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.