Correlation between total IgE level and asthma symptom severity in hospitalized children.

Rationale: Elevated total serum IgE levels are associated with asthma independent of allergen sensitization, suggesting a role for genetic factors regulating IgE levels in asthma pathogenesis. This study aimed to characterize asthma phenotypes in adults that are influenced by genetic factors associated with elevated total IgE levels. Methods: This study population comprised Japanese adult healthy controls (N=1379) and adult asthma patients (N=750). We performed a genome-wide association study (GWAS) of total IgE levels in healthy adults without asthma or atopic dermatitis and developed a polygenic risk score (IgE_PRS) for total serum IgE using PRSice-2 with clumping and thresholding method. This IgE_PRS was then calculated in adult asthma patients using the same SNP set. A two-step cluster analysis was performed in asthma patients based on total serum IgE, pFEV1, age at asthma onset, and IgE_PRS to delineate distinct clusters. In addition, we evaluated the distribution of these clusters among newly diagnosed asthma cases in a 10-year prospective cohort of Japanese healthy adults (N=1303) using a decision tree model to validate the cluster distribution. Results: IgE_PRS was derived from 16,169 SNPs, and showed the strongest association with total IgE levels (p=0.0018, r2=0.017) but not with allergen sensitization (p=0.595) in healthy adults. Total IgE levels were significantly elevated in asthmatic patients compared to healthy controls (p=2.4×10-25), while IgE_PRS levels were not significantly different between groups (p=0.235). The two-step cluster analysis of asthmatic patients identified four distinct subgroups, two of which had significantly higher IgE_PRS compared to healthy controls. Cluster 1 (N=194), with the highest IgE_PRS, was characterized by adult-onset allergic asthma, elevated total IgE levels, high allergen sensitization (75.3%), mild airflow obstruction, and a predominance of females (64.4%). Cluster 2 (N=172), with the second highest IgE_PRS, included individuals with adult-onset asthma, moderate to severe airflow obstruction, and a high prevalence of smoking (52.3%). Of 79 newly diagnosed asthma cases, 26.6% were classified in the highest IgE_PRS cluster. Conclusions: Our findings reveal a distinct phenotype of adult-onset asthma characterized by a genetic predisposition to elevated total IgE levels. This study highlights the potential of IgE_PRS-driven clustering to identify asthma endotypes that may be particularly influenced by genetic susceptibility to high IgE levels, with implications for more tailored therapeutic approaches.

Objective This study aims to evaluate the impact of early mobilization (EM) after pediatric liver transplantation in the pediatric intensive care unit (PICU). Design A 14-month prospective before and after study. Setting Multivalent PICU with 20 beds at a tertiary children's hospital. Patients A total of 57 patients aged younger than 16 years who received liver transplantation and were admitted to the PICU after surgery. Interventions EM project, a multifaceted framework for successful EM practice in the PICU focusing on a multidisciplinary team approach. Measurements and Main Results Compared with the period before the implementation of the EM project, there was a significant increase in the proportion of patients who received physical therapy in the PICU (43 vs. 97%, p < 0.001). Also, there were greater median numbers of physical therapy per eligible patient (0 vs. 3, p < 0.001). Moreover, patients achieved higher functional mobility level within a shorter time. Length of intubation, PICU stay, and hospital stay were not significantly different. There were no adverse events or deaths. Conclusion Using an EM project process, the proportion of patients who received physical therapy after liver transplantation increased. However, there was no difference in the length of PICU or hospital stay. Our findings indicated that EM for pediatric patients who received liver transplantation was well tolerated and safe.

Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis

To determine if omalizumab (anti-IgE) above the standard dosing ranges can be beneficial in severe asthmatics and compare responses to patients who are within normal dosing ranges.In Australia, most patients receiving government-funded omalizumab are enrolled in the Australian Xolair Registry. This registry includes 21 sites, with patients ≥12 years old who have severe, uncontrolled asthma; patients with serum IgE levels ≥76 IU/mL; and patients who have failed to achieve adequate control with optimized asthma therapy.Registry data were obtained (including demographics, medical history, disease status and control, current treatment, lung function, medical resource use, and patient-reported outcomes) by using the Asthma Control Questionnaire (ACQ-5) and the Asthma Quality of Life Questionnaire (AQLQ). Patients were assessed at 6, 12, 18, and 24 months after starting omalizumab. Participants were classified according to their baseline weight and/or IgE level and whether these variables were above or within the standard dosing table (Australia and the US use the same dosing tables). The primary outcome measured was the change in symptom control as measured by the ACQ-5. Secondary outcomes measured were changes in the AQLQ mean score and pre- and postbronchodilator forced expiratory volume in 1 second (FEV1). In a small portion of patients, changes in hospital admissions and exacerbations were also evaluated.A total of 179 participants were included, with 55 (31%) dosing above the standard dosing and 124 (69%) within standard dosing. Above-range participants had higher baseline IgE levels (812 IU/mL; range 632–1747) compared with in-range participants (209 IU/mL; range 134–306). Baseline AQLQ scores were significantly lower for above-range asthmatics versus in-range patients (3.21 [SD 1.14] vs 4.01 [SD 1.21, P = .02]). Above-range participants received a median dose of omalizumab of 750 mg (IQR 650–750) compared with in-range participants who received a median dose of 450 mg (IQR 300–600). After 6 months of therapy, there was a statistically significant improvement in ACQ-5 scores for both the above-range group (3.61 to 2.10, P < .0001) and the in-range group (3.47 to 1.93, P < .0001). AQLQ also reflected statistical improvement for both groups (above-range group: 3.22 to 4.41; in-range group: 3.71 to 4.88, P < .0001). Above-range participants demonstrated statistically significant improvements in pre- and postbronchodilator FEV1 that were similar to the changes seen for the in-range participants. There was no difference in the exacerbation rate for either group.Omalizumab dosing (750 mg monthly) in severe asthmatic patients who are above established criteria because of weight or baseline IgE levels demonstrate significantly improved symptom control, quality of life measures, and lung function, and these improvements are similar to changes seen in individuals treated with in-range doses.These results provide literature support for above-range dosing of omalizumab (Xolair) for severe asthmatic patients. According to EPR-3 for asthma management, severe allergic asthmatic patients who are poorly controlled on combination therapy are good candidates for targeted therapy with this monoclonal antibody. Dose and frequency of omalizumab in the US are based on weight and total IgE level, leading to a higher calculated dose for patients with either a higher starting IgE level or elevated body weight. Patients with severe persistent asthma who are highly atopic experience significant costs and morbidity, with decreased options for asthma treatment if their IgE level is too high. Additional studies of omalizumab dosing for this group of patients are needed to further support its benefit.

Background. Pneumonia is one of the leading causes of under-5 death in South Africa and accounts for a substantial burden of paediatric intensive care unit (PICU) admissions. However, little is known about PICU outcomes in HIV-exposed uninfected (HIV-EU) children with pneumonia, despite the growing size of this vulnerable population.Objectives. To determine whether HIV exposure without infection is an independent risk factor for mortality and morbidity in childrenadmitted to PICU with pneumonia.Methods. This retrospective review included all patients with pneumonia admitted to the PICU at Chris Hani Baragwanath AcademicHospital between 1 January 2013 and 31 December 2014. Patients were classified as HIV-unexposed (HIV-U), HIV-EU and HIV-infected.Medical records were reviewed to determine survival to PICU discharge, duration of PICU admission and duration of mechanicalventilation. Survival analysis was used to determine the association between HIV infection/exposure with mortality, and linear regression was used to examine the association with length of stay and duration of mechanical ventilation. This study included 107 patients: 54 were HIV-U; 28 were HIV-EU; 23 HIV-positive; and 2 had an unknown HIV status.Results. Overall, 84% (n=90) survived to PICU discharge, with no difference in survival based on HIV infection or exposure. Both HIV-EUand HIV-U children had significantly shorter PICU admissions and fewer days of mechanical ventilation compared with HIV-infectedchildren (p=0.011 and p=0.004, respectively).Conclusion. HIV-EU children behaved similarly to HIV-U children in terms of mortality, duration of PICU admission and length ofmechanical ventilation. HIV infection was associated with prolonged length of mechanical ventilation and ICU stay but not increasedmortality

Important Outcomes for Parents of Critically Ill Children.

