FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2534482609> ?p ?o ?g. }

• W2534482609 endingPage "705.e4" @default.
• W2534482609 startingPage "703" @default.
• W2534482609 abstract "Recurrent severe asthma exacerbations are associated with decreased lung growth or accelerated loss of lung function and add substantially to both the cost and morbidity associated with asthma. Risk factors for acute exacerbations include previous acute exacerbation, young age, poorly controlled asthma, and, in particular, viral respiratory tract infections. Exacerbations in school-aged children have been associated with sensitization to aeroallergens, particularly severe exacerbations requiring hospitalization, in which up to 90% of the affected group is atopic and has a viral infection.1Holt P.G. Sly P.D. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment.Nat Med. 2012; 18: 726-735Crossref PubMed Scopus (201) Google Scholar This apparent comorbidity is the subject of ongoing controversy, but recent studies have provided a plausible and testable hypothesis that might explain how atopy contributes to the exacerbation process.1Holt P.G. Sly P.D. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment.Nat Med. 2012; 18: 726-735Crossref PubMed Scopus (201) Google Scholar Notably, cross-linking of high-affinity IgE receptors (FcεRI) on plasmacytoid dendritic cells2Gill M.A. Bajwa G. George T.A. Dong C.C. Dougherty I.I. Jiang N. et al.Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells.J Immunol. 2010; 184: 5999-6006Crossref PubMed Scopus (241) Google Scholar and myeloid dendritic cells3Subrata L.S. Bizzintino J. Mamessier E. Bosco A. McKenna K.L. Wikström M.E. et al.Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children.J Immunol. 2009; 183: 2793-2800Crossref PubMed Scopus (177) Google Scholar of atopic subjects at airway mucosal infection sites, leading to attenuation of type 1 interferon production and enhancement of proinflammatory TH2 cytokine production, respectively, markedly amplifies local inflammation.1Holt P.G. Sly P.D. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment.Nat Med. 2012; 18: 726-735Crossref PubMed Scopus (201) Google Scholar, 2Gill M.A. Bajwa G. George T.A. Dong C.C. Dougherty I.I. Jiang N. et al.Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells.J Immunol. 2010; 184: 5999-6006Crossref PubMed Scopus (241) Google Scholar, 3Subrata L.S. Bizzintino J. Mamessier E. Bosco A. McKenna K.L. Wikström M.E. et al.Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children.J Immunol. 2009; 183: 2793-2800Crossref PubMed Scopus (177) Google Scholar This amplification process is IgE dependent, and hence blocking of available IgE during winter periods, which are at high risk for viral infection, might protect against these events.1Holt P.G. Sly P.D. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment.Nat Med. 2012; 18: 726-735Crossref PubMed Scopus (201) Google Scholar Several recent studies support this general concept. First, the addition of omalizumab, a humanized IgG1 anti-IgE mAb, to regular inhaled steroids given to children with inadequately controlled atopic asthma reduced their exacerbations by 43% compared with placebo.4Lanier B. Bridges T. Kulus M. Taylor A.F. Berhane I. Vidaurre C.F. Omalizumab for the treatment of exacerbations in children with inadequately controlled allergic (IgE-mediated) asthma.J Allergy Clin Immunol. 2009; 124: 1210-1216Abstract Full Text Full Text PDF PubMed Scopus (268) Google Scholar Second, in the Inner-City Asthma Study the addition of omalizumab to guidelines-based therapy reduced the number of days with asthma symptoms and reduced the proportion of study participants having 1 or more exacerbations from 48.8% to 30.3% across the 1-year treatment period. The strongest effect was on exacerbations occurring during the fall virus season.5Busse W.W. Morgan W.J. Gergen P.J. Mitchell H.E. Gern J.E. Liu A.H. et al.Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children.N Engl J Med. 2011; 364: 1005-1015Crossref PubMed Scopus (691) Google Scholar Third, short-term preseasonal treatment with omalizumab blunted the ensuing fall asthma “epidemic” in atopic schoolchildren.6Teach S.J. Gill M.A. Togias A. Sorkness C.A. Arbes Jr., S.J. Calatroni A. et al.Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations.J Allergy Clin Immunol. 