Department of Otorhinolaryngology - Head and Neck Surgery

McGovern Medical School

ORL Progress Notes

ORL Progress Notes, our second on-line departmental newsletter, provides information about developments in the Department. The newsletter’s target audience includes physicians and health care professionals as well as patients and members of the general public.

ORL’s 360 Research Program Translates New Laboratory Discoveries to Patient Care

Since her 2008 arrival at Memorial Hermann-Texas Medical Center and the McGovern Medical School, Amber Luong, MD, PhD, FACS, has focused much of her attention on building a translational otorhinolaryngology research program from the ground up. Today, those efforts are paying off in better outcomes for patients with chronic rhinosinusitis (CRS), as physicians in the department of Otorhinolaryngology-Head and Neck Surgery quickly move novel treatments from the laboratory to direct patient care through clinical trials.

Amber Luong, MD, PhD

Amber Luong, MD, PhD

“We don’t fully understand the disease process of chronic rhinosinusitis, a condition diagnosed in more than 30 million Americans annually,” says Dr. Luong, an associate professor and research director in the department of Otorhinolaryngology who also directs a laboratory at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. “The disease accounts for about $6 billion annually in treatment costs, making it one of the most costly non-fatal diseases to manage. We have knowledge of some of the potential triggers for CRS – viruses, bacteria and fungal exposure – but we aren’t certain which of the triggers affects individual patients. Our research goal is to develop directed curative treatment options for CRS through a better understanding of the triggers and molecular mechanisms that are important in the disease process. Learning more about CRS will give us a better idea of how to treat the cause of the disorder rather than just the symptoms, which is the focus of most current treatment. We’re not stopping with basic science. We’re taking our laboratory discoveries all the way through to patient care.”

The department’s robust translational research program stems from Dr. Luong’s training in the National Institutes of Health-sponsored Medical Scientist Training Program at UT Southwestern Medical Center, where she received her MD/PhD Two Nobel laureates, Michael S. Brown, MD, and Joseph L. Goldstein, MD, served as mentors for her PhD work during the eight-year program.

“They were great role models,” Dr. Luong says. “Here were two physicians who evolved from caring for individual patients to conducting research to acquire new knowledge that will help hundreds of patients. For the first time I understood the possibility of a medical career that combines clinical medicine and basic science research in a distinctive way. As a physician-scientist you can learn about the disease process as it manifests in patients, each of whom is very different, and use the knowledge and experience of treating patients to frame research questions and interpret the results in the lab, and vice versa. Information I gain as a scientist makes me think about the applicability to treatment or the understanding of human diseases. By bringing together these two worlds, translational medicine is born.”
Her desire to meld basic science with clinical treatment has led to the publication of several groundbreaking studies focused on understanding the pathophysiology of allergic fungal rhinosinusitis as a model for studying immune dysregulation of the paranasal sinuses; IL-33 as a pathway in chronic rhinosinusitis; the role of intranasal capsaicin as a diagnostic tool and a treatment for non-allergic irritant rhinitis; and molecular pathways by which fungus can stimulate chronic rhinosinusitis. One study, conducted by researchers at the McGovern Medical School and Baylor College of Medicine, demonstrated for the first time the functional importance of innate lymphoid cells in type 2-mediated inflammatory disease in humans (1).

Schematic of molecular pathophysiology of chronic rhinosinusitis.  This pictorial highlights the role of the epithelial cell barrier and epithelial cell derived cytokines, IL-25, IL-33 and TSLP, as orchestrators of the innate and adaptive immune response leading to chronic sinonasal inflammation.

Schematic of molecular pathophysiology of chronic rhinosinusitis.
This pictorial highlights the role of the epithelial cell barrier and epithelial cell derived cytokines, IL-25, IL-33 and TSLP, as orchestrators of the innate and adaptive immune response leading to chronic sinonasal inflammation.

