ケニアの成人コホートにおける結核後肺疾患の臨床的およびトランスクリプトミクス的危険因子

Post-tuberculosis lung disease (PTLD), which includes restrictive and obstructive patterns of impairment, develops in 50% or more of survivors of tuberculosis, yet mechanisms and associated risk factors are poorly understood.

We sought to identify clinical and transcriptomic risk factors for PTLD phenotypes.

In a prospective, observational, cohort study, we enrolled adults (month 0) with newly diagnosed pulmonary tuberculosis in Nairobi, Kenya and evaluated clinical and transcriptomic risk factors for PTLD. Participants completed 6 months of standard anti-tuberculosis therapy. PTLD was defined as abnormal spirometry at month 12 (i.e., 6-months post-treatment) with either a restrictive- or obstructive-pattern.

We enrolled 205 participants of whom 103 (50.2%) had PTLD, including 60 with restrictive-PTLD and 43 obstructive-PTLD. Participants with PTLD had lower mid-upper arm circumference and cough peak flow. In multivariable analyses, more lung quadrants involved on radiograph at diagnosis was a risk factor for both restrictive- (aOR 2.1, P < .001) and obstructive-PTLD (aOR 2.2, P < .001). Prior tuberculosis was associated with obstructive-PTLD (aOR 5.4, P < .001). Gene expression improved clinical predictive models. In transcriptomic analyses, restrictive-PTLD was associated with upregulation of IL-6/JAK/STAT3 and TNF-α signaling at diagnosis (FDR < 0.2). In contrast, obstructive-PTLD was associated with transcriptomic upregulation of IFN-α and IFN-γ signaling responses (FDR < 0.2) at month 6.

Despite common clinical risk factors (lower mid-upper arm circumference, radiographic lung involvement), PTLD phenotypes have unique transcriptional signatures. Restrictive-PTLD is marked by early pro-fibrotic inflammation. In contrast, obstructive-PTLD is characterized by persistent inflammation at treatment completion.