Nebulized Fluticasone Propionate vs. Budesonide as Adjunctive Treatment in Children with Asthma Exacerbation

Objectives: To compare the effects of nebulized fluticasone propionate (FP) and nebulized budesonide (BUD) in addition to inhaled salbutamol in children with mild asthma exacerbation. Methods: The study was a multicenter, randomized, single-blind, parallel group design. One hundred and sixty-eight children, aged 4-15 years, were randomly allocated to receive either nebulized FP (250 mcg) or nebulized BUD (500 mcg) twice daily for 10 days. On presentation, at the end of treatment, and after a 7-day follow-up, clinical assessment and pulmonary function measurements were performed. Daytime and nighttime asthma symptom scores, the use of rescue salbutamol, and morning/evening peak expiratory flow (PEF) values were recorded at home during the treatment period. Morning cortisol concentration (51 children) and overnight urinary cortisol excretion (30 children) were also measured in six centers at the start and at the end of the treatment. Results: Improvement of morning PEF was significantly higher in patients treated with FP (p = 0.032). The percentage of symptom-free nights was significantly higher in the BUD group (p = 0.006), but no difference was found in symptom-free days. No intergroup difference was detected in the percentage of days/nights free from rescue medication and in pulmonary function tests performed in outpatient settings. There was no evidence of hypothalamo-pituitary-adrenal axis suppression. Conclusions: A short course of nebulized FP has the same effects as a double dose of nebulized BUD, when either drug is added to bronchodilator therapy in children with mild asthma exacerbation.     

丙酸氟替卡松治疗哮喘患者的疗效评价

目的 评价短期使用新型吸入型糖皮质激素—丙酸氟替卡松的有效性和安全性。方法 50例未达到控制的支气管哮喘患接受6周的吸入丙酸氟替卡松治疗，于用药前后比较日、夜间症状评分，短效β2—受体激动剂按需使用次数，晨间、夜间PEF值及试验开始和结束时的FEVl值。结果 治疗后各项指标均有明显改善。在症状改善方面优于肺功能改善。肺功能指标的改善在中、重度哮喘患明显。上述剂量短期内使用安全可靠。结论 中等剂量的丙酸氟替卡松临床疗效显、安全性好是目前治疗哮喘的最佳的吸入激素制剂之一。     

Once-Daily Fluticasone Propionate in Stable Asthma: Study on Airway Inflammation

Children with stable asthma receiving twice-daily fluticasone propionate (FP) were studied. Spirometry, exhaled nitric oxide (eNO) and sputum eosinophils were measured at baseline and 8 weeks after FP was changed to once-daily use while keeping the same total dosage. Visual analogue scores on asthma severity, symptoms, and dosing regimen preference were obtained. Twenty-nine children of mean age 10.6 years (SD 2.5) were recruited. There was significant improvement in eNO (47.1 ppb [30.3] vs. 39.9 ppb [27.1], p = 0.037), and sputum eosinophils (5.7% [6.5] vs. 2.5% [3.9], p = 0.024] after 8 weeks. All subjects preferred the once-daily dosing regimen. Once-daily FP is effective in controlling airway inflammation. This frequency of medication use is also the preferred regimen.     

Once-Daily Fluticasone Propionate in Stable Asthma: Study on Airway Inflammation

Children with stable asthma receiving twice-daily fluticasone propionate (FP) were studied. Spirometry, exhaled nitric oxide (eNO) and sputum eosinophils were measured at baseline and 8 weeks after FP was changed to once-daily use while keeping the same total dosage. Visual analogue scores on asthma severity, symptoms, and dosing regimen preference were obtained. Twenty-nine children of mean age 10.6 years (SD 2.5) were recruited. There was significant improvement in eNO (47.1 ppb [30.3] vs. 39.9 ppb [27.1], p = 0.037), and sputum eosinophils (5.7% [6.5] vs. 2.5% [3.9], p = 0.024] after 8 weeks. All subjects preferred the once-daily dosing regimen. Once-daily FP is effective in controlling airway inflammation. This frequency of medication use is also the preferred regimen.     