“The aim of the study was to investigate the role of the epithelial cell-derived cytokine interleukin-33 (IL-33) and IL-33-responsive innate lymphoid cells in the pathophysiology of chronic rhinosinusitis,” Dr. Luong says. “From previous studies in an animal model we knew that IL-33 plays a key role in the development and regulation of a type 2 immune response, mediated by an IL-33-responsive innate lymphoid cell population, but until now there was little direct evidence of an important role for these cells in type 2-mediated inflammatory disease in humans. We were able to show that the percentage of innate lymphoid cells is significantly elevated in diseased mucosa in chronic rhinosinusitis with nasal polyps – a type 2-mediated inflammatory process – and that these cells represent a consistent and potentially important source of IL-13 in response to IL-33 stimulation.”

Dr. Luong’s study is one of a handful to identify a human disease in which the IL-33 pathway is important. Currently, she and other rhinologists in the department are actively recruiting participants for a randomized, double-blind, placebo-controlled clinical trial examining ways to block the IL-33 molecule for management of CRS with nasal polyps.

In the same study, the researchers also found that epithelial cells release IL-33 upon challenge with fungus. Later, Dr. Luong was a collaborator in a related study at Baylor College of Medicine, the results of which were published in Science in 2013 (2). Led by David Corry, MD, a professor in the departments of Pathology & Immunology and Medicine-Pulmonary and Critical Care at Baylor, the research team described how fungus signals through epithelial and immune cells to trigger a type 2 inflammatory response leading to airway hypersensitivity.

Through their protease activity, fungus cleaves fibrinogen-releasing degradation products that bind and activate toll-like receptor 4. The researchers found that toll-like receptor 4 does not directly activate T cells but instead leads to the expression of the IL-13 receptor, causing the typical symptoms of asthma and suggesting a connection between fungal infections and asthma. In another collaborative study with Dr. Corry, Dr. Luong showed that fungal load is elevated within diseased sinus cavities but also can be found in non-diseased cavities. However, only immune memory to fungal species specifically found within diseased sinus cavities were evident in patients with CRS and not in healthy controls, linking an active role of fungi in the pathophysiology of some CRS patients (3). Today, a clinical trial under way at Memorial Hermann-Texas Medical Center is investigating the addition of antifungal agents to typical post-operative treatment to treat CRS patients with fungal sensitivity.

“Because our basic science work demonstrated that fungus stimulates an immune response seen in chronic rhinosinusitis and asthma, it made sense to us that an antifungal agent would help by eradicating the thing that’s driving the immune response,” she says. “That’s one more example our 360 direction, translating basic science quickly to patient care.”

Dr. Luong and her research team are also investigating the use of intranasal capsaicin as a diagnostic tool and as a treatment for nonallergic irritant rhinitis (NAIR). Patients with NAIR have symptoms of nasal congestion, nasal irritation, rhinorrhea and sneezing in response to nasal irritants. Until recently, physicians had no reliable objective means of making the diagnosis of NAIR; it was a diagnosis of exclusion. Using capsaicin as an intranasal challenge, they compared changes in blood flow with optical rhinometry between subjects with NAIR and healthy controls. In addition, studies have suggested that multiple intranasal exposure to high dose capsaicin can serve as a treatment for NAIR(4).

“Study participants with NAIR showed a significant increase in blood flow relative to patients who don’t have this diagnosis,” she says. “Today, we’re continuing the development of this diagnostic tool and conducting a randomized blinded clinical trial in which we’re objectively identifying patients with NAIR and then randomizing patients to treatment with a high dose of capsaicin administered in five doses a day, each given one hour apart, or to placebo. We’re evaluating them at one month and three months to determine if the diagnostic response to capsaicin disappears, suggesting a positive treatment for NAIR.
“Laboratory breakthroughs like these mean that ultimately we’ll be able to help many more patients,” she adds. “It’s very rewarding to successfully treat one patient, but it’s also great to be able to help many patients through research. Our translational research program is a grand project: we’re looking for a cure for chronic sinus disease. Our long-term goal is to put ourselves out of business.”

