It can’t be an easy task to combine a full-time job as a Medical Doctor in Anesthesiology and Intensive care at Lund University Hospital at the same time as completing your PhD thesis. Nevertheless, Martin Stenlo took the time to meet up for an interview to tell us about his research in Sandra Lindstedt’s group “Translational lung transplantation and lung cell therapy research” at the SCC.
Can you tell us about the main focus of your PhD?
My doctoral studies have had two main focus areas in the field of lung injury and transplantation. The first part of my thesis is dedicated to investigate a novel method to evaluate lung injury with the aim of improving the intensive care of lung patients, while the second part focuses on improving the quality of donor lungs to increase the success rate upon transplantation.
I work with Acute Respiratory Distress Syndrome (ARDS), which is an inflammatory syndrome of the lungs that can best be described as ‘sepsis of the lungs’. Needless to say, it’s a very serious condition that requires treatment with a ventilator and sometimes even with ECMO, which functions as an artificial lung that pumps and oxygenates the patient's blood outside the body. The key to successful treatment of ARDS is an early diagnosis and since these patients often are in a fragile state, the clinicians are in need of non-invasive diagnostics. One potential approach is to analyse the flow of particles in the exhaled air while patients are connected to a ventilator where an increased particle flow could indicate lung injury.. Exhaled Particles collected from alveoli and small airways have been shown in previous studys to reflect the composition of substances in bronchial lavage.
In the first study, we wanted to investigate if we could evaluate the flow of particles as a method to detect ARDS in an early stage. To do so, we integrated a machine called PExA (Particles in Exhaled Air) with a ventilator and used an animal model of ARDS that allow us to study the progression of induced lung injury. The results were clearly showed that we could correlate the increased particle flow with the increased severity of the lung injury.
In a follow-up study in the clinic, we investigated if this held true for Covid-19 patients that had developed ARDS and were being treated with ECMO. We monitored the patients for three weeks and could detect a decreased flow of particles in the two recovering patients, while the two patients that didn’t recover displayed an increased particle flow. Although our cohort was small (n=4), the results indicate that PExA has the potential to be a reliable technique to evaluated the injury progression during intensive care of lung patients.
In our third study, we used the PExA to evaluate the mechanical stress upon the three different main modes of ventilation support in 30 patients with healthy lungs (patients were intubated and supported by a ventilator due to surgery unrelated to the lungs). The main types of ventilation support are: Volume Control Ventilation (VCV) - where the ventilator is set to pump a certain volume of air, Pressure Control Ventilation (PCV) - where the ventilator is set to pump air until a certain pressure, and Pressure Regulated Volume Control (PRVC) – where the ventilator pumps a desired volume but at a rate that causes the lowest possible pressure. Our results showed a great difference in particle flow between the patients in which different ventilation modes were used, where the patients treated with PRVC had the lowest particle flow, i.e. causing the least mechanical damage.
The results taken together from these three studies open up the possibility to use particles in exhaled air to examine the lung status of intubated patients supported with a ventilator or ECMO using a non-invasive technique, avoiding examination methods such as bronchial lavage or moving the patient to an X-ray, which can be very challenging for these fragile patients to handle.
The second focus during my doctoral studies was to increase the success rate of lung transplantation by improving the function of donor lungs. This is very much needed since there is a severe lack of functional donor lungs and lung transplantation has a lower success rate than many other organ transplantations. One aspect that makes lung transplantation challenging is the delicate nature of the lungs, which increases the risk of deterioration during mechanical ventilation prior to transplantation into the recipient. Another aspect is that transplanted lungs require a heavy immunosuppression regime to avoid rejection which then makes them prone to infections.
In this part of the thesis we evaluated the impact of a cytokine adsorber, both during ex vivo lung perfusion of injured lungs after removal from the donor as well as after transplantation into the recipient with hemoperfusion. A cytokine adsorber is a porous polymer sorbent bead that removes cytokines from the blood, reducing the degree of inflammation in the body. In our animal model we showed an increased health status of the donated lungs that were treated with cytokine adsorption compared to the control group. We could also show an increased lung function with significant lower incidence of primary graft dysfunction in the transplanted group that received cytokine adsorption.
With this approach you buy time, maybe several hours, which allows you to evaluate the health status of the donor lungs prior to surgery, reducing the risk of transplanting lungs of inadequate condition. So not only would you increase the number of viable donor lungs, but also increase the success rate upon transplantation.
How did you end up doing a PhD in Lund?
After I finshed my recidency in Anesthesiology and Intensive care in Helsingborg, I moved to the Department of Cardiothoracic surgery and anesthesia in Lund. That’s where I came in contact with my main supervisor Sandra Lindstedt, who’s research caught my interest. She is a Cardiac surgeon and her main area of research is lung transplantation, but I could also apply and integrate my background in anesthesiology into her research which got me excited to start my doctoral studies.
Which aspects of your PhD have you found the most valuable?
I have found the collaborative research environment between the hospital and the university very stimulating and I feel so privileged to have worked with many brilliant minds in various areas of expertise.
Another positive thing I’d like to mention is the Research school for clinical medical doctors that really enabled me to combine my job as a medical doctor with being a researcher since it streamlined the compulsory courses for PhD students to my work schedule.
What did you find the most challenging during your PhD?
It has been a challenge to combine a full-time job as a medical doctor with a part time job as a researcher.
Tell me about the cover of your thesis?
It’s a photo capturing the autofluorescence of alveoli, the tiny air sacs where the lungs and the blood exchange oxygen and carbon dioxide during the process of breathing.
What are your future plans?
I’m going to continue my job as a Medical doctor in Thoracic Anesthesiology, and hope to maintain some of my projects in my current research group.
What do you like to do when you are not researching?
Now that life is slowly returning after finishing my thesis, I plan to devote my time to my family. Any leftover time will be spent training for my newly acquired interest: triathlon.