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1.
JAMA ; 331(10): 866-877, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470381

RESUMO

Importance: Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations: Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance: Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.


Assuntos
Glucocorticoides , Antagonistas dos Receptores Histamínicos , Rinite Alérgica , Humanos , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Cetirizina/uso terapêutico , Fluticasona/administração & dosagem , Fluticasona/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Imunoglobulina E/imunologia , Furoato de Mometasona/administração & dosagem , Furoato de Mometasona/uso terapêutico , Cloridrato de Olopatadina/administração & dosagem , Cloridrato de Olopatadina/uso terapêutico , Prurido/etiologia , Rinite Alérgica/complicações , Rinite Alérgica/diagnóstico , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Rinorreia/etiologia , Espirro , Triancinolona/administração & dosagem , Triancinolona/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Rinite/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Administração Intranasal
2.
Adv Ther ; 41(3): 1245-1261, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38310193

RESUMO

INTRODUCTION: Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA). METHODS: This retrospective cohort study included commercial and Medicare Advantage with Part D administrative claims data from September 01, 2016, to March 31, 2020, of patients diagnosed with COPD. The index date was the date of the first FF/UMEC/VI claim (September 2017-March 2019). The 12 months prior to index (baseline) were used to assess patient characteristics and outcomes; the 12 months following index (follow-up) were used to assess study outcomes. All patients had ≥ 30 consecutive days' supply of any ICS/LABA dual therapy during the 12 months prior to FF/UMEC/VI initiation. Subgroup analyses included patients with ≥ 30 consecutive days' supply of budesonide/formoterol (BUD/FORM) during baseline. Analyses of patients with ≥ 1 COPD exacerbation during baseline were reported as well. RESULTS: The overall population included 1449 patients (mean age 70.75 years; 54.18% female), of whom 540 were patients in the BUD/FORM subgroup. Significantly fewer patients experienced any exacerbation during follow-up versus baseline (overall population 53.49% vs 62.59%; p < 0.001; BUD/FORM subgroup 55.00% vs 62.41%; p = 0.004). Effects on exacerbation reduction were more pronounced among patients with ≥ 1 exacerbation during baseline. Lower COPD-related HCRU was observed during the follow-up compared with baseline for both the overall population and the BUD/FORM subgroup. CONCLUSION: Patients with COPD treated with ICS/LABA during baseline, including patients specifically treated with BUD/FORM and those with a history of ≥ 1 exacerbation, had fewer COPD exacerbations and lower COPD-related HCRU after initiating FF/UMEC/VI.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Estados Unidos , Humanos , Feminino , Idoso , Masculino , Estudos Retrospectivos , Administração por Inalação , Medicare , Fluticasona , Androstadienos , Álcoois Benzílicos , Clorobenzenos , Quinuclidinas , Nebulizadores e Vaporizadores , Corticosteroides/uso terapêutico , Combinação de Medicamentos
3.
Am J Manag Care ; 30(2): 74-81, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38381542

RESUMO

OBJECTIVES: For patients with asthma who remain symptomatic on a medium-dose inhaled corticosteroid/long-acting ß2 agonist, addition of a long-acting muscarinic antagonist as a supplementary controller is a recommended option. However, real-world data on the characteristics and treatment patterns of these patients are limited. This study described the demographics and clinical characteristics of new users of single- or multiple-inhaler triple therapy and treatment patterns preceding triple-therapy initiation. STUDY DESIGN: This retrospective cohort study used medical and pharmacy claims data from the IQVIA PharMetrics Plus database. METHODS: The study population comprised adults with asthma with or without chronic obstructive pulmonary disease (COPD) initiating triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25 µg) or multiple-inhaler triple therapy (MITT) between September 18, 2017, and September 30, 2019. Demographics, clinical characteristics, and treatment patterns in the 12 months preceding triple-therapy initiation were described (baseline period). RESULTS: A total of 12,395 patients were included. Among FF/UMEC/VI initiators with asthma (n = 1301), the mean age was 49.0 years and 59.3% were women. During the baseline period, 81.5% of patients used controller therapy, 94.7% used rescue medications, and 42.0% reported at least 1 asthma-related exacerbation; the annual mean exacerbation rate was 0.96. Similar trends were observed among patients with asthma initiating MITT and patients with comorbid asthma-COPD initiating FF/UMEC/VI or MITT. CONCLUSION: In real-world practice, triple therapy is often utilized following other asthma controller medication use. High disease burden, as evidenced by substantial use of rescue medications and continued asthma-related exacerbations, suggests that patients may not have achieved adequate asthma control prior to triple-therapy initiation.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Broncodilatadores/uso terapêutico , Estudos Retrospectivos , Administração por Inalação , Asma/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fluticasona/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Combinação de Medicamentos
4.
Adv Ther ; 41(3): 1201-1225, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38296921

