Urine Marker Could Help in Screening for CF Lung Infections, Study Finds

Measuring levels of a molecule called lipoarabinomannan, or LAM, in a person’s urine could be an easier way of screening for airway infections due to nontuberculous mycobacteria in people with cystic fibrosis (CF), a study suggests.

The study, “Urine lipoarabinomannan as a marker for low-risk of NTM infection in the CF airway,” was published in the Journal of Cystic Fibrosis.

Nontuberculous mycobacteria (NTM) are bacteria from the genus mycobacteria other than Mycobacterium tuberculosis, which causes tuberculosis, and Mycobacterium leprae, which causes leprosy. NTM can cause infections in people, particularly in those with pre-existing lung conditions.

CF patients are at risk of NTM infection, with previous research indicating that about 1 in 5 will test positive for NTM. The current gold standard for diagnosing NTM infection is a bacterial culture test of the airways. However, this method has notable drawbacks: it can be costly, take weeks to get results, its sensitivity is low, and it can be difficult to obtain samples from certain individuals, especially children.

LAM is a molecule found in all mycobacteria species, and released by the bacteria when they are active. Recent research has suggested that LAM detected in urine might serve as a marker for tuberculosis.

“We hypothesized that urine LAM would be a useful, non-invasive test to screen for individuals with low risk of having a positive [NTM] culture,” the researchers wrote.

To test their hypothesis, researchers analyzed 45 urine samples taken from 44 CF patients with a well-documented NTM culture status. These individuals included were “representative of the CF population in general,” the researchers wrote. Their average age was 24.6 (ranging from 11 to 63), and there were 16 males and 28 females.

Two different methods were used to detect LAM: an antibody-based assay (ELISA), and an assay utilizing mass spectrometry. Results from both were generally in agreement. Some samples were only analyzed by one method due to quantity limitations.

In total, 31 of these patients had a history of positive NTM cultures, including seven who had been treated and had been NTM culture-negative on a sputum test for at least a year. All of these patients had LAM detected in their urine.

Fourteen others had no history of NTM infection at the time of a urine analysis, with 407 negative NTM sputum cultures recorded over an average of 2.75 years. None of these patients had LAM detected in their urine.

“In a CF cohort well characterized for NTM status, we were able to demonstrate complete correlation between the presence of LAM in the urine and a history of NTM recovered from sputum samples,” the researchers wrote.

Of note, one patient who was initially negative for both NTM sputum culture and LAM had positive NTM culture results about two years after the initial urine sample. Repeat collection showed that, following this culture result, LAM was detected in the patient’s urine.

Additional analyses showed that LAM levels may also be linked with a particular type of NTM — higher urine LAM levels were significantly associated with positive culture for the bacterium M. abscessus.

No clear association was found between urine LAM levels and “traditional markers of disease activity or bacterial burden in this small cohort,” the researchers wrote.

These results indicate that detecting LAM in urine can help to rule out individuals who probably do not need an NTM culture. That is, patients who test negative for urine LAM are likely to also test negative in a NTM sputum culture, so this test would not be necessary.

“The great majority of people with CF will not develop NTM infection, and in the absence of clinical suspicion, a negative urine LAM result could potentially replace sputum cultures as a method of annual screening,” the researchers wrote. “In particular, children are at low risk for NTM infection, and are also often unable to expectorate sputum.”

Based on this work, the team suggested that “urine LAM could be part of a lifetime screening strategy for the diagnosis of NTM, and that a larger, prospective longitudinal clinical trial is warranted to validate these results and to establish the durability of the signal.”