Biomarker for Low Risk NTM Infection in the Airway of Cystic Fibrosis Patients

NJH ID: #20-03

Background
Cystic fibrosis (CF) is a progressive, chronic disease characterized by the production of thick, sticky mucus that can clog the lungs. This mucus is an ideal environment for the colonization of different bacteria.
Nontuberculous mycobacteria (NTM) are environmental organisms found in soil and water worldwide. In recent years, NTM have become a real problem causing chronic lung infections.
CF has been identified as the disease population at greatest risk for NTM airway infection and the lack of sensitive and specific markers of NTM in the airway is a significant barrier for patient care. Culture from the airway is the only method currently utilized for screening, and the gold standard by which all diagnosis and treatment decisions are made. But there are several limitations to this modality, including slow growth (up to 8 weeks), high cost and low sensitivity. In addition, CF sputum samples contain bacterial co-pathogens, resulting in the need to decontamination procedures, which could significantly reduce NTM viability and can be source of false negative results.
Lipoarabinomannan (LAM) is a cell wall lipoglycan found in all mycobacteria species that is released into circulation from metabolically active or degrading bacteria. It has recently gained attention as a biomarker for active tuberculosis because it is found in the urine of infected patients.
LAM could be a useful, non-invasive test to screen for individuals with low risk of having a positive culture for NTM.

 

Technology
Dr. Nick from National Jewish Health and Dr. Chatterjee from Colorado State University have developed a novel non-invasive first screening tool to segregate patients for which NTM sputum cultures are not needed. This test measures urine LAM by gas chromatography–mass spectrometry. In a very well characterized CF population they demonstrated a significant correlation between the presence of LAM in urine samples and a history of NTM recovered in sputum. As part of these studies, they also developed a urine sample handling protocol where LAM is separated from other endogenous neutral polysaccharides, increasing the specificity and sensitivity of this test.

 

Potential Applications
Diagnostics: This method may be effectively used as an inexpensive, highly sensitive, non-invasive screening test to identify individuals with an extremely low risk of having a positive NTM sputum culture, and could be performed as part of a two-step screening/diagnosis strategy for the CF population.

 

State of Development
Additional studies are being performed to verified the correlation between negative urine LAM with a negative NTM sputum cultures and the sensitivity of a positive urine LAM with a positive sputum culture.

 

Publications

  • Nick JA, Chatterjee D. Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway. J Cyst Fibros. 2020 Sep;19(5):801-807. PMID: 32624408

 

Patent Status
PCT Patent Application filed. 

 

Inventors
Jerry A. Nick, MD and Delphi Chatterjee, PhD

 

Licensing Status
This technology is available for licensing.

 

For Further Information, Contact:
Emmanuel Hilaire, PhD
Director
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: 303.398.1262
HilaireE@njhealth.org