The host immune response to a viral immune stimulus has not been examined in children during a li... more The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6–17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared w...
BackgroundThere is no generalizable transcriptomics signature of pediatric acute respiratory dist... more BackgroundThere is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200.ResultsWe used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked...
Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and childre... more Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and children in the United States. The prevalence of critically ill children who are exposed to ACEs is not known. Our objective was to compare the frequency of ACEs of critically ill children with that of the general pediatric population of Georgia and the United States using publicly available National Survey of Children’s Health (NSCH) data. The impact of ACEs on patient-reported outcome measures of emotional, social, and physical health in critically ill children is not known. We sought to determine whether a higher total number of ACEs was associated with poorer patient-reported measures of emotional, social, and physical health. We conducted a prospective cross-sectional study of children < 18 years of age who were admitted to a 36-bed free-standing, quaternary academic pediatric intensive care unit in Atlanta, Georgia from June 2020—December 2021. Parents of patients who were admitted to ...
The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of trea... more The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of treatment effect. We previously reported a binary septic shock endotype classification based on expression of 100 genes. This binary classification provides information regarding prognosis and corticosteroid responsiveness but does not capture the endotypes continuum. Here, we describe a continuous metric for endotype assignment, the Z value, and its relationship with septic shock outcomes and corticosteroid responsiveness. In a derivation cohort, a lower Z value was independently associated with increased odds of mortality. When the Z value was fit using cubic splines, the odds of mortality increased considerably below a Z value of 15 among patients exposed to corticosteroids. A similar interaction between Z value and corticosteroid exposure was observed when the model was applied to pediatric and adult validation cohorts. The Z value provides more detailed evidence of patients with septic ...
Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children wi... more Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children with pediatric acute hypoxemic respiratory failure. Seventy-four immunocompetent children, 41 (55.4%) with pediatric acute respiratory distress syndrome (PARDS), who were between 2 days to 18 years of age and within 72 h of intubation for acute hypoxemic respiratory failure, were enrolled. We used hierarchal clustering and partial least squares-discriminant analysis to profile the tracheal aspirate airway fluid using quantitative LC–MS/MS to explore clusters of metabolites that correlated with acute hypoxemia severity and ventilator-free days. Three clusters of children that differed by severity of hypoxemia and ventilator-free days were identified. Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top f...
Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signa... more Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients, undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting criteria for MODS were screened, consented (n=24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n=4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. 61 patient samples over 3 time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63% - 3.19%; vs. controls 0.22%). Fou...
Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recr... more Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosph...
Complex in vitro models of the tissue microenvironment, termed microphysiological systems, have e... more Complex in vitro models of the tissue microenvironment, termed microphysiological systems, have enormous potential to transform the process of discovering drugs and disease mechanisms. Such a paradigm shift is urgently needed in acute respiratory distress syndrome (ARDS), an acute lung condition with no successful therapies and a 40% mortality rate. Here, we consider how microphysiological systems could improve understanding of biological mechanisms driving ARDS and ultimately improve the success of therapies in clinical trials. We first discuss how microphysiological systems could explain the biological mechanisms underlying the segregation of ARDS patients into two clinically distinct phenotypes. Then, we contend that ARDS-mimetic microphysiological systems should recapitulate three critical aspects of the distal airway microenvironment, namely, mechanical force, inflammation, and fibrosis, and we review models that incorporate each of these aspects. Finally, we recognize the subs...
Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (AR... more Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrate...
Objective: To derive and validate clinical prediction models to identify children at low risk of ... more Objective: To derive and validate clinical prediction models to identify children at low risk of clinically significant intoxications for whom intensive care admission is unnecessary. Design: Retrospective review of data in the National Poison Data Systems from 2011 to 2014 and Georgia Poison Center cases from July to December 2016. Setting: United States PICUs and poison centers participating in the American Association of Poison Control Centers from 2011 to 2016. Patients: Children 18 years and younger admitted to a United States PICU following an acute intoxication. Interventions: None. Measurements and Main Results: The primary study outcome was the occurrence of clinically significant intoxications defined a priori as organ system–based clinical effects that require intensive care monitoring and interventions. We analyzed 70,364 cases. Derivation (n = 42,240; 60%) and validation cohorts (n = 28,124; 40%) were randomly selected from the eligible population and had similar distri...
