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Soluble Programmed Death-1 as a Biomarker of Severity and Progression in Nodular-bronchiectatic Nontuberculous
Sheng-Wei Pan1, Koji Furuuchi2, Yung-Che Chen3
1Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Background:
Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasingly prevalent, yet no validated biomarker predicts progression in nodular-bronchiectatic (NB) NTM-PD. A Taiwan study linked soluble programmed death-1 (sPD-1), an immune exhaustion marker, to cavitary lesions and progression in NB-pattern NTM-PD, highlighting the need for broader validation.
Methods:
In this multicountry cohort study, patients with NB-pattern NTM-PD and healthy controls were enrolled in East Asia. Blood sPD-1 levels were measured using enzyme-linked immunosorbent assay, and their associations with cavitary NB pattern and disease progression requiring anti-NTM treatment were analyzed using Cox regression.
Results:
Overall, a total of 68 healthy controls and 400 patients with NB-pattern NTM-PD were included. sPD-1 levels were lower in the NTM-PD group than in the control group: 44.2pg/mL (IQR, 26.0-65.4pg/mL) vs 61.5pg/mL (IQR, 38.0-81.4pg/mL); P<.001. Cavitary NB patterns were identified in 59 patients (14.8%), who had lower sPD-1 levels than those with noncavitary NB pattern: 31.8pg/mL (IQR, 19.6-54.9pg/mL) vs 46.9pg/mL (IQR, 27.4-66.7pg/mL); P=.007. After excluding 11 patients who were receiving treatment at baseline, antibiotics were initiated in 167 patients (42.9%) during a median follow-up of 1.3 years. In multivariable analysis, risk factors for disease progression within 3 years were lower body mass index, per 1-kg/m2 increase: HR, 0.901; 95%CI, 0.842-0.963; P=.002; cavitary NB pattern: HR, 3.262; 95%CI, 2.166-4.914; P<.001; low sPD-1 level, <30.5pg/mL: HR, 1.957; 95%CI, 1.241-3.087; P=.004; and intermediate sPD-1 level, 30.5-55.5pg/mL: HR, 1.583; 95%CI, 1.007-2.488; P=.047, compared with high sPD-1 level, >55.5pg/mL.
Conclusions:
This multicountry validation cohort study shows that sPD-1 is associated with cavitary NB-pattern NTM-PD at baseline and with treatment initiation during follow-up, supporting its potential role in risk stratification.
