Indicators for prediction of Mycobacterium tuberculosis positivity detected with bronchoalveolar lavage fluid

Abstract

BackgroundThe diagnosis of active pulmonary tuberculosis (TB) remains a challenge in clinic, especially for sputum negative pulmonary TB. Bronchoalveolar lavage fluid (BALF) has higher sensitivity than sputum for detection of Mycobacterium tuberculosis (Mtb). However, bronchoscopy is invasive and costly, and not suitable for all patients. In order to make TB patients get more benefit from BALF for diagnosis, we explore which indicator might be used to optimize the choice of bronchoscopy.MethodsA total of 1539 sputum-smear-negative pulmonary TB suspects who underwent bronchoscopy were recruited for evaluation. The sensitivity, specificity and accuracy of Mtb detection in sputum and BALF were compared. Odds ratios and 95% confidence intervals were used to assess variables that associated with positive acid-fast bacilli (AFB) smear, Mtb culture and nucleic acid amplification test (NAAT) of BALF in sputum-negative and non-sputum-producing pulmonary TB suspects.ResultsBALF has significantly higher sensitivity (63.4%) than sputum (43.5%) for Mtb detection by culture and NAAT. 19.7% (122/620) sputum-negative and 40.0% (163/408) non-sputum-producing suspects had positive bacteriological results in BALF. Among sputum-negative and non-sputum-producing pulmonary TB suspects, the positivity of Mtb detection in BALF is associated with a younger age, the presence of pulmonary cavities and a positive result of interferon-gamma release assay (IGRA). Sputum-negative patients under 35 years old with positive IGRA and pulmonary cavity had 84.8% positivity of Mtb in BALF.ConclusionsOur study indicated that combination of age, the presence of pulmonary cavity, and the result of IGRA is useful to predict the positivity of Mtb detection in BALF among sputum-negative and non-sputum producing pulmonary TB suspects. Those who are under 35 years old, positive for the presence of pulmonary cavity and IGRA, should undergo bronchoscopy to collect BAFL for Mtb tests, as they have the highest possibility to get bacteriologically confirmation of TB.Electronic supplementary materialThe online version of this article (10.1186/s40249-018-0403-x) contains supplementary material, which is available to authorized users.

Comprehensive Determination of Mycobacterium tuberculosis and Nontuberculous Mycobacteria From Targeted Capture Sequencing

“…In our study, samples sequenced from BALF had a higher reference genome coverage as compared with those obtained from sputum, and this was correlated to the number of lineage-specific reads in BALF samples that was significantly more than in sputum samples, and the drug resistance was mostly discovered in BALF samples ( Figure 4 ). These results indicated that the BALF sample might be more suitable for detecting MTB types and drug resistance by targeted capture sequencing, which are consistent with a previous study: Liu et al ( 2018 ) found BALF has significantly higher sensitivity (63.4%) than sputum (43.5%) for MTB detection by culture and nucleic acid amplification test; To et al ( 2018 ) discovered that the sensitivity and specificity of GeneXpert for TB diagnosis using BALF was 80 and 98% in sputum AFB smear negative patients, respectively. The main reason is that some patients were bacteriologically negative due to lack of sputum or false-negative due to poor sputum sample quality.…”

“…In addition, NGS directly from sputum can quickly generate a complete genetic drug resistance profile, faster than MGIT culture sequencing (Nimmo et al, 2017 ). Otherwise, BALF specimens have been applied widely in the detection of pulmonary pathogenic bacteria infection including MTB and NTM (Theron et al, 2013 ; Yamasaki et al, 2015 ; Liu et al, 2018 ). In our study, samples sequenced from BALF had a higher reference genome coverage as compared with those obtained from sputum, and this was correlated to the number of lineage-specific reads in BALF samples that was significantly more than in sputum samples, and the drug resistance was mostly discovered in BALF samples ( Figure 4 ).…”

Identifying predictors to gain sensitivity of nucleic acid amplification tests for Mycobacterium tuberculosis

“…Together, about 50% and 15% patients bene ted from NAAT tests compared with smear and culture, respectively. NAAT test improved the positive detectable rate of PTB diagnosis as well as contributed to the effective anti-TB therapy by identifying species and drug susceptibility testing (12).…”

Different source of sample strains corresponds to different characteristics of patients with non-tuberculous mycobacterium

“…BALF is superior to the expectorated sputum in the diagnosis of lower respiratory tract tuberculosis [12,13]. Indeed in patients with suspected sputum-smear-negative pulmonary tuberculosis, Liu et., al, found that the sensitivity of 63.4% by culture or nucleic acid ampli cation test from BALF was higher than the sensitivity of 43.5% from sputum [13]. In addition, the presence of the Mycobacterium tuberculosis complex (MTBC) was detected in BALF specimen from patients who could no produce sputum.…”

“…In addition, adenosine deaminase activity in BALF is useful in the diagnosis of tuberculosis with negative sputum smears [14]. The authors found that, among all the collected samples, BALF samples positive for MTBC is associated with patients' characteristics including younger age, existence of pulmonary cavity and positive interferon-gamma release assay [13]. As suggested by studies on tuberculosis, the pathogens from various specimen sources may not only differ in susceptibility and speci city in smear or culture assay for diagnosis, but also re ect different risk factors for the host.…”