RESUMO

INTRODUCTION: Even though increased use of reliever medication, including short-acting beta agonists (SABA), provides an indirect measure of symptom worsening, there have been limited efforts to assess how different patterns of reliever use correlate with symptom control and future risk of exacerbations. Here, we evaluate the effect of individual baseline characteristics on reliever use in patients with moderate-severe asthma on regular maintenance therapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: A drug-disease model describing the number of 24-h puffs and overnight occasions was developed with data from five clinical studies (N = 6212). The model was implemented using a nonlinear mixed effects approach and a Poisson function, considering clinical and demographic baseline characteristics. Goodness of fit and model predictive performance were assessed. Heatmaps were created to summarise the effect of concurrent baseline factors on reliever utilisation. RESULTS: The final model accurately described individual patterns of reliever use, which is significantly increased with time since diagnosis, smoking, higher Asthma Control Questionnaire (ACQ-5) score and higher body mass index (BMI) at baseline. Whilst the number of puffs decreases slowly after an initial drop relative to the start of treatment, exacerbating patients utilise significantly more reliever than those who do not exacerbate. The mean effect of FP/SAL (median dose: 250/50 µg BID) on reliever use was slightly higher than that of BUD/FOR (median dose: 160/4.5 µg BID), i.e. a 75.3% vs 69.3% reduction in reliever use, respectively. CONCLUSIONS: The availability of individual-level patient data in conjunction with a parametric approach enabled the characterisation of interindividual differences in the patterns of reliever use in patients with moderate-severe asthma. Taken together, individual demographic and clinical characteristics, as well as exacerbation history, can be considered an indicator of the degree of asthma control. High SABA reliever use suggests suboptimal clinical management of patients on maintenance therapy.


In this study, we tried to understand how patients with moderate to severe asthma use their quick-relief inhalers (like albuterol), how it relates to their symptoms and the risk of having asthma attacks. To evaluate whether differences in reliever inhaler use between patients are associated with factors like smoking or their asthma symptoms at the beginning of treatment, we gathered data from five clinical studies (n = 6212 patients). These data allowed us to create a model that predicts how often patients use their reliever inhalers (expressed as number of puffs in 24 h) during maintenance therapy with inhaled corticosteroids alone or in combination with long-acting beta agonists. The final model showed that reliever inhaler use is higher in patients who have been diagnosed with asthma for > 10 years, are smokers, have higher asthma symptom scores, and are obese or extremely obese. Patients who had asthma attacks also used their reliever inhalers more often. In addition, to understand how relief inhalers are used in real-life situations, we also created heatmaps that include a wide range of patient characteristics. By using individual patient data together with this model, we have learned that smoking, asthma control, BMI, long history of asthma and previous asthma attacks significantly influence reliever use. This information can help physicians and healthcare professionals understand know how well someone's asthma is managed. A patient who uses their reliever inhaler often is likely not to have their asthma well controlled by their regular medications.


Assuntos
Antiasmáticos , Asma , Humanos , Administração por Inalação , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Combinação de Medicamentos , Fluticasona/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Artigo em Inglês | MEDLINE | ID: mdl-38292138

