|Year : 2021 | Volume
| Issue : 4 | Page : 398-404
Evaluation of radiological sequelae after treatment completion in new cases of pulmonary and pleural tuberculosis
Rajeev Tandon, Anoushka Agarwal, Pradeep Nirala, Ansha Sinha
Department of Respiratory Medicine, SRMS IMS, Bareilly, Uttar Pradesh, India
|Date of Submission||17-Sep-2021|
|Date of Decision||18-Oct-2021|
|Date of Acceptance||19-Oct-2021|
|Date of Web Publication||13-Dec-2021|
Department of Respiratory Medicine, SRMS IMS, Bareilly, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background: The objective of this study was to evaluate the residual parenchymal and pleural lesions on chest X-ray posttherapy in new tuberculosis (TB) cases. Methods: This prospective study was done from January 2018 to December 2020, which involved the evaluation of medical records of 60 pulmonary or pleural TB patients who underwent successful treatment. Chest X-rays of the patients at the start and end of treatment were studied as per the guidelines by Revised National Tuberculosis Control Program. The primary outcome measures were residual chest X-ray lesions after the complete treatment of new cases of TB. Secondary outcomes measures were significant factors affecting the chest X-ray clearance. Results: Chest X-ray showed clearing in 48.33% of cases. Residual chest X-ray findings were present in 31 cases which mainly included fibrosis in 23.33% and pleural thickening in 20%. None of the clinical and demographic characters and biochemical parameters showed significant association with chest X-ray clearance (P > 0.05). Sputum microscopy was done in 45 cases of which 25 (41.66%) were positive for acid-fast bacilli. Sputum positivity showed no significant correlation with chest X-ray clearance (odds ratio [OR]: 0.734, confidence interval [CI]: 0.224–2.411, P = 0.592). Compared to nonstandardized regimen, standardized regimen showed no significant correlation with chest X-ray clearance (OR: 0.664; CI: 0.233–1.892, P = 0.426). Conclusion: Residual radiological sequelae were seen in more than half of the study subjects who were successfully treated for TB (51.67%). Demographic, clinical characteristics, sputum positivity, and treatment regimen showed no significant association with chest X-ray clearance.
Keywords: Pleural tuberculosis, pulmonary, tuberculosis
|How to cite this article:|
Tandon R, Agarwal A, Nirala P, Sinha A. Evaluation of radiological sequelae after treatment completion in new cases of pulmonary and pleural tuberculosis. Int J Mycobacteriol 2021;10:398-404
|How to cite this URL:|
Tandon R, Agarwal A, Nirala P, Sinha A. Evaluation of radiological sequelae after treatment completion in new cases of pulmonary and pleural tuberculosis. Int J Mycobacteriol [serial online] 2021 [cited 2022 Aug 16];10:398-404. Available from: https://www.ijmyco.org/text.asp?2021/10/4/398/332356
| Introduction|| |
Tuberculosis (TB) is a serious public health issue worldwide, owing to widespread morbidity and mortality. It ranks above HIV when it comes to infectious diseases with the highest mortality rate. In 2019, 10 million people got affected with TB (5.6 million among males, 3.2 million among females, and 1.2 million among children) and 1.4 million people died., In 2018, India had 2.69 million cases of TB. India ranks first in TB cases globally. According to the WHO, diagnosis and treatment of TB saved around 60 million lives during 2000–2019.
Literature shows that even after giving proper chemotherapy and attaining appropriate clinical response in the new TB patients, most cases were left with residual radiological sequelae. In one of the studies, higher levels of plasma cytokines (IL-2 and IL-4) were attributed as the reason for slow response with residual lesions. Various forms of thoracic sequelae and complications may result from TB and may involve the lungs, airways, vessels, mediastinum, pleura, chest wall, or any combination of these structures, causing significant levels of hemoptysis and recurrent chest infections.
To understand the residual deteriorating effects of TB, it is imperative to know the correct pathogenesis of the disease. Mycobacterium tuberculosis spread occurs through the respiratory route, and within the alveoli, they are ingested by macrophages. With higher bacterial load, there is overwhelming immune response, leading to spread of disease.
A few bacilli remain inactive. They might cause postprimary TB on reactivation, which can lead to complications and residual lesions. Complications and residual lesions can surface in cured and affected pulmonary tuberculosis (PTB) cases.
Kim et al. described numerous residual lesions as shown in [Table 1].
