Nighttime Asthma Symptom Scores Research Articles

Effects of sublingual-specific immunotherapy on pulmonary function and exhaled nitric oxide levels in asthmatic children with and without allergic rhinitis.

BackgroundAllergic asthma and allergic rhinitis are common chronic respiratory diseases in children. The prevalence rate of disease is increasing year by year. And avoid allergens, drug treatments and special immunotherapy (SIT) is the fundamental treatment for respiratory allergies diseases. But there are few comprehensive studies on the control level of asthma, improvement of lung function, and changes of exhaled nitric oxide (FeNO) after SLIT treatment in children with allergic asthma and rhinitis.MethodsIn all, 71 child asthma patients who received sublingual-specific immune therapy for 1 year or more were divided into an asthmatic rhinitis group (31 cases) and an asthma-alone group (40 cases). The two groups of patients were compared before and after treatment in terms of rhinitis symptom scores, daytime and nighttime asthma symptom scores, visual analog scale (VAS) score, drug score, pulmonary function, and exhaled nitric oxide level (FeNO).ResultsAfter treatment, daytime symptom scores, VAS scores, drug scores, and FeNO levels of the asthma-alone group were all lower than before treatment, and the lung function was significantly improved (P<0.05), while the difference in night symptom scores before and after treatment was not statistically significant (P>0.05). The lung function and FeNO level of children in the asthmatic rhinitis group were lower after treatment than before treatment, with statistically significant differences (P<0.05). The scores of rhinitis and VAS in the asthmatic rhinitis group were higher than those in the asthma-alone group, and the differences were statistically significant. There was no significant difference in other scores between the two groups. There was no significant difference in lung function and FeNO level between the two groups.ConclusionsSLIT for children with or without allergic asthma or with or without rhinitis has a significant effect, but its effect on children with asthma combined with rhinitis is not superior to that of children with asthma alone.

Effect of montelukast combined with budesonide formoterol treatment for acute bronchial asthma

Objective To explore the effect of montelukast combined with budesonide for treating acute bronchial asthma, pulmonary function improvement and to provide the basis for clinical treatment. Methods 192 patients with acute asthma were selected. They were divided into the control group and the observation group according to the admission order and odd and even numbers randomly, 96 patients in each group. The control group was treated with budesonide based on routine treatment, and the observation group was given budesonide formoterol based on the control group. The clinical effect, pulmonary function (forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC) and peak expiratory flow (PEF) the percentage of predicted value index percentage were observed. The daytime and night asthma symptoms and airway reactivity score: early respiratory resistance (Rrsc) and response threshold (Dmin) were assessed. Results The cough disappeared, shortness of breath, wheezing relieving, moist rales disappeared and wheeze disappeared time of the observation group after treatment were (5.92±1.03)d, (3.48±0.71)d, (3.74±0.69)d, (5.32±0.96)d and (5.12±0.77)d, which were lower than those of the control group (t=9.31, 7.26, 8.11, 9.02, 8.31, all P<0.05). The daytime and nighttime asthma symptom scores of the observation group after treatment were (0.54±0.31)points and (0.62±0.29)points, which were lower than those of the control group (t=7.90, 7.33, all P<0.05). Rrsc score of the observation group after treatment was (2.20±0.56)points, which was lower than that of the control group (t=7.86, P<0.05). The Dmin score of the observation group after treatment was (8.33±0.81)points, which was higher than that of the control group (t=9.15, P<0.05). FEV1, FEV1/FVC and PEF of the two groups after treatment were significantly higher than those before treatment(all P<0.05). FEV1, FEV1/FVC and PEF of the observation group after treatment were (2.95±0.58)L, (71.91±0.69) and (96.45±6.11), which were higher than those of the control group after treatment (t=7.60, 9.45, 10.21, all P<0.05). Conclusion Montelukast combined with budesonide formoterol in the treatment of acute attack of bronchial asthma has better effect, could significantly reduce the symptoms of asthma patients and shorten the treatment time with synergistic effect, and improve the pulmonary ventilation function of the patients. Key words: Asthma; Montelukast; Budesonide formoterol

Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial

Benralizumab is a humanised, anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils, reduces asthma exacerbations, and improves lung function for patients with severe eosinophilic asthma. The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate, persistent asthma. In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients aged 18-75 years, weighing at least 40 kg, and with a postbronchodilator reversibility in forced expiratory volume in 1 s (FEV1) of at least 12% at screening, from 52 clinical research centres in six countries. Patients must have been receiving either low- to medium-dosage inhaled corticosteroids (ICS) or low-dosage ICS plus long-acting β2 agonist fixed-combination therapy at screening, had a morning prebronchodilator FEV1 of more than 50% to 90% predicted at screening, and had one or more of the following symptoms within the 7 days before randomisation: a daytime or night-time asthma symptom score of at least 1 for at least 2 days, rescue short-acting β2 agonist use for at least 2 days, or night-time awakenings due to asthma for at least one night. We converted patients' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients' respective countries and randomly allocated them (1:1; stratified by blood eosinophil count [<300 cells per μL vs ≥300 cells per μL] and region [USA vs the rest of the world]) with an interactive web-based voice response system to receive subcutaneous placebo or benralizumab 30 mg injections every 4 weeks for 12 weeks. All patients and investigators involved in patient treatment or clinical assessment and those assessing outcomes were masked to treatment allocation. The primary endpoint was change from baseline prebronchodilator FEV1 at week 12. Efficacy analyses used an intention to treat approach. This trial is registered with ClinicalTrials.gov, number NCT02322775. Between Feb 2, 2015, and April 24, 2015, we enrolled 351 patients, with 211 (60%) randomly assigned (105 [50%] to placebo and 106 [50%] to benralizumab). Benralizumab resulted in an 80 mL (95% CI 0-150; p=0·04) greater improvement (least-squares mean difference) in prebronchodilator FEV1 after 12 weeks than did placebo (placebo group: 2246 mL [SD 768] at baseline vs 2261 mL [796] at week 12, change from baseline of 0 mL; benralizumab group: 2248 mL [606] vs 2310 mL [670], 70 mL). 44 (42%) patients in the benralizumab group had adverse events compared with 49 (47%) in the placebo group. The most common adverse events for both groups were nasopharyngitis (eight [8%] patients in each group) and upper respiratory tract infections (five [5%] patients in each group). Serious adverse events occurred in two (2%) patients each in the benralizumab (pancytopenia and a suicide attempt, both considered unrelated to treatment) and placebo (cervix carcinoma and colon adenoma) groups. This study suggests that active and modifiable disease processes might be ongoing in patients with mild to moderate, persistent asthma receiving ICS. Although the lung function improvement observed does not warrant use of benralizumab in this population because it did not reach the minimum clinically important difference of 10%, further studies to assess this finding should be considered. AstraZeneca.

Effects of house dust mite sublingual immunotherapy in children with allergic rhinitis and asthma

To evaluate the efficacy of SLIT with Dermatophagoides farinae drops in children with allergic rhinitis and allergic asthma according to its different duration. The efficacy of Dermatophagoides farinae SLIT in 100 children (aged 3-14 yr) with allergic rhinitis and allergic asthma induced by house dust mites was retrospectively analyzed. All children were treated with Dermatophagoides farinae drops for 4 years and followed-up at the interval of 3 months. Total nasal symptom scores (TNSS), total rhinitis symptomatic medication scores (TRMS), daytime asthma symptom scores (DASS), nighttime asthma symptom scores (NASS), total asthma symptomatic medication scores (TAMS), visual analog scale scores (VAS) and lung function were assessed during follow-up visit. SPSS 20.0 software was used for data analysis. After 2 years' SLIT, compared with 1-year duration, besides NASS (0.00[0.00;0.00], 0.00[0.00;0.00]; Z = 1.811; P > 0.05), TNSS (2.00[1.00;2.00], 0.00[0.00;0.00]; Z = 7.021, P < 0.01), TRMS (2.00[2.00;2.00], 0.00[0.00;0.00]; Z = 8.855; P < 0.01), VAS scores (3.00[2.00;4.00], 1.00[0.00;1.00]; Z = 4.494, P < 0.01), DASS (1.00[0.00;1.00]; 0.00[0.00;0.00]; Z = 4.383, P < 0.01) and TAMS (0.00[0.00;1.00], 0.00[0.00;0.00]; Z = 8.944; P < 0.01) all showed significant improvement. After 3-year duration, compared with 2-year duration, VAS scores (1.00[0.00;1.00], 0.00[0.00;0.00]; Z = 3.645, P < 0.05) in patients were significantly decreased. Other results showed no significant difference. The comparison of efficacy between 3 and 4-year duration showed no significant difference in global clinical outcomes (all P > 0.05). Patients receiving 2 year' SLIT achieve more clinical benefits than those who receiving 1-year duration. The higher efficacy of 3-year duration compared with 2-year duration is supported by a significant improvement in VAS. Besides, the comparison between 3 and 4-year duration shows no significant difference in global clinical outcomes. Therefore, 3 years' duration is optimal in this study.

Prevalence of gastro-esophageal reflux disease in patients with difficult to control asthma and effect of proton pump inhibitor therapy on asthma symptoms, reflux symptoms, pulmonary function and requirement for asthma medications.

