Percentage Of Symptom-free Days Research Articles

Evaluating the Clinical Outcomes of Three Medication Regimens for Treating a Sample of Iraqi Persistent Asthmatic patients

Abstract
 Asthma is a complex disease defined by chronic airway inflammation and airflow limitation causing variable respiratory symptoms which include shortness of breath (SOB), wheezing, chest tightness and cough. Asthma guidelines advocate adding a second long acting bronchodilator to medium doses of inhaled corticosteroids (ICS) rather using high doses of ICS alone to control moderate to severe persistent asthma. The aim of this study was to evaluate the clinical outcomes of three medication regimens indicated for Iraqi patients suffering from persistent asthma. 
 This study was interventional randomized clinical study conducted on a sample of adult Iraqi asthmatic patients in Baghdad City. The study composed of three visits distributed over eight weeks; baseline visit followed by first follow up and second follow up visits after four and eight weeks respectively. The study enrolled 78 adult patients with moderate to severe persistent asthma as diagnosed by specialist physician according to patient history and baseline pulmonary function test (PFT) and allocated them randomly to three groups (each group included 26 patients) to receive equivalent medium doses of budesonide inhaler in addition to either formoterol inhaler, oral modified release aminophylline tablets or tiotropium inhaler (first, second and third group respectively). Sixty four patients completed this study. The mean ages of patients were above 35 years with slightly more male predominance.
 The study groups developed significant increase of peak expiratory flow rate (PEFR) and forced vital capacity (FVC) values at the first follow up visit compared to baseline values (p<0.001). Thereafter, the first and third groups achieved significant higher values at the second follow up visit compared to first follow up visit (p<0.001), while second group produced no change. All the groups developed significant improvement of Mini asthma quality of life questionnaire (MiniAQLQ) scores and percentage of symptom free days (SFD) at first follow up visit and continued further significant improvement at the second follow up visit (p<0.001). Generally, between groups comparison according to extent of change of study parameters revealed that third group produced the greatest improvement over the entire study period followed by the first group, whereas the second group was associated with the least extent of improvement.
 This study concluded that all groups caused significant improvement in study parameters compared to baseline values and also concluded that the third group of inhaled [tiotropium/budesonide] was associated with the highest extent of improvement followed by first group, while the second group was the least. 

Antibiotics for exacerbations of asthma.

Antibiotics for exacerbations of asthma.

Effect of a mobile health, sensor-driven asthma management platform on asthma control

BackgroundAsthma inflicts a significant health and economic burden in the United States. Self-management approaches to monitoring and treatment can be burdensome for patients. ObjectiveTo assess the effect of a digital health management program on asthma outcomes. MethodsResidents of Louisville, Kentucky, with asthma were enrolled in a single-arm pilot study. Participants received electronic inhaler sensors that tracked the time, frequency, and location of short-acting β-agonist (SABA) use. After a 30-day baseline period during which reference medication use was recorded by the sensors, participants received access to a digital health intervention designed to enhance self-management. Changes in outcomes, including mean daily SABA use, symptom-free days, and asthma control status, were compared among the initial 30-day baseline period and all subsequent months of the intervention using mixed-model logistic regressions and χ2 tests. ResultsThe mean number of SABA events per participant per day was 0.44 during the control period and 0.27 after the first month of the intervention, a 39% reduction. The percentage of symptom-free days was 77% during the baseline period and 86% after the first month, a 12% improvement. Improvement was observed throughout the study; each intervention month demonstrated significantly lower SABA use and higher symptom-free days than the baseline month (P < .001). Sixty-nine percent had well-controlled asthma during the baseline period, 67% during the first month of the intervention. Each intervention month demonstrated significantly higher percentages than the baseline month (P < .001), except for month 1 (P = .80). ConclusionA digital health asthma management intervention demonstrated significant reductions in SABA use, increased number of symptom-free days, and improvements in asthma control. Trial RegistrationClinicalTrials.gov Identifier: NCT02162576.

Efficacy of acupuncture for chronic asthma: study protocol for a randomized controlled trial.

