The authors have declared that no competing interests exist.
Conceived and designed the experiments: JWJ JCC. Performed the experiments: BWC JYK JWJ JWS. Analyzed the data: JWJ IWP. Contributed reagents/materials/analysis tools: JWJ JCC JWS JYK BWC. Wrote the paper: JWJ IWP.
Pulmonary tuberculosis (TB) can affect lung function, but studies regarding long-term follow-up in patients with no sequelae on chest X-ray (CXR) have not been performed. We evaluated lung functional impairment and persistent respiratory symptoms in those with prior pulmonary TB and those with prior pulmonary TB with no residual sequelae on CXR, and determined risk factors for airflow obstruction.
We used data from adults aged ≥ 40 years from the annual Korean National Health and Nutrition Examination Surveys conducted between 2008 and 2012.
In total of 14,967 adults, 822 subjects (5.5%) had diagnosed and treated pulmonary TB (mean 29.0 years ago). The FVC% (84.9 vs. 92.6), FEV1% (83.4 vs. 92.4), and FEV1/FVC% (73.4 vs. 77.9) were significantly decreased in subjects with prior pulmonary TB compared to those without (
In addition to subjects with inactive TB lesion on CXR, subjects with no sequelae on CXR can show impaired pulmonary function and respiratory symptoms. Prior TB is a risk factor for airflow obstruction and that the risk is more important when they have inactive lesions on chest X-ray. Hence, the patients with treated TB should need to have regular follow-up of lung function and stop smoking for early detection and prevention of the chronic airway disease.
Tuberculosis (TB) is a distressing disease, as its prevalence and associated mortality continue to increase. In 2013, the prevalence of tuberculosis was 11.9 million, and the number of tuberculosis related deaths was 1.4 million [
Numerous studies have reported that chronic airflow obstruction is a sequela to pulmonary TB [
In Korea, the prevalence of active TB on CXR decreased from 5,168 in 100,000 in 1965 to 767 in 100,000 in 1995 [
Therefore, we evaluated impaired pulmonary function and the presence of persistent respiratory symptoms and also identified risk factors for long-term pulmonary function impairment in subjects with diagnosed prior pulmonary TB. Data was analyzed from five years of data from the Korean National Health and Nutrition Examination Survey (Korean NHANES), a large-scale, nationwide representative survey. In addition, we investigated if subjects with history of prior pulmonary TB without CXR sequelae were associated with impaired pulmonary function.
We collected five years of data from the Korean NHANES (2008–2012). This study protocol was approved by the Institutional Review Board of the Korea Centers for Disease Control and Prevention (approval no. 2008-04EXP-01-C, 2009-01CON-03-2C, 2010-02CON-21-C, 2011-02CON-06-C, and 2012-01EXP-01-2C). Written informed consent was obtained from all participants. The Korean NHANES is a population-based nationwide cross-sectional surveillance system conducted annually by the Korea Center for Disease Control and Prevention [
Of the total 45,811 subjects, 14,967 adults aged ≥ 40 years were included in the study. Age, sex, smoking status, and history of pulmonary TB, or asthma diagnosed by a doctor were assessed through a questionnaire. Questions about age and treatment institution of subjects with prior pulmonary TB were also included in the questionnaire. Questions about respiratory symptoms, physical activity limitations due to pulmonary symptoms and the visual analogue scale to assess the global quality of life were used. Visual analogue scale is ranked between 0 ("worst imaginable health state") and 100 ("best imaginable health state"). The participants indicated where they perceive their present state of health to lie to this domain range [