The hypothesis that GER can trigger or exacerbate asthma is supported by several clinical trials that have shown amelioration in asthma symptoms and/or an improvement in pulmonary function after antireflux therapy. To investigate the prevalence of GER in patients with difficult to control asthma and to determine the effect of omeprazole on asthma symptoms, reflux symptoms, pulmonary function and on the requirement of asthma medications. Patients with difficult to control asthma were recruited into the study. All patients underwent esophageal manometry and 24 hour esophageal pH monitoring. Pulmonary function tests were done before and after treatment. The severity of asthma and reflux was assessed by a 1 week pulmonary symptom score(PSS) and reflux symptom score(RSS) respectively before and after treatment. Those who had an abnormal pH study (pH <4 in the distal esophagus for >5% of the time) underwent anti-GER treatment with lifestyle changes, and a proton pump inhibitor (omeprazole 40 mg, bid) for 3 months. Asthma medications were added or deleted based on severity of asthma. Out of 250 asthmatic patients screened, forty patients fulfilled the inclusion criteria. Twenty eight of 40 patients(70%) were diagnosed to have GERD. Of the patients 28 with GER, 8 patients(28.5%) had no reflux symptoms. On 24 hr pH metry, the percentage time pH <4.0 was 10.81 ± 4.72 and 1.11 ± 1.21; Deemester score was 37.65 ± 14.54 and 4.89 ± 6.39 (p-value is 0.0001) in GERD and non-GERD patients respectively.In GERD group, post treatment reflux symptom score(RSS) improved from 22.39 ± 14.99 to 1.04 ± 1.07, pulmonary symptom score(PSS) improved from 27.14 ± 7.49 to 13.82 ± 4.21 and night time asthma symptom score(NASS) improved from 6.71 ± 1.80 to 3.04 ± 1.23 (p-value <0.0001). After treatment, FEV1 and PEFR increased from 1.38 ± 0.57 and 4.14 ± 1.97 to 1.47 ± 0.54 and 5.56 ± 1.72, respectively (p-value 0.00114). PPI therapy improves nocturnal asthma symptoms, daytime asthma symptoms, pulmonary function and decreases requirement of asthma medications in these patients.

Development and validation of a nighttime sleep diary in asthmatic children

The aim of this study was to derive a shorter version of the asthma diary, 'a nighttime sleep diary' from the traditional asthma diary (original version). The nighttime sleep diary mainly consisted of nighttime awakening that met the criteria of validity and practicality necessary for monitoring clinical control in infants and young children with asthma symptoms. Validation of the diary was performed in a 6-week prospective study of 40 children aged 6 months to 6 years treated with nebulized budesonide inhalation suspension or cromolyn sodium nebulized solution. The nighttime awakening score was significantly and positively associated with the nighttime asthma symptom score and daytime asthma symptom score along with the number of days with a cough. Therefore, the nighttime sleep diary is a simple and useful instrument to monitor day-to-day fluctuations in young children with asthma.

The Efficacy and Tolerability of Inhaled Montelukast Plus Inhaled Mometasone Compared with Mometasone Alone in Patients with Chronic Asthma

Background. The efficacy of oral montelukast in chronic asthma is well established. Montelukast is also an effective adjunctive therapy to inhaled corticosteroids (ICS) in asthma uncontrolled on ICS alone. Inhaled montelukast was recently shown to provide significant bronchodilation compared with placebo in patients with chronic asthma. The purpose of this study was to evaluate the efficacy of inhaled montelukast added to inhaled mometasone. Methods. This was an 8-week, multicenter, randomized, double-blind, placebo-controlled study comparing once-daily inhaled montelukast 1 mg plus inhaled mometasone 220 μg (delivered by separate dry powder inhalers) with placebo plus inhaled mometasone 220 μg. Men and women aged 15–85 years with chronic asthma, forced expiratory volume in 1 second (FEV1) 50–80% of the predicted value, and β-agonist reversibility ≥12% were eligible. Patients were required to meet a minimum symptom threshold while receiving open-label inhaled mometasone during a 3-week prestudy/run-in period. Patients received blinded (montelukast vs. placebo) treatment for 2 weeks, entered a 1-week washout period, then crossed over to the other treatment for 2 weeks. The primary endpoint was the average change from baseline in FEV1 over the 2-week treatment period. Secondary endpoints included daytime and nighttime symptom scores. Other endpoints included short-acting β-agonist (SABA) use, asthma exacerbations, asthma control, peak expiratory flow (PEF), and blood eosinophil count. Results. A total of 134 patients were randomized. For the primary endpoint, change from baseline in FEV1, inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone (least squares mean 0.22 L vs. 0.17 L; p = .033 [two-sided at α = 0.05]). Inhaled montelukast plus inhaled mometasone was also significantly more effective than placebo plus inhaled mometasone in improving daytime asthma symptom scores (p = .005) and nighttime asthma symptom scores (p = .015), increasing the percentage of days with asthma control (p = .004), decreasing the percentage of days with asthma exacerbations (p ≤ .001), and decreasing the blood eosinophil count (p = .013). Differences were not significant on AM or PM PEF or SABA use, although the latter approached significance (p = .073). Both treatments were well tolerated. Conclusion. Inhaled montelukast plus inhaled mometasone was significantly more effective than placebo plus inhaled mometasone in improving FEV1, symptoms, asthma control, and blood eosinophil count.

Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma

Phosphodiesterase-4 (PDE4) inhibitors have potential utility as a new therapeutic approach to improving symptoms and pulmonary function in asthma and COPD. This study evaluated the efficacy and safety of MK-0359, a selective and potent oral PDE4 inhibitor, in chronic asthma. Adults (N=88) with > or =1 year asthma history and an FEV(1) 50-80% predicted were randomized to double-blind treatment with MK-0359 (15mg/day) or placebo for 14 days, then crossed-over to the other treatment for 14 days. The primary endpoint was the change from baseline in FEV(1) at the end of each 2-week treatment period. Secondary and other endpoints included the changes from baseline in Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use (puffs/day), AM and PM peak expiratory flow (PEF) and overall asthma-specific quality-of-life. Safety and tolerability were assessed by clinical adverse experiences. MK-0359 significantly improved the primary endpoint (versus placebo): the least-squares mean difference in change from baseline in FEV(1) (L) was 0.09L (95% CI 0.01, 0.18). Endpoints of Daytime asthma symptom score, Nighttime asthma symptom score, Total daily beta-agonist use, AM PEF, PM PEF, and quality-of-life were also significantly improved. Nineteen patients (24.1%) on MK-0359 and 8 patients (10.4%) on placebo reported gastrointestinal clinical adverse experiences. Serious gastrointestinal clinical adverse experiences were reported in 3 patients while receiving MK-0359. Over a 14-day treatment period, the oral PDE4 inhibitor MK-0359 improved lower airway function, symptoms and rescue medication use in chronic asthma, although at the expense of gastrointestinal adverse experiences. (Clinical trial registry number: NCT00482898.).

Asthma Control in Young Children Treated with Once-Daily Budesonide Turbuhaler®Who Were Previously Treated with Budesonide Inhalation Suspension

Budesonide inhalation suspension (Pulmicort Respules®), administered through jet nebulization, and budesonide dry powder inhaler (Pulmicort Turbuhaler®) are used for the treatment of asthma; however, the age indication for these products varies by country. In the United States, the indication for budesonide inhalation suspension is limited to children aged 12 months to 8 years. In many countries, budesonide Turbuhaler is indicated for use in children as young as 5 years. This clinical study assessed asthma control in children aged 4–6 years when transitioning from budesonide inhalation suspension to budesonide Turbuhaler. Ten children maintained on once-daily budesonide inhalation suspension (0.25 or 0.5 mg) were transitioned to once-daily budesonide Turbuhaler (200 μg) for 6 weeks after a 2-week run-in period, during which the original dose of budesonide inhalation suspension was continued. The primary outcome assessment was the change from baseline to the average during the last 2 weeks of treatment in morning and evening peak expiratory flow (PEF) measurements. Secondary outcomes were short-acting β2-adrenergic agonist (SABA) use, asthma symptom scores, and adverse events; peak inspiratory flow (PIF) also was assessed. Patients were able to maintain asthma control when transitioned from budesonide inhalation suspension to budesonide Turbuhaler. Mean improvements from baseline in morning and evening PEF were 19.1 and 16.8 L/min, respectively. At study end, no differences were observed in SABA use or daytime and nighttime asthma symptom scores compared with baseline. All but one patient demonstrated PIF values ≥30 L/min at all visits throughout the study. No unexpected adverse events were observed, and no patients discontinued from the study. These results suggest that children with asthma aged 4–6 years can successfully be transitioned from once-daily budesonide inhalation suspension to budesonide Turbuhaler while maintaining asthma control.