Objectives: To determine risk factors associated with admission to a PICU with or without endotra... more Objectives: To determine risk factors associated with admission to a PICU with or without endotracheal intubation for an asthma exacerbation. We hypothesized that children with critical and near-fatal asthma would have distinguishing clinical features but varying degrees of asthma severity and measures of type 2 inflammation. Design: Retrospective analysis of prospectively collected data of children with asthma recruited into outpatient asthma clinical research studies at Emory University between 2004 and 2015. Setting: Large, free-standing academic quaternary care children’s hospital in Atlanta, GA. Patients: Children 6–18 years old with physician-diagnosed and confirmed asthma. Interventions: None. Measurements and Main Results: A total of 579 children were analyzed with 170 children (29.4%) being admitted to the PICU for an asthma exacerbation in their lifetime. Of these 170 children with a history of critical asthma, 24.1% were classified as having mild-to-moderate asthma, and 8...
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2018
Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if ... more Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock. Retrospective analysis of a pediatric septic shock database. Twenty-nine PICUs in the United States. Eight hundred ninety children 10 years and younger with septic shock. None. We considered the minimum, maximum, and mean chloride values during the initial 7 days of septic shock for each study subject as separate hyperchloremia variables. Within each category, we considered hyperchloremia as a dichotomous variable defined as a serum concentration greater than or equal to 110 mmol/L. We used multivariable logistic regression to determine the association between the hyperchloremia variables and outcome, adjusted for illness severity. We considered all cause 28-day mortality and complicated course as the primary outcome variables. Compli...
We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive im... more We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes. Observational cohort study including existing and newly enrolled participants. Multiple PICUs. Children with septic shock. None. We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype ...
Objectives: Outcomes associated with a sedative regimen comprised ketamine + propofol for pediatr... more Objectives: Outcomes associated with a sedative regimen comprised ketamine + propofol for pediatric procedural sedation outside of both the pediatric emergency department and operating room are underreported. We used the Pediatric Sedation Research Consortium database to describe a multicenter experience with ketamine + propofol by pediatric sedation providers. Design: Prospective observational study of children receiving IV ketamine + propofol for procedural sedation outside of the operating room and emergency department using data abstracted from the Pediatric Sedation Research Consortium during 2007–2015. Setting: Procedural sedation services from academic, community, free-standing children’s hospitals, and pediatric wards within general hospitals. Patients: Children from birth to less than or equal to 21 years old. Interventions: None. Measurements and Main Results: A total of 7,313 pediatric procedural sedations were performed using IV ketamine + propofol as the primary sedativ...
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, Aug 10, 2017
Video (indirect) laryngoscopy is used as a primary tracheal intubation device for difficult airwa... more Video (indirect) laryngoscopy is used as a primary tracheal intubation device for difficult airways in emergency departments and in adult ICUs. The use and outcomes of video laryngoscopy compared with direct laryngoscopy has not been quantified in PICUs or cardiac ICUs. Retrospective review of prospectively collected observational data from a multicenter tracheal intubation database (National Emergency Airway Registry for Children) from July 2010 to June 2015. Thirty-six PICUs/cardiac ICUs across the United States, Canada, Japan, New Zealand, and Singapore. Any patient admitted to a PICU or a pediatric cardiac ICU and undergoing tracheal intubation. Use of direct laryngoscopy versus video laryngoscopy for tracheal intubation. There were 8,875 tracheal intubations reported in the National Emergency Airway Registry for Children database, including 7,947 (89.5%) tracheal intubations performed using direct laryngoscopy and 928 (10.5%) tracheal intubations performed using video laryngosc...