2015; 136: 1476-1485Abstract Full Text Full Text PDF PubMed Scopus (394) Google Scholar An important question arising from these observations is whether reducing virus-associated exacerbations in a single season is a sufficient “circuit breaker” to decelerate progression of asthma toward chronicity. To test this, we conducted a double-blind, randomized, controlled 2-year pilot study of 27 children (58 screened; age, 6-15 years [mean, 11.45 ± 2.99 years]; 14 male subjects) with a history of a severe asthma exacerbation in the previous winter (clinical trial registration ACTRN12611001106921). Details of the study protocol and methods are shown in the Methods section in this article's Online Repository at www.jacionline.org. All children were sensitized to aeroallergens and had asthma for a mean of 7.7 years (SD, 4.5 years). Demographic and clinical characteristics are shown in Table I, with no important differences between groups. Children received omalizumab (n = 14) or placebo (n = 13) injections every 2 (n = 15) to 4 (n = 12) weeks based on their baseline total IgE level, per the manufacturer's recommendations (see Table E1 in this article's Online Repository at www.jacionline.org), for 5 months to cover the winter viral season in Australia. Severe and moderate asthma exacerbations were defined according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) consensus statement on asthma control.7Reddel H.K. Taylor D.R. Bateman E. Boulet L.P. Boushey H.A. Busse W.W. et al.An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations.Am J Respir Crit Care Med. 2009; 180: 59-99Crossref PubMed Scopus (0) Google Scholar Children were assessed at the time of each injection at the end of the treatment period and then followed without treatment through the following year (follow-up period). The study schedule and procedures are shown in the Methods section in this article's Online Repository (also see Table E2 in this article's Online Repository at www.jacionline.org). Primary comparisons between groups were made by using negative binomial regression.Table IBaseline demographic and clinical characteristics of randomized subjectsActive (n = 14)Placebo (n = 13)P value∗The Wilcoxon rank sum test was used for continuous variables, and the χ2 test was used for categorical variables.Age (y), mean ± SD11.51 ± 2.9411.40 ± 3.15.92Male sex (%)5446.84Total IgE (kU/L), mean ± SD474.57 ± 248.76372.80 ± 287.21.31Lung function†Z scores were calculated by using the GLI calculator. FVC Z score, mean ± SD−0.13 ± 0.86−0.15 ± 1.02.85 FEV1 Z score, mean ± SD−1.06 ± 1.25−1.17 ± 1.00.89 FEV1/FVC Z score, mean ± SD−1.38 ± 1.36−1.55 ± 1.31.70Asthma Control Test score, mean ± SD16 ± 5.817 ± 4.2.85Inhaled corticosteroid dose (μg of BDP equivalent), mean ± SD705.56 ± 531.891088.46 ± 666.51.08Length of asthma (y), mean ± SD7.9 ± 5.187.5 ± 3.75.78Asthma exacerbations in previous 12 mo, median (25% to 75%)2.5 (1.75-3.00)2.0 (1.50-3.00).83Family history of asthma1110.99Failed to complete study Lost to follow-up22 Withdrew consent01 Withdrew because of AEs10AEs, Adverse events; BDP, beclomethasone dipropionate.∗ The Wilcoxon rank sum test was used for continuous variables, and the χ2 test was used for categorical variables.† Z scores were calculated by using the GLI calculator. Open table in a new tab AEs, Adverse events; BDP, beclomethasone dipropionate. Twenty-five children completed the treatment, and 22 completed the follow-up. Despite the small number, significantly fewer severe asthma exacerbations were seen in children treated with omalizumab (n = 1) than placebo (n = 6), with an incident rate in the placebo group 10.8 times greater than that in the omalizumab group (P = .024). The time to first severe exacerbation was longer in those receiving omalizumab (mean, 240.5 days [SD, 87.9 days] vs 107.0 days [SD, 115.9 days]; P = .08; Fig 1). There were no differences in the number of moderate exacerbations (incident rate, 1.24; P = .58), time to first moderate exacerbation (177.3 days [140.6 days] vs 87.3 days [89.6 days], P = .91), or rate of lower respiratory tract illnesses (incident rate, 1.52; P = .11) between the study groups. The reduction in severe exacerbations was not seen during the follow-up period (incident rate, 0.45; P = .45). No statistically significant or clinically important changes were seen in lung function. We attempted to perform methacholine challenges at baseline, after treatment, and after follow-up, but many of the children were not able to perform the test because of low baseline lung function. In those able to participate (n = 15), there were no differences in PD20 values between the groups at any time point or any trend for reduction in methacholine responsiveness in either group. The small numbers of children in this study means that our results must be treated with caution because our prestudy sample size calculations suggested that we needed 42 subjects per group to have 80% power to detect a 50% reduction in severe exacerbations with omalizumab. In addition, members of the placebo group were taking higher doses of inhaled corticosteroids, raising the possibility of less-well controlled asthma. However, they had a similar number of severe exacerbations in the previous 12 months (Table I). Nevertheless, taken in conjunction with similar recent findings on omalizumab-mediated blunting of the “fall” epidemics in susceptible children,6Teach S.J. Gill M.A. Togias A. Sorkness C.A. Arbes Jr., S.J. Calatroni A. et al.Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations.J Allergy Clin Immunol. 2015; 136: 1476-1485Abstract Full Text Full Text PDF PubMed Scopus (394) Google Scholar they do support the general concept of targeted disruption of atopy-associated pathways during periods of high risk as an asthma treatment strategy. Our findings of a lack of carryover of the protective effect of omalizumab treatment in a single virus season into the subsequent year leaves open the question of whether omalizumab can halt disease progression. This important question needs to be addressed in subsequent prospective studies. This study was a phase 3, multicenter, double-blind, randomized, placebo-controlled study testing the efficacy of winter-only treatment with omalizumab for the reduction of asthma exacerbations in children aged 6 to 15 years. Clinical sites included the Royal Children's Hospital, Brisbane, Australia (site investigator: Professor Peter Sly); Royal Children's Hospital, Melbourne, Australia (site investigator: Professor Mimi Tang); and Princess Margaret Hospital, Perth, Australia (site investigator: Professor Peter LeSouef). The study population included children aged 6 to 15 years with asthma who were prone to acute exacerbations. Ninety-six children will be randomized. Randomization occurred in blocks stratified by study site based on predetermined block sizes. Participants who met all of the following criteria were eligible for enrollment:1.children of either sex, aged 6 to 15 years, with current asthma;2.admission to a hospital emergency department in the previous winter season for acute asthma exacerbation, as defined by the ATS/ERS statement on asthma control and exacerbations;3.positive skin prick test responses to aeroallergens;4.atopic family history; and5.written informed consent form signed and dated by parent/legal guardian according to local regulations. Participants who met any of the following criteria were not eligible for enrollment:1.hypersensitivity to omalizumab;2.treatment with omalizumab within 30 days before screening;3.use of prolonged high-dose oral steroids;4.participation in another randomized controlled trial within the 3 months preceding inclusion in the study; and5.a significant medical disease or condition other than asthma likely to interfere with the child's ability to complete the entire protocol. The study was conducted as a multicenter, double-blind, randomized, placebo-controlled study testing the efficacy of omalizumab treatment during winter for the reduction of asthma exacerbations in children with exacerbation-prone asthma. Children identified from emergency department records as having an acute asthma exacerbation during the previous winter viral season and found eligible in the screening visit were randomized into 2 groups. The active group received omalizumab every 2 or 4 weeks for 5 months timed to cover the winter viral season (April/May to September/October). The control group received identical placebo. Omalizumab was administered by means of subcutaneous injection every 2 or 4 weeks based on the baseline serum total IgE level (in international units per milliliter) measured before the start of treatment and body weight (in kilograms). The dosing regimen is shown in Table E1.E1Katelaris C. Douglass J. Gibson P. Heddle R. Rimmer J. Ruffin R. et al.Omalizumab: recommendations for use in the Australasian context. Thoracic Society of Australia and New Zealand, Sydney2009Google Scholar All children also received standard asthma therapy, as prescribed by their treating pediatrician. The primary efficacy end point was the proportion of children with acute asthma exacerbations, as defined by the ATS/ERS statement on asthma control and exacerbations,E2Reddel H. Taylor D. Bateman E. Bouler L.-P. Boushey H. Busse W. et al.An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice.Am J Respir Crit Care Med. 2009; 180: 59-99Crossref PubMed Scopus (1468) Google Scholar during the treatment period (ie, from visit 1 [first dosing] to visit 6 [1 month after the last dose]). Severe and moderate exacerbations were treated separately. Secondary efficacy end points were as follows:•the proportion of viral respiratory tract infections that result in lower airway symptoms during the treatment period (ie, from visit 1 [first dosing] to visit 6 [1 month after the last dose]) and•lung function and airway responsiveness over the follow-up period (ie, from visit 6 [1 month after the last dose] until visit 18 [12 months after the last dose]). Safety end points were as follows:•urticarial or anaphylactic reaction to omalizumab;•treatment-related adverse events; and•hematology and clinical chemistry. Safety data were presented by group in a blinded fashion to the Data Safety Monitoring Board (DSMB) at scheduled