Mechanisms of lung disease development in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that causes joint inflammation and damage. Extra-articular manifestations occur in many patients and can include lung involvement in the form of airway or parenchymal inflammation and fibrosis. Although the pathophysiology of articular RA has been extensively investigated, the mechanisms causing airway and parenchymal lung disease are not well defined. Infections, cigarette-smoking, mucosal dysbiosis, host genetics and premature senescence are all potentially important contributors to the development of lung disease in patients with RA. RA-associated lung disease (which can predate the onset of articular disease by many years) probably originates from chronic airway and alveolar epithelial injury that occurs in an individual with a genetic background that permits the development of autoimmunity, leading to chronic inflammation and subsequent airway and lung parenchymal remodelling and fibrosis. Further investigations into the specific mechanisms by which lung disease develops in RA will be crucial for the development of effective therapies. Identifying mechanisms by which environmental and host factors cooperate in the induction of autoimmunity in the lung might also help to establish the order of early events in RA. Rheumatoid arthritis (RA)-associated lung disease is difficult to treat and is associated with increased morbidity and mortality. A better understanding of the pathogenic pathways involved in lung disease in patients with RA should aid the development of specific therapies. Key points Rheumatoid arthritis (RA) is a systemic autoimmune disease that can present with a variety of lung manifestations including airway disease and interstitial lung disease. Seropositive RA develops following an asymptomatic pre-RA phase characterized by the emergence of autoantibodies and systemic immune activation that might be initiated at mucosal surfaces such as the lung. Cigarette smoking, host genetic factors, dysbiosis in the oral cavity and airways and senescence are all potentially important in the pathogenesis of lung disease in RA. Identifying specific mechanisms that permit the breakdown of tolerance and generation of disease in the lung are important for the development of therapies that address lung complications in RA. Screening individuals with RA at risk of lung complications is now feasible and should be the focus of future studies.