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Aug 4, 2017
Racial disparities are evident among children with asthma in the United States, with non-Hispanic... more Racial disparities are evident among children with asthma in the United States, with non-Hispanic black children at particularly high risk for poor asthma outcomes, including frequent emergency department (ED) use for asthma exacerbations. To compare asthma features in non-Hispanic black vs white children in Atlanta, Georgia, and determine what clinical features predict future ED use for asthma. Self-reported black and white children 6 to 17 years of age with persistent asthma treated with controller medications completed medical history questionnaires, lung function testing, aeroallergen sensitization testing, and venipuncture. Medical records were reviewed for asthma-related ED visits for 12 months after the initial study visit. A total of 276 children were enrolled. Black children, compared with white children, resided in more disadvantaged zip code areas and were more likely to have public insurance. Black children also had more features of asthma severity and more ED visits dur...
Our understanding of the intrinsic effects of cystic fibrosis (CF) transmembrane conductance regu... more Our understanding of the intrinsic effects of cystic fibrosis (CF) transmembrane conductance regulator (cftr) deletion on resident neonatal alveolar macrophage (AM) remains limited. We previously demonstrated that diminished glutathione (GSH) or excessive AM transforming growth factor beta one (TGFβ1) contributes to AM dysfunction in a variety of disease states. In this study, using a gut-corrected cftr neonatal knockout (KO) mouse model and a siRNA-manipulated macrophage-like cell line (THP-1 cell), we hypothesized (1) that cftr mutation alone increases neonatal AM oxidant stress and cellular TGFβ1 signaling via altered GSH, thereby impairing cellular function, and (2) that exogenous GSH attenuates AM alterations and dysfunction in the KO AM In neonatal KO mice, the baseline bronchoalveolar lavage fluid demonstrated a near doubling in mixed disulfides (P ≤ 0.05) and oxidized GSSG (P ≤ 0.05) without concurrent inflammation compared to WT littermates. KO AM demonstrated diminished AM...
The host immune response to a viral immune stimulus has not been examined in children during a li... more The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6–17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared w...
BackgroundThere is no generalizable transcriptomics signature of pediatric acute respiratory dist... more BackgroundThere is no generalizable transcriptomics signature of pediatric acute respiratory distress syndrome. Our goal was to identify a whole blood differential gene expression signature for pediatric acute hypoxemic respiratory failure (AHRF) using transcriptomic microarrays within twenty-four hours of diagnosis. We used publicly available human whole-blood gene expression arrays of a Berlin-defined pediatric acute respiratory distress syndrome (GSE147902) cohort and a sepsis-triggered AHRF (GSE66099) cohort within twenty-four hours of diagnosis and compared those children with a PaO2/FiO2 < 200 to those with a PaO2/FiO2 ≥ 200.ResultsWe used stability selection, a bootstrapping method of 100 simulations using logistic regression as a classifier, to select differentially expressed genes associated with a PaO2/FiO2 < 200 vs. PaO2/FiO2 ≥ 200. The top-ranked genes that contributed to the AHRF signature were selected in each dataset. Genes common to both of the top 1,500 ranked...
Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and childre... more Adverse childhood experiences (ACEs) are linked to adverse health outcomes for adults and children in the United States. The prevalence of critically ill children who are exposed to ACEs is not known. Our objective was to compare the frequency of ACEs of critically ill children with that of the general pediatric population of Georgia and the United States using publicly available National Survey of Children’s Health (NSCH) data. The impact of ACEs on patient-reported outcome measures of emotional, social, and physical health in critically ill children is not known. We sought to determine whether a higher total number of ACEs was associated with poorer patient-reported measures of emotional, social, and physical health. We conducted a prospective cross-sectional study of children < 18 years of age who were admitted to a 36-bed free-standing, quaternary academic pediatric intensive care unit in Atlanta, Georgia from June 2020—December 2021. Parents of patients who were admitted to ...
