This is a nationwide, multicenter, prospective, observational cohort study, which will be conducted among 7 tertiary hospitals across mainland China. The baseline clinical characteristics, including respiratory symptom burden, lung function measurements and radiological features, will be described and compared between the subjects with tuberculosis-associated COPD and non-tuberculosis-associated COPD. All of the eligible subjects will be followed up for 1 year. During the follow-up period, the frequency of COPD exacerbation, as well as dynamic changes of respiratory symptoms, lung function and chest radiological features, will be evaluated. Our study will provide a more detailed profile of tuberculosis-associated COPD and propose potential treatment options for this special phenotype.
Both tuberculosis and COPD are major public health problems, especially in developing countries. Meanwhile, tuberculosis is an important risk factor of COPD, which has been confirmed by several observational studies as well as meta-analysis [5–7, 34]. Previous studies generally concentrated on the relationship between tuberculosis and COPD, while few attached attentions on this phenotype per se, indicating more clinical studies regarding disease characteristics, evolution, prognosis, and even the definition of this phenotype are warranted. Besides the definition of tuberculosis-associated COPD proposed on the 1st International Post-Tuberculosis Symposium, diverse definitions applied in previous studies indicate classical radiological TB sequel findings play an important role in diagnosing and categorizing [18, 20, 35–37]. Nevertheless, whether these definitions can accurately describe or reflect the essence of tuberculosis-associated COPD still requires further researches. Our study puts forward an innovative diagnosis criterion of tuberculosis-associated COPD, which integrates the medical history of pulmonary tuberculosis, IGRAs result and chest CT radiological signs and may embody improved sensitivity and specificity.
COPD exacerbations are important events in the management of COPD for accelerating the deterioration of health status, causing frequent hospitalization and readmission and increasing the risk of mortality [1]. A retrospective study conducted in Korea found that COPD patients with a history of tuberculosis had higher exacerbation prevalence, compared to those without prior tuberculosis history [38]. Another prospective study with a small sample size found that patients with post Tuberculosis Obstructive Airway Disease (Post-TB OAD) experienced more severe exacerbation and frequency of hospitalization than those patients with “classic” COPD, during 12 months follow-up [15]. However, the evidences regarding disease exacerbation and relevant clinical outcomes in patients with tuberculosis-associated COPD are still limited. The heterogeneity among studies were noticeable, including the study design, region, participants and endpoint of observation. In addition, the patterns of lung function among patients with tuberculosis-associated COPD also had heterogeneity and the response to bronchodilators was different [20, 39]. Therefore, the risk factors and characteristics for disease exacerbation in this population will be significantly different from those without tuberculosis and our study may address this issue.
The mechanism underlying in tuberculosis-associated COPD is distinctive from smoking-related COPD. Previous studies revealed that submucosal tuberculous and nonspecific inflammation, as well as bronchiectasis lesions were frequently seen in patients with tuberculosis [40]. Lymph node involvement in primary infection syndrome could result in bronchial obstruction and dilation [41]. In addition, the destruction of lung parenchyma after pulmonary tuberculosis could affect lung compliance and cause the collapse of peripheral small airways, which in turn led to the occurrence of air trapping and emphysema [42]. Therefore, the clinical features and chest imaging findings in patients with tuberculosis-associated COPD were distinctive. Our previous study found that COPD patients with prior tuberculosis had unique features of emphysema and more bronchiectasis, which was consistent with previous studies [15, 43, 44]. Air trapping due to small airway obstruction were more often in tuberculosis-associated COPD in expiration CT scan, compared to those with smoking-related COPD [45]. Patients with tuberculosis-associated COPD had an increased decline in forced expiration volume in 1 second than those without prior tuberculosis [38]. In this prospective study, we will also investigate the clinical features including respiratory symptoms and quality of life, and the dynamic changes of spirometry function and chest imaging findings, in order to understand this disease phenotype better.
Long-acting bronchodilators are the foundation medications for patients with COPD, while inhaled glucocorticoids are conditionally recommended for certain patient, who has concomitant asthma, a blood eosinophil count ≥ 300/µL or experiences moderate exacerbation ≥ 2 or severe exacerbation requiring hospitalization ≥ 1 [1]. However, there is a lack of evidence regarding the effect of bronchodilators in tuberculosis-associated COPD. The efficacy of bronchodilators in this group of patients is still worth exploring. How to determine the "treatable traits" of patients with tuberculosis-associated COPD is of clinical significance. In addition, inhaled glucocorticoids may increase the risk of tuberculosis recurrence and thereby are not recommended in patients with prior tuberculosis history. However, for those patients with tuberculosis-associated COPD concomitant with asthma-like manifestation or high eosinophil count in blood or sputum, whether they can benefit from inhaled glucocorticoids also requires further researches.
Another prominent strength of this study is that participants are recruited from 7 tertiary hospitals which locate in 6 provinces across mainland China. Economic level and medication accessibility have an intense influence on tuberculosis prevalence and COPD treatment compliance, this multicenter study will help to make the results more representative. With the application of more plausible screening criteria, it is expected that more insights of clinical significance will be disclosed, in terms of the characteristics of tuberculosis-associated COPD.
The study has some limitations. Firstly, although the criteria we propose is comprehensive, its sensitivity and specificity still need to be verified for the lack of "gold standard". Secondly, we choose the annual moderate/severe exacerbation as primary outcome, while comorbidity as well as long-term outcome will not be evaluated in this study, which both have an influence on the life quality of COPD patients.