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BackTable / ENT / Podcast / Transcript #122

Podcast Transcript: Evaluation & Management of Patients with Olfactory Dysfunction

with Dr. Zara Patel

In this episode of BackTable ENT, Dr. Zara Patel, director of endoscopic skull base surgery and professor of otolaryngology at Stanford, joins Dr. Shah to discuss the physiology behind olfactory dysfunction and evidence-based cutting-edge therapies. You can read the full transcript below and listen to this episode here on BackTable.com.

Table of Contents

(1) Smell Disorders 101

(2) Assessment of Olfactory Function

(3) Etiologies Behind the Loss of Smell

(4) Medications Associated with Smell Loss

(5) Physical Examination of the Patient with Olfactory Dysfunction

(6) Questionnaires to Assess Olfactory Dysfunction

(7) Workup of the Patient with Olfactory Dysfunction

(8) Smell Retraining: An Underutilized Tool for Smell Loss

(9) Nutritional Supplements & Platelet-Rich Plasma for Smell Loss

(10) Equitable Care for Olfactory Dysfunction Patients

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Evaluation & Management of Patients with Olfactory Dysfunction with Dr. Zara Patel on the BackTable ENT Podcast)
Ep 122 Evaluation & Management of Patients with Olfactory Dysfunction with Dr. Zara Patel
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[Dr. Gopi Shah]
This week on the BackTable Podcast.

[Dr. Zara Patel]
Keep in mind that this is highly impactful on patients' lives. When you think about how we interact with other human beings, how so often we come together with our friends, our families, our strangers over food and drink, and how not being able to enjoy that or sometimes being repulsed by that slowly causes social withdrawal, depression, people having anxiety about their own bodily hygiene and not being sure about how they are in social situations, you can see how all of that will weigh on a person.

Not just that, but people say that there is just a wall of gray that has come over between them and the rest of the world. They feel separate. They feel like there's no joy anymore. Imagine going through the rest of your life like that. It's just so difficult for these people. I would say truly open yourself to empathizing with these patients, validate their experience, give them some hope.

[Dr. Gopi Shah]
Hello, everyone, and welcome to the BackTable ENT Podcast, where we discuss all things ENT. We bring you the best and brightest in our field with the hope that you can take something from our show to your practice. My name is Gopi Shah. I'm a pediatric ENT, and I have a very special guest today. I have Dr. Zara Patel. She's the director of endoscopic skull base surgery and a professor of otolaryngology at Stanford. She has served as chair of the education committee and member of the board of directors for the American Rhinologic Society.

Dr. Patel has published widely in topics such as avoiding complications in endoscopic sinus surgery, chronic rhinosinusitis in the immunosuppressed patient population, new devices and techniques for endoscopic skull base surgery, and olfactory dysfunction. She was lead author for the international consensus statement for allergy and rhinology, for olfaction released in 2022. She is here today to talk to us about the evaluation and management of patients with difficulties with smell. Welcome to the show, Zara. How are you?

[Dr. Zara Patel]
I am great. Thank you so much for having me. It's a pleasure to be here with you.

[Dr. Gopi Shah]
I'm really happy you're here. I've gotten to see you speak at different conferences and meetings, but I'll tell you, the big impact for me was when COVID hit. When COVID hit, you had the courage to voice, hey, this is serious. We need to protect ourselves. We need to, for what we do specific to sinus surgery, skull base surgery, and anything erstwhile generating in ENT, we need to protect ourselves. I just want to tell you thank you, because it pushed our societies, it pushed our departments, it pushed people to actually make recommendations and protocols.

I'll tell you, I found myself in a very precarious situation, a difficult professional situation early on for a skull base surgery and having, listen, this is what's happening at Stanford. This is what's happening at our academies. We have guidelines now. Really, really, I think, helped me and our team, and our patients. That was the impact. I'm like, this is the impact of Zara Patel. Thank you for doing that, because I know that took a lot of courage, being able to voice and speak up and seeing what's right, especially for something so early on, it was impactful for all of us. I just want to tell you thank you for that. That was huge.

[Dr. Zara Patel]
Oh, well, thank you for saying that. I think that I've heard from some people like you that it was helpful at their institutions to get the protection they needed to do the surgeries that we needed to do. I had a lot of backlash, honestly, at the very beginning from understandably people in private practice who didn't want to go out of business. It was their livelihood, and people were upset also. It is really nice of you to say that, that it helps you in some way.

[Dr. Gopi Shah]
It helped me tremendously.

[Dr. Zara Patel]
Good.

[Dr. Gopi Shah]
As you said, I think it probably helped most of us more so as a whole. Thank you for doing that.

[Dr. Zara Patel]
Of course.

[Dr. Gopi Shah]
All right. Before we get into it, can you tell us a little bit about yourself and your practice?

[Dr. Zara Patel]
Sure. As you mentioned, I'm at Stanford and I am an endoscopic sinus and skull base surgeon. I'm also an expert in smell disorders, something that only I and a handful of other ENTs cared about before the pandemic, but now certainly a lot of other people care about that, which is really great, actually, to see. My practice, I would say I do OR twice a week. I do clinic twice a week. I actually limit the amount of smell clinics specifically that I do, because as you might be able to guess, there are just hundreds and hundreds of patients desperate for help with their smell disorders.

If I opened up my entire clinic to them, it would overwhelm my whole practice and I would never do sinus and skull base surgery anymore. I hold my smell clinic once a month and the rest of my clinics are sinus and skull base-oriented, but there's a huge wait list. I'm really happy that you want to do a podcast about this so that other ENTs can learn about all the ways to treat patients with smell loss, and hopefully take some of that huge patient load that really needs to get seen.

[Dr. Gopi Shah]
With the international consensus statement, is that the first statement we've had for olfaction? Was this the first of its kind, or is this a second version?

[Dr. Zara Patel]
This is the first of its kind. Actually, the first time ever that there's been a peer-reviewed compendium of really all the clinical knowledge that we have in olfaction, it was really a labor of love. It took, I think, two years or something like that to put us together. Just gathering all the experts in smell all around the world was a challenge in and of itself, because again, before the pandemic, people were just working on their own. Even here in the US, we knew the few others of us within ENT that had a specific interest in it and were doing research in it, but it was not that many people, to be honest.

The pandemic really allowed us to find out who the other people were that were working on this around the world. There's something called the Global Consortium of Chemosensory Research that I joined that got started from people at Monell in Philadelphia and really people all around the world joined. That was a really great way to start making connections and really learning who all the experts were that had an interest in this before the pandemic.

[Dr. Gopi Shah]
I don't think I really appreciated how multidisciplinary smell is until I was looking at the preparation for this podcast. I was looking at the consensus statement and seeing all the different disciplines because of all the potential risk factors and reasons that smell can lead to. I'm sure that was pretty cool as well because it just makes it stronger.

[Dr. Zara Patel]
Exactly. I think that not just hearing from otolaryngologists, but also hearing from neurologists and endocrine experts, people who are experts in all the different organ systems of the body that can affect smell. Really, the olfactory system is dependent on so many other parts of your system to be functioning correctly, and is impacted by so many things not working correctly. That was a really great way of not just seeing our perspective as otolaryngology, but getting everyone's perspective around the world and from all these different fields to really get the strongest review and compendium, and statement possible.

(1) Smell Disorders 101

[Dr. Gopi Shah]
I wanted to first start with terminology, because I know anosmia, but then we have hyposmia, parosmia, phantosmia. I don't know if there's other “-osmias,” but can we just go into some of the terminology that we should know, and the differences?