Simultaneously Evaluating the Effects of One-week Fluticasone Propionate Inhalation Therapy on Lung Ventilation and Permeability in Children with Asthma

This study evaluated the effects of fluticasone propionate inhalation therapy on lung ventilation and alveolar permeability by quantitative Tc-99m DTPA radioaerosol inhalation lung scintigraphy in 15 children with asthma. Lung ventilation was evaluated as the distribution percentage (D%) of Tc-99m DTPA radioaerosols in the central, intermediate and peripheral regions of the right lung. Alveolar permeability was measured by the rate of Tc-99m DTPA radioaerosol clearance curve from the peripheral alveoli of the right lung and represented as slope. The D% and slopes were calculated before and after one-week inhalation therapy (100 µg fluticasone propionate two times daily for one-week) to evaluate the effects of inhalation therapy on lung ventilation and alveolar permeability. The preliminary results revealed statistically significantly improved lung ventilation but no significant change of alveolar permeability in the right lung after one-week fluticasone propionate inhalation therapy in children with asthma. We suggest that the widely available and noninvasive Tc-99m DTPA radioaerosol inhalation lung scintigraphy can simultaneously evaluate lung ventilation and alveolar permeability in one study and should contribute to any disorder involving both alveoli and airways.     

Improved Ability to Perform Strenuous Activities After Treatment with Fluticasone Propionate/Salmeterol Combination in Patients with Persistent Asthma

Patients with asthma experience disruptions in usual activities that can impair their quality of life, and in patients whose daily routine involves an active lifestyle, these disruptions can be severe. We assessed the patient-perceived effect of treatment with fluticasone propionate/salmeterol combination (FSC), compared with fluticasone propionate (FP) or salmeterol (SAL) alone, on activity limitations, particularly strenuous physical activities. The Asthma Quality of Life Questionnaire (AQLQ) was administered in two 12-week, randomized, double-blind, placebo-controlled trials comparing FSC 100/50 or 250/50 µg twice daily vs. the individual components alone in 686 adults and adolescents with asthma. In one study, patients were stratified by prior treatment [low to medium doses of inhaled corticosteroids (ICS) or SAL], and in the other study, all patients were previously treated with medium to high doses of ICS. Patients prospectively identified five activities they performed regularly and were asked how these activities were limited by their asthma. The effect of randomized treatment on strenuous activities (e.g., aerobics, cycling, hiking, and basketball) was assessed. In both studies, treatment with FSC resulted in clinically meaningful improvements (i.e., change in AQLQ of ≥0.5) and was statistically significantly better than SAL in both studies and FP in one study. Treatment of the two main components of asthma—inflammation and bronchoconstriction—with FSC results in clinically meaningful improvements in the ability of patients with persistent asthma to perform not only their usual activities but also strenuous activities.     

Improvement in Health Care Utilization and Pulmonary Function with Fluticasone Propionate in Patients with Steroid-Dependent Asthma at a National Asthma Referral Center

The impact of switching from other inhaled corticosteroids to fluticasone propionate was studied in patients with severe oral-steroid-dependent asthma over a 1-year period. In this open-label prospective study, patients on maintenance doses of oral and inhaled steroids were referred to a national asthma treatment center and were switched from their previous inhaled corticosteroid to fluticasone propionate 880 μg BID. Compared with data collected from the year prior to enrollment, treatment with fluticasone propionate resulted in significant improvements in pulmonary function, oral steroid requirements, and health resource utilization. In addition, five patients were completely weaned off oral steroids.     

