The “high attenuation” range of -640 to -250 is the range associated with ILD. The percentage of total pixels in this range is the percentage of high attenuation area (%HAA)—and this is the key number used to assess disease when using quantitative CT densitometry.
Dr. Danoff and her team have already found that using densitometry is more reliable than using expert readers. An expert with extensive experience had an intra-observer kappa score of variability of 65%. But the correlation coefficient of %HAA on 2,653 scans that were re-run, as part of a different study, was .93, showing that it is highly repeatable.
Researchers have also found that quantitative CT densitometry is much better at predicting poor performance on pulmonary function tests at 18 months of follow-up than the expert reads of the CT scans.
Dr. Danoff, whose project is also beginning to look at biomarkers of ILD, said she hopes this could be the beginning of a very useful tool for doctors and patients.
“I would like a very simple test that every radiologist could take to their office and when they met an RA patient for the first time they could say, ‘Here’s what your lifetime risk of developing interstitial lung disease is.’ Not just because we want to know who we should be screening but because it allows us to do primary prevention. And I think that’s where we have to go with this”.
A Better Mouse Model for RA-related Lung Disease
With as many as 80% of RA patients developing signs of disease in the lung, and as many as 20% developing diffuse fibrotic lung disease, the more that is known about how the lung becomes affected, the better. But there is a lot to learn.
“Really, little is known about the mechanism of lung disease in rheumatoid arthritis,” said Rebecca Keith, MD, a researcher with National Jewish Health in Denver.
She and other researchers there—including David Riches, PhD, professor of pediatrics—are trying to address this with a project that received REF funding in 2009. Using a mouse model meant to mimic the development of RA-related ILD in patients, they are exploring the underlying mechanisms.
These investigators know that the prevalence of the disease rises with age, that joint disease is more common in women and that ILD is six times more common in men than women. Now they have a mouse model that reflects those tendencies.
The point of this effort is not simply to establish biomarkers of these different stages of lung disease but hopefully to gain insight regarding molecular pathways in the process.
—Dana Ascherman, MD
Most mouse models of arthritis do not develop lung disease, and vice versa. However, National Jewish Health researchers have found that the SKG mouse—in which arthritis is brought about by the injection of inflammation-inducing zymosan—is a reliable representation of both RA and lung disease. They tracked the progression of arthritis in female mice and found that it progressed more quickly than in male mice, and that aged male mice had higher levels of hydroxyproline and lower static compliance, which is associated with ILD. They also found that the lung disease is characterized by infiltrating macrophages and CD4-positive T cells.
