study outcomes were assessed by Wilcoxon signed rank test or McNemar ' s test. Results : 1,188 patients were included (average age: 47 yrs; 58.4% female). Most were prescribed intranasal corticosteroids (60.4%) and Inhaled corticosteroid (ICS)/long- acting β2 - agonist (59.3%) at baseline. MP- AzeFlu initiation was associated with significantly fewer acute respiratory events ( P = .013). Significantly more patients had well- controlled asthma in the year after MP- AzeFlu initiation ( P = .004). These asthma control benefits were noted despite significant reduction in short- acting β2 - agonist (SABA) dose ( P 2 SABA puffs/week ( P < .001) and the average ICS dose remaining stable (64.0% of patients) or reduced (20.4% of patients). Conclusion : MP- AzeFlu initiation is associated with reduced acute respiratory events, improved asthma control and reduced SABA and maintenance ICS dose in patients with AR and asthma. This study was funded by BGP Products Operations GmbH (A Mylan Company).

Introduction The phase 3 InforMing the PAthway of COPD (chronic obstructive pulmonary disease) Treatment (IMPACT) trial, single-inhaler therapy with fluticasone furoate (FF) 100 μg, umeclidinium (UMEC) 62.5 μg, and vilanterol (VI) 25 μg demonstrated a reduction in the rate of moderate or severe exacerbations compared with FF/VI or UMEC/VI in patients with symptomatic COPD at risk of exacerbations. This article reports additional evidence of improvements in symptoms and health-related quality of life (HRQoL) with FF/UMEC/VI compared with either FF/VI or UMEC/VI from the IMPACT study. Methods Patient-reported HRQoL assessments and symptom measures included as pre-specified IMPACT end points were the St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), and Baseline Dyspnea Index (BDI) as the anchor for the Transitional Dyspnea Index (TDI) focal score (BDI/TDI) in a subset of patients enrolled at study sites in North America and Europe. Change from baseline was assessed at weeks 4, 28, and 52. Results The intent-to-treat population included 10,355 patients (TDI population: 5058 patients). Clinically meaningful improvements in SGRQ total score between baseline and week 52 favored FF/UMEC/VI over FF/VI (− 1.8 units, p