Form and function of the human nasal airways: biomechanical assessment

Lead Research Organisation: Imperial College London
Department Name: Dept of Aeronautics

Abstract

The nose preconditions air entering the respiratory system by warming, humidifying, and filtering the air and thus protecting the delicate lining of the lungs. The nose is an important sensory organ, and a portion of the inspired air is directed towards the upper portion of the interior nasal cavity where the olfactory receptors are located. In order to perform these different physiological functions, the internal nasal cavity possesses protrusions (turbinates) which interact with the jet of inspired air, producing complex flow patterns to improve heat and water exchange and retain samples of air for olfaction. Understanding the mechanisms governing the interaction between nasal geometry and airflow is not only of fundamental physiological importance, but of great potential benefit in health care, therapeutic drug delivery and environmental hazard assessment. Detailed in-vivo measurement of air-flow and particle deposition in humans is extremely difficult, and the large disparities in anatomical features between species means that extrapolation of the flow and transport characteristics from animal studies is of questionable validity. Computational modeling is thus needed to build predictive capabilities. This will help doctors to understand and assess nasal function in health and disease, they will provide a more rational basis for surgeons to plan and judge the success of interventions, they will allow scientists to investigate the mechanics of gas transport and particle deposition which is needed to improve drug delivery and environmental assessment, and they can be used for many other beneficial purposes. Recently computational techniques combined with in-vivo imaging have been developed which provide a means to model nasal air flow, and a number of studies have recently shed some light on the complex nature of flow in the nasal cavity. However no attempt has yet been made to develop and to apply systematic procedures to characterize the functional significance of the wide variation in normal nasal airway anatomy found in the population. Even for a given individual, there is a lack of detailed information on how changes in airway geometry affect the air flow and transport characteristics. Our first aim is to determine the geometric form of the nasal airway, initially from more than twenty individuals. We will develop and apply mathematical techniques to characterize the ways in which nasal geometry varies, and assess the significance of these variations for physiological performance. The initial data set will gradually grow through contributions from colleagues in other countries, and will provide a valuable resource to provide more accurate modeling and prediction of physiological function and for many applications. Our second aim is to investigate how the variation in nasal geometry in an individual affects flow and transport. There are several factors which produce intra-individual geometric changes, for example in most normal adults, each side of the nasal airways alternately congests and decongests to a varying extent in a process termed the nasal cycle, altering the flow (and often sensation), and rapid sniffing causes partial collapse of the external nose. We will apply novel imaging techniques to investigate these changes. By studying the flow through simulation and by experiments in replica models, we will then be able to understand the significance of such alterations in the conditions that determine the flow. Our third aim is to study the very complex physical processes which cause the air flow in the nose to become unstable at higher inspiratory rates, to determine how to model such processes, and to study their impact for transport in the nasal airways. Overall we aim to provide both the data and the techniques needed for the first systematic exploration of nasal air flow and transport across a broad range of individuals.

Technical Summary

The research is intended to provide the first comprehensive study of air flow and transport in the nasal cavity, encompassing both inter- and intra-individual variations in the morphology of the airways. Firstly we aim to produce a database of reconstructed normal nasal airway geometries, derived by processing existing in-vivo CT and MR scans. Our initial database of 20-25 datasets will be extended through international collaboration. We will use procedures we have developed and are refining for compact topological representation to characterize the modes of variation in nasal morphology across the set of bi-lateral nasal airway reconstructions. Using computational simulations, and experiments in replica models for validation, we will determine ranges of relevant parameters such as pressure loss, regional wall shear and transport distributions, and regional deposition maps, in steady inspiratory flow. Secondly, we will investigate the significance of intra-individual variations in morphology for a smaller number (2-3) of representative geometries. Novel high-speed MR techniques adapted from cardiovascular imaging will be investigated to determine dynamic variations in internal passage caliber. Dynamic computational simulations, backed up by experiments in replica geometries with fixed boundaries will be applied to map variations in the above parameters due to alterations in temporal and spatial boundary conditions. Thirdly, we will investigate the complex interactions between the flow issuing from the nasal valve and the cavity which leads to the development of unsteadiness in the nasal flow at higher inspiratory rates. Using direct numerical simulation coupled with well controlled experiments in replica and appropriately simplified anatomical geometries, we will address a well-recognized deficiency in current modeling, and provide tools for a more comprehensive analysis of the data gathered in the first part.

