Prognostic models hold great potential for predicting asthma exacerbations, providing opportunities for early intervention, and are a popular area of current research. However, it is unclear how models should be compared and contrasted, given their differences in both design and performance, particularly with a view to potential implementation in routine practice. This systematic review aimed to identify novel predictive models of asthma attacks in adults and compare differences in construction related to populations, outcome definitions, prediction time horizons, algorithms, validation, and performance estimation. Twenty-five studies were identified for comparison, with varying definitions of asthma attacks and prediction event time horizons ranging from 15 days to 30 months. The most commonly used algorithm was logistic regression (20/25 studies); however, none of the six which tested multiple algorithms identified it as highest performing algorithm. The effect of various study design characteristics on performance was evaluated in order to provide context to the limitations of highly performing models. Models used a variety of constructs, which affected both their performance and their viability for implementation in routine practice. Consultation with stakeholders is necessary to identify priorities for model refinement and to create a benchmark of acceptable performance for implementation in clinical practice.

BACKGROUND: Acute respiratory infections are a major trigger of asthma exacerbations. This study sought to estimate the overall proportion of viruses, atypical pathogens, and bacteria detected in adults with asthma exacerbations.
METHODS: PubMed, EMBASE, and Cochrane Library databases and all related studies from the reviews and references were searched from inception to February 13, 2020. Two authors independently performed study selection, data extraction, as well as quality evaluation. Subsequently, meta-analysis, between-study heterogeneity, and publication bias assessment were conducted on RStudio.
RESULTS: Forty-three eligible studies comprising 3511 adults were included, of which 21 publications mentioned multiple infections during acute asthma attacks. Meta-analysis showed an acute infection prevalence of 40.19% (95% confidence interval [CI] 34.53%-45.99%). Viruses, atypical pathogens, and bacteria were detected in 38.76% (95% CI 32.02%-45.71%), 8.29% (95% CI 2.64%-16.27%), and 7.05% (95% CI 3.34%-11.81%) of asthmatics during exacerbations, respectively. Rhinovirus infections are always the dominant trigger for exacerbations with a proportion of 20.02% (95% CI 14.84%-25.73%). Substantial heterogeneity across studies (Cochran Q test: 479.43, P < 0.0001, I2 = 91.2%) was explained by subgroup analysis, indicating that year, region, population, respiratory secretion, detection method, pathogen, and study quality were all influencing factors.
CONCLUSIONS: This meta-analysis provided the first quantitative epidemiological data for adults, and in the future, more research and health-care supports are necessary in this area.

UNASSIGNED: To systematically review the scientific literature examining parents\' experiences and information needs for the management of their child\'s asthma exacerbations.
UNASSIGNED: We searched five databases for quantitative and qualitative studies in Canada and the United States from 2002 onwards. A convergent integrated approach and the Mixed Method Appraisal Tool were used to analyze and appraise the evidence, respectively.
UNASSIGNED: We included 84 studies (27 quantitative, 54 qualitative, 3 mixed methods). Some parents lacked confidence in recognizing or managing exacerbations. A few parents were uncertain when and where to seek medical help. The main barrier to accessing care was cost. Impacts on parents included poor sleep, distress, and lifestyle disruptions. Parents felt they lacked information and wanted education on treatments and how to recognize and manage exacerbations via education sessions, written materials, community outreach and online resources.
UNASSIGNED: Improved education for parents may help reduce parents\' stress, asthma-related morbidities for children and use of urgent health services.
UNASSIGNED: The development of tailored interventions and knowledge translation strategies with input from target audiences (e.g. parents, health care providers) is necessary to meet their information needs and support adherence to clinical recommendations.

Tumor-necrosis factor (TNF) is recognized as a therapeutic target in inflammatory diseases, including asthma. In severe forms of asthma, biologics such as anti-TNF are rendered to be investigated as therapeutic options in severe asthma. Hence, this work is done to assess the efficacy and safety of anti-TNF as a supplementary therapy for patients with severe asthma. A systematic search of 3 databases (Cochrane Central Register of Controlled Trials, MEDLINE, ClinicalTrials.gov) was performed to identify for published and unpublished randomized controlled trials comparing anti-TNF (etanercept, adalimumab, infliximab, certolizumab pegol, golimumab) with placebo in patients diagnosed with persistent or severe asthma. Random-effects model was used to estimate risk ratios and mean differences (MDs) with confidence intervals (95% CIs). PROSPERO registration number is CRD42020172006. Four trials with 489 randomized patients were included. Comparison between etanercept and placebo involved 3 trials while comparison between golimumab and placebo involved 1 trial. Etanercept produced a small but significant impairment in forced expiratory flow in 1 second (MD 0.33, 95% CI 0.09-0.57, I2 statistic = 0%, P = 0.008) and a modest improvement of asthma control using the Asthma Control Questionnaire. However, using the Asthma Quality of Life Questionnaire, the patients exhibit an impaired quality of life with etanercept. Treatment with etanercept showed a reduced injection site reaction and gastroenteritis compared with placebo. Although treatment with anti-TNF is shown to improve asthma control, severe asthma patients did not benefit from this therapy as there is limited evidence for improvement in lung function and reduction of asthma exacerbation. Hence, it is unlikely to prescribe anti-TNF in adults with severe asthma.