[Dr. Zara Patel]
Anosmia is no smell. They have no smelling ability. Hyposmia would just be a decrease in smelling ability. Parosmia is the distortion or alteration of smell. Phantosmia is when someone is smelling something that just isn't there actually in the environment, a phantom smell. Then there's other asmias that more specifically characterize parosmias. For example, a very unfortunately common parosmia is cacosmia, where someone smells feces anytime they smell something or eat something that smells like feces. There's like very specific “-osmias” characterizing exactly the way that smell is altered also.

[Dr. Gopi Shah]
I did peds and what I enjoy is pediatric sinus. I'd see some of the adolescents with small distortion. I recall one patient specifically. He's there with mom and every time they would sit down for dinner, it would smell like garbage. Any dinner that they would have. Is that a parosmia or a phantosmia?

[Dr. Zara Patel]
It sounds like it's a parosmia because he wasn't smelling garbage all day long no matter where he was or what he was doing. It sounds like specifically when he was trying to eat, that is what smelled and probably tasted like garbage. That's a parosmia. Unfortunately, it is never a good smell. It's always some terrible smell. People will say feces or rotting flesh, or garbage, or a sweet chemical scent.

There's very specific categories of parosmias. We don't know exactly why, but I suspect that just from an evolutionary standpoint, when our brain is receiving a signal that it is not familiar with, it wants us to avoid whatever that unknown thing is and not put it in our body, and so it automatically distorts into this bad odor and taste that we are repulsed by it.

[Dr. Gopi Shah]
Leading into how patients present to you, if the chief complaint is something like parosmia, or when they're eating dinner but it smells like trash or something like that, is that workup differential or question set your history different than if a patient comes in with just anosmia?

[Dr. Zara Patel]
It really is not that different because when you think about why we have parosmia, again, there's a lot of research going on about specifically what's wrong, and it likely may be on a multi-level process of what's going wrong with parosmias, but what we do know is that we see parosmia quite often when we have hyposmia or anosmia, especially in a post-viral situation, and especially with COVID-19. The percentage of people with parosmia after COVID-19 is much higher than other post-viral illnesses, honestly. It's almost a mark of the smell loss that occurs with COVID-19.

Likely, one of the major reasons why we develop parosmia is that we have not been able to have our full complement of olfactory neurons bounce back and regenerate after the initial insult. It is intuitive that if you lose some neurons, they're not able to regenerate correctly, then you're not going to be able to smell as well. You'll have a decrease in smell. Also, if you think about the way in which we smell, take a complex odor like coffee, for example. That's dozens or hundreds of different molecules that are filtering into your nose, dissolving into the mucus layer, and then attaching to many, many different olfactory receptor neurons.

What happens with parosmia is that some of those neurons are still there. They're able to pick up on particular molecules in that entire aroma, but they're not able to pick up on all of them. Instead of smelling that full complement of both the slightly bitter but also the warm and toasty aspects of coffee, some people will only be able to pick up on that acrid, bitter component and miss the pleasant component because they don't have those neurons to pick up on those particular molecules.

It makes sense that when you're missing some neurons, that you may not be able to pick up on the entire odor, and that tends to end up being a bad odor or smell. There may be, on the higher level in the olfactory bulb or olfactory cortex, other things also going on that are causing this aberrant signaling, but I suspect that the majority of it is just that you're not able to send the entire signal correctly.

[Dr. Gopi Shah]
I see. I love how you explain that. Can we kind of think of the same pathophys explanation for the phantosmias as well, or is there something different going on, you think?

[Dr. Zara Patel]
I think phantosmia might be a little different. We think about it slightly differently than those other two. There are different reasons why people might have phantom smells that are separate from the smell loss and smell distortion. When you have just a phantom smell, a very common one, for example, a cigarette smoke that people will say they smell, that can be from just irritation or inflammation of the neurons. Often if I see a patient with phantosmia and I get them on a high-volume steroid irrigation, it can make it go away. Also there are other things that cause phantosmias that are likely much more on the higher level olfactory cortex type of side.

We know, for example, that phantosmias could be an aura for migraine. They could be an aura for seizure activity. Some people have a phantom smell during their seizure or right before their seizure. There's a lot of different reasons why people might have phantosmias. Some may be on the distal end of the actual olfactory neurons and likely are much more just an inflammation irritation type of issue. Also, many can be on the higher end within the olfactory cortex. Of course, for any of these smell loss, smell distortion, or phantom smells, you do want to make sure that you're starting to think about other things within the system that could go wrong, like tumor formation right around the olfactory nerves and bulb, and things like that.

[Dr. Gopi Shah]
When you do see patients in your small clinic, what percent are anosmia? What percent are hyposmia? How does it break up among who you see?

(2) Assessment of Olfactory Function

[Dr. Zara Patel]
I'd say the vast majority are hyposmia. I will tell you that the way that we define that and the way that we test smell in general is fairly limited. We have these scratch and sniff booklets like the UPSIT, which is what many of our listeners will be familiar with, the University of Pennsylvania Smell Identification Test. Then there's more granular type of tests like Sniffin’ Sticks, which don't just test identification, but also test threshold and discrimination. That's also just smelling pens and introducing them to someone and asking them whether they can pick up on it and what they smell.

Can they discriminate? Things like that. All of those types of tests. Honestly, if you look at that review, that ICARs team, you'll see there are dozens of different smell tests out there on the world. There's a 23-page table outlining all of the different smell tests that we have. That shows you that when we have so many different options, there is no one really amazing option to test smell. That's actually something that I'm currently working on right now, an objective measure of smell function. Because if you think about those ways that we test smell, the main problems are the subjectivity.

It matters whether someone was born in the US versus a different country, the smells that they're going to be able to identify and that they're familiar with. It even matters whether you're testing someone who has lived their entire life in an inner city, urban environment, or if they were raised in the countryside within the US. It matters whether someone can speak English to participate in a test. It matters whether someone is literate, whether they can read and circle the correct answer on something like the UPSIT. Of course, cognition plays a huge role in whether someone understands how to do a test like that.

Because of all these barriers and biases, it really prompted me to start developing this device that I'm currently working on, an endoscopic device to actually directly record the neuronal signal from the olfactory epithelium, which I think will be just a huge change in the way that we think about smell. We think about the way that we test vision and the way that we test hearing, it's all very objective at this point.

We really need to bring our field of olfaction into the realm of objectivity. To get back to your question the reason that probably a lot of the people that come to see me are hyposmic but they still feel, they say that they can't smell anything, and that's because we're just really testing for the one facet of smell in that UPSIT. There's so much more nuance of whether people can pick up on smells in their environments. We're missing probably a lot of information when we test smell.

(3) Etiologies Behind the Loss of Smell

[Dr. Gopi Shah]
I love that you brought up all of those factors regarding language, where people have lived most of their lives, where they are by the time they get tiers at a new country, city, place, because that has a lot of different aspects of equity to it. I wanted to ask you about more equitable care, but we're going to get to that. We'll get to that because all that-- When a patient comes in to clinic, what is always part of your list of questions? What are you always, in your history, checking for? Are you looking at the medication list? What are the key things?

[Dr. Zara Patel]
I probably will not list everything here that you could potentially think about. I will just mention that in that ICAR document and that statement, at the very end of that document, because it's a huge document, it's like 600 pages or something, but at the very end, there is an algorithm that takes people all the way from diagnosis through treatment. At the beginning of that algorithm, we really list out all the different factors that can affect it. The highlights of what I ask about are certainly any history of sinus or nasal inflammation, that's still really the number one reason why people have smell issues.

Also, of course, any preceding post-viral type of event. COVID-19 is a very common reason why people come into our clinics now for smell loss, but even before the pandemic, I was treating and researching post-viral smell loss for the last decade before the pandemic even hit. That has always been one of the reasons. COVID-19 is one, but other coronaviruses, influenza viruses, rhinoviruses. It's not just whether they had COVID or not, but any viral events is important to ask about. Then any trauma. Certainly, you go through their medication list.

