Validation of soluble programmed death-1 in predicting progression of nodular-bronchiectatic form of nontuberculous mycobacterial lung disease: a Multi-Country Research

<bold>Background:</bold> The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing and leads significant morbidity and mortality. But the treatment rate is low because the course of NTM-LD is indolent, especially in nodular-bronchiectatic (NB) form. Recently, it has been reported that soluble form programmed death-1 (PD-1) in patients with NTM-LD was reversed associated with disease severity and progression. However, this has not been validated in other countries and ethnicities. Therefore, we apply this project to investigate the role of soluble PD-1 in NTM-LD through a multi-country cooperation. <bold>Methods:</bold> This multi-country study was conducted in Taiwan, Japan and Korea. Healthy participants were also enrolled as comparators. Serum from all participants were collected for sPD-1 measurement. The difference in sPD-1 level between groups were compared. <bold>Research results:</bold> During 2024, 55 healthy controls and 488 patients with NTM-LD (n=128, 300, and 60 in Taiwan, Korea, and Japan sites, respectively) were included. NTM-LD group and healthy control were similar in age and male gender ratio, but the BMI was lower in NTM-LD group. Notably, the sPD-1 was lower in NTM-LD than in control. Among patients with NTM-LD, 79% of them were infected by Mycobacterium avium complex and 17% were Mycobacterium abscessus complex. The levels of sPD-1 were relatively low in the cavitary groups than the non-cavitary NB. <bold>Conclusions:</bold> Our findings included that patients with NTM-LD had lower sPD-1 than the healthy controls and that patients with cavitary NTM-LD had further decreased sPD-1 level, warranting further validation.