Display options
Share it on

Am J Respir Crit Care Med. 2020 Mar 09; doi: 10.1164/rccm.201908-1595WS. Epub 2020 Mar 09.

Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care: NHLBI Working Group Report.

American journal of respiratory and critical care medicine

Matthew W Semler, Gordon R Bernard, Shawn D Aaron, Derek C Angus, Michelle H Biros, Roy G Brower, Carolyn S Calfee, Elizabeth A Colantuoni, Niall D Ferguson, Michelle N Gong, Ramona O Hopkins, Catherine L Hough, Theodore J Iwashyna, Bruce D Levy, Thomas R Martin, Michael A Matthay, Joseph P Mizgerd, Marc Moss, Dale M Needham, Wesley H Self, Christopher W Seymour, Renee D Stapleton, B Taylor Thompson, Richard G Wunderink, Neil R Aggarwal, Lora A Reineck

Affiliations

  1. Vanderbilt University Medical Center, 12328, Department of Allergy, Pulmonary, and Critical Care Medicine, Nashville, Tennessee, United States.
  2. Ottawa Health Research Institute, Ottawa, Ontario, Canada.
  3. University of Pittsburgh, Pittsburgh, Pennsylvania, United States.
  4. University of Minnesota, 5635, Department of Emergency Medicine, Minneapolis, Minnesota, United States.
  5. School of Medicine, Johns Hopkins University, Pulmonary and Critical Care, Baltimore, Maryland, United States.
  6. UCSF, Medicine, San Francisco, California, United States.
  7. Johns Hopkins University, Biostatistics, Baltimore, Maryland, United States.
  8. University Health Network, Department of Medicine, Division of Respirology, Toronto, Ontario, Canada.
  9. University of Toronto, Interdepartmental Division of Critical Care Medicine, Toronto, Ontario, Canada.
  10. Montefiore Medical Center, Division of Critical Care Med, Bronx, New York, United States.
  11. Brigham Young University, Psychology, Provo, Utah, United States.
  12. Intermountain Medical Center, Critical Care Medicine, Murray, Utah, United States.
  13. University of Washington, Pulmonary and Critical Care Medicine, Seattle, Washington, United States.
  14. University of Michigan, Division of Pulmonary and Critical Care Medicine, Ann Arbor, Michigan, United States.
  15. Brigham and Women's Hospital Biomedical Research Institute, 278479, Pulmonary and Critical Care Medicine, Boston, Massachusetts, United States.
  16. University of Washington, 7284, Medicine, Seattle, Washington, United States.
  17. Cardiovascular Research Institute (CVRI), University of San Francisco, Medicine and Anesthesia, San Francisco, California, United States.
  18. BU School of Medicine, Pulmonary Center, Boston, Massachusetts, United States.
  19. University of Colorado/ Emory University, Division of Pulmonary Sciences and Critical Care Medicine, Denver, Colorado, United States.
  20. Johns Hopkins University, Pulmonary & Critical Care Medicine, Baltimore, Maryland, United States.
  21. Vanderbilt University Medical Center, 12328, Department of Emergency Medicine, Nashville, Tennessee, United States.
  22. University of Vermont College of Medicine, 12352, Division of Pulmonary Disease and Critical Care Medicine, Burlington, Vermont, United States.
  23. Massachusetts General Hospital, Harvard School of Medicine,, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Boston, Massachusetts, United States.
  24. Northwestern University, Chicago, Illinois, United States.
  25. National Heart Lung and Blood Institute Division of Lung Diseases, 377197, Bethesda, Maryland, United States.
  26. NHLBI, 35035, Division of Lung Diseases, Bethesda, Maryland, United States; [email protected].

PMID: 32150460 PMCID: PMC7427373 DOI: 10.1164/rccm.201908-1595WS

Abstract

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the National Heart, Lung, and Blood Institute. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising pre-clinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data", causal inference using observational data, novel clinical trial designs, pre-clinical disease modeling, and understanding recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state, research priorities, and future directions for adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including: (1) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment-response with the goal of developing targeted, personalized interventions; (2) optimizing pre-clinical models by incorporating comorbidities, co-interventions, and organ support; (3) developing and applying novel clinical trial designs; and (4) advancing mechanistic understanding of injury and recovery in order to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

Keywords: acute respiratory failure; clinical trials; mechanical ventilation; pneumonia; sepsis