The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of trea... more The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of treatment effect. We previously reported a binary septic shock endotype classification based on expression of 100 genes. This binary classification provides information regarding prognosis and corticosteroid responsiveness but does not capture the endotypes continuum. Here, we describe a continuous metric for endotype assignment, the Z value, and its relationship with septic shock outcomes and corticosteroid responsiveness. In a derivation cohort, a lower Z value was independently associated with increased odds of mortality. When the Z value was fit using cubic splines, the odds of mortality increased considerably below a Z value of 15 among patients exposed to corticosteroids. A similar interaction between Z value and corticosteroid exposure was observed when the model was applied to pediatric and adult validation cohorts. The Z value provides more detailed evidence of patients with septic ...
Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children wi... more Hierarchal clustering of amino acid metabolites may identify a metabolic signature in children with pediatric acute hypoxemic respiratory failure. Seventy-four immunocompetent children, 41 (55.4%) with pediatric acute respiratory distress syndrome (PARDS), who were between 2 days to 18 years of age and within 72 h of intubation for acute hypoxemic respiratory failure, were enrolled. We used hierarchal clustering and partial least squares-discriminant analysis to profile the tracheal aspirate airway fluid using quantitative LC–MS/MS to explore clusters of metabolites that correlated with acute hypoxemia severity and ventilator-free days. Three clusters of children that differed by severity of hypoxemia and ventilator-free days were identified. Quantitative pathway enrichment analysis showed that cysteine and methionine metabolism, selenocompound metabolism, glycine, serine and threonine metabolism, arginine biosynthesis, and valine, leucine, and isoleucine biosynthesis were the top f...
Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signa... more Glycero- and sphingo-lipids are important in plasma membrane structure, caloric storage and signaling. An un-targeted lipidomics approach for a cohort of critically ill pediatric intensive care unit (PICU) patients, undergoing multi-organ dysfunction syndrome (MODS) was compared to sedation controls. After IRB approval, patients meeting criteria for MODS were screened, consented (n=24), and blood samples were collected from the PICU at HDVCH, Michigan; eight patients needed veno-arterial extracorporeal membrane oxygenation (VA ECMO). Sedation controls were presenting for routine sedation (n=4). Plasma lipid profiles were determined by nano-electrospray (nESI) direct infusion high resolution/accurate mass spectrometry (MS) and tandem mass spectrometry (MS/MS). Biostatistics analysis was performed using R v 3.6.0. 61 patient samples over 3 time points revealed a ceramide metabolite, hexosylceramide (Hex-Cer) was high across all time points (mean 1.63% - 3.19%; vs. controls 0.22%). Fou...
Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recr... more Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosph...
Complex in vitro models of the tissue microenvironment, termed microphysiological systems, have e... more Complex in vitro models of the tissue microenvironment, termed microphysiological systems, have enormous potential to transform the process of discovering drugs and disease mechanisms. Such a paradigm shift is urgently needed in acute respiratory distress syndrome (ARDS), an acute lung condition with no successful therapies and a 40% mortality rate. Here, we consider how microphysiological systems could improve understanding of biological mechanisms driving ARDS and ultimately improve the success of therapies in clinical trials. We first discuss how microphysiological systems could explain the biological mechanisms underlying the segregation of ARDS patients into two clinically distinct phenotypes. Then, we contend that ARDS-mimetic microphysiological systems should recapitulate three critical aspects of the distal airway microenvironment, namely, mechanical force, inflammation, and fibrosis, and we review models that incorporate each of these aspects. Finally, we recognize the subs...
Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (AR... more Neutrophils are recruited to the airways of patients with acute respiratory distress syndrome (ARDS) where they acquire an activated pro-survival phenotype with an enhanced respiratory burst thought to contribute to ARDS pathophysiology. Our in vitro model enables blood neutrophil transepithelial migration into cell-free tracheal aspirate fluid from patients to recapitulate the primary airway neutrophil phenotype observed in vivo. Neutrophils transmigrated through our model toward airway fluid from children with lower respiratory viral infections coinfected with bacteria had elevated levels of neutrophil activation markers but paradoxically exhibited an inability to kill bacteria and a defective respiratory burst compared with children without bacterial coinfection. The airway fluid from children with bacterial coinfections had higher levels of neutrophil elastase activity, as well as myeloperoxidase levels compared to children without bacterial coinfection. Neutrophils transmigrate...
Objective: To derive and validate clinical prediction models to identify children at low risk of ... more Objective: To derive and validate clinical prediction models to identify children at low risk of clinically significant intoxications for whom intensive care admission is unnecessary. Design: Retrospective review of data in the National Poison Data Systems from 2011 to 2014 and Georgia Poison Center cases from July to December 2016. Setting: United States PICUs and poison centers participating in the American Association of Poison Control Centers from 2011 to 2016. Patients: Children 18 years and younger admitted to a United States PICU following an acute intoxication. Interventions: None. Measurements and Main Results: The primary study outcome was the occurrence of clinically significant intoxications defined a priori as organ system–based clinical effects that require intensive care monitoring and interventions. We analyzed 70,364 cases. Derivation (n = 42,240; 60%) and validation cohorts (n = 28,124; 40%) were randomly selected from the eligible population and had similar distri...
Objectives: To determine risk factors associated with admission to a PICU with or without endotra... more Objectives: To determine risk factors associated with admission to a PICU with or without endotracheal intubation for an asthma exacerbation. We hypothesized that children with critical and near-fatal asthma would have distinguishing clinical features but varying degrees of asthma severity and measures of type 2 inflammation. Design: Retrospective analysis of prospectively collected data of children with asthma recruited into outpatient asthma clinical research studies at Emory University between 2004 and 2015. Setting: Large, free-standing academic quaternary care children’s hospital in Atlanta, GA. Patients: Children 6–18 years old with physician-diagnosed and confirmed asthma. Interventions: None. Measurements and Main Results: A total of 579 children were analyzed with 170 children (29.4%) being admitted to the PICU for an asthma exacerbation in their lifetime. Of these 170 children with a history of critical asthma, 24.1% were classified as having mild-to-moderate asthma, and 8...
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2018
Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if ... more Hyperchloremia is associated with poor outcome among critically ill adults, but it is unknown if a similar association exists among critically ill children. We determined if hyperchloremia is associated with poor outcomes in children with septic shock. Retrospective analysis of a pediatric septic shock database. Twenty-nine PICUs in the United States. Eight hundred ninety children 10 years and younger with septic shock. None. We considered the minimum, maximum, and mean chloride values during the initial 7 days of septic shock for each study subject as separate hyperchloremia variables. Within each category, we considered hyperchloremia as a dichotomous variable defined as a serum concentration greater than or equal to 110 mmol/L. We used multivariable logistic regression to determine the association between the hyperchloremia variables and outcome, adjusted for illness severity. We considered all cause 28-day mortality and complicated course as the primary outcome variables. Compli...
We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive im... more We previously identified septic shock endotypes A and B based on 100 genes reflecting adaptive immunity and glucocorticoid receptor signaling. The endotypes differ with respect to outcome and corticosteroid responsiveness. We determined whether endotypes change during the initial 3 days of illness, and whether changes are associated with outcomes. Observational cohort study including existing and newly enrolled participants. Multiple PICUs. Children with septic shock. None. We measured the 100 endotyping genes at day 1 and day 3 of illness in 375 patients. We determined if endotype assignment changes over time, and whether changing endotype is associated with corticosteroid response and outcomes. We used multivariable logistic regression to adjust for illness severity, age, and comorbidity burden. Among the 132 subjects assigned to endotype A on day 1, 56 (42%) transitioned to endotype B by day 3. Among 243 subjects assigned to endotype B on day 1, 77 (32%) transitioned to endotype ...
