Smoking Raises Risk of Lung Disease in RA
BIRMINGHAM, England -- Risk factors for the development of interstitial lung disease among patients with rheumatoid arthritis (RA) included male sex, smoking, and seropositivity, a researcher reported here.
In contrast to RA patients overall, where there is a large female predominance, almost half of RA patients who developed interstitial lung disease were men, according to Clive Kelly, MBBS, of Queen Elizabeth Hospital in Gateshead, England.
In addition, all patients with the lung disease were past or present smokers, respectively, compared with only 60% of those with RA but no lung disease, he said in a poster session at the annual meeting of the British Society for Rheumatology.
Seropositivity also was significantly higher in the lung disease patients, with 89% and 94% being positive for rheumatoid factor and anti-CCP antibodies, respectively, compared with 58% of controls having rheumatoid factor (P=0.01) and 55% having anti-CCP antibodies (P=0.006).
Moreover, median titers of anti-CCP antibodies were very high, at 180 U/mL in patients with lung disease, compared with 78 U/mL in those without lung involvement (P=0.02). "In genetically susceptible individuals, tobacco smoking may precipitate site-specific citrullination in the lungs, leading to the generation of anti-CCP antibodies in early RA," he explained.
Citrullination is a process during the inflammatory state in which arginine is enzymatically converted to citrulline, which then may be seen as antigenic by the immune system. "This process in the lungs can trigger the activation of B cells, which then mediate disease," Kelly told MedPage Today.
Interstitial lung disease is the only complication of RA that continues to rise, and now accounts for 6% of deaths among this patient population. To examine possible risk factors for the lung disease, Kelly's group collected data from six U.K. centers between 1987 and 2012, identifying 230 RA patients with pulmonary involvement.
A total of 110 were male, and median age was 64 at the time of lung diagnosis. In 82% of cases, the joint manifestations of RA appeared before the lung disease, in 10% the lung symptoms appeared first, and in the remainder both manifestations occurred synchronously.
Men with interstitial lung disease were more commonly smokers than women (75% versus 60%,P=0.02), and had significantly greater pack-years of smoking (35 versus 20, P=0.01).
Among age- and sex-matched controls with RA but no clinical or radiographic evidence of lung disease, smoking was less common and pack-years were fewer among those who did smoke (P=0.03).
An additional finding was that in this cohort, lung disease developed at a younger age than in previous studies.
In a subgroup analysis of mortality, Kelly and colleagues found that among the 230 patients, 73 died. Nonetheless, although the incidence of interstitial lung disease has been rising, the mortality rate has been falling and deaths have been occurring at later ages.
For instance, during the years 1987 to 1993, a total of 67% of lung disease patients died from pulmonary causes at a median age of 63. But between 2006 and 2012, the percentage dying from interstitial lung disease fell to 30% and the median age at death was 76 (P<0.01 for both).
These changes are likely to reflect the earlier use of older immunosuppressive agents such as cyclophosphamide and the wider use of newer agents such as mycophenolate mofetil (CellCept) and rituximab (Rituxan), Kelly suggested. Earlier detection also is now possible with the use of high-resolution CT, he noted.
Source: Med Page Today