A Whole-blood Transcriptional Signature Associated With Obstructive Post-tuberculosis Lung Disease

Post-tuberculosis (TB) lung disease (PTLD) affects ∼50% of persons with pulmonary TB (PTB). We recently discovered whole blood transcriptional signatures associated with PTLD. We examined whether a minimum gene signature predicts PTLD as a clinically useful biomarker.

We prospectively enrolled 301 treatment naive adults with newly diagnosed PTB (cohort A). We collected whole blood at 0 and 6-month visits, isolated RNA, and measured a modified MTB host response (HR) signature (mHR) based on expression of DUSP3, GBP5, and TMBIM6. We recorded spirometry at 6 (n = 216) and 12 months (n = 210) after treatment initiation and examined the association of the mHR score with PTLD and Mtb aerosolization. We recruited household contacts of cohort A to compare mHR score with non-PTB participants (cohort B).

mHR was associated with TB (P = 4.15e-66) when compared to HHCs, treatment response (P = 1.07e-53), and characteristics including CD4 count (P = .003), bacillary load (P = 3.02e-05), lung cavities (P = 1.59e-04), and lung quadrants involved (P = 3.87e-06). The mHR score was not associated with Mtb aerosolization. In total, 105 (50%) participants had PTLD at 12 months including 61 with restriction, 26 with obstruction, and 18 with mixed obstruction and restriction. Baseline mHR was associated with obstructive PTLD at both 6 (P = .003) and 12 months (P = .012) in bivariate and multivariate analyses. The mHR score was not associated with restrictive lung disease.

Baseline mHR was associated with obstructive PTLD at 6 and 12 months and may have applications in targeting treatment and prognostication.