You ask them about their environment, so their job. Sometimes you'll be surprised what people are exposed to in their jobs. Then you certainly want to just take a really full medical history. You want to know if people have had cancer, whether they've had radiation or chemotherapy. It doesn't matter if it's a head and neck cancer or a cancer of their leg, if they had chemotherapy, then that certainly will still affect neuronal ability and function. You want to ask about metabolic issues, endocrine issues. We know that things like diabetes and hypothyroidism affect smell. You want to ask about other neurotransmitter or cognitive issues.

Any depression, any schizophrenia, any autism, all of those types of issues will have an impact on smell. Of course, especially in our older patient population, you want to ask them about any other neurodegenerative-type symptoms. You want to ask about any family history of that to know if they have any risk factors, because as we're learning more and more in the last five years or so, smell loss really is probably the very earliest sign of neurodegenerative disease. I suspect that a lot of the smell loss that in the past was categorized in the idiopathic category, we didn't know why, will eventually end up being proven to be early signs of neurodegenerative disease.

[Dr. Gopi Shah]
Wow. Do you talk to your patients about that as a potential? How does that conversation go?

[Dr. Zara Patel]
Yes, I do. It is definitely a delicate conversation. You certainly don't want to scare people or make them worry unnecessarily. The way that I frame it, and I really tend to bring this up in people who are already 65 and older, or if they have a direct family member like their mother or father, a neurodegenerative disease, then I frame it and I go through all the different possible things that are contributing to their smell loss or smell dysfunction. Often when I see patients, there's more than just one factor that could potentially be contributing, either causing the smell loss or preventing people from being able to bounce back from a smell loss from something else like COVID-19.

I talk about all the different factors that are in their history that could be contributing. Then I do mention at the end, just to give you the information that we do know now that smell loss can be one of the earliest signs of neurodegenerative disease. Most of the time I say this, after having this conversation with you, I feel like you are currently mentally completely intact and have high cognitive function, and so I wouldn't worry about that currently, but if you start noticing any difference in your memory, any difference in your motor movement ability, I want you to remember what I've told you about smell loss being an early sign.

I do think it would be a good idea for you to get a baseline cognitive test now, so that if you ever do develop those other symptoms, you have something to compare against. That's how I frame it. Every so often, I will see a patient who I actually do think has cognitive dysfunction during my interview with them. I gently make note of that to them, and I ask them to see one of my neurology colleagues to be further evaluated.

[Dr. Gopi Shah]
That makes sense. Does time play a role for you, like how long they've had difficulties with smell? How does somebody that comes in with three months of decreased smell compared to somebody that comes in with two years, how does that play a role in your initial visit?

[Dr. Zara Patel]
I would love it if everybody came to see me within a week of their smell loss.

[Dr. Gopi Shah]
Setting smell loss.

[Dr. Zara Patel]
Then of course that never happens. Exactly. Unfortunately, first, so many people just think, oh, this is going to come back on its own. It's just a temporary thing, so they themselves often delay seeking care. Then unfortunately, often, especially at the very beginning of the pandemic, but this still happens a lot, when patients go to see their primary care doctor, knowledge about smell loss is not really high within the primary care community still at this point, and so often patients are told, oh, just give it some time, it'll come back. Or, oh, it's just your smell.

It's not your vision or your hearing, at least. No big deal. It's something to just deal with. Of course, we know that, number one, the duration of loss before definitive intervention is highly impactful on how much I can bring someone's smell back. The sooner I see someone after smell loss, the better for them. Two, of course we know this is highly impactful on people's quality of life. It really makes it even harder for people to deal with the issues that they're facing when they are dismissed by a physician or by a provider and made to feel that it's not actually as important or impactful as they initially felt like it was.

Unfortunately, I often am the fifth or sixth provider that patients are seeing about their smell loss, and sometimes the first person that is actually validating how impactful this is to their quality of life. That certainly it can lead to depression and anxiety, and all those problems. The way that I address people, whether it's three months or two years, is really the same as far as validating what they're feeling, taking the same history. Then I do tell patients that prognostic factor. I do tell people that the longer you go, the harder it is for any of these interventions that I'm about to tell you about to actually have impact.

I still will tell them about everything. I don't think that anyone is hopeless. I've been really surprised how long people can go with not having smelled anything and that after they start doing the types of things that we'll talk about soon, they can start getting some smell back. Even 5 years out, even I've been surprised 10 years out. I would never tell a patient that it's hopeless and that they're not going to get their smell back.

There are certainly some people that it's much less likely. People who have had some head trauma and had scar formation. Then, whatever we do to try to stimulate this regenerative capacity of the smell system, there's this big scar that the nerves are not able to get through to actually synapse in the right place. Certainly some people have a decreased prognosis compared to other people, but many of the things that we do to bring smell back are so simple and easy, and low side effect and risk profile that I do think it's really worth trying in everybody.

[Dr. Gopi Shah]
Tell me about age in terms of the youngest, and mine was all peds, so most of my kids were adolescents. Were you seeing any really young kids, and how did that go? Even with your adolescents, with the older population, we start thinking of maybe especially the neurodegenerative things to kind of keep in mind or metabolic, endocrine. In the younger kids, you know, I'm thinking trauma, I'm thinking infection, polyps, or maybe I'll ask about development for a girl specific to menarche, things like that. In your head, how do you think about that group?

[Dr. Zara Patel]
You're exactly right that there's slightly different questions that you ask. You certainly want to delineate. Is this a change or have they really never had smell? Because kids won't always really voice that to their parents or to other people. Sometimes kids aren't even really aware.

[Dr. Gopi Shah]
Because they never smelled before.

[Dr. Zara Patel]
Exactly. Until a very specific moment in life where someone specifically asks them what they think about a smell or why aren't they reacting to a smell. Then definitely if you try to tease out and they really can't remember ever having had a sense of smell, then doing things like genetic testing and making sure that you look for genetic congenital smell loss, and then the types of syndromes like Kallmann syndrome that can lead to things like that is important.

Then the other thing to consider in kids is just that they're lucky and that it's happening when their body is at its full regenerative capacity. If you're going to have a hit to the smell system, better to have it when you're young because you are much, much more likely to be able to spontaneously recover. Certainly, doing things like olfactory training and the easy things to spur that regenerative capacity allows kids to bounce back just much faster and more completely than in someone who is in their later stages of life.

(4) Medications Associated with Smell Loss

[Dr. Gopi Shah]
Tell me about the high red flag medications. Are there medications that you're always looking for on their list of medications? Then are there any nasal sprays that you found patients use that are at high risk for causing smell loss too?

[Dr. Zara Patel]
As far as the medication list, I would say that the two big things are any chemotherapeutic type of regimen. ENTs are, I think, very familiar with how chemotherapeutic agents can affect hearing, but smell is just like that. These are tiny, sensitive little neurons at the top of the nose, and they are sensitive to any of those agents that affect cell turnover and regeneration. Any chemotherapeutic agent, whether it's full-on traditional like cisplatin, or even the newer agents that a lot of people are on for breast cancer, things like that, those are all pretty impactful on smell.

Then of course, any neurologic type of medication, so antidepressants, anti-anxiety medications, seizure medications, all of those types of medications certainly can impact smell. It doesn't mean that everyone who's on it is going to have smell loss, but definitely anything that affects nerve transmission will affect smell potentially. As far as sprays, the classic example that thankfully is not sold over the counter anymore was Zicam nasal spray. This intranasal zinc spray unfortunately could just be one spray once in their life, causing an irreversible loss of smell. Such a tragic story, honestly, when you see patients who have had that happen.

