Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial

PURPOSE: To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescue-free days. SUBJECTS AND METHODS: Participants aged 15 to 85 years with mild persistent asthma (n = 400) were randomized to oral montelukast (10 mg once nightly) or inhaled fluticasone (88 mug twice daily) in a year-long, parallel-group, multicenter study with a 12-week, double-blind period, followed by a 36-week, open-label period. RESULTS: The mean percentage of rescue-free days was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% confidence interval [CI]: -3.2% to 6.8%) but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8% to 11.7%). Although both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, greater improvements occurred with fluticasone in lung function during both periods and in asthma control during open-label treatment. Post hoc analyses revealed a difference in rescue-free days favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline. CONCLUSION: In patients with mild persistent asthma, rescue-free days and most asthma control measures improved similarly with fluticasone or montelukast over the short term, but with prolonged open-label treatment, asthma control improved more with fluticasone. Improved asthma control with fluticasone appeared to occur in those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that classification criteria for mild persistent asthma may need to be re-evaluated.     

Efficacy of high-dose sublingual immunotherapy in children allergic to house dust mites in real-life clinical practice

BackgroundThe aim of the study was to evaluate the efficacy and safety of high-dose mite sublingual immunotherapy (SLIT) administered in children with allergic rhinitis in real-life clinical practice. Moreover, we analysed the clinical course of asthma severity.MethodsRetrospective, observational, monocentre study. Medical records of patients treated between 2001 and 2008 were reviewed. Patients received a standardised Dermatophagoides pteronyssinus+Dermatophagoides farinae extract (300 IR/ml) manufactured by Stallergenes (Staloral^® 300). Patients were evaluated before SLIT initiation and at 6, 12, 24, 36 and 48 months. Global assessment of SLIT efficacy was measured using a visual analogue scale (VAS) and a rhinitis medication consumption score (RMCS). A global asthma score was used to estimate the clinical course of asthma severity.ResultsWe obtained data from 78 patients, 43.6% male. The mean (±SD) age was 11.0±3.0 years. Most patients (69.2%) suffered from allergic rhinitis plus asthma. Patient evaluation of allergy severity (VAS) revealed a highly significant improvement between baseline and six months (p<0.001, Wilcoxon test): 4.0±1.7 cm vs. 7.3±4.6 cm. This improvement was maintained throughout the four-year follow-up period. The use of medications (RMCS) was significantly reduced in the first six months (4.6±2.5 points at baseline vs. 0.8±1.6 points at six months visit, p<0.001, Wilcoxon test) and remained very low until the end of follow-up. We did not find a temporal improvement in asthma severity.ConclusionsThis retrospective study indicates that high-dose SLIT in children with rhinitis caused by house dust mites is well-tolerated and could be an effective treatment.     

Maintaining asthma control in persistent asthma: comparison of three strategies in a 6-month double-blind randomised study

