Symptom-free Days Research Articles

Internet-Based Self-management Plus Education Compared With Usual Care in Asthma

The Internet may support patient self-management of chronic conditions, such as asthma. To evaluate the effectiveness of Internet-based asthma self-management. Randomized, controlled trial. 37 general practices and 1 academic outpatient department in the Netherlands. 200 adults with asthma who were treated with inhaled corticosteroids for 3 months or more during the previous year and had access to the Internet. Asthma-related quality of life at 12 months (minimal clinically significant difference of 0.5 on the 7-point scale), asthma control, symptom-free days, lung function, and exacerbations. Participants were randomly assigned by using a computer-generated permuted block scheme to Internet-based self-management (n = 101) or usual care (n = 99). The Internet-based self-management program included weekly asthma control monitoring and treatment advice, online and group education, and remote Web communications. Asthma-related quality of life improved by 0.56 and 0.18 points in the Internet and usual care groups, respectively (adjusted between-group difference, 0.38 [95% CI, 0.20 to 0.56]). An improvement of 0.5 point or more occurred in 54% and 27% of Internet and usual care patients, respectively (adjusted relative risk, 2.00 [CI, 1.38 to 3.04]). Asthma control improved more in the Internet group than in the usual care group (adjusted difference, -0.47 [CI, -0.64 to -0.30]). At 12 months, 63% of Internet patients and 52% of usual care patients reported symptom-free days in the previous 2 weeks (adjusted absolute difference, 10.9% [CI, 0.05% to 21.3%]). Prebronchodilator FEV1 changed with 0.24 L and -0.01 L for Internet and usual care patients, respectively (adjusted difference, 0.25 L [CI, 0.03 to 0.46 L]). Exacerbations did not differ between groups. The study was unblinded and lasted only 12 months. Internet-based self-management resulted in improvements in asthma control and lung function but did not reduce exacerbations, and improvement in asthma-related quality of life was slightly less than clinically significant. Netherlands Organization for Health Research and Development, ZonMw, and Netherlands Asthma Foundation.

Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children.

Long-acting ss(2)- agonists (LABA) in combination with inhaled corticosteroids (ICS) are increasingly prescribed in asthmatic children. To compare the safety and benefit of adding LABA to ICS with the same or an increased dose of ICS in children with persistent asthma. We searched the Cochrane Airways Group Asthma Trials Register (May 2008). We included randomised controlled trials testing the combination of LABA and ICS versus the same or an increased dose of ICS for minimum of at least 28 days in children and adolescents with asthma. The main outcome was the rate of exacerbations requiring rescue oral steroids. Secondary outcomes included pulmonary function, symptoms, adverse events, and withdrawals. Studies were assessed independently by two review authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. A total of 25 trials representing 31 control-intervention comparisons were included in the review randomising 5572 children. Most of the participants were inadequately controlled on current ICS dose. We assessed the addition of LABA to the same dose of ICS and to an increased dose of ICS:(1) The addition of LABA to ICS was compared to same dose ICS, namely 400 mcg/day of beclomethasone or less in 16 of the 24 studies. The mean age of participants was 10 years and males accounted for 64% of the study populations. The mean FEV(1) at baseline was 80% of predicted or above in 10 studies; FEV(1) 61% to 79% of predicted in eight studies; and unreported in the remaining study. Participants were inadequately controlled before randomisation in all but seven studies. Compared to ICS alone, the addition of LABA to ICS was not associated with a significant reduction in exacerbations requiring oral steroids (seven studies, RR 0.92 95% CI 0.60 to 1.40). Compared to ICS alone, there was a significantly greater improvement in FEV1 with the addition of LABA (nine studies; 0.08 Litres, 95% CI 0.06 to 0.11) but no statistically significant group differences in symptom-free days, hospital admission, quality of life, use of reliever medication, and adverse events. Withdrawals occurred significantly less frequently with the addition of LABA.(2) A total of seven studies assessed the addition of LABA to ICS therapy compared with an increased dose of ICS randomising 1021 children. The mean age of participants was 8 years with 67% of males. The baseline mean FEV(1) was 80% of predicted or above in 2 of the 3 studies reporting this characteristic. All trials enrolled participants who were inadequately controlled on a baseline dose equivalent to 400 mcg/day of beclomethasone or less. There was no group significant difference in the risk of an exacerbation requiring oral steroids with the combination of LABA and ICS compared to a double dose of ICS (two studies, RR 1.5 95% CI 0.65 to 3.48). The increased risk of hospital admission with combination therapy was also not statistically significant (RR 2.21 95% CI 0.74 to 6.64). Compared to double dose ICS, use of LABA was associated with a significantly greater improvement in morning PEF (four studies; MD 7.55 L/min 95% CI: 3.57 to 11.53) and evening PEF L/min (three studies, MD 5.5 L/min; 95% CI 1.21 to 9.79), but there were insufficient data to aggregate data on FEV(1), symptoms, rescue reliever use, and quality of life. There was no statistically significant difference in the overall risk of all cause withdrawals (five studies; RR 0.71; 95% CI 0.42 to 1.20. There was no group difference in the risk of overall adverse effects detected. Short term growth was significantly greater in children treated with combination therapy compared to double dose ICS (two studies: MD 1.2 cm/year; 95% CI 0.72 to 1.7). In children with persistent asthma, the addition of LABA to ICS was not associated with a significant reduction in the rate of exacerbations requiring systemic steroids, but was superior for improving lung function compared to the same dose of ICS. Similarly, compared to a double dose ICS, the combination of LABA and ICS did not significantly increase the risk of exacerbations requiring oral steroids, but was associated with a significantly greater improvement in PEF and growth. The possibility of an increased risk of rescue oral steroids and hospital admission with LABA therapy needs to be further examined.

