Mary K Dahmer1, Michael W Quasney1, Anil Sapru2, Ginny Gildengorin3, Martha A Q Curley4,5, Michael A Matthay6, Heidi Flori1. 1. Division of Pediatric Critical Care Medicine, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI. 2. Department of Pediatrics, University of California, Los Angeles, CA. 3. Children's Hospital Oakland Research Institute, UCSF Benioff Children's Hospitals, Oakland, CA. 4. Division of Anesthesia and Critical Care Medicine, Department of Family and Community Health (School of Nursing), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. 5. Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA. 6. Departments of Medicine and Anesthesia, Cardiovascular Research Institute, University of California, San Francisco, CA.
Abstract
OBJECTIVES: To 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. DESIGN: Prospective cohort study. SETTING: Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622). SUBJECTS: Children 2 weeks to 17 years old treated with invasive mechanical ventilation for acute airways and/or parenchymal lung disease. MEASUREMENTS AND MAIN RESULTS: Three-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. CONCLUSIONS: Plasma 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.
OBJECTIVES: To 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. DESIGN: Prospective cohort study. SETTING: Twenty-two PICUs participating in the multisite clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (U01 HL086622). SUBJECTS:Children 2 weeks to 17 years old treated with invasive mechanical ventilation for acute airways and/or parenchymal lung disease. MEASUREMENTS AND MAIN RESULTS: Three-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. CONCLUSIONS: Plasma 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.
Authors: T H Beaty; M D Fallin; J B Hetmanski; I McIntosh; S S Chong; R Ingersoll; X Sheng; R Chakraborty; A F Scott Journal: Genetics Date: 2005-06-18 Impact factor: 4.562
Authors: G R Bernard; A Artigas; K L Brigham; J Carlet; K Falke; L Hudson; M Lamy; J R Legall; A Morris; R Spragg Journal: Am J Respir Crit Care Med Date: 1994-03 Impact factor: 21.405
Authors: W Y Park; R B Goodman; K P Steinberg; J T Ruzinski; F Radella; D R Park; J Pugin; S J Skerrett; L D Hudson; T R Martin Journal: Am J Respir Crit Care Med Date: 2001-11-15 Impact factor: 21.405
Authors: Matt S Zinter; Benjamin E Orwoll; Aaron C Spicer; Mustafa F Alkhouli; Carolyn S Calfee; Michael A Matthay; Anil Sapru Journal: Crit Care Med Date: 2017-05 Impact factor: 9.296
Authors: Mary K Dahmer; Heidi Flori; Anil Sapru; Joseph Kohne; Heidi M Weeks; Martha A Q Curley; Michael A Matthay; Michael W Quasney Journal: Chest Date: 2020-04-08 Impact factor: 9.410
Authors: Shan L Ward; Mary K Dahmer; Heidi M Weeks; Anil Sapru; Michael W Quasney; Martha A Q Curley; Kathleen D Liu; Michael A Matthay; Heidi R Flori Journal: Pediatr Pulmonol Date: 2020-08-07
Authors: Mary K Dahmer; Guangyu Yang; Min Zhang; Michael W Quasney; Anil Sapru; Heidi M Weeks; Pratik Sinha; Martha A Q Curley; Kevin L Delucchi; Carolyn S Calfee; Heidi Flori Journal: Lancet Respir Med Date: 2021-12-06 Impact factor: 30.700
Authors: Elizabeth W Tindal; Brandon E Armstead; Sean F Monaghan; Daithi S Heffernan; Alfred Ayala Journal: Expert Opin Ther Targets Date: 2021-04-12 Impact factor: 6.902
Authors: Heidi Flori; Anil Sapru; Michael W Quasney; Ginny Gildengorin; Martha A Q Curley; Michael A Matthay; Mary K Dahmer Journal: Crit Care Date: 2019-04-17 Impact factor: 9.097
Authors: Christian Bime; Nancy Casanova; Radu C Oita; Juliet Ndukum; Heather Lynn; Sara M Camp; Yves Lussier; Ivo Abraham; Darrick Carter; Edmund J Miller; Armand Mekontso-Dessap; Charles A Downs; Joe G N Garcia Journal: Crit Care Date: 2019-12-16 Impact factor: 9.097
Authors: Erin F Carlton; Heidi M Weeks; Mary K Dahmer; Michael W Quasney; Anil Sapru; Martha A Q Curley; Heidi R Flori Journal: Crit Care Explor Date: 2021-07-13