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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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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:OBJECTIVES:To determine whether weight extremes impact clinical outcomes in pediatric acute respiratory distress syndrome. DESIGN:Post hoc analysis of a cohort created by combining five multicenter pediatric acute respiratory distress syndrome studies. SETTING:Forty-three academic PICUs worldwide. PATIENTS:A total of 711 subjects prospectively diagnosed with pediatric acute respiratory distress syndrome. INTERVENTION:Subjects 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 RESULTS:A 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). CONCLUSIONS:These 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:OBJECTIVES:The prevalence and importance of early right ventricular dysfunction and pulmonary hypertension in pediatric acute respiratory distress syndrome are unknown. We aimed to describe the prevalence of right ventricular dysfunction and pulmonary hypertension within 24 hours of pediatric acute respiratory distress syndrome diagnosis and their associations with outcomes. DESIGN:Retrospective, single-center cohort study. SETTING:Tertiary care, university-affiliated PICU. PATIENTS:Children who had echocardiograms performed within 24 hours of pediatric acute respiratory distress syndrome diagnosis. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Between July 1, 2012, and June 30, 2016, 103 children met inclusion criteria. Echocardiograms were analyzed using established indices of right ventricular and left ventricular systolic function and for evidence of pulmonary hypertension. Echocardiographic abnormalities were common: 26% had low right ventricular fractional area change, 65% had low tricuspid annular plane systolic excursion, 30% had low left ventricular fractional shortening, and 21% had evidence of pulmonary hypertension. Abnormal right ventricular global longitudinal strain and abnormal right ventricular free wall strain were present in 35% and 40% of patients, respectively. No echocardiographic variables differed between or across pediatric acute respiratory distress syndrome severity. In multivariable analyses, right ventricular global longitudinal strain was independently associated with PICU mortality (odds ratio, 3.57 [1.33-9.60]; p = 0.01), whereas right ventricular global longitudinal strain, right ventricular free wall strain, and the presence of pulmonary hypertension were independently associated with lower probability of extubation (subdistribution hazard ratio, 0.46 [0.26-0.83], p = 0.01; subdistribution hazard ratio, 0.58 [0.35-0.98], p = 0.04; and subdistribution hazard ratio, 0.49 [0.26-0.92], p = 0.03, respectively). CONCLUSIONS:Early ventricular dysfunction and pulmonary hypertension were detectable, prevalent, and independent of lung injury severity in children with pediatric acute respiratory distress syndrome. Right ventricular dysfunction was associated with PICU mortality, whereas right ventricular dysfunction and pulmonary hypertension were associated with lower probability of extubation.

Project description:ObjectivesThere is limited evidence on the impact of protocolized ventilator weaning in pediatric acute respiratory distress syndrome, despite utilization in clinical trials and clinical care. We aimed to determine whether protocolized ventilator weaning shortens mechanical ventilation duration and PICU length of stay in pediatric acute respiratory distress syndrome survivors.DesignSecondary analysis of a prospective pediatric acute respiratory distress syndrome (Berlin definition) cohort from July 2011 to June 2019 analyzed using interrupted time series analysis pre- and postimplementations of a ventilator-weaning pathway. We compared duration of invasive ventilation and PICU length of stay in survivors before and after implementation of a ventilator-weaning pathway. We excluded PICU nonsurvivors and subjects with greater than 100 ventilator days.SettingLarge academic tertiary-care PICU.PatientsChildren with acute respiratory distress syndrome who survived to PICU discharge with less than or equal to 100 days of invasive mechanical ventilation.InterventionsImplementation of a ventilator-weaning pathway on May 2016.Measurements and main resultsOf 723 children with acute respiratory distress syndrome, 132 subjects died and six subjects with ventilation greater than 100 days were excluded. Of the remaining 585 subjects, 375 subjects had acute respiratory distress syndrome prior to pathway intervention and 210 after. Patients in the preintervention epoch were younger, more likely to have infectious acute respiratory distress syndrome, and had increased use of alternative ventilator modes. Pathway adoption was rapid and sustained. Controlling for temporality, pathway implementation was associated with a decrease of a median 3.6 ventilator days (95% CI, -5.4 to -1.7; p < 0.001). There was no change in the reintubation rates. Results were robust to multiple sensitivity analyses adjusting for confounders.ConclusionsVentilator-weaning pathway implementation shortened invasive ventilation duration in pediatric acute respiratory distress syndrome survivors with no change in reintubation. The effect size of this intervention was comparable with those targeted in acute respiratory distress syndrome trials.

Dataset Information

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

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

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