Dataset Information

Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome.

ABSTRACT:

Objectives

Infectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respiratory distress syndrome is unknown. We aimed to characterize the epidemiology of viral pneumonia in pediatric acute respiratory distress syndrome and compare characteristics and outcomes between pneumonia subjects with and without viruses. Secondarily, we examined the association between specific viruses and outcomes.

Design

We performed a secondary analysis of a prospectively enrolled pediatric acute respiratory distress syndrome cohort. Subjects with pneumonia acute respiratory distress syndrome underwent testing of respiratory secretions for viruses and culture for bacteria and fungi and were stratified according to presence or absence of a virus.

Setting

Tertiary care children's hospital.

Patients

Children with acute respiratory distress syndrome.

Interventions

None.

Measurements and main results

Of 544 children with acute respiratory distress syndrome, 282 (52%) had pneumonia as their inciting etiology, of whom 212 were virus-positive. In 141 of 282 (50%) pneumonia acute respiratory distress syndrome cases, a virus was the sole pathogen identified. Virus-positive pneumonia had fewer organ failures but worse oxygenation, relative to virus-negative pneumonia, with no differences in antibiotic use, ventilator duration, or mortality. Subjects with respiratory syncytial virus-associated acute respiratory distress syndrome had lower mortality (0%), and subjects with influenza-associated acute respiratory distress syndrome had shorter ventilator duration, relative to other viral acute respiratory distress syndrome. Nonadeno herpesviruses, tested for exclusively in immunocompromised subjects, had greater than 80% mortality.

Conclusions

Pneumonia was the most common cause of pediatric acute respiratory distress syndrome, and viruses were commonly isolated as the sole pathogen. Respiratory syncytial virus and influenza were associated with better outcomes relative to other viral etiologies. Viral pneumonias in immunocompromised subjects, particularly nonadeno herpesviruses, drove the mortality rate for pneumonia acute respiratory distress syndrome. Specific viral etiologies are associated with differential outcomes in pediatric acute respiratory distress syndrome and should be accounted for in future studies.

SUBMITTER: Roberts AL

PROVIDER: S-EPMC6726524 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome.

Roberts Anna L AL Sammons Julia S JS Mourani Peter M PM Thomas Neal J NJ Yehya Nadir N

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20190901 9

<h4>Objectives</h4>Infectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respiratory distress syndrome is unknown. We aimed to characterize the epidemiology of viral pneumonia in pediatric acute respiratory distress syndrome and compare characteristics and outcomes between pneumonia subjects with and without viruses. Secondarily, we examined the association bet ...[more]

PMID: 31246746

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Project description:ObjectivesPediatric acute respiratory distress syndrome is heterogeneous, with a paucity of risk stratification tools to assist with trial design. We aimed to develop and validate mortality prediction models for patients with pediatric acute respiratory distress syndrome.DesignLeveraging additional data collection from a preplanned ancillary study (Version 1) of the multinational Pediatric Acute Respiratory Distress syndrome Incidence and Epidemiology study, we identified predictors of mortality. Separate models were built for the entire Version 1 cohort, for the cohort excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths. Models were externally validated in a cohort of intubated pediatric acute respiratory distress syndrome patients from the Children's Hospital of Philadelphia.SettingThe derivation cohort represented 100 centers worldwide; the validation cohort was from Children's Hospital of Philadelphia.PatientsThere were 624 and 640 subjects in the derivation and validation cohorts, respectively.InterventionsNone.Measurements and main resultsThe model for the full cohort included immunocompromised status, Pediatric Logistic Organ Dysfunction 2 score, day 0 vasopressor-inotrope score and fluid balance, and PaO2/FIO2 6 hours after pediatric acute respiratory distress syndrome onset. This model had good discrimination (area under the receiver operating characteristic curve 0.82), calibration, and internal validation. Models excluding neurologic deaths, for intubated subjects, and for intubated subjects excluding neurologic deaths also demonstrated good discrimination (all area under the receiver operating characteristic curve ≥ 0.84) and calibration. In the validation cohort, models for intubated pediatric acute respiratory distress syndrome (including and excluding neurologic deaths) had excellent discrimination (both area under the receiver operating characteristic curve ≥ 0.85), but poor calibration. After revision, the model for all intubated subjects remained miscalibrated, whereas the model excluding neurologic deaths showed perfect calibration. Mortality models also stratified ventilator-free days at 28 days in both derivation and validation cohorts.ConclusionsWe describe predictive models for mortality in pediatric acute respiratory distress syndrome using readily available variables from day 0 of pediatric acute respiratory distress syndrome which outperform severity of illness scores and which demonstrate utility for composite outcomes such as ventilator-free days. Models can assist with risk stratification for clinical trials.

