Association Between RA and Upper Respiratory Diseases

In this podcast, Dr Vanessa Kronzer discusses her research into the possible association between chronic and acute sinusitis and rhinitis and the risk of developing rheumatoid arthritis.

Vanessa Kronzer, MD, is an assistant professor of medicine and rheumatology fellow at Mayo Clinic in Rochester, Minnesota.

TRANSCRIPT:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm Rebecca Mashaw, and today I'm pleased to welcome Dr. Vanessa Kronzer, a rheumatologist and assistant professor of medicine at the Mayo Clinic in Rochester, Minnesota. She's going to give us an overview of her recent research into the possible association of sinusitis and upper respiratory tract diseases with incident rheumatoid arthritis. Thank you for joining us today, Dr. Kronzer.

Dr Kronzer: Thank you so much for having me.

RALN: What caused you to look into the possibility that this association might exist between respiratory tract disease and rheumatoid arthritis?

Dr Kronzer: The reason we were inspired to do this study was that the lungs are increasingly implicated in RA pathogenesis and as an assistant professor at Mayo and someone who just wants to know where RA comes from, I'm growing my expertise in this area of respiratory tract diseases and RA. And a project I led previously in the Mayo Biobank showed that asthma was associated with an increased risk of RA, and then a next project that I led using the large population-based EIRA study in Sweden and that found upper and lower acute and chronic respiratory tract disease groups were associated with an increased risk of RA. So those two studies led us to wonder whether other specific respiratory tract diseases besides asthma also increase the risk of RA, and the key message that I want you to remember, which we'll come back to I know in a bit, is that in addition to asthma, upper respiratory tract diseases, including sinusitis and pharyngitis, are also associated with an increased risk of RA.

RALN: Can you give us a brief overview of the study?

Dr Kronzer: Certainly. The key points about the methods that you should know are that it was a case control study, it was conducted within the Mass General Brigham Biobank, it included 741 incident RA cases, each matched to 3 controls on age, sex, and the length of preceding EHR history, and we studied 7 respiratory tract diseases, including acute sinusitis, acute pharyngitis, chronic rhinitis/pharyngitis, chronic sinusitis, pneumonia, asthma, and COPD. And these came from EHR codes, which had an 86% accuracy by physician diagnosis when we did our manual review.

RALN: And what did you find?

Dr Kronzer: Well, we found that even more than asthma, acute sinusitis, chronic sinusitis, acute pharyngitis, and chronic pharyngitis or rhinitis, were all associated with the increased risk of RA. And in addition to that, the number of acute respiratory tract diseases that a person had, which we called the acute respiratory tract disease burden, during the pre-RA period, was also associated with an increased risk of RA. So again, the key message is that in addition to asthma, upper respiratory tract diseases, including sinusitis and pharyngitis also seem to be associated with an increased risk of RA.

RALN: Did your findings indicate anything about why this might be the case, what the association is between RA and these upper respiratory diseases?

Dr Kronzer: These findings support the so-called mucosal origins hypothesis that has been circulating for several years now for RA origination, and that is that we think that RA originates in mucosal surfaces, such as the lungs before later migrating to target the joints. As far as exactly how that happens, that's an area of further research that I think we'd all like to know the answer to.

RALN: How do you think your findings could impact clinical practice—both for primary care physicians who may be faced with patients who come in with chronic sinusitis or rhinitis, and also with rheumatologists who have patients who have RA, who are also suffering from these upper respiratory tract diseases? How would this apply to their practice?

Dr Kronzer: Besides helping us to understand where RA comes from, which is something that everybody wants to know when they get a new disease, this study will help primary care doctors and rheumatologists know what respiratory risk factors to look for in patients coming in with symptoms resembling RA. For example, in patients with a history of uncontrolled sinusitis, like you mentioned, I'm now more suspicious that their arthralgia is maybe true RA and maybe pay a little closer attention to those patients. It also helps us to counsel patients on a question that they frequently ask us, which is how their family members can reduce their RA risk. I think that the answer to that is that we need to better prevent and control their respiratory tract diseases in addition to what we already know about reducing smoking and obesity.

RALN: So the control of the respiratory tract illnesses could in fact lead to reducing the risk of the development of RA later?

Dr Kronzer: Yeah, that's what we expect and that's what we hope, we're actually considering doing a clinical trial preventing or controlling respiratory tract diseases to see if that would be beneficial in concrete data or not.

RALN: Well, that sort of answers my last question, which is, do you plan to continue this research? To see if you can find out more about these possible causes and relationships? Clearly, you've got several ideas already in the works.

Dr Kronzer:  Yeah, and as a step, I mentioned maybe doing a clinical trial, but as a step before that, we're actually planning sooner to see if patients with a certain genetic signature have a particularly increased risk of developing RA in the setting of respiratory tract diseases, and this type of genetic study would not only help us to discover who would best benefit from such an intervention study later, but also to help us figure out how respiratory tract diseases might be creating this association with an increased risk of rheumatoid arthritis.

RALN: Well this is very interesting and we look forward to getting in touch with you again later when you've done some more of this research and finding out what you discover.

Dr Kronzer: Yeah, that sounds great, and if it's okay, I'd like to take a moment to thank my coauthors too—Senior Author Jeff Sparks was very instrumental in this study as well as the coauthors, Weixing Huang, Alessandra Zaccardelli, Cynthia Crowson, John Davis III, Robert Vassallo, Tracy J. Doyle, and Elena Losina—for their help with this project and thank you for hosting and for our audience's attention today.