BackgroundAlthough asthma symptoms can be temporarily controlled, it is recommended to use effective low-risk, non-drug strategies to constitute a significant advance in asthma management. Acupuncture has been traditionally used to treat asthma; however, the evidence for the efficacy of this treatment is still lacking. Previous clinical trials of acupuncture in treating asthma were limited by methodological defects; therefore, high-quality research is required.Methods/DesignThis trial is designed as a multi-center, randomized, double-blind, parallel-group controlled trial. Patients with mild to moderate asthma will be randomly allocated to either a verum acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group or a sham acupuncture plus as-needed salbutamol aerosol and/or prednisone tablets group. Acupoints used in the verum acupuncture group are GV14 (Da Zhui), BL12 (Feng Men), BL13 (Fei Shu) and acupoints used in the sham acupuncture group are DU08 (Jin Suo), BL18 (Gan Shu), BL19 (Dan Shu). After a baseline period of 1 week, the patients in both groups will receive verum/sham acupuncture once every other day with a total of 20 treatment sessions in 6 weeks and a 3-month follow-up. The primary outcome will be measured by using the asthma control test and the secondary outcomes will be measured by using the percentage of symptom-free days, the average dosage of salbutamol aerosol and/or prednisone tablets, lung functions, daily asthma symptom scores, asthma quality of life questionnaire, and so on.DiscussionThis trial will assess the effect of acupuncture on asthma and aims to provide reliable clinical evidence for the efficacy of acupuncture in treating asthma.Trial registrationClinicalTrials.gov Identifier: NCT01931696, registered on 26 August 2013

Measurement properties of an asthma symptom and rescue medication use diary

Introduction: Assessment of symptoms and rescue medication use are well-established endpoints for clinical trials evaluating asthma treatment. Objective: To evaluate the measurement properties of an asthma symptom and rescue medication use (ASRMU) diary for clinical trials involving asthma patients aged ≥12 years. Methods: Interviews with 35 patients were conducted to confirm the importance of key concepts in the ASRMU diary. Scores of symptom and rescue medication use were converted to symptom-free days (SFD) and rescue-free days (RFD). Test–retest reliability and equivalence (based on intra-class correlation coefficients [ICCs]) between paper-and-pencil and electronic (eDiary) versions were evaluated in a prospective study in 47 patients. Responsiveness of the ASRMU diary was evaluated through differences in percentage of SFD and of RFD by treatment group in eight asthma clinical trials that assessed inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA), alone or in combination. A ninth placebo-controlled study calculated effect sizes. Minimal important differences (MID) were determined using anchor-based methods from two trials and by interviewing 11 patients. Results: Patient interviews supported content validity for the ASRMU diary. Test–retest reliability was acceptable for SFD (ICC:0.70–0.75), but varied for RFD (ICC:0.58–0.78). Paper-and-pencil and eDiary modes of administration were equivalent (SFD, ICC = 0.84; RFD, ICC = 0.70). ICS/LABA had the largest percentage of SFD and RFD, followed by monotherapy and then placebo. MIDs were 7.7–14.7% for SFD and 8.4–15.6% for RFD. Conclusions: The ASRMU diary captures the disease-specific concepts of greatest importance to asthma patients and provides important information for asthma diagnosis and treatment evaluation.

Addition of a 5-lipoxygenase-activating protein inhibitor to an inhaled corticosteroid (ICS) or an ICS/long-acting beta-2-agonist combination in subjects with asthma