References

  1. Shaw JL, Fakhri S, Citardi MJ, Porter PC, Corry DB, Kheradmand F, Liu Y-J, Luong A. IL-33-responsive Innate Lymphoid Cells Are an Important Source of IL-13 in Chronic Rhinosinusitis with Nasal Polyps. American Journal of Respiratory and Critical Care Medicine. 2013 Aug 15:188(4):432-9.  Link
  2. Millien VO, Lu W, Shaw J, Xuan X, Mak G, Roberts L, Song L-Z, Knight JM, Creighton CJ, Luong A, Kheradmand F, Corry DB. Cleavage of Fibrinogen by Proteinases Elicits Allergic Responses Through Toll-Like Receptor 4. Science. 2013 Aug 16;341(6147):792-6.  Link
  3. Porter PC, Lim DJ, Maskatia ZK, Mak G, Tsai CL, Citardi MJ, Fakhri S, Shaw JL, Fothergil A, Kheradmand F, Corry DB, Luong A. Airway surface mycosis in chronic TH2-associated airway disease. Journal of Allergy and Clinical Immunology. 2014 Aug;134(2):325-31.  Link
  4. Lambert EM, Patel CB, Fakhri S, Citardi MJ, Luong A. Optical rhinometry in nonallergic irritant rhinitis: a capsaicin challenge study. International Forum of Allergy and Rhinology. 2013 Oct;3(10):795-800. [Epub 2013 Jun 3]  Link

