Clinical, Radiological, and Lung Function Characteristics of Post-tuberculosis Bronchiectasis: An Experience From a Tertiary Care Center in India

Introduction Among chronic respiratory diseases, bronchiectasis is one of the important causes of mortality and morbidity in developing countries. Objective This study aimed to assess the clinical, radiological, microbiological, and pulmonary function profiles of adult patients with post-tubercular bronchiectasis. Methods We enrolled 138 patients with bronchiectasis confirmed by high-resolution CT scans from July 2017 to August 2018. Results A total of 138 patients with bronchiectasis were enrolled. The data from 132 patients were analyzed; six patients were excluded from the study. The mean age of post-TB bronchiectasis (post-tuberculosis bronchiectasis) patients was 36.08±13.08, which was lower than the non-tuberculosis bronchiectasis group. The proportion of the male population was more in the post-TB bronchiectasis group (54.55% vs. 37.88%, p=0.48). Smoking prevalence was high in post-TB bronchiectasis (27.27% vs. 12.12%, p=0.04). The predominant symptom was cough in the post-tubercular bronchiectasis group (48.5% vs. 41.7%, p=0.019). The history of the recurrent common cold was seen most frequently in non-post-tubercular bronchiectasis (40.9% vs. 12.9%, p=0.001). The most common radiological variant of bronchiectasis found in all patients was a cystic type (75%). The most common site of involvement was the left lower lobe, followed by the lingula in all patients and post-tuberculosis bronchiectasis patients. Pulmonary function on spirometry revealed obstructive, restrictive, and mixed patterns in 55%, 25%, and 15%, respectively. Patients with post-tuberculosis bronchiectasis had lower lung function post-FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio (70.31±15.56 vs. 76.85±11.82, p=0.015). Binary multivariate logistic regression analysis showed that only recurrent cough cold was a significant independent risk factor for post-TB bronchiectasis. Conclusion Post-tuberculosis, and bronchiectasis followed by post-infectious causes, were the most common causes of bronchiectasis and poor lung function.


Introduction
Bronchiectasis is a chronic respiratory disease and an emerging global health problem. It is an umbrella term defined by abnormal, permanent dilatation of bronchi seen on the CT thorax characterized by respiratory symptoms, cough, sputum production resulting from chronic infection, and inflammation [1]. The trinity of bronchiectasis is an infection, airway inflammation, and destruction. It is a heterogeneous disease with different etiologies associated with various syndromes. Due to the heterogeneous nature of the illness and varied etiology, there are differences in the presentation and natural course of the disease. The growing prevalence of bronchiectasis in recent years is an area of concern. In Europe and North America, the prevalence of bronchiectasis has been shown to range from 53 to 566 per 100,000 people [2,3]. In Europe and the USA, the disease prevalence has increased by more than 40% in the last ten years [4].
Even though there has been significant improvement in our understanding of this condition, most of the large-scale epidemiological databases on bronchiectasis have come from the USA, Australia, and European nations. Small cohorts from China and South America suggest that the characteristics of patients from lowincome and middle income countries might differ from those in Europe. There is no data to define the exact burden of bronchiectasis in India. The first multicentre, prospective, and observational European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) India registry highlighted the etiology, disease severity, microbiology, treatment, and demographic characteristics of bronchiectasis patients [5]. Data from European countries found that 40% of bronchiectasis cases are idiopathic and are most commonly seen in female and older age groups [6]. The EMBARC India registry revealed that tuberculosis is the most common etiology for bronchiectasis [5]. Post-tuberculosis bronchiectasis is an emerging phenotype in Asian countries. Tuberculosis (TB) and bronchiectasis are interlinked, although bronchiectasis can occur during tuberculosis or be a sequela of TB. A systematic review evaluated the prevalence of 35-86% in post-tuberculosis bronchiectasis patients diagnosed with CT imaging [7]. Here we describe the clinical characteristics, spirometry, and radiology of post-tuberculosis bronchiectasis.

Materials And Methods
This prospective, observational, non-interventional study enrolled 138 adult patients aged 18 years with bronchiectasis. Diagnosis of bronchiectasis was made on the clinical symptoms, cough, sputum production or recurrent respiratory infections, and CT thorax. Informed consent was taken from all enrolled patients. The patients with cystic fibrosis, bronchiectasis due to interstitial lung disease, hemodynamic instability, chronic kidney disease, acute myocardial infarction, and patients unable to consent were excluded from the study. The institution's ethics committee King George's Medical University approved the study. Post-TB bronchiectasis was assigned when history or clinical evidence of TB was evident and radiological findings of bronchiectasis were suggestive of TB, including scarring of the upper lobes, granuloma, and cavitation ( Figure 1).

FIGURE 1: CT thorax shows bilateral bronchiectasis and fibro-cavitary (red arrow) changes in the upper zone with volume loss (posttuberculosis)
The post-infectious etiology was defined as bronchiectasis caused by a prior infection other than TB. ( Figure  2).