Every so often, I will still get a patient who lives in a very rural area, they went to a store that hasn't changed what's on their shelves for 20, 30 years, and they somehow got their hands on that Zicam zinc nasal spray, and they still now can cause that dysfunction, and so the more public awareness that we can get out there that that's not okay. Really, honestly, I tell people that there are a lot of other over-the-counter nasal sprays that are not great for your nose, and that unless you've spoken with your physician, your ENT doctor, to really not put random things in the nose, you never know, especially in things that have not been studied, exactly how they might be impacting your olfactory system.

Out here in California, I have a lot of people who are just making some nasal spray on their own. They're taking some herbs or crushing up something they found in a naturopathic pharmacy and putting that in a liquid, and spraying it in their nose because they heard that that's going to help them prevent colds or get over a sinusitis infection. There's so many things that could cause damage to the system. It's actually a very sensitive system in some ways, even though it applies to the environment your whole life. I would say there's a lot of different things that can make it go bad if you put it in your nose.

[Dr. Gopi Shah]
There's people I've heard of like Vicks Vapor Rub, getting it, really putting it in their nose, whether applying or using it as a steamer, or Tiger Balm even. That seems strong.

[Dr. Zara Patel]
Specifically for those types of things like Vicks and Tiger Balm, you what I tell people is that really what they're doing is they're stimulating their trigeminal system. Menthol, although the olfactory system picks up on the menthol smell, really what you're stimulating is a trigeminal nerve. That's why those types of things make people feel like they can breathe better because it's not actually changing the odometer of your airway at all.

It's just stimulating the same receptors that sense airflow, and so you feel like you're breathing better. If you keep putting something on those receptors over and over to stimulate them, you are likely desensitizing those receptors over time, and I suspect over a long period of time, you may not feel like you're breathing as well if you've used that over and over. That's really the reason why I tell people to not put those menthol things directly in their nose.

(5) Physical Examination of the Patient with Olfactory Dysfunction

[Dr. Gopi Shah]
As we get to like the physical exam portion, I assume everybody would get a scope because we are looking for things like polyps, CRS, tumors, to see what the nasal cavity looks like. Do you decongest your patients? Do you not decongest? Do you scope twice? Tell me about that detail.

[Dr. Zara Patel]
In all my patients, whether they're just nasal, sinus, skull base, or olfactory patients, I basically use my endoscope to just look at the very front of their nose, see what their baseline is before any decongestion. Then I give them the spray that numbs them up and decongest them. Then I look further in with that endoscope, and I'm looking at everything. I'm looking at the turbinates down low. I'm looking all the way back to the nasopharynx. I'm looking at all the sinus drainage pathways. Specifically in our olfactory patients, I take a really good look at the olfactory cleft.

A lot of patients that I see in my clinic have already seen other ENTs and been told that they have a totally normal exam, but when you take some time to really examine the olfactory cleft, you can find things that other people haven't necessarily picked up on. Sometimes really the main thing that you see is just a lot of inflammation. You see swelling within the olfactory cleft, effacement of the cleft. If your olfactory cleft is closed off, you're not going to be able to smell very well. Just doing a high-volume stearate irrigation and making sure people are using the right head position to actually get that irrigation to the olfactory cleft can make a huge difference in the amount that people can smell.

Also, sometimes, especially actually after COVID-19, but in certain other circumstances also of chronic inflammation, you actually see scarring within the olfactory cleft. Sometimes people think that you can only see scarring from trauma or prior surgery, but really just chronic inflammation can create scar. It's not uncommon that I see scar bands at the top or back of the olfactory cleft just from chronic inflammation. That really does affect prognosis. When you no longer have the normal anatomy and you no longer are able to get odorants to the olfactory nerves in a normal fashion, then all these other things that we do are probably going to be less effective for those patients.

[Dr. Gopi Shah]
How do you maximize your view of the olfactory cleft? Are you using a 30-degree, a skinny scope, a flex? Then do you ever have to stick pledgets medial to the middle turbinate, and high? How do you get a good view of it?

[Dr. Zara Patel]
In just a regular screening scope exam, I don't use pledgets. I just use the spray. I do use, for all my patients, for all of our visits, we use a pediatric 30-degree nasal endoscope. That gives a really good view. You just gently maneuver that into position. You can really see all the way from the top and run down and look from the bottom. Just use your angle and move your angle around so that you're really getting a good view. You can get a really nice view that way. For patients that I'm doing injections in the olfactory cleft, like PRP injections that maybe we'll talk about later, then I do use pledgets to actually really numb up and decongest the cleft so that I have really good access to inject there.

(6) Questionnaires to Assess Olfactory Dysfunction

[Dr. Gopi Shah]
Then tell me: do you use questionnaires? Is there a small questionnaire that you're routinely using? Which small tests do you use, and why you're using? I guess to get an idea of degree, but exactly why and then how, and over time.

[Dr. Zara Patel]
As far as questionnaires, I use right now just our typical nasal sinus questionnaire and the SNOT-22, but I am going to incorporate soon, I'm getting the logistics of this ready, to start doing an actual olfactory questionnaire. The QOD is a very common one that I'll be incorporating for that specific patient population in clinic. It's been more of a logistic issue why I haven't done that up to this point with our clinic, but I'm hopefully going to be able to start doing that now. Then as far as the smell test, the smell test that I use in clinic as just a screening test to kind of just get one data point as to where people are is the UPSIT, that University of Pennsylvania smell identification test.

Like I mentioned before, it really is just one data point. We know that it doesn't tell us everything about a patient's smelling ability. I tell that to patients, because sometimes they'll be surprised at what their score was. Either they'll score better than they thought they would, or a lot lower than they thought they would. We know that patients' subjective feeling of how they smell does not correlate very well with these tests that we do.

Because that's just one data point, once I am actually enrolling patients in a study like a randomized controlled trial, which I often run on my smell patients, then I switch to a different, more granular type of test like the Sniffin’ Sticks so that I can get more data about every part of their smell, like the threshold, the identification, and discrimination. It does take a lot longer to do that test, which is why I don't use it as a screening test in my clinic because I just simply do not have the time. Even now my smell clinic is booked out until, I think, February or something like that.

I'm trying to get as many patients into my smell clinic as possible, and it just is not feasible to do a very long test. Even the UPSIT, you'll see some patients just take forever because they are really trying their best to smell it, scratch it and smell it, and then smell it again. They are really trying their hardest, and so it can take a really long time, even if they can't smell at all, to get the results of the test.

[Dr. Gopi Shah]
The UPSIT, there's a short one, like a 13-item. Then there's one that's, I guess, the standard one that's, I don't remember, maybe 30, 33 questions or something. Which one do you use?

[Dr. Zara Patel]
The BSIT, the Brief Smell Identification Test, has 12 items, and the full UPSIT has 40 items. I use the full UPSIT because we know that although the BSIT can just give us a yes or no answer, like can they smell or not smell? It does not give us enough data to track a person's smelling progress over time. You need the full 40 to do that. If you just want to make sure that they can smell or not smell, maybe the BSIT's fine. I would say that's not really helpful in a smell loss patient population.

I already know that they think they can't smell, and so a BSIT is not really helpful. Now, some people use a BSIT in studies where they're doing some intervention and they just want to get some smell signal on there. Again, I think that it's actually not very informative as to exactly how well people can smell. It's just a yes or no. The full UPSIT is the one I use even as just my most basic screening test.

[Dr. Gopi Shah]
I'm glad you said that because these tests, you have to order them. They're not cheap. The pencils or whatever, things expire, and so it's important to make sure to have the right one. In terms of the 40-question UPSIT, you know, once my patients would do it, I'd look on the graph or the chart that would give me an idea if it was mild, moderate, severe, or completely anosmic. I would use it as a way to help me give them some maybe prognostic type of, well, look, it's just mild, so I think we have a better chance than if it was completely gone. How do you use it when you talk to your patients at that initial visit?