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value < 0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p<0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p<0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

UNASSIGNED: To compare the efficacy of tezepelumab with other approved biologics via indirect treatment comparisons (ITCs) in patients aged ≥ 12 years with severe uncontrolled asthma.
UNASSIGNED: Data from randomized controlled trials (RCTs) identified from a systematic literature review were synthesized using two different ITC approaches: network meta-analysis (NMA) and simulated treatment comparison (STC). Outcomes of interest were annualized asthma exacerbation rate (AAER) and AAER for exacerbations leading to hospitalization. To address potential heterogeneity between study populations, various subgroup analyses were performed for the NMA (based on blood eosinophil count, fractional exhaled nitric oxide level, and presence of allergic asthma), and for the STC, models were adjusted for potential treatment effect modifiers. Sensitivity analyses were performed to assess the impact of study design (exclusion of non-placebo-controlled studies and non-phase 3 or 4 studies). Results were reported as rate ratios (RRs) with 95% credible/confidence intervals and ranking statistics were computed for the NMAs.
UNASSIGNED: Sixteen RCTs were included in at least one of the ITCs. All biologics (tezepelumab, dupilumab, benralizumab, mepolizumab, reslizumab, and omalizumab) had similar efficacy, with no statistically significant RRs for either exacerbation outcome; however, tezepelumab was favorably associated with numerically lower AAERs and was ranked first in the network for both types of exacerbation outcome. This trend was consistent in the subgroup and sensitivity analyses. As with the primary NMA, the STC results did not demonstrate any significant differences between biologics, but point estimates were favorable towards tezepelumab.
UNASSIGNED: Heterogeneity between trials was observed among eligibility criteria and clinically important patient characteristics; however, the impact on findings is expected to be low, based on consistency across analyses.
UNASSIGNED: Findings from both ITCs (NMA and STC) support the use of tezepelumab in a broad patient population of severe uncontrolled asthma of any phenotype.

Pneumorachis is characterized by the presence of free air in the spinal canal. It is referred by different names in literature such as epidural emphysema, intraspinal air, intraspinal pneumoc(o)ele, spinal epidural and subarachnoid pneumatosis, spinal and epidural emphysema, aerorachia, pneumosaccus, air myelogram, etc. Pneumorachis can be broadly classified as traumatic, iatrogenic, or spontaneous. In this case-based review, we present a case of spontaneous pneumorachis secondary to asthma exacerbation. This is followed by a systematic review of all cases of spontaneous pneumorachis identified in PubMed. The aim of this review is to understand the pathophysiology, common causes and the management of spontaneous pneumorachis.

BACKGROUND: Gastroesophageal reflux disease (GORD) is highly prevalent and often coexists with asthma exacerbation. Divergent findings about the association between the two diseases were reported. We conducted a systematic review and meta-analysis to determine whether there exists an association between GORD and asthma.
METHODS: We searched MEDLINE, EMBASE, and other databases and then performed a manual search, to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using fixed- and random-effect models. We evaluated the quality of included studies, explored heterogeneity between studies, undertook subgroup analyses, assessed publication bias, and performed sensitivity analyses.
RESULTS: We identified 32 eligible studies, conducted in 14 countries and including a total of 1,612,361 patients of all ages. Overall, GORD shows a weak association with asthma exacerbation (OR = 1.27; 95% CI 1.18-1.35). This association was observed in cohort, case-control, and cross-sectional designs and in European as well as non-European populations. Subgroup analyses show that GORD is associated with frequent asthma exacerbations (≥3 exacerbations, OR = 1.59; 95% CI 1.13-2.24) and with exacerbations needing oral corticosteroid therapy (OR = 1.24; 95% CI 1.09-1.41). GORD pediatric patients are at higher odds of asthma exacerbation than adults. We did not detect any evidence of publication bias and the association between GORD and asthma exacerbation held in all undertaken sensitivity analyses.
CONCLUSIONS: Gastroesophageal reflux disease and asthma exacerbation are weakly associated.

OBJECTIVE: To systematically review the literature on pediatric asthma readmission risk factors.
METHODS: We searched PubMed/MEDLINE, CINAHL, Scopus, PsycINFO, and Cochrane Central Register of Controlled Trials for published articles (through November 2019) on pediatric asthma readmission risk factors. Two authors independently screened titles and abstracts and consensus was reached on disagreements. Full-text articles were reviewed and inclusion criteria applied. For articles meeting inclusion criteria, authors abstracted data on study design, patient characteristics, and outcomes, and 4 authors assessed bias risk.
RESULTS: Of 5749 abstracts, 74 met inclusion criteria. Study designs, patient populations, and outcome measures were highly heterogeneous. Risk factors consistently associated with early readmissions (≤30 days) included prolonged length of stay (OR range, 1.1-1.6) and chronic comorbidities (1.7-3.2). Risk factors associated with late readmissions (>30 days) included female sex (1.1-1.6), chronic comorbidities (1.5-2), summer discharge (1.5-1.8), and prolonged length of stay (1.04-1.7). Across both readmission intervals, prior asthma admission was the most consistent readmission predictor (1.3-5.4).
CONCLUSIONS: Pediatric asthma readmission risk factors depend on the readmission interval chosen. Prior hospitalization, length of stay, sex, and chronic comorbidities were consistently associated with both early and late readmissions.
BACKGROUND: CRD42018107601.

Asthma is the commonest obstructive airway disease and the leading cause of morbidity in children. In the pediatric population, acute exacerbations of asthma are a frequent cause of presentations and hospital admissions. An acute asthma exacerbation is potentially life-threatening; it is predominantly treated using conventional oxygen therapy with bronchodilators and systemic corticosteroids. The treatment of those who do not respond to conventional therapy is escalated to noninvasive positive pressure ventilation (NIPPV) before invasive ventilation. Although NIPPV has demonstrated benefits and safety, it still has limitations such as treatment intolerance caused mainly by discomfort and complications. High-flow oxygen therapy administered through a nasal cannula (HFNC) provides respiratory support with adequate airway humidity and has demonstrated safety and benefits in clinical practice. In the present review, we discuss HFNC and variations in HFNC use, focusing on its feasibility and current evidence of using it on children with asthma exacerbations.