ERCOFTAC SIG48 Summer School

Modeling the Formation of Respiratory Aerosols

23rd – 27th September 2024

eScience Center - Lorentz Center, Leiden, The Netherlands

O​rganisers:

  • Chantal Darquenne, PhD, Professor, University of California, San Diego (expertise: lung physiology, aerosol science, in-silico modeling)
  • Stavros Kassinos, PhD, Professor, University of Cyprus
    (expertise: fluid-particles complex interactions, in-silico modeling, inhaled medicine, biomedical applications)
  • Stefan Hickel, PhD, Professor and Chair of Aerospace Engineering, TU Delft (expertise: modeling, computational fluid dynamics, turbulence, multiphase flows)
  • Anna-Carin Olin, MD PhD, Professor, University of Gothenburg and Research Director, PExA AB, Gothenburg, Sweden (expertise: occupational respiratory disease, exhaled biomarkers, exhaled aerosols)
  • Wilbur de Kruijf, MSc, CEO Thaerapy BV, Enschede, The Netherlands (expertise: aerosol scientist, medical device development)

 

Scientific case:

Why? The recent COVID-19 pandemic has highlighted the important role respiratory droplets and aerosols play in infectious disease transmission. Disease outbreaks, such as measles, tuberculosis, influenza and coronavirus, can be driven, in whole or large part, by emissions of pathogen-laden particles that infect nearby individuals. While epidemiological and/or physiological in-silico simulations have become key technologies for optimizing responses by clinicians and policy makers around the world, modeling the formation of respiratory aerosols is still largely an unsolved problem.

Challenges: it is generally established that respiratory droplets are formed from the fluid lining of the respiratory tract. However, unlike modeling of the fate of inhaled aerosols, modeling the formation of respiratory aerosols is a much less studied area. This is largely due to the unresolved nonlinear viscoelastic nature of airway mucus and nasopharyngeal liquids that prevents faithful predictions of droplet formation and size distributions. To date, there is very little mechanistic understanding from first principles of the rupture of viscoelastic liquids caused by high shear arising from high-Reynolds number airflow or from the closing and opening of wet membranes. Predicting the mucus breakup and droplet size distribution resulting from shear stress fragmentation is non-trivial because mucus is a viscoelastic shear-thinning fluid subject to surface tension. This enables multiple instabilities to bear on this problem. Similarly, rupture of a fluid meniscus generated by closing and opening of wet membranes is difficult to predict given the major role of moving boundaries, the large range of length and time scales implicated in this phenomenon, and especially the unresolved non-Newtonian properties of the fluids involved, i.e., mucus in the small airways and vocal cords, and saliva in the mouth, tongue, and lips.

Workshop aim and output: this Workshop will bring together the key players to promote multidisciplinary collaboration and to specify the scientific, medical, computational, and engineering needs requires to solve the challenge at hand. We aim at hosting a mix of international and local scientists, both senior and early career, as well as students, to create opportunities for exchanges, collaboration, and networking. Required expertise includes aerosol science related to respiratory droplets and their experimental and clinical aspects, mathematical and computational modelling of viscoelastic fluids, and software engineering.

The workshop will be a mix of podium presentations, working groups (WG) sessions and roundtable discussions. There will be three working groups focusing on:

  1. the mathematical formulation of the problem
  2. the experimental data needed to inform the model
  3. the computational methods to solve the problem

Each working group will be co-chaired by one senior level and one early career participant. WG sessions will typically be 90 minutes long: the first 60 minutes will be dedicated to break-out sessions where each WG will discuss the session topics based on their focus. This will be followed by a 30-minutes general session where each WG will summarize their findings and identified needs/gaps followed by a discussion on how the different WG could work together to address these needs/gaps. Inputs from these discussions will be used to draft a roadmap to solve the problem at hand.