[Dr. Zara Patel]
It really depends on the exact patient, how I use it. Some people are really encouraged when they see that they didn't score that bad actually on the UPSIT, even though they felt like they couldn't smell almost at all. Then I say, it means we've got something to work with here. We definitely have small nerves and we can try to regenerate more. I definitely tell them, that's a good prognostic sign. Alternatively, when people score really poorly, sometimes that can actually be validating where they say, I just can't smell anything. You say, that's what it looks like on your test.

They say, good, I feel like no one's really been able to confirm that, but it validates how I'm feeling. I use it in different ways, depending on what the patient really seems like they need to hear and what's true about what I can tell them from that smell test. So much of treating smell loss and smell distortion patients is about validation and about just listening and confirming to them that what's going on is real and impactful, and often giving hope that there is maybe something that can be done. Then when they hear all the different things that could potentially help, even just a little, that's really wonderful news to them.

All the things that we have, there's no magic wand right now that is going to bring back someone's smell, except for, I would say, separate from our chronic sinusitis patients, we can really bring back smell quite well in those people. Everyone else, there's no magic wand right now. All of these things that we do have incremental improvements, but even that is so impactful for some patients. Even just being able to smell one more thing than they have the last three years can be a life-changing event for some of these patients. Just because they are not a magic wand doesn't mean that they aren't impactful.

[Dr. Gopi Shah]
Then for the patients that you do follow up, do you give them the smell test every time to see if there's change in it?

[Dr. Zara Patel]
Yes. I separate these patients. Again, the chronic sinusitis or nasal sinus inflammation patients away from all the other smell loss patients, because I tend to see those sinus and nasal inflammatory patients more frequently in shorter follow-up than I would a smell loss from, for example, COVID-19. Let's talk just about the other smell loss patients. I typically tell them, you don't have to follow up, but if you'd like to, you can come back in six months if you'd like to take that test again, and see how you do on it, or if you just want to see if there's anything new or have me look inside your nose again, or anything.

Six months is really the earliest, I think, that it's reasonable to, number one, expect a significant difference in their smelling ability, and number two, expect to see a change on that test. Because when you think about the natural regenerative process of the olfactory system, we have millions of neurons in the olfactory epithelium. Each neuron is turning over at every about three to four months. That doesn't all happen at the same time. They're all happening at different times.

You really want to cover all that time for all of those neurons to potentially turn over once or twice and be supporting that natural regenerative process, be creating the right non-inflammatory environment, be giving them everything they can to help that along, and give it enough time so that you really see the impact of all of those neurons having turned over, hopefully being supported by all the things you're doing. Then probably you're going to see a difference.

Patients sometimes want to come back in a month or two months. I tell them, not enough neurons will have turned over by then for us to see any difference, so just have a little patience. You can actually use that also as motivation for people who get frustrated by doing things like olfactory training and not seeing a difference in the first month and then some people will just give up. I tell them, this whole story, and that really motivates them to keep at it for the full six months. That's really when you see like a big difference when people do this.

(7) Workup of the Patient with Olfactory Dysfunction

[Dr. Gopi Shah]
I can imagine how much of a difference it makes when you actually sit down and explain the pathophys even on the micro level, Patients want to know and for any of us, right? When we ourselves are patients about anything, regardless if we have a medical background or not, it's nice to understand what's going on and why, and how the decision-making is taking place. Tell me about workup. When are labs, and what labs are indicated? When do you consider imaging? The two big ones, CT and MRI.

[Dr. Zara Patel]
I almost never send labs. There aren't really any particular labs for most patients. Now, certainly if I get a history, very specific, like, oh, this patient sounds like they definitely have hypothyroidism, then certainly I'll send some thyroid labs. As far as imaging goes, if I have a history of people with chronic sinusitis or any sinus or nasal inflammatory issue, and they don't come in with imaging, then a CT, a CT sinus is typically a really good one to get because often that is the reason why they're having smell problem. That sometimes can correlate very well with your endoscopy, but sometimes, as you know, in our sinus patients, it's all in the sinus.

If you haven't had surgery, you don't actually see anything emanating out of the sinus outflow paths, and so the CT can be really helpful in those cases. If patients do not have any sinus or nasal history like that and they don't actually have any other good history, so there's no viral events, there's no other metabolic or endocrine, or medication, or work-related exposure, or anything else that I can pick up on that is a reason, truly an idiopathic patient, like I have no idea why this happened, then I will order an MRI. Because again, so often, you have the answer right there in your history.

For a COVID-19 smell loss patient, I don't need imaging. I know exactly why they have their smell loss and I don't need to get some MRI to show me that. If I really have no other idea, that's when you start thinking about, could there be a tumor there that I don't know about? Or could there be some other issue going on, especially in elderly patients? Sometimes you'll see extreme-- we often get MRIs in our patients and see in the report small vessel ischemic change, normal for a given age. That's a very common thing we see in our patients as they get older.

Sometimes you get much more small vessel ischemic change in and around the olfactory bulb and olfactory sulcus. That can give you an indication, maybe this patient's longstanding hypertension is actually the reason why these tiny little nerves don't work anymore. They're just not getting enough blood flow because of those tiny vessels not working. Or similarly, patients with diabetes, sometimes you can see that small vessel ischemic change in that area. That's something else you can try to pick up on an MRI. Then the last reason why sometimes I'll get MRI is for a prognostic factor.

Say, for example, there's a patient with COVID-19. I don't need imaging to tell me why they have this smell loss, but three years in, they really want to know what's my prognosis here. You can talk through all the different things that can impact their smell, like their age, their ration loss, things like that. What we can do is actually show you the volume of the olfactory bulb and the depth of the olfactory sulcus. Those can be prognostic factors as to how much smell is already gone, how much of that nerve tissue has regressed. Are we going to be able to get it back? That's another reason to order imaging sometimes.

[Dr. Gopi Shah]
That's a great point. Question. If you have a history of COVID-19 or any URI, is there an amount of minimum time you should wait before you get an MRI for persistent loss of smell? If you're looking at volume of the olfactory bulb, are we going to see a difference in two years or should it be like, we should really wait if this is still going on five years out, otherwise we're not going to see anything right now? Is there a time where it's just too early to look for that?

[Dr. Zara Patel]
I would say two years, you probably would see something. As far as too early, it's really more a question of what is your intention with the MRI? In the first six months to a year, I think people still have quite a good chance of recovery. Maybe you don't really need that MRI for prognostication, and so there's no real point in doing it then. After about a year, again, it really depends, and it's not every patient that I would get this on just for prognosis.

It's really only if the patient really desires some other objective thing other than what you've already told them that you can look at to talk about prognosis. That's when I might consider ordering an MRI for those reasons. Maybe just after a year or so might be an appropriate time if you really feel like you're pushed to do that.

[Dr. Gopi Shah]
I feel like with the adolescents, with moms and families and the kids, I do feel pushed because they're worried, worried parents. I get it. Their kids are young and this is their first health issue potentially. Sometimes, it gets so bad where I've seen them lose weight, can't do their sports. Because of this, like you said, it's the impact on the quality of life and their overall well-being can be so much that sometimes I feel like, what else can I do, whether it's just provide more information because there is no magic button. I'm glad that you mentioned that. Let's talk about some of the medical management. You've mentioned steroid rinses. Are we just talking about the Pulmicort ampoules and the rinse bottle? Is it the 0.5, the 0.25 milligrams per ml? What are we using?