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD) and asthma are associated with chronic inflammation of the respiratory tract; despite some overlap of symptoms, they are considered separate disorders. Triple therapy is recommended for patients with COPD and asthma whose symptoms remain uncontrolled despite dual therapy. There are limited real-world studies evaluating outcomes among patients with COPD and asthma who are receiving inhaled triple therapy. This United States (US)-based real-world study aimed to evaluate clinical and economic outcomes among patients with COPD and asthma receiving single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI]). Patients and Methods: Retrospective pre-post study using claims data from the Optum Clinformatics® database. Patients with COPD and asthma were indexed on the first date of FF/UMEC/VI prescription (1 October 2017-31 March 2019). Each patient acted as their own control. Patients were required to have continuous health plan enrollment for 12 months prior to (pre-treatment) and following (post-treatment) index. Exacerbations, all-cause and COPD-related healthcare resource utilization, and costs were compared before and after FF/UMEC/VI initiation. Results: Overall, 2743 patients were included (mean age: 71 years; 64% female). Cardiovascular disease was the most prevalent comorbidity during both the pre- and post-treatment periods (90% for both periods). There was a lower proportion of patients with ≥1 COPD exacerbation or ≥1 asthma exacerbation post-treatment versus pre-treatment (51% vs 57%, p<0.0001, and 22% vs 32%, p<0.0001, respectively). Fewer patients had ≥1 all-cause office visit post-treatment versus pre-treatment (99.3% vs 99.7%, p=0.0329); more patients had ≥1 COPD-related office visit post-treatment versus pre-treatment (89.6% vs 87.5%, p=0.0035). Total all-cause healthcare costs were significantly higher post-treatment versus pre-treatment ($72,809 vs $63,734, p<0.0001). The driver of increased costs appeared to be primarily non-COPD-related (COPD-related costs: post-treatment $27,779 vs pre-treatment $25,081, p=0.0062). Conclusion: FF/UMEC/VI reduced exacerbations among patients with COPD and asthma in a real-world setting in the US.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Estados Unidos/epidemiologia , Idoso , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Broncodilatadores/efeitos adversos , Estudos Retrospectivos , Fluticasona/uso terapêutico , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/epidemiologia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Clorobenzenos/efeitos adversos , Álcoois Benzílicos/efeitos adversos , Quinuclidinas/efeitos adversos , Combinação de Medicamentos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38226396

RESUMO

Purpose: Patients with chronic obstructive pulmonary disease (COPD) have been shown to benefit from triple therapy commonly delivered by multiple-inhaler triple therapy (MITT); however, the complexity of MITT regimens may decrease patient adherence. Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI), a once-daily single-inhaler triple therapy (SITT), became available in the United States (US) in 2017, but real-world data comparing outcomes for SITT versus MITT are currently limited. This study compared outcomes among patients with COPD initiating MITT versus SITT with FF/UMEC/VI who were either Medicare Advantage with Part D (MAPD) beneficiaries or commercial enrollees in the US. Methods: Retrospective study using administrative claims data from the Optum Research Database for patients with COPD who initiated FF/UMEC/VI or MITT between September 1, 2017, and March 31, 2019 (index date: first pharmacy claim for FF/UMEC/VI cohort; earliest day of ≥30 consecutive days-long period of overlap in the day's supply of all triple therapy components for MITT cohort). COPD exacerbations, adherence to triple therapy, and all-cause and COPD-related health care resource utilization (HCRU) and costs were compared between FF/UMEC/VI and MITT initiators. Results: In total, 4659 FF/UMEC/VI initiators and 9845 MITT initiators for the MAPD population, and 821 FF/UMEC/VI initiators and 1893 MITT initiators for the commercial population were included in the study. MAPD beneficiaries initiating FF/UMEC/VI had a significantly lower annual rate of severe exacerbations compared to MITT initiators (0.26 vs 0.29; p=0.014). They also had a significantly higher mean adherence (proportion of days covered) (0.51 vs 0.37; p<0.001) and significantly lower all-cause and COPD-related inpatient stays compared to MITT initiators ([32.02% vs 34.27%; p=0.017], [16.09% vs 17.72%; p=0.037]). Trends were similar among the commercial population, but the results were not statistically significant. Conclusion: FF/UMEC/VI initiators had significantly fewer severe exacerbations, higher triple therapy adherence, and lower HCRU costs compared to MITT initiators for MAPD beneficiaries.


