Melanie Cole, MS (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we're highlighting a study that discusses the association between sinus surgery and the development of asthma and non-cystic fibrosis bronchiectasis in patients with chronic rhinosinusitis.

Joining me is Dr. Kevin Welch. He's a professor of Otolaryngology Head and Neck Surgery at Northwestern Medicine. Dr. Welch, thank you so much for joining us today. And to start off, before we talk about the study, can you talk about how nasal airway obstruction presents a little bit in clinical practice and why it can become such a persistent issue for patients?

Dr. Kevin Welch: Thank you, Melanie, for having me. I'm happy to be here to talk about these conditions. And these conditions or these problems that patients have create, in some cases, health issues—but in large degrees, tremendous quality-of-life problems for patients.

So, nasal obstruction by itself can present in many ways. Sometimes it can be a slowly progressive process due to allergies or something we call non-allergic rhinitis. It can be due to the development of chronic sinusitis. Some of these patients have polyps and that can become obstructing in nature. Oftentimes nasal obstruction results from nasal trauma or simply just growth and development.

So, nasal obstruction creates a tremendous quality-of-life issue for a lot of patients, and can impact sleep. It can impact their daily functioning, their occupational functioning, and simply self-worth. There are a lot of studies that show that nasal obstruction can lead to depression. So, it has a tremendous impact on patients and their wellbeing.

Melanie Cole, MS: Wow. Well, thank you for explaining that so much. So, what motivated your team? I mean, other than what you just were telling us about quality of life of patients, what motivated your team to investigate whether endoscopic sinus surgery could influence the development of asthma or bronchiectasis in these patients with chronic rhinosinusitis?

Dr. Kevin Welch: Absolutely. Well, Northwestern is a high-volume hospital, and our rhinology clinic within the Department of Otolaryngology sees a very large volume of patients with chronic rhinosinusitis, or I'm just going to say chronic sinusitis. To be short, we work in a very collaborative manner with our colleagues in Allergy and Immunology because chronic sinusitis really is a syndrome or a condition that, in many cases, requires multidisciplinary care, in order to effectively treat the disease and to treat the symptoms that patients have.

So for this study, first of all, I want to give a lot of credit to Dr. Peters, who is a professor of Allergy and Immunology, and to Dr. Walt, and the rest of my colleagues who played a large role in this sort of collaborative effort. But to answer your question specifically, chronic rhinosinusitis, as everybody knows, is inflammation of the sinuses. It's not simply a chronic infection, which is what some of the original thought and teachings were. But it's widespread inflammation within the sinuses, and it comes in two forms or what we call phenotypes. And those are patients who have polyps and those are patients who do not have polyps.

Now, it's been long appreciated and discussed that there seems to be a relationship between chronic sinusitis with nasal polyps and the development of asthma. And in some studies, patients who do not have polyps may have the development of bronchiectasis, which is a chronic inflammatory or infectious condition of the lower airways in the lungs, which result in enlargement of the airways and thickening of the tissue. And it can make it harder for patients to expel mucus and secretions there.

So again, a lot of patients who have polyps will develop asthma and patients who have asthma have a higher likelihood of developing polyps. So, these upper and lower airway conditions affect a significant number of people. And as I mentioned earlier, they cause health-related quality of life decrements, but they increase doctor utilization. They increase antibiotic and steroid usage. They increase procedures and surgery for patients who have these problems.

Now if the hypothesis or the premise is that lower airway problems—such as bronchiectasis and asthma—are possibly tied to upper airway problems, in other words, chronic sinusitis, and if upper airway problems usually come before lower airway problems, what we sought out to investigate is if there's any evidence that more aggressive treatment of chronic sinusitis—meaning surgery—if that could potentially prevent or lower the incidence or delay the onset of asthma or bronchiectasis. So, that was sort of the motivation and, I think, that's what we set out to clarify.

Melanie Cole, MS: That is so interesting and we're certainly going to get to that study in a second. But when you mentioned the multidisciplinary team and patient quality of life—before patients do undergo procedural treatments—many cycle through the medications, as you mentioned, antibiotics. And that can cause its own whole host of other issues and repeated doctor visits. What does the typical treatment pathway look like before you start discussing surgery?

Dr. Kevin Welch: So, patients who have chronic sinusitis almost always have to go through a process of medical treatment. I think the problem with chronic sinusitis is that, in some cases, it is a chronic infection, but in many cases is simply chronic inflammation. So, a lot of patients get antibiotics as an initial treatment. And for some of those patients, it can be effective. For many patients, it is completely ineffective because it's not a chronic infection.

