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

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.

Study Overview

• Status: Recruiting
• Conditions: Nontuberculous Mycobacterial Lung Disease

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

• Study Contact: Name: Chin-Chung Shu; Phone Number: 53087 +886-2312-3456; Email: ccshu@ntu.edu.tw

Study Locations

• Taiwan
  • Taipei, Taiwan
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chin-Chung Shu; Phone Number: +886223123456

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with NTM-LD at National University Hospital, Taiwan ,Fukujuji Hospital, Japan and Seoul National University, Korea.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
NTM-LD; 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; 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); Those with respiratory specimen culture positive for Mycobacterium tuberculosis or typical TB pulmonary pathology.
Healthy control

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 31, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 23, 2022
• First Submitted That Met QC Criteria: January 9, 2023
• First Posted (Actual): January 10, 2023

Study Record Updates

• Last Update Posted (Estimate): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases
• Other Study ID Numbers: 202210007RINC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No