Pulmonary function tests were performed to each subjects (14,967 adults) using a dry rolling-seal spirometer (Vmax-2130, Sensor-Medics, Yorba Linda, CA, USA). Spirometry was conducted by well-trained pulmonary laboratory technicians. The test was terminated if the curve obtained from 3 measurements of pulmonary function was appropriate or if the test results met repeatability criteria. Otherwise, the test was conducted up to 8 times and until the subjects were no longer able to tolerate the test. Appropriateness curves were based on the 1994 recommendation of the American Thoracic Surgery [
CXR were taken with DigiRAD-PG (Sitec Medical Co., Ltd, Kimpo-si, Gyeonggi-do, Korea) installed on the examination vehicle. Two independent radiologists read transmitted CXR according to the standard criteria for reporting radiological abnormalities. By using CXR, an inactive TB lesion was defined as a lesion with discrete linear or reticulofibrotic opacities with or without calcification that was confined to the upper lobes, while the other lobes were intact [
All statistical analyses were performed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as the mean and standard deviation (SD), and categorical variables were presented as numbers and percentages. Comparisons of age, sex, and smoking history were made using the Chi-square and Student’s
This study included a total of 14,967 adults aged ≥ 40 years. There were 6,486 males (43.3%), and the mean age of the subjects was 57.1 ± 10.9 years (
N = 14,967 | |
---|---|
Age (years) | 57.1 ± 10.9 |
Male sex | 6,486 (43.3%) |
Smoking status | |
Current smoker | 2,828 (18.9%) |
Ex-smoker | 3,292 (22.0%) |
Nonsmoker | 8,823 (59.0%) |
Smoking status (pack-year) | 9.6 ± 16.9 |
Prior pulmonary tuberculosis | 822 (5.5%) |
Age of diagnosis (years) | 30.6 ± 14.3 |
Timing of diagnosis (years ago) | 29.0 ± 13.7 |
Medical institution for treatment | |
Hospital | 233 (28.3%) |
Public health center | 183 (22.3%) |
Other | 26 (3.2%) |
No answer | 380 (46.2%) |
Pulmonary function tests | |
FVC % | 92.2 ± 12.1 |
FVC (mL) | 3,415.1 ± 850.5 |
FEV1% | 92.2 ± 13.8 |
FEV1 (mL) | 2,645.4 ± 680.6 |
FEV1/FVC % | 77.7 ± 7.8 |
FEV6 (mL) | 3,332.00 ± 808.36 |
FEF25-75% (mL/sec) | 3,631.51 ± 2,063.75 |
PEF (mL/sec) | 7,050.90 ± 1,916.25 |
COPD | 1,978 (13.2%) |
Mild | 899 (6.0%) |
Moderate | 978 (6.5%) |
Severe | 90 (0.6%) |
Very severe | 11 (0.1%) |
Chest X-ray | |
Normal X-ray | 12,885 (86.1%) |
Inactive tuberculosis lesion | 1,178 (7.9%) |
Cardiac disease | 112 (0.7%) |
Other lung diseases | 792 (5.3%) |
Data are means ± SD or percentages.
FVC: forced vital capacity; FEV1: forced expiratory volume in 1 second; FEV6: forced expiratory volume in 6 seconds; FEF25-75%: forced expiratory flow 25–75%; PEF: peak expiratory flow; COPD: chronic obstructive pulmonary disease.
Clinical characteristics were assessed in the entire study population according to TB history of physician-diagnosed prior pulmonary TB (
(A) In all study subjects; (B) In subjects with normal chest X-rays. FVC: forced vital capacity; FEV1: forced expiratory volume in 1 second.
Prior pulmonary tuberculosis (-) n = 14,145 (94.5%) | Prior pulmonary tuberculosis (+) n = 822 (5.5%) | ||
---|---|---|---|
Age (years) | 56.9 ± 10.9 | 59.5 ± 10.9 | < 0.001 |
Male sex | 6,048 (42.8%) | 438 (53.3%) | < 0.001 |
Smoking status | < 0.001 | ||
Current smoker | 2,679 (19.0%) | 149 (18.2%) | |
Ex-smoker | 3,039 (21.5%) | 253 (30.9%) | |
Nonsmoker | 8,405 (59.5%) | 418 (51.0%) | |
Smoking status (pack-year) | 9.45 ± 16.81 | 11.95 ± 18.61 | < 0.001 |
Asthma |
438 (3.1%) | 57 (6.9%) | |
Pulmonary function tests |
< 0.001 | ||
FVC % | 92.4 ± 12.0 | 88.4 ± 13.5 | < 0.001 |
FVC (liters) | 3.4 ± 0.9 | 3.4 ± 1.0 | < 0.001 |
FEV1% | 92.6 ± 13.5 | 84.9 ± 17.2 | |
FEV1 (liters) | 2.7 ± 0.7 | 2.5 ± 0.7 | < 0.001 |
FEV1/FVC % | 77.9 ± 7.5 | 73.4 ± 10.2 | < 0.001 |
FEV6 (liters) | 3.3 ± 0.8 | 3.2 ± 0.9 | < 0.001 |
FEF25-75% (liters/sec) | 3.7 ± 2.1 | 3.1 ± 2.1 | < 0.001 |
PEF (liters/sec) | 7.1 ± 1.9 | 6.6 ± 2.1 | < 0.001 |
COPD |
1,739 (12.3%) | 239 (29.1%) | < 0.001 |
Mild | 820 (5.8%) | 79 (9.6%) | < 0.001 |
Moderate | 847 (6.0%) | 131 (15.9%) | < 0.001 |
Severe | 67 (0.5%) | 23 (2.8%) | < 0.001 |
Very severe | 5 (0.04%) | 6 (0.7%) | < 0.001 |
Data are means ± SD or percentages.