A 12-week, multicenter, randomized, partially blinded, active-controlled, parallel-group study of budesonide inhalation suspension in adolescents and adults with moderate to severe persistent asthma previously receiving inhaled corticosteroids with a metered-dose or dry powder inhaler

Nebulized budesonide inhalation suspension (BIS) is approved in the United States for children with asthma aged 1 to 8 years. The primary objective of this study was to compare the efficacy of BIS 0.5 mg QD and 2.0 mg BID in terms of the mean change from baseline to end of treatment in predose forced expiratory volume in 1 second (FEV1). In this 12-week, partially blinded, randomized study, subjects aged >or=12 years with moderate to severe persistent asthma previously receiving inhaled corticosteroids (ICSs) by dry powder inhaler (DPI) or metered-dose inhaler (MDI) continued therapy during a 2- to 3-week run-in period and then switched to BIS 0.5 mg QD, 1.0 mg QD, 1.0 mg BID, or 2.0 mg BID, or budesonide DPI 400 microg BID (active reference arm). Besides FEV1 (the primary variable), other outcome variables included changes in forced vital capacity (FVC) from baseline to weeks 4, 8, and 12 and to the average over the treatment period; as well as changes from baseline to the end of treatment in diary-collected daytime and nighttime asthma symptom scores, rescue medication use, nighttime awakenings due to asthma, morning and evening peak expiratory flow (PEF), percentages of symptom-free and medication-free periods, and the incidence of predefined asthma events. Adverse events were recorded by subjects. Steady-state pharmacokinetics of budesonide were assessed in all treatment arms. Efficacy analyses included data in a modified intent-to-treat approach. Differences in the change from baseline to end of treatment in FEV1 were assessed using analysis of covariance (ANCOVA). For secondary variables, changes from baseline to each visit or to the treatmentperiod average were compared among groups using an ANCOVA model. P <or= 0.05 was considered statistically significant. The randomized population consisted of 758 subjects: 57 (7.5%) aged 12 to <17 years, 667 (88.0%) aged 17 to <65 years, and 34 (4.5%) aged >or=65 years. There was no significant difference in mean change in predose FEV1 between BIS 0.5 mg QD and BIS 2.0 mg BID (0.02 vs 0.01 L). On average, mean values for the BIS dosage groups did not indicate any deterioration from baseline to the treatment period for variables associated with asthma control such as FEV1, FVC, daytime and nighttime asthma symptom scores, rescue medication use, nighttime awakenings, morning and evening PEF, percentages of symptom-free and rescue medication-free periods, and predefined asthma events. The BIS 1.0-mg BID treatment appeared to be closest to budesonide DPI in plasma budesonide concentrations and improvement in predose FEV1 (0.08 vs 0.12 L). All treatments were well tolerated. In this study, no difference in efficacy between BIS 2.0 mg BID and 0.5 mg QD was found in adolescents and adults with persistent asthma when transitioned from ICSs delivered with a DPI or MDI. Subjects taking all BIS dosages experienced similar responses for variables associated with asthma control.

Therapeutic comparison between low-dose sustained-release theophylline dry syrup and capsule in children with mild persistent asthma

Purpose : Theophylline has recently been reported to have concurrent anti-inflammatory effects at low therapeutic plasma concentrations which are below the doses at which significants, clinically useful bronchodilatation is evident. Sustained-release formulation in capsule and dry syrup forms were developed to reduce its adverse effects and improve its clinical effects. We compared the therapeutic effects of theophylline dry syrup and capsules in children with mild asthma. Methods : Ninety children with mild asthma were randomized to receive either theophylline dry syrup (n=44) or theophylline capsules (n=46); 4 mg per kilogram of body weight, twice a day, for 12 weeks. Baseline and serial measurements of daytime and nighttime asthma symptom score were performed. Compliance scores, drug swallowing scores, and drug usability scores were measured every 4 weeks. Each scoring was rated on a scale of 0-4. Serum theophylline concentration were measured at 4 and at 12 weeks. To examine the anti-inflammatory effect of theophylline on asthma, Serum eosinophilic cationic protein as a marker of airway inflammation caused by eosinophil was measured 12 weeks pre- and post-administration. Results : The daytime and nighttime asthma symptom scores of the two groups after 4 weeks significantly improved over the baseline score. Daytime and nighttime asthma symptom scores in the dry syrup group were statistically lower at all time points except for the nighttime symptom scores at 4 weeks. Compliance scores, drug swallowing scores, and drug usability scores in the dry syrup group were significantly higher at the end time point. Only in the dry syrup group was the serum ECP at the end time point statistically lower than baseline. Conclusion : Low-dose sustained-release theophylline may be safe and effective in bronchial asthma and this effect may be mediated by its anti-inflammatory action mechanisms. Especially, when used in children with asthma, dry syrup formulation is recommended because of its higher compliance than capsule formulation.