Objective:To investigate the clinical benefits of ‘add-on’ therapy with GSK2190915 in combination with the inhaled corticosteroid (ICS) fluticasone propionate (FP) and the ICS/long-acting beta 2 agonist (LABA) combination FP/salmeterol in asthmatic subjects.Methods:Both studies were cross-over, randomized, double-blind, double-dummy and placebo-controlled in subjects with a forced expiratory volume in 1 second (FEV1) best of >50 and ≤80% of predicted. Add-on to ICS: Subjects (n = 162) aged ≥12 years received FP 100 µg twice daily (BID) plus GSK2190915 100 mg once daily (QD); GSK2190915 300 mg QD; montelukast 10 mg QD; salmeterol 50 µg BID or placebo. Add-on to ICS/LABA: Female subjects (n = 145) aged ≥18 years received FP/salmeterol 250/50 µg BID plus GSK2190915 300 mg QD, montelukast 10 mg QD or placebo. In both studies, the primary endpoint was trough FEV1 at the end of the treatment period. Secondary endpoints included a range of objective and patient-reported measures of efficacy.Results:Add-on to ICS: There was no statistically significant difference in the primary endpoint between either dose of GSK2190915 (add-on to FP) and placebo. Nominally statistically significant increases were demonstrated for GSK2190915 300 mg add-on relative to placebo for mean morning peak expiratory flow (p = 0.049), percentage of symptom-free days (p = 0.035) and percentage of symptom-free 24 h periods (p = 0.030). Add-on to ICS/LABA: There were no statistically significant differences on the primary endpoint between treatment regimens. Nominally statistically significant decreases were demonstrated in daytime (p = 0.023), night-time (p = 0.041) and 24 h (p = 0.019) short-acting beta 2 agonist usage with FP/salmeterol + GSK2190915 300 mg vs. FP/salmeterol + placebo.Conclusion:There was no clinically significant improvement in the primary endpoint following GSK2190915 add-on treatment; however, improvements in a range of secondary endpoints and biomarker data provided evidence of pharmacological activity. Improvements in response to background treatment may have been a limitation in both studies.Trial registration:Clinicaltrials.gov identifiers: NCT01156792 and NCT01248975.

An Electronic Diary Is Shown to Be More Reliable than a Paper Diary: Results from a Randomized Crossover Study in Patients with Persistent Asthma

Objectives. Test–retest reliability of an asthma paper diary versus an electronic diary (e-diary) with an integrated peak flow meter was investigated. The equivalence of the two modes was also evaluated. Methods. Prospective, randomized crossover study design in adolescents (12–17 years) and adults (≥18 years). Key inclusion criteria were persistent asthma, Asthma Control Test (ACT) scores ≥16, use of inhaled corticosteroid with or without long-acting beta-agonist for ≥12 weeks, nocturnal awakenings <2 times in the past week, and activity limitations <1 per week. Participants were randomized to either paper then e-diary or e-diary then paper, to be completed for 14 days each. Results. Forty-seven participants completed all study visits. Weekly percentage of symptom-free days (SFDs) and rescue-free days (RFDs) were calculated. Intraclass correlation coefficients (ICCs) of Week 1 mean SFD and RFD (test) and Week 2 mean SFD and RFD (retest), respectively, were estimated in three groups defined as stable: (i) minimal changes in asthma symptoms, as measured by the global patient reported symptom change question, (ii) less than 15% change (absolute value) in 1 second FEV1 at adjacent study visits, and (iii) changes in ACT scores less than three points for each mode. SFD demonstrated acceptable ICC (≥0.70) using all three definitions of asthma stability for both modes. Conclusion. Acceptable reproducibility of the percentage of RFD (ICC = 0.78) was only observed for the e-diary using the FEV1 stability criterion. The ICCs for SFD and RFD were acceptable, 0.84 and 0.70, respectively, suggesting better reliability for the e-diary.

Combination Therapy Salmeterol/Fluticasone Versus Doubling Dose of Fluticasone in Children With Asthma