UT ORL Progress Notes Archives

  1. ORL’s 360 Research Program Translates New Laboratory Discoveries to Patient Care
  2. With a Bone-anchored Hearing Aid, One Good Ear Helps the Other
  3. Department of Otorhinolaryngology Extends Facial Plastic & Reconstructive Surgery Expertise to The Woodlands
  4. Rapid Response and Multidisciplinary Teamwork Save a Young Man’s Life
  5. Transoral Robotic Surgery for Airway Obstruction in Pediatric Patients
  6. Kunal Jain, MD joins the Department’s Head and Neck Surgery Program
  7. Zi Yang Jiang, MD joins UTHealth Pediatric ENT Service
  8. Surgeon-performed Ultrasound Provides X-Marks-the-Spot Accuracy for Parathyroid Adenoma
  9. The Watson Case: An “Impossible” Surgery Makes a Night-and-Day Difference for a Patient with Proteus Syndrome
  10. Christian Conderman, MD joins UTHealth Otorhinolaryngology at its New Woodlands Location
  11. James Owusu, MD joins UTHealth Otorhinolaryngology at its New Woodlands Location
  12. New Clinical Learning Guidelines Transform How Medical Residency Programs Prepare Future Physicians
  13. TORS-L Eliminates the Need for Adjuvant Therapies in an Oropharyngeal Cancer Patient
  14. William Yao, MD joins Texas Sinus Institute and Texas Skull Base Physicians
  15. AAO-HNS President-elect to Speaks at 2015 Otorhinolaryngology Frontiers
  16. Surgical Fire Prevention in Laser Laryngeal Surgery
  17. A Gift of Hearing
  18. Breath of Fresh Air
  19. Current Pediatric Guidelines for Tonsillectomy
  20. Profile in Caring: José Elías, RN, CORLN
  21. Amber Luong, MD, PhD, Awarded CCTS Grant in Support of Continued Chronic Rhinosinusitis Investigations
  22. Two ORL Faculty Members Named to Top Doctor Lists
  23. Sialendoscopy: An Innovative Minimally Invasive Approach to the Treatment of Sialolithiasis
  24. Physicians’ Mission Satisfied
  25. A Second Pair of Ears
  26. Two ORL Faculty Members Receive Dean’s Teaching Excellence Award
  27. More Than 100 People Participate in UTHealth Otorhinolaryngology’s Annual Free Cancer Screening Clinic
  28. Etan Weinstock, MD, Selected Faculty Member of the Year
  29. Amber Luong, MD, PhD, Named Fellow of American College of Surgeons and Promoted to Associate Professor
  30. Memorial Hermann and UTHealth Welcome New Team Members
  31. Texas Hill Country ENT Symposium Recap
  32. Internationally Renowned Expert in Facial Cosmetic Surgery Speaks at 2014 ORL Frontiers
  33. Congratulations to Graduating Residents and Fellows
  34. Samer Fakhri, MD, Chairs Rhinology Program at Middle East Conference in Dubai, Serves as Invited Faculty in Tehran
  35. TORS-L: Transoral Robotic Surgery with CO2 Laser Offers Greater Precision for Surgeons and De-intensification of Adjuvant Therapies for Patients
  36. Reevaluating Anaplastic Thyroid Cancer: Aggressive Treatment May Extend Life and Improve Its Quality
  37. UTHealth Audiology Offers Widex Zen Therapy for Tinnitus Management
  38. MicroSeismic, Inc. Gives Pediatric Patients the Gift of Hearing
  39. In Memoriam: Robert Jahrsdoerfer, MD
  40. Simultaneous Bilateral Cochlear Implants in an Infant After Meningitis
  41. Laryngotracheal Reconstruction Using Anterior Cricoid Suspension in a Three Year Old
  42. Single-Incision Minimally Invasive Parathyroidectomy
  43. Advanced Technology and a Strong Focus on Convenience Improve the Patient Experience
  44. Multidisciplinary Virtual Pre-surgical Planning Optimizes the Outcome for an Ameloblastoma Patient
  45. Dr. Fakhri Receives Regents’ Outstanding Teaching Award
  46. IL-33-responsive Innate Lymphoid Cells Are an Important Source of IL-13 in Chronic Rhinosinusitis with Nasal Polyps
  47. Randomized, Double-Blind, Controlled Trial of Oral Antifungal for the Treatment of Fungal-sensitive Chronic Rhinosinusitis with Nasal Polyps
  48. Dr. Fakhri Promoted to Professor of Otolaryngology-Head and Neck Surgery
  49. TLR4 Signaling in the Pathophysiology of Allergic Fungal Rhinosinusitis
  50. Two ORL Faculty Members Named to Texas Super Doctors 2013 List
  51. Transoral Robotic Surgery for the Treatment of Obstructive Sleep Apnea
  52. Lone Star Rhinology Course Attracts a National Audience
  53. Internationally Renowned Otolaryngologist Speaks at 2013 ORL Frontiers
  54. ORL Welcomes New Recruits
  55. UTHealth Otorhinolaryngology Holds Free Cancer Screening Clinic
  56. Two ORL Team Members Named Fellows of the American College of Surgeons
  57. Faculty Named Among Texas Super Doctors Rising Stars
  58. Two ORL Faculty Members Receive Dean’s Teaching Excellence Award
  59. Translational Science Program Working to Identify Therapeutic Targets in Chronic Rhinosinusitis
  60. Preventing Surgical Fires: UTHealth Otolaryngologist Provides Expert Advice for a New FDA Safety Initiative
  61. Improving Survivorship in Head and Neck Cancer: UTHealth Department of Otorhinolaryngology and Institute of Molecular Medicine Partner on CPRIT Research Award
  62. Using Intraoperative Staining to Identify the Parathyroid Adenoma
  63. Otorhinolaryngologists Named to 2012 Best Doctors in America List
