$2 Million Grant Targets Environmental Pathogens Linked to Chronic Lung Disease

Cincinnati—A $2 million grant from the National Institute for Occupational Safety and Health will support University of Cincinnati (UC) research to determine the link between environmental pathogens and lung disease in the workplace.

Led by Jagjit Yadav, PhD, this ongoing environmental health research study seeks to determine what specific mycobacteria (microscopic pathogens) and their antigens are linked to work-induced hypersensitivity pneumonitis, a pulmonary disease that leads to chronic inflammation of the lungs.

The immune-mediated disease is caused by the inhalation of microscopic substances, which trigger the body’s immune system leading to coughing as well as shortness of breath, chills, headaches and fatigue. The specific mycobacteria antigens causing this disease, however, remain to be determined.

"One of the problems with hypersensitivity pneumonitis is that it is difficult to diagnose clinically and there are no specific lab tests to aid in diagnosis,” explains Yadav, associate professor of environmental health at the UC College of Medicine. "Unless the patient is seeing a physician who is knowledgeable about occupational pulmonary medicine, hypersensitivity pneumonitis is often mistaken as asthma or bacterial pneumonia or some other lung condition. Left untreated, it can cause irreversible scarring on the lung.”

Yadav estimates that more than 1 million machine workers are exposed to potentially harmful machining fluids on a regular basis in the workplace.

Fluids used in many machining operations—cutting, metal grinding and cooling—often harbor harmful microorganisms, including mycobacteria. Once released into the air, these contaminants are inhaled by workers and can cause an inflammatory response in susceptible individuals.

UC’s study will focus on identifying the role of unique mycobacteria strains and their antigens associated with metal working fluids used in machining industries.

In previous work funded by NIOSH, Yadav and his colleagues identified unique strains of two mycobacteria species from machining fluids associated with hypersensitivity pneumonitis—M. immunogenum and M. chelonae. More research is needed, however, to identify the key antigens from these strains that lead to human disease.

"Once these critical antigens are identified, we will have potential targets for novel immunodiagnostic strategies and possibly future therapeutic or vaccine development options,” explains Yadav.

Yadav and his colleagues will analyze the molecular and cellular profile of hypersensitivity pneumonitis in both experimental lab models and human patients in an effort to hone in on a biological marker that could provide important clues on how to better diagnose the disease. 

Collaborators in the study include James Lockey, MD, and Paul Succop, PhD, of UC, Bill Eshenbacher, MD, of the Cincinnati Veterans Affairs Medical Center, Charles Pue, MD, of the Sleep and Breathing Research Institute in Columbus, Ohio, and Kenneth Rosenman, MD, of Michigan State University.