Short-term Treatment with a Low Dose of Inhaled Fluticasone Propionate Decreases the Number of CD1a+ Dendritic Cells in Asthmatic Airways

The activation of T-lymphocytes through the recognition of specific allergens is a crucial event in the development of allergic inflammation. Dendritic cells (DC) are potent accessory cells that play an important role in initiating bronchial immune responses by activation of T-lymphocytes. We investigated the distribution of CD1a+ DC in the bronchial biopsies from asthmatic patients, and evaluated the effects of a short course of low dose inhaled fluticasone propionate treatment. Twenty-three mild to moderate stable asthmatic patients and eight normal subjects were included in the study. Bronchoscopy with bronchial biopsies were performed in each subject. Eighteen of the 23 asthmatics underwent a second bronchoscopy after 6 weeks of low dose inhaled fluticasone propionate treatment (250 mcg bd) in a placebo-controlled double-blind study. Biopsies were embedded into glycolmethacrylate resin and analysed by immunohistochemistry methods using specific monoclonal antibodies against CD1a, which is a widely recognized marker for DC. In asthmatics, CD1a+ DC number was significantly higher in bronchial epithelium (P<0.001) and in lamina propria (P<0.001) when compared with normal controls. In addition, we observed that a short course of low dose inhaled fluticasone propionate treatment decreased the number of CD1a+ DC in both the bronchial epithelium (P<0.05) and lamina propria (P<0.01). The increased number of CD1a+ DC support the hypothesis that DC play an important role in the modulation of the immune response in chronic asthma. Short-term low dose fluticasone propionate treatment induces down-regulation of the CD1a+ DC number.     

The Effects of One-Week Fluticasone Propionate Inhalation Therapy for Tc-99m DTPA Radioaerosol Distribution in Asthma of Children: A Preliminary Report

This study evaluated the effects of fluticasone propionate inhalation therapy for the distribution pattern of Tc-99m DTPA radioaerosols in 10 children with asthma. The homogeneous degree of depositing Tc-99m DTPA radioaerosol was evaluated using a modified standard score system over the bilateral lungs. The baseline scores were calculated from Tc-99m DTPA radioaerosol inhalation lung scintigraphy before inhalation therapy (100 µg fluticasone propionate two times daily for one week), and the scores were recalculated after inhalation therapy to evaluate the effects of one-week of fluticasone propionate inhalation therapy for Tc-99m DTPA radioaerosol distribution patterns. After one week of fluticasone propionate inhalation therapy, the scores were decreased in all of the 10 children, which may mean that the bronchial constriction degree due to asthma is decreased. In addition, there was a significantly statistical difference in the scores before and after one-week fluticasone propionate inhalation therapy (p < 0.05). In conclusion, one-week fluticasone propionate inhalation therapy could significantly improve the bronchial constriction due to asthma in children based on the evidence of Tc-99m DTPA radioaerosol inhalation lung scintigraphic findings.     

Improved Ability to Perform Strenuous Activities After Treatment with Fluticasone Propionate/Salmeterol Combination in Patients with Persistent Asthma

Patients with asthma experience disruptions in usual activities that can impair their quality of life, and in patients whose daily routine involves an active lifestyle, these disruptions can be severe. We assessed the patient-perceived effect of treatment with fluticasone propionate/salmeterol combination (FSC), compared with fluticasone propionate (FP) or salmeterol (SAL) alone, on activity limitations, particularly strenuous physical activities. The Asthma Quality of Life Questionnaire (AQLQ) was administered in two 12-week, randomized, double-blind, placebo-controlled trials comparing FSC 100/50 or 250/50 µg twice daily vs. the individual components alone in 686 adults and adolescents with asthma. In one study, patients were stratified by prior treatment [low to medium doses of inhaled corticosteroids (ICS) or SAL], and in the other study, all patients were previously treated with medium to high doses of ICS. Patients prospectively identified five activities they performed regularly and were asked how these activities were limited by their asthma. The effect of randomized treatment on strenuous activities (e.g., aerobics, cycling, hiking, and basketball) was assessed. In both studies, treatment with FSC resulted in clinically meaningful improvements (i.e., change in AQLQ of ≥0.5) and was statistically significantly better than SAL in both studies and FP in one study. Treatment of the two main components of asthma—inflammation and bronchoconstriction—with FSC results in clinically meaningful improvements in the ability of patients with persistent asthma to perform not only their usual activities but also strenuous activities.     