[Dr. Zara Patel]
I actually ran a randomized control trial before the pandemic ever happened, adding budesonide Pulmicort Respules to nasal saline irrigation and seeing if doing that increased the efficacy of just olfactory training. Our placebo arm was just saline irrigation with olfactory training and the intervention was budesonide irrigation with olfactory training. Budesonide significantly increased the efficacy of olfactory training, significantly increased the percentage of patients who had improvement in their smell.

That was in patients who really had no sign of any sinus or nasal inflammation. I did all sorts of things to confirm that, not just nasal endoscopy, but actually rhinomanometry and things like that to just confirm there's no other reason why the budesonide was working. It's really microscopic-level inflammation that you are improving in these patients. It's the 0.5 milligrams per 2 ml Respule twice a day. That's the dosing that I used in that trial. That's the dosing I recommend to my patients.

It makes sense. There's a recent study that was published, my prior fellow, Carol Yan, who's now at UCSD, who's also doing research in smell, she and Brad Goldstein, who's at Duke now, and their colleagues looked at specifically COVID-19 olfactory epithelium and found that even in patients who didn't see any sign on endoscopy of inflammation, they did have chronic inflammatory compounds, molecule cytokines in that epithelium.

It does make sense that using a high volume steroid irrigation and all these other things that we know can impact the inflammatory environment in these patients, things like omega-3, things like PRP, can help these people because of that. Yes, the high-volume steroid irrigation is kind of a mainstay, along with olfactory training that I offer all of these patients.

[Dr. Gopi Shah]
Okay. Most of them will have tried the Flonase and stuff, but if their Flonase is naive somehow, should I start with Flonase or should I just jump to the rinses because we know it works, it's helpful?

[Dr. Zara Patel]
Yes.

[Dr. Gopi Shah]
Okay.

[Dr. Zara Patel]
I actually did a systematic review, again, prior to the pandemic, because so many people use Flonase, not just ENTs, but primary care doctors, everyone reaches for Flonase or some steroid spray when people come in with smell loss. Really for patients, again, we're talking not chronic sinusitis or allergy patients, but just smell loss patients, the nasal spray is not reaching the olfactory cleft.

There have been good high-level randomized control trials proving that steroid nasal spray does not help these patients. You are just wasting that precious time before definitive intervention if you're using nasal spray. You should not put these people on steroid nasal spray. That's not going to help them.

Interestingly, in that same systematic review, I looked at oral steroids, systemic steroid therapy because that's a very common one also that people are put on. there's actually not great evidence to show that oral steroids are actually helpful. Again, this is a non-sinus, non-allergy patient population of smell loss. Again, if I saw someone within a week, I'd try a steroid taper, but if not, then it's really getting the topical steroid right to that olfactory cleft. That is really what's going to give you the highest dose with the least systemic absorption. That's really your sweet spot. We have a randomized control trial showing that it works. Steroid irrigations, they're the way to go.

[Dr. Gopi Shah]
I'm glad you said that. Do you ever get insurance pushback for prescribing Pulmicort rinses? If so, is it just a quick peer-to-peer and you're good? Because sometimes I can't always get it.

[Dr. Zara Patel]
It's never a quick peer-to-peer. I wish any of us had that in our lives. Certainly, insurance coverage is always a challenge with budesonide or any high-dose steroid volume irrigation, whether it's in our sinus patients or our smell loss patients. Some insurances will just only cover it for asthma and that's it. I will try to get insurance coverage. Sometimes you can get it authorized with a peer-to-peer, but if they're just simply saying, "No, we're just not going to cover it for any other diagnosis," then I, like many others, use a compounding pharmacy.

There are many compounding pharmacies that are able to put this together for our patients, send it directly to their home address, and they charge much less than a typical pharmacy would. In our particular case here at Stanford, if the insurance is not covering it at the pharmacies around here, it could cost patients around $300 a month. I said, "If that's the case, don't just pay it. Let me know and we'll send it to this other area." At the compounding pharmacies we use, it's more like $40 to $50 a month, depending on how many months the patients get, things like that. Still expensive, but not nearly as expensive.

(8) Smell Retraining: An Underutilized Tool for Smell Loss

[Dr. Gopi Shah]
Tell me about smell retraining, how you prescribe it, if you will, meaning are there four standard smells? Many people will show me Amazon's got all these smell retraining sticks and kits, you can get 10, you can get 5. How often do they have to change the smells out? Do they change the smells out? Tell me the instructions that you have. What are your instructions? That's what we want to know. What are Zara Patel's instructions on smell retraining?

[Dr. Zara Patel]
There's a lot of people out there trying to make money on these patients. The first thing that I will tell you is that I ran a randomized control trial, the very first randomized control trial in olfactory training in the United States, proving that it does not matter the brand. It does not matter the concentration of the odorant. It does not matter the purity of the odorant. It just matters if the essential oil has a smell, a smell that the patient will recognize as what that smell is supposed to smell like.

All these fancy kits out there, all these really expensive, like, "Oh, this is organic, and this is the most pure," your patients do not need to be spending all their entire paycheck on olfactory training. It should be pennies on the dollar that it costs them to get these smells in just a very simple essential oil and do this on their own.

The instructions are, yes, we start with four particular odors. They are rose, lemon, eucalyptus, and clove. The reason we start with those four odors is that, number one, they've been studied the most, so we know that those are the ones that can have an impact. Number two, they're in different categories of odorants, so they will be stimulating different types of olfactory receptor neurons inside the epithelium. You don't want people to just train on all fruity or all floral. They'll miss stimulating a lot of those other neurons in there if they do that.

We start with those four. I tell people, you just hold it under your nose. You breathe in and out. You don't have to do a big sniff, and what you should do, what's the most important thing to do, is really focus their memory on what that smell is supposed to smell like to them. Your olfactory cortex is right next to your memory center in the brain, and it's integrally connected, and we are actually utilizing that, reinforcing that synaptic connectivity by doing this type of training.

There's functional MRI evidence showing that before you do olfactory training, if you give someone with smell loss an odor, there's just this kind of disparate chaotic array of connectivity lighting up in the brain. If you do training and then again present that odor and functional MR, just the olfactory cortex lights up right where it's supposed to, and that really shows that you are changing synaptic connectivity by doing this. It's not just some silly woo-woo aromatherapy type thing that's happening.

We are actually exercising the smell system, and I explain it to patients, and I think this actually resonates very well with people. They can understand this intuitively much better when you say this. If you had a stroke and you lost function of your arm, you would go to physical therapy and exercise that arm until you got that function back. You're doing the same exact thing with your smell system when you do olfactory training, so people really understand that. They say, "Oh, yes, that makes a lot of sense," then they're motivated to actually do it. As far as the odors, you start with those four, and then yes, at one month and then again at three months, I have people switch up these odors.

If the listeners want to, I think you just Google or search on the internet for the JAMA Otolaryngology patient education page I wrote about olfactory training, and it gives some examples of other combinations of odors that you can switch up to at one in three months. I just have that JAMA education page printed out in my office and I just hand that to patients. It goes over the entire thing of olfactory training and it shows those other odors that you can start with and then switch to. So it really gives all the information to them right there.

[Dr. Gopi Shah]
Yes, we'll try to put that in the show notes to the link to that for patients as well as our providers to have that information that's right there for the patients will be helpful. If I'm smelling rose, I'm going to take a smell and I'm going to think about how rose used to smell. That's going to take a second. Then I'm going to go to lemon and I'm going to think about how lemon used to smell and I'm going to do that, and I'm going to do it twice a day.

[Dr. Zara Patel]
Yes.

[Dr. Gopi Shah]
Okay, all right, all right. That's good to know.

[Dr. Zara Patel]
I tell people it takes a really long time to regenerate nerve, so you're going to do this for six months.

[Dr. Gopi Shah]
Then they'll just rotate it. After the three months then they're going to go back to those top four. Okay, got it.

