Exploring the frontiers of nasal, sinus, and upper airway biology

Immunology: Immune Systems and Immunity

The innate and adaptive immunologic microenvironment in chronic human upper airway diseases like chronic rhinosinusitis (CRS) has also been of ongoing interest of our group. We have shown altered levels of cytokines, oxidases, and Tregs in CRS patients and recently, through collaboration with Drs. Bruce Tan and Robert Schleimer at Northwestern University, IgD+ B cell populations that are selectively recruited into the chronically inflamed tissue beds within the upper airway. Our findings underscore numerous attractive opportunities to better understand immune dysregulation in the human upper airway.

1. Cho D.-Y, Bravo DT, Le W, Nguyen AL,Edward JA, Hwang PH, Illek B, Fischer H, Nayak JV. Air pollutants cause release of hydrogen peroxide and IL-8 in a human primary nasal tissue culture model. Int Forum Allergy Rhinol. 2014 Dec;4(12):966-71. doi: 10.1002/alr.21413. PMID: 25400124.
2. EdwardJA, Sanyal M, Ramakrishnan V, Hwang PH, Kingdom T Nayak JV. Systemic prednisone selectively alters granulocyte subsets in nasal polyps from AERD and CRS patients. Int Forum Allergy Rhinol. 2013 Nov;3(11):866-76.
3. RashanAR, Goshn E, Peterson A, Yang Y, Phillips M, Sahaf B, Herzenberg L, and Nayak JV. Characterization of IgE plasma cells that are elevated in the upper airway mucosa of non-atopic patients with chronic rhinosinusitis without nasal polyps (CRSsNP). Int Forum Allergy Rhinol. 2016 Apr; 6(4):378-84. PMID: 26878990.
4. Edward JA,Sanyal M, Le W, Soudry E, Ramakrishnan VR, Bravo DT, Nguyen AL, Zarabanda D, Kingdom T, Hwang PH, Fathman CG, and Nayak JV. Selective expansion of human regulatory T cells in nasal polyps, and not adjacent tissue microenvironments, in individual patients exposed to steroids. Clinical Immunol. 2017 Jun; 179:66-76. PMID:28279811.
5. Min J-Y,Nayak JV, Hulse KE, Raju PA, Herzenberg L, Schleimer R, and Tan BK. Evidence for altered levels of Immunoglobulin D in the nasal airway mucosa of patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2017 Dec;140(6):1562-1571.e5. PMID: 28625807.

Stem Cell Biology

Upper (and lower) airway diseases create significant morbidities and socioeconomic burdens, and improved understanding of the cellular and molecular mechanisms that maintain the upper airway epithelium in health, and repair and regenerate this barrier in disease, is critical to improving available treatments for these common disease processes. Military soldiers who have sustained facial or inhalant injuries would also benefit from these insights. Our laboratory has pioneered the discovery of mouse and human upper airway stem cells, termed nasal basal cells (NBCs), that are abundant, multi-potent progenitors. We have studied airway basal cells using a combination of microscopy, flow cytometry and cell culture, but recently confirmed their direct involvement in human airway tissue repair in vivo in patients through a collaboration with the University of Alabama. With our experimental foundation, we feel that basal cells represent an attractive candidate for future autologous stem cell therapy for transplantation as a novel modality for treating airway disorders.

1. Bravo DT,SoudryE, Edward JA, Nguyen A, Le, W, Sanyal M, Nayak JV. Characterization of human upper airway epithelial progenitors. Int Forum Allergy Rhinol. 2013 Oct;3(10):841-7. doi: 10.1002/alr.21205.

2. Cho KS, Park H-Y,RohH-J, Bravo DT, Hwang PH, Nayak JV. Human ethmoid sinus mucosa: a promising novel source of mesenchymal stem cells. Stem Cell Res Ther. 2014 Jan 24;5(1):15. doi: 10.1186/scrt404. PMID: 24460892.

3. VladarEK, Nayak JV, Milla C and Axelrod JD. Airway epithelial homeostasis and planar cell polarity signaling depend on multiciliated cell differentiation. J Clin Investigation Insight. 2016 Aug 18;1(13). pii: e88027. PMID: 27570836.

4. BösckeR, Vladar EK, Könnecke M, Hüsing B, Linke R, Pries R, Reiling N, Axelrod JD, Nayak JV, and Wollenberg B. Wnt signaling in chronic rhinosinusitis with nasal polyps. Am J Respir Cell Mol Biol. 2017 May; 56(5):575-584. PMID:28059551.

5. Nayak JV,Rathor A, Grayson JW, Bravo DT, Velasquez N, Noel JE, Beswick DM, Riley KO, Patel ZM, Cho DY, Dodd RL, Thamboo A, Choby GW, Walgama E, Harsh GR, Hwang PH, Clemons L, Lowman D, Richman JS, and Woodworth BA. Porcine small intestinal submucosal grafts improves remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling. Int Forum Allergy Rhinol. 2018 Jun 1. doi: 10.1002/alr.22156. [Epub ahead of print]. PMID: 29856526.