To determine if the addition of a long-acting bronchodilator is noninferior to doubling the dose of inhaled corticosteroids in children whose asthma is not controlled with use of low-to-moderate doses of inhaled corticosteroids alone.Children aged 6 to 16 years who were using fluticasone propionate (100 μg twice daily) to treat their asthma were enrolled in this study (N = 257). A 4-week run-in period was used to monitor these children. Those who were still symptomatic despite regular use of fluticasone propionate were included in the randomization of study groups (n = 158). The study was conducted at multiple pediatric medical centers throughout Europe.Symptomatic children were randomly assigned to 1 of 2 treatment groups: fluticasone propionate (200 μg twice per day) or salmeterol/fluticasone propionate (50/100 μg twice per day), used for a 26-week treatment period. Lung-function measurements were recorded at the start of the run-in period, at time of randomization, and at all visits during the treatment period. The provocative dose of methacholine that causes a 20% decrease (PD20) in the forced expiratory volume in 1 second (FEV1) and exhaled nitric-oxide levels were measured at the start and end of the treatment period. The number of symptom-free days and asthma exacerbations were logged at each clinic visit. Exacerbations were classified as mild, moderate, or severe on the basis of the medical interventions needed.There was no significant difference between the treatment groups in the percentage of symptom-free days. Each treatment group had an increase in symptom-free days by ∼25% while on treatment compared to baseline (P < .001). Furthermore, no significant difference was seen in the percentage of days in which rescue salbutamol was used; both groups had a gradual decline in use of the salbutamol. A combined ranked assessment of all exacerbations among the treatment groups revealed no statistically significant difference between the 2 groups. Lung-function parameters did not differ between groups other than a slightly greater effect on maximal expiratory flow seen in the salmeterol/fluticasone group during the first week of treatment. The 2 groups did not differ in statural growth or number of adverse events.The results of this study indicate that the combination of a long-acting bronchodilator with inhaled corticosteroid has equal efficacy in controlling symptoms and preserving lung function when compared with doubling the dose of inhaled corticosteroids in children who were symptomatic on a moderate dose of inhaled corticosteroids. Therefore, combination of a long-acting bronchodilator is likely an appropriate alternative in step-up therapy.This study provides us with an adequate alternative step 3 treatment option. The results of this study are in line with those of previous work. Further study is now needed to evaluate whether there might be specific asthma phenotypes that respond more favorably to 1 treatment option versus another. The fear of increased severe asthma exacerbations and asthma-related deaths associated with use of long-acting β2 agonists in children is still present. Further data from large numbers of children are needed to make a more definite conclusion about this possible risk.

Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children

BackgroundFew data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations.MethodsTo compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode.ResultsThe percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma.ConclusionsA 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.Trial RegistrationClinicalTrials.gov (NCT00497523)

Safety and efficacy of long-term treatment with fluticasone propionate and salmeterol via DISKUS versus fluticasone propionate alone

This 52 week study (ADA109057; ClinicalTrials.gov identifier: NCT00452348) was designed to assess the safety and efficacy of fluticasone propionate (FP)/salmeterol 250/50 mcg via DISKUS (FSC) vs FP 250 mcg in subjects with persistent asthma symptomatic on FP 100 mcg. The objective was to demonstrate superiority in lung function (FEV1) of FSC 250/50 mcg vs FP 250 mcg. Secondary objectives included AM PEF, percentage of symptom-free days, and rate of asthma attacks. Three hundred and ten subjects received FSC 250/50 mcg and 318 subjects received FP 250 mcg, both administered twice daily following a 14–21 days of open-label FP 100 mcg. Treatment with FSC 250/50 mcg resulted in an improvement in lung function vs FP 250 mcg (p = 0.09). Additionally, treatment with FSC 250/50 mcg improved AM PEF and increased the percentage of symptom-free days. The asthma attack rate was similar between treatments, as was the safety profile. FSC 250/50 mcg demonstrated improvements in lung function and asthma control vs FP 250...

Combination Therapy Salmeterol/Fluticasone Versus Doubling Dose of Fluticasone in Children With Asthma