There is a scarcity of previous studies related to the residual lesions of TB in India. Thus, the present study was conducted to assess the percentage of residual parenchymal and pleural lesions based on chest X-rays done posttherapy of new TB cases and the factors affecting the chest X-ray clearance.
| Methods|| |
A retrospective study was done for 3 years (January 2018 to December 2020), involving assessment of medical records of patients with PTB or pleural TB who underwent successful treatment. Radiographs (chest X-ray) taken at start and end of treatment of these patients were studied. Exclusion criteria included patients with a previously diagnosed or treated TB and patients known to have other respiratory diseases such as interstitial lung disease, chronic obstructive pulmonary diseases, and bronchiectasis.
The study of Ali et al. observed that 9% showed complete resolution posttreatment. Taking this value as reference, the minimum required sample size with 7.5% margin of error and 5% level of significance is 56 patients. To reduce margin of error, the total sample size taken is 60.
Medical records of 60 such patients were procured from MRD and demographic details (age, gender, residence, smoking history, and comorbidities) and clinical details were noted.
The basis of diagnosis of TB in these patients was recorded, which included:
- Microbiological confirmation: Based on history and positive sputum examination for acid-fast bacilli
- Clinical diagnosis: Based on history and radiological injuries.
Radiological evaluation (chest X-ray) done at the start and end of treatment of these patients was studied. Reports of other investigations such as complete blood counts (CBCs), liver function tests, kidney function tests, and pleural fluid ADA levels were also noted. Treatment regimens both standardized and nonstandardized were recorded along with total duration of treatment.
The primary outcome measures were residual radiographic lesions on chest X-ray after the complete treatment of new cases of TB.
Secondary outcomes measures were significant factors affecting the radiographic clearance.
The association of the variables (area of residence, smoking, cough, shortness of breath, weight loss, anorexia, leukocytosis, high urea, high creatinine, hypertransaminasemia, alkaline phosphatase increase, sputum, and regimen used), which were qualitative in nature, was analyzed using Chi-square test. Variables such as gender, alcohol, tobacco, fever, hemoptysis, chest pain, comorbidities, anemia, leukopenia, low urea, low creatinine, hyperbilirubinemia, and diabetes had at least one cell with an expected value of less than 5, so Fisher's exact test was used for their association. Odds ratio with 95% confidence interval (CI) was calculated. The association of ADA was analyzed using Mann–Whitney test, and independent t-test was used for association of age
The data entry was done in the Microsoft Excel spreadsheet, and the final analysis was done with the use of Statistical Package for the Social Sciences (SPSS) software, IBM manufacturer, Chicago, USA, ver. 21.0.
For statistical significance, P < 0.05 was considered statistically significant.
| Results|| |
The mean age of the patients was 43.57 ± 19.5 years, with majority of the patients being males (83.33%). 66.6% of the subjects were rural residents and 40% were chronic smokers.
Most common complaints of the patients at initial presentation included fever (85.00%), cough (65.00%), shortness of breath (63.33%), and anorexia (46.67%). 13.33% and 11.67% were known cases of hypertension and diabetes mellitus, respectively [Table 2].
|Table 2: Distribution of demographic and clinical characteristics of study subjects|
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Laboratory findings showed that high prevalence of anemia (85.00% cases), as well as deranged liver function with hyperbilirubinemia (>1.5 mg/dl) in 15.00% of cases, raised alkaline phosphatase in 75.00% of cases, and hypertransaminasemia in 56.67% of cases. Deranged kidney function described by high urea (>40 mg/dl) in 25.00% of cases, and raised creatinine (>0.8 mg/dl) was found in 58.33% of cases. In addition, leukocytosis (>11,000 cells/ml) was found in 28.33% of cases. Mean value of pleural fluid ADA was assessed in those with pleural effusion as initial radiographic finding was 65.77 ± 32.28.
Sputum evaluation for acid-fast bacilli was done in 45 cases. It was negative in 20 (33.33%) cases and positive in 25 (41.66%) cases: 1+ in 13.33% of cases, 2+ in 18.33% of cases, and 3+ in 10.00% of cases.