Effect of omeprazole and domperidone on adult asthmatics with gastroesophageal reflux

To study the effect of combined omeprazole (Ome) and domperidone (Dom) therapy on asthma symptoms and pulmonary function in asthmatics with gastroesophageal reflux. We selected 198 asthmatics with gastroesophageal reflux diagnosed by 24-h esophageal pH monitoring to receive Ome 20 mg twice daily and Dom 10 mg three times daily or placebo for 16 wk (1:1 double-blind randomization). Spirometry was done at baseline and after 16 wk of treatment. The primary outcome measures were: mean daily daytime and nighttime asthma symptom scores. Mean daily reflux symptom scores, albuterol use as rescue medication (number of puffs), daytime and nighttime peak expiratory flow rate (PEFR), postbronchodilator forced expiratory volume in 1 second (FEV1) and postbronchodilator forced vital capacity (FVC) were secondary outcome measures. Comparison of mean change from baseline between antireflux therapy and placebo groups revealed significant reduction in daytime asthma symptom score (17.4% vs 8.9%), nighttime asthma symptom score (19.6% vs 5.4%), reflux symptom score (8.7% vs 1.6%) and rescue medication use (23.2% vs 3.1%) after antireflux therapy compared to mean change in placebo group (P < 0.001). There was significant improvement in morning PEFR (7.9% vs 0.2%), evening PEFR (9.8% vs 0.5%), FEV1 (11.1% vs 3.78%) and FVC (9.3% vs 1.52%) in the antireflux therapy group compared to placebo on comparing the mean change from baseline after 16 wk (P < 0.01). Combined therapy with Ome and Dom in adult asthmatics with gastroesophageal reflux may be beneficial by reducing asthma symptoms, rescuing medication use, and improving pulmonary function.

Clinical and immunologic effects of sublingual immunotherapy in asthmatic children sensitized to mites: a double‐blind, randomized, placebo‐controlled study

Immunotherapy through oral routes is thought to be a valuable therapeutic option for asthma. The clinical and immunologic effects of sublingual immunotherapy (SLIT) in children with asthma caused by mites were evaluated in a double-blind, placebo-controlled study for 6 months. Patients (aged 6-12 yr) with mild-to-moderate asthma, with single sensitization to mite allergen, received either SLIT or placebo with a standardized Dermatophagoides pteronyssinus (D.p.)/D. farinae (D.f.) 50/50 extract. The cumulative dose was around 41824 IR, equivalent to 1.7 mg of D.p. and 3.0 mg of D.f. allergen. Symptom and medication scores were assessed throughout the study. Serum total immunoglobulin (Ig)E, eosinophil count, eosinophil cationic protein, specific IgE, specific IgG4, and skin sensitivity were evaluated before starting the treatment and after the treatment period. Twenty patients completed the study. At the beginning of the treatment, no differences were observed between the groups for symptom and medication scores, skin sensitivity, or immunologic parameters. After 6 months of treatment, there was a significant difference in nighttime asthma symptom scores and specific IgG4 (p < 0.05) in the SLIT group compared with the placebo group. Daytime symptom and medication scores, total IgE, eosinophil count, forced expiratory volume in 1 s, and mean evening peak expiratory flow rate reached significant differences in the SLIT group during the treatment period (p < 0.05). No severe adverse effects were reported. Our results revealed that treatment for 6 months with SLIT is clinically effective in decreasing asthmatic symptoms and medication use in children with mild-to-moderate asthma because of mite sensitivity. The clinical usefulness of this form of immunotherapy and the mechanism underlying its immunologic effects deserve further studies.

Safety and Efficacy of a New Albuterol Hydrofluoroalkane Formulation for Treating Asthma Symptoms in Children Two to Less Than Four Years of Age

Metered dose inhalers (MDIs) are being reformulated with hydrofluoroalkane (HFA) propellants because of the ozone-depleting effects of chlorofluorocarbons. Although currently indicated for children 4 years of age or older, albuterol (Ventolin®; GlaxoSmithKline, Research Triangle Park, NC) HFA is sometimes used to treat younger children. Therefore, its safety in children aged 2 to less than 4 years was determined in this randomized, doubleblinded, multicenter parallel-group study. Seventy-seven children with asthma received albuterol HFA 90 or 180 µg or placebo three times daily for 4 weeks via MDI with one of two holding chambers and a face mask. Because of the small sample size, the study was not powered to achieve statistically significant outcomes. Improvements in 24-hour and nighttime asthma symptom scores were not significantly different between groups. Compared to placebo, albuterol HFA groups had greater improvements in daytime asthma symptom scores, rescue albuterol use, nighttime awakenings, percent symptom-free days, and twice daily peak expiratory flow although these differences did not reach statistical significance. Adverse events were less frequent in albuterol HFA 90 µg (35% or 9 subjects) than in albuterol HFA 180 µg (52% or 13 subjects) and placebo (42% or 11 subjects). Frequently reported adverse events included pyrexia (placebo and albuterol HFA 90 µg:8% [2 subjects each]; albuterol HFA 180 µg:4% [1 subject]), vomiting (placebo: 8% [2 subjects]; albuterol HFA 90 µg:4% [1 subject]) and diarrhea (albuterol HFA 180 mcg:8% [2 subjects]). QT prolongation occurred in 4 subjects, 3 subjects in the albuterol HFA 180 µg and 1 subject in the albuterol HFA 90 µg group. Mild tremor occurred in 12% (3 subjects in albuterol HFA 90 µg), 8% (2 subjects in albuterol HFA 180 µg), and 4% (1 subject in placebo) of patients.

