Assessment of lung function in successfully treated tuberculosis reveals high burden of ventilatory defects and COPD

Abstract

Background Burden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear. Methods We performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVC<5 th percentile of Global Lung Initiative mixed-ethnicity reference (lower limit of normal [LLN]). Chronic obstructive pulmonary disease (COPD) was defined as post-bronchodilator FEV1/FVC<LLN among participants with obstruction. Restrictive spirometry pattern was defined as FVC<LLN among participants without obstruction. Multivariable logistic and linear regression was used to identify risk-factors for obstruction, restriction and low lung function despite successful treatment. Results Of the 172 participants included in the analysis, 82 (48%) were female, 22 (13%) had diabetes and 34 (20%) ever-smoked with a median (IQR) exposure of 3.5 (0.2–9.9) pack-years. Median (IQR) age and body-mass index (BMI) at enrollment was 32 (23–39) years and 18.1 (16.0–20.5) kg/m 2 respectively. Airflow obstruction was detected in 42 (24%) participants; of whom 9 (21%) responded to short-acting bronchodilators and 25 (56%) had COPD; and was associated with duration of illness prior to treatment (aOR = 1.32 per 30-days, 95%CI 1.04–1.68, p = 0.02). A restrictive spirometry pattern was detected in 89 (52%) participants and was associated with female sex (aOR = 3.73, 95%CI 1.51–9.17, p = 0.004) and diabetes (aOR = 4.06, 95%CI 1.14–14.42, p = 0.03). Higher HbA1c at treatment initiation was associated with greater odds of a restrictive spirometry pattern (aOR = 1.29 per unit higher HbA1c, 95%CI 1.04 to 1.60, p = 0.02). Conclusion We found a high burden of lung function defects and COPD in tuberculosis cases who successfully completed treatment. Screening for chronic lung diseases following treatment and linkage to respiratory health clinics should be included in the routine management plan of all tuberculosis cases in India, regardless of conventional COPD risk-factors such as older age and smoking.

Pulmonary restriction predicts long-term pulmonary impairment in people with HIV and tuberculosis

“…Our finding that restriction was the most commonly identified spirometric abnormality is similar to what has been reported from a cohort in India, where 52% of individuals had restriction and 24% had obstruction [ 10 ]. In contrast to India where obstruction was more symptomatic than restriction, we found that individuals with restriction were more symptomatic than those with obstruction alone.…”

“…At baseline, pulmonary symptoms were moderately inversely correlated with both FEV 1 (ρ = -0.28, p value 0.004) and FVC (ρ = − 0.28, p value 0.003), such that participants with worse symptoms tended to have a lower FEV 1 and FVC (Additional file 1: Figure S1). Participants with either restriction or a mixed pattern had a significantly greater symptom burden than those with normal spirometry (median [IQR] COPD Assessment Test score 10 [4-15] for restriction and 8 [2,[4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] for mixed vs. 4 [2][3][4][5][6][7][8][9] for normal), including greater cough, chest tightness, breathlessness, and lower energy levels. In contrast, participants with obstruction did not differ with respect to symptom burden when compared to those with normal spirometry ( Fig.…”

“…Post-tuberculosis lung impairment has traditionally been viewed as an obstructive phenomenon, similar to chronic obstructive pulmonary disease (COPD), where patients have difficulty exhaling as a result of inflammation and damage to the large airways. However, recent data suggest that pulmonary restriction may be as common, if not more so, among tuberculosis survivors [10][11][12]. Pulmonary restriction, which is characterized by the inability to inhale to full lung capacity, typically arises from scarring and fibrosis of the lung parenchyma.…”

Chronic Obstructive Pulmonary Disease Endotypes in Low- and Middle-Income Country Settings: Precision Medicine for All

“…Although population-based studies have found a high prevalence of COPD in individuals with prior TB ( 13 ), recent studies have shown considerable heterogeneity in the phenotype of post-TB lung disease ( 14 ). In contrast to smoking-associated COPD, a restrictive spirometry pattern, with or without airflow obstruction, that is largely unresponsive to bronchodilators is the predominant phenotype of post-TB lung disease ( 15 ). Furthermore, bronchiectasis is a common manifestation of treated TB, which is distinct from smoking-associated COPD ( 16 ).…”

Higher interleukin-6 levels and changes in transforming growth factor-β are associated with lung impairment in pulmonary tuberculosis

“…Our previous work in India found up to 50% of PTB cases had impaired lung function post-treatment [ 3 ]. We also found a positive correlation between the duration of symptomatic illness prior to PTB treatment and severity of lung impairment post-treatment.…”