Efficacy and tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler in adults and adolescents with asthma previously stable with twice-daily budesonide/formoterol dosing

The goal of asthma therapy is to control symptoms using minimal pharmacologic intervention. To evaluate the efficacy and tolerability of once-daily budesonide/formoterol vs once-daily budesonide in patients stable with twice-daily budesonide/formoterol. This double-blind, 12-week study enrolled 619 patients 12 years and older with mild to moderate asthma. After 4 to 5 weeks of twice-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI), 80/4.5 microg x 2 inhalations (320/18 microg/d), stable patients were randomized 1:1:1:1 to 2 inhalations twice daily of budesonide/formoterol pMDI, 80/4.5 microg (320/18 microg/d), or 2 inhalations once daily (evening) of budesonide/formoterol pMDI, 160/4.5 microg or 80/4.5 microg (320/9 microg or 160/9 microg/d), or budesonide pMDI, 160 microg (320 microg/d). All budesonide/formoterol groups maintained significantly more favorable evening predose forced expiratory volume in 1 second (FEV1), morning peak expiratory flow (PEF), daytime/nighttime asthma symptoms, nighttime rescue medication use, and rescue medication-free days vs budesonide. Variables evaluated during the end of the once-daily dosing interval (evening predose FEV1, evening PEF, daytime asthma symptoms, and daytime rescue medication use) significantly favored twice-daily budesonide/formoterol vs all treatments. Twice-daily budesonide/formoterol demonstrated significantly more favorable results for symptom-free and asthma control days vs all treatments and awakening-free nights vs budesonide. Asthma Quality of Life Questionnaire and Asthma Control Questionnaire results significantly favored twice-daily budesonide/formoterol vs budesonide (P < or = .018). All treatments were well tolerated. Pulmonary function and asthma control were more effectively maintained with all budesonide/formoterol regimens vs once-daily budesonide and with twice-daily budesonide/formoterol at twice the daily formoterol dose vs both once-daily budesonide/formoterol doses.

Quality Improvement Strategies for Children With Asthma

To evaluate the evidence that quality improvement (QI) strategies can improve the processes and outcomes of outpatient pediatric asthma care. Cochrane Effective Practice and Organisation of Care Group database (January 1966 to April 2006), MEDLINE (January 1966 to April 2006), Cochrane Consumers and Communication Group database (January 1966 to May 2006), and bibliographies of retrieved articles. Randomized controlled trials, controlled before-after trials, or interrupted time series trials of English-language QI evaluations. Must have included 1 or more QI strategies for the outpatient management of children with asthma. Clinical status (eg, spirometric measures); functional status (eg, days lost from school); and health services use (eg, hospital admissions). Seventy-nine studies met inclusion criteria: 69 included at least some component of patient education, self-monitoring, or self-management; 13 included some component of organizational change; and 7 included provider education. Self-management interventions increased symptom-free days by approximately 10 days/y (P = .02) and reduced school absenteeism by about 0.1 day/mo (P = .03). Interventions of provider education and those that incorporated organizational changes were likely to report improvements in medication use. Quality improvement interventions that provided multiple educational sessions, had longer durations, and used combinations of instructional modalities were more likely to result in improvements for patients than interventions lacking these characteristics. A variety of QI interventions improve the outcomes and processes of care for children with asthma. Use of similar outcome measures and thorough descriptions of interventions would advance the study of QI for pediatric asthma care.