FVC: forced vital capacity; FEV1: forced expiratory volume in 1 second; FEV6: forced expiratory volume in 6 seconds; FEF25-75%: forced expiratory flow 25–75%; PEF: peak expiratory flow; COPD: chronic obstructive pulmonary disease.
*
In 8,823 never smoker (1,014 males and 7,809 females), FEV1% (88.5 ± 13.6 vs. 93.2 ± 11.9), FVC% (86.2 ± 17.0 vs. 94.5 ± 13.2), and FEV1/FVC% (76.0 ± 8.3 vs. 79.6 ± 6.1) were significantly decreased in 418 subjects with prior pulmonary TB, as compared to 8,405 subjects without prior pulmonary TB (
Of all subjects, 12,885 (86.1%) showed normal CXR (
Prior pulmonary tuberculosis (-) n = 12,589 (97.7%) | Prior pulmonary tuberculosis (+) n = 296 (2.3%) | ||
---|---|---|---|
Age (years) | 56.0 ± 10.6 | 57.4 ± 10.9 | 0.048 |
Male sex | 5,261 (41.6%) | 136 (45.9%) | 0.130 |
Smoking status | 0.030 | ||
Current smoker | 2,361 (18.8%) | 44 (14.9%) | |
Ex-smoker | 2,604 (20.7%) | 78 (26.4%) | |
Nonsmoker | 7,605 (60.5%) | 173 (58.6%) | |
Smoking status (pack-year) | 9.0 ± 16.1 | 9.3 ± 15.8 | 0.702 |
Asthma |
364 (2.9%) | 17 (5.7%) | 0.009 |
Pulmonary function tests |
|||
FVC % | 93.1 ± 11.6 | 92.1 ± 12.1 | 0.369 |
FVC (liters) | 3.4 ± 0.8 | 3.5 ± 0.9 | 0.226 |
FEV1% | 93.4 ± 12.8 | 90.9 ± 13.9 | 0.001 |
FEV1 (liters) | 2.7 ± 0.7 | 2.7 ± 0.7 | 0.331 |
FEV1/FVC % | 78.4 ± 7.0 | 76.6 ± 7.4 | < 0.001 |
FEV6 (liters) | 3.4 ± 0.8 | 3.4 ± 0.9 | 0.328 |
FEF25-75% (liters/sec) | 3.7 ± 2.1 | 3.6 ± 2.2 | 0.628 |
PEF (liters/sec) | 7.2 ± 1.9 | 7.0 ± 1.9 | 0.023 |
COPD |
1,305 (10.4%) | 46 (15.5%) | 0.004 |
Mild | 670 (5.3%) | 19 (6.4%) | 0.407 |
Moderate | 607 (4.8%) | 25 (8.4%) | 0.004 |
Severe | 28 (0.2%) | 2 (0.7%) | 0.151 |
Very severe | 0 | 0 | - |
Data are means ± SD or percentages.
FVC: forced vital capacity; FEV1: forced expiratory volume in 1 second; FEV6: forced expiratory volume in 6 seconds; FEF25-75%: forced expiratory flow 25–75%; PEF: peak expiratory flow; COPD: chronic obstructive pulmonary disease.
*
In 7,778 never smoker with normal CXR (848 males and 6,930 females), FEV1% (92.2 ± 14.6 vs. 95.2 ± 12.6,
Subjects with prior pulmonary TB more frequently had cough of three or more months during last year (5.5% vs. 2.2%,
(A) In all study subjects; (B) In subjects with normal chest X-rays.