Undernutrition at PICU Admission Is Predictor of 60-Day Mortality and PICU Length of Stay in Critically Ill Children

BackgroundAnemia is prevalent at pediatric intensive care unit (PICU) admission and incident during PICU stay, but little is known about anemia at PICU discharge. Anemia after critical illness is an important issue because it could impact post-PICU outcome. We aimed to estimate the prevalence of anemia at PICU discharge and to determine its risk markers.MethodsThis is an ancillary study of a prospective observational study on transfusion practices conducted in the PICU of a tertiary care children’s hospital. All children consecutively admitted to the PICU during a 1-year period were considered for inclusion. Data were prospectively collected from medical charts, except for hemoglobin (Hb) levels at PICU and hospital discharge that were collected retrospectively. Anemia was defined by an Hb concentration below the lower limit of the normal range for age.ResultsAmong the 679 children retained for analysis, 390 (57.4%) were anemic at PICU discharge. After multivariate adjustment, anemia at PICU admission was the strongest risk marker of anemia at PICU discharge. The strength of this association varied according to age (interaction): The odds ratio (OR) (95% CI) of anemia at PICU discharge was 4.85 (1.67–14.11) for 1–5-month-old infants anemic versus not anemic at PICU admission, and it was 73.13 (13.43, 398.19) for adolescents anemic versus not anemic at PICU admission. Children admitted after a non-cardiac surgery had an increased risk of anemia at PICU discharge [OR 2.30 (1.37, 3.88), p = 0.002]. The proportion of anemic children differed between age categories, while the median Hb level did not exhibit significant variations according to age.ConclusionsAnemia is highly prevalent at PICU discharge and is strongly predicted by anemia at PICU admission. The usual age-based definitions of anemia may not be relevant for critically ill children. The consequences of anemia at PICU discharge are unknown and deserve further scrutiny.

BackgroundResearch on pediatric intensive care unit (PICU) readmission is lacking in China. This study was conducted to describe the risk factors associated with PICU readmission within 1 year after PICU discharge.MethodsThis retrospective case-control study included patients aged from 1 month to 16 years who were discharged between January 2018 and May 2020. The case group included readmitted patients with two or more PICU admissions within 1 year during the study period. The control group included survivors with only one PICU admission during the same study period, and the controls were matched on age and sex. Demographic and clinical variables were collected from the electronic administrative database. Risk factors were analyzed by univariate and multivariate analyses.ResultsFrom January 2018 to May 2020, 2,529 patients were discharged from the PICU, and 103 (4.07%) were readmitted within 1 year. In the univariate analysis, PICU readmission within 1 year was associated with lower weight, the presence of chronic conditions, a higher StrongKids score on admission, length of PICU stay of more than 2 weeks, the presence of dysfunction at discharge, sedation medications use, vasopressor use, and invasive mechanical ventilation in the first PICU stay. Patients had a higher StrongKids score as a surrogate for increased risk of malnutrition. In the multivariate analysis, the factors most significantly associated with PICU readmission within 1 year were the presence of chronic conditions, a higher StrongKids score on admission, and length of PICU stay of more than 2 weeks in the first PICU stay. In the subgroup analysis, compared with the control group, the factors most significantly associated with readmission within 48 h of discharge were the presence of chronic conditions, a higher StrongKids score on admission, and vasopressor use during the first PICU stay. The mortality rate was 8.74% (9/103) in patients with PICU readmission. The overall PICU mortality rate was 7.39% (201/2,721) during the study period.ConclusionsPatients with chronic conditions, a higher StrongKids score on admission, and length of PICU stay of more than 2 weeks were at much higher risk for PICU readmission within 1 year. Patients with vasopressor use during the first PICU hospitalization were more likely to be readmitted within 48 h of discharge.