Fluticasone propionate/salmeterol and exercise‐induced asthma in children with persistent asthma

Exercise is a common trigger in children with persistent asthma and inhaled corticosteroids have been shown to effectively treat clinical manifestations of persistent asthma, including protection from decrements in lung function caused by exercise. The goal of this study was to evaluate the effectiveness of fluticasone propionate/salmeterol 100/50 mcg compared with fluticasone propionate 100 mcg for the prevention of airflow limitation triggered by standardized exercise challenge in pediatric and adolescent patients with persistent asthma. Multicenter, randomized, double-blind, parallel group trial of 248 subjects with persistent asthma (age 4-17 years) randomized to receive fluticasone propionate/salmeterol (100/50 mcg twice daily) or fluticasone propionate alone (100 mcg twice daily) via Diskus for 4 weeks. Exercise challenge tests were performed during screening and approximately 8 hr after administration of the blinded study medication on Treatment Day 28. After 4 weeks of therapy both treatments provided protection following exercise challenge. The protection estimated by the maximal fall in FEV(1) was significantly better for fluticasone propionate/salmeterol (9.5 +/- 0.8% [mean +/- SE]) compared with fluticasone propionate alone (12.7 +/- 1.1%, P = 0.021). Statistically significant differences were not observed for asthma rescue-free days and asthma symptom-free days. Chronic dosing with fluticasone propionate/salmeterol in a single device provides superior protection compared with an inhaled corticosteroid alone in protecting against exercise-induced asthma in children with persistent asthma.

Budesonide improves decreased airway conductance in infants with respiratory symptoms

Objective:Inhaled corticosteroids (ICS) are commonly used to treat wheezing disorders in children, but few studies have investigated the effect of ICS on lung function in infants. We evaluated the efficacy...

Benefits of fixed‐dose combination therapy with inhaled corticosteroids and long‐acting bronchodilators as initial maintenance therapy in the management of asthma

Revised Australian guidelines for asthma management were released by the National Asthma Council (NAC) in 2006. One area where clinical opinion and trial data have changed recently concerns the place of fixed-dose combination (FDC) therapy with inhaled corticosteroid (ICS) and long-acting beta(2)-agonists as initial maintenance therapy. A systematic review of the literature commissioned by the NAC and undertaken by the University of Tasmania addressed several questions, including whether there was evidence for the use of FDC therapy as first-line asthma treatment in steroid-naïve patients. Nineteen relevant studies were identified, from which 20 comparisons contributed to the analyses. The definition of steroid-naïve ranged from no ICS therapy over the preceding 1 month to no ICS therapy ever. FDC therapy was effective in subjects who were steroid-naïve and was more effective than an equivalent dose of ICS, irrespective of the definition of steroid-naïvety. Compared with ICS alone, FDC therapy increased mean FEV(1) by 140 mL, mean morning PEF by 21 L/min and mean evening PEF by 20 L/min. There was a mean increase of 9.8% in symptom-free days, associated with a greater reduction in rescue medication use of -0.12 puff/24 h. FDC therapy was not superior to ICS alone for prevention of withdrawals or exacerbations requiring systemic corticosteroids. Adverse events were similar for FDC therapy and ICS, whether ICS were administered at the same or an increased dose. FDC therapy is effective as first-line treatment in steroid-naïve subjects and is superior to ICS alone for most outcomes, irrespective of the period of time since last exposure to ICS.