Subjects with prior pulmonary TB more frequently had physical activity limitations due to pulmonary symptoms, as compared to those without prior pulmonary TB in total patients (3.2% vs. 0.6%,
Scores of visual analogue scale, indicator of quality of life were significantly lower in subjects with prior pulmonary TB than in those without prior pulmonary TB (72.0 ± 18.0 vs. 73.7 ± 18.3,
Multivariate regression analysis was performed to identify risk factors for airflow obstruction (
FEV1/FVC % < 70 | FEV1/FVC % < 70 and FEV1% < 80 | FEV1/FVC % < 70 and FEV1% < 50 | FEV1/FVC % < 70 and FEV1% < 30 | |
---|---|---|---|---|
Age (years) | 1.089 (1.083–1.095), <0.001 | 1.061 (1.055–1.068), <0.001 | 1.060 (1.039–1.082), <0.001 | 1.048 (0.983–1.117), 0.152 |
Male sex | 3.368 (2.946–3.851), <0.001 | 2.473 (2.093–2.922), <0.001 | 2.469 (1.453–4.197), 0.001 | 9.462 (1.082–82.736), 0.042 |
Asthma | 5.014 (4.022–6.250), <0.001 | 5.978 (4.753–7.518), <0.001 | 19.968 (12.862–31.002), <0.001 | 34.095 (9.215–126.152), <0.001 |
Smoking amount (pack-year) | 1.017 (1.014–1.020), <0.001 | 1.017 (1.014–1.020), <0.001 | 1.019 (1.011–1.028), <0.001 | 1.012 (0.993–1.032), 0.210 |
Prior pulmonary tuberculosis | 2.314 (1.922–2.785), <0.001 | 2.691 (2.194–3.301), <0.001 | 4.407 (2.723–7.131), <0.001 | 8.879 (2.502–31.509), 0.001 |
Age (years) | 1.091 (1.084–1.098), <0.001 | 1.064 (1.055–1.072), <0.001 | 1.052 (1.016–1.091), 0.005 | - |
Male sex | 3.715 (3.170–4.353), <0.001 | 2.809 (2.275–3.470), <0.001 | 1.628 (0.642–4.131), 0.305 | - |
Asthma | 4.654 (3.584–6.042), <0.001 | 6.132 (4.607–8.163), <0.001 | 25.783 (11.997–55.411), <0.001 | - |
Smoking amount (pack-year) | 1.018 (1.014–1.021), <0.001 | 1.019 (1.015–1.023), <0.001 | 1.027 (1.011–1.042), 0.001 | - |
Prior pulmonary tuberculosis | 1.308 (0.912–1.876), 0.144 | 1.589 (1.034–2.444), 0.035 | 2.299 (0.527–10.021), 0.268 | - |
Age (years) | 1.066 (1.048–1.084), <0.001 | 1.032 (1.014–1.050), 0.001 | 1.035 (0.988–1.085), 0.142 | - |
Male sex | 1.247 (0.808–1.925), 0.319 | 0.986 (0.619–1.569), 0.952 | 1.595 (0.526–4.839), 0.409 | - |
Asthma | 4.622 (2.477–8.627), <0.001 | 4.467 (2.468–8.086), <0.001 | 8.722 (3.325–22.878), <0.001 | - |
Smoking amount (pack-year) | 1.027 (1.015–1.039), <0.001 | 1.017 (1.005–1.028), 0.004 | 1.011 (0.993–1.029), 0.244 | - |
Inactive TB lesion on chest X-ray | 2.300 (1.606–3.294), <0.001 | 2.479 (1.656–3.711), <0.001 | 5.585 (1.263–24.692), 0.023 | - |
Data are odds ratio (95% confidence interval) and
In subjects with normal chest x-rays and with prior pulmonary tuberculosis, there was no patient with FEV1/FVC % < 70 and FEV1% < 30.
FVC: forced vital capacity; FEV1: forced expiratory volume in 1 second; OR: odds ratio; TB: tuberculosis.
*Multivariate logistic regression with age, sex, asthma, smoking amount and prior pulmonary TB.
**Multivariate logistic regression with age, sex, asthma, smoking amount and inactive TB lesion on chest x-ray.
Multivariate regression analysis was performed in subjects with prior pulmonary tuberculosis. Inactive TB lesion on chest x-ray (OR, 2.300; 95% CI, 1.606–3.294), along with age, asthma and smoking amount, was risk factors of airflow obstruction. Inactive TB lesion was significantly related with FEV1% < 80 (OR, 2.479; 95% CI, 1.656–3.711) and FEV1% < 50 (OR, 5.585; 95% CI, 1.263–24.692) combined with airflow obstruction.