Assuntos
Androstadienos , Medicare Part C , Doença Pulmonar Obstrutiva Crônica , Humanos , Idoso , Estados Unidos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Broncodilatadores , Estudos Retrospectivos , Administração por Inalação , Fluticasona/uso terapêutico , Nebulizadores e Vaporizadores , Álcoois Benzílicos , Clorobenzenos , Quinuclidinas , Atenção à Saúde , Combinação de Medicamentos
7.
Artigo em Inglês | MEDLINE | ID: mdl-38249826

RESUMO

Purpose: Real-life effectiveness data on once-daily single-inhaler triple therapy (odSITT) with the inhaled corticosteroid fluticasone furoate (FF), the long-acting muscarinic antagonist umeclidinium (UMEC), and the long-acting ß2-agonist vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) are important to complement evidence from well-controlled randomized clinical trials. Effectiveness of odSITT was quantified by assessing health status and symptoms in usual care. Patients and Methods: ELLITHE was a single-country (Germany), multicenter, open-label, non-interventional effectiveness study between 2020 and 2022, evaluating the effect of treatment initiation with FF/UMEC/VI 100/62.5/25 µg once-daily via the ELLIPTA inhaler on improvements in clinical outcomes versus baseline in COPD patients. The primary endpoint was the change in the total COPD Assessment Test (CAT) score between baseline and month 12. Key secondary endpoints included change in CAT score over time, occurrence of exacerbations until month 12, changes in forced expiratory volume in one second (FEV1), inhaler adherence, and safety. Results: Nine hundred and six patients were included (age 66.6 years, 55.6% male, mean FEV1 52.6% of predicted, mean CAT 21.5 units, 1.4 exacerbations/year pre-study). About 63.9% of patients were escalated from dual therapies, and 18% were switched from multiple-inhaler triple therapies. Reductions in CAT score at month 12 were statistically significant and above the threshold of clinical importance (-2.6 units; p < 0.0001). CAT score also improved at interim visits. CAT improvements were more pronounced in patients with high baseline scores and better inhaler adherence. Exacerbations during follow-up were rare (0.2 events/year) compared to pre-study (1.4 events/year). FEV1 was improved by 93 mL (p < 0.0001). No new safety effects were observed. Conclusion: In usual care, treatment with odSITT resulted in significant and clinically relevant improvements of CAT score and FEV1 in COPD patients, regardless of the occurrence of exacerbations. These findings challenge the current guideline recommendations for SITT only in patients experiencing exacerbations.


Assuntos
Androstadienos , Álcoois Benzílicos , Clorobenzenos , Doença Pulmonar Obstrutiva Crônica , Quinuclidinas , Humanos , Masculino , Idoso , Feminino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fluticasona , Nebulizadores e Vaporizadores
8.
Pharmacology ; 109(1): 22-33, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37980896

RESUMO

INTRODUCTION: We investigated the potential of LPS (10-300 µg/rat) administered intratracheally (i.t.) to induce reproducible features of acute lung injury (ALI) and compared the pharmacological efficacy of anti-inflammatory glucocorticoids and antifibrotic drugs to reduce the disease. Additionally, we studied the time-dependent progression of ALI in this LPS rat model. METHODS: We conducted (1) dose effect studies of LPS administered i.t. at 10, 30, 100, and 300 µg/rat on ALI at 4 h timepoint; (2) pharmacological interventions using i.t. fluticasone (100 and 300 µg/rat), i.t. pirfenidone (4,000 µg/rat), and peroral dexamethasone (1 mg/kg) at 4 h timepoint; (3) kinetic studies at 0, 2, 4, 6, 8, 10, and 24 h post-LPS challenge. Phenotype or pharmacological efficacy was assessed using predetermined ALI features such as pulmonary inflammation, edema, and inflammatory mediators. RESULTS: All LPS doses induced a similar increase of inflammation, edema, and inflammatory mediators, e.g., IL6, IL1ß, TNFα, and CINC-1. In pharmacological intervention studies, we showed fluticasone and dexamethasone ameliorated ALI by inhibiting inflammation (>60-80%), edema (>70-100%), and the increase of cytokines IL6, IL1ß, and TNFα (≥70-90%). We also noticed some inhibition of CINC-1 (25-35%) and TIMP1 (57%) increase with fluticasone and dexamethasone. Conversely, pirfenidone failed to inhibit inflammation, edema, and mediators of inflammation. Last, in ALI kinetic studies, we observed progressive pulmonary inflammation and TIMP1 levels, which peaked at 6 h and remained elevated up to 24 h. Progressive pulmonary edema started between 2 and 4 h and was sustained at later timepoints. On average, levels of IL6 (peak at 6-8 h), IL1ß (peak at 2-10 h), TNFα (peak at 2 h), CINC-1 (peak at 2-6 h), and TGFß1 (peak at 8 h) were elevated between 2 and 10 h and declined toward 24 h post-LPS challenge. CONCLUSION: Our data show that 10 µg/rat LPS achieved a robust, profound, and reproducible experimental ALI phenotype. Glucocorticoids ameliorated key ALI features at the 4-h timepoint, but the antifibrotic pirfenidone failed. Progressive inflammation and sustained pulmonary edema were present up to 24 h, whereas levels of inflammatory mediators were dynamic during ALI progression. This study's data might be helpful in designing appropriate experiments to test the potential of new therapeutics to cure ALI.


