Examining opportunities to improve respiratory health and the broader healthcare system

If you would have told people in the mid-to-late 90’s that there will be a time in the not-too- distant future that prior to taking every flight, one had to take of their shoes, belts and jackets, limit the liquids in the hand luggage, take out all large electronics from the carry-on, go through a radiation emitting scanner and run the risk of a full body search, one probably would have said you’re crazy. And then 9/11 happened… and the world changed forever, especially the world of aviation. Extraordinary measures were implemented to prevent another terrorist attack using planes as weapons. Now almost 20 years later this has become the new normal.

Even though we are still in the middle of the COVID-19 pandemic with, unfortunately, many more lives to be lost in the coming weeks, it already is blatantly obvious that we cannot and should not return to business as usual. We have to take measures to prevent a future respiratory terrorist like COVID-19 to wreak havoc on our lungs, our healthcare systems and our economy.

Important to realize is, that what we are experiencing now, are the dire consequences of a respiratory illness for which we, as a respiratory field, were unprepared. It falls upon our field now to learn from this experience and to lead, to ensure we can prevent or at least mitigate the next outbreak or re-emergence of a respiratory virus.

What is COVID-19 doing to the body?

COVID-19 is a Coronavirus that attaches to the ACE2 receptors in the lung. As with all infections, the human body activates its immune system to fight off the infection by producing inflammatory cells. However, in a small percentage of the population the immune system over-reacts and ends up flooding the lung with edema, a liquid consisting of the inflammatory cells. This condition is call Acute Respiratory Distress Syndrome or ARDS [1-3] [Figure 1].

ARDS patients require very intensive care often including invasive mechanical ventilation, vasodilator and anti-inflammatory treatment for several weeks. The mechanical ventilation is designed to increase the pressure inside the lungs to push the edema to the other side of the membrane to restore alveolar function. While the overall percentage of people developing ARDS is low, if many people get infected at the same time the absolute number of patients requiring intensive care can be very high and can lead to a near collapse of the healthcare system in certain areas. This is what we are experiencing now with COVID-19. One of the primary solutions to the current crisis is the ability to identify patients with a high risk of developing full blown ARDS early and intervene accordingly to prevent the patient from ending up in the ICU for a long time. Early ARDS can be treated by using less complicated ventilators such as CPAP, more advanced masks and potentially by a range of anti-inflammatory and vasodilating drugs.

[source: https://european-biotechnology.com/up-to-date/latest-news/news/microrna-blocks-life-threatening-ards.html]

Shortcomings of current lung function tests and diagnostics

One of the major problems with early diagnosis is that the lung has a remarkable capability of compensating for disease that is already present, we see that across the board of respiratory diseases including pulmonary fibrosis, COPD and asthma. The lung can be already significantly affected by the disease without symptoms or function decline, as measured with the conventional lung function tests. This clinical image is reported in COVID-19, many patients are doing ok for around 7 to 10 days after which some of them rapidly decline [4]. Hence, early detection of the level of ongoing compensation is of critical importance. 

To make matters worse, conventional spirometry is counter-indicated for the current COVID-19 crisis [5] due to risk of exposure to the medical staff and the limited ability of severely ill patients to properly perform the maneuver. In other words, the test that the respiratory field heavily relies on and has a lot of experience with is effectively rendered useless during the worst respiratory crisis the world has ever seen. This should be food for thought for all of us.

Proven utility of CT in COVID-19, mainly as diagnostic

Even during the early days of this pandemic, the utility of High-resolution computed tomography (HRCT) became clear. Chinese medical professionals and researchers did a great job in being able to use HRCT scanners to screen and follow up patients. In a very short period of time they generated a substantial body of scientific literature that highlights the sensitivity of HRCT as a diagnostic tool for COVID-19 [6]. This sparked interest around the AI community to develop diagnostic algorithms at a rapid pace.

Future role of HRCT in respiratory medicine as diagnostic, prognostic and clinical trial endpoint

Arguably even more important, at this stage, than the development of diagnostics is to develop prognostics that could identify early on the patients at high risk of ending up in the ICU with full blown ARDS occupying a ventilator and ICU bed for several weeks and identifying patients with a potentially atypical ARDS presentation that require a different treatment approach. Patients that require intensive care for several weeks cause the healthcare system to collapse and necessitate the need for strict quarantine and social distancing measures. These latter measures in turn have a catastrophic effect on the economy leading to additional loss of lives and livelihoods.

HRCT scans, as part of the Functional Respiratory Imaging (FRI)/AI toolbox have demonstrated high prognostic accuracies for predicting COPD exacerbations [7] and lung transplant rejection [8]. Also, in other diseases such as IPF the utility of HRCT in combination with deep learning has resulted in accurate outcomes for diagnosis [9] and prediction of decline in Forced Vital Capacity (FVC) [10]

An increasing number of therapies for lung diseases are being assessed and developed using HRCT-based endpoints [11-22]. Particularly the studies focusing on invasive mechanical ventilation in ARDS [21] and non-invasive ventilation appear to be relevant today [22]. Treatments are being developed using techniques that have high diagnostic and prognostic capability, leading to  responder phenotyping and effective personalized medicine even in times of extraordinarily high demand that  we are experiencing today.

Conclusion

Our world has been redefined, a return to business as usual after this pandemic is over not only is unjust in the identification and treatment of patients but makes no economic sense. We have to realize that the current diagnostic and treatment options for respiratory conditions, such as but not limited to ARDS, failed us. We need to utilize more sophisticated techniques, and use this information to shape and mange  lung diseases and lung health in general and then share this knowledge to ensure a democratization of treatment options In a short time, the body of evidence supporting CT-based approaches for diagnosis, prognosis and treatment selection for lung diseases has grown substantially. We need to continue the transition to make these imaging tools the standard in respiratory medicine, this requires policy makers to adopt and sanction policy, upgrade guidelines and allow physicians to make the leap to treatment options that are better for patients, better for the payer and better for the wider economy and social environment. The time is now, the stakes couldn’t be higher.

References

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[5] https://www.thoracic.org/professionals/clinical-resources/disease-related-resources/pulmonary-function-laboratories.php

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[13] De Backer J, Van Holsbeke C, Vos W, Vinchurkar S, Dorinsky P, Rebello J, et al. Assessment of lung deposition and analysis of the effect of fluticasone/salmeterol hydrofluoroalkane (HFA) pressurized metered dose inhaler (pMDI) in stable persistent asthma patients using functional respiratory imaging. Expert Rev Respir Med. 2016;10(8):927-33.

[14] De Backer W, De Backer J, Vos W, Verlinden I, Van Holsbeke C, Clukers J, et al. A randomized study using functional respiratory imaging to characterize bronchodilator effects of glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler using co-suspension delivery technology in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:2673-84.

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[22] De Backer L, Vos W, Dieriks B, Daems D, Verhulst S, Vinchurkar S, Ides K, De Backer J, Germonpre P, De Backer W.The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study.Int J Chron Obstruct Pulmon Dis. 2011;6:615-24.