For children with symptomatic asthma despite low to moderate doses of inhaled corticosteroids, evidence is still lacking whether to add a long-acting bronchodilator or to increase the dose of inhaled corticosteroids. To evaluate whether salmeterol/fluticasone propionate (SFP), 50/100 μg twice a day, is noninferior regarding symptom control compared with fluticasone propionate (FP), 200 μg twice a day Diskus in children with symptomatic asthma. A multicenter, randomized, parallel-group, double-blind study was performed comparing SFP and FP treatment during 26 weeks on asthma control and lung function. A total of 158 children, 6-16 years old, still symptomatic on FP, 100 μg twice a day, during a 4-week run-in period, were included. Percentage of symptom-free days during the last 10 weeks of the treatment period did not differ between treatment groups (per protocol analysis: adjusted mean difference [FP minus SFP] 2.6%; 95% confidence interval, -8.1 to 13.4). Both groups showed substantial improvements of about 25 percent points in symptom-free days (both P < 0.001 from baseline). Lung function measurements (FEV(1), FVC, PEF rate, and maximal expiratory flow) did not differ between groups except for a slight advantage in maximal expiratory flow in the SFP group at 1 week. No differences were found between FP and SFP regarding exacerbation rates, adverse events, or growth. In our study the efficacy on symptom control and lung function of the combination of a long-acting bronchodilator with inhaled corticosteroid is equal to doubling the dose of the inhaled corticosteroid in children still symptomatic on a moderate dose of inhaled corticosteroid.

Regular vs prn nebulized treatment in wheeze preschool children

International guidelines recommend regular treatment with inhaled glucocorticoids for children with frequent wheezing; however, prn inhaled bronchodilator alone or in combination with glucocorticoid is also often used in practice. We aimed to evaluate whether regular nebulized glucocorticoid plus a prn bronchodilator or a prn nebulized bronchodilator/glucocorticoid combination is more effective than prn bronchodilator alone in preschool children with frequent wheeze. Double-blind, double-dummy, randomized, parallel-group trial. After a 2-week run-in period, 276 symptomatic children with frequent wheeze, aged 1-4 years, were randomly assigned to three groups for a 3-month nebulized treatment: (1) 400 microg beclomethasone bid plus 2500 microg salbutamol prn; (2) placebo bid plus 800 microg beclomethasone/1600 microg salbutamol combination prn; (3) placebo bid plus 2500 microg salbutamol prn. The percentage of symptom-free days was the primary outcome measure. Secondary outcomes included symptom scores, use of relief medication and exacerbation frequency. As compared with prn salbutamol (61.0 +/- 24.83 [SD]), the percentage of symptom-free days was higher with regular beclomethasone (69.6%, SD 20.89; P = 0.034) but not with prn combination (64.9%, SD 24.74). Results were no different in children with or without risk factors for developing persistent asthma. The effect of prn combination was no different from that of regular beclomethasone on the primary and on several important secondary outcomes. Regular inhaled glucocorticoid is the most effective treatment for frequent wheezing in preschool children. However, prn bronchodilator/glucocorticoid combination might be an alternative option, but it requires further study.

Inhaled sodium cromoglycate for asthma in children.

Sodium cromoglycate has been recommended as maintenance treatment for childhood asthma for many years. Its use has decreased since 1990, when inhaled corticosteroids became popular, but it is still used in many countries. To determine the efficacy of sodium cromoglycate compared to placebo in the prophylactic treatment of children with asthma. We searched the Cochrane Airways Group Trials Register (October 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007), MEDLINE (January 1966 to November 2007), EMBASE (January 1985 to November 2007) and reference lists of articles. We also contacted the pharmaceutical company manufacturing sodium cromoglycate. In 2007 we updated the review. All double-blind, placebo-controlled randomised trials, which addressed the effectiveness of inhaled sodium cromoglycate as maintenance therapy, studying children aged 0 up to 18 years with asthma. Two authors independently assessed trial quality and extracted data. We pooled study results. Of 3500 titles retrieved from the literature, 24 papers reporting on 23 studies could be included in the review. The studies were published between 1970 and 1997 and together included 1026 participants. Most were cross-over studies. Few studies provided sufficient information to judge the concealment of allocation. Four studies provided results for the percentage of symptom-free days. Pooling the results did not reveal a statistically significant difference between sodium cromoglycate and placebo. For the other pooled outcomes, most of the symptom-related outcomes and bronchodilator use showed statistically significant results, but treatment effects were small. Considering the confidence intervals of the outcome measures, a clinically relevant effect of sodium cromoglycate cannot be excluded. The funnel plot showed an under-representation of small studies with negative results, suggesting publication bias. There is insufficient evidence to be sure about the efficacy of sodium cromoglycate over placebo. Publication bias is likely to have overestimated the beneficial effects of sodium cromoglycate as maintenance therapy in childhood asthma.