Project description:ObjectivesTo test whether plasma interleukin-1 receptor antagonist or variants within the gene encoding for interleukin-1ra (IL1RN), or proteins involved in regulating interleukin-1β levels or interleukin-1β response, are associated with pediatric acute respiratory distress syndrome or outcomes in mechanically ventilated children with parenchymal lung disease.DesignProspective cohort study.SettingTwenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622).SubjectsChildren 2 weeks to 17 years old treated with invasive mechanical ventilation for acute airways and/or parenchymal lung disease.Measurements and main resultsThree-hundred seventy-eight of 549 patients had pediatric acute respiratory distress syndrome; DNA and plasma were obtained from 523 of 549 and 480 of 549 patients, respectively. Plasma interleukin-1ra was highest on the day of intubation (day 0) and decreased over the subsequent 3 days (p < 0.0001). Interleukin-1ra level was higher in patients with pediatric acute respiratory distress syndrome than those without pediatric acute respiratory distress syndrome (p < 0.0001). Multivariable regression analysis of data across all days demonstrated a significant association of interleukin-1ra (odds ratio, 1.30; 95% CI, 1.10-1.52; p = 0.002) and day (p < 0.05) with pediatric acute respiratory distress syndrome, independent of age and Pediatric Risk of Mortality-III score. Analysis on individual days indicated that plasma interleukin-1ra levels were associated with pediatric acute respiratory distress syndrome on days 0 and 2, independent of age and Pediatric Risk of Mortality-III score (p = 0.04 and 0.003, respectively), however did not quite reach significance on days 1 and 3 (p = 0.06 and 0.07, respectively). Interleukin-1ra was independently associated with mortality on day 1 (p = 0.02). Interleukin-1ra also correlated with length of mechanical ventilation, measures of oxygenation, and PICU length of stay. No genetic variants were associated with pediatric acute respiratory distress syndrome.ConclusionsPlasma interleukin-1ra is associated with pediatric acute respiratory distress syndrome, PICU length of stay, length of mechanical ventilation, and mortality in children with acute respiratory failure requiring mechanical ventilation.

Project description:ObjectivesTo determine whether weight extremes impact clinical outcomes in pediatric acute respiratory distress syndrome.DesignPost hoc analysis of a cohort created by combining five multicenter pediatric acute respiratory distress syndrome studies.SettingForty-three academic PICUs worldwide.PatientsA total of 711 subjects prospectively diagnosed with pediatric acute respiratory distress syndrome.InterventionSubjects more than 2 years were included and categorized by Center for Disease Control and Prevention body mass index z score criteria: underweight (< -1.89), normal weight (-1.89 to +1.04), overweight (+1.05 to +1.64), and obese (≥ +1.65). Subjects were stratified by direct versus indirect lung injury leading to pediatric acute respiratory distress syndrome. The primary outcome was in-hospital mortality. In survivors, secondary analyses included duration of mechanical ventilation and ICU length of stay.Measurements and main resultsA total of 331 patients met inclusion criteria; 12% were underweight, 50% normal weight, 11% overweight, and 27% obese. Overall mortality was 20%. By multivariate analysis, body mass index category was independently associated with mortality (p = 0.004). When stratified by lung injury type, there was no mortality difference between body mass index groups with direct lung injury; however, in the indirect lung injury group, the odds of mortality in the obese were significantly lower than normal weight subjects (odds ratio, 0.11; 95% CI, 0.02-0.84). Survivors with direct lung injury had no difference in the duration of mechanical ventilation or ICU length of stay; however, those with indirect lung injury, the overweight required longer duration of mechanical ventilation than other groups (p < 0.001).ConclusionsThese data support the obesity paradox in pediatric acute respiratory distress syndrome. Obese children with indirect lung injury pediatric acute respiratory distress syndrome have a lower risk of mortality. Importantly, among survivors, the overweight with indirect lung injury requires longer duration of mechanical ventilation. Our data require prospective validation to further elucidate the pathobiology of this phenomenon.