DSMB meetings during the trial. The DSMB had the authority to request unblinded data, if necessary. The DSMB had the authority to recommend that enrollment or study treatment be discontinued for the safety of participants. Although the DSMB was to examine all safety data, they were requested to pay particular attention to the number of episodes of anaphylaxis. Procedures conducted as a part of the participant's routine clinical management and obtained before informed consent were allowed to be used for screening purposes or assessment of eligibility criteria. However, the procedure must have met the protocol-defined criteria and have been performed within the timelines permitted by the protocol. A signed written informed consent form was obtained from the participant's parent/legal guardian before any study-specific assessments or procedures. The Childhood Asthma Control Test for children 11 years and younger and the Asthma Control Test for children 12 years and older were performed at visits 0, 6, and 18 to document asthma control. The following groups of participants will define samples for end point analysis:•Intention-to-treat sample: All participants who are randomized and have evaluable data for the end point under investigation. Participants will be analyzed in the group to which they were randomized, regardless of compliance with their allocated treatment. The number of participants who have evaluable data might differ for each end point being investigated.•Safety sample: All participants who take at least 1 dose of the investigational product. The primary data on asthma exacerbations and lower respiratory tract infections were not normally distributed and did not fit with a Poisson distribution. Because the dates were overdispersed (ie, the variance was greater than the mean), negative binomial regression was used for these primary analyses. Kaplan-Meier survival analyses were used to examine the time to first exacerbation, with the log-rank test used to test the difference in survival between treatment groups. Group differences in demographic data were tested by using the Wilcoxon rank sum test for continuous variables and the χ2 test for categorical variables. A schedule of study visits, procedures, and assessments is shown in Table E2. There were no differences in Asthma Control Test scores between groups at baseline (omalizumab group: mean, 16 [SD, 5.8] vs placebo group: mean, 17 [SD, 4.2]; P = .85), at the end of the treatment period (mean: 20 [SD, 3.6] vs 20 [SD, 3.1], respectively; P = .90), or at the end of the follow-up period (mean, 20 [SD, 5.5] vs 22 [SD, 1.7], respectively; P = .10). Treatment period:•Severe exacerbations: incident rate, 10.83 (P = .024)•Moderate exacerbations: incident rate, 1.24 (P = .58)•Lower respiratory tract infections: incident rate, 1.52 (P = .11) Follow-up period:•Severe exacerbations: incident rate, 0.45 (P = .10)•Moderate exacerbations: incident rate, 0.53 (P = .53)•Lower respiratory tract infections: incident rate, 1.05 (P = .86)Table E1Pediatric dosing schedule for omalizumab (in milligrams) per 4-week or 2-week intervalDosing intervalBaseline IgE (IU/mL)Body weight (kg)>20-25>25-30>30-40>40-50>50-60>60-70>70-80>80-90>90-125>125-150Q4 weeks≥30-100757575150150150150150300300>100-200150150150300300300300300225300>200-300150150225300300225225225300375>300-400225225300225225225300300>400-500225300225225300300375375>500-600300300225300300375>600-700300225225300375Do not administerQ2 weeks>700-800225225300375>800-900225225300375>900-1000225300375>1000-1100225300375>1100-1200300300>1200-1300300375 Open table in a new tab Table E2Schedule of assessments and proceduresStudy periodScreeningTreatmentFollow-upRTIUVVisit0123456789101112131415161718Week8 wk to 1 d048121620242832364044485256606472Visit window± 3d± 3d± 3d± 3d± 3d± 5d± 5d± 7d± 5d± 5d± 7d± 5d± 5d± 7d± 5d± 5d± 7dTelephone callxxxxxxxxInformed consentxReview eligibility criteriaxxRandomizationxHistoryxPhysical examinationxxxxxxxxxxxxDrug deliveryxxxxxSkin prick testxNasal washxxxxxxxxxxx∗When presenting to A&E for acute asthma exacerbation.Nasal swabx†Respiratory tract infections only.Posterior palatal swabxxxLung function/methacholine challengexxxPregnancy testxxxxxxxxxxxAsthma Control TestxxxDispense diary cardxxxxxxxxxDiary card reviewxxxxxxxxxxDispense rescue medicationxReview rescue medication proceduresxxxxCollect rescue medicationxAsthma severity scorex∗When presenting to A&E for acute asthma exacerbation.Blood collectionxxxx∗When presenting to A&E for acute asthma exacerbation.Adverse event reviewxxxxxxxxxxxxxxxxxxxConcomitant medication reviewxxxxxxxxxxxxxxxxxxxxRTI, Respiratory tract infections; UV, unscheduled visit.∗ When presenting to A&E for acute asthma exacerbation.† Respiratory tract infections only. Open table in a new tab RTI, Respiratory tract infections; UV, unscheduled visit." @default.