Risk-Benefit Assessment of Fluticasone Propionate in the Treatment of Asthma and Allergic Rhinitis

Benefits

Fluticasone propionate (FP) is a new topical corticosteroid spray for the treatment of allergic rhinitis and asthma. FP has been shown to be effective for the treatment of adult and pediatric asthma, even at rather low doses (25 μg twice daily [b.i.d.]); many studies in asthma have shown clinical efficacy of fluticasone at half the dose of the comparison steroid (such as beclomethasone dipropionate [BDP) or budesonide [BUD]). However, exact dose comparisons cannot be made because dose-ranging comparison studies have not been done. Studies in allergic rhinitis in children and adults have shown good efficacy in FP-treated patients at a dose of 200 μg once daily (o.d.), intranasally. In summary, FP is effective in both asthma and allergic rhinitis.

Risks

FP has minimal systemic activity because the portion of drug that is swallowed is not absorbed from the gut. Thus, the amount available for systemic activity is only that which is absorbed through the nasal mucosa (in the treatment of rhinitis) or through the alveoli of the lungs (in the treatment of asthma). When laboratory assays of adrenal function or bone formation are measured, FP and other inhaled corticosteroids can be shown to cause suppression of these markers, especially at high doses. There have been no consistent reports of clinical adrenal suppression or osteoporosis caused by FP.

In summary, the risk-benefit ratio of FP at the usual doses (therapeutic ratio) is very favorable. High doses may show evidence of suppression of the hypothalamic pituitary axis as measured by in vitro tests, but evidence of corresponding clinical adverse effects is lacking.     

Fluticasone Propionate HFA-134a Pressurized Metered-Dose Inhaler in Adolescents and Adults with Moderate to Severe Asthma

In this randomized, double-blind, placebo-controlled trial, 397 patients with moderate to severe asthma, previously treated with bronchodilators alone, received fluticasone propionate 88, 220, or 440 μg twice daily, or placebo via metered dose inhaler (MDI) for 12 weeks. Mean change from baseline to endpoint in pre-dose percent predicted forced expiratory volume in one second (FEV₁) was greater (p < 0.001) in each fluticasone propionate group (9.0%, 88 μg bid; 9.8%, 220 μg bid; 11.2%, 440 μg bid) versus placebo (3.4%). Morning and evening peak expiratory flow (PEF), asthma symptoms, and supplemental albuterol use also improved in all fluticasone propionate groups versus placebo. The incidence of adverse events and 24-hour urine cortisol excretion rates were similar between active treatments and placebo.     

Body Mass Index and Response to Asthma Therapy: Fluticasone Propionate/Salmeterol versus Montelukast

We studied the relationship between body mass index (BMI) on responses to asthma therapy using a retrospective analysis of four previously reported clinical trials. Fluticasone propionate (FP)/salmeterol via Diskus 100/50 μg twice daily and montelukast (MON) 10 mg daily were compared. BMI was classified as underweight (less than 20 kg/m²), normal (20–24.9 kg/m²), overweight (25–29.9 kg/m²), obese-1 (30–34.9 kg/m²), obese-2 (35–39.9 kg/m²), or obese-3 (at least 40 kg/m²). Outcomes assessed included forced expiratory volume in one second (FEV₁), asthma symptom score, and albuterol use. FP/salmeterol produced greater improvements compared to MON in each of the asthma outcomes studied over the entire BMI range at the week-12 endpoint, with statistically significant differences noted among normal, overweight, obese-1, and obese-3 subjects. The within-treatment responses to FP/salmeterol across BMI ranges at the week-12 endpoint was statistically significantly greater in normal compared to obese-3 for FEV₁ and albuterol use, and in overweight compared to the obese-3 for each outcome studied. The within-treatment comparisons of MON across BMI ranges were significant for albuterol use in normal and underweight compared to obese-3 at the week-12 endpoint. Compared to subjects with normal BMI, the onset to peak FEV₁ may require longer treatment exposure in the very obese. Treatment responses to FP/salmeterol were consistently greater compared to MON and persisted at higher BMI.     