The effect of budesonide and formoterol in one pressurized metered-dose inhaler on patient-reported outcomes in adults with mild-to-moderate persistent asthma

ABSTRACTObjective: To determine the effects of budesonide and formoterol administered via one pressurized metered-dose inhaler (budesonide/formoterol pMDI) on patient-reported outcomes (PROs) and to determine the contributions of budesonide and formoterol to those effects in adults with asthma.Research design and methods: A 12-week, random­ized, double-blind, double-dummy, placebo-controlled, multicenter study was conducted in 480 patients aged ≥ 12 years with mild-to-moderate persistent asthma. After a 2-week run-in period during which current asthma therapy was discontinued, patients were randomized to receive two inhalations twice daily of budesonide/formo­terol pMDI 80/4.5 μg (160/9 μg), budesonide pMDI 80 μg (160 μg), formoterol via dry powder inhaler (DPI) 4.5 μg (9 μg), or placebo.Main outcome measures: Analyses included a subpopulation of 405 patients aged ≥ 18 years. PROs included the standardized Asthma Quality of Life Questionnaire (AQLQ(S)), the Medical Outcomes Study (MOS) Sleep Scale, the Patient Satisfaction with Asthma Medication (PSAM) questionnaire, and asthma control variables (recorded via electronic diaries), such as asthma symptoms, rescue medication use, and nighttime awakenings due to asthma. Patient and physician global assessments were collected at the end of the study.Results: Patients aged ≥ 18 years receiving budesonide/formoterol pMDI reported significantly greater improvements from baseline in AQLQ overall and domain scores, MOS Sleep Scale domain scores, and asthma control variables than patients receiving placebo ( p ≤ 0.033). Improvements from baseline in AQLQ(S) overall and domain scores, daily asthma symptoms scores, percentage of symptom-free days, percentage of rescue medication-free days, and percentage of asthma control days were significantly greater in patients receiving budesonide/formoterol pMDI versus formoterol DPI ( p ≤ 0.042). Patients receiving budesonide/formoterol pMDI reported significantly greater PSAM scores than did patients in all other treatment arms ( p ≤ 0.004). Study limitations may include the fact that the formoterol-alone arm used a different device and formulation than the other active arms as well as the absence of a treatment arm with budesonide and formoterol administered concomit­antly in separate inhalers. In addition, these results may not be generalized to all patients with asthma, as this analysis included only patients aged ≥ 18 years.Conclusions: Patients receiving treatment with budesonide/for­moterol pMDI experienced significantly greater improvements from baseline in asthma-related quality of life, quality of sleep, and asthma control and greater satisfaction with treatment than patients receiving placebo. The combination of budesonide and formoterol in one pMDI is beneficial in improving how a patient feels and functions as a result of treatment.

Combined Salmeterol/Fluticasone Propionate versus Fluticasone Propionate Alone in Mild Asthma