Project description:ObjectivesCirculating nucleosomes and their component histones have been implicated as pathogenic in sepsis and acute respiratory distress syndrome in adults. However, their role in pediatric acute respiratory distress syndrome is unknown.DesignWe performed a prospective cohort study in children with acute respiratory distress syndrome, with plasma collection within 24 hours of acute respiratory distress syndrome onset. We associated nucleosome levels with severity of acute respiratory distress syndrome and with nonpulmonary organ failures and tested for association of nucleosomes with PICU mortality and ventilator-free days at 28 days in univariate and multivariable analyses. We also performed proteomics of DNA-bound plasma proteins in a matched case-control study of septic children with and without acute respiratory distress syndrome in order to identify specific histone proteins elevated in acute respiratory distress syndrome.SettingLarge academic tertiary-care PICU.PatientsIntubated children meeting Berlin criteria for acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsWe enrolled 333 children with acute respiratory distress syndrome, with 69 nonsurvivors (21%). Plasma nucleosomes were correlated with acute respiratory distress syndrome severity and with the number of nonpulmonary organ failures at acute respiratory distress syndrome onset. Nucleosomes were higher (p < 0.001) in nonsurvivors (0.40 [interquartile range, 0.20-0.71] arbitrary units) relative to survivors (0.10 [interquartile range, 0.04-0.25] arbitrary units). Nucleosomes were associated with PICU mortality in multivariable analysis (adjusted odds ratio 1.84 per 1 sd increase; 95% CI, 1.38-2.45; p < 0.001). Nucleosomes were also associated with a lower probability of being extubated alive by day 28 after multivariable adjustment (adjusted subdistribution hazard ratio, 0.74; 95% CI, 0.63-0.88; p = 0.001). Proteomic analysis demonstrated higher levels of the core nucleosome histones H2A, H2B, H3, and H4 in septic children with acute respiratory distress syndrome, relative to septic children without acute respiratory distress syndrome.ConclusionsPlasma nucleosomes are associated with acute respiratory distress syndrome severity, nonpulmonary organ failures, and worse outcomes in pediatric acute respiratory distress syndrome.

Project description:ObjectivesTo summarize the evidence for the Second Pediatric Acute Lung Injury Consensus Conference-2 (PALICC-2) recommendations for assessment of outcomes among patients surviving pediatric acute respiratory distress syndrome (PARDS).Data sourcesMEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost).Study selectionWe conducted a scoping review to identify studies evaluating outcomes following PARDS. We included studies of survivors of PARDS, acute respiratory failure with a high proportion of PARDS patients, or other critical illnesses if PARDS-specific outcomes could be extracted.Data extractionTitle/abstract review, full-text review, and data extraction using a standardized data collection form.Data synthesisThe Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. Of 8,037 abstracts screened, we identified 20 articles for inclusion. Morbidity following PARDS was common and affected multiple domains of pulmonary and nonpulmonary function. There was insufficient evidence to generate any evidence-based recommendations. We generated eight good practice statements and five research statements. A panel of 52 experts discussed each proposed good practice statement and research statement, and the agreement rate was measured with an online voting process. Good practice statements describe the approach to clinical outcome assessment, assessment of pulmonary outcomes of children surviving PARDS, and assessment of nonpulmonary outcomes of children surviving PARDS including health-related quality of life and physical, neurocognitive, emotional, family, and social functioning. The five research statements relate to assessment of patient preillness status, use of postdischarge endpoints for clinical trials, the association between short-term and longer term outcomes, the trajectory of recovery following PARDS, and practices to optimize follow-up.ConclusionsThere is increasing evidence that children are at risk for impairments across a range of pulmonary and nonpulmonary health domains following hospitalization for PARDS. The results of this extensive scoping review and consensus conference involving experts in PARDS research, clinical care, and outcomes assessment provide guidance to clinicians and researchers on postdischarge follow-up to optimize the long-term health of patients surviving PARDS.

