Validation of Soluble Programmed Death-1 in Predicting Progression of Nodular-bronchiectatic Form of Nontuberculous Mycobacterial Lung Disease: a Multi-Country Research

Study Overview
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Brief Summary
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The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide and in Eastern Asia. NTM-LD leads significant morbidity and mortality, around 25% within 5 years, but the treatment rate is low because the course of NTM-LD is indolent, especially in nodular-bronchiectatic (NB) form. However, there is no biomarker proven for predicting the progression in NB form of NTM-LD. Recently, it has been reported that the ratio of membrane-form programmed death-1 (PD-1) expressed T cells increased in patients with NTM-LD and it was associated with disease severity and progression. The mechanism has been speculated as a immune exhaustion. In contrast to PD-1 expressed in cell membrane, soluble-form PD-1 is another biomarker that can be easily detected in serum. We recently reported that soluble PD-1 significantly correlated with cavitary lesion and disease progression in patients with NB-form NTM-LD in Taiwan. However, this has not been validated in other countries and ethnicities. Furthermore, the usefulness of soluble PD-1 in diagnosis and predicting mortality warrants further studies.

Detailed Description
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The incidence of nontuberculous mycobacterial lung disease (NTM-LD) is increasing worldwide and in Eastern Asia. NTM-LD leads significant morbidity and mortality, around 25% within 5 years, but the treatment rate is low because the course of NTM-LD is indolent, especially in nodular-bronchiectatic (NB) form. However, there is no biomarker proven for predicting the progression in NB form of NTM-LD. Recently, it has been reported that the ratio of membrane-form programmed death-1 (PD-1) expressed T cells increased in patients with NTM-LD and it was associated with disease severity and progression. The mechanism has been speculated as a immune exhaustion. In contrast to PD-1 expressed in cell membrane, soluble-form PD-1 is another biomarker that can be easily detected in serum. We recently reported that soluble PD-1 significantly correlated with cavitary lesion and disease progression in patients with NB-form NTM-LD in Taiwan. However, this has not been validated in other countries and ethnicities. Furthermore, the usefulness of soluble PD-1 in diagnosis and predicting mortality warrants further studies. Moreover, it is worthwhile to measure soluble PD-1 in bronchoalveolar lavage to explore local immune pathogenesis of NTM-LD. Therefore, we apply this project to investigate the role of soluble PD-1 in NTM-LD through a multi-country cooperation.

Official Title
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Validation of Soluble Programmed Death-1 in Predicting Progression of Nodular-bronchiectatic Form of Nontuberculous Mycobacterial Lung Disease: a Multi-Country Research

Conditions
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Nontuberculous Mycobacterial Lung Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 20 years NTM-LD: (N=250) Diagnosis is made on the basis of the guidelines produced by the American Thoracic Society.Patients have pulmonary symptoms with identified chest image and fit with the microbiology criteria. NTM pulmonary colonizers and others: (N=100) Those without fulfilling the diagnostic criteria but having at least one set of positive sputum for MAC or patients infected with NTM other than MAC species. Pulmonary tuberculosis (TB): (N=100) Those with respiratory specimen culture positive for Mycobacterium tuberculosis or typical TB pulmonary pathology. Healthy control (N=50) Exclusion Criteria: Patients who have acquired immunodeficiency syndrome

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NTM-LD<br>Diagnosis is made on the basis of the guidelines produced by the American Thoracic Society . Briefly, Patients have pulmonary symptoms with identified chest image and fit with the microbiology criteria. | |
| NTM pulmonary colonizers and others<br>Those without fulfilling the diagnostic criteria but having at least one set of positive sputum for MAC or patients infected with NTM other than MAC species. | |
| Pulmonary tuberculosis (TB)<br>Those with respiratory specimen culture positive for Mycobacterium tuberculosis or typical TB pulmonary pathology. | |
| Healthy control<br>Healthy control | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma soluble PD-1 on NTM-LD diagnosis |  | within 2 years | 
| Mortality | Mortality, patient die within 2 years | within 2 years |