Introduction: Hidradenitis suppurativa is a chronic inflammatory skin disease with a typical formation of inflamed nodules, abscesses, and sinus tracts usually in the axillary, inguinal, and anogenital region. We decided to investigate the possible association of hidradenitis suppurativa and total IgE elevation and to explore the patients’ characteristics which can be related to high IgE levels. Methods: We performed a retrospective observational study which included 67 patients with moderate-to-severe stage of hidradenitis suppurativa followed up in our outpatient dermatology department. Total IgE, IgA, IgG, IgM, and CRP serum levels were measured. A personal and family history was taken. We asked them about allergic diseases and cigarette smoking and determined the basic parameters such as the weight and height of the patients. Results: Elevated total IgE levels were noticed in 21 patients (31.3%), of which 6 had a history of allergic disorder. Three of them had allergic rhinoconjunctivitis and the other three were suffering from atopic dermatitis. The mean total IgE level was 203.0 IU/ml with a maximum value of 1,954 IU/ml. Analysis of the factors, such as cigarette smoking, sex, elevated CRP, body mass index, and the number of affected areas, did not show an association with increased IgE levels. Conclusion: Our study showed a higher mean value of total IgE in patients with moderate to severe hidradenitis suppurativa than in the general population. However, we did not confirm an association with any characteristics of the patients. Limitations of this work include a small number of patients and a lack of the control group, therefore further and more extensive studies are needed to support these results.

ABSTRACTIntroductionNearly 40% of hospitalised oncology patients are admitted to the paediatric intensive care unit (PICU). Clinicians utilise serum lactate as a biomarker to guide resuscitation and ongoing management of critically ill children. The significance of raised serum lactate remains unknown in oncology patients. Those who require an admission to the PICU have relatively poorer outcomes compared to those only managed on hospital wards, where there may be an increased tendency to apply additional interventions to normalise lactate. We assessed the association between serum lactate and the length of stay in PICU in paediatric oncology patients.Patients and MethodsWe conducted a retrospective observational study of patients admitted to the oncology service, who had at least one PICU admission, at a tertiary children's hospital between 2015 and 2020. The outcome was PICU length of stay (LOS). Multilevel regression modelling assessed the association between lactate measured at PICU admission and PICU LOS, controlling for patient demographic and clinical covariates.ResultsThere were 633 admissions to PICU from 426 children. Of these 633 admissions, 197 (31.1%) had hyperlactatemia (serum lactate ≥ 2 mmol/L) on admission, 229 (36.2%) had normal lactate levels (< 2 mmol/L) and the remaining 207 (32.7%) did not have lactate measured on admission. Of the 426 patients, 292 (68.5%) were diagnosed with solid tumour, 82 (19.2%) hematologic malignancy, and 52 (12.2%) had received a bone marrow transplant (BMT). The median PICU length of stay was 29 h (interquartile range 21, 68). Hyperlactatemia was associated with an average 1.25‐fold (95% CI [1.04, 1.51]) increase in PICU LOS when we assumed that missing lactate indicated absence of hyperlactatemia. Interaction effects revealed that this association was only present in the solid tumour group. In sensitivity analyses including only admissions with measured lactate, this effect was reduced and no longer significant (β 1.20, 95% CI [0.99, 1.46]).ConclusionAfter adjusting for clinical and demographic covariates, increased lactate at PICU admission was associated with PICU LOS in paediatric solid tumour patients. While further larger prospective studies are required, serum lactate levels may serve as a predictive biomarker for PICU length of stay in children with solid tumours.