A Randomized Controlled Trial of Asthma Self-management Support Comparing Clinic-Based Nurses and In-Home Community Health Workers

To compare the marginal benefit of in-home asthma self-management support provided by community health workers (CHWs) with standard asthma education from clinic-based nurses.Randomized controlled trial.Community and public health clinics and homes.Three hundred nine children aged 3 to 13 years with asthma living in low-income households.All participants received nurse-provided asthma education and referrals to community resources. Some participants also received CHW-provided home environmental assessments, asthma education, social support, and asthma-control resources.Asthma symptom-free days, Pediatric Asthma Caretaker Quality of Life Scale score, and use of urgent health services.Both groups showed significant increases in caretaker quality of life (nurse-only group: 0.4 points; 95% confidence interval [CI], 0.3-0.6; nurse + CHW group: 0.6 points; 95% CI, 0.4-0.8) and number of symptom-free days (nurse only: 1.3 days; 95% CI, 0.5-2.1; nurse + CHW: 1.9 days; 95% CI, 1.1-2.8), and absolute decreases in the proportion of children who used urgent health services in the prior 3 months (nurse only: 17.6%; 95% CI, 8.1%-27.2%; nurse + CHW: 23.1%; 95% CI, 13.6%-32.6%). Quality of life improved by 0.22 more points in the nurse + CHW group (95% CI, 0.00-0.44; P = .049). The number of symptom-free days increased by 0.94 days per 2 weeks (95% CI, 0.02-1.86; P = .046), or 24.4 days per year, in the nurse + CHW group. While use of urgent health services decreased more in the nurse + CHW group, the difference between groups was not significant.The addition of CHW home visits to clinic-based asthma education yielded a clinically important increase in symptom-free days and a modest improvement in caretaker quality of life.

P01-145 Comparison of symptom-free days in generalized anxiety disorder following treatment with pregabalin or venlafaxine-XR

Aims:To estimate the clinical benefit of pregabalin and venlafaxine-XR for the short-term treatment of generalized anxiety disorder (GAD) using the metric of symptom-free days (SFDs).Methods:A post-hoc analysis of a clinical trial in which adults who met DSM-IV criteria for GAD, with a HAM-A total score ≥ 20, were randomized to 8-weeks of double-blind, flexible-dose treatment with pregabalin (300-600 mg/d), venlafaxine-XR (75-225 mg/d) or placebo. SFDs were estimated for each one-week period based on weekly HAM-A scores using a published algorithm. Differences were analyzed using pairwise comparisons from a GLM adjusting for baseline HAM-A and sites.Results:The sample consisted of 121 patients on pregabalin (female, 64%; mean age, 39.5 years; LS mean ± SE baseline HAM-A, 27.6 ± 0.5), 125 patients on venlafaxine-XR (female, 58%; mean age, 42.6 years; baseline HAM-A, 27.5 ± 0.5), and 128 patients on placebo (female, 61%; mean age, 40.2 years; baseline HAM-A, 26.8 ± 0.5). At endpoint, LS mean (± SE) number of SFDs was significantly higher for pregabalin (20.6 ± 1.4) compared with both venlafaxine-XR (16.5 ± 1.4; p=0.018) and placebo (15.5 ± 1.3; p=0.004). Values remained significant after adjusting for multiple comparisions (p=0.0447 and p=0.0107, respectively).Conclusion:Treatment with pregabalin resulted in more SFDs compared with venlafaxine-XR and placebo. The lack of difference in SFDs for groups treated with venlafaxine-XR compared to placebo contrasts with a previously reported study. Further studies are warranted to explore the application of the SFD metric.

Effect of Suplatast Tosilate on Antileukotriene Non-Responders with Mild-to-Moderate Persistent Asthma

Immunomodulatory therapy has been recently introduced for the management of asthma. Suplatast tosilate (ST), a new immune-modifying drug, is known to improve the airway function by inhibiting the release of Th-2 cytokines. However, its efficacy as a controller listed in the guideline, Global Initiative for Asthma 2005 has not been established. In this study we investigated the role of ST in leukotriene receptor antagonist (LTRA) non-responders with mild-to-moderate persistent asthma before initiating corticosteroids inhalation therapy. This was a prospective open-level clinical trial. LTRAs was given to 41 patients with asthma for 4 weeks and clinical efficacy was assessed using daily symptom scores. The 10 patients, aged 2.5-8.5 years, who failed to show clinical improvement, were defined as LTRA non-responders. After a 1-week washout period, the efficacy of ST was investigated and compared with LTRA non-responders for the following 4 weeks. LTRA non-responders showed a significant improvement in the average symptom score, peak expiratory flow, use of rescue medication and the proportion of symptom-free days with ST therapy. ST is a good choice for patients who have failed to respond to LTRAs. ST should therefore be added to the list of treatment options for such patients.