Publications

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Cotter C (2012) A Reparameterisation Based Approach to Geodesic Constrained Solvers for Curve Matching in International Journal of Computer Vision

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Denis Doorly (Author) (2008) The effects of sinonasal morphology on transport mechanisms in the maxillary sinus in Clinical Otolaryngology

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Doorly D (2008) Experimental investigation of nasal airflow. in Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine

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Doorly DJ (2008) Nasal architecture: form and flow. in Philosophical transactions. Series A, Mathematical, physical, and engineering sciences

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Doorly DJ (2008) Mechanics of airflow in the human nasal airways. in Respiratory physiology & neurobiology

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Gambaruto A (2009) Modelling nasal airflow using a Fourier descriptor representation of geometry in International Journal for Numerical Methods in Fluids

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Gambaruto AM (2012) Decomposition and description of the nasal cavity form. in Annals of biomedical engineering

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Hood CM (2009) Computational modeling of flow and gas exchange in models of the human maxillary sinus. in Journal of applied physiology (Bethesda, Md. : 1985)

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Kimura S (2019) Voxel-based modeling of airflow in the human nasal cavity. in Computer methods in biomechanics and biomedical engineering

 
Description The research has provided a detailed mechanistic understanding of nasal airflow, exploring the relation between flow and airway anatomy. Combining innovative experimental techniques (e.g. imaging in replica models and in-vivo) with computations, key parameters have been established and new phenomena discovered. Findings are important for physiology, medicine and applications such as drug delivery and toxicology.

First, the temporo-spatial profile of inspiration differs in key respects from that implied by prior steady flow studies, compounding the influence of local anatomical variability on the loading of mucosal tissues.

Secondly, we showed how nasal respiration affects gas exchange with the maxillary sinuses. It established how anatomic variations in sinus-airway ostia upset the milieu of the sinuses and gas exchange.

Results have stimulated clinical applied research, including (i) use of radioactive tracer gases to quantify sinus gas exchange, (ii) application of techniques to reconstruct and characterize clinical images quantifying therapies e.g. decongestants, surgical interventions.
Exploitation Route The research provides new means to guide clinical decision making and surgical intervention planning and assessment. It also establishes new methodologies for in-vitro and in-silco modelling of respiratory airflow in the human that provide more realistic conditions than animal models.
The findings and methodologies can be used by clinicians, toxicologists and bioengineers requiring in-vitro and/or in-silico models to develop aerosol delivery systems
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology

 
Description The main outcome of the research is that we now have a much better understanding of how the shape of the nasal airways, together with the manner in which we inhale enables the nose to accomplish its disparate physiological functions. We have also provided a rationale for the abandonment of a hitherto common surgical technique intended to improve sinunasal health. The research has provided a detailed mechanistic understanding of nasal airflow, exploring the relation between flow and airway anatomy. Combining innovative experimental techniques (e.g. imaging in replica models and in-vivo) with computations, key parameters have been established and new phenomena discovered. The findings are important for physiology, medicine and applications such as drug delivery and toxicology. The main findings of the grant were as follows. First, the temporo-spatial profile of inspiration differs in key respects from that implied by prior steady flow studies, compounding the influence of local anatomical variability on the loading of mucosal tissues. Secondly, we showed how nasal respiration affects gas exchange with the maxillary sinuses. It established how anatomic variations in sinus-airway ostia upset the milieu of the sinuses and gas exchange. The techniques developed in the research and its outputs research has been used for basic studies and for applied clinical research as follows: (i) to validate computational modelling of large airway flows, with more ambitious projects to map whole airway dynamics underway; (ii) to develop procedures which are now allowing us to quantify the effects of topical decongestants (iii) to suggest new imaging techniques to quantify sinunasal exchange (based on radioactive tracer gases) (iv) to develop computational means to assess the impact of different airway pathologies. This work is now being pursued by NHS-supported clinical researchers attached to the project. Since the project grant finished, three surgeons have been trained in the geometric reconstruction techniques used in the project and a fourth has just started her MD; collaborations with a number of different surgical groups to use the methodologies are now beginning. More advanced simulation techniques are also being developed in an international collaboration involving Spain and the US. The research led directly to further work on the dynamics of inspiration and the assessment of tracheal constriction, providing support to the surgical team involved in tracheal transplant at Great Ormond Street and to the thyroid surgical group at Imperial NHS trust.
First Year Of Impact 2008
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description HPC Europa
Amount € 500 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 07/2012 
End 07/2012
 
Description HPC Europa
Amount € 500 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 04/2010 
End 05/2010
 
Description HPC Europa
Amount € 800 (EUR)
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 05/2011 
End 09/2011
 
Title Airway geometry 
Description Whole airway model 
Type Of Material Computer model/algorithm 
Provided To Others? No  
Impact The model will be available via the Royal Society Journal Interface website following publication in Dec. 2014; also on request 
 
Description Simulation of airway flow dynamics 
Organisation Barcelona Supercomputing Center
Country Spain 
Sector Charity/Non Profit 
PI Contribution We provided virtual models of airway geometries
Collaborator Contribution They performed very large scale computations
Impact Exchanges of researchers, joint proposals for research facilities, publications.
Start Year 2009
 
Description Science Museum Lecture at Dana Centre 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Members of the public attended a series of presentations on the sense of smell at the Dana Centre in October 2007

Various members of the audience asked for further information
Year(s) Of Engagement Activity 2007
URL http://www.danacentre.org.uk/events/2007/10/09/268