[Dr. Zara Patel]
Yes, or they can add new ones. I tell people like the more variety, the better. If there's a particular smell you really want to smell again, you can add that. They can do anything like that.

(9) Nutritional Supplements & Platelet-Rich Plasma for Smell Loss

[Dr. Gopi Shah]
Tell me a little bit, are there vitamins that help, or people taking B vitamins or anything like that to help? What are your thoughts on that?

[Dr. Zara Patel]
There are certainly a lot of things that people are taking, but not a lot of evidence for most of the things that people are taking. The top things that people ask me about are vitamin A, alpha-lipoic acid, vitamin B, zinc.

Just to give a kind of brief overview of those, there is actually good evidence that taking vitamin A orally does not have an impact on smell. There's no reason for people to take that. There may be benefit in intranasal application of vitamin A, but the data is not very strong. There's no placebo-controlled trial on that. Also, the formulation to get vitamin A into the nose that's not irritating and not damaging to mucociliary clearance, for example, we don't really have here in the US.

There's some data from other countries where they have different formulations, but I have not utilized that in my patients because we just don't have the right formulation here. Perhaps in the future, we will and maybe we'll have better data to support its use, but right now I don't have people use vitamin A and certainly not by mouth, that's not helpful.

As far as vitamin B goes, really the only data about vitamin B is when people actually have tongue issues, actual taste, like sweet, salty, bitter, umami, those things are damaged or gone. Sometimes there can be a vitamin B deficiency leading to that type of thing. Sometimes that can be helpful for specifically tongue-related taste issues, but no data really.

The one study that is out there showing oral zinc is helpful is in post-traumatic anosmia. In those patients, sometimes I'll say, "Yes, that's fine, you can try that," but in other patients, I don't really recommend it. I think maybe perhaps if we had a much better, well-done randomized control trial in the future, perhaps we might find some benefit, but right now there's conflicting data, and some suggesting it may be harmful, so I do not have people on zinc.

As far as alpha-lipoic acid, it's another one that has some interesting data and it does not have a randomized control trial that's well-controlled as far as timing of enrollments and controlling for spontaneous recovery and those types of things. Something that's an option for patients, but not something that I routinely prescribe just because of the quality of the studies and the methodologies.

Finally, omega-3. I actually ran a randomized control trial on a post-endoscopic skull-based surgery patient population looking at smell loss after that. That was 7 or 10 years ago that I was doing that, and there was a precipitous drop in the number of patients that had long-term smell loss after that surgery. These were patients who we were preserving the olfactory system very carefully, but likely just because of all of the post-operative inflammation, we're having smell issues.

Omega-3, a high dose omega-3, so 1,000 milligrams twice a day was highly impactful and helpful for those patients. My same protocol was just replicated in a study by Thomas Hummel in Germany in COVID-19 patients. It was also found to be helpful in that patient population. so high dose omega-3 is something that I do recommend for all my patients as well. The only people I wouldn't recommend it for are people who have an underlying bleeding disorder or are on other blood-thinning medications because it can thin your blood, especially at that dose.

[Dr. Gopi Shah]
That's very helpful. That's a little extra tool in the armamentarium. What about, I saw in the guidelines, sodium citrate, and intranasal insulin? Tell me about those. Do you use those, not use those?

[Dr. Zara Patel]
Yes. In the guidelines, those were options. I think we don't have very good data. Sodium citrate in particular, there have been well-done randomized control trials showing it does not help people regain smell in the long-term. However, there is interesting data showing that it can cause a temporary shift in threshold. So, I'm just starting to experiment with this with my own patients because perhaps even if you just had a 40-minute window where you had improved threshold of smell, maybe that would allow people to enjoy their food.

Maybe if you just spray this right before you eat a meal and it improves your threshold for 40 minutes, that's certainly not going to change things long-term, but maybe that will have a major impact on quality of life. I'm starting to look into that to see if I can replicate those findings in my own patient population. I'll keep you guys posted on that.

[Dr. Gopi Shah]
It just makes me think of chronic vasomotor rhinitis with eating, do a little ipratropium 20 minutes before. If there's something like that, you're right, it would make a difference.

[Dr. Zara Patel]
Yes. Then as far as intranasal insulin, I do not prescribe that. There's such conflicting data. Every other year, there's a new study showing it doesn't work or it does work. In patients with normal smell, it actually shows a decrease in smelling ability if you use it. I don't think there's been a sort of gold standard randomized controlled trial convincing me to use that. I think that there's potential significant downsides to using a medication like that in the nose. So, I am not prescribing that right now, but I do hope that people do continue to study it.

[Dr. Gopi Shah]
All right. Let's get into the platelet-rich plasma. Just for our audience, I had to get the PRP initials correct. I think I called it protein-rich platelets, which doesn't even make sense. Just for anybody who was with me on the initials, platelet-rich plasma. Tell us a little bit about PRP.

[Dr. Zara Patel]
I first became interested in PRP, again, prior to the pandemic, I was starting to read a lot in the other medical fields, other literature about how it was being used. People are most familiar with it from orthopedic surgery where people will use PRP injections into knee joints and things like that to help with mild arthritis for cartilage regeneration. People use it in aesthetics, they get facials with the PRP injected into their face, like the vampire facial is what it's called. People inject into the scalp to regrow the hair.

PRP is really used all over the body. It's because all tissue in our body does use growth factors. PRP is when you draw someone's blood, you put it in a centrifuge, you spin it down, and all of the red blood cells, white blood cells, all that part of the blood goes off. What you're left with is this very platelet-rich and growth factor-rich portion of the plasma. Growth factors are used in the tissues all over our body to help regenerate.

The idea is really just that you are concentrating that and putting it right into the area that you need it most. Some people will kind of be suspicious of something that seems to be helpful no matter where you use it, no matter what you use it for. I was also kind of suspicious when I first started reading about it. It seemed like almost too good to be true or kind of woo-woo-type stuff, something that you could easily just charge for, and it might not have a lot of good data.

I was actually very cautious when I first started looking into it. I first ran a pilot study just to see, is this safe? Is this feasible for me to numb people up enough to inject something into their olfactory clefts and them not be bothered or uncomfortable? I did show that in my pilot study, again, prior to the pandemic. I did see a significant enough change in threshold in those patients that I thought, "Oh, maybe this is actually worthwhile studying in a true randomized control trial fashion."

Then the pandemic hit. I pivoted and made it specifically for COVID-19 smell loss. I ran this randomized control trial where I either injected patients with PRP in their olfactory cleft, or I did a sham placebo injection with saline. In that study, basically, the results were that the PRP arm had a greater than 12 times odds of more likely able to improve smell versus the placebo arm.

It didn't help everybody. Again, it wasn't some magic thing where people the next day said, "Oh, I smell normally again." These were incremental changes, different amounts in everybody, but it was a significant improvement. The most important thing is really that the improvement was a change in MCID, so minimally clinically important difference. Not just, "Oh, yeah, some numbers moved," but the amount of numbers that moved was the MCID for that particular test, the Simmons-Dix test that I was using.

[Dr. Gopi Shah]
What makes somebody a candidate, and when do you start considering?

[Dr. Zara Patel]
I would say everyone's a candidate at this point. I'll harken back to what I said multiple times, that the duration of loss before definitive intervention is one of the major prognostic factors in how much we can bring back. Certainly, in a trial setting, in that randomized control trial, I did not enroll anyone before six months because I didn't want spontaneous recovery to confound my results of my intervention, but off-study, of course, as soon as you can get patients some intervention that's going to possibly help them, the sooner the better.

