Seasonal variation in asthma exacerbations in the AUSTRI and VESTRI studies.
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ABSTRACT:
SUBMITTER: Szefler SJ
PROVIDER: S-EPMC6507548 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
Seasonal variation in asthma exacerbations in the AUSTRI and VESTRI studies.
Szefler Stanley J SJ Raphiou Ibrahim I Zeiger Robert S RS Stempel David D Kral Kenneth K Pascoe Steven S
ERJ open research 20190426 2
<b>Seasonal variation in the benefit of LABA/ICS <i>versus</i> ICS on asthma exacerbation rate is observed in children.</b> http://ow.ly/pcZF30o8hHk. ...[more]
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Project description:BACKGROUND:A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. OBJECTIVE:This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. METHODS:The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. RESULTS:A higher saEPI was associated with an exacerbation in both the GBT alone (P < .001; area under the curve, 0.76) and the GBT + omalizumab group (P < .01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with those who had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups. CONCLUSIONS:An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.
| S-EPMC5568982 | biostudies-literature
Project description:BackgroundAsthma exacerbations remain common, even in children and adolescents, despite optimal medical management. Identification of host risk factors for exacerbations is incomplete, particularly for seasonal episodes.ObjectiveWe sought to define host risk factors for asthma exacerbations unique to their season of occurrence.MethodsThis is a retrospective analysis of patients aged 6 to 20 years who comprised the control groups of the Asthma Control Evaluation study and the Inner City Anti-IgE Therapy for Asthma study. Univariate and multivariate models were constructed to determine whether patients' demographic and historical factors, allergic sensitization, fraction of exhaled nitric oxide values, spirometric measurements, asthma control, and treatment requirements were associated with seasonal exacerbations.ResultsThe analysis included 400 patients (54.5% male; 59.0% African American; median age, 13 years). Exacerbations occurred in 37.5% of participants over the periods of observation and were most common in the fall (28.8% of participants). In univariate analysis impaired pulmonary function was significantly associated with greater odds of exacerbations for all seasons, as was an exacerbation in the previous season for all seasons except spring. In multivariate analysis exacerbation in the previous season was the strongest predictor in fall and winter, whereas a higher requirement for inhaled corticosteroids was the strongest predictor in spring and summer. The multivariate models had the best predictive power for fall exacerbations (30.5% variance attributed).ConclusionsAmong a large cohort of inner-city children with asthma, patients' risk factors for exacerbation vary by season. Thus information on individual patients might be beneficial in strategies to prevent these seasonal events.
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Project description:INTRODUCTION:The genetics of severe asthma and asthma exacerbations are distinct from milder forms of asthma. Gene-environmental interactions contribute to the complexity and heterogeneity of severe asthma and asthma exacerbations, and pharmacogenomic studies have also identified genes that affect susceptibility to asthma exacerbations. AREAS COVERED:Studies on the genetics, gene-environment interactions, and pharmacogenomics of asthma exacerbations are reviewed. Multiple individual genetic variants have been identified to be associated with asthma exacerbations but each genetic polymorphism explains only a fraction of the disease and by itself is not able to translate into clinical practice. Research is shifting from candidate gene studies and genome wide association studies towards more integrative approaches to translate genetic findings into clinical diagnostic and therapeutic tools. EXPERT COMMENTARY:Integrative approaches combining polygenic or genomic data with multi-omics technologies have the potential to discover new biologic mechanisms and biomarkers for severe asthma and asthma exacerbations. Greater understanding of genomics and underlying biologic pathways will also lead to improved prevention and treatment, lowering costs, morbidity, and mortality. The utilization of genomic testing and personalized medicine may revolutionize asthma management, in particular for patients with severe, refractory asthma.