Assuntos
Lesão Pulmonar Aguda , Pneumonia , Edema Pulmonar , Piridonas , Ratos , Animais , Lipopolissacarídeos/toxicidade , Fluticasona/uso terapêutico , Fluticasona/farmacologia , Fator de Necrose Tumoral alfa/genética , Interleucina-6 , Cinética , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Pulmão , Pneumonia/induzido quimicamente , Inflamação , Mediadores da Inflamação , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Edema
9.
Heart Lung ; 63: 23-34, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37740997

RESUMO

BACKGROUND: Asthma is a chronic respiratory disease that affects millions of children worldwide and can impair their quality of life and development. Inhaled glucocorticoids are the mainstay of asthma treatment, but some children require step-up therapy with additional drugs to achieve symptom control. Fluticasone propionate and salmeterol (FSC) has been shown to reduce asthma exacerbations and improve lung function in adults. However, the evidence for its efficacy and safety in children is limited. OBJECTIVE: This study aims to provide a comprehensive basis for treatment selection by summarizing existing clinical randomized controlled trials (RCTs) on the efficacy of FSC compared to fluticasone propionate (FP) monotherapy in children with asthma who require step-up treatment. METHODS: Five online databases and three clinical trial registration platforms were systematically searched. The effect size and corresponding 95% confidence interval (CI) were calculated based on the heterogeneity among the included studies. RESULTS: Twelve RCTs were identified and a total of 9, 859 patients were involved. The results of the meta-analysis revealed that the use of FSC was associated with a greater reduction in the incidence of asthma exacerbations than FP alone when the dose of FP was the same or when the duration of treatment exceeded 12 weeks. In addition, FSC resulted in a greater proportion of time with asthma-free and without the use of albuterol compared to FP alone when the duration of treatment exceeded 12 weeks. No significant differences were observed between FSC and FP alone in the incidence of drug-related adverse events and other adverse events. CONCLUSION: Both FSC and FP alone are viable options for the initial selection of step-up treatment in asthmatic children. While, FSC treatment demonstrates a greater likelihood of reducing asthma exacerbations which is particularly important for reducing the personnel, social and economic burden in children requiring step-up asthma treatment.


Assuntos
Androstadienos , Asma , Adulto , Criança , Humanos , Fluticasona/uso terapêutico , Combinação Fluticasona-Salmeterol/uso terapêutico , Androstadienos/efeitos adversos , Asma/tratamento farmacológico , Albuterol/efeitos adversos , Xinafoato de Salmeterol/uso terapêutico , Resultado do Tratamento , Broncodilatadores/efeitos adversos , Administração por Inalação , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Drug Metab Pharmacokinet ; 54: 100541, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38150944

RESUMO

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.


Assuntos
Sprays Nasais , Humanos , Fluticasona/efeitos adversos , Fluticasona/farmacocinética , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Androstadienos/química , Androstadienos/farmacocinética
11.
BMC Pulm Med ; 23(1): 489, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053076

RESUMO

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.


