The incremental value of bronchoalveolar lavage for the diagnosis of pulmonary tuberculosis in a high-burden urban setting

Summary

Objectives

We prospectively evaluated the use of bronchoalveolar lavage fluid (BALF) specimens to assess their added incremental value to pulmonary tuberculosis (TB) diagnostic strategies used currently in a high-burden urban setting in China.

Methods

A prospective study was conducted of patients with presumptive pulmonary TB registered at the Fifth Hospital of Suzhou between March 2018 and July 2018. BALF samples from patients with initial Xpert-negative sputum results were tested to diagnose TB.

Results

Of 440 participants, 316 (71.8%) were initially diagnosed with TB from sputum, including 245 (55.7%) definitive TB cases based on a positive culture and/or Xpert result(s) and 71 (16.1%) positive cases based on clinical diagnosis. Of 153 patients with initial positive cultures, a significantly higher proportion were confirmed as TB-positive using Xpert (94.1%) versus smear microscopy (45.8%, P < 0.01). Xpert testing of BALF from 182 Xpert-negative cases exhibited greater detection sensitivity (97.4%) than did smear microscopy (23.4%, P < 0.01). Meanwhile, 74.1% of TB patients initially diagnosed as TB-negative via smear microscopy were identified using Xpert testing of BALF at reduced diagnostic cost/patient (from USD 266.9 to 171.5).

Conclusions

BALF samples added incremental value to pulmonary TB diagnostic strategies for patients with Xpert-negative sputum. Xpert outperformed smear microscopy for tubercle bacilli detection in both sputum and BALF.

Introduction

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB) complex, remains one of the most common and deadliest diseases worldwide, with an estimated global mortality rate of 1.6 million deaths in 2017.1, 2 Efforts to reduce mortality should focus on early diagnosis and immediate initiation of effective treatment in TB patients.² Despite recent advances, pulmonary TB is primarily diagnosed via identification of MTB using sputum smear microscopy. However, this simple method lacks both sensitivity and specificity that are urgently needed in high-incidence settings.3, 4 Mycobacterial culture, the gold standard diagnostic technique, yields high sensitivity for detecting MTB from clinical specimens.³ Unfortunately, the lengthy procedure, due to the slow growth rate of MTB, cannot meet clinical needs for point-of-care diagnostics⁵ and requires an extensive laboratory infrastructure that is lacking in resource-limited settings.³

Recently, the Xpert MTB/RIF (Xpert) assay (Cepheid, Sunnyvale, CA) has been developed as an integrated system incorporating a disposable cartridge that performs both specimen processing and molecular detection.6, 7 By targeting the rpoB gene sequence of MTB, Xpert detects both the presence of MTB and its susceptibility to rifampin within 2 h.⁶ Several multicenter studies have demonstrated that this assay offers a level of detection sensitivity approaching that of the culture-based gold standard method.6, 8 As a consequence, Xpert is endorsed by the World Health Organization (WHO) for use in TB diagnosis, particularly for HIV-infected individuals and suspected MDR-TB cases.⁹ Although the application of molecular diagnostics greatly accelerates the timely acquisition of results needed for patient management decision-making, a large number of pulmonary TB patients remain undiagnosed due to a lack of microbiological evidence.¹ According to a recent global TB epidemic annual report, nearly half of reported cases were diagnosed based only on patient symptoms and chest X-ray findings.¹ The situation is even worse in China, where laboratory results can confirm MTB organisms in only 30% of suspected TB cases, leaving no room for doubt that the current diagnostic algorithm based on non-specific clinical manifestations results in either over- or underdiagnosis of pulmonary TB.¹⁰ Therefore, there is an urgent need to formulate a new diagnostic algorithm that adds incremental value to currently recommended TB diagnostic strategies.

Bronchoalveolar lavage fluid (BALF) is a promising alternative to the commonly used sputum specimen for detecting MTB in individuals with suspected TB, especially for patients who fail to provide sputum specimens of adequate volume or quality.¹¹ Indeed, there is strong evidence that BALF is superior to sputum for use in bacteriological confirmation of pulmonary TB, especially for patients with smear-negative TB results.¹¹ Thus, it would be meaningful to investigate whether the use of BALF samples collected from patients without bacteriological evidence of TB would be beneficial for clinical TB diagnostic decision-making. Indeed, little has been reported regarding this issue to date, especially with regard to strategies incorporating both Xpert and BALF. Therefore, in this study we prospectively evaluated the use of BALF specimens to assess their added incremental value to pulmonary TB diagnostic strategies used currently in a high-burden urban setting in China.