Combined therapy with inhaled corticosteroids (ICSs) and long-acting beta(2)-adrenoceptor agonists (LABAs) is the recommended approach for the treatment of patients with asthma that is uncontrolled on ICSs alone. Additional studies are needed to assess the safety and efficacy of combination treatment with ICSs and LABAs in patients with mild asthma. The aim of this study was to compare the efficacy and tolerability of once-daily salmeterol/fluticasone propionate combination (SFC) with once-daily fluticasone propionate (FP) over a 12-week treatment period in patients with mild persistent asthma. This was a randomized, double-blind, placebo-controlled, parallel-group, multicentre study carried out in primary care or at a hospital outpatient department and included patients 12-79 years of age with mild persistent asthma (n = 458). After a 2-week run-in period, patients were randomized to receive SFC 50 microg/100 microg (n = 149), FP 100 microg (n = 154) or placebo (n = 155) once daily in the morning for 12 weeks. The primary efficacy endpoint was patient-recorded pre-dose mean morning peak expiratory flow (PEF). Other assessments included asthma symptom scores, use of rescue medication and investigator-recorded exacerbations. Lung function was measured and assessed during clinic visits. For the primary efficacy endpoint of mean change in morning PEF, SFC achieved significantly greater increases from baseline than both placebo (difference in adjusted means 23 L/min; 95% CI 15.0, 30.3; p < 0.001) and FP (difference in adjusted means 14 L/min; 95% CI 6.3, 21.7; p < 0.001). Compared with those who received FP, patients in the SFC group demonstrated significantly greater improvements in mean evening PEF (95% CI 11.7, 28.1; p < 0.001), forced expiratory volume in 1 second (95% CI 0.093, 0.257; p < 0.001), forced expiratory flow between 25% and 75% of forced vital capacity (95% CI 0.242, 0.617; p < 0.001), the percentage of symptom-free days (95% CI 0.34, 0.87; p = 0.011), and the percentage of rescue medication-free days (95% CI 0.34, 0.90; p = 0.018). During weeks 5-12, 52% of patients in the SFC group achieved 'well controlled' asthma, compared with 42% and 26% of patients in the FP and placebo groups, respectively. Only one patient (receiving placebo) had a severe asthma exacerbation during the study; the frequency of adverse events was similar across the three treatment groups. Once-daily SFC 50 microg/100 microg provided significantly greater improvements in lung function and in asthma symptoms than once-daily FP 100 microg alone in patients with mild persistent asthma. However, twice-daily treatment with either SFC or ICSs plus short acting beta(2)-adrenoceptor agonists could be required to achieve guideline-defined asthma control in some patients.

Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life

BackgroundImproving patients' health-related quality of life (HRQoL) is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP) and an adjustable maintenance dosing (AMD) regimen of formoterol/budesonide (FOR/BUD) where treatment is adjusted based on symptoms [SAM40056].MethodsA total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS) plus a long-acting β2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4. For Weeks 5–52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP.ResultsThe percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034) and the annual exacerbation rate was significantly lower (47%; p = 0.008) with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ) at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52). However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively). The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049); a trend for this difference remained at Week 52 (71% vs 65%) (p = 0.205).ConclusionIn this population of patients with persistent asthma, stable-dose SAL/FP resulted in significantly greater increases in symptom-free days, a reduction in exacerbation rates, and provided greater HRQoL benefits compared with FOR/BUD AMD.Trial registrationClinical Trials registration number NCT00479739

Long-term asthma treatment guided by airway hyperresponsiveness in children: a randomised controlled trial

Management plans for childhood asthma show limited success in optimising asthma control. The aim of the present study was to assess whether a treatment strategy guided by airway hyperresponsiveness (AHR) increased the number of symptom-free days and improved lung function in asthmatic children, compared with a symptom-driven reference strategy. In a multicentre, double-blind, parallel-group, randomised, 2-yr intervention trial, 210 children (aged 6-16 yrs) with moderate atopic asthma, selected on the basis of symptom scores and/or the presence of AHR, were studied. At 3-monthly visits, symptom scores, forced expiratory volume in one second (FEV(1)) and methacholine challenge results were obtained, and medication (five levels of fluticasone with or without salmeterol) adjusted according to algorithms based on symptom score (reference strategy, n = 104) or AHR and symptom score (AHR strategy, n = 102). After 2 yrs, no difference was found in the percentage of symptom-free days between treatment strategies. Pre-bronchodilator FEV(1) was higher in the AHR strategy (2.3% predicted). This was entirely explained by a gradual worsening of FEV(1) in a subgroup of 91 hyperresponsive children enrolled with low symptom scores (final difference between study arms was 6%). Asthma treatment guided by airway hyperresponsiveness showed no benefits in terms of number of symptom-free days, but produced a better outcome in terms of pre-bronchodilator forced expiratory volume in one second in allergic asthmatic children, especially those characterised by low symptom scores despite airway hyperresponsiveness.

