Researchers working on early diagnosis of RA-related lung disease

Researchers have made tremendous strides in treating rheumatoid arthritis, with overall mortality rates dropping as treatments for the debilitating aspects of RA continue to improve.

But with more RA patients living longer, other RA-related conditions have become more common. One of those conditions is interstitial lung disease (ILD) which causes scarring in the lung. Studies show that 40 percent to 60 percent of RA patients will develop some form of ILD, and it currently accounts for about 10 percent of RA-related deaths.

"The mortality associated with ILD in rheumatoid arthritis is increasing," says Sonye K. Danoff, MD, PhD, assistant professor in the division of pulmonary and critical care medicine and co-director of the Hopkins Interstitial Lung Disease Clinic at Johns Hopkins University. "What this really speaks to is the fact that now with much better therapeutic agents and clinical care, patients are beginning to live longer and developing new diseases — in this case, what often can be a life-limiting disease with damage to the lung."

In RA-related ILD, immune cells enter the lungs and stay, causing inflammation and scarring. A delayed diagnosis can mean irreversible lung damage.

Thanks to a grant from the American College of Rheumatology Research and Education Foundation, Dr. Danoff and her colleagues are investigating ways to diagnose ILD in RA patients before symptoms — typically coughing and shortness of breath during exertion — appear.

Working with a research group from the University of Iowa, Dr. Danoff is using quantitative densitometry with CT scans to look for damage in the lung. The CT scan takes an image of the lung and displays millions of three-dimensional pixels, called voxels. Over a three-year period, the researchers study two lung scans of RA patients and use assessments such as pulmonary function tests to identify evidence of ILD.

Through computer analysis of the voxels, researchers hope to determine what early-stage ILD looks like on a CT scan without relying solely on radiologist's subjective reading.

"We know from a lot of research that's been done that there is a tremendous amount of inter-observer variability with even expert radiologists," Dr. Danoff says. "If I show the same CT scan to two different radiologists, their degree of agreement with each other is going to be less than 60 percent. It's very hard because when the initial findings are subtle, it's easy to miss them because what you're asking a human to do is discriminate a very small amount of difference in a very large number of images of a CT scan."

By also analyzing blood tests taken along with the lung scans, Dr. Danoff's goal for this study was to develop a blood test that allows doctors to diagnose ILD or assess an RA patient's risk for ILD with a simpler, less costly method than a CT scan.

The basis for Dr. Danoff's current research came from a National Institutes of Health study, known as ESCAPE-RA, which examined cardiovascular disease in RA patients. Joan Bathon, MD, formerly director of the Arthritis Center at Johns Hopkins Medicine and now director of the division of rheumatology at Columbia University, led the ESCAPE-RA work.

The REF grant allows Dr. Danoff to re-examine the ESCAPE-RA data.

"We're getting added value out of the original study because we're using part of it in a way that wasn't originally envisioned," Dr. Danoff explains. "The original ESCAPE-RA design that Dr. Bathon came up with was an incredibly powerful one, and they've done a tremendous amount of work on cardiovascular disease. But the current study has allowed a very well characterized patient group to be used to understand yet another critical feature in terms of RA-associated disease."

Dr. Danoff and John Giles, MD, MPH, assistant professor of medicine in the division of rheumatology at Columbia University, recently applied for an NIH grant to start a more in-depth study of which patients are likely to develop ILD.

According to Dr. Danoff, "ultimately everybody wants to have NIH funding." However, in order to get there, researchers need to have initial disease-specific funding from organizations like the REF. This gives them the chance to develop the strong preliminary data that forms the building blocks for future grants such as those from the NIH, the largest funding source. "Without the kind of disease-directed funding that the REF is doing, it would be almost impossible," Dr. Danoff says.

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Want to learn about the immune system and its link to rheumatic diseases?

The American College of Rheumatology publishes a series of fact sheets on rheumatic diseases that are an excellent source of reliable information. The fact sheet on The Immune System and Its Link to Rheumatic Diseases includes information about causes, diagnosis and treatment.