Novel mechanisms and therapeutic approaches for nasal obstruction and olfactory losses

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Project Summary 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 health care expenditures 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 is widely believed to be induced in part by airflow blockage that prevents sufficient ambient odor from reaching the olfactory region; however, no tool has been able to evaluate and target such conductive causes. Without validated clinically tools, current treatment of these symptoms relies primarily on the patient’s subjective feedback and the doctor’s personal training and experience, which can lead to inconsistent and unsatisfactory outcomes. Through a series of preliminary studies, we demonstrated that the symptom of nasal obstruction may be caused not by obstruction per se but by poor sensing of airflow during breathing, through the trigeminal cool-sensitive (TRPM8) pathway, and that such sensing may be worsened by impaired trigeminal function. However, which trigeminal sensory regions and what nasal airflow anomalies are most critical to disrupt the sensing of airflow are still unknown. To establish a more direct link, in Aim 1 of this proposal, we will examine the critical trigeminal sensory regions and critical nasal airflow distortions that may better predict airflow perception and obstruction symptoms. TRPM8 is a major component of the cool afferent pathway that is also activated chemically, which offers a unique dual investigatory tool to broaden our understanding of chemosensory function in nasal sinus disease and open up new therapeutic directions. So in Aim 2, we will investigate the efficacy of a novel patent-pending “nasal aid” to improve patients’ symptoms by modulating nasal airflow and trigeminal sensory feedback and to improve future treatment outcomes based on what we have learned and will continue to learn about the airflow trigeminal perception mechanisms. We have also shown in a series of published studies that complicated relationships exist between nasal obstruction and olfactory function. Based on these findings, in Aim 3 we propose to explore how to potentially improve olfactory function in patients with likely conductive olfactory loss, by enhancing nasal odor/air flow to the olfactory region (another pending US patent), analogous to hearing aids or eye glasses that amplify peripheral sensory stimuli. The outcomes from this research may potentially validate several novel clinical tools to better identify factors that most affect patients’ obstructive symptoms and to relieve symptoms by modulating nasal airflow patterns. The ultimate goal is to assist patients and clinicians in planning effective, well-informed, personalized treatment strategies, potentially saving millions of health care dollars annually while improving patient satisfaction.