In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Goday et al (1) report on the outcomes of children with acute pancreatitis discharged from the Pediatric Intensive Care Units (PICU) using a multicenter database, Virtual PICU Systems (VPS)LLC. They found that mortality from acute pancreatitis was rare compared to the adult series. Recent studies estimate the annual incidence of pediatric acute pancreatitis similar to the rates reported in adults (2). Most children with acute pancreatitis have a mild course (3, 4). In a subset of patients, the disease becomes severe with the emergence of local and systemic complications (i.e. peripancreatic fluid collections, single or multiple organ failure) (5). Adults who develop persistent organ failure and/or infected pancreatic necrosis are at increased risk of death from acute pancreatitis (35-50%) (6). The overall outcomes are better in children compared to adults: the death rate from acute pancreatitis is less than 10% in children and associated with severe disease and presence of systemic complications (3, 4, 7). In children, the etiologies of acute pancreatitis are diverse. Biliary/obstructive factors, medications and multisystem diseases are the main causes of acute pancreatitis in the pediatric age group (3, 4, 8). Goday et al (1) focused their questions on the outcome of children admitted to PICU with acute pancreatitis, utilizing VPS. VPS is a clinical database with over 110 hospital members who collect information from all PICU admissions, including demographics, discharge diagnoses (primary and secondary), interventions, severity of illness scores and mortality data. The authors used two severity of illness scores: Pediatric Index of Mortality-2 (PIM2, based on data obtained at the time of PICU admission) and PRISM III scores (based on data obtained during the first 24 hours of PICU admission). Other outcome measures included PICU length of stay, incidence and duration of mechanical ventilation and mortality rate. Of the 360,612 PICU discharges over a 4 year-period, they analyzed 2,076 patients with the diagnosis of acute pancreatitis. In 331 patients, acute pancreatitis was the primary diagnosis; in 1,695 patients, acute pancreatitis was a secondary diagnosis (other diagnoses were also present). The authors found a low mortality rate in children who were admitted to PICU with acute pancreatitis as the primary diagnosis (0.3%, only 1 patient died) compared to children with secondary acute pancreatitis (6.8%). Children with primary acute pancreatitis had lower PIM2 and PRISM III scores, shorter PICU stays and fewer days of mechanical ventilation compared to the secondary acute pancreatitis group. The data from this large cohort of patients confirm the findings in other single-center pediatric studies that reported similar mortality rates that were mostly related to multisystem disease rather than acute pancreatitis alone (3, 4). Whether it was a primary or secondary diagnosis, the mortality rate from acute pancreatitis in children is much lower compared to the adult population. There are limitations in our understanding of pediatric pancreatitis and the reasons why the mortality rate is lower in children compared to adults. Goday et al (1) were not able to study whether this striking difference is due to fewer cases of severe acute pancreatitis in children. They were not able to assess the etiologies of acute pancreatitis nor evaluate for the presence of complications and disease severity. It is also not known whether patients with acute pancreatitis were diagnosed using well-established criteria (9) or they were all uniformly in critical condition to be admitted to the PICU at all centers. It is possible that the diagnosis of acute pancreatitis was missed or inaccurate. The database did also not allow the authors to determine whether acute pancreatitis was present upon admission or developed during the course of PICU stay. Nevertheless, the study analyzes a large group of children admitted to PICU and reports that acute pancreatitis possibly has a different course in children with lower mortality rates compared to adults. The authors found that the weight z scores were much higher in patients with primary acute pancreatitis compared to the secondary acute pancreatitis group. Therefore, the obesity did not seem to correlate with disease mortality as observed in adults (10). However, it is not known whether obesity is associated with disease severity in pediatric acute pancreatitis. Large pediatric inpatient databases are useful in understanding relatively rare diseases by defining demographics, assessing for comorbidities, identifying disease burden and evaluating national trends. Goday et al (1) followed a strategy similar to a recent study that utilized the Healthcare Cost and Utilization Projects Kids' Inpatient Database (HCUP-KID) to demonstrate an increased incidence and disease burden of pediatric acute pancreatitis (7). The data are not collected prospectively or with the study question in mind, therefore may not be suitable for a thorough analysis. Future studies should include a multicenter, prospective design to analyze the epidemiology and severity of acute pancreatitis, its outcomes and disease predictors in children.