  64. Four Studies Evaluate the Effectiveness of Optical Rhinometry
  65. A Collaborative Approach Offers Patients a Less Invasive Alternative for Surgical Excision of Pituitary Tumors
  66. Internationally Renowned Otolaryngologist Speaks at 2012 ORL Frontiers
  67. Ron Karni, MD, Selected Faculty Member of the Year by Graduating Residents
  68. Samer Fakhri, M.D., Receives AAO Foundation Honor Award
  69. Two Audiologists Join UTHealth Otorhinolaryngology
  70. 2012 Residency and Fellowship Update
  71. Five UTHealth Medical Students Matched to Top Choice Otorhinolaryngology Residency Programs
  72. Two ORL Faculty Members Receive Dean’s Teaching Excellence Award
  73. Chair of Otorhinolaryngology Named to Texas Super Doctors 2012 List
  74. Minimally Invasive Surgery for Skull Base Cancer
  75. UTHealth/Memorial Hermann Physician Joins a Medical Mission to Honduras
  76. Online Patient Access Library Offers Medical Information About ENT Diseases & Conditions to Patients
  77. Facial Reanimation Surgery Brightens a Young Boy’s Future
  78. Morphoproteomics: Driving a Shift to Personalized Care for Sinonasal Undifferentiated Carcinoma
  79. Internationally Renowned Otolaryngologist to Speak at 2012 ORL Frontiers
  80. UTHealth Otorhinolaryngology Department Exceeds the National Averages in Quality and Safety
  81. Rhinologist Invited to Serve as Board Examiner in the Middle East
  82. Dr. Citardi Named to the 2011 Texas Super Doctors List
  83. Make Your Voice Count!
  84. Research Update
  85. Advanced Rhinology Concepts CME Attracts a National and International Audience of Otolaryngologists
  86. Outside the Box with Chronic Rhinosinusitis
  87. The Vargas Case: Excision of a Large Benign Goiter
  88. The Reverend Williams Regains His Voice
  89. Nihal Uddin’s Journey to 360-Degree Hearing
  90. Residents Receive Research Grants
  91. Two ORL Faculty Members Receive Dean’s Teaching Excellence Award
  92. Otorhinolaryngologists Named to Best Doctors in America List
  93. Russell Kridel, MD, Reelected to AMA Council Position
  94. From Bench to Bedside: Physician Researcher Amber Luong, MD, PhD Blends Basic Science with Clinical Care
  95. 2011 Advanced Rhinology Concepts Scheduled for November
  96. Internationally Renowned Otolaryngologist Speaks at 2011 ORL Frontiers
  97. Michael Byrd, MD Recruited to UTHealth and Memorial Hermann
  98. UT Physicians Opens Facial Plastic Surgery Clinic in Southwest Houston
  99. UTHealth Audiology Program Expands
  100. 9 UTHealth Medical Students Match in Otorhinolaryngology
  101. Residency and Fellowship Update
  102. Ron Karni, MD Invited to Speak in Panama
  103. Finding the Unknown Primary in Head & Neck Cancer
  104. A Meta-Analysis of Topical Amphotericin B for the Treatment of Chronic Rhinosinusitis
  105. Cytokine Profile Comparison Between Inflamed Sinus Mucosa and Sinonasal Polyps from Chronic Rhinosinusitis
  106. The Distribution of Normal Saline Delivered by Large-Particle Nasal Nebulizer versus Large-Volume/Low-Pressure Squeeze Bottle
  107. Averting the "Limping Larynx" with a Multidisciplinary Approach
  108. Repair of Nasal Obstruction with Functional Septorhinoplasty
  109. Definitive Endoscopic Resection of Inverted Papilloma
  110. Facial Reanimation and Facelift for Facial Paralysis
  111. Mometasone Furoate Gel: A Novel In-Office Treatment of Recalcitrant Postoperative Chronic Rhinosinusitis
  112. Rhinologic Applications of Radiofrequency Coblation
  113. Rhinoplasty for Nasal Obstruction
  114. Producing Quality Outcomes in Thyroid Surgery
  115. Functional Rhinoplasty: Repairing Nasal Valve Obstruction
  116. A Cancer Patient Regains His Voice
  117. Soham Roy, M.D., Named Director of Pediatric Otorhinolaryngology
  118. From Bench to Bedside with New Treatments for Chronic Sinus Disease
  119. Comprehensive Rhinology Program Offers State-of-the-Art Care for Patients with Chronic Rhinosinusitis Refractory to Standard Treatments
  120. Rhinology Update: Advanced Rhinology Concepts CME Scheduled for November
  121. The Comprehensive Voice Program: From Advanced Office-Based Procedures to Community Outreach
  122. Designing the Future: ORL’s New Office Space Features High-Tech Tools
  123. Welcome!

Subscribe to our newsletters

ORL Update UT ORL Update, our first on-line departmental newsletter, summarizes current topics in otorhinolaryngology. The newsletter’s target audience includes both physicians and other healthcare providers, although subscriptions are not limited to members of these groups.

ORL Progress Notes ORL Progress Notes, our second on-line departmental newsletter, provides information about developments in the Department. The newsletter’s target audience includes physicians and healthcare professionals as well as patients and members of the general public.

To subscribe, please fill in your contact information and select the newsletter(s) you would like to receive. Of course, you may opt out of any of the newsletters at any time.