In patients controlled with SFC250 Diskus bd, this double-blind, randomised 6-month study compared continuing SFC250 to stepping down to either SFC100 bd or FP250 bd. Six hundred and three patients previously using 1,000 microg BDP (or equivalent) daily +LABA and controlled according to investigator's judgement were recruited. Patients received SFC250 bd during an 8-week open run-in period. Four hundred and seventy six patients (mean age=43 years, mean FEV(1)=2.9+/-1.0) who fulfilled the randomisation criterion ('Well-controlled' asthma according to the GOAL weekly definition for the last 2 weeks of the run-in period) entered a 24-week treatment period. The statistical hypothesis was based on a non-inferiority of SFC100 or FP250 compared to SFC250. The main criterion was the change from baseline in morning PEF over weeks 1-12 in the per-protocol population. The non-inferiority limit was -15 L/min. At inclusion, the three treatment groups were well balanced. Mean morning PEF was 476, 470 and 465 L/min in the SFC250, SFC100 and FP250 groups, respectively. The adjusted mean change in morning PEF over weeks 1-12 was +1.76+/-2.43 L/min for SFC250, -3.07+/-2.32 L/min for SFC100 and -16.51+/-2.46 L/min for FP250. SFC100 was at least as effective as SFC250 (treatment difference -4.83 [-12.39; 2.72], p=0.151) whereas FP250 was not (treatment difference -18.27 [-26.05; -10.49], p<0.001). Similar results were observed over weeks 13-24 in morning PEF (SFC100-SFC250=-4.54+/-3.84, p=0.238; FP250-SFC250=-20.11+/-3.92, p<0.0001). Secondary endpoints showed a similar pattern. Over weeks 1-12, SFC250 was significantly more effective than FP250 on evening PEF, daily symptoms and bronchodilator use. There was no difference between SFC100 and SFC250. The mean annual rate of moderate exacerbations was 0.16 in both SFC 250 and SFC 100 groups, and 0.21 in FP 250 group (ns, Poisson analysis). All treatments were well tolerated. CONCLUSION: In patients achieving asthma control with SFC250, stepping treatment down with SFC100 was at least as effective on lung function and symptoms as continuing SFC250, whereas FP250 was not.     

Daclizumab improves asthma control in patients with moderate to severe persistent asthma: a randomized, controlled trial

Rationale: Airway inflammation in asthma is associated with increased activated CD25(+) T cells, IL-2, and soluble IL-2 receptors (IL-2Rs). Objectives: A randomized, double-blinded, placebo-controlled study was used to evaluate the safety and efficacy of daclizumab, a humanized IgG1 monoclonal antibody against the IL-2R alpha chain (CD25) of activated lymphocytes, in adults with moderate to severe persistent asthma. Methods: Patients with obstructive pulmonary functions, despite inhaled corticosteroids (ICS), were switched to equivalent dose inhaled triamcinolone acetate acetonide (TAA). Patients dependent on ICS were randomized (3:1) to daclizumab (intravenous loading dose, 2 mg/kg, then 1 mg/kg) or placebo every 2 weeks, added to stable-dose TAA through Week 12 (Treatment Period 1). Over Weeks 12-20 (Treatment Period 2), patients tapered TAA while on the study drug, and were followed for 16 weeks off the study drug. Measurements and Main Results: Among 115 evaluable patients (88 daclizumab, 27 placebo), groups had similar age, disease duration, and length of ICS use. During Treatment Period 1, daclizumab improved FEV(1) (daclizumab, 4.4 +/- 1.80% vs. placebo, 1.5 +/- 2.39%; P = 0.05), and reduced daytime asthma symptoms (P = 0.018) and short-acting inhaled beta(2)-agonist use (P = 0.009). Daclizumab treatment prolonged time to exacerbation (P = 0.024). Adverse events were evenly distributed between groups, although there were more serious adverse events in the patients treated with daclizumab. Conclusions: Daclizumab improved pulmonary function and asthma control in patients with moderate to severe chronic asthma inadequately controlled on ICS. The mechanism of action likely involves inhibition of proinflammatory cytokine generation by IL-2R blockade in activated T cells. Clinical trial registered with www.clinicaltrials.gov (NCT00028288).     

Cost-effectiveness of omalizumab in severe persistent asthma in Spain: a real-life perspective

