Abstract/Text: BACKGROUND: Some patients with severe asthma have frequent exacerbations associated with persistent eosinophilic inflammation despite continuous treatment with high-dose inhaled glucocorticoids with or without oral glucocorticoids.
METHODS: In this randomized, double-blind, double-dummy study, we assigned 576 patients with recurrent asthma exacerbations and evidence of eosinophilic inflammation despite high doses of inhaled glucocorticoids to one of three study groups. Patients were assigned to receive mepolizumab, a humanized monoclonal antibody against interleukin-5, which was administered as either a 75-mg intravenous dose or a 100-mg subcutaneous dose, or placebo every 4 weeks for 32 weeks. The primary outcome was the rate of exacerbations. Other outcomes included the forced expiratory volume in 1 second (FEV1) and scores on the St. George's Respiratory Questionnaire (SGRQ) and the 5-item Asthma Control Questionnaire (ACQ-5). Safety was also assessed.
RESULTS: The rate of exacerbations was reduced by 47% (95% confidence interval [CI], 29 to 61) among patients receiving intravenous mepolizumab and by 53% (95% CI, 37 to 65) among those receiving subcutaneous mepolizumab, as compared with those receiving placebo (P<0.001 for both comparisons). Exacerbations necessitating an emergency department visit or hospitalization were reduced by 32% in the group receiving intravenous mepolizumab and by 61% in the group receiving subcutaneous mepolizumab. At week 32, the mean increase from baseline in FEV1 was 100 ml greater in patients receiving intravenous mepolizumab than in those receiving placebo (P=0.02) and 98 ml greater in patients receiving subcutaneous mepolizumab than in those receiving placebo (P=0.03). The improvement from baseline in the SGRQ score was 6.4 points and 7.0 points greater in the intravenous and subcutaneous mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 4 points), and the improvement in the ACQ-5 score was 0.42 points and 0.44 points greater in the two mepolizumab groups, respectively, than in the placebo group (minimal clinically important change, 0.5 points) (P<0.001 for all comparisons). The safety profile of mepolizumab was similar to that of placebo.
CONCLUSIONS: Mepolizumab administered either intravenously or subcutaneously significantly reduced asthma exacerbations and was associated with improvements in markers of asthma control. (Funded by GlaxoSmithKline; MENSA ClinicalTrials.gov number, NCT01691521.).

Abstract/Text: BACKGROUND: It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma.
METHODS: We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 mug twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year.
RESULTS: During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P=0.006) and a lower rate of exacerbations (P<0.001) and of supplementary use of controller medication (P<0.001). In the inhaled-corticosteroid group, as compared with the placebo group, the mean increase in height was 1.1 cm less at 24 months (P<0.001), but by the end of the trial, the height increase was 0.7 cm less (P=0.008). During treatment, the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth, albeit temporarily and not progressively.
CONCLUSIONS: In preschool children at high risk for asthma, two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued. (ClinicalTrials.gov number, NCT00272441.).

Copyright 2006 Massachusetts Medical Society.

Abstract/Text: BACKGROUND: Omalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng/ml (target level of suppression).
METHODS: Thirty-eight Japanese children (6-15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg/day fluticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open-label study.
RESULTS: The geometric mean serum free IgE level at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were significantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p < 0.001), versus baseline. Quality-of-life scores were also significantly improved (p < 0.001). In addition, 11 (28.9%) patients reduced the dose of any asthma controller medications. Thirty-six (94.7%) patients experienced at least one adverse event during the treatment period. All adverse events were mild or moderate in severity and no new safety concerns were detected. No patients discontinued the study.
CONCLUSIONS: In Japanese children with severe allergic asthma, omalizumab decreased free IgE levels to less than 25 ng/mL. Omalizumab improved asthma control and was well-tolerated, as well.

Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Abstract/Text: BACKGROUND: Omalizumab has demonstrated clinical benefits in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efficacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng/ml (target level of suppression).
METHODS: Thirty-eight Japanese children (6-15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg/day fluticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open-label study.
RESULTS: The geometric mean serum free IgE level at 24 weeks was 15.6 ng/mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were significantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p < 0.001), versus baseline. Quality-of-life scores were also significantly improved (p < 0.001). In addition, 11 (28.9%) patients reduced the dose of any asthma controller medications. Thirty-six (94.7%) patients experienced at least one adverse event during the treatment period. All adverse events were mild or moderate in severity and no new safety concerns were detected. No patients discontinued the study.
CONCLUSIONS: In Japanese children with severe allergic asthma, omalizumab decreased free IgE levels to less than 25 ng/mL. Omalizumab improved asthma control and was well-tolerated, as well.

Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Abstract/Text: BACKGROUND AND OBJECTIVE: The efficacy and safety of the anti-IgE antibody, omalizumab, has been widely studied in patients with asthma. However to date, no large studies have been performed in Asian populations. The aim of this study was to compare the efficacy and safety of omalizumab with placebo, as add-on therapy in Asian patients with moderate-to-severe persistent asthma.
METHODS: Japanese patients (20-75 years of age) with uncontrolled asthma, despite receiving high-dose inhaled corticosteroids and other standard therapies, were randomized to receive add-on treatment with omalizumab or placebo in a 16-week, double-blind, parallel-group, multicentre study.
RESULTS: Altogether, 315 treated patients were included in the efficacy and safety analyses. The change from baseline in morning PEF was 15.45 L/min (least squares mean) with omalizumab versus 2.25 L/min with placebo, a statistically significant difference of 13.19 L/min (P = 0.0004). Clinically significant asthma exacerbations occurred in six patients (4.0%) treated with omalizumab and in 18 patients (11.0%) treated with placebo. The odds ratio for the risk of experiencing an asthma exacerbation was 0.32 in favour of omalizumab (P = 0.0192). Changes in asthma symptom scores, daily life activity scores, sleep scores and rescue medication use were in favour of omalizumab, but group differences did not reach statistical significance. Adverse event rates were similar between omalizumab and placebo, except for injection site reactions, which were more frequently observed in the omalizumab group.
CONCLUSIONS: Add-on treatment with omalizumab improved asthma control without significant adverse events in Japanese patients with moderate-to-severe persistent asthma.

Abstract/Text: BACKGROUND AND OBJECTIVE: The efficacy and safety of the anti-IgE antibody, omalizumab, has been widely studied in patients with asthma. However to date, no large studies have been performed in Asian populations. The aim of this study was to compare the efficacy and safety of omalizumab with placebo, as add-on therapy in Asian patients with moderate-to-severe persistent asthma.
METHODS: Japanese patients (20-75 years of age) with uncontrolled asthma, despite receiving high-dose inhaled corticosteroids and other standard therapies, were randomized to receive add-on treatment with omalizumab or placebo in a 16-week, double-blind, parallel-group, multicentre study.
RESULTS: Altogether, 315 treated patients were included in the efficacy and safety analyses. The change from baseline in morning PEF was 15.45 L/min (least squares mean) with omalizumab versus 2.25 L/min with placebo, a statistically significant difference of 13.19 L/min (P = 0.0004). Clinically significant asthma exacerbations occurred in six patients (4.0%) treated with omalizumab and in 18 patients (11.0%) treated with placebo. The odds ratio for the risk of experiencing an asthma exacerbation was 0.32 in favour of omalizumab (P = 0.0192). Changes in asthma symptom scores, daily life activity scores, sleep scores and rescue medication use were in favour of omalizumab, but group differences did not reach statistical significance. Adverse event rates were similar between omalizumab and placebo, except for injection site reactions, which were more frequently observed in the omalizumab group.
CONCLUSIONS: Add-on treatment with omalizumab improved asthma control without significant adverse events in Japanese patients with moderate-to-severe persistent asthma.

Abstract/Text: BACKGROUND AND OBJECTIVE: The efficacy and safety of the anti-IgE antibody, omalizumab, has been widely studied in patients with asthma. However to date, no large studies have been performed in Asian populations. The aim of this study was to compare the efficacy and safety of omalizumab with placebo, as add-on therapy in Asian patients with moderate-to-severe persistent asthma.
METHODS: Japanese patients (20-75 years of age) with uncontrolled asthma, despite receiving high-dose inhaled corticosteroids and other standard therapies, were randomized to receive add-on treatment with omalizumab or placebo in a 16-week, double-blind, parallel-group, multicentre study.
RESULTS: Altogether, 315 treated patients were included in the efficacy and safety analyses. The change from baseline in morning PEF was 15.45 L/min (least squares mean) with omalizumab versus 2.25 L/min with placebo, a statistically significant difference of 13.19 L/min (P = 0.0004). Clinically significant asthma exacerbations occurred in six patients (4.0%) treated with omalizumab and in 18 patients (11.0%) treated with placebo. The odds ratio for the risk of experiencing an asthma exacerbation was 0.32 in favour of omalizumab (P = 0.0192). Changes in asthma symptom scores, daily life activity scores, sleep scores and rescue medication use were in favour of omalizumab, but group differences did not reach statistical significance. Adverse event rates were similar between omalizumab and placebo, except for injection site reactions, which were more frequently observed in the omalizumab group.
CONCLUSIONS: Add-on treatment with omalizumab improved asthma control without significant adverse events in Japanese patients with moderate-to-severe persistent asthma.

