OBJECTIVES: To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months. DESIGN: Secondary analysis of a prospective multisite cohort study. SETTING: Eight academic PICUs in the United States (2019–2020). PATIENTS: Critically ill children with ARDS and follow-up survey data collected at 3 and/or 9 months after the event. INTERVENTIONS: None. METHODS AND MEASUREMENT: We evaluated family healthcare burden, a measure of healthcare provided by families at home, and child health resource use including medication use and emergency department (ED) and hospital readmissions during the initial 3- and 9-month post-ARDS using proxy-report. Using multivariable logistic regression, we evaluated patient characteristics associated with family healthcare burden at 3 months. MAIN RESULTS: Of 109 eligible patients, 74 (68%) and 63 patients (58%) had follow-up at 3- and 9-month post-ARDS. At 3 months, 46 families (62%) reported healthcare burden including (22%) with unmet care coordination needs. At 9 months, 33 families (52%) reported healthcare burden including 10 families (16%) with unmet care coordination needs. At month 3, 61 patients (82%) required prescription medications, 13 patients (18%) had ED visits and 16 patients (22%) required hospital readmission. At month 9, 41 patients (65%) required prescription medications, 19 patients (30%) had ED visits, and 16 (25%) required hospital readmission were reported. Medication use was associated with family healthcare burden at both 3 and 9 months. In a multivariable analysis, preillness functional status and chronic conditions were associated with healthcare burden at month 3 but illness characteristics were not. CONCLUSIONS: Pediatric ARDS survivors report high rates of healthcare burden and health resource utilization at 3- and 9-month post-ARDS. Future studies should assess the impact of improved care coordination to simplify care (e.g., medication management) and improve family burden.
Objectives: The 2015 definition for pediatric acute respiratory distress syndrome did not require the presence of bilateral infiltrates. We tested the hypothesis that pediatric patients meeting oxygenation criteria for pediatric acute respiratory distress syndrome but without bilateral infiltrates would have different inflammatory biomarker levels and clinical outcomes than those with bilateral infiltrates. Design: Secondary analysis of a prospective cohort study. Setting: Twenty-two PICUs. Patients: Four-hundred forty-six patients age 2 weeks to 17 years intubated for respiratory failure with oxygenation index greater than or equal to 4 or oxygenation saturation index greater than or equal to 5 on the day of intubation or the day after. Interventions: None. Measurements and Main Results: Patients with bilateral infiltrates, either on the day of intubation or within the following 2 days, were compared with children who never developed bilateral infiltrates. Two analyses were performed to test 1) whether bilateral infiltrates are associated with elevated interleukin-1 receptor antagonist or interleukin-8 and 2) whether bilateral infiltrates are associated with worse clinical outcomes. Patients with bilateral infiltrates more often had a primary diagnosis of pneumonia (41% vs 28%; p = 0.02) and less often asthma (8% vs 23%; p < 0.01). After controlling for age, gender, and primary diagnosis, interleukin-1 receptor antagonist was higher on study days 1 and 2 in patients with bilateral infiltrates. There was no difference in interleukin-8 levels. After adjusting for age, gender, Pediatric Risk of Mortality score, and severity of oxygenation defect, presence of bilateral infiltrates was associated with longer duration of mechanical ventilation in survivors (hazard ratio, 0.64; 95% CI, 0.49–0.82; p < 0.01); this association was independent of primary diagnosis. Overall mortality was 9%; mortality was higher in those without bilateral infiltrates (14% vs 8%; p = 0.04). Conclusions: Children meeting pediatric acute respiratory distress syndrome oxygenation criteria with bilateral infiltrates on chest radiograph experience a more intense early inflammatory response. Bilateral infiltrates are associated with longer time on the ventilator independent of oxygenation defect severity.