Now, depending on your educational background and what patient needs are, patients can repeatedly go on antibiotics to no effect. And the same can be said for steroids. Sometimes steroids are very helpful for patients with chronic sinusitis. And for some patients, they're not helpful. It is confusing and it is difficult, but we want all patients to receive what we call appropriate medical therapy. So basically, we're saying not everybody needs surgery, and certainly very few people need surgery out of the gate. We really should try to pin down the medical issues and try to treat them medically before moving on to surgery. So, a small percentage will move on to surgery. But in these patients, ideally, we have looked at them more intently and have tried medical treatments to help avoid having to have surgery.

Melanie Cole, MS: Well, thank you for that. So, the study followed patients for up to 17 years. Walk us through the key aspects of the study design and what makes the data set uniquely valuable.

Dr. Kevin Welch: The study, first of all, was retrospective, meaning we looked back into the patient records over time to identify patients who have chronic sinusitis and to see what their outcomes ended up being with respect to asthma and to bronchiectasis. So, there are some problems with doing a retrospective study, and those are that you can't really control the projections of patients or control as much as you want to. But with a larger database, it becomes a little bit more understandable and helpful to analyze.

So, there are a number of notable things with the methodology here that I think are important to clarify. It's important to show that we looked at patients who have chronic sinusitis and we looked at patients who ended up having surgery and those who did not end up having surgery. So, we looked at all patients that we could identify with chronic sinusitis. Importantly, we excluded patients who have cystic fibrosis, which of course is a genetic condition, which can cause sinusitis and bronchiectasis. We also eliminated patients who already had a diagnosis of asthma, because the goal was not to see how many have asthma, but to see how many develop asthma or bronchiectasis.

So if you already had asthma or bronchiectasis, you were excluded from this analysis. We wanted clean patients who have chronic sinusitis and none of these other lower airway conditions. We looked at about 1900 patients in the surgery group and about 14,000 patients who did not have surgery. So right away, that kind of tells you that the vast majority of patients with chronic sinusitis are not getting surgery, and most of them are being managed medically. And that goes to what I said earlier about, you know, the fact that the majority of patients do not need surgery or don't have to have surgery right out of the gate.

Now, obviously, or could be interpreted from the study—rightfully so—is that patients who had sinus surgery had more severe forms of chronic sinusitis. They were more symptomatic. Their nasal endoscopies or their examinations looked worse, their CAT scans looked worse. So if you look at the data, if you had surgery, you were more likely to have polyps. You are more likely to have severe symptoms and worse disease. So, the way we set out to look at these patients, we wanted to exclude things that—you know, our target's asthma and bronchiectasis, we wanted to control for things like age, gender, race, cigarette smoking, or whether they had other autoimmune or inflammatory conditions of the nose, such as allergies. We really wanted to look strictly at chronic sinusitis and rule out other things that could have led to asthma and bronchiectasis.

Melanie Cole, MS: So, discuss a little bit about the results. They showed a reduced likelihood of developing asthma in patients who underwent the sinus surgery, even though those patients had more severe disease at baseline. So, interpret the findings for us a little bit, Dr. Welch, and where do you see this being used in clinical practice, the importance.

Dr. Kevin Welch: Yeah, absolutely. It's an interesting finding, and I think it adds evidence to what many of us have observed over the years And what some other smaller studies and retrospective reviews have started to show, and that's the relationship between chronic sinusitis and asthma. If you look at the inflammatory pathways that precede asthma and the inflammatory pathways thats precede chronic sinusitis, they're both very eosinophilic-driven. They're what we call type 2 inflammatory disorders in most cases. So under the microscope, so to speak, chronic sinusitis and asthma look very similar. The cells look the same. The immune markers look the same. They're very similar conditions. So at a minimum, the study helps support the conclusion that if you can control the source of the inflammation or the original cause of the inflammation, which is chronic sinusitis, then potentially you can delay or prevent the development of a similar lower airway condition.

So, as I mentioned before, it's typical that patients who have more severe chronic sinusitis are the ones that are going to undergo surgery. So if surgery in severe chronic sinusitis can lower the risk of asthma, then it does imply that the more severe your chronic sinusitis is, the more likely you are to develop asthma. So, the results were also interesting when we looked at people who developed or did not develop asthma as well.