References

  1. Am J Respir Cell Mol Biol. 2011 May;44(5):725-38 - PubMed
  2. JAMA. 2019 May 28;321(20):2003-2017 - PubMed
  3. JAMA. 2016 Apr 12;315(14):1469-79 - PubMed
  4. JCI Insight. 2018 Feb 8;3(3): - PubMed
  5. N Engl J Med. 2016 Jul 7;375(1):11-22 - PubMed
  6. Crit Care Med. 2017 Jun;45(6):1001-1010 - PubMed
  7. JAMA. 2000 Apr 19;283(15):1995-2002 - PubMed
  8. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1469-78 - PubMed
  9. Ann Am Thorac Soc. 2019 Mar;16(3):356-362 - PubMed
  10. Am J Respir Crit Care Med. 2015 Nov 1;192(9):1045-51 - PubMed
  11. Thorax. 2016 Dec;71(12):1130-1136 - PubMed
  12. Nat Rev Immunol. 2016 Jan;16(1):51-67 - PubMed
  13. PLoS One. 2011;6(8):e22847 - PubMed
  14. Ann Am Thorac Soc. 2014 Mar;11(3):435-41 - PubMed
  15. N Engl J Med. 2000 May 4;342(18):1301-8 - PubMed
  16. N Engl J Med. 2013 Jun 6;368(23):2159-68 - PubMed
  17. N Engl J Med. 2018 Mar 1;378(9):819-828 - PubMed
  18. Am J Respir Crit Care Med. 2015 Feb 1;191(3):255-60 - PubMed
  19. N Engl J Med. 2006 Jun 15;354(24):2564-75 - PubMed
  20. Am J Respir Crit Care Med. 2018 Sep 15;198(6):810-813 - PubMed
  21. JAMA. 2016 Feb 23;315(8):801-10 - PubMed
  22. JAMA. 2018 Mar 27;319(12):1248-1260 - PubMed
  23. JAMA. 2014 Apr 2;311(13):1308-16 - PubMed
  24. Lancet. 1967 Aug 12;2(7511):319-23 - PubMed
  25. Intensive Care Med Exp. 2018 Aug 14;6(1):26 - PubMed
  26. Ann Am Thorac Soc. 2019 Jan;16(1):116-123 - PubMed
  27. PLoS One. 2009 Nov 30;4(11):e7824 - PubMed
  28. N Engl J Med. 2019 May 23;380(21):1997-2008 - PubMed
  29. JAMA. 2016 Feb 23;315(8):788-800 - PubMed
  30. Am Rev Respir Dis. 1974 Nov;110(5):556-65 - PubMed
  31. Ann Am Thorac Soc. 2019 Apr;16(4):488-495 - PubMed
  32. Crit Care. 2016 Oct 26;20(1):345 - PubMed
  33. Am J Respir Crit Care Med. 2010 May 15;181(10):1121-7 - PubMed
  34. Lancet. 2012 Jan 21;379(9812):229-35 - PubMed
  35. Crit Care Med. 2005 Jan;33(1):1-6; discussion 230-2 - PubMed
  36. N Engl J Med. 2004 Nov 11;351(20):2049-57 - PubMed
  37. Clin Infect Dis. 2017 Nov 13;65(11):1806-1812 - PubMed
  38. Ann Am Thorac Soc. 2017 Jan;14(1):124-133 - PubMed
  39. Am J Respir Crit Care Med. 2008 Jun 1;177(11):1242-7 - PubMed
  40. BMJ. 2014 Nov 24;349:g6652 - PubMed
  41. Clin Infect Dis. 2007 Jul 15;45(2):158-65 - PubMed
  42. JAMA. 2015 Aug 25;314(8):767-8 - PubMed
  43. N Engl J Med. 2013 Jun 27;368(26):2455-66 - PubMed
  44. Thorax. 2014 Sep;69(9):819-25 - PubMed
  45. Nat Med. 2012 May 04;18(5):716-25 - PubMed
  46. Crit Care Med. 2003 Apr;31(4 Suppl):S305-11 - PubMed
  47. Thorax. 2019 Jan;74(1):43-50 - PubMed
  48. Am J Emerg Med. 2018 Jan;36(1):18-23 - PubMed
  49. Am J Respir Crit Care Med. 2016 May 15;193(10):1101-10 - PubMed
  50. Crit Care Med. 2015 Aug;43(8):1595-602 - PubMed
  51. N Engl J Med. 2017 Aug 10;377(6):562-572 - PubMed
  52. Crit Care Med. 2005 May;33(5):952-61 - PubMed
  53. N Engl J Med. 1997 Mar 27;336(13):912-8 - PubMed
  54. N Engl J Med. 2017 Jun 8;376(23):2235-2244 - PubMed
  55. PLoS Biol. 2010 Jun 29;8(6):e1000412 - PubMed
