SQI Diagnostics, a medtech company based in Canada, is developing the TORdx LUNG Test. The technology is intended to assist clinicians in assessing donor lungs in their suitability for transplantation.
At present, clinicians typically assess donor lungs using qualitative variables, such as donor health and lung size. One of the most important factors, lung inflammation, is difficult to assess, and clinicians will often play it safe and reject an organ if there is any doubt about it.
This means that lungs that might actually be suitable for transplantation are often rejected, further compounding the lack of donor organs. At present, approximately 20% of donated lungs are accepted for transplantation with the remaining 80% being rejected. To provide concrete data on donor lung inflammation, SQI Diagnostics is developing the TORdx LUNG Test.
The technology involves measuring levels of four biomarkers of inflammation in a lung sample. The system can provide results within 40 minutes, meaning that it is suitable for the time demands of a transplant assessment. If levels of inflammatory proteins are high in donor lungs, then there is a greater chance of complications, whereas lungs with lower levels are more likely to result in better outcomes.
Medgadget had the opportunity to speak with Eric Brouwer, Chief Scientific Officer at SQI Diagnostics, about the technology.
Conn Hastings, Medgadget: Please give us an overview of the shortage of donor organs and the consequences this has for patients.
Eric Brouwer, SQI Diagnostics: The two key components of an organ transplant are the donor organ and the recipient. On the donor side of the equation, only 20 – 25% of the available donor lungs are deemed suitable by surgeons for transplant to the recipient.
Transplant surgeons are concerned about damage and trauma to the lung – damage that is visible, and damage, primarily inflammation, which is at the molecular level. A lack of quantitative and objective decision-making tools regarding lung damage – especially at the molecular level, where inflammation is a grave concern — lead many donor lungs to be rejected for transplant.
The consequences of this donor lung scarcity for patients include long recipient wait times, potential recipients deteriorating while on the wait list, and complications post-transplant because recipient was not as healthy due to long wait times for donor lungs.
Medgadget: Has the COVID-19 pandemic affected the need for and supply of donor lungs?
Eric Brouwer: COVID-19 has had some impact on the availability of donor organs, specifically restricted access to surgery, new screening procedures being implemented, and exacerbation of shortages in specialized medical staff. Surprisingly, there was no significant drop in the number of donors. So overall, the availability of donor lungs was mostly stable.
The recipient side has seen a bigger impact due to an increased number of recipients. In 2021, it is estimated that 10% of U.S. lung transplant recipients were due to COVID-19 complications, where COVID-19 had led to severe damage of lungs requiring transplant. The increase in number of recipients has translated into long wait times, which has meant the average recipient has progressed further in their lung disease and makes the transplant more complicated.
We expect that COVID-19 complications will continue to increase the number of recipients in need of transplant in the coming years.
Medgadget: How are donor lungs currently assessed as suitable or unsuitable for transplant?
Eric Brouwer: Assessment of donor lungs begins at the donor site, where the health of the donor is a consideration, as well as blood tests for matching blood type and screening for disease.
After harvest of the organs and transport to the transplant center, the lungs are assessed using mostly qualitative parameters (size, radiography, visually inspection, bronchoscopy) by surgical experts. Inflammation in the donor lungs, which is difficult to assess with qualitative parameters, is a general concern as inflammation is known to lead to poor recipient outcomes.
New technologies have been adopted where donor lungs are placed on a pumping system called Ex Vivo Lung Perfusion (EVLP) before transplanting to the recipient. EVLP provides the donor lungs with a blood substitute to sustain the organ cells, and a pressurized system to oxygenate the lungs – essentially mimicking breathing. EVLP allows the transplant team to quantitatively assess the lung’s oxygenation capability before transplant.
Even with EVLP, there are no precision medicine measurements to measure one of the primary concerns of the transplant team: inflammation of the donor lungs. The state of donor lung inflammation and its projected impact on the recipient remains a matter of surgical team judgement, relying on interpretation of mostly qualitative measurements in the context of past experience. Our technology provides a precision medicine approach to measure inflammation in the lungs.
Medgadget: What inspired SQI Diagnostics to develop this technology and how did it come about?
Eric Brouwer: Dr. Peter Lea, the founder of SQI Diagnostics, was a professor in spectroscopy and microscopy at the University of Toronto. Dr. Lea’s research focus on optical measurements led to SQI Diagnostics’ technology of highly reproducible diagnostic sensors which could be used to detect and measure many different proteins simultaneously in a single test using a small biological sample.
This technology had been developed and improved over time for diagnostic tests for autoimmune diseases such as celiac, rheumatoid arthritis, lupus nephritis, and more generally, cardiac health and dementia. These diseases are characterized by the presence of inflammatory proteins, and SQI has developed deep expertise in measuring inflammation biomarkers.
In 2018, SQI Diagnostics began collaborating with Dr. Shaf Keshavjee, who is the Surgeon-in-Chief at Toronto’s University Health Network (UHN) and a global leader in lung transplantation. Dr. Keshavjee had identified inflammatory biomarkers that predicted the outcome of the lung transplant in recipients, and he needed an innovative diagnostic system to rapidly measure these proteins during the transplant procedure. His current test turnaround time was over 3 hours, too long to provide results within the decision timeframe. We were able to solve the timing problem with a four-fold reduction in the time to result.
Medgadget: Please give us an overview of the technology and how it works.
Eric Brouwer: SQI Diagnostics’ TORdx LUNG Test measures four inflammation biomarkers in a series of samples drawn from the EVLP circuit. The testing method is an immunoassay sandwich ELISA format with fluorescent detection. The testing format is a 96 well microtiter plate. For each well on the plate, there are groups of sensors for each of the four biomarkers that are being measured.
The plate and samples are loaded on the automated sqidlite instrument, which then robotically processes the samples, reagents, and wash solutions. Results are generated in 40 minutes – well within the timing for donor lung assessment.
The results of the test tell us that when the inflammation protein concentrations are high, or are trending higher over time, the lung is experiencing inflammation and will likely cause complications with the recipient. Conversely, when the inflammation protein concentrations are low, the lungs are more likely to have a good outcome with the recipient
Medgadget: How did you decide on the biomarkers and other quantitative metrics of donor lung suitability for transplant? Please give us a brief overview of these and how they relate to the overall chances of transplant success.
Eric Brouwer: Over the past 3 – 4 decades, immunology research has identified many biomarkers that are involved with inflammation and has also identified the associated biological pathways. Using this general understanding, the UHN clinical research team began with the hypothesis that poor recipient outcomes are related to donor lung inflammation, and inflammatory markers might be correlated to recipient outcome as measured by primary graft dysfunction and patient care in the ICU.
As one of the largest transplant centers in the world, UHN assessed its large repository of samples from prior lung transplants to identify the biomarkers best correlated to recipient outcomes. A key innovation was to aggregate the inflammation biomarker results into a single score, called the Toronto Lung Score, and this score is correlated to recipient outcome. A recent publication in The Journal of Heart and Lung Transplantation shows that using two of the inflammation biomarker results gives a transplant predictive accuracy of 68%. Predictive accuracy climbs to 87% when combining the lung oxygenation parameters with the Toronto Lung Score.
Medgadget: In terms of regulatory approval and commercial availability, what stage is the technology at currently?
Eric Brouwer: The TORdx LUNG Test is available currently as a Research Use Only product. SQI Diagnostics has engaged with a number of leading U.S. transplant centers to collect additional clinical data to support our U.S. FDA application. We anticipate that the product will be under review into 2023.