Jeffrey Sparks, MD, MMSc, on Rheumatoid Arthritis and Pulmonary Function

In this podcast, Dr Sparks discusses his research into the association of rheumatoid arthritis with pulmonary dysfunction, irrespective of smoking.

Jeffrey Sparks, MD, MMSc, is an assistant professor of medicine at Harvard Medical School, and an associate physician in Rheumatology at Brigham and Women's Hospital in Boston, Massachusetts.

TRANSCRIPT:

Hello everyone, and welcome to another podcast from Rheumatology and Arthritis Learning Network. I'm your moderator, Rebecca Mashaw, and today we're here with Dr. Jeffrey Sparks, who is assistant professor of Medicine at Harvard Medical School, and an associate physician in rheumatology at Brigham and Women's Hospital in Boston, Massachusetts.

We're going to be talking about some recent research he and colleagues did into the relationship between pulmonary function and rheumatoid arthritis. Good morning, Dr. Sparks. Thanks for joining us today.

Dr Jeffery Sparks:  Good morning. Thank you for having me.

RALN:  What initiated your interest in studying this relationship between RA and pulmonary function?

Dr Sparks:  There's been a lot of interest in the relationship between respiratory diseases and rheumatoid arthritis. It's kind of thought of as a bidirectional relationship, meaning that perhaps the respiratory diseases might increase risk of developing RA and then vice versa, having RA might also increase the risk of developing respiratory disease. Probably the entity that is best described, best known, is interstitial lung disease, and rheumatoid arthritis is a RA manifestation. That's one of the prototypic restrictive lung diseases when you try to subtype the kinds of lung diseases.

We think that's been known for quite a while, but the other relationships of, first off how the respiratory diseases impart RA risk, and then whether RA might also impact obstructive lung disease related to the airways and emphysema.

So we felt that looking at spirometric measures of lung function could help us understand both sides of that equation, and also to look at obstructive and restrictive lung disease.

RALN:  Could you give us a brief overview of this particular research? Who did you study? What was your focus? What kind of outcomes? What did you find out?

Dr Sparks:  Well, we used a very large data set in the UK Biobank. If you're not familiar, this is a fantastic resource that's composed of over 500,000 participants in the UK. It’s population-based. It's sort of from the mantra of, "If you will build it, they will come." They collected the data without a single goal in mind. They just wanted a huge data set. There's many papers that have been generated from the UK Biobank, and it's starting to hit the rheumatology landscape as well. It's a really interesting protocol, in that they measure about everything you could think of that is done clinically and some for research purposes as well.

For the purpose of this study, within the UK Biobank, they offered everyone spirometry measures. These were done under research protocol, meaning that they did not have a clinical indication to obtain spirometry. They also had quality control where it was the same protocol, the same machine, so the data quality was really good.

We decided to first off identify patients with RA within the UK Biobank, and then identify participants, both RA cases and controls, who had spirometry data that passed quality control. That was over 350,000 participants in the UK Biobank, a really large sample size.

It was really simple after we constructed the data set. We wanted to see whether there are differences between RA cases and controls based upon the pulmonary spirometry measures.

RALN:  What findings were of particular importance from your study? What did you find out about the risk for airflow obstruction among patients with RA?

Dr Sparks:  Well, the nice thing about spirometry is, it's a single test that gets you a lot of data. These are things that we do as clinicians all the time, and we know how to interpret them. There were a lot of strengths that way, and that a single measure could classify someone as having pulmonary abnormalities. It could also subset them into obstructive versus restrictive pulmonary abnormalities. It can also talk about severity — mild, moderate, severe.

Then there is also some other measures looking at the small airways. We looked at all of those things. The first batch of measures that we looked at were the continuous measures. The FEV1% predicted, FVC% predicted, the ratio of the FEV1 to FVC, and then the FEF 25-75%, which is a measure of small airways. Again, we knew clinically that patients with RA would more than likely have restrictive lung disease, meaning that the FVC was lower.

What we were interested to find is that all the measures were actually worse within the RA patients. The other thing that was interesting is that this was not explained by smoking. We had great data on smoking, both status and pack-years to able to adjust for smoking, to look among nonsmokers, to look just among the ever-smokers, and to see whether there were particular interactions that emerged.

