Lung health after respiratory infections:
Respiratory infections still play a particularly significant role in shaping lung health in low- and middle-income countries (LMICs). While childhood chest infections are known to influence overall lung development and maximally attained lung volumes, also respiratory infections in adults can represent a significant challenge to long-term lung health.
The UGH focuses specifically on the long-term respiratory sequelae of Mycobacterium tuberculosis (M.tb) infection, collectively termed post-TB lung disease (PTLD), which occurs in up to 50% of microbiologically cured TB patients. PTLD represents a heterogeneous pattern of respiratory pathology ranging from airway disease, pulmonary fibrosis, bronchiectasis and pulmonary arterial hypertension, leading to increased morbidity burden and shortened life expectancy.
Our research activities at the UGH are aiming for improving the clinical characterization of distinct PTLD-patterns (phenotypes) and the description of underlying patho-mechanisms. Furthermore, we want to contribute to an improved understanding of environmental and clinical cofactors modulating PTLD development and long-term disease behaviour. Our research is based on several longitudinal PTLD cohorts, conducted in sub-Saharan Africa and Eastern Europe, including the TB Sequel cohort (www.tbsequel.org), the currently worldwide largest (post-) TB cohort.
In addition to longitudinal cohort studies of PTLD, the UGH is conducting therapeutic studies of PTLD, including randomised host-directed therapy (HDT) trials. Our group together with our collaborators was the first to show that N-acetylcysteine (NAC), a well-known antioxidant already used in the treatment of COPD patients, improves the recovery of functional lung impairment in TB patients when given together with antibiotic treatment. In accompanying laboratory studies, we have shown that M.tb induces an oxidative burst in neutrophils, leading to the release of reactive oxygen species (ROS), and that preventing the oxidative burst by neutralising ROS with antioxidants or ROS scavengers such as NAC significantly reduces neutrophil necrosis and M.tb cell growth. These findings provide the basis for further investigation into the mechanisms of oxidative stress leading to lung injury in human samples to identify patient subgroups that will benefit from NAC treatment in a larger randomised NAC HDT trial starting in 2024.
