Culture independent markers of nontuberculous mycobacterial (NTM) lung infection and disease in the cystic fibrosis airway

Abstract

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that affect a relatively small but significant portion of the people with cystic fibrosis (CF), and may cause increased morbidity and mortality in this population. Cultures from the airway are the only test currently in clinical use for detecting NTM. Culture techniques used in clinical laboratories are insensitive and poorly suited for population screening or to follow progression of disease or treatment response. The lack of sensitive and quantitative markers of NTM in the airway impedes patient care and clinical trial design, and has limited our understanding of patterns of acquisition, latency and pathogenesis of disease. Culture-independent markers of NTM infection have the potential to overcome many of the limitations of standard NTM cultures, especially the very slow growth, inability to quantitate bacterial burden, and low sensitivity due to required decontamination procedures. A range of markers have been identified in sputum, saliva, breath, blood, urine, as well as radiographic studies. Proposed markers to detect presence of NTM or transition to NTM disease include bacterial cell wall products and DNA, as well as markers of host immune response such as immunoglobulins and the gene expression of circulating leukocytes. In all cases the sensitivity of culture-independent markers is greater than standard cultures; however, most do not discriminate between various NTM species. Thus, each marker may be best suited for a specific clinical application, or combined with other markers and traditional cultures to improve diagnosis and monitoring of treatment response.

Keywords: CFTR modulator therapy; Cystic fibrosis; Immunoglobulin; Lipoarabinomannan; Mycobacterium abscessus; Mycobacterium avium complex; Nontuberculous mycobacterial (NTM) lung disease.

Fig. 1.. Clinical utilization of NTM markers.

A. Screening for presence of infection in the majority of individuals who have never had NTM (white figures) and are at low annual risk for NTM infection. B. Species or complex identification among those found to have positive cultures. C. Diagnosis of indolent infection (yellow figures) versus individuals with NTM disease who may benefit from treatment (right column). D. Within subject determination of treatment response or eradication.