The Role of Caregivers' Depressive Symptoms and Asthma Beliefs on Asthma Outcomes Among Low-income Puerto Rican Children

Objective. To examine the relationship between depressive symptoms and asthma beliefs (self-efficacy and empowerment), child asthma outcomes, and caregiver's quality of life among Puerto Rican caregivers of children with asthma. Methods. The caregivers of 221 children with persistent bronchial asthma were stratified into those with no/low or high levels of depressive symptoms. Differences between the groups in caregiver self-efficacy, family empowerment, child asthma outcomes, and quality of life were examined. Results. Caregivers with more depressive symptoms reported lower self-efficacy, less empowerment, less symptom-free days and nights for their children, and a lower quality of life compared to caregivers with no or fewer depressive symptoms. Conclusions. Depressive symptoms among Puerto Rican caregivers were associated with asthma beliefs, children's asthma symptoms, and caregiver quality of life. Our findings reinforce the importance of physician screening skills in recognizing caregiver depression in parents of asthma patients.

Daily Telemonitoring of Exhaled Nitric Oxide and Symptoms in the Treatment of Childhood Asthma

Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home. We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma. Children with atopic asthma (n = 151) were randomly assigned to two groups: FeNO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FeNO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks. Telemonitoring was feasible with reliable FeNO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FeNO0.05 group. Thirty weeks of daily FeNO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FeNO0.05 monitoring compared with daily symptom monitoring only.

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.

Endoskopische Asthmatherapie

In this review a new therapeutic procedure, named bronchial thermoplasty, for patients suffering from asthma will be discussed. The technology targets the smooth airway muscles, which play an important role especially during an acute asthma attack. By means of thermal energy the muscles are destroyed and the contractility minimized. Initial studies demonstrated the effectiveness of this new approach; in particular, the number of symptom-free days or the frequency of exacerbation could be positively influenced. However, a short-term increase in morbidity due to bronchoscopy is to be expected. Further trials are needed to investigate the value of this method, particularly with regard to long-term effects.

Efficacy and tolerability of salmeterol/fluticasone propionate versus montelukast in childhood asthma: A prospective, randomized, double-blind, double-dummy, parallel-group study

Background: Asthma control remains suboptimal in adults and children worldwide. Inhaled salmeterol/fluticasone propionate combination (SFC) and oral montelukast (MON) are 2 treatments available for childhood asthma. Objective: This study, the PEdiatric Asthma Control Evaluation (PEACE), investigated the efficacy and tolerability of SFC compared with MON for the control of persistent asthma in children. Methods: Children with asthma (forced expiratory volume in 1 second [FEV 1] 55%–80% predicted; reversibility ≥12%) aged 6 to 14 years who were receiving only short-acting β 2-agonists entered a 2-week run-in period. Symptomatic patients (rescue use or symptoms during 4 of the last 7 days) were randomized to double-blind, double-dummy treatment with SFC 50/100 µg BID via multidose dry powder inhaler or MON 5-mg tablet QD for 12 weeks. The primary end point was change from baseline in morning peak expiratory flow (PEF). Efficacy assessments included lung function, asthma symptoms, rescue medication use, and asthma control. Tolerability was assessed by recording the number and type of adverse events (AEs) and the number of asthma exacerbations. Results: Of 607 patients screened, 548 were randomized to treatment. The SFC group contained 281 patients and the MON group included 267. Demographic characteristics and baseline data were similar for both groups (mean age, 9.3 years for both groups; mean [SD] FEV 1, 1.49 [0.43] L in the SFC group and 1.48 [0.43] L in the MON group). There were more males in the MON group (179 [67%]) than in the SFC group (156 [56%]). The adjusted mean (SE) changes from baseline in morning PEF were 45.88 (2.82) L/min with SFC and 28.7 (2.86) L/min with MON (treatment difference, 17.16 L/min; 95% CI, 9.23–25.08; P < 0.001). Compared with MON, the SFC group had significantly more asthma symptom-free days (odds ratio [OR], 1.74; 95% CI, 1.07–2.82; P = 0.025), more rescue-free days (OR, 3.24; 95% CI, 2.09–5.02; P < 0.001), and more asthma-controlled weeks (difference in treatment medians over weeks 1–12, 16.77%; 95% CI, 8.3–16.77; P < 0.001). Both treatments were well tolerated, with a similar number of patients reporting AEs (SFC group, 155/281 [55%]; MON group, 153/267 [57%]); the most common AE in both groups was headache (SFC group, 66 [23%]; MON group, 72 [27%]). The mean exacerbation rates over 12 weeks (post hoc analysis) were 0.12 in the SFC group and 0.30 in the MON group (SFC/MON ratio, 0.40; 95% CI, 0.29–0.57; P < 0.001). Conclusions: In these children with uncontrolled asthma previously on short-acting β 2-agonist monotherapy (% predicted FEV 1 <80%, frequent asthma symptoms and rescue medication use), treatment with SFC was significantly more effective in improving morning PEF and other measures of asthma control and in decreasing exacerbation rates (in a post hoc analysis) than treatment with MON. The 2 drugs were both well tolerated, with similar numbers and types of AEs reported.

