The National Institute of General Medical Sciences (NIGMS) announces its participation in Administrative Supplements to Expand Vaping Research and Understand EVALI (NOT-HL-19-724). This Notice of Special Interest (NOSI) calls for research on the causes, disease mechanisms, and long-term prognosis of individuals with electronic cigarette (e-cigarette), or vaping associated lung injury (EVALI) and related health effects of vaping.

Background

As of October 29, 2019, 1,888 cases of e-cigarette, or vaping, associated lung injury (EVALI) have been reported to the Centers for Disease Control and Prevention (CDC), and 37 deaths have been attributed to this illness. All EVALI patients have a history of e-cigarette use or vaping and, while the majority report using tetrahydrocannabinol- (THC-) containing vaping products, no specific single product or substance has so far been linked to all cases.

Patients diagnosed with this illness have reported symptoms such as:

• cough, shortness of breath, or chest pain
• nausea, vomiting, or diarrhea
• fatigue, fever, or weight loss

Behavioral, chemical, device-related, and biological causes remain unclear and there is no clear common pathogenesis that has been discovered. This illness may in fact have multiple causes and mechanisms. Importantly, whether EVALI represents the most severe cases of a more common and milder illness, and the long-term consequences of EVALI, remain unknown.

The CDC, the US Food and Drug Administration (FDA), state and local health departments, and other clinical and public health partners continue to investigate this outbreak and its causes. For updated information on EVALI, see: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease.html.

Research Objectives

To better understand the causes and pathogenic mechanisms of EVALI, NIGMS encourages the submission of applications for Administrative Supplements to funded and active grants that seek to explore vaping-related pulmonary injury; its etiology or etiologies; and the roles of vaping devices, constituents, aerosols, and behaviors on the development of and recovery from this illness. Of particular interest are studies that take advantage of human research or novel model systems to study the consequences of vaping. Supported research will have substantial public health impact and will inform the ongoing investigation into this illness as well as its diagnosis, treatment, and prevention.

Research interests include, but are not limited to:

• What are the constituents of e-liquids designed for vaping THC or other cannabinoids that may be causing EVALI?
• What role do the following factors play in health outcomes from vaping, including EVALI?
  • behaviors related to e-cigarette use (including dripping and dabbing)
  • constituents in e-liquid and aerosols (such as propylene glycol, vegetable glycerin, cutting agents, flavorings, degradation products, contaminants, or other additives and toxins)
  • aerosol characteristics (such as size and patterns of lung deposition)
  • device characteristics (including electronic power and resistance). At what temperatures do e-liquid components degrade, and what are the resultant products?
• Are there population-specific contributions for susceptibility to health effects of vaping such as EVALI; e.g. based on age, gender, race and ethnicity, pregnancy status, or comorbid psychiatric or other health conditions, such as cardiopulmonary disease? Based on current case reports, applications exploring health effects in younger populations are strongly encouraged.
• Are there individual susceptibility factors that influence risk for developing disease after potentially causative e-cigarette exposures?
• Are there any health effects associated with secondary or environmental exposures to e-cigarette aerosols?
• Can informatics-based cohort discovery tools be utilized across linked electronic health record networks to identify additional cases of EVALI?
• What are the physiological and behavioral effects, such as those relevant to EVALI, of using e-liquids containing THC or other cannabinoids in combination with those containing nicotine, either in the same mixture or in subsequent vaping sessions?
• Are device users adjusting the properties of their devices and what is the impact of those modifications?
• What can we learn about mechanisms involved in the development of health outcomes of vaping, including EVALI? How do the agents in e-liquids, including thermal degradation products, affect the inflammatory state of pulmonary epithelia, endothelia, or immune cells?
• What aspects of EVALI pathology or biological response can be recapitulated and studied in cell or animal models of e-cigarette exposure?
• What are the causes of the digestive dysfunction and fever that frequently precede pulmonary symptoms of EVALI?
• Are there biomarkers that are predictive of EVALI development or EVALI-related health outcomes?
• How can vaping-related health outcomes, such as EVALI, be treated?
• What is the prognosis of EVALI patients after recovery? Is there a susceptibility to subsequent diseases and infections such as influenza?

Supplementary funds may be used for the collection of lung samples from human cohorts of individuals who vape, and/or development of novel model systems to expose animals and cells to e-cigarette aerosols and aerosol constituents.

Eligibility

Eligibility for this supplement program is limited to current awardees of the following NIGMS programs:

• Institutional Development Award Program Infrastructure for Clinical and Translational Research (IDeA-CTR)
• Native American Research Centers for Health (NARCH)
• IDeA Networks of Biomedical Research Excellence (INBRE)
• Centers of Biomedical Research Excellence (COBRE) with ongoing research activity related to vaping, EVAL, or other lung-related diseases.

Only one supplement request per IDeA-CTR, NARCH, INBRE, or COBRE grant will be accepted. The proposed activity must be within the scope of the parent grant.

Active awards with project end dates in FY 2021 or later are eligible. The award may not be in terminal no-cost extension or going into a no-cost extension in FY 2020.

Application and Submission Information

Applications for this initiative must be submitted to PA-18-591 "Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional)".

All instructions in the SF424 (R&R) Application Guide and PA-18-591 must be followed, with the following additions:

• Applications will be accepted on a rolling basis from January 8, 2020 through March 27, 2020 by 5:00 PM local time of the applicant organization.
• For funding consideration, applicants must include “NOT-GM-20-008” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form.
• Requests can be for no more than $100,000 in direct costs exclusive of Facilities and Administrative costs on sub-contracts.
• Requests may not exceed one year of support.
• The Research Strategy section of the application is limited to 6 pages.
• A?pplications that are not responsive to the terms of this Notice will be not be considered for this initiative.

Eligible investigators are strongly encouraged to contact the Scientific/Research contact listed below prior to submitting an application.