Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion.
An interesting finding was the favorable performance of the LBP compared to fluticasone furoate, a widely studied FDA-approved inhaled corticosteroid found in COPD combination therapies.
The LBP reduced MMP-9 and other pro-inflammatory cytokines as well as, and in some cases better than, the steroid in the PPE + LPS COPD mouse model. Prolonged use of steroids for COPD exacerbations is associated with side effects, including increased risk of pneumonia, skin thinning, sepsis, and death.
Neutrophilic inflammation is steroid-resistant, a major therapeutic gap in the COPD therapeutic landscape.
In the future, our LBP may reduce or replace the need for inhaled steroids by virtue of their strong anti-inflammatory action combined with a more tolerable safety profile and additional potential structural benefits. Safety and biodistribution, as studied in the PPE emphysema model, indicated that inhalation of the LBP did not initiate adverse reactions in diseased mice. The Lactobacilli did not translocate to distal tissues or accumulate in the lungs, supporting the hypothesis that the bacteria have a localized yet transient presence in the airways. Furthermore, the LBP is susceptible to the antibiotics Cefuroxime, Azithromycin, Amoxicillin-clavulanate, Piperacillin-tazobactam, and Ceftriaxone, all of which are currently used to treat COPD exacerbations and may be used as rescue medication in a clinical setting.
Preclinical animal data is suggestive, and the safety of the potential drug in humans will be tested in a forthcoming clinical trial.