Pretreatment chest X-ray showed consolidation in majority in 24 (40%) cases, Pleural effusion in 16 (26.67%), Infiltrates in 11 (18.33%), Miliary shadows in 5 (8.33%), cavity in 6 (10%) cases, and hydropneumothorax, hyperinflation, and pneumothorax in two cases each [Table 3].
|Table 3: Distribution of chest X-ray findings on admission of study subjects|
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Standardized treatment was given to 37 (61.67%) patients and nonstandardized treatment to 23 (38.33%) patients. Standardized treatment was given for a median duration of 6 months and non-standardized treatment for median duration of 9 months. Various nonstandardized treatments are shown in [Table 4].
Chest X-ray showed clearing in 29 (48.33%) cases; however, there were residual radiographic lesions in 31 cases which included 14 (23.33%) of fibrosis, pleural thickening in 12 (20%), and hyperinflation, fibrocavitary lesion, reticular shadowing, aspergilloma, and destroyed left lung in 1 case (1.67%) each [Table 5].
None of the clinical and demographic characters (age, gender, area of residence, residence, presenting complaints, and comorbidities) showed a significant association with chest X-ray clearance [Table 6].
|Table 6: Association of demographic and clinical characteristics with clear chest X-ray findings|
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Even the biochemical investigations showed no significant association with chest X-ray clearance [Table 7].
Sputum positivity showed lower odds of chest X-ray clearance (OR: 0.734, 95% CI: 0.224-2.411), however, it failed to cross the statistical boundaries (P = 0.592) [Figure 1].
Compared to nonstandardized regimen, standardized regimen showed no significant odds of chest X-ray clearance (OR: 0.664; 95% CI: 0.233-1.892) (P = 0.426) [Figure 2].
Representative images of the cases (pre and post) are shown in [Figure 3], [Figure 4], [Figure 5].
|Figure 3: (a) Pretreatment chest X-ray showing bilateral upper zone exudative lesions (cotton wool appearance) typical of active tuberculosis. (b) Posttreatment X-ray showing residual fibrosis|
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|Figure 4: A 58-year-old male (a) before treatment right upper zone cavity. (b) Posttreatment, healed cavity with fibrosis|
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|Figure 5: A case of 56-year-old male with clinical history of right-sided chest pain, fever, and weight loss. (a) Chest X-ray at primary evaluation showed signs of right-sided pleural effusion. Diagnostic pleurocentesis was performed, and fluid was sent for investigations, which was reported as tubercular etiology. Antitubercular treatment was started, and (b) posttreatment X-ray showing resolution with residual pleural thickening on the right side|
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| Discussion|| |
The treatment success rate has been reported by the 2021 India TB Report to be 84% in newly diagnosed drug-sensitive TB. However, despite adequate chemotherapy and clinical response in new cases of TB, a large proportion of patients are left with residual radiological sequelae.
In our study, chest X-ray clearance was seen in only 29 (48.33%) as compared to the study by Menon et al., which reported a clearance rate of 59.64%. Ali et al. and Yeison et al. found complete resolution in 9% and 11.35% of cases, respectively, which is lesser than our study. The most frequently observed posttreatment residual lesion in PTB was fibrosis (23.33%), while in pleural TB, 12 of 16 subjects had residual pleural thickening. Other residual lesions included hyperinflation, fibrocavitary lesion, reticular shadowing, aspergilloma, and fibrosis with hyperinflation.
This was in concordance with other studies such as that by Menon et al., which reported fibrosis in 38.7% and pleural thickening in 21.2% of the 120 cases with residual lesions. Cavitating lesions were present in 21.4% of cases, bronchiectasis in 4.3%, and pulmonary calcifications in 3%. Yeison et al. found that parenchymal sequelae, respiratory tract sequelae, mediastinal sequelae, pleural sequelae, and vascular sequelae were present in 79.43%, 41.1%, 34.8%, 26.2%, and 5%, respectively. Ali et al. reported the sequelae as the presence of unilateral fibrosis with loss of lung volume in 33% of cases, unilateral pleural thickening with fibrosis and volume loss in 14%, bilateral fibrosis and loss of lung volume in 9.4%, unilateral bronchiectasis with fibrosis in 6%, bilateral bronchiectasis with fibrosis in 6%, and bilateral pleural thickening with fibrosis in 6%. In nearly 40% of the cases with postprimary TB, there is marked fibrotic response, manifesting in the form of upper lobe atelectasis with hilum retraction, compensatory hyperinflation of lower lobe, and mediastinal shift toward the fibrotic lung. The present study also found these findings as fibrosis was present in 23.33% of cases.
