By Michael H. Broder, PhD
Reviewed by Ware Kuschner, MD, Chief, Pulmonary Section, US Department of Veterans Affairs Palo Alto Health Care System
Rheumatoid arthritis (RA) is primarily an articular disease; however, extra-articular disease may also be present. Pulmonary disease, in fact, occurs commonly in people with seropositive RA, among whom it is a leading cause of morbidity and mortality. Recent studies have addressed the connection between antibodies to citrullinated protein/peptide antigens and lung disease among people with RA. Other studies have provided evidence for a potential role of the lung as well as the generation of RA-associated autoantibodies in a pathogenic phase known as preclinical RA.1
In short, the lung is an important issue in RA. “Evidence shows that RA may in part start due to inflammation in the airways of the lung,” said Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine in the Division of Rheumatology, Immunology and Allergy in the Department of Medicine at Brigham and Women’s Hospital and Harvard Medical School. “Patients with RA are at increased risk for pneumonia and other lung complications, including respiratory-related mortality, compared to the general population.” Dr. Sparks is the lead author of a recent study among a high-risk cohort of first-degree relatives of people with RA who did not have RA themselves. Among the participants, the study found that smoking and age were associated with inflammatory joint signs at typical RA sites.2
A number of studies have shown a marked association between the lung and RA. These studies have provided evidence for a high prevalence of lung disease, both airways and parenchymal disease, in people who meet clinical criteria for RA. Some studies have suggested that lung disease in RA is due to circulating autoimmunity that targets the lung. Other factors have been suggested as well, such as medications. Other data, however, suggest that inflammatory airways disease, as well as autoimmunity in the lung, may be present prior to the manifestation of joint symptoms. This suggests a role for autoimmune response in the lung in the genesis of RA-related autoimmunity.3
There are barriers to dealing with the lung as a factor in RA. “The major barrier is recognition from both a patient and clinician perspective,” said Dr. Sparks. “Patients with RA should let their clinician know if they develop symptoms such as shortness of breath, cough, or chest pain. Clinicians should consider screening patients with RA for lung diseases,” Dr. Sparks added.
A recent study by Demoruelle and colleagues provides a detailed overview of the relevant issues, and offers a research agenda aimed at comprehending the course of lung involvement in RA and its connection with the overall pathogenesis of RA. Key findings of the studies include a high prevalence of lung disease in clinically classified RA. In fact, the prevalence of lung disease is about 60%-80% among patients with clinically defined RA.3
While it is only minimally symptomatic in most patients, lung disease may have severe manifestations for some. Even though airway disease and parenchymal lung disease may both be present, they may have differential impact on the pathogenesis of RA. Moreover, lung disease, especially airway disease, may manifest prior to the onset of articular RA. Indeed, a substantial prevalence of airway disease when RA is in its preclinical period argues strongly that RA-related inflammation and autoimmunity may begin at the airway mucosa or manifest in such tissue quite early in the process of the disease.3
Recent studies showing RA-associated autoantibodies in the sputum of people at risk for RA indicate that RA-related autoimmunity may be initiated in the pulmonary mucosa.3 A study by Willis and colleagues detected RA-associated autoantibodies in sputum in people at risk of RA and in those with early RA.4 These autoantibodies were detected in some at-risk subjects even in the absence of seropositivity; increased autoantibody-to–total immunoglobulin ratios were also found in the sputum of such people. Together, these findings provide evidence for the lung as a site of autoantibody generation in the early in the development of RA, suggesting a significant role of the lung in the RA pathogenesis.4
osteoarthritis thumb surgery recoveryhow to osteoarthritis thumb surgery recovery for In addition, smoking or bacteria may play a causative role in pulmonary RA, although the mechanism by which these factors may trigger immunity requires additional study. Development of inducible bronchus-associated lymphoid tissue may be one of the mechanisms leading to RA in the lung, initiated from an inflammatory immune response to inhaled environmental factors. Longitudinal studies of lung disease in RA are needed to shed further light on the various ways in which the lungs may be involved in for 1 last update 2020/08/05 the development and progression of RA.3In addition, smoking or bacteria may play a causative role in pulmonary RA, although the mechanism by which these factors may trigger immunity requires additional study. Development of inducible bronchus-associated lymphoid tissue may be one of the mechanisms leading to RA in the lung, initiated from an inflammatory immune response to inhaled environmental factors. Longitudinal studies of lung disease in RA are needed to shed further light on the various ways in which the lungs may be involved in the development and progression of RA.3
osteoarthritis thumb surgery recoveryhow to osteoarthritis thumb surgery recovery for Fortunately, there are some promising opportunities for dealing with the lung as a factor in RA. “Research is ongoing to understand which patients with RA are more likely to develop lung complications,” said Dr. Sparks. “Once these patients are identified, researchers are trying to understand the best way to treat patients to improve their health,” Dr. Sparks noted.
Published: February for 1 last update 2020/08/05 20, 2018Published: February 20, 2018
- 1. Kelmenson LB, Demoruelle MK, Deane KD. The complex role of the lung in the pathogenesis and clinical outcomes of rheumatoid arthritis. Curr Rheumatol Rep. 2016;18:69.
- 2. Sparks JA, Chang SC, Deane KD, et al. Associations of smoking and age with inflammatory joint signs among unaffected first-degree relatives of rheumatoid arthritis patients: results from studies of the etiology of rheumatoid arthritis. Arthritis Rheumatol. 2016;68:1828-1838.
- 3. Demoruelle MK, Solomon JJ, Fischer A, Deane KD. The lung may play a role in the pathogenesis of rheumatoid arthritis. Int J Clin Rheumtol. 2014;9:295-309.
- 4. Willis VC, Demoruelle MK, Derber LA, et al. Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease. Arthritis Rheum. 2013;65:2545-2554.