  56. Am J Respir Crit Care Med. 2009 Sep 1;180(5):388-95 - PubMed
  57. Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1249-56 - PubMed
  58. Physiol Rev. 2018 Jul 1;98(3):1417-1464 - PubMed
  59. Crit Care Resusc. 2012 Sep;14(3):211-5 - PubMed
  60. Crit Care Med. 2002 Jan;30(1):1-6 - PubMed
  61. Crit Care. 2017 Aug 15;21(1):213 - PubMed
  62. N Engl J Med. 2006 Apr 27;354(17):1775-86 - PubMed
  63. Am J Epidemiol. 2016 Apr 15;183(8):758-64 - PubMed
  64. Trials. 2018 May 25;19(1):294 - PubMed
  65. Am J Respir Crit Care Med. 2018 Oct 1;198(7):859-867 - PubMed
  66. Am J Respir Crit Care Med. 2017 Nov 1;196(9):1122-1130 - PubMed
  67. N Engl J Med. 2013 Aug 29;369(9):840-51 - PubMed
  68. Thorax. 2018 Jan;73(1):7-12 - PubMed
  69. Intensive Care Med. 2018 Mar;44(3):345-355 - PubMed
  70. JAMA. 2016 Jun 28;315(24):2694-702 - PubMed
  71. J Appl Physiol Respir Environ Exerc Physiol. 1984 Dec;57(6):1809-16 - PubMed
  72. N Engl J Med. 1991 Mar 21;324(12):781-8 - PubMed
  73. N Engl J Med. 2012 May 31;366(22):2055-64 - PubMed
  74. Lancet Respir Med. 2014 Aug;2(8):611-20 - PubMed
  75. J Clin Invest. 1981 Feb;67(2):409-18 - PubMed
  76. Proc R Soc Med. 1954 Jan;47(1):72-4 - PubMed
  77. Thorax. 2019 Jan;74(1):33-42 - PubMed
  78. Rev Bras Ter Intensiva. 2013 Mar;25(1):56-62 - PubMed
  79. Clin Trials. 2011 Apr;8(2):183-95 - PubMed
  80. J Law Med Ethics. 2018 Mar;46(1):72-78 - PubMed
  81. Crit Care Med. 2012 Jul;40(7):2182-9 - PubMed
  82. Am J Respir Crit Care Med. 2014 Jul 1;190(1):70-6 - PubMed
  83. J Clin Invest. 2018 Jul 2;128(7):2657-2669 - PubMed
  84. N Engl J Med. 2010 Sep 16;363(12):1107-16 - PubMed
  85. JAMA. 2014 Mar 19;311(11):1109-10 - PubMed
  86. Am J Respir Crit Care Med. 2011 Jun 1;183(11):1451-3 - PubMed
  87. BMJ. 2018 Jan 3;360:j5748 - PubMed
  88. Nat Rev Dis Primers. 2019 Mar 14;5(1):18 - PubMed
  89. Am J Respir Crit Care Med. 2020 Jan 15;201(2):178-187 - PubMed
  90. Chest. 2002 May;121(5):1602-9 - PubMed
  91. Intensive Care Med. 2016 May;42(5):756-767 - PubMed
  92. N Engl J Med. 2018 Mar 1;378(9):829-839 - PubMed
  93. Nature. 2016 Apr 28;532(7600):512-6 - PubMed
  94. Am J Respir Crit Care Med. 2018 Jul 15;198(2):256-263 - PubMed
  95. JAMA. 2018 Aug 28;320(8):769-778 - PubMed
  96. Am J Respir Crit Care Med. 2018 Feb 1;197(3):337-347 - PubMed
  97. Lancet Respir Med. 2019 Oct;7(10):870-880 - PubMed
  98. Chest. 2017 Oct;152(4):707-711 - PubMed
  99. Physiol Rev. 2018 Jul 1;98(3):1335-1370 - PubMed
  100. N Engl J Med. 2014 May 1;370(18):1683-93 - PubMed
  101. Clin Ethics. 2018 Sep;13(3):107-111 - PubMed
  102. Hastings Cent Rep. 2013 Jan-Feb;Spec No:S16-27 - PubMed
  103. Curr Opin Crit Care. 2018 Oct;24(5):401-409 - PubMed
  104. Am J Physiol Lung Cell Mol Physiol. 2018 Jul 1;315(1):L25-L40 - PubMed
  105. JAMA. 2020 Feb 18;323(7):616-626 - PubMed
  106. PLoS One. 2016 Nov 17;11(11):e0166733 - PubMed
  107. BMJ. 2015 May 08;350:h2147 - PubMed
  108. Crit Care Med. 2012 Jul;40(7):2022-32 - PubMed
  109. J Crit Care. 2015 Jun;30(3):653.e1-7 - PubMed

Publication Types

Grant support