Ahmed Lazrak, Dr.Sc., associate professor in the UAB Department of Anesthesiology and Perioperative Medicine, has been awarded a two-year, $409,750 R21 grant from the National Institute of Environmental Health Sciences, part of the National Institutes of Health, to investigate a potential treatment for chlorine-induced lung edema. The project, titled “Therapeutic Potential for NPS-2143 as Treatment for Chlorine-Induced Lung Edema,” will run through June 30, 2028.
The research focuses on understanding how the calcium-sensing receptor (CaSR) contributes to lung injury and fluid accumulation following chlorine exposure. Chlorine is widely used in products and processes such as sanitation, water treatment, and bleaching, and exposure to high levels of the chemical can cause severe respiratory injury.
“Chlorine-induced lung injury has been well documented, but many of the underlying biological mechanisms remain poorly understood,” Lazrak said. “Our research will investigate the role of the calcium-sensing receptor in lung edema formation and explore whether targeting this receptor could provide a new therapeutic approach for treating patients exposed to chlorine.”
CaSR is best known for helping regulate blood calcium levels and parathyroid hormone release. While initially identified in the parathyroid gland, researchers have since discovered the receptor in numerous organs and tissues throughout the body, where it plays roles in a variety of physiological and disease processes. Studies have linked CaSR to conditions including hypertension, diabetes, myocardial infarction, cancer, and asthma.
Lazrak and his team will examine how CaSR contributes to lung edema development following chlorine inhalation. The study will use receptor inhibitors and genetic models to determine whether blocking CaSR activity can prevent or reverse damage from chlorine exposure.
“This study aims to clarify the pathogenic role of CaSR in chlorine-induced lung injury and determine its potential as a therapeutic target,” Lazrak said. “By better understanding how this receptor affects fluid accumulation in the lungs, we hope to identify strategies that can significantly reduce injury and improve respiratory outcomes.”
Chlorine inhalation can impair the lung’s ability to regulate ion and water transport, leading to fluid buildup in the alveoli and the development of pulmonary edema. Preliminary findings demonstrated that treatment with the calcilytic compound NPS2143 after chlorine exposure restored critical lung functions in experimental models and reduced signs of lung injury.
Lazrak said the long-term goal is to develop new treatments that directly address the biological mechanisms responsible for lung edema rather than simply managing symptoms.
“We hypothesize that specific inhibitors targeting CaSR function can significantly mitigate injury propagation and reverse lung edema formation,” Lazrak said. “If successful, this work could pave the way for new therapies that improve outcomes for individuals exposed to chlorine and other harmful inhaled substances.”
The implications of the research may extend beyond chlorine exposure alone. Lazrak expects the findings to provide broader insights into how CaSR contributes to injuries caused by both naturally occurring and industrially produced particles and chemicals.
“We hope this research will clearly define the functional role of CaSR in lung injury and inspire new avenues of investigation across multiple respiratory diseases,” Lazrak said. “Ultimately, our goal is to advance the development of treatments that restore normal lung function and improve patient care.”