Outputs of a successful workshop will be:

  1. producing a written document, suitable for publication, that will detail the state of the art of the current models, existing experimental datasets and important milestones of a roadmap to solve the problem at hand, highlighting its scientific, technical, and organizational challenges. We expect a rough draft by the end of the workshop, and a final version 2 months later;
  2. identification of new partners, and collaborations on an international level through relevant funding calls, so that progress can be made on the tasks identified in the roadmap. We expect a draft of the aims of potential grant application(s) by the end of the workshop, and grant applications submission within the following 12 months (exact timing will depend upon submission deadlines of identified funding calls);
  3. identification of gaps in linking current state-of-the-art computational modeling to real-world applications, e.g. achieving impact on emerging medical diagnostics; and
  4. proposing and announcing community-wide benchmark cases to help establish best practice guidelines and recommendations for the computational/mathematical modeling of bioaerosol generation phenomena.

 

T​entative programme:

The program foresees a mix of experimental, mathematical formulation and computational modeling sessions. During the workshop we will explore how in-vivo/in-vitro data can be used to inform and validate modeling. An effort will be made to identify key gaps in the available data. The program has been developed to maximize open format interactions. Each breakout session will have a set of questions/topics to be addressed by the working groups.

Monday: Opening lecture
  • Overview of what we know about site and formation mechanisms of respiratory droplets (Chantal Darquenne)
  • Challenges for modelers (Stavros Kassinos)
In-vivo/in vitro data-session 1 (Mucus/surfactant/saliva properties)
  • Physicochemical properties of airway lining fluid: saliva, mucus and surfactant
  • Aerosol generation from film bursting: an experimental study (Evert Ljundstrom)
Modeling session 1 (Modeling droplet formation from shear stress)
  • Mucus fragmentation due to shear stress (Francesco Romanò or James Grotberg)
  • Talk 2 TBD (speaker)
Tuesday Breakout session 1
  • How to improve current models of droplet formation from shear stress?
  • what can we model? What can we measure?
  • do we need new maths? new methods?
Modeling session 2 (Modeling aerosol generation from film bursting)
  • Effects of the non-Newtonian characteristics of the mucus on airway closure (J. Grotberg or P. Koullapis)
  • Talk 2 (speaker) Breakout session 2
  • How to improve current models of droplet formation from film bursting?
  • what can we model? What can we measure?
  • do we need new maths? new methods?
Modeling session 2 (Computational needs/techniques for these models)
  • Review of state-of-the-art computational techniques (Stefan Hickel)
  • Limitations of current techniques and definition of benchmark case challenge to address them (F. Romanò)
Wednesday
In-vivo/in vitro data-session 2 (Exhaled droplets size)
  • Characterization of respiratory droplets under various activities: breathing, talking, singing, walking, heavy exercise (Jacob Londhal or Gerard Scheuh)
  • Effect of age and BMI on exhaled aerosol production (David Edwards or Benedikt Schumm)
Breakout session 3
  • How to relate exhaled droplet size to size at generation site?
  • Can exhaled droplet size be used for model validation?
  • What data are needed for validation?

Thursday
Break-out sessions 4: Conceptual work/implementation strategies

  • What would be the best mathematical approach to solve the problem?
  • What would be a good benchmark case to use for standardization of models?
  • How to leverage the 460 h support from the Netherlands eScience Center research software engineers (RSEs)?
Real-world applications session
  • Indoor spreading of respiratory droplets/aerosols, growth and evaporation of exhaled droplets (Detlef Lohse or Michael Kahnert)
  • Viral particle spread within the respiratory tract (Gregory Forest)
Break-out session 5: Conceptual work/implementation strategies
  • Discussion with RSE engineers from the Netherlands eScience Center on how they can support the benchmark case challenge.
Friday
Funding opportunities session
  • Short presentation by organizers with identified funding opportunities
  • General discussion
Breakout session 6
  • Specific aims brainstorming

 

Participants:

We would like to invite mix of international and local scientists, both senior and early career, as well as students.