Objectives: To determine the cost-effectiveness of omalizumab compared with routine clinical practice in the treatment and control of severe persistent asthma. Methods: Cost-effectiveness analysis using pre- and post-treatment with omalizumab after 10 months of 47 patients diagnosed with uncontrolled severe persistent asthma attended by the Pneumology Service, Hospital Universitario Virgen de la Victoria, Malaga. Effectiveness was assessed by the number of emergency room (ER) visits for exacerbations and quality-adjusted life years (QALY) gained. The costs of treatment with omalizumab and ER visits were analyzed using the National Health System perspective. Results are expressed in cost per QALY gained and cost per ER visit avoided (costs €2012). Results: Exacerbations with ER visits decreased significantly (p?<?0.001) after 10 months of omalizumab treatment compared with the previous 10 months [7.94 (6.52–9.37) vs 0.19 (0.03–0.35)]. Health utilities increased significantly (p?<?0.001) during the same period [0.5967 (0.5722–0.6212) vs 0.7566 (0.7232–0.7900)], representing 0.1333 (0.1053–0.1612) QALYs gained (p?<?0.001).The mean cost per patient was €1850.78 (1519.46–2182.10) in the 10 months before treatment and €5431.87 (4930.72–5933.02) after 10 months of omalizumab treatment. The incremental cost-effectiveness ratios (ICERs) were €462.08/exacerbation avoided (347.65–606.22) and €26?864.89/QALY gained (21?632.07–33?859.49). Conclusions: Our results confirm that adding omalizumab to the treatment of patients with uncontrolled severe persistent asthma reduces the number of exacerbations with ER visits and increases health-related quality of life after 10 months of treatment and produces ICERs favorable to omalizumab and acceptable from the health system perspective.     

支气管哮喘和变应性鼻炎的舌下特异性免疫疗法进展

舌下特异性免疫疗法在支气管哮喘和变应性鼻炎的治疗方面发挥了重要作用,它提供了一种可以替代传统皮下免疫疗法的变应原免疫治疗方法。目前已经有两种制剂（滴剂和片剂）可以用于舌下特异性免疫疗法。研究表明舌下特异性免疫疗法是安全、有效的。     

支气管哮喘和变应性鼻炎的舌下特异性免疫疗法进展

舌下特异性免疫疗法在支气管哮喘和变应性鼻炎的治疗方面发挥了重要作用,它提供了一种可以替代传统皮下免疫疗法的变应原免疫治疗方法.目前已经有两种制剂(滴剂和片剂)可以用于舌下特异性免疫疗法.研究表明舌下特异性免疫疗法是安全、有效的.     

舌下免疫治疗变应性支气管哮喘疗效与安全性的Meta分析

目的 评价舌下免疫治疗(SLIT)变应性支气管哮喘(以下简称哮喘)的疗效与安全性,为SLIT的临床应用提供可靠的循证医学证据.方法 检索中国知网、万方数据库、Pubmed、Medline国内外公开发表的SLIT变应性哮喘的随机对照试验(RCT);采用Jadad评分法评估各项研究的质量;Meta分析用Stata 11.0软件完成;采用固定或随机效应模型分析研究结果;无法进行合并的效应量采用描述性分析;采用Egger's和Begg's检验评价发表偏倚.结果 纳入6项RCT研究,Meta分析结果显示,与对照组比,SLIT组哮喘症状评分显著降低[标准化均数差(SMD)=-0.89,95％ CI-1.36～-0.43,P=0.000],哮喘药物使用评分降低(SMD=-4.53,95％CI-6.97～-2.08,P=0.000);第1秒用力呼气容积(FEV1)(SMD =0.19,95％ CI-0.02～0.41,P=0.078)和血清变应原特异性IgE水平(SMD=0.05,95％ CI-0.58 ～0.69,P=0.870)差异无统计学意义(P＞0.05);SLIT无明显不良反应;Egger's和Begg's检验结果显示无发表偏倚.结论 SLIT可以明显降低变应性哮喘症状评分、药物使用评分,是一种安全有效的免疫途径;但需要开展更高质量的RCT研究,为SLIT的广泛应用提供更加有力的证据.     

Role of sublingual immunotherapy in the treatment of asthma: An updated systematic review

Background

The purpose of the systematic review is to evaluate the efficacy and safety of sublingual immunotherapy (SLIT) for the treatment of allergic asthma.