I think that's really a big takeaway is that these findings of worse spirometric measures are not explained by smoking, which is something that had been still on the table. I think with this sample size and this granularity of smoking data, I'm still seeing strong associations that this really is intrinsic to RA and not related to their smoking habits.

RALN:  Do you have a hypothesis about why this relationship exists in the absence of smoking?

Dr Sparks:  It's something to do with RA. [laughs] Probably the few things that could do it would be...this could be part of the RA disease process that while we think clinically, mostly that this is an articular disease, that's where patients have symptoms, that's where we're monitoring disease activity, but certainly, within interstitial lung disease, we know that that's really a RA manifestation.

A big suspicion of mine is that the airway involvement and some of the other abnormalities that can happen in the lungs are really part and parcel of the RA disease process. Hopefully, treating RA could also treat that, which I think is still an unknown question.

The other is, maybe this is just a remnant of the systemic inflammation and the damage that's been done with RA. Maybe it's an innocent bystander, if you will, as opposed to the RA itself causing the problem.

I think another one which is going to be a tough one to sort out is, perhaps the treatment of RA might have some residual damage on the lungs. Again, those 3 things are probably in some combination contributing to what we're finding.

I think the treatment one would be particularly important because it could be a double-edged sword, if you will, if that's both helping patients but also hurting them. Again, we don't really know that at this point. Certainly, the medication that comes to mind is methotrexate. There's been a lot of research showing that that does not seem to impact future ILD risk. There is a very rare risk of drug-associated pneumonitis with methotrexate, but it's really uncommon, and probably this is helping way more than it's hurting, even the lungs.

But I think this is something that needs to be studied, as far as how the medications themselves might have some impact on the lungs, both positive or negative.

RALN:  Are these research topics that you're going to be looking at yourself in the near future?

Dr Sparks:  Of course. I think, again, there is always strengths and limitations to studies. The strength for this study was the large sample size, the granular data on spirometry, the fact that it was done without research purposes, and also having smoking data.

However, we didn't have the entire disease history of rheumatoid arthritis. This was a cross-sectional study, so we weren't really sure how long they'd had RA, what their disease activity in the past was, and then how this impacts actual clinical outcomes. We really looked to see at that moment in time were RA cases doing worse from a pulmonary perspective than controls.

We did see that, but it doesn't necessarily mean that they're getting admitted more for pulmonary exacerbations, having ER visits, or getting prescribed medications and health care utilization. A lot of the clinical outcomes that would be of importance.

And of course, the medications were just as of the moment they happen to be enrolled in the study, so I think future studies should try to think about how medication initiation, and duration, and dose, how that might impact lung health.

Certainly, this is one of those prototypic studies where there is a few questions that are answered, but it certainly opened the doors for many others to be answered, hopefully soon.

RALN:  What advice do you have for rheumatologists who are treating patients with RA in regard to monitoring them for pulmonary function?

Dr Sparks:  I think just awareness that this issue is there. Over the last decade, there is a lot more awareness about lung disease in rheumatoid arthritis that it's not necessarily just interstitial lung disease, it's not necessarily people who have severe pulmonary imaging abnormalities and who are symptomatic that there's probably a spectrum of lung disease that is affecting rheumatoid arthritis patients.

It's still not prime-time as far as how to decide when to order these tests. This one was done for research purposes, but certainly, there’s a lot of patients that if you did do pulmonary measures on them, they would have abnormalities.

Sorting out what to do with them, when to get pulmonary involved, how to decide whether a patient is symptomatic or not, is still to be determined. But I think a major thing is that these abnormalities are found. It's not something necessarily you can just chalk up to their smoking, but this is something that is part and parcel of the RA disease process. It's not just restrictive lung disease, it's not just interstitial lung disease, but even airways disease that might look and act very similar to asthma and COPD might be an RA manifestation.

That's new territory for rheumatologists. It does open up the avenue for even more collaboration with pulmonologists and other specialists that might help these patients.

RALN:  This is very interesting, and we're going to look forward to hearing more about your continuing research. Thank you for your time today.

Dr Sparks:  Thank you for having me.