Assuntos
Antiasmáticos , Asma , Criança , Humanos , Acetatos/efeitos adversos , Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Ciclopropanos/uso terapêutico , Fluticasona/efeitos adversos , Quinolinas/efeitos adversos
12.
Int J Chron Obstruct Pulmon Dis ; 18: 2367-2379, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37933243

RESUMO

Purpose: Oral corticosteroids (OCS) play a role in the treatment of acute chronic obstructive pulmonary disease (COPD) exacerbations; however, chronic use is not recommended due to the high rate of systemic complications, development of comorbidities, and increased mortality. Data assessing the real-world impact of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) on OCS utilization rates are limited. This study assessed the impact of FF/UMEC/VI on OCS use among patients with COPD previously treated with OCS. Patients and Methods: A retrospective database study of patients with COPD aged ≥40 years who initiated FF/UMEC/VI from 1 November 2017 to 31 December 2018, identified through the MarketScan® Commercial and Medicare Supplemental databases. Patients were required to have ≥1 dispensing of an OCS prior to initiation of FF/UMEC/VI (index) and were followed up for 12 months post-index. OCS utilization patterns, potential OCS-related adverse events, healthcare resource utilization (HCRU), and costs were compared between the 12-month pre- and post-index periods. Results: A total of 2013 patients were identified (mean age 63.5 years, 55.7% female). The proportion of patients with ≥1 OCS claim decreased by 32.2% between the pre- and post-index period (67.8% vs 100%; p < 0.001). Comparing the post-index period to the pre-index period, mean number of OCS pharmacy claims per patient decreased from 3.3 to 2.5 (p < 0.001) and mean daily dose was reduced from 3.1 to 2.6 mg/day (p = 0.004); 30.0% of patients reduced their daily dose by 90-100%. Reductions were also seen in COPD-related HCRU. The proportion of patients with an inpatient admission for COPD decreased from 11.4% to 7.1% (p < 0.001), emergency room visits decreased from 23.1% to 17.4% (p < 0.001), and office visits from 97.5% to 90.1% (p < 0.001). Similar results were seen for all-cause HCRU. Conclusion: Among patients with COPD with prior OCS use, FF/UMEC/VI initiation resulted in significant reductions in OCS utilization, COPD-related HCRU (including hospitalization), and all-cause HCRU.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Estados Unidos , Humanos , Idoso , Feminino , Pessoa de Meia-Idade , Masculino , Broncodilatadores , Estudos Retrospectivos , Administração por Inalação , Androstadienos , Medicare , Fluticasona , Corticosteroides/uso terapêutico , Álcoois Benzílicos , Clorobenzenos , Quinuclidinas , Combinação de Medicamentos
14.
Rev Mal Respir ; 40(9-10): 834-837, 2023.
Artigo em Francês | MEDLINE | ID: mdl-37743223

RESUMO

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.


Assuntos
Síndrome de Cushing , Feminino , Humanos , Adulto , Síndrome de Cushing/induzido quimicamente , Síndrome de Cushing/tratamento farmacológico , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Androstadienos/efeitos adversos , Fluticasona/efeitos adversos , Corticosteroides/efeitos adversos , Interações Medicamentosas , Claritromicina/efeitos adversos , Doença Iatrogênica
15.
Pediatr Pulmonol ; 58(12): 3487-3497, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37728224

RESUMO

INTRODUCTION: Growth impairment is a known adverse event (AE) of corticosteroids in children. This study aimed to assess the effect of once-daily (QD) inhaled fluticasone furoate (FF) versus placebo on growth velocity over 1 year in prepubertal children with well-controlled asthma. MATERIALS AND METHODS: This randomized, double-blind, parallel-group, placebo-controlled, multicenter study (NCT02889809) included prepubertal children, aged 5 to <9 years (boys), and 5 to <8 years (girls), with ≥6 months' asthma history. Children received inhaled placebo QD plus background open-label montelukast QD for a 16-week run-in period and were then randomized 1:1 to receive inhaled FF 50 µg QD or placebo QD (whilst continuing background open-label montelukast) for a 52-week treatment period. The primary endpoint was the difference in growth velocity (cm/year) over the treatment period. Other growth endpoints were measured, as were incidence of AEs and asthma exacerbation. Growth analyses included all intent-to-treat (ITT) participants with ≥3 post-randomization, on-treatment clinic visit height assessments (GROWTH population). RESULTS: Of 644 children in the run-in period, 477 (mean age 6.2 years, 63% male) entered the 52-week treatment period (ITT population: FF N = 238, placebo N = 239; GROWTH population: N = 457 [FF N = 231; placebo N = 226]). The least-squares mean difference in growth velocity for FF versus placebo was -0.160 cm/year (95% confidence interval: -0.462, 0.142). There were no new safety signals. CONCLUSIONS: Over 1 year, FF 50 µg QD had a minimal effect on growth velocity versus placebo, with no new safety signals.