So, patients with chronic sinusitis who did not have polyps, they actually had a higher reduction in asthma diagnosis than patients with polyps. So, we've already kind of established a relationship between polyps and asthma. But this study interestingly showed that patients who don't have polyps, their risk of developing asthma was even lower if they had sinus surgery. So, how do we interpret this?

So, it's not to say that patients who have polyps don't benefit from surgery and don't have a reduction in asthma, because they absolutely do. But it's possible that some of these patients who don't have polyps are being caught early in the disease process, and they would have otherwise gone on to develop polyps. It's just a theory. But it makes sense given the results of this study.

So, I think the take-home message for patients and physicians, if you have polyps, there's going to be a high degree of associated asthma or a likelihood of developing asthma. If you don't have polyps, there still is a higher prevalence of developing asthma. And if it gets to the point where you need sinus surgery, it can reduce the likelihood of developing asthma down the road.

Melanie Cole, MS: So, do you have an explanation for the difference compared to the asthma findings as you were just describing them, but the study didn't find that association between sinus surgery and bronchiectasis development. So, explain that difference a little bit for us.

Dr. Kevin Welch: Well, bronchiectasis and asthma, they're both lung disorders, but they're very different in their inflammatory pathways and what effect they can have on a patient. Secondly, bronchiectasis is not nearly as common as asthma. So, the data for this study showed that there were significantly more patients who had asthma in the end than there were patients who had bronchiectasis.

So, you're already starting with a lower number of patients who have bronchiectasis. And when you have lower numbers of a certain disease, you obviously need more and more patients to determine whether a treatment has a benefit at all or an effect on that patient population. So, we did see that patients who had polyps had a reduction in developing bronchiectasis.

But after looking at multiple variables, the rate of reduction after surgery was not significant in this study. And significance is important for studies because it determines whether there is a likelihood of this treatment effect being real versus chance, but you also need to interpret the data properly as well. If you don't have enough patients, then it is hard to know whether the lack of significance or actual significance is meaningful. Now, that's not to say we don't have enough patients, but that's one possible explanation as to why we didn't see a bronchiectasis reduction in patients who have had sinus surgery. The other possible explanation is that, in fact, sinus surgery does not reduce the likelihood of bronchiectasis.

Melanie Cole, MS: Wow. So, this is really an interesting topic. And Dr. Welch, as we get ready to wrap up for clinicians and patients that are managing chronic sinusitis, do you have some practical insights, considerations you think that this research adds to the conversation about when to pursue surgery? Take us from bench to bedside, the importance of this, and the key takeaways you'd like for other providers.

Dr. Kevin Welch: Absolutely. I think it's important to maintain the patient at the center. Every patient comes in with a different understanding of their disease. And for every patient, their disease affects them in different ways. So, the trite expression is no two patients are the same. And that's very true of patients with chronic sinusitis.

So when you counsel patients with chronic sinusitis, it's important not only to tell them what their options are and their options are many medical treatments as well as surgery. So if you've tried medicines, whether it be antibiotics or steroids, or injectable biologic drugs or allergy treatment, and if you are thinking about sending a patient for a consultation regarding sinus surgery, it's important, number one, to make sure that you've exhausted the medical therapy, or at least the patient knows the options for medical therapy.

Obviously, we tell patients about the risks of undergoing surgery. But I think we also need to tell patients the potential risks of not undergoing surgery or not having medical treatment. Some people are left to think that their sinuses are just, you know, an annoying issue that causes nasal obstruction or a drippy nose, or problems with smell and taste. But patients need to know that they have the potential of developing other significant medical conditions down the road. Now, some studies show that can be five years down the road. Other studies, much longer. None of us has a crystal ball, but we all need to tell patients, "Look, if you're going to entertain a treatment, then great." There's some evidence to show that the surgery is helpful not only with your symptoms, but is also helpful in reducing the likelihood of developing asthma, for example, possibly for reducing the likelihood of bronchiectasis.

But simultaneously, we also need to counsel patients who are not interested in surgery or not considering surgery, that they may develop some of these conditions down the road. And I don't intend to tell patients that as sort of a threat or, in retrospect, say, "Well, I told you so." But I think patients make decisions based on the information that they have. And it's important for all physicians to really arm patients with as much knowledge as possible so they can make an informed decision about their treatment pathways.

Melanie Cole, MS: Absolutely. And that's such an important point, that informed decision-making and that shared decision-making between the physician and the patient. Thank you so much, Dr. Welch, for joining us today and sharing the study results with us. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/ent to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm Melanie Cole.