Cough Capture as a Portal Into the Lung

Summary

The lung is a privileged organ; blood does not reflect most lung processes well, if at all. Therefore, for population scale diagnostics, the investigator team is developing non-invasive portals to the lung, for eventual early detection/risk assessment and diagnostic purposes. However, large macromolecules are not likely suspended nor readily detected in the breath. In particular, genomic DNA in the breath condensate (EBC) is very sparse, and where present, generally highly fragmented, not readily amenable to sequencing based assessments of DNA somatic mutation burden or distribution. Because gDNA (and protein) is challenging to obtain non-invasively from EBC, the study team considered alternative surrogate lower airway specimens. Cough capture is rarely done, and the investigator team is in the process of optimizing its collection. Importantly, the team will be evaluating how much of coughed material is from saliva contamination. Additionally, analyzing material that is target captured by capturing deep lung extracellular vesicles (EVs) using immobilized CCSP/SFTPC antibodies targeting EVs from distal bronchiole Club and alveolar type 2 cells could circumvent the mouth contamination problem, leaving a non-invasive portal to the deep lung suitable for large molecules, and in turn suitable for myriad epidemiologic and clinical applications.

The investigator team proposes (Aim 1) to pursue optimizing cough collection, and testing the efficacy and practicality of partitioning cough specimen for deep-lung specific extra-cellular vesicles (EVs). This cough specimen will be compared to that from invasively collected deep lung samples BAL/bronchial brushings, and to the potential contaminating mouth rinse, all from the same individuals. (Aim 2) The study team initially proposes to examine these cough specimens for somatic mutations by SMM bulk sequencing for single nucleotide variation, developed in the Vijg/Maslov labs. Finally, the investigator team will (Aim 3) test all airway specimens (cough, mouthwash and BAL) for lung surrogacy of cough, using proteins known to be specific for lung, as opposed to oral cavity/saliva, in the Sidoli/proteomics core.

The investigator team envisions that the translational impact of non-invasively obtained DNA or protein markers could allow for more rapid acute clinical diagnoses, and facilitate precision prevention and/or early detection of many acute and chronic respiratory disorders, including lung cancer, asthma and COPD, acute and chronic infectious diseases, and indeed systemic disorders of inflammation and metabolism.

Conditions

• Lung Diseases
• Lung Cancer
• Lung Diseases, Obstructive
• Lung Diseases, Interstitial
• Lung Inflammation

Interventions

OTHER

Observational only, all subjects; measure DNA mutation and proteomic survey.

Observational only, all subjects; measure DNA mutation and proteomic survey.

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS)

  collaborator NIH

• National Cancer Institute (NCI)

  collaborator NIH

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• National Institute of Environmental Health Sciences (NIEHS)

  collaborator NIH

• Evaluate Diagnostics

  collaborator UNKNOWN

• James J. Peters Veterans Affairs Medical Center

  collaborator FED

• Touro University

  collaborator OTHER

• Hackensack Meridian Health

  collaborator OTHER

• The Scripps Research Institute

  collaborator OTHER

• Weill Medical College of Cornell University

  collaborator OTHER

• Cold Spring Harbor Laboratory

  collaborator OTHER

• Albert Einstein College of Medicine

  lead OTHER

Principal Investigators

• Simon D Spivack, MD · Albert Einstein College of Medicine

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-03-28

Primary Completion

2027-06-30

Completion

2027-06-30

Countries

• United States

Study Locations