Cough Capture as a Portal Into the Lung

NCT05854563 | Recruiting DMC

• 5 other identifiers: 2007-407U01ES029519U01HL145560R33HL156279UM1TR004400
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief 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 Cancer; Lung Diseases, Obstructive; Lung Diseases, Interstitial; Lung Inflammation; Lung Diseases

Outcome Measures

Primary Outcomes (4)

• Number of smoker and non-smoker participants demonstrating somatic DNA mutations as evidenced by mutation burden

  Somatic DNA analysis will be conducted using Single Molecule Mutation sequencing (SMM-seq) to identify mutations in EV-partitioned cough samples. The number will be determined by statistical testing using Fishers Exact Test to determine if there is a nonrandom association between the two variables

  Up to 30 minutes for collection of all airway samples

• Aggregate Median Mutation Rate in smoker and non-smoker participants

  Somatic DNA analysis will be conducted using Single Molecule Mutation sequencing (SMM-seq) to identify mutations in EV-partitioned cough samples. The aggregate median mutation rate (somatic mutation burden) in the cough from the group of smokers, as compared to that of non-smoking individuals, will be determined by statistical T-test.

  Up to 30 minutes for collection of all airway samples

• Number of smoker and non-smoker participants demonstrating altered protein expression

  Proteomic analysis will be conducted via LC-MS on the collected and EV-partitioned cough samples, MW samples, and BAL samples, respectively. To evaluate cough surrogacy for the deep lung (BAL) specimen, Spearman correlations of the most highly expressed 80 proteins among the three specimen types will be compared. The number of participant specimens demonstrating Spearman inter-tissue correlation values in excess of their corresponding threshold (0.3) will be tabulated.

  Up to 30 minutes for collection of all airway samples

• Proteomic signature comparison in smoker and non-smoker participants

  Proteomic analysis will be conducted via LC-MS on the collected and EV-partitioned cough samples, MW samples, and BAL samples, respectively. The proteomic signature of the most highly expressed 80 proteins in each of three specimen types will be compared between the current smoker and the non-smoker participants using PCA.

  Up to 30 minutes for collection of all airway samples

Study Arms (2)

Bronchoscopy subjects, current or former smokers

Bronchoscopy subjects \>=21 yo, current or former smokers

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

Bronchoscopy subjects, never smokers

Bronchoscopy subjects \>=21 yo, never smokers

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

Interventions

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

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

Also known as: Observational study to develop a cough diagnostic

Bronchoscopy subjects, current or former smokers; Bronchoscopy subjects, never smokers

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All consenting subjects \>=21 y.o.with a clinical indication/imminent bronchoscopy.

You may qualify if:

• Age: minimum age of 21 years
• Gender: Male and Female adults
• Ethnicity: All ethnic groups and races
• Subjects undergoing bronchoscopy for diagnostic purposes or therapy
• Subjects without a known diagnosis of lung cancer who are not scheduled for lung tissue collection procedures
• Subjects with a known or suspected diagnosis of asthma or COPD and are scheduled for a visit at Montefiore Asthma or COPD Center and individual practices, and/or in-hospital with exacerbation

You may not qualify if:

• Bleeding diathesis or known coagulopathy precluding clinically indicated biopsy (e.g., INR\>1.3, PTTr\>1.3), thrombocytopenia \<50,000, uremia with serum creatinine \>3.0
• Unstable angina
• Recent myocardial infarction (within 3 months),
• Uncontrolled congestive heart failure or severe pulmonary hypertension (mean PAP\>75 mmHg)

Sponsors & Collaborators

• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Cancer Institute (NCI): collaborator
• Albert Einstein College of Medicine: lead
• National Institute of Environmental Health Sciences (NIEHS): collaborator
• Touro University: collaborator
• The Scripps Research Institute: collaborator
• Weill Medical College of Cornell University: collaborator
• Cold Spring Harbor Laboratory: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Evaluate Diagnostics: collaborator
• James J. Peters Veterans Affairs Medical Center: collaborator
• Hackensack Meridian Health: collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

RECRUITING

Related Publications (8)

• Mitchell MI, Ben-Dov IZ, Ye K, Liu C, Shi M, Sadoughi A, Shah C, Siddiqui T, Okorozo A, Gutierrez M, Unawane R, Biamonte L, Parikh K, Spivack S, Loudig O. Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed. J Extracell Vesicles. 2024 Apr;13(4):e12440. doi: 10.1002/jev2.12440.

