VANCOUVER, B.C. — New-onset pulmonary abnormalities in patients with rheumatoid arthritis should keep rheumatologists and pulmonologists on the edge of their seats, clinically speaking. The lung is a frequent site of extra-articular arthritis, and its most common manifestation – interstitial lung disease – carries significant morbidity and mortality risks, according to Dr. Kevin R. Flaherty.

Pulmonary Manifestations of RA

The lifetime risk of interstitial lung disease is nearly 8% in patients with RA, compared with 1% in the general population (Arthritis Rheum. 2010;62:1583-91).

And this disease confers a poor prognosis, with a near tripling of the risk of death and with a median survival after diagnosis of 2.5 years, noted Dr. Flaherty, who is a pulmonologist and associate professor at the University of Michigan Health System in Ann Arbor.

High-resolution computed tomography (HRCT) and pulmonary functioning testing appear to be useful for identifying interstitial lung disease early in its course, according to Dr. Flaherty.

For example, among patients within 2 years of a RA diagnosis, 44% have been found to have HRCT, pulmonary function test, and other abnormalities consistent with interstitial lung disease in the absence of symptoms (Am. J. Respir. Crit. Care Med. 1997;156:528-35).

“The [HRCT] features were mild – reticular thickening, ground glass, and not much honeycombing – suggesting maybe that we might be able to impact the disease, because I think once you get to honeycomb lung and end-stage fibrosis, our ability to impact this disease is likely to be lower,” he said.

As for which patients to screen for interstitial lung disease, the predictors of abnormal pulmonary function testing in the RA population are respiratory symptoms, smoking, anti–cyclic citrullinated peptide positivity, and use of prednisone (Arthritis Res. Ther. 2010;12:R104).

When it comes to monitoring interstitial lung disease, HRCT appears to be more sensitive than pulmonary function testing for detecting disease progression (Arch. Intern. Med. 2008;168:159-66).

And carbon monoxide diffusing capacity at diagnosis is the best predictor of progression (Ann. Rheum. Dis. 2002;61:517-21).

“We are starting … to see data emerging that really mirrors what we see in idiopathic lung disease, that the histopathology and the CT appearance can help us in terms of stratifying patients for risk of subsequent mortality,” Dr. Flaherty said.

A study of patients with RA-associated interstitial lung disease found 50% mortality in those with a usual interstitial pneumonia (UIP) histology, compared with none in those with a nonspecific interstitial pneumonia (NSIP) histology after a similar median follow-up of about 4 years (Chest 2005;127:2019-27).

A honeycomb pattern on HRCT was found only in the UIP group, suggesting that this radiographic pattern is a good surrogate for this histology, Dr. Flaherty noted. And indeed, patients having a definite UIP radiographic appearance have poorer survival (Eur. Respir. J. 2010;35:1322-8).

Rigorous studies are lacking when it comes to treating interstitial lung disease in the RA population, according to Dr. Flaherty.

Pulmonary Adverse Effects of RA Therapy

Pneumonitis is often a concern in patients using methotrexate to treat RA. But with low-dose therapy, only 3% of patients develop this complication after a mean treatment duration of 23 months (Chest 1996;109:933-8), Dr. Flaherty pointed out.

Anti–tumor necrosis factor agents such as infliximab have been associated with pulmonary adverse effects and complications, including infection, atypical presentation of tuberculosis, and pulmonary fibrosis.

Some research reports have also raised concern that anti-TNF agents may hasten progression of interstitial lung disease in patients with RA and thus increase mortality.

“The data on that are still out,” Dr. Flaherty said. Evidence thus far suggests that mortality in patients treated with these agents is similar to that in their counterparts treated with traditional disease-modifying antirheumatic drugs (Ann. Rheum. Dis. 2010;69:1086-91).

Rituximab has been linked to severe infections in patients with RA, the largest share of which (40%) are pulmonary (Arthritis Rheum. 2010;62:2625-32). Only a single infection was opportunistic, and most were bacterial.

Pulmonary Cancers

Patients with RA have increased risk of lung cancer (standardized incidence ratio, 1.63) as well as for another malignancy that can involve the lung, lymphoma (Arthritis Res. Ther. 2008;10:R45), as a result of their underlying disease, long-term immunosuppression, or both.

Treatment with biologic agents has not been associated with a significantly elevated risk of lung cancer among patients with RA, according to Dr. Flaherty.

But treatment with methotrexate has, with the incidence of lung cancer among methotrexate users about triple that of the general population (Arthritis Rheum. 2008;59:794-9).

Users of this drug also have sharply increased rates of non-Hodgkin's lymphoma and melanoma.

Dr. Flaherty did not report any disclosures.

Consider Cancer in RA Patients With Lung Pathology