Adrenal Function as Assessed by Low-Dose Adrenocorticotropin Hormone Test Before and After Switching from Inhaled Beclomethasone Dipropionate to Inhaled Fluticasone Propionate

Low-dose adrenocorticotropin hormone (ACTH) tests (0.5 µg/L 73 m²) were done before and after switching from inhaled beclomethasone dipropionate to inhaled fluticasone propionate in 12 patients 33–77 years old who had mild-to-severe asthma to compare the effects of these drugs on adrenal function. Low-dose ACTH tests were performed after the subjects had received inhaled beclomethasone dipropionate (200–900 µg/day) for at least 12 wk. Treatment was then switched to inhaled fluticasone propionate (200–600 µg/day) for at least 12 wk, and a second low-dose ACTH test was done. Pulmonary function was assessed on the basis of peak expiratory flow rate (PEFR, % of predicted value). After switching treatment, the daily dose of inhaled corticosteroid decreased by about 40%. Basal serum cortisol and ACTH levels were similar with both treatments. The adrenal response, as assessed by incremental rise in the serum cortisol level (peak minus basal) after ACTH challenge, improved significantly (5.6–7.9 µg/dL, p<0.01) after switching to fluticasone. All three patients who had lower serum cortisol levels during beclomethasone treatment than during fluticasone treatment showed improvement in both the peak cortisol level and the incremental rise in cortisol. Mean morning and evening PEFRs significantly increased after switching from beclomethasone to fluticasone (morning: 71.2 to 76.0%, p<0.01; evening: 67.3 to 72.1%, both p<0.05). The diurnal variation of PEFR significantly decreased from 10.9% to 8.3% after switching treatment (p<0.01). We conclude that switching from beclomethasone to fluticasone reduces the risk of adrenal dysfunction associated with inhaled steroids and improves pulmonary function.     

Initiation of Maintenance Therapy with Salmeterol/Fluticasone Propionate Combination Therapy in Moderate Asthma: A Comparison with Fluticasone Propionate

The objective of this study was to investigate initial maintenance treatment with salmeterol/fluticasone propionate (Seretide) 50/250 μ g twice daily (SFC) compared with fluticasone propionate (Flixotide) 250 μ g twice daily (FP) (both via Diskus inhaler, GlaxoSmithKline, Greenford, UK) in patients with moderate persistent asthma currently only treated with inhaled short-acting β₂-agonists. A total of 362 adults and adolescents (12 to 80 years of age) were randomized to this 12-week double-blind parallel-group study. The primary endpoint was mean morning peak expiratory flow (PEF). Secondary efficacy endpoints included median percentages of symptom-free and rescue-free days and nights; the percentage of patients who achieved the pre-defined criteria for well-controlled asthma over weeks 5 to 12; and the incidence of asthma exacerbations. Safety was assessed by the incidence of adverse events. Superiority of SFC over FP alone was demonstrated for the primary and each secondary endpoint. The difference in adjusted mean change from baseline in morning PEF between SFC and FP was 21 L/min (95%CI: 11, 31; p < 0.001). Significantly more patients achieved well-controlled asthma during treatment with SFC (46%) compared with FP (32%) (odds ratio 1.84; 95%CI: 1.17, 2.89; p = 0.008). Both treatments were safe and well-tolerated. This study demonstrates that initial maintenance treatment with SFC 50/250 μg twice daily provides superior efficacy to FP 250 μ g twice daily alone in patients with moderate persistent asthma.     