Abstract/Text: BACKGROUND: Factors contributing to either "complete" or "clinical" remission of asthma are important to know since there is no cure for the disease.
METHODS: A cohort of 119 allergic asthmatic children was examined three times with a mean follow up of 30 years. They were aged 5-14 years at visit 1 (1966-9), 21-33 years at visit 2 (1983-6), and 32-42 years at visit 3 (1995-6). Complete remission of asthma at visit 3 was defined as no asthma symptoms, no use of inhaled corticosteroids, normal lung function (FEV1 >90% predicted), and no bronchial hyperresponsiveness (PC10 >16 mg/ml). Clinical remission was defined as no asthma symptoms and no use of inhaled corticosteroids.
RESULTS: 22% of the group was in complete remission of asthma at visit 3 and a further 30% was in clinical remission (total 52%); 57% of subjects in clinical remission had bronchial hyperresponsiveness and/or a low lung function. Logistic regression analyses showed that a higher FEV1 in childhood and more improvement in FEV1 from age 5-14 to 21-33 were associated with both complete and clinical asthma remission at age 32-42.
CONCLUSIONS: Complete remission of asthma was present in a small subset of asthmatics while half the subjects showed clinical remission. Both complete and clinical remission were associated with a higher lung function level in childhood and a higher subsequent increase in FEV1. These results support the view that defining remission only on the basis of symptoms and medication use will overlook subjects with subclinical active disease and possibly associated airway remodelling.

Abstract/Text: A group of children with a past history of wheezing was randomly selected from the Melbourne community at the age of 7 years in 1964, and a further group of children with severe wheezing was selected from the same birth cohort at the age of 10 years. These subjects have been followed prospectively at 7-year intervals, with the last review in 1999, when their average age was 42 years. Eighty-seven percent of the original cohort who were still alive participated in the 1999 review. This study showed that the majority of children who had only a few episodes of wheezing associated with symptoms of a respiratory infection had a benign course, with many ceasing to wheeze by adult life. Most who continued with symptoms into adult life were little troubled by them. Conversely, those children with asthma mostly continued with significant wheezing into adult life, and the more troubled they were in childhood, the more likely symptoms continued. There was a loss in lung function by the age of 14 years in those with severe asthma, but the loss did not progress in adult life. The childhood asthma had been treated before the availability of inhaled steroids. There was no significant loss of lung function in those with milder symptoms.

Abstract/Text: A group of children with a past history of wheezing was randomly selected from the Melbourne community at the age of 7 years in 1964, and a further group of children with severe wheezing was selected from the same birth cohort at the age of 10 years. These subjects have been followed prospectively at 7-year intervals, with the last review in 1999, when their average age was 42 years. Eighty-seven percent of the original cohort who were still alive participated in the 1999 review. This study showed that the majority of children who had only a few episodes of wheezing associated with symptoms of a respiratory infection had a benign course, with many ceasing to wheeze by adult life. Most who continued with symptoms into adult life were little troubled by them. Conversely, those children with asthma mostly continued with significant wheezing into adult life, and the more troubled they were in childhood, the more likely symptoms continued. There was a loss in lung function by the age of 14 years in those with severe asthma, but the loss did not progress in adult life. The childhood asthma had been treated before the availability of inhaled steroids. There was no significant loss of lung function in those with milder symptoms.

Abstract/Text: BACKGROUND: Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment.
METHODS: In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5-18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 μg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 μg) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329.
RESULTS: 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)-555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37-61), the frequency of exacerbations was lower in the daily (28%, 18-40, p=0·03), combined (31%, 21-43, p=0·07), and rescue (35%, 24-47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14-43) in the placebo group, compared with 5·6% (1·6-14) in the combined (p=0·012), 2·8% (0-10) in the daily (p=0·009), and 8·5% (2-15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.
INTERPRETATION: Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided.
FUNDING: National Heart, Lung and Blood Institute.

Copyright © 2011 Elsevier Ltd. All rights reserved.

Abstract/Text: BACKGROUND: The use of inhaled glucocorticoids for persistent asthma causes a temporary reduction in growth velocity in prepubertal children. The resulting decrease in attained height 1 to 4 years after the initiation of inhaled glucocorticoids is thought not to decrease attained adult height.
METHODS: We measured adult height in 943 of 1041 participants (90.6%) in the Childhood Asthma Management Program; adult height was determined at a mean (±SD) age of 24.9±2.7 years. Starting at the age of 5 to 13 years, the participants had been randomly assigned to receive 400 μg of budesonide, 16 mg of nedocromil, or placebo daily for 4 to 6 years. We calculated differences in adult height for each active treatment group, as compared with placebo, using multiple linear regression with adjustment for demographic characteristics, asthma features, and height at trial entry.
RESULTS: Mean adult height was 1.2 cm lower (95% confidence interval [CI], -1.9 to -0.5) in the budesonide group than in the placebo group (P=0.001) and was 0.2 cm lower (95% CI, -0.9 to 0.5) in the nedocromil group than in the placebo group (P=0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (-0.1 cm for each microgram per kilogram of body weight) (P=0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (-1.3 cm; 95% CI, -1.7 to -0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants.
CONCLUSIONS: The initial decrease in attained height associated with the use of inhaled glucocorticoids in prepubertal children persisted as a reduction in adult height, although the decrease was not progressive or cumulative. (Funded by the National Heart, Lung, and Blood Institute and the National Center for Research Resources; CAMP ClinicalTrials.gov number, NCT00000575.).