Overview
The AI2 score is a way of measuring whether inflammation is actively happening inside a transplanted lung right now.
The distinction matters more than it might sound. A breathing test or a biopsy can show that a lung has been damaged. Neither reliably shows whether the process that caused the damage is still running. That is the thing a doctor actually needs to know, because a process that is still active might respond to treatment, while damage that is already done will not.
The score is calculated from a small sample of cells brushed from the lining of the airway. Rather than looking at the tissue under a microscope, we measure which genes those cells have switched on, and condense that into a single number reflecting how much active inflammation is present. Two recipients with identical breathing tests can have very different scores, and that difference is what tells them apart.
Where the score came from
The score came out of work identifying inflammatory gene programs that were conserved across different compartments of the airway. That consistency suggested a compact set of genes could report whether inflammation is currently active, rather than whether damage has already occurred.
Testing it across centers
A finding at one hospital may not hold at another, with different patient populations and sampling practices. The Airway Brush in CLAD study, known as ABC, is a prospective study evaluating airway brush molecular approaches across North American lung transplant programs. It is designed both to test the approach in a broader population than any single center provides and to build infrastructure for later studies that use molecular results to guide treatment.
Toward a usable clinical test
A collaboration between UCSF and the University of Pennsylvania is developing point-of-care methods, with the aim of moving airway molecular measurement out of a research laboratory and into a test that can be run where patients are actually seen, on a timescale that allows the result to affect the decision being made. The score is also being used to select patients for mechanism-directed trials, including recipients with a high interferon gamma signature for TIGER-Lung.