What is Empty Nose Syndrome?

Empty Nose Syndrome (ENS)  is a devastating problem caused by the over-resection of the inferior turbinates and/or middle turbinates of the nose.  The turbinates are structures in the nose that dilate and/or contract to control humidity, temperature, and filter air that is transported to the lungs.  Many years ago, radical resection of these structures were performed often in an attempt to improve nasal breathing, allergic rhinitis, or sleep apnea.

Afterwards, patients who underwent these radical resections developed chronic nasal dryness, inability to feel airflow through the nose, alternating sensations of too much openness and severe nasal congestion, chronic nasal infections, and in worst cases, pain with each breath.  Many patients with empty nose syndrome suffer severe depression as they battle with these disease. Empty nose syndrome prevents patients from sleeping well, exercising well, and constantly reminds patients of their disabling condition with each breath.


mucus cell culture

Our researchers have developed advanced cultures of human respiratory epithelium from resected turbinates and reproduced normal mucociliary function. (Click here to see video). We are working to translate current advances in laboratory science to meaningful therapies for patients with rare sinus disorders.

Why does resection of the turbinates lead to worse nasal congestion?

Recent research suggests that the feeling of nasal congestion is likely related to the body sensing different levels of pressure and/or temperature in each nasal cavity.  These pressure and temperature receptors are likely located on the turbinate structures themselves, typically within the surface mucosal layer.  With over aggressive resection of these turbinate structures, particularly with resection of the mucosal layer of the turbinates, people with ENS lose the ability to feel their nasal breathing.   Furthermore, exquisite control of the diameter of the inferior turbinates is necessary to maintain laminar airflow (through organized streamlines) that allows greater volumes of air to flow through the nose per a given breath.   Without control of the diameter of the nasal airway, or with altered structures such as a septal perforation, nasal airflow becomes turbulent (disorganized streams of airflow) which limits the volume of airflow through the nose.  Finally, the mucosal layer of the turbinates is an important immune-system organ, providing the first line of defense against bacteria and other pathogens that are inhaled.  Through host defense peptides and other effectors of innate immunity, the mucosal layer of our turbinate epithelium maintains a population of harmless bacteria that helps to crowd out dangerous bacteria from entering the nose.  Patients with ENS lose these regulators of bacterial homeostasis, and dangerous and harmful bacteria slowly colonize the nose.  These bacteria can cause crusting, bleeding, worsening nasal congestion, and worsening dryness and dessication of the remaining nasal lining which leads to a vicious cycle and worsens the symptoms associated with ENS. 

 

Why are so few doctors aware of this problem?

ENS is rare problem that is a complication of poor surgical technique.  In the vast majority of patients, resection of the turbinates by any means, including older techniques which simply resected turbinate structures with surgical scissors, was effective in improving symptoms of nasal obstruction.  Many otolaryngologists who utilize these older techniques are unaware of ENS and have had good surgical outcomes for most patients.  As a result, when patients complain of persistent nasal obstruction after an overly-aggressive turbinate resection, it was often incorrectly assumed that the patient's nasal airflow was significantly improved and that the symptoms were psychosomatic.  Otolaryngologists are the experts in nasal airflow, so primary care physicians would often defer to their judgment.  As a result, many patients with ENS suffer the double victimization of having an iatrogenic problem created by over-aggressive surgery and then being told that their symptoms "do not make sense" and can be cured with behavioral therapy.

 

What treatments are available for empty nose syndrome? Why are they mostly ineffective?

Empty nose syndrome can be treated with topical therapies that attempt to moisturize the nose. Unfortunately, many of these therapies are probably harmful and provide limited benefit.  For example, repeated saline irrigations or saline gel provide temporary relief of nasal dryness but wash out the proteins and mucins in the gel layer of the gel-sol layer of the mucociliary blanket.  These proteins include host defense peptides such as lactoferrin, human beta-defensins, and others that regulate the commensal bacteria that exist within the nose.  Washing these proteins away also interferes with the nose's ability to protect the nasal mucosa from dangerous bacteria, such as Klebsiella ozenae.

Humidifiers are helpful since oxygen transfer in the alveoli of our lungs is most efficient at 100% humidity, however, most commercial humidifiers become rapidly contaminated with fungus.  Constant fungal exposure in the setting of ENS is likely more harmful than the benefit gained from using a humidifier.  More helpful than a humidifier is living in a warm, humid climate, particularly with salty air, such as close to a tropical beach.

Antibiotic nasal irrigations are often necessary in advanced forms of ENS to kill and deter growth of harmful bacteria such as Klebsiella species.  Certain creams and oral therapies have been tried as well to hypertrophy (increase the size) of any remaining turbinate tissue. These include estrogen creams (turbinates enlarge during pregnancy) and recently medications like Viagra. Phosphodiesterase inhibitors are known to cause nasal congestion, possibly by inducing hypertrophy of nasal mucosa.

 

What are some of the surgical and newer therapies available for empty nose syndrome?