We conducted an analysis of five years of data from the Korean NHANES. The prevalence of prior pulmonary TB was 5.5% in subjects aged ≥ 40 years and pulmonary TB were diagnosed an average of 29 years prior to this study participation. The proportions of airflow obstruction or chronic respiratory symptoms in subjects with prior pulmonary TB were higher than those in subjects without prior pulmonary TB. The impaired pulmonary function was also observed in subjects with no TB sequelae on CXR. Tuberculosis may be associated with permanent pulmonary impairment even in persons with normal chest x-ray.
Important risk factors for airflow obstruction, including COPD, include smoking status, exposure to indoor and outdoor air pollution, occupational hazard, and infection [
In this study, FVC%, FEV1% and FEV1/FVC% were significantly decreased in those with prior pulmonary TB than in those without prior pulmonary TB. Pulmonary function becomes decreased as the recurrence rate of pulmonary TB increases [
The FEV1% and FEV1/FVC% were significantly decreased in those with prior pulmonary TB than in those without among subjects without abnormalities on CXR although the absolute values of FEV1 were not significantly different. Furthermore, 15.5% of subjects with prior pulmonary TB and no sequelae of pulmonary TB showed airflow obstruction. This data suggests that a history of pulmonary TB might be a predictor of pulmonary function deterioration, despite the absence of pulmonary TB sequelae on CXR. There was no study about pulmonary function impairment in subjects with prior pulmonary TB and no sequelae of pulmonary TB.
In our study, subjects with prior pulmonary TB showed a decrease in FVC% compared with those without prior TB. However, in subjects with normal chest x-ray, there was no difference of FVC% according to prior TB. Pulmonary TB affects FVC through lung tissue scaring, bronchial stenosis, bronchiectasis, and pleural changes [
In this study, prior pulmonary TB (OR, 2.314), along with age, male, asthma, and smoking mount was risk factor for airflow obstruction. Furthermore, OR of prior pulmonary TB for airflow obstruction were increased according to increment of severity of airflow obstruction. Furthermore, prior pulmonary TB was risk factor for COPD even in subjects with normal chest x-ray. In addition, we found that, in the presence of prior pulmonary TB, inactive TB lesions on CXR were risk factors for occurrence of airflow obstruction (OR, 2.300). Prior TB is a risk factor for airflow obstruction and that the risk is more important when they have inactive lesions on chest X-ray. Therefore, subjects newly diagnosed with pulmonary TB should be meticulously treated to prevent the occurrence of sequelae. Furthermore, subjects with sequelae of pulmonary TB on CXR require early detection and management of impaired pulmonary function, and if they are current smokers, they should be advised to quit smoking. In addition, they should also be given other treatment such as pneumococcal and influenza vaccination.
In a previous study that used data from the 2001 KNHANES, a considerable number of subjects with inactive TB lesions on CXR developed airflow obstruction [
In our study, a past history of physician-diagnosed prior pulmonary TB (mean, 29.0 years prior) was related to impaired pulmonary function, as well as respiratory symptoms, including cough, sputum, and dyspnea. In addition, physical activity limitations due to respiratory symptoms increased by 400% and visual analogue scale scores decreased, indicating a poorer quality of life. In subjects without sequelae of pulmonary TB, cough and physical activity limitations were more frequently observed in subjects with prior TB than those without. One study reported that the quality of life decreased by a mean of 13% after TB treatment [
There were some limitations to this study. First, self-reported data obtained through the questionnaire may present with a recall bias. Second, this study did not have detailed clinical data about bacteriological status of the patients, type and duration of treatment, radiological extension of the disease which can have important influence in results. And discrepancy was observed between total subjects diagnosed with pulmonary TB who received treatment by physicians and subjects with inactive lesions on CXR (5.5% vs. 7.9%). Since pulmonary TB can be spontaneously cured without any treatment [
In conclusion, the results of this study suggest that the presence of prior pulmonary TB might be an independent risk factor for airflow obstruction and respiratory symptoms after a significant period following a pulmonary TB infection. And that the risk for airway obstruction is more important when they have inactive lesions on chest X-ray. Considering the significant increase in prevalence of chronic airway disease and burden of medical cost, the spread of TB must be prevented through treatment of latent TB infection and early detection, isolation and treatment of active TB. In addition, subjects with no sequelae of pulmonary TB on CXR can also show impaired pulmonary function, which requires regular follow-ups of lung function for early detection and treatment and smoking cessation.