A multinational, 12-week, randomized study comparing the efficacy and tolerability of ciclesonide and budesonide in patients with asthma

Ciclesonide is a new lung-activated inhaled corticosteroid (ICS) that has shown efficacy in previous placebo-controlled and comparative studies in patients with persistent asthma. It is important to compare new treatments with existing ICSs to obtain relative data concerning their efficacy and tolerability. This study compared the efficacy and tolerability of ciclesonide QD with budesonide BID in patients with asthma. This 12-week, randomized study was conducted at 62 study sites across Europe. Male and female patients aged 12 to 75 years with primarily mild to moderate asthma were enrolled. This study was double blind with respect to the ciclesonide dose and open label for budesonide, as placebofor budesonide was not available. Patients were randomly assigned to receive inhaled ciclesonide 80 or 320 microg QD (morning) or budesonide 200 microg BID for 12 weeks. Efficacy and tolerability assessments were performed at weeks 0 (baseline), 4, 8, and 12. The primary end point was the change from baseline in forced expiratory volume in 1 second (FEV1) at 12 weeks. Secondary end points were changes from baseline in morning peak expiratory flow (PEF), asthma symptom scores, and rescue medication use. Tolerability was assessed throughout the study by monitoring of standard laboratory variables (hematology and biochemistry); physical examination, including vital signs; reporting of adverse events (AEs); and 24-hour urinary cortisol as a measure of hypothalamic-pituitary-adrenal-axis function. Five hundred fifty-four patients were randomized (301 men, 253 women; mean age, 41.3 years; ciclesonide 80 microg QD, 182 patients; ciclesonide 320 microg QD, 195; budesonide 200 microg BID, 177). Demographic and baseline clinical characteristics, including age, sex, weight, and (FEV1) were similar between the 3 groups. Compared with baseline values, week-12 FEV1 (least squares mean [LSM] [SEM] A, +0.267 [0.035], +0.256 [0.033], and +0.355 [0.034] L, respectively; all, P<0.001) and morning PEF (LSM [SEM] Delta, +12 [5], +17 [4], and +21 [4] L/min, respectively; all, P<or=0.008) were significantly improved with ciclesonide 80 and 320 microg QD and budesonide 200 microg BID. At 12 weeks, ciclesonide was found to be noninferior to budesonide with regard to mean changes from baseline in (FEV1) (intent to treat [ITT]: 97.5% CI for ciclesonide 80 microg QD vs budesonide 200 microg BID, -0.192 to 0.015; 97.5 CI for ciclesonide 320 microg QD vs budesonide 200 microg BID, -0.200 to 0.001) and morning PEF (ITT. 97.5% CI for ciclesonide 80 microg QD vs budesonide 200 microg BID, -22 to 5; 97.5% CI for ciclesonide 320 microg QD vs budesonide 200 microg BID, -17 to 10). Similar findings were seen in the per-protocol population. Week-12 daily, daytime, and nighttime asthma symptom scores and rescue medication use were significantly decreased from baseline in all 3 treatment groups (all, P<0.001). The prevalences of AEs were similar across all 3 treatment groups. Week-12 mean urinary cortisol excretion was statistically similar to baseline with both ciclesonide doses (Delta, -0.54 and +0.16 nmol/mmol creatinine with ciclesonide 80 and 320 microg QD, respectively) but was significantly reduced from baseline with budesonide (Delta, -1.42 nmol/mmol creatinine; P<0.05). The results of this study in patients with primarily mild to moderate asthma suggest that ciclesonide 80 and 320 microg QD were similar to budesonide 200 microg BID in improving pulmonary function, controlling asthma symptoms, and reducing the need for rescue medication use. Unlike budesonide, ciclesonide was not associated with significant urinary cortisol suppression in these patients.