Project description:ObjectivesTo describe mechanical ventilation management and factors associated with nonadherence to lung-protective ventilation principles in pediatric acute respiratory distress syndrome.DesignA planned ancillary study to a prospective international observational study. Mechanical ventilation management (every 6 hr measurements) during pediatric acute respiratory distress syndrome days 0-3 was described and compared with Pediatric Acute Lung Injury Consensus Conference tidal volume recommendations (< 7 mL/kg in children with impaired respiratory system compliance, < 9 mL/kg in all other children) and the Acute Respiratory Distress Syndrome Network lower positive end-expiratory pressure/higher Fio2 grid recommendations.SettingSeventy-one international PICUs.PatientsChildren with pediatric acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsAnalyses included 422 children. On pediatric acute respiratory distress syndrome day 0, median tidal volume was 7.6 mL/kg (interquartile range, 6.3-8.9 mL/kg) and did not differ by pediatric acute respiratory distress syndrome severity. Plateau pressure was not recorded in 97% of measurements. Using delta pressure (peak inspiratory pressure - positive end-expiratory pressure), median tidal volume increased over quartiles of median delta pressure (p = 0.007). Median delta pressure was greater than or equal to 18 cm H2O for all pediatric acute respiratory distress syndrome severity levels. In severe pediatric acute respiratory distress syndrome, tidal volume was greater than or equal to 7 mL/kg 62% of the time, and positive end-expiratory pressure was lower than recommended by the positive end-expiratory pressure/Fio2 grid 70% of the time. In multivariable analysis, tidal volume nonadherence was more common with severe pediatric acute respiratory distress syndrome, fewer PICU admissions/yr, non-European PICUs, higher delta pressure, corticosteroid use, and pressure control mode. Adherence was associated with underweight stature and cuffed endotracheal tubes. In multivariable analysis, positive end-expiratory pressure/Fio2 grid nonadherence was more common with higher pediatric acute respiratory distress syndrome severity, ventilator decisions made primarily by the attending physician, pre-ICU cardiopulmonary resuscitation, underweight stature, and age less than 2 years. Adherence was associated with respiratory therapist involvement in ventilator management and longer time from pediatric acute respiratory distress syndrome diagnosis. Higher nonadherence to tidal volume and positive end-expiratory pressure recommendations were independently associated with higher mortality and longer duration of ventilation after adjustment for confounding variables. In stratified analyses, these associations were primarily influenced by children with severe pediatric acute respiratory distress syndrome.ConclusionsNonadherence to lung-protective ventilation principles is common in pediatric acute respiratory distress syndrome and may impact outcome. Modifiable factors exist that may improve adherence.

Project description:ObjectivesThe trajectory and importance of right ventricular systolic function and pulmonary hypertension during the course of pediatric acute respiratory distress syndrome are unknown. We hypothesized that new or persistent right ventricular systolic dysfunction and pulmonary hypertension would be associated with worse patient outcomes.DesignRetrospective, single-center cohort study.SettingTertiary care, university-affiliated PICU.PatientsChildren who had at least two echocardiograms less than 8 days following pediatric acute respiratory distress syndrome diagnosis.InterventionsNone.Measurements and main resultsBetween July 1, 2012, and April 30, 2018, 74 children met inclusion criteria. The first echocardiogram was performed a median of 0.61 days (interquartile range, 0.36-0.94 d) and the second echocardiogram was performed a median of 2.57 days (interquartile range, 1.67-3.63 d) after pediatric acute respiratory distress syndrome diagnosis. Univariate analyses showed that new or persistent right ventricular systolic dysfunction as defined by global longitudinal strain or free wall strain was associated with a greater number of ICU days in survivors (global longitudinal strain p = 0.04, free wall strain p = 0.04), lower ventilator-free days at 28 days (global longitudinal strain p = 0.03, free wall strain p = 0.01), and higher rate of PICU death (global longitudinal strain p = 0.046, free wall strain p = 0.01). Mixed-effects multivariate modeling showed that right ventricular global longitudinal strain and right ventricular fractional area change stayed relatively constant over the course of the first 8 days in nonsurvivors and that there was a linear improvement in global longitudinal strain (p = 0.037) and fractional area change (p = 0.05) in survivors. Worsening right ventricular dysfunction at the time of repeat echocardiogram as defined by global longitudinal strain and free wall strain were independently associated with decreased probability of extubation (subdistribution hazard ratio, 0.30 [0.14-0.67]; p = 0.003 and subdistribution hazard ratio, 0.47 [0.23-0.98]; p = 0.043, respectively). In univariate and multivariate analyses, pulmonary hypertension had no significant associations with outcomes in his cohort.ConclusionsNew or persistent right ventricular systolic dysfunction over the first week following pediatric acute respiratory distress syndrome onset is associated with worse patient outcomes, including decreased probability of extubation and higher PICU mortality.

Dataset Information

Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome.

Objectives

Design

Setting

Patients

Interventions

Measurements and main results

Conclusions

Publications

Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome.

Similar Datasets

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