European Journal of Cardiovascular Medicine

Tuberculosis (TB) represents a significant global health challenge, with its history intertwined with humanity since ancient times.  While the discovery of the tubercle bacillus by Robert Koch in 1882 marked a milestone in TB research, the disease continues to affect approximately one- quarteroftheworld'spopulation. India bearsa particularly heavy burden, accounting for 27% of global tuberculosis cases, with 2.42 million casesreported in 2022. ,

Despite remarkable progress in medical research and treatment, large proportion(40-97%)  of successfully treated pulmonary tuberculosis patientsdevelopchronic respiratoryabnormalities, collectively termed as Post Pulmonary TB Sequelae (PostPTBsequelae). , , , , , Despite adequate treatment, post pulmonary TB cases may develop range of morbidities, such as bronchiectasis, airway stenosis, pleural and parenchymal fibrosis, calcification, kyphoscoliosis.These result in pulmonary function abnormalities in the form of obstructive changes, restrictive changes, or mixed defects. Diffuse airway obstruction has been reported in 30%-60% of cases with pulmonary TB. , Because of diffuse parenchymal fibrosis, pleural thickening, and fibrothorax, a restrictive type of pulmonary function defect develops. Thus, in a patient with pulmonary

TB, obstructive, restrictive, or a mixed type of lung function abnormality is possible depending upon the type and extent of involvement or residual damage.

Pathogenesisinvolves

Complex interactions between direct tissue damage from tubercle bacilli and the host's immune response, When patient becomes infected, bacilli are engulfed by alveolar macrophages, spread to regional lymph nodes and dissemiate hematogenously.The subsequent immune response, primarily driven by CD4-T lymphocytes, initiates a cascade of events leading to granuloma formation and potential tissue destruction.  Post PTB sequelae emerges from the intricate interplay between tissue damage and immune response, transitioning from a treatable infectious diseasetoa chronic morbidity. The First International Symposium on Post-tuberculosislung health defines these sequelae as "Evidence of chronic respiratory abnormality, with or without symptoms, attributable at least in part to previous pulmonary tuberculosis".  These abnormalities manifest across multiple systems, affecting airways, lung parenchyma, pleura, and pulmonary vasculature.

The burden of pulmonary function abnormalities are particularly pronounced in regions with high tuberculosis prevalence, such as India. Research, including the Burden of Obstructive Lung Disease (BOLD) and PLATINO studies, consistently demonstrates a correlation between past TB infection and abnormal lung function. , Moreover, individuals with post-TB sequelae exhibit a mortality risk 3.76 times higher than the general population.

This research is particularly relevant given the need for increased advocacy to recognize the post-TB pulmonary function abnormalities, aiming to improve the long-term health outcomes of affected individuals.

This hospital-based observational study was conducted at the Department of Respiratory Medicine, Mahatma Gandhi Medical College & Hospital, Jaipur, spanning from September2022 to March2024. The study protocol received approval from the institutional ethics committee, andwritten informed consent was obtained from all participants. A total of 300 post-pulmonary TB patient swereenrolledinthe study, with the sample size calculated based on the prevalence of post-TB sequelae reported in previous studies, using a confidence level of 95% and a margin of error of 5%. Among these, Spirometry was successfully performed in 242 cases. In remaining cases, spirometry was not performed due to several factors including the physical inability of patients to perform the test or the lack of patient consent.

The study population (n=242) was selected based on pre-defined inclusion and exclusion criteria. Eligible participants were required to be over 18 years of age, have a definite history of pulmonary tuberculosis treatment for more than 1 month, demonstrate abilityto cooperate during evaluation procedures, and provide informed consent. Exclusion criteria encompassed current anti-tubercular treatment, active mycobacterium tuberculosis infection, co-existent pulmonary or extra-pulmonary disease impairing lung function, acute coronary syndrome, and immunocompromised state.

Data collection employed a multi-modal approach utilizing several assessment tools. Clinical assessment began with obtaininga detailed history through a pre-designed proforma. Physicalexaminationwas conducted with particular emphasis on respiratory system findings. Pulmonary function testing was conducted using a computerized spirometer (true flow NDD700-1- 01UPC).Spirometry assessments were conducted to evaluate lung function.Statisticalanalysis.

wasperformedusingappropriate statistical software, employing both descriptive and inferential statistical methods. Demographic and clinical characteristics were analyzed using descriptive statistics, while categorical variables were assessed using the Chi-square test. The Krustal Wallis test was applied for continuous variables. Statistical significance was established at two levels: p≤0.05 was considered significant, while p≤0.001 was deemed highly significant. This comprehensive statistical approach enabled thorough evaluation of the pulmonary function abnormalities in post pulmonary TB sequelae patients.

