U of T research on biomarkers may reduce lung-donor waitlist times dramatically

Lung transplants save hundreds of lives each year and are among the most vital operations in the medical field. Unfortunately, the procedure comes with an array of risks and, to this day, the leading cause of post-operational death is poor donor lung viability. To maximize success, only a select few donor lungs are deemed appropriate for transplant. But despite rigorous and time consuming assessments of donor lung viability, nearly a fifth of lungs are rejected by their new hosts every year, causing devastating complications and often death.

Recent research conducted at the University of Toronto could revolutionize this procedure. Dr. Shana Kelley, a professor of pharmaceutical sciences and biochemistry, worked in tandem with Dr. Shaf Keshavjee, a professor of thoracic surgery, to develop a quick and accurate method to analyze donor lung viability. Their innovation relies on microchips, called fractal circuit sensors (FraCS) initially designed by Dr. Kelley to test for infection. Modified, the microchip can now locate biomarkers in lung tissue, virtually eliminating all error.

While the study focuses on lung transplants, Dr. Kelley points out that, “any assessment that can be made on the basis of specific molecular markers can be carried out with our chip.” The chip, then, has the power to completely overturn the field of clinical practice.

The chip operates by analyzing a biopsied sample of lung tissue. It detects mRNA biomarkers to determine the lung’s viability. The innovation is unique in that it requires virtually no sample purification before analysis, making the process remarkably fast.

Using biomarkers as a method of aiding medical decision-making is widely accepted and promoted. The current methods available, however, require anywhere between six and 12 hours to perform, rendering the practice obsolete for such a time-sensitive operation. This pioneering innovation, in contrast, can determine lung viability in under 20 minutes.

The new research will allow doctors to not only analyze lung function when considering donor viability, but also assess lung damage. Most lungs used for transplant today are chosen for their suitability as functioning organs. However, around a third of deaths following transplant are due to a complication known as ‘primary graft dysfunction,’ which is commonly caused by damage  already present in the lungs.

In a powerful demonstration, the microchip analyzed 52 lung transplants that had already taken place, and yielded a 74 per cent rate of sensitivity and 91 per cent rate of specificity, correctly identifying numerous instances of primary graft dysfunction.

The benefits of this new technology go beyond preventing complications.

Another major issue in the field of lung transplants is the staggering wait list. In Canada, nearly 300 people died between 1997 and 2006 while waiting for lung transplants. In part, this is due to the fact that surgeons are very conservative with their use of donor lungs to maximize success; only 15 per cent of donated lungs are considered suitable. However, estimates show that around 40 per cent of the lungs deemed unusable may be viable organs. This technology would improve our ability to identify this 40 per cent accurately, thereby reducing wait-lists, and saving lives.

The first successful lung transplant in history was performed at Toronto General
Hospital in 1983. Since then, success rates have burgeoned and access has become relatively widespread. Now, Canadian innovation is making it possible to reach more patients and save more lives. The scope if this technology is seemingly endless, but when can we hope to see the innovation used in hospitals?

As Dr. Kelley put it, “What we reported […] was a proof-of-concept study.  We now need to do a much larger clinical validation study to show that our accuracy is sufficient for clinical use.” Doctors Kelley and Keshavjee are now working to fine tune their innovation, making it ready for clinical use.

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