Flagship 1: Model-based diagnostics & therapeutics in pulmonary medicine

Leaders:
Professor Geoff Chase, University of Canterbury
Professor Merryn Tawhai, University of Auckland

The challenge

Mechanical ventilation (MV) is a primary therapy for intensive care unit (ICU) patients who have respiratory failure. MV provides external pressure/volume support to assist with breathing when the patient is at risk of airway or tissue closure or collapse, or when the drive to breath is compromised. Up to ~60% of all ICU patients require MV, and this patient group stays 50-100% longer in the ICU: MV almost doubles the cost of an ICU stay. When MV-associated damage to the lung occurs, this further increases the ICU stay, complicates patient management (leading to increased cost), and has long term consequences for patient quality of life.

A computer rendering of a model of the human upper airway.

Patient-specific characteristics and distribution of injury and/or underlying disease means that MV patient response to therapy is highly variable, and thus a “one size fits all” protocol to standardise care is not appropriate. Clinicans are presented with an overwhelming amount of patient data that is difficult to interpret, letalone to use for predicting how patients will respond to treatment. Current clinical practice therefore relies heavily on subjective assessment of the patient (“clinician experience”), and less on objective assessment of patient data. So, while therapy is specific to each patient, the care itself is not ‘patient-specific’ and often doesn’t take account of the specific, transient needs of the patient, nor their respiratory status as it evolves in response to the injury and in response to treatment. The main limitation is that it is not currently possible to titrate care to desired clinical endpoints. What is needed is the ability to quantify and monitor the patient-specific state of the lung with regard to MV care, and the ability to do so at every breath so clinicians can be alerted to changes in patient response as soon as they occur.

Our approach

Our Flagship is developing and validating new technologies that are aimed at minimising lung damage in MV, identifying patients who are at risk of developing lung injury, and titrating ventilation protocols to individual patients to optimise their outcome. The goal is to provide clinicians with the tools and information that they need to improve patient care and reduce cost.

The Flagship brings together — for the first time — previous work from the Universities of Auckland and Canterbury in modelling patient-specific lung tissue mechanics and gas exchange into a single software platform, and in the context of MV. We are developing a novel comprehensive and easy-to-use software package that will integrate seamlessly with existing sensors in the ICU, to provide summary metrics to assist with clinical decision-making. CURE Soft (see Figure 1) is a new model-based software tool (developed at the University of Canterbury) that is currently part of a large randomised clinical trial to optimize MV care in the Christchurch Hospital ICU. CURE Soft has been developed to monitor patient-specific respiratory mechanics at every breath, and the patient’s evolution of respiratory mechanics in response to care and their particular disease state, in real-time. CURE Soft currently uses a simple model of lung mechanics that works well for fitting and tracking total lung elastance and resistance, but not for predicting patient-specific response to different treatment strategies or for optimising arterial blood gases as a clinical endpoint. Our Flagship is integrating advanced biophysically-based computational models of patient-specific lung function (Figure 2, developed at the University of Auckland) into the CURE Soft framework. Our new approach will provide novel integrated model-based biomarkers of respiratory system function, for classifying current patient status and for predicting patient response to a range of ventilation strategies.

See caption.

Figure 1 CURE Soft (left hand side) with a ventilator in Christchurch Hospital, and the lung model used to guide MV, where the goal is maximum lung volume for minimum pressure to minimise patient-specific, model-based lung elastance. And a case example of CURE Soft (right hand side), monitoring lung mechanics and gas exchange.

A diagram of a model between parenchymal mechanics (PM), ventilation and perfusion. PM relates to ventilation through transmural pressure and volume changes, and ventilation relates to PM through alveolar pressure and airway collapse. Ventilation is related bidirectionally to perfusion through local control mechanisms. Perfusion is related to PM through blood pressure, and PM is related to perfusion through transmural pressure.

Figure 2: Biophysical models of lung function, including ventilation, perfusion, gas exchange, and regional lung mechanics.