Spirometry assessments were conducted on 242 cases to evaluate lung function. The demographic profile revealed a mean age of 59.33±12.18 years, with a significant majority (51.7%) aged above 60 years, followed by 40.1% in the 40-60 years age group, and 8.3% under 40 years. Male predominance was observed with 184 (76.03%) male patients compared to 58 (23.97%)

female patients, yieldingamale-to-femaleratioof3.17:1. Rural residents constituted 79.8% (193) of the study population, while 20.2% (49) were from urban areas. Regarding occupation, farming was the predominant occupation (27.7%), followed by dependents (25.2%) and unskilled laborers (23.1%). Business/merchandising accounted for 11.2%, skill-based work for 10.3%, and academics/paraprofessionals for 2.5% of cases. Analysis of risk factors revealed that 52.1% (126) of patients were smokers, with higher prevalence among males (56.5%) compared to females (37.9%). Biomass fuel exposure was reported in 19.8% (48) of cases. Treatmenthistoryanalysisshowedthat79.3 %( 192) of patients had completed their anti- tubercular treatment, with70.2%(170)completing it once and 9.1% (22) requiring multiple courses.20.7% of patients (50) had history of incomplete treatment.(Table 1).

Table1:DemographicandClinicalCharacteristicsofStudyPopulation (N=242)

Table2:DistributionofClinicalManifestationsinPost-TBSequelaeCases(N=242)

The study demonstrated a predominant respiratory symptom burden in post-TB cases. Shortness of breath (87.6%) and cough (77.7%), expectoration (59.5%) were the most common manifestations, followed bychest pain (17.4%) and hemoptysis (8.3%). (Table 2).

Figure 3: Distribution of Study Population according to m MRC grading of Shortness of Breath

Out of the 242 cases, 30 (12.4%) were classified as grade 0, 22 (9.1%) as grade 1, 62 (25.6%) as grade 2, 96 (39.7%) as grade 3, and 32 (13.2%) as grade 4. mMRC Grade Number of Cases (n-242) Percentage 0 30 12.4% 1 22 9.1% 2 62 25.6% 3 96 39.7% 4 32 13.2%

Table4:PulmonaryFunctionAbnormalitiesinPost-TBCases(N=242)

Fig. 3: Distribution of Study Population according to Pulmonary Function Abnormalities

Pulmonary function testswereconducted in 242 cases. Most patients (88.26%) exhibited abnormal lung function, with restrictive pattern predominating (37.19%),followedbymixed(26.45%)andobstructive patterns (25.62%). (Table 3& Fig 3).

Table4:SeverityofPulmonaryFunctionAbnormalities

Among cases with an obstructive pattern, 19.35% were mild, 45.16% moderate, 22.58% severe, and 12.90% very severe. Amongthe restrictive pattern, 24.44% were mild, 37.78% moderate, 18.89% severe and 18.89%very severe. Among the cases with mixed pattern, 7.81% were mild, 26.56% moderate, 43.75%severe, and 21.88%very severe.  (Table 4).

Out of 242 cases, 98 cases (40.5%) had severe to very severe abnormalities. Severe to very severe pulmonary function abnormalities were observed in 33.9% of cases with complete ATT and 66.0% of cases with incomplete ATT, 45.2% of cases with smoking history while 34.17% of nonsmoker cases.

Table 25: Pulmonary Function Abnormality – Severe to Very Severe (n=98)

In this hospital-based observational study conductedatatertiarycarecenter, weanalyzed.

242 cases of post-pulmonary TB sequelae with pulmonary function test. The demographicprofilerevealedameanageof59.33±12.18years, with majority (51.7%)aged above 60years.Thehigher manage in our study could be attributed to the cumulative effect of TB sequelae becoming more apparent with advancing age. A significant male predominancewasobservedwitha male-to-female ratio of3.17:1. Reason for the consistent male predominance might include biological differences, higher exposure to TB risk factors among men like smoking and occupational hazards.

The geographical distribution showed a significant rural predominance (79.8%) compared to urban areas (20.2%), which may reflect the healthcare access patterns in our region and the higher prevalence of risk factors in rural settings. Occupationaldatarevealedfarming (27.7%)as the most common occupation, followed by dependents (25.2%) and unskilled laborers (23.1%) in our study population.