Asthma Control during the Year after Bronchial Thermoplasty

Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma. We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting beta2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed. The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16+/-0.37 vs. 0.04+/-0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3+/-48.7 vs. 8.5+/-44.2 liters per minute), scores on the AQLQ (1.3+/-1.0 vs. 0.6+/-1.1) and ACQ (reduction, 1.2+/-1.0 vs. 0.5+/-1.0), the percentage of symptom-free days (40.6+/-39.7 vs. 17.0+/-37.9), and symptom scores (reduction, 1.9+/-2.1 vs. 0.7+/-2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment. Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov].).

Efficacy and safety of fluticasone propionate hydrofluoroalkane inhalation aerosol in pre–school-age children with asthma: A randomized, double-blind, placebo-controlled study

To evaluate the efficacy and tolerability of fluticasone propionate (FP) hydrofluoroalkane (HFA) in children age 1 to < 4 years with asthma. Children were assigned (2:1) to receive FP HFA 88 mug (n = 239) or placebo HFA (n = 120) twice daily through a metered-dose inhaler with a valved holding chamber and attached facemask for 12 weeks. The primary efficacy measure was mean percent change from baseline to endpoint in 24-hour daily (composite of daytime and nighttime) asthma symptom scores. The FP-treated children had significantly greater (P < or = .05) reductions in 24-hour daily asthma symptom scores (-53.9% vs -44.1%) and nighttime symptom scores over the entire treatment period compared with the placebo group. Daytime asthma symptom scores and albuterol use were slightly more decreased with FP than with placebo; however, the differences were not statistically significant. Increases in the percentage of symptom-free days were comparable. The percentage of patients who experienced at least 1 adverse event was similar in the 2 groups. Baseline median urinary cortisol excretion values were comparable between the groups, and there was little change from baseline at endpoint. FP plasma concentrations demonstrated that systemic exposure was low. FP HFA 88 mug twice daily was effective and well tolerated in pre-school-age children with asthma.

Once versus twice daily formoterol via Novolizer ® for patients with moderate to severe COPD—A double-blind, randomised, controlled trial

Study objectives To evaluate in patients with moderate to severe COPD whether a single morning dose of 24 μg formoterol from the Novolizer ® is not inferior to two divided doses of 12 μg formoterol inhaled in the morning and in the evening. Design Randomised, double blind, active-controlled, parallel-group, multi-centre study with a 2-week run-in period and a 12-week treatment phase. Setting Forty-seven outpatient centres in Germany, including private practices. Participants N = 321 symptomatic patients with moderate to severe COPD aged 40–70 years with an FEV 1 of 30–80% predicted and the requirement of 3–12 actuations of salbutamol per day on ⩾5 days during the run-in period. Treatment Eligible patients were randomised to inhale formoterol either (a) as a single 24 μg dose in the morning (OD) or (b) in two divided 12 μg doses in the morning and in the evening (b.i.d.). Measurements and results The mean age was 60.3 (SD 7.3) years, and mean baseline pre-dose FEV 1 was 1.5 l (0.5 l) or 50% (12%) of predicted, respectively. After 12 weeks of treatment, pre-dose FEV 1 improved in both groups (mean: OD, +104 ml, b.i.d., +135 ml, mean difference between groups: 31 ml). The 95% CI exceeded the pre-determined margin of 100 ml by 2 ml, so that the statistical hypothesis of non-inferiority of once daily dosing was not confirmed. No statistically significant differences were seen for improvements in PEF, MEF 75, MEF 50, and MEF 25. COPD symptoms, percentage of symptom-free days and quality of life (SGRQ) improved in both groups to a similar degree. There were no relevant differences in the incidence of adverse events. Conclusions Based on a comparable efficacy and tolerability, the dosing schedule with formoterol via Novolizer ® as once daily in the morning seems to be an alternative compared to twice daily treatment. The primary endpoint suggests the equivalence of both treatment schedules from a clinical perspective. This regimen can be considered as an alternative therapeutic approach for a subgroup of COPD patients and may help to improve patient compliance.