RESPIRATORY IMPAIRMENT IN TUBERCULOSIS AND HIV (RESPITH): TRENDS, PREDICTORS AND IMPLICATIONS
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Gupte, Akshay N
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Tuberculosis (TB) and human immunodeficiency virus (HIV) have been associated with chronic lung injury and obstructive lung disease (OLD). Despite the enormous global burden of TB and HIV, their epidemiological overlap in resource-limited settings, and their collective threat to lung health, key knowledge gaps remain: (1) TB and HIV patients at greatest risk of poor respiratory health despite treatment are yet to be characterized, preventing the identification of individuals likely to benefit from targeted interventions to limit lung injury and disability; (2) inflammatory mechanisms associated with lung injury in TB and HIV are unclear, preventing the identification of potentially modifiable immune pathways that may be targeted with pharmacotherapy to prevent pulmonary sequelae. We conducted two prospective cohort studies among: (1) new adult drug-sensitive pulmonary TB (PTB) patients in India to identify host factors, including systemic inflammatory markers, associated with poor respiratory health status, measured by the Saint Georges Respiratory Questionnaire (SGRQ), during and following successful treatment; (2) South African adults with well controlled HIV-disease to identify factors associated with spirometry-defined OLD and excess annual lung function decline. We found that successfully treated PTB patients in India had poor respiratory health status that was associated with older age, being underweight, elevated levels of circulating interleukin-6 (IL-6) and transforming growth factor β-1 (TGFβ-1), and worsening SGRQ scores despite 2 months of treatment. Among HIV-infected South African adults, prevalent OLD was associated with older age, current smoking and high C-reactive protein (CRP) levels. Importantly, prior TB, despite being treated, was associated with excess lung function decline in this cohort. We conclude that PTB is associated with chronic respiratory impairment and excess lung function decline despite successful treatment, and patients who are older, underweight or those who fail to improve their respiratory health status following initial treatment may benefit from routine monitoring for early detection and management of chronic lung diseases. We recommend further studies to substantiate the role of IL-6 and TGFβ-1 in lung injury, CRP as a marker for underlying OLD, and clinical trials to evaluate the utility of targeted host-directed immunomodulatory therapies to prevent pulmonary sequelae in TB.