Chronic Rhinosinusitis Symptoms: Beyond the Nose

[Dr. Aria Jafari]
All I do is nose and sinus disorders in my clinic and so I see this 20, 30 times a day, it's more than just a stuffy nose. Imagine having a cold that never goes away and that cold slowly invades every corner of your life. I think it's not surprising to me, maybe other folks who are listening in that when we look at quality of life impact and compare it to other common diseases like congestive heart failure, and COPD, and asthma, and Parkinson's disease, CRS is right on par with those. It highlights the fact that this is so, so, so impactful.

Another measure that I think is pretty helpful in terms of understanding what our patients are experiencing relative to other conditions is something called a health utility value. This is something that was introduced to me through Tim Smith and his group and his work in this topic. A health utility value is basically how people rate their own health on a scale of zero to one. One is perfect health. I was just surprised that the score for patients with CRS is 0.65. This is on par with end-stage renal disease on dialysis and Parkinson's disease. Again, I think it just highlights how deeply CRS can reach into every aspect of health. It's not just like a physical condition, but it's also like a mental and an emotional one too.

On top of that, we spend millions and millions of dollars, $10 billion a year managing it, perform half a million surgeries. The patients incur a huge cost in addition to what they experience. Financially, they can experience a loss of about $7,500 a year, higher in patients with nasal polyps. That's the cost of medications, lost work productivity, something called presenteeism, where you're at work, but you're underperforming, anyways, just a huge amount of expenditure and cost to society and patients themselves.

Anyways, yes, when I talk to patients, I always like to ask this question, which is-- Obviously we ask the cardinal symptoms, we ask facial pain and pressure, discolored nasal drainage, nasal obstruction, loss of sense of smell but I always like to ask, how is this condition affecting your life? I think you'd be really surprised to hear what people say. [chuckles] We hear poor sleep, fatigue, that comes up over and over again. We know that patients with CRS are twice as likely to have poor sleep and much more likely to be depressed, but increasingly and increasingly recognized this component called cognitive dysfunction or brain fog. That keeps coming up when I talk to patients and probe that.

I think that's really fascinating and I think requires a lot of our attention because it's really those non-nasal symptoms that drive patients to seek care, number one, but also to make medical decisions, specifically escalating treatment and deciding to undergo endoscopic sinus surgery. There was a really interesting study that showed that patients who have a higher psychological domain within the SNOT 22, which is the sino-nasal outcome test. If we look at the psychological and sleep components of that test, folks who tend to score higher on that dimension of it tend to elect surgery more so than folks who have a lower score on that. Anyways, I found that that's interesting and impactful and important for a lot of reasons, including how we treat patients and the treatments that we offer patients.

[Dr. Ashley Agan]
Do we understand any of the pathophysiology? Is there a pathophysiology or, something now that we're saying, "Hey, there's a link here. Do we know why?"

[Dr. Aria Jafari]
Yes. That's a great question. I think the honest answer is probably we don't fully know yet, but we have some strong theories. I think the two leading ideas are one, could this be like a neurodegenerative process? Are we speeding up Alzheimer's disease or something like that? Is chronic inflammation causing neurodegeneration? Then the second theory or idea is chronic inflammation, triggering neuro-hormonal changes that affect cognition. I would say that the preponderance of evidence actually supports the second theory, which is that there's like a neuro-hormonal change that changed the milieu within the brain and changes the brain functioning based on the inflammatory response that is present in CRS, but also many other conditions.

We did a study and we looked at neurodegenerative markers and spinal fluid in patients who had sinus inflammation and we didn't see any difference. That supports the fact that, it's probably not cell death. It's probably just dysregulation. Clinically, we also see that, like I had mentioned, the patients like will fluctuate in terms of the severity of their cognitive fog. That's usually coincident with the level of inflammation. What is neuroimmune or neuro-hormonal? What does that pathway look like?

Well, I think we all experience it and know it on a personal level. Like if you cut your skin with a paper cut, it feels warm. It could be tender. Those are inflammatory cytokines that rush to the site to help us, to help us heal. In CRS, we know that there are cytokines like IL-1, IL-4, IL-6, tons of cytokines. They feed signals actually back to the brain to regulate the immune process.

Cytokines aren't just these factors that cause physical symptoms like fever and body aches and redness, that kind of thing. They actually are increasingly known to cause behavioral changes and that's called sickness behavior. If you ever had like a bad cold or a flu, you know what that means, right? You don't want to do much. You want to hang out at home, maybe not socialize. It's actually an evolutionary adaptation, we think.

When your body is fighting an infection, it wants to conserve energy. We only have like a certain amount of energy and calories. Your body like turns everything down in terms of the non-essential activities, including higher cognitive processes. If you think about the last time you were sick, you probably felt withdrawn or tired, you had trouble concentrating and maybe felt a little depressed. That's actually your immune system deliberately influencing your brain to prioritize your healing.

It's crazy because I always thought blood-brain barrier in medical school, but turns out there's more of a communication than we think. The immune system communicates with the brain through structures like the choroid plexus. It's like this fluffy material within the ventricles and it regulates what can pass. One of the things that can pass is actually cytokines. When inflammation is prolonged, like it is in sinusitis, but also things like inflammatory bowel disease, or even obstructive sleep apnea, when it becomes this persistent state, the inflammation and the cytokines can actually influence the neural signaling within the brain.

There's even animal studies that back this up. I think, I don't know, this is a funny one, but at a basic level tells me that there's probably some component of our immune system that influence our behavior. Reptiles, there's a study of iguanas, and every time they get sick, they seek out sunlight to raise their body temperature because they're cold-blooded. That's just at a basic level. It's like their behavior is changing to promote their survival. I think for us and states of chronic sinus inflammation, that's also happening, which is crazy.

[Dr. Ashley Agan]
Have we found any links between a patient on biologics? I would imagine if I'm on biologics for nasal polyps, I'm going to feel better because my nose and sinuses have less inflammatory mucosal disease. I can breathe better, but do the biologics affect the cytokines in my brain to then make that neuro-hormonal shift that may have occurred with my brain fog go back to the baseline? Are we seeing that?

[Dr. Aria Jafari]
It's a great question. I think I don't know of any studies that have specifically looked at that. Thanks for the idea, but it would make sense, right? We're directly impacting these signals and so we would expect that the brain fog would improve. I do know that when we look at quality of life overall, the SNOT-22 I know is a commonly used measure of disease control and studies that have looked at biologics, dupilumab and others, obviously patients are improving quite a bit on their SNOT-22. If it's particularly dramatic in certain domains or in cognition, actually, I don't know the answer to that, but it'd be interesting to further dive into it.