2026/02/13 by Jerry S Zifodya, L Akeyo Kijaro, Videlis Nduba +10 · 1 voice
Medicine · #Chronic Obstructive Pulmonary Disease (COPD) Research #Pneumocystis jirovecii pneumonia detection and treatment #Tuberculosis Research and Epidemiology
paper · doi:10.1093/ajrccm/aamag063
openalex publication_date 2026/02/13 · openalex created_date 2026/02/22 · openalex updated_date 2026/07/12
RATIONALE: Post-tuberculosis lung disease (PTLD), which includes restrictive and obstructive patterns of impairment, develops in 50% or more of survivors of tuberculosis (TB), yet mechanisms and associated risk factors are poorly understood. OBJECTIVES: We sought to identify clinical and transcriptomic risk factors for PTLD phenotypes. METHODS: In a prospective, observational, cohort study, we enrolled adults (month 0) with newly diagnosed pulmonary TB in Nairobi, Kenya, and evaluated clinical and transcriptomic risk factors for PTLD. Participants completed 6 months of standard anti-TB therapy. PTLD was defined as abnormal spirometry at month 12 (ie, 6 months posttreatment) with either a restrictive or obstructive pattern. MEASUREMENTS AND MAIN RESULTS: 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 (MUAC) and cough peak flow. In multivariable analyses, having more lung quadrants involved on radiograph at diagnosis was a risk factor for both restrictive PTLD (adjusted odds ratio [aOR], 2.1; P <.001) and obstructive PTLD (aOR, 2.2; P <.001). Prior TB 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 (false discovery rate [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. CONCLUSIONS: Despite common clinical risk factors (lower MUAC, radiographic lung involvement), PTLD phenotypes have unique transcriptional signatures. Restrictive PTLD is marked by early profibrotic inflammation. In contrast, obstructive PTLD is characterized by persistent inflammation at treatment completion.