Notice of Special Interest (NOSI): The Influence of Host Resilience on Heterogeneity of Acute Respiratory Distress Syndrome/Acute Lung Injury (ARDS/ALI)
Notice Number:

Key Dates

Release Date:

September 15, 2020

First Available Due Date:
October 05, 2020
Expiration Date:
July 06, 2024

Related Announcements

PA-20-183 - Research Project Grant (Parent R01 Clinical Trial Required)

PA-20-185 - Research Project Grant (Parent R01 Clinical Trial Not Allowed)

Issued by

National Heart, Lung, and Blood Institute (NHLBI)


The purpose of this Notice of Special Interest (NOSI) is to inform potential applicants of the special interest of NHLBI in research to understand host resilience as a critical determinant of outcomes in acute respiratory distress syndrome (ARDS) /acute lung injury (ALI).


Acute respiratory distress syndrome (ARDS) occurs as a result of acute lung injury characterized by acute onset of hypoxemia resulting from fluid and neutrophil accumulation in the alveolar space due to endothelial and alveolar epithelial damage and influx of inflammatory cells. Despite extensive investigation over the last 50 years, proven interventions are limited to supportive care, including lung protective ventilation, prone positioning, and conservative fluid strategies; there are no known effective pharmacological interventions. ARDS mortality rate remains high - up to 40%. This poor outcome may be largely attributed to the heterogeneity of ARDS/ALI that occurs after diverse infectious and non-infectious insults and involves various molecular pathways along with a general imbalance between injurious and reparative mechanisms. Heterogeneous transmission of SARS-CoV-2 and outcomes of COVID-19 patients as well as the occurrence of electronic cigarette (e-cigarette), or vaping associated lung injury (EVALI) are further evidence of the need to better understand ARDS heterogeneity.

Host resilience is a key component that determines the outcome of ARDS patients. Host resilience reflects the ability of a host to tolerate the effects of an infection or other significant perturbation and return to a state of health. Resilience can be at cell, tissue, organ, organism or individual level. Low levels of resilience confer vulnerability to a perturbation that leads to adverse outcomes, while higher levels of resilience can result in desirable clinical or functional outcomes, thus serving as goals for health maintenance or therapeutic strategies. However, less is known about how host resilience mechanisms impact the resolution and recovery from injury after ARDS has already been established. There is an unmet urgent need to investigate how resilience effects the heterogeneous outcome of ARDS patients.

Research Objectives

This NOSI seeks to support investigation into the factors and molecular mechanisms that address the heterogeneity dictated by the host resilience. Research on general host responses to injurious challenges and their effects on lung function as well as mechanisms that impact susceptibility to ARDS is not considered to be responsive to this announcement.

This NOSI encourages, but is not limited to, research applications in the following areas:

  • What are the host resilience factors (e.g., epigenetics, preexisting structural lung/heart/vascular or immune deficiencies, the severity of the lung inflammatory response) that influence resolution and recovery from ARDS/ALI?
  • What are the reparative or regenerative mechanisms that contribute to the resolution of lung injury and a return to a healthy host state?
  • What are the underlying host-response mechanisms that contribute to the disparity of resilience to ARDS/ALI in different race/ethnic groups and different age populations?
  • What are the underlying host-response mechanisms that determine the outcomes in patients with COVID-19 related ARDS?
  • What is the molecular mechanism underpinning the effect of metabolic changes and lifestyle on host resilience determining the resolution and recovery in ARDS?
  • Development of quantitative cell/organ/systems models and measures to identify resilience mechanisms involving inflammation resolution pathways in ARDS.

Application and Submission Information

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice. This notice applies to due dates on or after October 5, 2020 and subsequent receipt dates through July 5, 2024 of reissued FOAs.

  • PA-20-183 Research Project Grant (Parent R01 Clinical Trial Required)
  • PA-20-185 Research Project Grant (Parent R01 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the FOA used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-HL-20-814” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the Scientific/Research, Peer Review, and Financial/Grants Management contacts in Section VII of the listed funding opportunity announcements.

Scientific/Research Contact(s)

Guofei Zhou, PhD
National Heart, Lung, and Blood Institute (NHLBI)/Division of Lung Diseases
Telephone: 301-827-7825

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