Evaluation Of The Lung Microbiome In NTM Bronchiectasis

A biomarker cohort study design is proposed to study whether specific airway microbiota alterations are associated with pulmonary Non-tuberculous mycobacteria (NTM) disease. In a cohort of 200 subjects suspected of having pulmonary NTM disease, the investigators will evaluate the airway microbiome using an aliquot of the induced sputum and upper airway samples. Since induced sputum may reflect different regions of the upper/lower airways, the investigators will evaluate the upper and lower airway microbiome in a subgroup (case-control group) of patients using samples obtained through upper airway sampling and bronchoscopy, respectively.

Study Overview

• Status: Recruiting
• Conditions: Bronchiectasis; Nontuberculous Mycobacteria
• Intervention / Treatment: Procedure: Bronchoscopy

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Rosemary Schluger; Email: Rosemary.Schluger@nyulangone.org
• Study Contact Backup: Name: Lisa Guiterrez; Email: Lira.Gutierrez@nyulangone.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University School of Medicine
      • Sub-Investigator: Stephanie Lau, MD
      • Sub-Investigator: Ashwin Basavaraj, MD
      • Contact: Maria Tarallo, MD; Email: taralm01@nyumc.org
      • Contact: Adrienne Scott; Email: scotta06@nyumc.org
      • Principal Investigator: Leopoldo Segal, MD
      • Sub-Investigator: Milan Amin, MD
      • Sub-Investigator: David Kamelhar, MD
      • Sub-Investigator: Doreen Addrizzo-Harris, MD
      • Sub-Investigator: Katrina Bantis, MD
      • Sub-Investigator: Benjamin Wu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Utilizing cohorts built at NYU over the last several years, this project is uniquely positioned to investigate the microbiome signatures among subjects with NTM disease.

Description

Inclusion Criteria:

• History of pulmonary symptoms: cough, fatigue, malaise, fever, weight loss, dyspnea, hemoptysis, or chest discomfort
• Imaging abnormalities (within 2 years): defined as nodular or cavitary opacities on chest radiograph, or a computed tomography scan that shows bronchiectasis or bronchial wall thickening with associated multiple small nodules.

Definition of NTM case:

• Subjects that meet inclusion criteria and have culture positivity for NTM: at least two separate expectorated induced sputum samples or from one bronchoalveolar lavage (BAL) or lung biopsy

Definition of NTM control:

• Subjects that meet inclusion criteria and have less than two separate expectorated induced sputum samples culture negative or culture negative bronchoalveolar lavage (BAL) or lung biopsy.

Exclusion Criteria for cohort study (Aim 1-2):

• Recent (<1 months prior) oral antibiotic or steroid use. (Continuous treatment with macrolides and inhaled steroids are acceptable >1 month prior)
• Recent smoking history

Exclusion Criteria for bronchoscopic study (Aims 3-4):

• Forced expiratory volume at one second (FEV1) < 70%of predicted.
• Significant cardiovascular disease defined as abnormal EKG, known or suspected coronary artery disease or congestive heart failure.
• Diabetes mellitus
• Significant liver or renal disease
• Severe coagulopathy (INR > 1.4, Partial Thromboplastin Time (PTT) > 40 seconds and platelet count < 150x103 cells).
• Pregnancy
• Ethanol (ETOH) use of more than >6 beers or >4 mixed drinks daily
• Lack of capacity to provide informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Positive NTM Culture; Subjects that meet inclusion criteria and have culture positivity for NTM: at least two separate expectorated induced sputum samples or from one bronchoalveolar lavage (BAL) or lung biopsy	Procedure: Bronchoscopy
Negative NTM Culture; Subjects that meet inclusion criteria and have less than two separate expectorated induced sputum samples culture negative or culture negative bronchoalveolar lavage (BAL) or lung biopsy.	Procedure: Bronchoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of airway microbiome in subjects with active pulmonary NTM disease and compare with controls	Investigators will use sputum samples and brushed samples from areas of the upper airway from a cohort of 200 subjects with chronic cough and pulmonary infiltrates or airway abnormalities in whom NTM disease was suspected. Cultures positive for NTM (cases) will be compared to those with culture negatives (controls). Bacterial load by quantitative polymerase chain reaction (qPCR) will be used to characterize microbiome by high throughput sequencing looking for microbial biomarkers associated with NTM disease.	4 Hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Eating Assessment Tool (EAT-10) to evaluate the prevalence of laryngopharyngeal reflux and dysphagia/aspiration in subjects with active pulmonary NTM disease compared with controls	1 Hour
Laryngoscopy to calculate the Reflux finding score (RFS, a validated quantitative measurement of impact of laryngopharyngeal reflux on the upper airway in adults	4 Hours
Reflux Symptom Index evaluate the prevalence of laryngopharyngeal reflux and dysphagia/aspiration in subjects with active pulmonary NTM disease compared with controls	1 Hour

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Leopoldo Segal, MD, New York University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2014
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (Estimated): May 20, 2016

Study Record Updates

• Last Update Posted (Actual): August 15, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: NTM; chronic obstructive pulmonary disease (COPD); cavitary; nodular bronchiectatic disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: 14-01400

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No