• W2534482609 created "2016-10-28" @default.
• W2534482609 creator A5011316528 @default.
• W2534482609 creator A5022482109 @default.
• W2534482609 creator A5023500821 @default.
• W2534482609 creator A5025551303 @default.
• W2534482609 creator A5027878821 @default.
• W2534482609 creator A5048175603 @default.
• W2534482609 creator A5057746121 @default.
• W2534482609 creator A5064260982 @default.
• W2534482609 creator A5087647894 @default.
• W2534482609 date "2017-02-01" @default.
• W2534482609 modified "2023-09-26" @default.
• W2534482609 title "Severe winter asthma exacerbations can be prevented by omalizumab, but there is no carryover effect" @default.
• W2534482609 cites W1525354362 @default.
• W2534482609 cites W1876031798 @default.
• W2534482609 cites W1983832849 @default.
• W2534482609 cites W2054909400 @default.
• W2534482609 cites W2115252063 @default.
• W2534482609 cites W2146852572 @default.
• W2534482609 cites W2601675613 @default.
• W2534482609 doi "https://doi.org/10.1016/j.jaci.2016.07.035" @default.
• W2534482609 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27637383" @default.
• W2534482609 hasPublicationYear "2017" @default.
• W2534482609 type Work @default.
• W2534482609 sameAs 2534482609 @default.
• W2534482609 citedByCount "7" @default.
• W2534482609 countsByYear W25344826092017 @default.
• W2534482609 countsByYear W25344826092018 @default.
• W2534482609 countsByYear W25344826092020 @default.
• W2534482609 countsByYear W25344826092022 @default.
• W2534482609 countsByYear W25344826092023 @default.
• W2534482609 crossrefType "journal-article" @default.
• W2534482609 hasAuthorship W2534482609A5011316528 @default.
• W2534482609 hasAuthorship W2534482609A5022482109 @default.
• W2534482609 hasAuthorship W2534482609A5023500821 @default.
• W2534482609 hasAuthorship W2534482609A5025551303 @default.
• W2534482609 hasAuthorship W2534482609A5027878821 @default.
• W2534482609 hasAuthorship W2534482609A5048175603 @default.
• W2534482609 hasAuthorship W2534482609A5057746121 @default.
• W2534482609 hasAuthorship W2534482609A5064260982 @default.
• W2534482609 hasAuthorship W2534482609A5087647894 @default.
• W2534482609 hasBestOaLocation W25344826091 @default.
• W2534482609 hasConcept C141105273 @default.
• W2534482609 hasConcept C159654299 @default.
• W2534482609 hasConcept C187212893 @default.
• W2534482609 hasConcept C203014093 @default.
• W2534482609 hasConcept C2776042228 @default.
• W2534482609 hasConcept C2778564945 @default.
• W2534482609 hasConcept C2909082789 @default.
• W2534482609 hasConcept C71924100 @default.
• W2534482609 hasConceptScore W2534482609C141105273 @default.
• W2534482609 hasConceptScore W2534482609C159654299 @default.
• W2534482609 hasConceptScore W2534482609C187212893 @default.
• W2534482609 hasConceptScore W2534482609C203014093 @default.
• W2534482609 hasConceptScore W2534482609C2776042228 @default.
• W2534482609 hasConceptScore W2534482609C2778564945 @default.
• W2534482609 hasConceptScore W2534482609C2909082789 @default.
• W2534482609 hasConceptScore W2534482609C71924100 @default.
• W2534482609 hasIssue "2" @default.
• W2534482609 hasLocation W25344826091 @default.
• W2534482609 hasLocation W25344826092 @default.
• W2534482609 hasOpenAccess W2534482609 @default.
• W2534482609 hasPrimaryLocation W25344826091 @default.
• W2534482609 hasRelatedWork W1985174507 @default.
• W2534482609 hasRelatedWork W2051805098 @default.
• W2534482609 hasRelatedWork W2106578444 @default.
• W2534482609 hasRelatedWork W2217625724 @default.
• W2534482609 hasRelatedWork W2337475218 @default.
• W2534482609 hasRelatedWork W2415904844 @default.
• W2534482609 hasRelatedWork W2469136300 @default.
• W2534482609 hasRelatedWork W2565464084 @default.
• W2534482609 hasRelatedWork W2779475057 @default.
• W2534482609 hasRelatedWork W2884050659 @default.
• W2534482609 hasVolume "139" @default.
• W2534482609 isParatext "false" @default.
• W2534482609 isRetracted "false" @default.
• W2534482609 magId "2534482609" @default.
• W2534482609 workType "article" @default.