52.1% (126) of study subjects were current smokers or ex-smokers, while 19.8% (48) cases reported biomass fuel exposure. Both these riskfactorshavebeenassociated with poorer outcomes in post-TB sequelae, as smoke exposure impairs mucociliary clearance and alveolar macrophage function, potentially exacerbating lung damage.

Treatment history analysis revealed that 79.3% of patients had completed their anti-tubercular treatment, with 70.2% completing it once and9.1% requiring multiple courses. However, a considerable proportion (20.7%) had incomplete treatment, correlating with higher rates of complications.Thisfindingemphasizesthecritical importance of treatment adherence in preventing severe sequelae.

In our study, the common clinical symptoms were shortness of breath (87.6%), followed by cough (77.7%) & expectoration (59.5%). Less common symptoms were chest pain (17.4%), hemoptysis (8.3%). These findings highlight the respiratory difficulties encountered even after cure of pulmonary tuberculosis.

Our study employed the Modified Medical Research Council (MMRC) scale to assess the severity of shortness of breath. The most frequently observed severity was Grade 3 shortness of breath, reported in 39.7% of cases. This was followed by Grade 2 (25.6%), Grade 4 (13.2%), with Grade 1 being the least common (9.1%). Shortness of breath in post-tuberculosis sequelae cases is attributed to pulmonary fibrosis, reduced lung function, alterations in lung compliance, and pleural thickening.

In our study, spirometry assessments for lung physiology function were successfully conducted in 242 cases. The majority of the cases, 37.19% (90cases), exhibited a restrictive pattern. This was followed by a mixed pattern in 26.45% (64 individuals) and an obstructive pattern in 25.62% (62 individuals). Similar to our observation, Gordon et al. (1971)79 (n=1403) found restrictive pulmonary defects in 24%, obstructive pulmonary defects in 23% and mixed defect in 19% cases.  It demonstrated a majority of cases having restrictive pattern, suggesting a consistent finding across both the studies. Despite the slight variation in prevalence, the occurrence of obstructive defects remains a comparable pattern in numerous studies. André F.S. Amaral et al. (2015)84

reported an adjusted odds ratio of 2.51 for obstructive defects and 2.13 for restrictive defects in post pulmonary tuberculosis cases, indicating a marked increase in the likelihood of these pulmonary impairments in individuals.  This supports our study that significant association between a history of tuberculosis and subsequent pulmonary function abnormalities exist.

Obstructive defects in post-pulmonary TB sequelae cases are due to chronic airway inflammation and damage leading to airway narrowing and resulting in obstructive patterns on spirometry. Restrictive defects may be attributed to lung fibrosis or other structural changes such as parenchymal destruction or pleural thickening. These changes reduce lung compliance and volume, leading to a restrictive pattern on spirometry. Mixed defects, combining elements of both obstructive and restrictive physiology, might reflect the complex interplay of airway narrowing and parenchymal loss typically seen in post-tuberculosis cases. This indicates more severe or widespread pulmonary damage, resulting in both reduced airflow and lung volume. Our findings explain the existence of significant obstructive and restrictive patterns in individuals with a history of tuberculosis, aligning with previous studies while also providing detailed insights into the prevalence of mixed defect patterns. Our findings have implications for post- TB care. They emphasize that successful completionofanti-tuberculartreatment, while crucial, is not the endpoint of patient care. The high prevalence of long-term sequelae suggests the need for a comprehensive post-TB care program thatincludesregular monitoringof lung function, early detection and management of complications, and rehabilitation services.

This study highlights the burden of chronic pulmonary function abnormalities persisting in individuals following pulmonary tuberculosis treatment, emphasizing the transition from acute infection to chronic respiratory morbidity. The restrictive, obstructive, and mixed pulmonary impairment patterns reflect the underlying parenchymal, pleural or skeletal sequelae from the previoustuberculosisinfection. Demographic factors

Such as advanced age, male gender, rural residence, and exposure to smoking or biomass fuels emerged as contributors to worsened outcomes, emphasizing the role of socio-environmental determinants in post-TB lung health.Incomplete anti-tubercular treatment was associated with higher risk of severe functional impairment, reiterating the critical need for treatment adherence. The high prevalence of debilitating symptoms, particularly dyspnoea and chronic cough, highlights the profound impact on quality of life, even after microbiological cure. These findings advocate for a paradigm shift in TB management, urging systematic integration of post-TB pulmonary rehabilitation, longitudinal functional monitoring, and targeted interventions to mitigate modifiable risk factors. Strengthening public health strategies to ensure treatment completion, alongside multidisciplinary care pathways addressing chronic respiratory morbidity, is essential to alleviate the lifelong health consequences of post-tuberculosis sequelae.

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