Surgery for ENS has typically involved using implants or bulking materials to increase the size of any remaining turbinate tissue, or to increase nasal resistance by implanting materials in other locations (such as the nasal septum) in an attempt to recreate a nasal turbinate.  These implants have been partially successful in reducing the turbulence of nasal airflow that occurs.  However, these implants do not reproduce the humidification or immune protection aspects of the original turbinate mucosa.  The choice of implant is also difficult for surgeons.  Initially surgeons prefer to use absorbable materials such as hyaluronic acid to see if patients will benefit from an implant.  Later, more permanent implants such as with Gore-Tex or acellular dermis have been tried.  Many patients report modest benefit with these implant options.  Recently, our Institute has been implementing platelet-rich plasma combined with acellular extracellular matrix implants (Matristem(TM) from Acell, Inc.) for the therapy of ENS.

 

What is platelet-rich plasma?  How does it work?  Is it safe?

Platelet-rich plasma (PRP) is a patient's plasma (part of blood that has had red and white blood cells removed) enriched with platelets. Platelets are fragments of megakaryocytes from the bone marrow that degranulate in areas of injury to activate the clotting cascade. In addition, they contain numerous growth factors such as platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), insulin-like growth factor 1 and 2, (IGF-1, IGF-2), vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF), and others which start the healing/regenerative process in areas of injury.  PRP has been used extensively in the orthopaedics field and in oral-maxillofacial surgery in attempt to speed the healing of tissue injury.  It is thought to work by bringing additional growth factors to areas of tissue injury and thereby augmenting the regenerative processes occurring in a particular tissue field.

PRP has been described as a promising but unproven therapy.  There have been anecdotal reports of significant improvement with the use of PRP, and many elite athletes have utilized PRP therapies for the treatment of their orthopedic injuries.  However, well-blinded, placebo controlled, randomized clinical trials investigating the use of PRP have not found a consistent benefit for all patients using PRP particularly in relation to the advanced healing of orthopedic injuries. 

PRP is thought to carry promise as a therapy for ENS. Benefits include possible enhanced tissue growth, reciliation of epithelium, increased production of goblet cells and other mucus producing cells.  Further, increased inflammation is not seen as a deleterious side effect for therapy of the turbinates, unlike structures such as a knee capsule.  However, there are many limitations to PRP.  The benefits of PRP may only be temporary, repeated injections maybe required, benefits may be found only in a subset of patients (theoretically younger patients have greater regenerative capabilities), and unknown harmful side effects could occur.  A personal consultation with an otolaryngologist familiar with the use of PRP is required prior to the consideration of such therapy.

PRP is thought to be very safe for the use as a therapy in the turbinates.  It is obtained from a venipuncture.  Risks include hematoma formation and/or inability to obtain blood from a venipuncture, pain on injection, bleeding from the injection site, and others.  We are currently mixing PRP with acellular dermis as a bulking material in our patients who are deemed suitable candidates for the procedure.

What therapies for ENS do you offer?

Effective August 1, 2016, our institute will begin offering 3 types of therapies for ENS.  The first is the use of PRP/Acell injections for patients with turbinate dysfunction following surgery without significant volume loss.  We have treated over 250 patients with this therapy and have a greater than 75% improvement rate with this therapy.  The prices for this therapy will remain $1985 for the first injection and consultation and $1635 for subsequent injections.

We are also pleased with our initial efforts and experience using PRP/Acell/Adipose Derived Stem Cells harvested from a liposuction from patients.  We will continue to offer this as an alternative to our traditional PRP/Acell injections.  We have treated 20 patients with these procedures and have not seen any adverse side effects with this therapy. We expect these injections to have a success rate similar to or greater than our traditional PRP/Acell injections.  The prices for this therapy will be $2850 for the first injection and $2500 for subsequent injections.

We will also begin offering implants for patients with significant volume loss.   We will be impregnating these implants with PRP/Acell. The prices for this therapy will be $8350. Unfortunately we have explored obtaining insurance coverage for these procedures and they have been deemed experimental and therefore non-covered by any insurance company.

What research is being performed to prevent ENS?

We have been actively pursuing the development of objective airflow analysis via computational flow dynamics.  We are trying to objectify the art of turbinate surgery, so that otolaryngologists will perform virtual surgery prior to the real operation and perform the most minimal surgery necessary to obtain an optimal improvement in airflow.  Click below to see our research presented at the Computer Assisted Radiology and Surgery conference in Pisa, Italy.

 

How can I learn more about ENS?

Patients should contact Melanie Clark to schedule an appointment for a personalized consultation about ENS with one of our experienced surgeons in this area.  She can be reached at usasinus@gmail.com or (614) 867-3681.

 

 

Photograph of Platelet rich plasma injection mixed with Matristem prior to injection into a patient with Empty Nose Syndrome visiting us from Italy.

Photograph of Platelet rich plasma injection mixed with Matristem prior to injection into a patient with Empty Nose Syndrome visiting us from Italy.