Nasal sinus disease is one of the most common medical conditions in the US, affecting an estimated 13% of adults, or some 30 million people and responsible for 5.8 billion in healthcare costs annually (National Health Interview Survey 2009, CDC). Nasal obstruction and smell loss are two of the major symptoms of the disease; however, the field currently lacks a clear, objective understanding to the mechanisms causing these symptoms, which thwarts effective treatment. For example, patients' complaints of nasal obstruction correlate poorly or inconsistently with objective measurements of actual physical obstruction. Olfactory loss has been widely believed to be induced in part by airflow blockage; however, no tool has been able to quantify or predict such conductive mechanism. Without validated clinically tools, current evaluation and treatment on these symptoms rely primarily on the patient's subjective feedback and the doctor's personal training and experience. We propose to objectively evaluate the conductive components underling nasal obstructive symptoms, based on two hypotheses (a) that perception of nasal obstruction (lack of patency) may be caused not by obstruction per se but by lack of nasal cooling, and that such perception can be worsened by inadequate trigeminal feedback in the nasal airways, and (b) that insufficient air/odorant flow specifically to the olfactory region causes conductive olfactory losses. To test these hypotheses and pursue a clinical tool, we will study several types of patients with chronic complaints of nasal obstruction or smell loss: turbinate hypertrophy, septal deviation, idiopathic nasal obstruction, and nasal polyps.
In Aim 1, we will use individualized CFD models based on easily obtained office CT scans to capture the insufficient mucosal cooling due to airway abnormalities and determine if this alone or in combination with conventional rhinometric measurements predicts patient complaints of nasal obstruction at several time points post treatment/surgery. A nasal dilator and decongestant will be used to temporarily perturb patients' nasal airways, to test whether our approach can predict perceptual symptom changes.
In Aim 2, we will broadly assess the trigeminal cool sensitivity of patients with the symptom of nasal obstruction, and determine whether abnormal trigeminal cool sensitivity (including the TRPM8 pathway) contributes to symptoms. TRPM8 is a major component of the cool afferent pathway that is also activated chemically, which offers a unique dual investigatory tool and potentially broadens our understanding of chemosensory functions in nasal inflammatory disease. Variables from both aims will be combined to form the final evaluation tool for nasal obstruction symptom.
In Aim 3, we will specifically target nasal polyp patients with olfactory losses, track their treatment/surgery progress, and determine if the CFD-predicted airflow and odorant sorption rate to the olfactory region correlate with olfactory losses and recovery. The outcomes from this research may validate how to combine one or several measurements into an effective clinical tool to evaluate the causal factors leading to a patient's conductive symptoms, to potentially identify the site that most affects the symptom, and to assist patients and clinicians n planning effective, well-informed, personalized treatment/surgery strategies, potentially saving millions of healthcare dollars annually while improving patient satisfaction.

Public Health Relevance

Some 29.3 million people (13% of adults) in the US suffer from nasal sinus disease. Nasal obstruction and smell loss are two of the major symptoms of the disease that are crucial to disease management. Currently, we lack clinical tools to objectively evaluate the conductive mechanisms contributing to these symptoms. The proposed study aims to develop and validate such an objective tool by combining novel computational models with existing rhinometry and sensory measurements, which would enable patients and clinicians to make informed, personalized treatment/surgery strategy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC013626-03
Application #
8974826
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2014-12-01
Project End
2018-11-30
Budget Start
2015-12-01
Budget End
2016-11-30
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Ohio State University
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Li, Chengyu; Farag, Alexander A; Maza, Guillermo et al. (2018) Investigation of the abnormal nasal aerodynamics and trigeminal functions among empty nose syndrome patients. Int Forum Allergy Rhinol 8:444-452
Eichaker, Lauren; Li, Chengyu; King, Nakesha et al. (2018) Quantification of tissue-engineered trachea performance with computational fluid dynamics. Laryngoscope 128:E272-E279
Patel, Tirth R; Li, Chengyu; Krebs, Jillian et al. (2018) Modeling congenital nasal pyriform aperture stenosis using computational fluid dynamics. Int J Pediatr Otorhinolaryngol 109:180-184
Lee, Thomas S; Goyal, Parul; Li, Chengyu et al. (2018) Computational Fluid Dynamics to Evaluate the Effectiveness of Inferior Turbinate Reduction Techniques to Improve Nasal Airflow. JAMA Facial Plast Surg 20:263-270
Maza, Guillermo; Li, Chengyu; Krebs, Jillian P et al. (2018) Computational fluid dynamics after endoscopic endonasal skull base surgery-possible empty nose syndrome in the context of middle turbinate resection. Int Forum Allergy Rhinol :
Li, Chengyu; Jiang, Jianbo; Kim, Kanghyun et al. (2018) Nasal Structural and Aerodynamic Features That May Benefit Normal Olfactory Sensitivity. Chem Senses 43:229-237
Li, Chengyu; Dong, Haibo; Zhao, Kai (2018) A balance between aerodynamic and olfactory performance during flight in Drosophila. Nat Commun 9:3215
Li, Chengyu; Jiang, Jianbo; Dong, Haibo et al. (2017) Computational modeling and validation of human nasal airflow under various breathing conditions. J Biomech 64:59-68
Li, Chengyu; Farag, Alexander A; Leach, James et al. (2017) Computational fluid dynamics and trigeminal sensory examinations of empty nose syndrome patients. Laryngoscope 127:E176-E184
Otto, Bradley A; Li, Chengyu; Farag, Alexander A et al. (2017) Computational fluid dynamics evaluation of posterior septectomy as a viable treatment option for large septal perforations. Int Forum Allergy Rhinol 7:718-725

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