Bronchiectasis and residual cavities are the sequelae generally present in the upper lobes. In the present study, no case of bronchiectasis was found as sequelae, partly due to the study being limited to chest X-ray. Compared to our study, Menon et al. reported that bronchiectasis in the form of sequelae was present in 4.3% of patients. On the contrary, Hatipoğlu et al. found bronchiectasis to be present on high-resolution computed tomography (CT) among 71%–86% of the patients having inactive disease and among 30%–60% of the patients having active postprimary TB.
Even in cases where treatment is not given, tuberculous pleuritis is usually observed to be completely resolved. On the other hand, chronic complications are reported to take place in certain patients after the healing of the tuberculosis lesions or are found in the form of late sequelae. Choi et al. mentioned that post-TB, the residual lesions appears as thickening of pleura, pleural calcification, and fibrothorax.
In the present study, pleural residual lesions were present in 12 of 16 patients with pleural effusion on the pretreatment radiograph. Similarly, Menon et al. found that pleural residual lesions were present in 23.6% of the patients. However, in the study by Kwon et al., after completion of antituberculosis treatment for pleural effusion, the residual pleural opacity was found in 68.3% of patients.
Longer duration between the onset of symptoms and starting treatment may be the reason for the spread as well as progression of lung lesions, resulting in further residual damage. Moreover, inflammatory response to mycobacterial invasion varies from patient to patient, and a more heightened inflammatory response in some individuals may be related to greater local tissue destruction resulting in greater residual damage.
On analyzing other factors, we found that none of the sociodemographic factors (age, gender, area of residence, residence, presenting complaints, and comorbidities) and biochemical investigations showed significant association with chest X-ray clearance.
Compared to the present study, Al-Hajjaj and Joharjy. found advanced age (>40 years), being female, longer duration of symptoms (>8 weeks), poor adherence with treatment, and history of tuberculosis as the factors associated with poor radiological outcomes. Yeison et al. found that the factors associated with the development of PTB sequelae included age >65, diagnosis using fiber-optic bronchoscopy while in acute phase, anticholinergics use, beta-2 agonists use, exacerbations history, and symptoms such as dyspnea and cough.
As far as sputum positivity was concerned, in our study, out of 45 cases in which sputum test was done, it was positive in 25 (41.66%) cases. However, statistically positivity of sputum was not associated with chest X-ray clearance. Sputum positivity holds importance as it can be negative in few cases and may affect the outcomes.
In contrast, in the study by Menon et al., in majority of patients with sputum-positive tuberculosis, there was the presence of a residual lesion, in comparison to sputum-negative patients (70% vs. 28.5%). They reasoned it to be due to the presence of greater bacterial load in the sputum-positive cases, leading to more damage.
Treatment-wise, it is a possibility that among patients without residual lesion on chest X-ray following treatment, healing of lesions occurs before the development of necrosis. Moreover, it is possible that at the Anti-tubercular therapy (ATT) initiation, severe lesions may result in residual lesions following management completion.
However, in the present study, where standardized treatment was given to 37 (61.67%) patients (median duration = 6 months) and nonstandardized treatment to 23 (38.33%) patients (median duration = 9 months), there was no significant association of treatment regimen with chest X-ray clearance (P = 0.426).
However, Al-Hajjaj and Joharjy reported that there was an association between good compliance of ATT with better outcomes on chest X-ray. It was mentioned that there are no known particular effect of ATT on the histopathology of the tuberculous inflammatory reaction, and early initiation tends to boost the possibility of radiological clearance. It is likely that eradication of tubercle bacilli causes an end to the inflammatory response, which slows or prevents advancement to the fibrotic stage.
One of the limitations of the present study was that it was a single-center study; therefore, findings cannot be generalized. Another limitation was that the duration between onset of symptoms and treatment was not measured, the effect of which on chest X-rays clearance was not assessed. In addition, we have not studied the effect of compliance towards treatment on radiological clearance.
| Conclusion|| |
Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life.
Demographics, clinical characteristics, sputum positivity, and interestingly different treatment regimens showed no significant association with chest X-ray clearance. The disabling sequelae posttreatment of tuberculosis may have a great adverse psychosocial as well as financial impact. Therefore, one should have knowledge about the complete spectrum of such disorders for facilitating early diagnosis as well as treatment.
More research is required to investigate the genetic as well as environmental factors that render one person more prone to residual lesions.
The study was approved by the institutional Ethics Committee of Shri Ram Murti Institute of Medical Sciences, SRMS IMS/ IEC/ 2021-22/014
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]