Methods

PubMed, Embase, and CENTRAL databases were searched, updating an earlier review (January 1, 2005 through May 8, 2017). Randomized, controlled studies (RCTs) were included, which reported one of the prespecified outcomes: asthma symptoms measured by control composite scores; quality of life; medication use; pulmonary physiology; and health‐care utilization. For safety outcomes, RCTs and observational studies were included. Two independent reviewers extracted data, assessed risk of bias, and graded strength of evidence (SOE) for each outcome.

Results

Fourteen RCTs (n = 2585) assessed the efficacy of SLIT for asthma. The RCTs utilized house dust mite (HDM), birch, or grass allergen. SLIT improved asthma symptoms (high SOE), decreased use of long‐term control medication, and improved forced expiratory volume in 1 second (FEV₁) (moderate SOE). SLIT may decrease quick‐relief medication use, and improve disease‐specific quality of life (low SOE). For safety, 20 RCTs and 10 observational studies (n = 3621) were identified. Local (risk differences ranged from ?0.03 to +0.765) and systemic allergic reactions (risk differences ranged from ?0.03 to +0.06) were a common occurrence in SLIT and control groups. Life‐threatening reactions were uncommon, with 3 cases of anaphylaxis and no deaths reported.

Conclusion

There is moderate‐to‐high strength evidence that SLIT improves allergic asthma symptoms, reduces long‐term control medication use, and improves FEV₁ based on studies of HDM, birch, and grass. SLIT rarely is associated with life‐threatening adverse events.

     

EXCEL: A randomised trial comparing salmeterol/fluticasone propionate and formoterol/budesonide combinations in adults with persistent asthma

OBJECTIVES: This multicentre, parallel group, double-blind, double-dummy, randomised 24-week study was designed to compare the efficacy of salmeterol/fluticasone propionate combination (SFC) 50/250 microg one inhalation twice daily (bid) with formoterol/budesonide combination (FBC) 6/200 microg two inhalations bid in patients with persistent asthma, currently receiving 1000-2000 microg/day of inhaled corticosteroids. METHODS: The intent-to-treat population comprised 694 patients in the SFC group and 697 patients in the FBC group. RESULTS: The primary endpoint, mean rate of all exacerbations over 24 weeks, was similar in both treatment groups (SFC: 2.69; FBC: 2.79; SFC/FBC ratio 0.96; 95% CL 0.84, 1.10; P=0.571). A reduction in the rate of exacerbations over time was observed in both treatment groups. Overall, there was a 30% lower annual rate of moderate/severe exacerbations in the SFC group compared with the FBC group (95% CI 0-49%, 52% reduction vs. 1% increase; P=0.059). This effect increased with time: in weeks 17-24 the moderate/severe exacerbation rate was 57% lower in the SFC group compared with the FBC group (95% CI 21-77% reduction; P=0.006). Similar improvements in lung function, asthma symptoms and rescue medication usage were seen with both treatments and both were well tolerated. CONCLUSIONS: Twice-daily treatment with SFC and FBC over 6 months significantly improved asthma symptoms and lung function in patients with persistent asthma. The rate of exacerbations was significantly reduced over time on both treatments but SFC was found to be significantly superior to FBC in reducing the rate of moderate/severe exacerbations with sustained treatment.     

Modes of administration of inhaled corticosteroids in mild to moderate persistent asthma

Inhaled corticosteroids are the treatment of choice for asthma. However, poor compliance by patients is one of the principal difficulties forced by clinicians. Thus, it seems important to propose the minimal daily number of doses. This study has compared the various modes of administration of inhaler corticosteroids and was carried out in patients with mild to moderate persistent asthma. Thus, comparing two to four doses per day shows an identical efficacy if the dose is less than 800 micrograms per day. At higher doses only two studies have been carried out and there are discordant results. The studies compare two doses versus one single dose per day and equally disagree with numerous works in favor of a single daily dose. In the single study carried out for at least twelve months the twice daily dose was the most effective. Thus it seems reasonable to suggest a single dose for mild persistent asthmatics. For moderate persistent asthmatics the choice between a single or twice daily dose would depend on the therapeutic compliance of the patient.