  PMID: 38659349 BACKGROUND

• Shi M, Han W, Loudig O, Shah CD, Dobkin JB, Keller S, Sadoughi A, Zhu C, Siegel RE, Fernandez MK, DeLaRosa L, Patel D, Desai A, Siddiqui T, Gombar S, Suh Y, Wang T, Hosgood HD, Pradhan K, Ye K, Spivack SD. Initial development and testing of an exhaled microRNA detection strategy for lung cancer case-control discrimination. Sci Rep. 2023 Apr 24;13(1):6620. doi: 10.1038/s41598-023-33698-8.

  PMID: 37095155 BACKGROUND

• Huang Z, Sun S, Lee M, Maslov AY, Shi M, Waldman S, Marsh A, Siddiqui T, Dong X, Peter Y, Sadoughi A, Shah C, Ye K, Spivack SD, Vijg J. Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking. Nat Genet. 2022 Apr;54(4):492-498. doi: 10.1038/s41588-022-01035-w. Epub 2022 Apr 11.

  PMID: 35410377 BACKGROUND

• Zefi O, Waldman S, Marsh A, Shi MK, Sonbolian Y, Khulan B, Siddiqui T, Desai A, Patel D, Okorozo A, Khader S, Dobkin J, Sadoughi A, Shah C, Spivack S, Peter Y. Distinctive field effects of smoking and lung cancer case-control status on bronchial basal cell growth and signaling. Respir Res. 2024 Aug 19;25(1):317. doi: 10.1186/s12931-024-02924-w.

  PMID: 39160511 RESULT

• Khulan B, Ye K, Shi MK, Waldman S, Marsh A, Siddiqui T, Okorozo A, Desai A, Patel D, Dobkin J, Sadoughi A, Shah C, Gera S, Peter Y, Liao W, Vijg J, Spivack SD. Normal bronchial field basal cells show persistent methylome-wide impact of tobacco smoking, including in known cancer genes. Epigenetics. 2025 Dec;20(1):2466382. doi: 10.1080/15592294.2025.2466382. Epub 2025 Feb 20.

  PMID: 39980243 RESULT

• S.D. Spivack, M.W. Azam, A. Okorozo, K. Batbayar, A.Y. Maslov, M. Lee, J. Vijg, and O. Loudig. Development of Cough Access to the Deep Lung for Somatic Mutagenesis Assessment [abstract]. Am J Respir Crit Care Med 2025;211:A4800. https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A4800

  RESULT

• S.D. Spivack, O. Zefi, S. Waldman, M. Shi, T. Siddiqui, A. Desai, D. Patel, A. Okorozo, J.B. Dobkin, A. Sadoughi, and C. Shah. Altered Bronchialbasal Cell Morphology and Growth Phenotypes in Field Carcinogenesis Correspond With Altered Notch Signaling Patterns [abstract]. Am J Respir Crit Care Med 2025;211:A7917. https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A791

  RESULT

• S.D. Spivack, K. Batbayar, A. Maslov, M. Lee, M.W. Azam, and J. Vijg. Genome-wide Tobacco Smoke Mutagenesis Modelled in Long Term HBEC Bronchial Basal Epithelial Cells In Vitro [abstract]. Am J Respir Crit Care Med 2025;211:A4801. https://doi.org/10.1164/ajrccm.2025.211.Abstracts.A4801

  RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Cough is captured by voluntary cough singlets, with a subject handheld mouthpiece in place, currently Aerochamber or equivalent. Sample is collected by rinse, solvated in PBS or other buffer appropriate to the analyte.

MeSH Terms

Conditions

Lung Diseases; Lung Neoplasms; Lung Diseases, Obstructive; Lung Diseases, Interstitial; Pneumonia

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Respiratory Tract Infections; Infections

Study Officials

• Simon D Spivack, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aham Okorozo, MD

CONTACT

718-678-1035; ahamefule.okorozo@einsteinmed.edu

Khulan Batbayar, PhD

CONTACT

718-678-1040; Khulan.Batbayar@einsteinmed.edu

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2023
• First Posted: May 11, 2023
• Study Start: March 28, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Within 6 months of study publication/conclusion

Locations

US (1)