FIGURE 2: CT thorax of bilateral cystic bronchiectasis (red arrow) middle and lower zone
According to the guidelines, idiopathic bronchiectasis was defined when no specific etiology was determined after a diagnostic workup. TB was ruled out in another bronchiectasis group by sputum smear examination for acid-fast bacilli (AFB) and molecular tests like cartridge-based nucleic acid amplification (CBNAAT). Line probe assay (LPA) tests were also conducted to rule out tuberculosis.
The demographic data, biochemical laboratory parameters, lung function testing, chest X-ray, HRCT thorax, and sputum microbiology were conducted. A pulmonary function test was done according to American Thoracic Society guidelines. The parameter percentage of predicted forced expiratory volume in one second (FEV1) was calculated using reference values for South Asian patients. Obstructive airway was defined by a FEV1:forced vital capacity (FVC) ratio of less than 0.7. Patients with a FEV1:FVC ratio of 0.7 or more and FEV1 and FVC less than 80% of the predicted values were classified as restricted lung disease [8]. A detailed history of respiratory symptoms was taken. Breathlessness was assessed on a modified Medical Research Council (mMRC) scale. The history and investigations exploring the etiology of bronchiectasis and allergic bronchopulmonary aspergillosis were diagnosed according to the guideline [9]. HRCT scans were done to diagnose bronchiectasis and other pulmonary abnormalities.

Statistical analysis
The data were expressed as appropriate mean, standard deviation (SD), and number (%). All categorical data were compared by using the chi-square test. Continuous variables in the two groups were compared by ttest. The binary logistic regression was used to analyze the independent risk factor for post-TB bronchiectasis. The p-value <0.05 was considered significant. The statistical analysis was done using SPSS Statistics v. 21.0 for Windows (IBM Corp., Armonk, NY).

Results
A total of 132 patients with bronchiectasis were enrolled in the study. The distributions of patients based on different age groups are shown in Figure 3.

TABLE 1: Comparisons of baseline parameters between Group 1 and Group 2
The mean age of patients was significantly lower in Group 1 than in Group 2 (36.08±13.08 vs. 46.5±14.17, p=0.005). The frequencies were significantly higher in patients with smoking and cough and markedly lower in recurrent cold atopy. At the same time, the frequencies of dyspnea, chest pain, fever, and expectoration were not significantly different between groups. The number of smokers (27.27%) was more prevalent in the post-tuberculosis bronchiectasis group ( Figure 6). Hemoptysis was more commonly (42.42%) seen in Group 1 but is nonsignificant. The most common symptoms were cough (48.5%), followed by hemoptysis (42.42%), dyspnea (37.9%), chest pain (17.4%), and fever (15.2%) in post-TB bronchiectasis patients. Cough was significantly higher in Group 1 (48.5% vs. 41.7%, p=0.019). Mucoid expectoration was common in group one; however, mucopurulent expectoration was common in Group 2 but the difference was non-significant (43.94% vs. 43.94%, p=0.44). Table 2 shows comparisons of general examination, radiological findings, and microbiology between the two groups.  The frequencies of physical examination such as anaemia, clubbing, crepitus, and rhonchi were not significantly different between the two groups. Anaemia was present in 46.97% of patients in the posttuberculosis bronchiectasis group. Clubbing was seen in 65% of the post-tuberculosis bronchiectasis group. The most common auscultatory finding was crepitations seen in 95.45% of Group 1. Cystic bronchiectasis was the dominant pattern in HRCT in non-tuberculosis bronchiectasis. The difference was significant (86.36% vs. 66.67%, p=0.014); the proportion of tractional and cylindrical bronchiectasis was higher in the post-TB bronchiectasis group. The "tram track" appearance and fibro-cavitary changes were significantly higher in the post-tuberculosis bronchiectasis group. The "finger-in-glove" appearance and "signet ring" sign were considerably lower in Group 1, and the difference was significant. The distribution of bronchiectasis according to the lobes affected showed almost equal distribution in both groups: the most common site of infection was the left lower lobe followed by the lingula, right middle lobe, right lower lobe, left upper lobe, and right lower lobe. The mean serum IgE was lower in post-TB bronchiectasis but not significant (

Group 2
The binary logistic regression was used to find the independent risk factor for post-TB bronchiectasis only; recurrent cough and cold were considered significant independent risk factors for post-TB bronchiectasis.
Other variables included age, sex, smoking, FEV1 pre, FEV1 post, FVC pre, FVC post, FEV1/FVC pre, FEV1/FVC post, AEC, serum IgE, duration of illness, and pseudomonas in culture were considered not significant and independent of risk factors for post-TB bronchiectasis ( Table 4).

