UToledo Researchers Help Uncover How Asthma Attacks Permanently Reshape Airway Tissue

UToledo Researchers Help Uncover How Asthma Attacks Permanently Reshape Airway Tissue

A team of University of Toledo researchers from the College of Medicine and Life Sciences played a key role in a multi-institution study revealing how asthma attacks cause lasting, physical changes to airway tissue, damage that occurs independently of the inflammation traditionally associated with the disease.

Drs. Lakshminarayan Reddy Teegala, Sailaja M. Paruchuri and Charles Thodeti, all from the Department of Physiology and Pharmacology, contributed to the research, published this week in the prestigious journal Nature Biomedical Engineering. The study was led by Dr. Jungwook (Jay) Paek from Binghamton University and Dr. Dan Huh from the University of Pennsylvania in collaboration with Pacific Northwest National Laboratory and The University of Toledo.

Using advanced lung-on-a-chip technology, the research team demonstrated for the first time that the repeated mechanical stress generated during asthma attacks, and not just chronic inflammation, drives tissue remodeling in the airways. That remodeling includes both fibrosis, an overproduction of structural proteins that stiffen tissue, and angiogenesis, abnormal blood vessel growth. Over time, these changes can permanently narrow airways and worsen breathing.

Asthma affects roughly 25 million people in the United States, or about eight in 100 people, and can be triggered by allergens, air pollution, extreme weather and other irritants. While inflammation has long been the primary target of asthma treatment, this research points to mechanical force as a separate and previously underappreciated driver of long-term lung damage.

The organ-on-a-chip platform used in the study relies on microfabrication techniques adapted from the semiconductor industry to recreate conditions inside the human body using small cultures of living cells. Researchers engineered the device to physically deform lung tissue by pressurizing and evacuating a connected chamber, simulating the mechanical strain of an asthma attack. The team also tested whether targeted medication delivery could modulate cell activity under these conditions, laying groundwork for potential future therapies.

The University of Toledo team made several important contributions to the study. Teegala and Paruchuri validated the organ-on-a-chip findings in an animal model of asthma, helping establish the physiological relevance of the platform. Thodeti provided mechanistic insights into the role of TRPV4 mediated mechanotransduction in driving airway remodeling under conditions of repetitive mechanical stress. Together, these contributions strengthened the study's translational impact and highlighted UToledo's leadership in physiology and pharmacology research and its commitment to advancing collaborative, cross-institutional science aimed at improving respiratory health.