Efficacy of montelukast during the allergy season in patients with chronic asthma and seasonal aeroallergen sensitivity

Montelukast has proven efficacy in the treatment of chronic asthma and seasonal allergic rhinitis, but it has not been evaluated in the subpopulation of asthmatic patients with seasonal asthma symptoms. To determine the effectiveness of montelukast treatment in improving the control of asthma symptoms during the allergy season in patients with active asthma and seasonal aeroallergen sensitivity. Adults with a history of chronic asthma who are also symptomatic during the allergy season and with skin test sensitivity to seasonal aeroallergens were enrolled in a randomized, parallel-group, multicenter study with a 1-week, single-blind, placebo run-in period followed by 3 weeks of double-blind treatment during the spring of 2004. After the run-in period, eligible patients were randomly assigned to receive either oral montelukast (10 mg) or placebo. Daytime and nighttime asthma symptom scores, beta-agonist use, and morning and evening peak expiratory flow rates were recorded daily using an electronic diary. The primary end point was mean change from baseline to week 3 in the daytime asthma symptom score. Of 455 randomized patients, 433 completed the study. Compared with placebo, treatment with montelukast resulted in a significant improvement from baseline in the daytime asthma symptom score (-0.54 vs -0.34; P = .002) and in beta-agonist use, nighttime symptoms, and peak expiratory flow rates. Few patients in the montelukast and placebo groups discontinued study participation because of asthma (1.3% and 3.0%, respectively). In patients with chronic asthma and seasonal aeroallergen sensitivity, montelukast treatment provided significant asthma control during the allergy season compared with placebo.

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

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

Review: inhaled long acting β2 agonists are effective and safe in stable chronic asthma

Walters EH, Walters JA, Gibson MD. Inhaled long acting beta agnonists for stable chronic asthma. Cochrane Database Syst Rev 2003(4):CD001385. Q In people with stable chronic asthma, are inhaled long...

Salmeterol/Fluticasone Propionate in???a???Single Inhaler is Superior to Budesonide Alone in Control of Chinese Asthmatic Adults

There is comparatively little information on asthma management in China. A multicentre, randomised, open-label, parallel-group, 6-week treatment study was conducted to evaluate the efficacy and safety of salmeterol/fluticasone propionate combination treatment in Chinese adult asthmatic patients. 398 patients with a documented history of moderate-to-severe asthma were randomised to treatment. Salmeterol 50mug/fluticasone propionate 100mug twice daily for 6 weeks via Accuhaler((R)) (Diskustrade mark) inhaler and budesonide 400mug twice daily for 6 weeks via Turbuhaler((R)) inhaler. Morning peak expiratory flow (PEF) was investigated as the primary efficacy endpoint; evening PEF, use of salbutamol (albuterol) as rescue medication, and day- and night-time asthma symptom scores were secondary efficacy endpoints. Safety was assessed according to adverse events recorded. Over the 6-week treatment period, salmeterol/fluticasone propionate led to a significantly greater increase in morning (p < 0.0001) and evening (p = 0.0066) PEF compared with budesonide. Moreover, the significant benefit of salmeterol/fluticasone propionate was evident from the first week. Similarly, salmeterol/fluticasone propionate led to significantly greater improvements in the use of rescue medication and day- and night-time asthma symptom scores, compared with budesonide. Both treatments were well tolerated, with a similar incidence (23%) of adverse events in both treatment groups and no serious adverse events. Salmeterol/fluticasone propionate 50mug /100mug twice daily was significantly more effective than budesonide 400mug twice daily in improving lung function and reducing symptoms and use of rescue medication in Chinese asthmatic patients who were poorly controlled on low-dose inhaled corticosteroids. This confirms the findings of superior efficacy of this combination product over budesonide in other populations.

Comparison of Subjective and Objective Measures in Recurrently Wheezy Infants

Objectives: The aim of this study was to compare subjective measures (overall health assessment both by the study physician and the child’s mother) with objective measurements of forced expiratory volumes (FEV_t) and maximal flow at functional residual capacity v̇_maxFRC) in recurrently wheezy infants. Methods: Sixteen wheezy infants (12 boys) aged 8–26 months were studied. A clinical assessment at visit 1 was followed by the run-in period during which day- and nighttime asthma symptom scores were obtained. The actual study period consisted of 2 visits when patient’s lung function was assessed. The first of which was during an acute exacerbation (visit 2), while the second was when the infant was asymptomatic (visit 3). FEV_t were obtained by the raised volume rapid thoracic compression technique (RVRTC) and v̇_maxFRC by the tidal volume rapid thoracic compression technique (TVRTC). Results: Mean FEV_t but not mean v̇_maxFRC were significantly lower at visit 2 compared to visit 3 (FEV_0.5: p = 0.005, and FEV_0.75: p = 0.002; v̇_maxFRC: p = 0.15) and correlated well with overall health assessment by the study physician (FEV_0.5: r = 0.82, and FEV_0.75: r = 0.84), but not with the overall health assessment by the mother. Conclusions: We have shown in the present study that objective measurements of FEV_t from a raised lung volume correlate well with the overall health assessment by the study physician; this was in contrast to measurements of v̇_maxFRC in the tidal volume range. We therefore conclude that the RVRTC technique is a feasible method to assess and monitor obstructive lung disease in infancy.