Rheumatoid lung disease

Abstract

Rheumatoid arthritis (RA) is a common, functionally disabling disease with genetic and environmental contributors. It occurs in approximately 1% of the population and adversely affects quality of life, functional status, and survival. Beyond its impact on the joints, pulmonary involvement occurs regularly and is responsible for a significant portion of the morbidity and mortality. Although pulmonary infection and/or drug toxicity are frequent complications, lung disease directly associated with the underlying RA is more common. The airways, vasculature, parenchyma, and pleura can all be involved, with variable amounts of pathologic inflammation and fibrosis. The true adverse clinical impact of the most important of these directly associated disorders, RA-associated interstitial lung disease (RA-ILD), has only recently begun to reveal itself. Our knowledge of the underlying pathobiology and the impact of our current immunomodulatory and biologic therapies on the lung disease are less than incomplete. However, what is clear is the importance of progressive lung fibrosis in shortening survival and impairing quality of life in RA as well as in other connective tissue diseases. The impact of historically available and newer biologic therapies in altering the outcome of RA-ILD is unknown; translational studies focused on the pathobiology and clinical studies focused on the treatment of RA-ILD are needed.

Figure 1.

Survival in patients with rheumatoid arthritis (RA) and RA after first presentation of severe extraarticular disease manifestations (ExRA) compared with the expected survival from the general population. Reprinted by permission from Reference .

Figure 2.

Comparison of the survival curves of all subject groups. CVD-NSIP = nonspecific interstitial pneumonia associated with collagen vascular disease; CVD-UIP = usual interstitial pneumonia associated with collagen vascular disease; I-NSIP = idiopathic nonspecific interstitial pneumonia; UIP = usual interstitial pneumonia. Reprinted by permission from Reference .

Figure 3.

Comparison of the Kaplan-Meier survival curves between the subject groups and the UIP pattern associated with rheumatoid arthritis (RA-UIP). CVD-NSIP = nonspecific interstitial pneumonia associated with collagen vascular diseases; I-NSIP = idiopathic nonspecific interstitial pneumonia; IPF/UIP = idiopathic pulmonary fibrosis/usual interstitial pneumonia; non–RA-UIP = usual interstitial pneumonia in the patients with non–rheumatoid arthritis–collagen vascular diseases. The statistical significances between groups were as follows: RA-UIP versus non–RA-UIP, p = 0.015; RA-UIP versus CVD-NSIP, p = 0.043; RA-UIP versus I-NSIP, not significant; RA-UIP versus IPF/UIP, not significant. Reprinted by permission from Reference .

Figure 4.

Cox model–based survival estimates for patients across three levels of FVC percentage change adjusted for usual interstitial pneumonia (UIP), onset of symptoms, female sex, and positive smoking history. Average patient profiles for UIP, onset of symptoms, sex, and smoking were used in the estimates. Dotted line, at least 10% increase in FVC; solid line, at least 10% decrease in FVC; dashed line, less than 10% increase or decrease in FVC; p = 0.01. Reprinted by permission from Reference .

Figure 5.

Fibroblast foci appear to be isolated accumulations of matrix and myofibroblasts in usual interstitial pneumonia (left); however, when reconstructed in three dimensions, they appear to be physically connected and forming a reticulum. Reprinted by permission from Reference .