Arrhythmias are common in patients admitted to the paediatric intensive care unit. We sought to identify the rates of occurrence and types of arrhythmias, and determine whether an arrhythmia was associated with illness severity and paediatric intensive care unit length of stay. This is a prospective, observational study of all patients admitted to the paediatric intensive care unit at the Children's Hospital at Montefiore from March to June 2012. Patients with cardiac disease or admitted for the treatment of primary arrhythmias were excluded. Clinical and laboratory data were collected and telemetry was reviewed daily. Tachyarrhythmias were identified as supraventricular tachycardia, ventricular tachycardia, and arrhythmias causing haemodynamic compromise or for which an intervention was performed. A total of 278 patients met the inclusion criteria and were analysed. There were 97 incidences of arrhythmia in 53 patients (19%) and six tachyarrhythmias (2%). The most common types of arrhythmias were junctional rhythm (38%), premature atrial contractions (24%), and premature ventricular contractions (22%). Tachyarrhythmias included three supraventricular tachycardia (50%) and three ventricular tachycardia (50%). Of the six tachyarrhythmias, four were related to placement or migration of central venous lines and two occurred during aminophylline infusion. Patients with an arrhythmia had longer duration of mechanical ventilation and paediatric intensive care unit stay (p<0.001). In multivariate analysis, central venous lines (odds ratio 3.1; 95% confidence interval 1.3-7.2, p=0.009) and aminophylline use (odds ratio 5.1; 95% confidence interval 1.7-14.9, p=0.003) were independent predictors for arrhythmias. Arrhythmias were common in paediatric intensive care unit patients (19%), although tachyarrhythmias occurred rarely (2%). Central venous lines and use of aminophylline were identified as two clinical factors that may be associated with development of an arrhythmia.

Risk Factors and Outcomes Related to Pediatric Intensive Care Unit Admission after Hematopoietic Stem Cell Transplantation: A Single-Center Experience

Severity and organ dysfunction (OD) scores are increasingly used in pediatric intensive care units (PICU). Therefore, this review aims to provide 1/ an updated state-of-the-art of severity scoring systems and OD scores in pediatric critical care, which explains 2/ the performance measurement tools and the significance of each tool in clinical practice and provides 3/ the usefulness, limits, and impact on future scores in PICU. The following two pediatric systems have been proposed: the PRISMIV, is used to collect data between 2 h before PICU admission and the first 4 h after PICU admission; the PIM3, is used to collect data during the first hour after PICU admission. The PELOD-2 and SOFApediatric scores were the most common OD scores available. Scores used in the PICU should help clinicians answer the following three questions: 1/ Are the most severely ill patients dying in my service: a good discrimination allow us to interpret that there are the most severe patients who died in my service. 2/ Does the overall number of deaths observed in my department consistent with the severity of patients? The standard mortality ratio allow us to determine whether the total number of deaths observed in our service over a given period is in adequacy with the number of deaths predicted, by considering the severity of patients on admission? 3/ Does the number of deaths observed by severity level in my department consistent with the severity of patients? The calibration enabled us to determine whether the number of deaths observed according to the severity of patients at PICU admission in a department over a given period is in adequacy with the number of deaths predicted, according to the severity of the patients at PICU admission. These scoring systems are not interpretable at the patient level. Scoring systems are used to describe patients with PICU in research and evaluate the service's case mix and performance. Therefore, the prospect of automated data collection, which permits their calculation, facilitated by the computerization of services, is a necessity that manufacturers should consider.