Bronchial thermoplasty for asthma: A critical review of a new therapy

Bronchial thermoplasty (BT) is a novel experimental procedure involving the application of controlled heat from a radiofrequency source to the airway wall as a means to reduce airway smooth muscle in the airway wall. After BT was shown to reduce airway smooth muscle in preclinical studies in dogs, clinical studies in humans revealed that BT resulted in a significant improvement in asthma outcomes including mild asthma exacerbations, asthma symptom-free days, asthma rescue medication use, and airway hyperresponsiveness as measured by methacholine PC(20). A second trial in humans revealed that BT was safe and effective in patients with severe asthma refractory to the current standard of care. While current trials are ongoing, BT holds promise as an exciting novel therapy in the management of patients with asthma.

Study of Montelukast for the Treatment of Respiratory Symptoms of Post–Respiratory Syncytial Virus Bronchiolitis in Children

A pilot study (Bisgaard H; Study Group on Montelukast and Respiratory Syncytial Virus. A randomized trial of montelukast in respiratory syncytial virus postbronchiolitis. Am J Respir Crit Care Med 2003;167:379-383) reported the efficacy of montelukast in post-respiratory syncytial virus (RSV) bronchiolitic respiratory symptoms. To evaluate the efficacy and safety of montelukast, 4 and 8 mg, in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large, multicenter study. This was a double-blind study of 3- to 24-month-old children who had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV. Patients (n = 979) were randomized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks (period I) and 20 weeks (period II). The primary end point was percentage symptom-free days (%SFD; day with no daytime cough, wheeze, and shortness of breath, and no nighttime cough). No significant differences were seen between montelukast and placebo in %SFD over period I: mean +/- SD for placebo and for montelukast at 4 and 8 mg were 37.0 +/- 30.7, 38.6 +/- 30.4, and 38.5 +/- 29.9, respectively. Least-squares mean differences (95% confidence interval) between montelukast (4 mg) and placebo and between montelukast (8 mg) and placebo were 1.9% (-2.9, 6.7) and 1.6% (-3.2, 6.5), respectively. Secondary end points were similar across treatments. Both doses were generally well tolerated. During the first two treatment weeks, average %SFD was approximately 29%. In post hoc analyses of patients (n = 523) with persistent symptoms (%SFD < or = 30% over Weeks 1-2), differences in %SFD were seen between montelukast and placebo over Weeks 3-24: difference were 5.7 (0.0, 11.3) for montelukast (4 mg) minus placebo and 5.9 (0.1, 11.7) for montelukast (8 mg) minus placebo. In this study, montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children.

Asthma control in pediatric patients treated with once-daily or twice-daily nebulized budesonide inhalation suspension (Pulmicort Respules)

Composite end points may represent more meaningful assessments of asthma control compared with traditional discrete measures. The effects of budesonide inhalation suspension (BIS) on composite measures of asthma control have not been investigated. The purpose of this study was to assess changes from baseline in percentages of asthma control days (ACDs; days without asthma symptoms and rescue medication use; primary outcome), symptom-free days (SFDs), and rescue medication-free days (RFDs) with BIS treatment. We retrospectively analyzed separately data from three randomized, double-blind, placebo-controlled, 12-week studies (N = 1018) of BIS. Study I patients (4-8 years) were dependent on daily inhaled corticosteroids (ICS; n = 178). Study II patients (6 months to 8 years) were using one or more asthma medications (n = 481). Study III patients (6 months to 8 years) were using daily non-ICS asthma medication (n = 359). Patients treated with BIS showed substantial improvements from baseline in all composite variables (ACDs, 21-31% versus placebo [PBO], 10-18%; SFDs, 20-29% versus PBO, 11-18%; RFDs, 24-47% versus PBO, 12-28%). In study I, each BIS regimen statistically significantly improved all three asthma control measures versus PBO. In study II, BIS 0.5 mg twice daily (b.i.d.) improved ACDs, BIS 0.25 mg b.i.d. and 0.5 mg b.i.d. improved SFDs, and all BIS regimens improved RFDs statistically significantly. In study III, BIS 0.25 mg once daily (q.d.) improved all three measures, BIS 0.5 mg q.d. improved SFDs, and 1.0 mg q.d. improved RFDs statistically significantly. In conclusion, BIS improved composite measures of asthma control in children.