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Project description:RationaleAlthough airway oxidative stress and inflammation are central to asthma pathogenesis, there is limited knowledge of the relationship of asthma risk, severity, or exacerbations to mitochondrial dysfunction, which is pivotal to oxidant generation and inflammation.ObjectivesWe investigated whether mitochondrial DNA copy number (mtDNA-CN) as a measure of mitochondrial function is associated with asthma diagnosis, severity, oxidative stress, and exacerbations.MethodsWe measured mtDNA-CN in blood in two cohorts. In the UK Biobank (UKB), we compared mtDNA-CN in mild and moderate-severe asthmatics to non-asthmatics. In the Severe Asthma Research Program (SARP), we evaluated mtDNA-CN in relation to asthma severity, biomarkers of oxidative stress and inflammation, and exacerbations.Measures and main resultsIn UK Biobank, asthmatics (n = 29,768) have lower mtDNA-CN compared to non-asthmatics (n = 239,158) (beta, -0.026 [95% CI, -0.038 to -0.014], P = 2.46×10-5). While lower mtDNA-CN is associated with asthma, mtDNA-CN did not differ by asthma severity in either UKB or SARP. Biomarkers of inflammation show that asthmatics have higher white blood cells (WBC), neutrophils, eosinophils, fraction exhaled nitric oxide (FENO), and lower superoxide dismutase (SOD) than non-asthmatics, confirming greater oxidative stress in asthma. In one year follow-up in SARP, higher mtDNA-CN is associated with reduced risk of three or more exacerbations in the subsequent year (OR 0.352 [95% CI, 0.164 to 0.753], P = 0.007).ConclusionsAsthma is characterized by mitochondrial dysfunction. Higher mtDNA-CN identifies an exacerbation-resistant asthma phenotype, suggesting mitochondrial function is important in exacerbation risk.
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Project description:PoolSeq analysis of seasonal variation in a natural population of the non-biting midge Chironomus riparius
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Project description:BackgroundThe fall peak in childhood asthma exacerbations is thought to be related to an increase in viral infections and allergen exposure when children return to school. Whether the seasonality of asthma attacks among children from different geographic regions follows similar trends is unclear.ObjectiveTo compare seasonal trends in asthma exacerbations among school-age children who lived in different geographic locations, with different climates, within the United States.MethodsHospital billing data bases were examined to determine the monthly number of school-age children who were hospitalized or treated in the emergency department (ED) for asthma exacerbations. Data from four cities within three states were compared. Climate data were obtained from archives of the National Climate Data Center, U.S. Department of Commerce.ResultsAn annual peak in asthma exacerbations was observed during the fall months (September through November) among children who lived in Charlottesville, Virginia, as well as throughout the state of Virginia. An increase in exacerbations, which peaked in November, was observed for exacerbations among children who lived in Tucson, Arizona, and Yuma, Arizona. In contrast, exacerbations among children from New Orleans, Louisiana, increased in September but remained elevated throughout the school year. Although there was annual variation in the frequency of exacerbations over time, the seasonal patterns observed remained similar within the locations from year to year. A nadir in the frequency of attacks was observed during the summer months in all the locations.ConclusionSeasonal peaks for asthma exacerbations varied among the children who lived in geographic locations with different climates, and were not restricted to the beginning of the school year.
| S-EPMC5080535 | biostudies-literature
Project description:Rhinovirus (RV) is ubiquitous and typically causes only minor upper respiratory symptoms. However, especially in children and adolescent asthmatics, RV is responsible for most exacerbations. This ability of RV to drive exacerbations typically requires the concomitant presence of exposure to a bystander allergen. Susceptibility to RV-mediated exacerbations is also related to the genetic background of the host, which contributes to greater infectivity, more severe infections, altered immune responses, and to greater inflammation and loss of asthma control. Given these responses, there are several treatments available or being developed that should improve the control of exacerbations related to RV infection.
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Project description:To investigate mechanisms underlying frequent asthma exacerbation, we profiled the nasal transcriptome of both frequent and non-frequent asthma exacerbators.
2023-10-17 | GSE211158 | GEO
Project description:INTRODUCTION:Effective home management of childhood asthma by caregivers requires education along with a written asthma action plan (AAP), which should outline clear instructions for treatment during exacerbations. However, a large number of asthma exacerbations continue to be managed in the emergency department (ED) and in hospitals, particularly in Canada. The objective of this study was to assess caregiver management of acute asthma at home following the 2015 Global Initiative for Asthma (GINA) guidelines and to identify factors that may be associated with deviations from these guidelines. METHODS:122 caregivers of children, aged 3-17 years, with physician diagnosed asthma, completed a paper-based questionnaire. Correct caregiver management (defined according to the GINA guidelines) of acute asthma as well as their use of an AAP were assessed. RESULTS:Out of all caregivers, 74.6% incorrectly treated their child's asthma exacerbation in a home setting. Among those who used an AAP, we observed significantly more ED visits (0.9 ± 1.2 versus 0.5 ± 0.9, p = 0.04) and hospitalizations (0.2 ± 0.4 versus 0.0 ± 0.0, p = 0.02) when compared to non-AAP users in the past 1 year. CONCLUSIONS:Caregivers of children with asthma in Canada may still lack skills for proper home management of asthma exacerbations. We found a higher number of ED visits and hospitalizations in those using an AAP compared to those who did not use an AAP. These data suggest that current AAPs may not be sufficient for home asthma management.
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