Background: Lower respiratory tract infections (LRTI) are a leading cause of mortality in children with critical illness. Despite this, the pathogenic microbes in this vulnerable demographic frequently remain unknown. Metagenomic next generation sequencing (mNGS) can complement traditional diagnostics in epidemiologic surveillance studies by providing broad-range pathogen detection.Methods: We conducted a prospective, multicenter cohort study of critically ill children ages 31 days to 17 years with respiratory failure requiring prolonged mechanical ventilation. Using a combination of clinically-ordered testing and tracheal aspirate mNGS we determined the prevalence, seasonal variation, and genetic relatedness of respiratory pathogens in children with clinically adjudicated LRTI (n=276) or no LRTI (n=121).Findings: A presumptive microbiologic etiology was identified in 92% of children, with RSV (46%), Haemophilus influenzae (25%) and Moraxella catarrhalis (24%) being most common. mNGS identified uncommon pathogens including Ureaplasma parvum (<1%) and Bocavirus (3%). Co-detection of viral and bacterial pathogens occurred in 52% of cases. Incidental carriage of potentially pathogenic microbes was observed in 68% of children without LRTI, with rhinovirus (25%) most prevalent. RSV, H. influenzae and M. catarrhalis were statistically more prevalent in children under five. Both viral and bacterial LRTI occurred predominantly during winter months, and RSV infection was characterized by seasonal and geographic clusters of related strains.Interpretation: The combination of clinical diagnostics and mNGS enabled comprehensive pathogen surveillance in critically ill children with LRTI. RSV, H. influenzae , and M. catarrhalis were disproportionately represented. Carriage of potentially pathogenic microbes was common in children without LRTI.Funding Statement: NIH, Chan Zuckerberg BiohubDeclaration of Interests: All authors declare no competing interests.Ethics Approval Statement: The study was approved by a central IRB at the University ofUtah.
Rationale: MMPs (Matrix metalloproteinases) and their endogenous tissue inhibitors may contribute to lung injury through extracellular matrix degradation and modulation of inflammation and fibrosis.Objectives: To test for an association between MMP pathway proteins and inflammation, endothelial dysfunction, and clinical outcomes.Methods: We measured MMPs in plasma collected on acute respiratory distress syndrome (ARDS) Day 1 from 235 children at five hospitals between 2008 and 2017. We used latent class analysis to identify patients with distinct MMP profiles and then associated those profiles with markers of inflammation (IL-1RA, -6, -8, -10, and -18; macrophage inflammatory protein-1α and -1β; tumor necrosis factor-α and -R2), endothelial injury (angiopoietin-2, von Willebrand factor, soluble thrombomodulin), impaired oxygenation (PaO2/FiO2 [P/F] ratio, oxygenation index), morbidity, and mortality.Measurements and Main Results: In geographically distinct derivation and validation cohorts, approximately one-third of patients demonstrated an MMP profile characterized by elevated MMP-1, -2, -3, -7, and -8 and tissue inhibitor of metalloproteinase-1 and -2; and depressed active and total MMP-9. This MMP profile was associated with multiple markers of inflammation, endothelial injury, and impaired oxygenation on Day 1 of ARDS, and conferred fourfold increased odds of mortality or severe morbidity independent of the P/F ratio and other confounders (95% confidence interval, 2.1–7.6; P < 0.001). Logistic regression using both the P/F ratio and MMP profiles was superior to the P/F ratio alone in prognosticating mortality or severe morbidity (area under the receiver operating characteristic curve, 0.75; 95% confidence interval, 0.68–0.82 vs. area under the receiver operating characteristic curve, 0.66; 95% confidence interval, 0.58–0.73; P = 0.009).Conclusions: Pediatric patients with ARDS have specific plasma MMP profiles associated with inflammation, endothelial injury, morbidity, and mortality. MMPs may play a role in the pathobiology of children with ARDS.
Objectives: To identify trajectories and correlates of caregiver distress and family functioning in families of children who survived community-acquired septic shock. We hypothesized that: 1) a substantial subset of families would demonstrate trajectories of persistent elevated caregiver distress and impaired family functioning 12 months after hospitalization and 2) sociodemographic and clinical risk factors would be associated with trajectories of persistent distress and family dysfunction. Design: Prospective cohort. Setting: Fourteen PICUs in the United States. Patients: Caregivers of 260 children who survived community-acquired septic shock. Interventions: None. Measurements and Main Results: Caregivers completed ratings of distress on the Brief Symptom Inventory and of family functioning on the Family Assessment Device at baseline, 1, 3, 6, and 12 months after hospitalization. Results from group-based trajectory modeling indicated that 67% of the current sample was characterized by persistent low caregiver distress, 26% by persistent moderate to high distress that remained stable across 12 months (high-risk caregiver distress group), and 8% by initial high distress followed by gradual recovery. Forty percent of the sample was characterized by stable high family functioning, 15% by persistent high dysfunction across 12 months (high-risk family functioning group), 12% by gradually improving functioning, and 32% by deteriorating function over time. Independently of age, child race was associated with membership in the high-risk caregiver distress group (non-white/Hispanic; effect size, –0.12; p = 0.010). There were no significant sociodemographic or clinical correlates of the high-risk family functioning group in multivariable analyses. Conclusions: Although the majority of families whose children survived community-acquired septic shock were characterized by resilience, a subgroup demonstrated trajectories of persistently elevated distress and family dysfunction during the 12 months after hospitalization. Results suggest a need for family-based psychosocial screening after pediatric septic shock to identify and support at-risk families.