咳嗽变异性哮喘患者疗效与布地奈德福莫特罗疗程的相关性研究

背景 咳嗽变异性哮喘(CVA)是引起成年人慢性咳嗽的主要原因,布地奈德福莫特罗作为治疗此病的重要药物,其最佳疗程目前尚无统一定论,如何在保证治疗安全性的同时尽可能使患者获益是当前临床研究热点和难点.目的 探讨CVA患者疗效与布地奈德福莫特罗疗程的相关性.方法 选取廊坊市人民医院门诊2018年8月至2020年3月收治的C...     

布地奈德雾化吸入联合西替利嗪治疗小儿哮喘急性发作的临床疗效

目的探讨布地奈德雾化吸入联合西替利嗪治疗小儿哮喘急性发作的临床疗效。方法选择2010年12月—2012年12月我院收治的哮喘急性发作患儿92例,根据治疗方法将患儿分成对照组和观察组,各46例。在对症治疗基础上对照组患儿给予布地奈德雾化吸入;观察组在对照组基础上口服西替利嗪,疗程均为5 d。比较两组患者临床疗效、相关临床症状消失时间及肺功能改善情况。结果观察组患儿总有效率为91.3%,高于对照组的65.2%(P0.05);咳嗽消失时间、喘息消失时间和哮鸣音消失时间短于对照组(P0.05);第一秒呼气末容积(FEV1)和FEV1占预计值的百分比(FEV1%)高于对照组(P0.05)。结论布地奈德雾化吸入联合西替利嗪治疗小儿哮喘急性发作疗效显著,能有效改善患儿肺功能,且药物起效快。     

The Role of Budesonide in Adults and Children with Mild-to-Moderate Persistent Asthma

Asthma, a chronic and potentially life-threatening disease of the airways, affects patients of all ages. Inhaled corticosteroids (ICS) are the recommended first-line therapy for patients with persistent asthma. To review the clinical efficacy and tolerability data available on budesonide in the treatment of mild-to-moderate persistent asthma, a MEDLINE database search was performed for 1996-2003 using the following key words: budesonide, inhaled corticosteroid, efficacy, safety, systemic. When administered once or twice daily, budesonide effectively controls asthma in children, adolescents, and adults with mild-to-moderate asthma. Budesonide can be delivered effectively via a dry powder inhaler (Pulmicort Turbuhaler®) in patients aged ≥ 6 years or as an inhalation suspension (Pulmicort Respules®) in children as young as 12 months. With over 20 years' clinical exposure, budesonide has been demonstrated to be well tolerated in the treatment of chronic asthma in patients as young as 12 months. Specifically, at doses required to treat mild or moderate persistent asthma, budesonide does not affect hypothalamic-pituitary-adrenal axis function, bone mineral density, cataract formation, or final adult height. As Pulmicort Turbuhaler®, budesonide is the only ICS to achieve a Food and Drug Administration pregnancy category B rating. Early intervention with budesonide is recommended in asthma management: maximum benefit from therapy is reported in patients treated within 2 years of disease recognition. Budesonide is effective and well tolerated in the control of mild-to-moderate persistent asthma in patients aged 12 months and older. There is no evidence for variation in efficacy in population subgroups.     

Once-Daily Administration of Budesonide Turbuhaler® was as Effective as Twice-Daily Treatment in Patients with Mild to Moderate Persistent Asthma

In a double-blind, randomized, placebo-controlled trial, 288 patients with mild to moderate persistent asthma currently on inhaled glucocorticosteroids (GCSs) were treated with budesonide Turbuhaler®, 200 µg once every night (q.n.), 100 µg twice-daily (b.i.d.), or placebo b.i.d. After 12 weeks, morning peak expiratory flow (PEF) increased in both groups treated with budesonide but decreased in placebo-treated patients. Symptom scores and bronchodilator use were significantly reduced in both groups receiving active treatment (p = 0.023-0.0001) compared with patients treated with placebo. There was no significant difference in outcome measurements between the two budesonide regimens. Thus, patients with mild to moderate persistent asthma receiving b.i.d. treatment with inhaled GCSs can usually be switched to budesonide Turbuhaler®, 200 µg, q.n. without loss of asthma control.