Empty Nose Syndrome (ENS) and Upper Airway Physiology

I am a national/international academic leader in disorders of nasal physiology and nasal breathing, particularly with regard to the debilitating disease termed empty nose syndrome (ENS). My practice of >100 patients with ENS has allowed the design and validation of what are now considered gold standard subjective (ENS6Q) and provocative (nasal cotton test) tests to more accurately identify patients suffering from ENS. Our validation study of the ENS6Q questionnaire was named the Best Clinical Research Paper at the American Rhinologic Society at the 2016 national meeting, and the cotton test validation received cover article honors. Through international patient assessment, we have also measured the functional and psychological burden presented by empty nose syndrome and have assessed how the nasal mucosa remodels in ENS patients over time compared to controls using imaging. We are currently assessing the benefit/impact of candidate treatments for ENS patients using subjective and objective outcome measures.

1. Velasquez N, Huang Z,Humphreys IM, andNayak JV. Inferior turbinate reconstruction using porcine small intestine submucosal xenograft demonstrates improved quality of life outcomes in patients with empty nose syndrome. Int Forum Allergy Rhinol. 2015 Sep 2. doi: 10.1002/alr.21633. PMID: 26332403.

2. ThambooA, Velasquez N, Ayoub N, and Nayak JV. Distinguishing computed tomography findings in patients with empty nose syndrome. Int Forum Allergy Rhinol. 2016 Jul 13. doi: 10.1002/alr.21774. [Epub ahead of print] PMID: 27409044.

3. Velasquez N,Thamboo A, Habib A-R, Huang Z, and Nayak JV. The Empty Nose Syndrome 6-item Questionnaire (ENS6Q): A validated 6-item questionnaire as a diagnostic aid for empty nose syndrome patients. Int Forum Allergy Rhinol. 2017 Jan; 7(1):64-71. PMID: 27557473.

4. ThambooA, Velasquez N, Habib A-R, Zarabanda D, Paknezhad H, and Nayak JV. Steps towards diagnostic criteria for empty nose syndrome: Validation of the office-based cotton test and clinical interpretability of the empty nose syndrome 6-item questionnaire (ENS6Q). The Laryngoscope. 2017 Jun; 179:66-76. PMID:28349563.

5. Manji J,Nayak JV, Thamboo A. The functional and psychological burden of empty nose syndrome. Int Forum Allergy Rhinol. 2018 Jun;8(6):707-712. doi: 10.1002/alr.22097. Epub 2018 Feb 14. PMID: 29443458.

Clinical / Translational Research

I am committed to increasing our pre-surgical armamentarium to combat the pervasive problems with inflammatory sinus disease, to make sinus surgery both less common overall, but also safer when performed. Rhinology is still in an emerging specialty when compared to other disciplines like cardiac and ophthalmologic surgery, which have a smorgasbord of medical and minimally-invasive procedural options available prior to surgery. In my practice, I routinely evaluate patients who have experienced a variety of avoidable and unavoidable complications from sinus surgery, which speaks to the need for improved medical options for sinus and allergy treatment, novel tools for minimally invasive sinus approaches (one of which I have designed and patented), improved surgical education, and realistic access to surgical simulation training.

1. Ramakrishnan V, Kingdom T, Nayak JV,Hwang PH, Orlandi, R. Nationwide incidence of major complications in endoscopic sinus surgery. Int Forum Allergy Rhinol. 2012 Jan-Feb;2(1):34-9. doi: 10.1002/alr. 20101. PMID: 22311839.

2. Patel ZM, Hwang PH, Chernomorsky A, Bravo DT, Nguyen BL, Nesterova K, Nayak JV.Low frequency pulsed ultrasound in the nasal cavity and paranasal sinuses: a feasibility and distribution study. Int Forum Allergy Rhinol. 2012 Jul-Aug;2(4):303-8. doi: 10.1002/alr.21039. PMID: 22528624.

3. Soudry E, Psaltis AJ, Lee KH, Vaezeafshar R, Nayak JV, Hwang PH. Complications associated with pedicled nasoseptal flap for skull base reconstruction. Laryngoscope. 2015 Jan;125(1):80-5. doi: 10.1002/lary.24863. PMID: 25111727.

4. Patel ZM, Thamboo A, Rudmik L,Nayak JV, Smith TL, and Hwang PH. Surgical therapy versus continued medical therapy for medically refractory chronic rhinosinusitis: a systematic review and meta-analysis. Int Forum Allergy Rhinol. 2016 Nov 11. doi: 10.1002/alr.21872. [Epub ahead of print] PMID: 27863163.

5. Velasquez N, Thamboo A, Abuzeid WM, and Nayak JV. Safe and effective treatment of ethmoid sinusitis utilizing minimally invasive ethmoid punch sinusotomy (EPS) in chronic rhinosinusitis without polyposis (CRSsNP) patients. Laryngoscope. 2017 Feb 14. doi: 10.1002/lary.26493. [Epub ahead of print] PMID: 28194802.