Assuntos
Asma , Broncodilatadores , Feminino , Humanos , Criança , Masculino , Broncodilatadores/uso terapêutico , Administração por Inalação , Asma/tratamento farmacológico , Método Duplo-Cego , Resultado do Tratamento , Fluticasona/uso terapêutico
16.
Respir Res ; 24(1): 226, 2023 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-37742015

RESUMO

BACKGROUND: Small airways disease plays a key role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and is a major cause of obstruction; therefore, it is a critical pharmacotherapy target. This study evaluated lung deposition of two inhaled corticosteroid (ICS)/long-acting ß2-agonist/long-acting muscarinic antagonist single-inhaler triple therapies using in silico functional respiratory imaging (FRI). Deposition was assessed using real-world inhalation profiles simulating everyday use where optimal inhalation may be compromised. METHODS: Three-dimensional airway models were produced from 20 patients with moderate-to-very severe COPD. Total, central, and regional small airways deposition as a percentage of delivered dose of budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) 160/7.2/5 µg per actuation and fluticasone furoate/umeclidinium/vilanterol (FF/UM/VI) 100/62.5/25 µg were evaluated using in silico FRI based on in vitro aerodynamic particle size distributions of each device. Simulations were performed using multiple inhalation profiles of varying durations and flow rates representing patterns suited for a pressurized metered-dose inhaler or dry-powder inhaler (four for BGF, two for FF/UM/VI, with one common profile). For the common profile, deposition for BGF versus FF/UM/VI was compared post-hoc using paired t-tests. RESULTS: Across inhalation profiles, mean total lung deposition was consistently higher with BGF (47.0-54.1%) versus FF/UM/VI (20.8-22.7%) and for each treatment component, with greater deposition for BGF also seen in the central large airways. Mean regional small airways deposition was also greater across inhalation profiles with BGF (16.9-23.6%) versus FF/UM/VI (6.8-8.7%) and for each treatment component. For the common profile, total, central, and regional small airways deposition were significantly greater for BGF versus FF/UM/VI (nominal p < 0.001), overall and for treatment components; notably, regional small airways deposition of the ICS components was approximately five-fold greater with budesonide versus fluticasone furoate (16.1% vs. 3.3%). CONCLUSIONS: BGF was associated with greater total, central, and small airways deposition for all components versus FF/UM/VI. Importantly, using an identical inhalation profile, there was an approximately five-fold difference in small airways deposition for the ICS components, with only a small percentage of the ICS from FF/UM/VI reaching the small airways. Further research is needed to understand if the enhanced delivery of BGF translates to clinical benefits.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fluticasona , Budesonida , Inaladores de Pó Seco , Pulmão/diagnóstico por imagem
17.
Molecules ; 28(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37764395

RESUMO

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


Assuntos
Técnicas Biossensoriais , Glucocorticoides , Fluticasona , Imunoensaio , Hidrocortisona
18.
EMBO Mol Med ; 15(9): e17748, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37538042

RESUMO

Hematopoietic cell transplantation (HCT) treats many blood conditions but remains underused due to complications such as graft-versus-host disease (GvHD). In GvHD, donor immune cells attack the patient, requiring powerful immunosuppressive drugs like glucocorticoids (GCs) to prevent death. In this study, we tested the hypothesis that donor cell conditioning with the glucocorticoid fluticasone propionate (FLU) prior to transplantation could increase hematopoietic stem cell (HSC) engraftment and reduce GvHD. Murine HSCs treated with FLU had increased HSC engraftment and reduced severity and incidence of GvHD after transplantation into allogeneic hosts. While most T cells died upon FLU treatment, donor T cells repopulated in the hosts and appeared less inflammatory and alloreactive. Regulatory T cells (Tregs) are immunomodulatory and survived FLU treatment, resulting in an increased ratio of Tregs to conventional T cells. Our results implicate an important role for Tregs in maintaining allogeneic tolerance in FLU-treated grafts and suggest a therapeutic strategy of pre-treating donor cells (and not the patients directly) with GCs to simultaneously enhance engraftment and reduce GvHD upon allogeneic HCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Camundongos , Animais , Fluticasona/farmacologia , Fluticasona/uso terapêutico , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores
19.
Pak J Pharm Sci ; 36(3(Special)): 1001-1007, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37587710