Cost-effectiveness of escitalopram for generalized anxiety disorder in Canada

ABSTRACTBackground: Generalized Anxiety Disorder (GAD) is a common chronic disease with a lifetime prevalence estimated to range from 4.2% to 12.7%. GAD places a sub­stantial burden upon patients and healthcare resources.Objective: To determine the cost-effectiveness of escitalopram for GAD in a Canadian primary care setting from two perspectives [Ministry of Health (MoH) and society (SOC)].Methods: A 24-week decision-analytic model was constructed using Data/TreeAge software. Patients were treated with escitalopram or generic paroxetine. Clinical rates were determined from the literature; expert opinion guided model pathway development. Effectiveness was measured as ‘symptom-free days’ (SFDs). Analyses from MoH perspective focused on direct costs of treatment (drugs, physician visits), while SOC also accounted for indirect costs associated with workdays lost due to GAD. Unit costs of healthcare services and wage rates were obtained from standard Canadian sources (2005 Canadian $ values). Cost-effectiveness was expressed as the incremental cost-effectiveness ratio (ICER). Extensive one-way and probabilistic sensitivity analyses were conducted.Results: Escitalopram was associated with higher expected number of SFDs than paroxetine (86.4 vs. 77.0 SFD, respectively). From the MoH perspective, expected costs were Can$724 and Can$663 for escitalopram and paroxetine arms, respectively, resulting in the ICER for escitalopram vs. paroxetine of Can$6.56/SFD (Can$2362/symptom-free year). From the SOC perspective, escitalopram dominated paroxetine as more effective on SFDs and less costly. Sensitivity analyses demonstrated robustness of the model. Limitations include the absence of comorbidities, which are common in practice, lack of long-term data, and assuming that dropouts in trials reflect those in practice.Conclusion: Escitalopram was found to be cost-effective compared with paroxetine in treatment of GAD from the Canadian MoH perspective, and dominating paroxetine from the SOC perspective. Therefore, a possible advantage may exist at the population level in the treatment of GAD with escitalopram in Canada.

Add‐on omalizumab improves day‐to‐day symptoms in inadequately controlled severe persistent allergic asthma

Omalizumab is efficacious in the treatment of moderate-to-severe and severe persistent allergic (immunoglobulin E-mediated) asthma, reducing exacerbations, emergency visits and improving quality of life (QoL). However, as exacerbations are relatively infrequent, assessment of efficacy on day-to-day symptoms is warranted. To investigate the effect of add-on omalizumab on day-to-day symptoms, and how they correlate with QoL in severe persistent asthma. The correlation between asthma symptom scores and QoL [Asthma Quality of Life Questionnaire (AQLQ)] was assessed. Symptom-free days (total symptom score = 0) and symptom-controlled days (definition 1: total symptom score </=1; and definition 2: morning peak expiratory flow >/=90% of baseline, daytime asthma score </=1 and night-time asthma score = 0) were compared between the omalizumab-treated group, omalizumab responders and placebo. Four hundred and nineteen patients (omalizumab, n = 209; placebo, n = 210) were included in the efficacy analyses, and 61% (118/195) of patients with response data were classified as responders. Total symptom score strongly correlated with AQLQ overall and symptom scores and individual domains. AQLQ overall score correlated well with symptom scores. Responders had significantly more symptom-free days than the omalizumab-treated and placebo groups (45.8%, 37.2% and 22.6% respectively), and more symptom-controlled days (definition 1: 56.1%, 47.9% and 35.3%, respectively, and definition 2: 50.8%, 43.9% and 28.0%, respectively). In patients with inadequately controlled severe persistent asthma, day-to-day symptoms correlate well with QoL. Add-on omalizumab significantly improves day-to-day symptoms compared with placebo. Further improvement in responders confirms the physician's assessment as a response measure.