Pulmonary Tuberculosis Identified as Possible Risk Factor for COPD

Patients with a history of pulmonary tuberculosis (TB) were found to have an increased risk and higher prevalence of developing chronic obstructive pulmonary disease (COPD) than patients without TB, according to a recent meta-analysis published in Annals of Translational Medicine.

“Our findings add to existing knowledge and support the association between prior pulmonary TB and COPD, which can provide a basis for clinicians to improve the early diagnosis of COPD, especially in areas where TB is prevalent,” the authors wrote.

Interestingly, a subgroup analyses showed that the association between pulmonary TB and COPD was independent of several confounding factors: income level, definition of COPD, definition of TB, and smoking status, the most common risk factor for COPD development.

Identification of COPD risk factors is currently incomplete because over 90% of COPD-related morbidity and mortality occurs in low- and middle-income countries, where many patients with COPD are never-smokers.

TB is the global leading infectious disease, accounting for over 10 million new cases and 1.5 million deaths annually. Despite the ability to treat TB, the disease can lead to permanent lung damage and loss of lung function. It’s presently unknown whether TB-related lung function impairment is related to airflow obstruction, a main characteristic of COPD.

To assess a possible relationship between TB and COPD, the investigators searched Embase, Web of Science, and PubMed databases for cross-sectional, case-controlled, or cohort studies that compared COPD prevalence with a control group or group of patients with TB.

Of the 5174 abstracts identified, 23 observational studies were included in the analysis. In 22 of the studies, there were 36,641 patients with COPD and 491,538 patients without COPD. The remaining study didn’t report how many participants had COPD. The mean age of participants in the 19 studies that reported age was 52.2 years. Five studies were from high-income countries and 14 were from low- to middle-income countries.

Twenty-two studies looked at a possible association between COPD and TB. A pooled analysis found that patients with a history of TB had a significantly increased risk of COPD compared with patients who did not have a TB history (odds ratio [OR], 2.59; 95% CI, 2.12-3.15; P < .001).

Adjustment for confounding factors occurred in 19 studies, and the association between TB and COPD did not change (OR, 2.53; 95% CI, 2.04-3.13; P < .001). The association also remained consistent in the sensitivity analysis.

The pooled analysis of the 7 studies that analyzed never-smokers found that TB was a significant risk factor for COPD in patients who have never smoked (OR, 2.41; 95% CI, 1.74-3.32; P < .001).

Low- and middle-income countries (OR, 2.70; 95% CI, 2.08-3.51; P < .001) had a significantly increased risk of COPD compared with high-income countries (OR, 2.44; 95% CI, 1.70-3.49; P < .001), according to the pooled analysis.

Different definitions of TB, such as whether a study used a chest x-ray or patient self-reports, did not influence the results. This was also true for studies with conflicting definitions of COPD, which were based on various lung function values and prescribed medications.

“Future studies identifying the underlying immune mechanisms for TB-associated COPD, relative to the natural history of TB disease, are needed to help inform prognostic and therapeutic strategies for post–TB lung disease,” the authors noted.

COPD had a primary prevalence between 8% and 58% among the 16 studies, including 1694 patients with TB, that reported such results. The meta-analysis revealed a pooled COPD prevalence of 21% (95% CI, 15%-25%; P < .001) in patients with a history of pulmonary TB.

The investigators listed several limitations, including that they were unable to establish a causal relationship between TB and COPD due to the evidence primarily coming from cross-sectional and case-controlled studies. Additionally, significant heterogeneity in the effect estimates across studies may impact the credibility of the results and a recall bias or underreporting of TB may have occurred because many studies relied on self-reporting to define TB.

“With aging of the world’s population, it is vital to improve our understanding of the mechanisms linking pulmonary TB to COPD and airflow obstruction, and to develop effective strategies to deal with this problem,” the authors concluded.

Reference

Fan H, Wu F, Liu J, et al. Pulmonary tuberculosis as a risk factor for chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ann Transl Med. March 2021;9(5):390. doi:10.21037/atm-20-4576