RESUMO

This study was to evaluate the clinical efficacy and safety of fluticasone/ salmeterol inhalation powder plus Huaiqihuang Granules for children with cough variant asthma (CVA). From June 2019 to May 2021, 60 children with CVA were hospitalized to the Pediatrics Department of Cangzhou Central Hospital and randomized to the observation (fluticasone/salmeterol inhalation powder plus huaiqihuang granules) and control group (fluticasone/salmeterol inhalation powder) using the random number table method. The outcome measures include clinical efficacy, forced vital capacity (FVC), forced expiratory volume per second (FEV1), peak expiratory flow (PEF), FeNO, high-sensitivity C-reactive protein (hs-CRP), interleukin-17 (IL-17) and IL-23, airway anatomical indicators and T lymphocyte subsets levels. Both groups exhibited remarkable improvements in FVC, FEV1, PEF and FeNO and hs-CRP, IL-17 and IL-23, with higher FVC, FEV1 and PEF and lower FeNO, hs-CRP, IL-17 and IL-23 in the observation group (all P<0.05). Significantly higher levels of CD4+ and CD4+/CD8+ were observed in the observation group versus control group, but lower airway wall thickness, basement membrane thickness, total airway wall area and CD8+ in the observation group (all P<0.05). Fluticasone/salmeterol inhalation powder plus Huaiqihuang Granules improves lung function, FeNO and airway inflammation in children with CVA and boosts cellular and humoral immune function.


Assuntos
Asma , Interleucina-17 , Criança , Humanos , Fluticasona , Pós , Proteína C-Reativa , Tosse , Resultado do Tratamento , Asma/tratamento farmacológico , Xinafoato de Salmeterol , Interleucina-23
20.
Adv Ther ; 40(10): 4606-4625, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37589831

RESUMO

INTRODUCTION: The assessment of future risk has become an important feature in the management of patients with asthma. However, the contribution of patient-specific characteristics and treatment choices to the risk of exacerbation is poorly understood. Here we evaluated the effect of interindividual baseline differences on the risk of exacerbation and treatment performance in patients receiving regular maintenance doses of inhaled corticosteroids (ICS) or ICS/long-acting beta-agonists (LABA) combination therapy. METHODS: Exacerbations and changes to asthma symptoms 5-item Asthma Control Questionnaire (ACQ-5) were simulated over a 12-month period using a time-to-event and a longitudinal model developed from phase III/IV studies in patients with moderate-severe asthma (N = 16,282). Simulations were implemented to explore treatment performance across different scenarios, including randomised designs and real-world settings. Treatment options included regular dosing with ICS monotherapy [fluticasone propionate (FP)] and combination therapy [fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR)]. Exacerbation rate was analysed using the log-rank test. The cumulative incidence of events was summarised stratified by treatment. RESULTS: Being a woman, smoker, having higher baseline ACQ-5 and body mass index (BMI) and lower forced expiratory volume in the first second (FEV1) are associated with increased exacerbation risk (p < 0.01). This risk is bigger in winter because of the seasonal variation effect. Across the different scenarios, the use of FP/SAL resulted in a 10% lower annual incidence of exacerbations relative to FP or regular dosing BUD/FOR, independently of baseline characteristics. Similar differences in the annual incidence of exacerbations were also observed between treatments in obese patients (BMI ≥ 25-35 kg/m2) (p < 0.01) and in patients who do not achieve symptom control on FP monotherapy. CONCLUSIONS: Individual baseline characteristics and treatment choices affect future risk. Achieving comparable levels of symptom control whilst on treatment does not imply comparable risk reduction, as shown by the lower exacerbation rates in FP/SAL vs. BUD/FOR-treated patients. These factors should be considered as a basis for personalised clinical management of patients with moderate-severe asthma.


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


Assuntos
Asma , Feminino , Humanos , Asma/tratamento farmacológico , Índice de Massa Corporal , Combinação Budesonida e Fumarato de Formoterol , Terapia Combinada , Fluticasona/uso terapêutico , Combinação Fluticasona-Salmeterol , Masculino
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