Discussion
India has a high population and a high prevalence of tuberculosis. Laennec first noted the co-existence of bronchiectasis and TB in 1819. The following pathogenesis theory of bronchiectasis states that bronchiectasis occurs because of the destruction of the elastic and muscular components of the bronchial wall, usually due to acute or chronic infection. Traction bronchiectasis is a common finding in post-TB sequelae patients. It occurs due to the destruction and fibrosis of the lung parenchyma with irreversible secondary bronchial dilatation [10,11].
The study showed that India's most common etiology of non-cystic fibrosis bronchiectasis was posttubercular, unlike Europe and the USA. The prevalence of tuberculosis is very high in India; as a result, the most common etiology of bronchiectasis is tuberculosis in India [12,13]. As in our study, 50% population had post-tubercular bronchiectasis. A systematic review showed that bronchiectasis was seen in 40-80% of treated cases of tuberculosis [14].
The dominant symptoms in the study group were chronic cough with expectoration and dyspnea, with rates comparable to previously reported series. Haemoptysis, the most devastating sign of bronchiectasis, was noted with a frequency of 42.42% vs 30.30% among patients with post-TB bronchiectasis and nontuberculous post-infectious, respectively. Post-tubercular bronchiectasis patients had a more significant degree of pulmonary function impairment. Post-tubercular bronchiectasis is an emerging phenotype with high male preponderance, younger age, smokers, and poor lung function. Cough and hemoptysis were the most common presenting symptoms. The most commonly affected age group by bronchiectasis is the 60-70year age group, and most were females, in line with previous studies [15].
Post-tubercular bronchiectasis patients were in the younger age group than 50 years of age. The majority were male. Cough followed by hemoptysis were the most frequent symptoms with daily expectoration in post-tubercular bronchiectasis. Mucoid expectoration was seen in the post-tubercular bronchiectasis group, comparable with the EMBARK study from India [5]. Interestingly, despite numerous patients having posttubercular bronchiectasis, they complained of day-by-day sputum generation rather than dry bronchiectasis.
The productive cough in this study can be clarified by the truth that post-TB sequelae are not limited to bronchiectasis. These patients can have bronchial mutilation, obstructive airway malady disconnected to bronchiectasis, fibrosis, cavitation, etc. [16]. For the same reasons, despite having localized bronchiectasis, some patients had a severe hindrance or nonspecific impairment with exceptionally low FEV1 and FVC. Thus in post-TB patients, it is difficult to comment on the chance that all side effects are due to bronchiectasis only. Among the etiologies, post-infectious causes prevail in this cohort, with 50% of patients having a history of pulmonary TB and 36.36% of patients having a history of other infections in the past.
The prevalence of post-TB bronchiectasis is steady with the high burden of TB in South Asia, with India being positioned second among countries with a high TB burden according to the WHO TB report of 2021.
Our study found that the extent of post-TB bronchiectasis is even greater than the data in the information from the previously published Indian bronchiectasis registry, i.e., 50% vs. 35.5% [5]. This is probably the case as our institute established this registry as one of India's biggest nodal TB centers. In our study, 4.54% of the cases stay idiopathic, similar to the more significant part of the past studies where idiopathic cases contain 18-55% of the study population [17].
About 70% were nonsmokers; however, the proportion of smokers was higher in the post-TB bronchiectasis group. Although smoking is not directly associated with bronchiectasis, it causes a worse outcome. In our study, pulmonary function showed obstructive (55%), restrictive (25%), and mixed patterns (15%). Previous studies also showed obstructive impairment was the predominant spirometric pattern [18]. Patients with post-tubercular bronchiectasis had a greater degree of impedance than other types. Pseudomonas was the major ordinary pathogen confined in microbiology, which is consistent with recent data; however, it varies from other studies where Haemophilus influenza was the most standard organism among bronchiectasis patients. In previous studies, Pseudomonas colonization was the critical factor in more severe outcomes among bronchiectasis patients.
Mean serum IgE and absolute eosinophil counts were lower in the post-tubercular group. Serum IgE and eosinophil counts were performed in all patients to know the etiology of bronchiectasis. However, overall serum IgE was raised in 86.4% study population. The Korean Multicentre Bronchiectasis Audit and Research Collaboration (KMBARC) showed that 19.7% had post-tubercular bronchiectasis and a more severe radiological extent. In this registry 65.7% post-TB bronchiectasis group had obstructive airway disease and lower FEV1 than other groups [19]. Our study also showed that 55% post-tuberculosis bronchiectasis group had obstructive airway disease followed by restrictive and mixed patterns in 25% and 15%, respectively. Some of the patients (5%) could not perform spirometry. Patients with post-tubercular bronchiectasis were predominantly males, younger, and had lower lung function as well as more significant functional impairments. Cough and hemoptysis were the most common presenting symptoms.

Conclusions
According to our research, post-TB bronchiectasis affected around half of the individuals with bronchiectasis. The individuals who had post-TB bronchiectasis were younger, coughed more frequently, had colds, and smoked more. In post-TB bronchiectasis, fibrocavitatory changes, cylindrical and varicose types of bronchiectasis, and the tram track sign on the CT thorax were frequently observed. In bronchiectasis groups, there were no appreciable intergroup differences in the site of involvement. Patients who had post-TB bronchiectasis had worse lung function than those who had the other types of bronchiectasis.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethical Committee, King George's Medical University, Lucknow issued approval Ref code: 96th ECM IIA/P3, dated 2019/07/31. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.