Risk Factors and Biomarkers for Post-tuberculosis Lung Damage in a Chinese Cohort: Protocol for a Prospective Observational Study
Conditions: Pulmonary TB
Sponsor: Peking University Third Hospital

 
Risk factors and biomarkers for post-tuberculosis lung damage 
in a Chinese cohort: protocol for a prospective observational 
study  
 
 

ABSTRACT 
Introduction: Post-tuberculosis lung damage (PTLD) refers to the residual pulmonary 
impairment following the completion of tuberculosis (TB) treatment, characterized by 
persistent respiratory symptoms and abnormal pulmonary function. The risk factors and 
biomarkers for PTLD have been scarcely investigated. Additionally, it remains unclear 
whether and to what extent cigarette smoking affects PTLD in patients with TB.  
Methods and analysis: This prospective observational study will enroll 400 adult male 
ever-smoker or never-smoker patients aged 25–60 years, with newly confirmed active 
TB between 2022 and 2024 from the Department of Respiratory and Critical Care 
Medicine at Peking University Third Hospital and the Tuberculosis Department at 
Beijing Geriatric Hospital. Baseline data (age, smoking history, and smoking pack-
years), clinical symptoms, lung functions, and chest CT (computed tomography) 
findings will be prospectively collected. Respiratory questionnaires, lung function 
measurements, and chest CT examinations will be completed during follow-up visits 6 
months after the initiation of TB treatment, immediately after the completion of TB 
treatment, and 1 year, 2 years, and 3 years after the completion of TB treatment. 
Peripheral blood samples will be obtained at baseline, and a Luminex xMAP-based 
multiplex immunoassay will be used to measure 40 inflammatory mediators and 
cytokines in serum. The collected data will be analyzed to determine the incidence and 
factors/biomarkers of PTLD after TB treatment.  
Ethics and dissemination: The study was approved by the Ethics Committee of 
Peking University Third Hospital (approval number: (2022)271-03; approval date: 
June 8, 2022). The research results will be disseminated through scientific and 
medical conferences and will be published in an academic journal. 
Keywords: tuberculosis; post-tuberculosis lung damage; clinical epidemiology; 
cigarette smoking; respiratory infection 
 

 
Objectives 
This prospective study aims to determine the incidence of PTLD, examine trends in 
the changes in lung function, and investigate the impact of smoking and other factors 
on respiratory symptoms, lung function, and chest CT findings, which will aid in the 
development of prognostic and therapeutic strategies for PTLD. 
 
METHODS AND ANALYSIS 
Study participants 
This prospective observational study will enroll male patients who were newly 
diagnosed with active TB from the Department of Respiratory and Critical Care 
Medicine at Peking University Third Hospital and the Tuberculosis Department at 
Beijing Geriatric Hospital between 2022 and 2024. The study team will screen patients 
who were newly diagnosed with active TB in an outpatient setting. 
 
Inclusion criteria 
Male patients aged 25–60 years newly diagnosed with pulmonary TB—based on the 
2018 diagnostic criteria for TB released by the National Health and Family Planning 
Commission of the People’s Republic of China—will be included in the study. Sputum 
smear microscopy and TB culture tests will be performed for patients exhibiting 
persistent respiratory symptoms until 6 months after treatment initiation or until the 
completion of treatment. 
 
Exclusion criteria 
The following patients will be excluded from analysis: (1) patients with positive 
sputum smear or TB culture results; (2) human immunodeficiency virus-positive 
patients; (3) patients infected with multidrug-resistant TB; (4) patients with malignant 
neoplasms (e.g., lung cancer) or severe cardiovascular and cerebrovascular diseases; 
(5) non-compliant patients who were unable to complete the lung function tests; and 
(6) patients without lung parenchymal destruction (such as tuberculous pleurisy). 

 
All study participants provided written informed consent. The study flowchart is 
presented in Figure 1. 
 
Study content 
This study will be conducted at Peking University Third Hospital, and Beijing 
Geriatric Hospital 6 months after the initiation of TB treatment, immediately after the 
completion of the treatment, and 1 year, 2 years, and 3 years after the completion of 
treatment. 
The following general data obtained from the study participants will be recorded: age, 
socioeconomic status (employment and income), number of years of smoking, 
smoking index (smoking index = number of cigarettes smoked per day × years of 
smoking), symptoms, St. George’s Respiratory Questionnaire (SGRQ) scores, COPD 
Assessment Test (CAT) scores, blood test results (complete blood count, CD4 
lymphocyte count, plasma glucose, glycated hemoglobin). Peripheral blood samples 
will be obtained at baseline for the measurement of inflammatory mediators and 
cytokines will be detected. A symptom questionnaire survey, chest CT, and lung 
function tests will be performed according to standard procedures (Table 1).  
Prior to enrollment, patients will be informed of the study as well as of the relevant 
examinations that will be performed. 
 
 
 
 
  
Primary outcome measures 
Trends in the changes in lung function, including forced expiratory volume (FEV1), 
forced vital capacity (FVC), and FEV1/FVC.a 
Secondary outcome measures 
Absorption of TB lesions on lung CT scans after TB treatment 
Chest CT images will be interpreted by a respiratory physician and a radiologist. 
Parenchymal and airway lesions detected on CT scans will be recorded.[14, 15] 
 
Quality of life and respiratory symptoms 

The CAT (self-administered), SGRQ, and UK Medical Research Council (MRC) 
Dyspnea Scale will be utilized. 
 
Serum inflammatory markers and their correlation with airflow limitation 
Serum cytokines will be detected at baseline prior to TB treatment.