The Prevalence and Clinical Manifestations of Post-Tuberculosis Lung Disease in Immunocompetent HIV-Negative Individuals: A Scoping Review

1. Prevalence and Clinical Manifestations: Post-Tuberculosis Lung Disease (PTLD) affects 20% to 45% of immunocompetent, HIV-negative individuals, with chronic respiratory symptoms like cough, dyspnoea, pulmonary fibrosis, and bronchiectasis.
2. Diagnostic and Long-Term Care: HRCT and spirometry are essential for diagnosing PTLD, and patients often require long-term follow-up care and pulmonary rehabilitation due to recurrent infections and chronic disability.
3. Need for Research and Standardized Care: There is limited research on PTLD in HIV-negative individuals, highlighting the need for standardized diagnostic criteria and treatment protocols for better management.

Tuberculosis lung disease (PTLD). PTLD encompasses a range of conditions, including pulmonary fibrosis, bronchiectasis, and chronic obstructive pulmonary disease (COPD) [3] These complications can significantly impair lung function and diminish the quality of life for survivors.

Table 1: Summary of study characteristics

The prevalence of PTLD in immunocompetent, HIV-negative individuals varied between 20% and 45% across the included studies. This wide range is likely due to differences in the severity of TB infection, extent of lung involvement, and treatment duration [7,8]. Higher rates of PTLD were observed in regions with high TB burdens, such as India and Ethiopia.

Clinical Manifestations

Common clinical manifestations of PTLD included chronic respiratory symptoms such as persistent cough, dyspnoea, and chest pain. Pulmonary fibrosis and bronchiectasis were frequently identified on imaging [9,10] Some patients exhibited significant lung function impairment, characterized by reduced forced

 Expiratory volume (FEV1) and forced vital capacity (FVC) [11].

Diagnostic Tools

The most frequently utilized diagnostic tools were high-resolution computed tomography (HRCT) and spirometry. HRCT was especially useful for detecting structural abnormalities such as fibrosis and bronchiectasis [8,12]. Spirometry was employed to evaluate the degree of airflow obstruction and restrictive lung disease, providing essential information for managing PTLD.

Long-Term Outcomes

Long-term outcomes in patients with PTLD often included chronic respiratory symptoms, recurrent infections, and chronic disability. Many patients require long-term follow-up care, including pulmonary rehabilitation and ongoing medical management [8]. The burden of PTLD on healthcare systems is significant, and efforts to improve post-TB care are essential to improving long-term outcomes.

Discussion

Comparison of PTLD in HIV-Negative and HIV-Positive Individuals

Comparing PTLD in HIV-negative individuals to that in HIV-positive individuals reveals key differences. In HIV-positive populations, the risk of developing opportunistic infections and the impact of immunosuppression are critical factors in the progression of PTLD. HIV-positive patients are more likely to develop atypical TB presentations and experience greater systemic complications, resulting in more widespread lung damage [4,5].

Conversely, HIV-negative individuals generally exhibit localized lung damage, typically characterized by fibrosis and bronchiectasis [9]. Although immunocompetent, these individuals can still suffer from significant post-TB complications, as evidenced by the relatively high prevalence of PTLD in this population [8]. This highlights the importance of understanding PTLD's trajectory in HIV-negative individuals to develop more targeted interventions.

Several studies have noted that HIV-positive individuals often develop more severe forms of disseminated TB, which can affect multiple organs and lead to extensive lung damage [4,5]. In contrast, HIV-negative individuals experience more localized pulmonary complications, with long-term outcomes centered on structural changes in the lungs.

Despite the differences in the underlying mechanisms of lung disease, both populations face challenges with chronic respiratory symptoms and reduced lung function. Pulmonary rehabilitation, early diagnosis of PTLD, and long-term management are essential for improving outcomes in both HIV-negative and HIV-positive patients.[8]

Clinical Implications

The management of PTLD in HIV-negative individuals requires a multifaceted approach. Emerging diagnostic tools such as advanced imaging techniques, including artificial intelligence-assisted HRCT analysis, offer the potential to identify subtle structural changes in the lungs that may precede overt clinical symptoms. Moreover, biomarkers such as specific inflammatory mediators are being investigated to differentiate PTLD from other chronic respiratory diseases.[17]

In terms of treatment, pulmonary rehabilitation has shown promising outcomes, including improved quality of life and reduced hospital admissions for individuals with PTLD [8]. The integration of pulmonary rehabilitation programs into existing TB care frameworks could enhance the management of PTLD. Furthermore, the role of adjunct therapies, such as corticosteroids or antifibrotic agents, is being explored, particularly for patients with significant structural lung damage.

At the public health level, early intervention strategies, including screening for PTLD during routine TB follow-up visits, are critical. Integrating PTLD management into national TB programs and leveraging digital health technologies for remote monitoring and follow-up could mitigate the long-term burden of PTLD.

Finally, addressing the social determinants of health, such as poor nutrition and environmental exposures, remains essential for comprehensive PTLD management. Collaboration between healthcare providers, policymakers, and community organizations is vital to creating sustainable models of care.

Research Gaps

This scoping review has identified several gaps in the literature:

1. There is limited research focusing on immunocompetent, HIV-negative individuals with PTLD. Most studies either focus on HIV-positive populations or include both groups without sufficient differentiation.
2. There is a lack of consensus regarding standardized diagnostic criteria for PTLD, complicating comparisons across studies.
3. More research is needed to explore the long-term outcomes of PTLD in different populations and develop evidence-based management protocols.

Conclusion

Post-tuberculosis lung disease is a significant complication among HIV-negative, immunocompetent TB survivors. The high prevalence of structural lung damage, including fibrosis and bronchiectasis, underscores the need for comprehensive post-TB care, including pulmonary rehabilitation and long-term follow-up. Understanding the unique pathophysiological mechanisms in this population can lead to the development of more effective diagnostic and treatment strategies. This scoping review calls for continued research and the creation of standardized protocols to improve the care of TB survivors, especially in resource-limited settings where the TB burden remains high.

Limitations

This scoping review has several limitations that must be acknowledged. Firstly, the heterogeneity of the included studies, in terms of study design, sample size, geographical distribution, and diagnostic criteria for PTLD, makes it difficult to directly compare the findings across studies. This variability in methodologies may have led to inconsistencies in reporting the prevalence and clinical manifestations of PTLD. Secondly, although the review focused specifically on immunocompetent, HIV-negative individuals, some studies may have included populations with mixed HIV statuses, potentially confounding the results. Additionally, most of the studies included in the review were conducted in regions with high TB burden, which may limit the generalizability of the findings to populations in lower-burden regions. Finally, given the reliance on published literature, this review may be subject to publication bias, as studies reporting positive outcomes or significant findings are more likely to be published, potentially leading to an overrepresentation of PTLD cases in the results. Future research should aim to address these limitations by conducting large-scale, longitudinal studies with standardized diagnostic criteria to better understand the long-term impact of PTLD in HIV-negative, immunocompetent individuals.

Funding Information:

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of Interest:

The authors declare no conflict of interest.

Author Contributions:

Somasundram Pillay and Davashni Pillay conceptualized the study and oversaw the entire process, including methodology and manuscript preparation. Both authors contributed to the revision of the manuscript and approved the final version.