In the trial, I also had people already try and fail to improve on things like olfactory training and budesonide irrigations because again, when I do a study, I want to make sure I'm actually significantly contributing to our literature of what more, what is going to help people even more than what we've already showed before. I don't want to just show some equivalence to things that we're already doing that are just a little bit better here and there.

These were people who improved, people who had already failed olfactory training and budesonide irrigation, but again, now that we're off-study, if I see a patient, I tell them about everything, and I would want them to do everything as soon as possible right away. Why hold something back when we know that time is brain, time is nerve? The longer you go, the less likely you are able to get that back.

[Dr. Gopi Shah]
What size needle, what size syringe, and how much do you put in?

[Dr. Zara Patel]
In this study, it was 1 CC on either side. The easiest way to inject that is with a 1.5-inch 25 gauge needle on a 3 CC syringe. I would say at this point, when you actually draw the blood and get PRP, there's a variable amount that you can actually get when you spin it down the centrifuge. I just have my nurses separate whatever I get into the two syringes. Sometimes it's 1 CC, sometimes it's more like 1.5 CC, sometimes it's almost 2 CC. I'm going to give that patient as much as I get out of them, I'm not going to hold back any of their good PRP.

Again, off-study, I'm much more liberal. I'm also much more liberal with the type of patients that I'm offering this to. Now that I know that it helps this COVID-19 patient population, I've opened it up to all etiologies of smell loss. I think one of the interesting things about smell loss is that so many different etiologies have this very common endpoint of inflammation, persistent inflammation, and we know that PRP can help the microenvironment and decrease that inflammation in the microenvironment, and help with nerve regeneration.

Because of that, I'm offering it to post-traumatic people, post-inflammatory people, post-surgical, really anyone. I now have an IRB open to just do an observational longitudinal cohort type of study where I can just see in all these different patients, again, I'm not controlling the timeline of how long they've had a duration of loss before I'm giving it to them, so all those things will be new data points that I can collect and will inform me and hopefully everyone else, once I have enough data to analyze and publish about who exactly we can help with this type of intervention.

[Dr. Gopi Shah]
Does a nurse just draw a tube of blood when there's standard red tubes, or whatever, that's enough, or do they need to at least get 5 CCs?

[Dr. Zara Patel]
There's a specific kit, and I actually don't remember off the top of my head how many CCs is in that first tube, but there's a specific kit that we use that gives you the tube to draw it up in. The kit that we use is from the MSI Corporation and that's the centrifuge that we have. I was lucky that my facial plastics colleague, Dr. Sam Most, already had a centrifuge to create PRP because he was already using it for his aesthetic purposes. I was able to just use that for my pilot study, for this randomized control trial, and now for these patients that are coming to my small clinic.

[Dr. Gopi Shah]
Is it just blood between the thin mucosa and the cribriform, how do you know when you've injected enough?

[Dr. Zara Patel]
It's basically a submucosal injection, and yes, you're aiming to get it as high and deep into the olfactory cleft as you can, to affect all those olfactory neurons as they coalesce into those olfactory fila.

[Dr. Gopi Shah]
Do you have to bend your needle at all? What are some of the tricks that you use?

[Dr. Zara Patel]
I bend the needle just slightly, just the tip of it, maybe 45 degrees to get around any subtle deviation and really get it nicely into the submucosal layer. There are some other people out there that are trying to just put PRP on a sponge and just leave it in the olfactory cleft, but I would say that there is really no data from any other medical field that just placing PRP on the surface of skin or aligning is going to allow it to have effect.

Even when people get facials with PRP, that's with micro-needling to inject it under the surface. Your basal stem cells are not just sitting on the surface of the mucosa, you really need to get it deep to where they're going to be able to utilize this. Of course, everyone can study using PRP in whatever methodology they want, but it makes the most sense to me, logically that you would inject it and that's where you would find benefit.

[Dr. Gopi Shah]
Are there any risks for when you inject the PRP?

[Dr. Zara Patel]
Happily, no. Through the pilot study, and through my randomized control trial, I was certainly looking for any adverse events or any downside. I certainly didn't want to make anyone worse, but happily, no, there has been no downside, no adverse event. Even just the discomfort of injecting, you can take away by just numbing the area really well, topically. First, people might feel a little pinch, a little burn, a little pressure, but that is really the extent of any adverse anything that anyone's told me about. People tolerate this extremely well and the great thing about using your own blood is that you're not going to have any reaction to it.

(10) Equitable Care for Olfactory Dysfunction Patients

[Dr. Gopi Shah]
As we slowly start to wrap up, sorry, I wanted to come back to the equitable care because there is a section at the end in the guidelines about equity and you started out talking about how the testing and how all these factors play a role. How can we be more equitable when we take care of our patients with loss or decreased sense of smell?

[Dr. Zara Patel]
That was really, for me personally, to include in the discussion, inclusion portion of that statement because I see it all the time in my own clinic. The things that you can try to do currently are, have a translator there, for when patients are doing the smell test, someone that can read English, and tell them, that is the very least that we can do right now with the type of smell tests we have, but hopefully, in the not too distant future, I'll have this device ready for people to actually be objective in their testing, and that really wipes clear still many of these barriers and biases that are involved in our current smell testing methods.

I would just say do your best to include people who don't speak the language, specifically asking if people are literate. Patients often will not tell their doctors, whether they are illiterate. It's an embarrassing thing for most people, they don't want to tell someone, especially someone that they respect and hold in a position of authority that they are not able to read, so you might have a patient score miserably on that smell test, just because they didn't want to tell you, they were just guessing and just circling whatever they wanted.

Just trying to be aware of those types of issues when you're doing smell testing, I think, can go a long way, but I do think that until we have a truly objective test, and I'm working as hard as I can with my tiny amount of research time to get it to you guys, but I do think that that really is going to be what allows us to do a much better job at testing in the future.

[Dr. Gopi Shah]
As we wrap up, any final pearls, for our listeners?

[Dr. Zara Patel]
I think that probably the most important thing is something we've already touched on throughout this discussion and that is really keeping in mind that these patients are suffering, even though it may not seem like a big deal to you. When we see patients throughout our clinics, and they're going through what seems like so much more, we see cancer patients who are dying, we see people who are losing half their face from tumor resection, and people who can't hear anything and they're having to go through their lives, of course, those are much easier to relate to and empathize with, but keep in mind that this is highly impactful on patients’ lives.

When you think about how we interact with other human beings has so often, we come together with our friends, our families, our strangers over food and drink and how not being able to enjoy that or sometimes being repulsed by that slowly causes social withdrawal, depression, people having anxiety about their own bodily hygiene and not being sure about how they are in social situations, you can see how all of that will weigh on a person.

Not just that, but people say that there's just a wall of grey that has come over between them and the rest of the world, they feel separate. They feel like there's no joy anymore. Imagine going through the rest of your life like that. It's just so difficult for these people. I would say the last final pearl is just truly open yourself to empathizing with these patients, validate their experience, give them some hope with the things that we've just discussed so that there are interventions that can be helpful, and you'll be their favorite doctor for the rest of their lives if you just do those few things.

Podcast Contributors

Dr. Zara Patel discusses Evaluation & Management of Patients with Olfactory Dysfunction on the BackTable 122 Podcast

Dr. Zara Patel

Dr. Zara Patel is director of endoscopic skull base surgery and a professor of otolaryngology and neurosurgery at Stanford in California.

Dr. Gopi Shah discusses Evaluation & Management of Patients with Olfactory Dysfunction on the BackTable 122 Podcast

Dr. Gopi Shah

Dr. Gopi Shah is a practicing ENT at UT Southwestern Medical Center in Dallas, TX.

Cite This Podcast

BackTable, LLC (Producer). (2023, August 1). Ep. 122 – Evaluation & Management of Patients with Olfactory Dysfunction [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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