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Publications

Journal Article Preprint Epublish

PubMed: 39148848 DOI: 10.1101/2024.08.08.24311698

Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) study: Rationale and trial design for testing urine lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis.

medRxiv

Authors: Kara M Calhoun, Emily Armantrout, Katie Poch, Silvia Caceres, Valerie K Lovell, Marion Jones, Kenneth C Malcolm, Brian Vestal, Emily Wheeler, Noel Rysavy, Jordan Manzer, Ibrahim Aboellail, Delphi Chatterjee, Jerry A Nick

Affiliations

  • Department of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
  • Department of Medicine, National Jewish Health, Denver, CO, 80206, USA.
  • Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA.
  • Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, 1682 Campus Delivery, Fort Collins, CO, USA.

Abstract

Background

Routine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This is particularly challenging in the cystic fibrosis (CF) population due to reduced sputum production and low culture sensitivity. Biomarkers of infection that do not rely on sputum may lead to earlier diagnosis, but validation trials require a unique prospective design.

Purpose

The rationale of this trial is to investigate the utility of urine lipoarabinomannan (LAM) as a test to identify people with CF with a new positive NTM culture. We hypothesize that urine LAM is a sensitive, non-invasive screening test with a high negative predictive value to identify individuals with a relatively low risk of having positive NTM sputum culture.

Study design

This is a prospective, single-center, non-randomized observational study in adults with CF, 3 years of negative NTM cultures, and no known history of NTM positive cultures. Patients are followed for two year-long observational periods with the primary endpoint being a positive NTM sputum culture within a year of a positive urine LAM result and a secondary endpoint of a positive NTM sputum culture within 3 years of a positive urine LAM result. Study implementation includes remote consent and sample collection to accommodate changes from the COVID-19 pandemic.

Conclusions

This report describes the study design of an observational study aimed at using a urine biomarker to assist in the diagnosis of NTM lung infection in pwCF. If successful, urine LAM could be used as an adjunct to traditional sputum cultures for routine NTM screening.

MeSH

Research Design, Lung, Fibrosis, Biomarkers, Cystic Fibrosis, Sputum, Covid-19, Diagnosis, Infections