The Way the Wind Blows: Implications of Modeling Nasal Air low Kai Zhao, PhD, and Pamela Dalton, PhD, MPH Corresponding author Pamela Dalton, PhD, MPH Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104-3308, USA. E-mail: pdalton@pobox.upenn.edu Current Allergy and Asthma Reports 2007, 7: 117–125 Current Medicine Group LLC ISSN 1529-7322 Copyright © 2007 by Current Medicine Group LLC Nasal airlow is important for the many physiological functions of the nose, which include the warming and humidifying of inspired air; the iltration of airborne pollutants; and the sense of smell and nasal pungency. Until recently, airlow properties in the nose could only be understood using qualitative in vitro models of humans or in vivo studies in rodents. Recent advances in constructing three-dimensional geometric models of human nasal passages from CT scans, coupled with computational luid dynamic modeling, has been a valuable tool for quantifying airlow and transport of gases, heat, particles, and aerosols in the human nose. Additionally, these techniques hold signiicant promise for evaluating and predicting the impact and successful remediation of a variety of clinical conditions on olfac- tion and nasal patency and setting guidelines for safe levels of exposure to inhaled materials. Introduction As the structure that provides access of ambient air to the respiratory tract, the nose serves several important physiological functions [1]: 1) it ilters, warms, and humidi ies inspired air; 2) it conserves water by retain- ing the moisture in expired air; and 3) it is the initial site for interaction with the chemical senses, where airborne chemicals contact olfactory receptors and/or trigeminal nerve endings. The anatomical design of the nose also relects its functional needs. Inside the nose of terrestrial mammals lies an intricate internal skeleton of scrolls and plates of bone, collectively known as turbinates. Covered with epithelium and mucus, turbinates provide a large surface for trapping airborne particles and chemicals, for heat and gas exchange, and for the location of olfactory and trigeminal receptors. The turbinates unavoidably also diverge the inspiratory and expiratory nasal airlow into different parallel channels; the resulting airlow can exhibit dramatic intra- and inter-individual differences due to congenital anatomical features, inlammation aris- ing from acute or chronic conditions (eg, rhinosinusitis or allergic rhinitis), or the presence of polyps. Signi icantly, even small deviations in the path of airlow may lead to large functional changes in the ability to smell or sense chemical irritation (pungency). Although clinicians have employed standard mea- surements of airlow (ie, rhinomanometry, acoustic rhinometry) for many years, the results of such measures are often poorly correlated with patients’ subjective symp- toms or post-treatment improvements. The goal of this article is to review recent developments in the realm of nasal airlow modeling for humans and animals and their implications for 1) predicting the degree to which inlam- matory conditions or anatomical features of the airways will affect local airlow patterns and thereby impair olfac- tory function; 2) optimizing treatment plans (surgical and nonsurgical) to improve local airlow to areas that subserve olfaction and perceived nasal patency; 3) evalu- ating the deposition, dosimetry, and toxicity of airborne pollutants in the nose for setting guidelines for safe levels of exposure to inhaled materials; and 4) optimizing the characteristics (aerosol size, low speed) of nasal drug delivery systems targeting speci ic nasal regions. The History of Nasal Airlow Investigation Although the small size and structural complexity of the nasal cavity has prevented detailed in vivo experimental measurements of nasal airlow, a number of in vitro stud- ies have been reported using physical models cast from noses of cadavers or from computed tomography (CT) images for humans [2–5], and for monkeys and rats [6]. However, measurements of airlow properties in these models were generally crude or descriptive, accomplished by visualizing smoke in airlow [2]; or by using miniature Pitot tubes [3], laser Doppler velocimetry [4], or radio- active tracers [5]. In an attempt to increase the spatial resolution and the quantitative accuracy in measurement, enlarged models of the nasal cavity based on coronal magnetic resonance imaging (MRI) were constructed [7,8] where velocities for inspiratory and expiratory lows