Objectives: Outcomes associated with a sedative regimen comprised ketamine + propofol for pediatr... more Objectives: Outcomes associated with a sedative regimen comprised ketamine + propofol for pediatric procedural sedation outside of both the pediatric emergency department and operating room are underreported. We used the Pediatric Sedation Research Consortium database to describe a multicenter experience with ketamine + propofol by pediatric sedation providers. Design: Prospective observational study of children receiving IV ketamine + propofol for procedural sedation outside of the operating room and emergency department using data abstracted from the Pediatric Sedation Research Consortium during 2007–2015. Setting: Procedural sedation services from academic, community, free-standing children’s hospitals, and pediatric wards within general hospitals. Patients: Children from birth to less than or equal to 21 years old. Interventions: None. Measurements and Main Results: A total of 7,313 pediatric procedural sedations were performed using IV ketamine + propofol as the primary sedativ...
Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, Aug 10, 2017
Video (indirect) laryngoscopy is used as a primary tracheal intubation device for difficult airwa... more Video (indirect) laryngoscopy is used as a primary tracheal intubation device for difficult airways in emergency departments and in adult ICUs. The use and outcomes of video laryngoscopy compared with direct laryngoscopy has not been quantified in PICUs or cardiac ICUs. Retrospective review of prospectively collected observational data from a multicenter tracheal intubation database (National Emergency Airway Registry for Children) from July 2010 to June 2015. Thirty-six PICUs/cardiac ICUs across the United States, Canada, Japan, New Zealand, and Singapore. Any patient admitted to a PICU or a pediatric cardiac ICU and undergoing tracheal intubation. Use of direct laryngoscopy versus video laryngoscopy for tracheal intubation. There were 8,875 tracheal intubations reported in the National Emergency Airway Registry for Children database, including 7,947 (89.5%) tracheal intubations performed using direct laryngoscopy and 928 (10.5%) tracheal intubations performed using video laryngosc...
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Aug 4, 2017
Racial disparities are evident among children with asthma in the United States, with non-Hispanic... more Racial disparities are evident among children with asthma in the United States, with non-Hispanic black children at particularly high risk for poor asthma outcomes, including frequent emergency department (ED) use for asthma exacerbations. To compare asthma features in non-Hispanic black vs white children in Atlanta, Georgia, and determine what clinical features predict future ED use for asthma. Self-reported black and white children 6 to 17 years of age with persistent asthma treated with controller medications completed medical history questionnaires, lung function testing, aeroallergen sensitization testing, and venipuncture. Medical records were reviewed for asthma-related ED visits for 12 months after the initial study visit. A total of 276 children were enrolled. Black children, compared with white children, resided in more disadvantaged zip code areas and were more likely to have public insurance. Black children also had more features of asthma severity and more ED visits dur...
Our understanding of the intrinsic effects of cystic fibrosis (CF) transmembrane conductance regu... more Our understanding of the intrinsic effects of cystic fibrosis (CF) transmembrane conductance regulator (cftr) deletion on resident neonatal alveolar macrophage (AM) remains limited. We previously demonstrated that diminished glutathione (GSH) or excessive AM transforming growth factor beta one (TGFβ1) contributes to AM dysfunction in a variety of disease states. In this study, using a gut-corrected cftr neonatal knockout (KO) mouse model and a siRNA-manipulated macrophage-like cell line (THP-1 cell), we hypothesized (1) that cftr mutation alone increases neonatal AM oxidant stress and cellular TGFβ1 signaling via altered GSH, thereby impairing cellular function, and (2) that exogenous GSH attenuates AM alterations and dysfunction in the KO AM In neonatal KO mice, the baseline bronchoalveolar lavage fluid demonstrated a near doubling in mixed disulfides (P ≤ 0.05) and oxidized GSSG (P ≤ 0.05) without concurrent inflammation compared to WT littermates. KO AM demonstrated diminished AM...
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