Development of Persistent Respiratory Morbidity in Previously Healthy Children After Acute Respiratory Failure*

Abstract

Objectives: Acute respiratory failure is a common reason for admission to PICUs. Short- and long-term effects on pulmonary health in previously healthy children after acute respiratory failure requiring mechanical ventilation are unknown. The aim was to determine if clinical course or characteristics of mechanical ventilation predict persistent respiratory morbidity at follow-up. Design: Prospective cohort study with follow-up questionnaires at 6 and 12 months. Setting: Ten U.S. PICUs. Patients: Two-hundred fifty-five children were included in analysis after exclusion for underlying chronic disease or incomplete data. One-hundred fifty-eight and 130 children had follow-up data at 6 and 12 months, respectively. Interventions: None. Measurements and Main Results: Pulmonary dysfunction at discharge a priori defined as one of: mechanical ventilation, supplemental oxygen, bronchodilators or steroids at 28 days or discharge. Persistent respiratory morbidity a priori defined as a respiratory PedsQL, a pediatric quality of life measure, greater than or equal to 5 or asthma diagnosis, bronchodilator or inhaled steroids, or unscheduled clinical evaluation for respiratory symptoms. Multivariate backward stepwise regression using Akaike information criterion minimization determined independent predictors of these outcomes. Pulmonary dysfunction at discharge was present in 34% of patients. Positive bacterial respiratory culture predicted pulmonary dysfunction at discharge (odds ratio, 4.38; 95% CI, 1.66–11.56). At 6- and 12-month follow-up 42% and 44% of responders, respectively, had persistent respiratory morbidity. Pulmonary dysfunction at discharge was associated with persistent respiratory morbidity at 6 months, and persistent respiratory morbidity at 6 months was strongly predictive of 12-month persistent respiratory morbidity (odds ratio, 18.58; 95% CI, 6.68–52.67). Positive bacterial respiratory culture remained predictive of persistent respiratory morbidity in patients at both follow-up points. Conclusions: Persistent respiratory morbidity develops in up to potentially 44% of previously healthy children less than or equal to 24 months old at follow-up after acute respiratory failure requiring mechanical ventilation. This is the first study, to our knowledge, to suggest a prevalence of persistent respiratory morbidity and the association between positive bacterial respiratory culture and pulmonary morbidity in a population of only previously healthy children with acute respiratory failure.

High burden of acquired morbidity in survivors of pediatric acute respiratory distress syndrome

“…22 Pulmonary dysfunction after survival might be or steroids. 14 Our study showed that 73.3% and 37.8% of our cohort needed assisted enteral feeding at PICU and hospital discharge, respectively.…”

SNP–SNP Interactions of Surfactant Protein Genes in Persistent Respiratory Morbidity Susceptibility in Previously Healthy Children

“…We prospectively enrolled 250 previously healthy children from 0 to 24 months of age that required invasive ventilation for an index case of ARF secondary to respiratory illness at 10 participating pediatric intensive care units (PICUs) over 5 consecutive years. This multicenter cohort has been described in detail elsewhere ( Gandhi et al, 2020a ; Keim et al, 2020 ). Briefly, previously healthy children, who met at least one of the three criteria, 1) chest radiograph with either focal or diffuse infiltrative pulmonary process, 2) radiographic evidence of air trapping, or 3) clinical exam findings of lower respiratory tract illness, were determined to have primary respiratory cause of ARF.…”

“…Studies have shown a significant decline in the functional status of pediatric ARF survivors at discharge ( Pollack et al, 2009 ). More specifically, persistent respiratory morbidity (PRM) occurred after 6 and 12 months of an ARF episode even in previously healthy children ( Keim et al, 2020 ). In addition, there is a considerable heterogeneity in the progression of the disease and long-term outcomes of pediatric ARF patients ( Keim et al, 2020 ), indicating a complex interaction between genetic and environmental factors.…”

“…More specifically, persistent respiratory morbidity (PRM) occurred after 6 and 12 months of an ARF episode even in previously healthy children ( Keim et al, 2020 ). In addition, there is a considerable heterogeneity in the progression of the disease and long-term outcomes of pediatric ARF patients ( Keim et al, 2020 ), indicating a complex interaction between genetic and environmental factors. Nonetheless, studies of long-term sequelae of ARF in children are limited ( Yehya and Thomas, 2016 ).…”

Mechanical Ventilation in Pediatric and Neonatal Patients

“…One of the challenges to investigating mechanical ventilation in the pediatric population is that mortality is frequently used as a therapeutic endpoint, but the majority of deaths in pediatric patients on mechanical ventilation are due to neurologic causes rather than refractory hypoxemia ( Dowell et al, 2018 ). Up to 44% of children with no previous respiratory co-morbidities have long-term outcomes of pulmonary dysfunction after a pediatric intensive care unit (ICU) stay for acute respiratory failure including persistent need for adjunct therapies such as oxygen supplementation, bronchodilators, and corticosteroids, or persistent asthma or recurrent pneumonia ( Keim et al, 2020 ). These secondary markers of lung injury may therefore make for a useful alternative marker mortality ( Keim et al, 2018 ).…”