This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.

The current literature states the prevalence of methotrexate pneumonitis (MTX-P) to be 3.5-7.6%. This is based on retrospective data. Consequently, clinicians remain cautious in using methotrexate especially in patients with pre-existing lung disease. To get a true idea of the incidence of MTX-P we designed an ongoing prospective study, which is the largest to date. We recruited all patients starting low-dose methotrexate in our department, and followed them up for 2 years or until development of MTX-P. All patients had their pulmonary spirometry checked at baseline. Patients were excluded if they did not give consent for methotrexate therapy, or had a forced expiratory volume in 1 s (fev1) or full vital capacity (FVC) of less than 1 l. So far, 223 patients have been recruited of whom 223 have completed 6 months and 185 have finished 2 years of follow-up from commencing methotrexate. Only two patients developed MTX-P. This gave an incidence of one case every 192 patient years of MTX-P. The results of this ongoing prospective study suggest that MTX-P when diagnosed using Carson's criteria and Chest HRCT scanning, does not occur as often as previously thought. Also it would appear from our data that baseline spirometry rather than full pulmonary function tests can be used routinely as an immediate screening of lung function prior to commencement of methotrexate. Interestingly the patients who developed MTX-P did not have any specific abnormalities at baseline.

This is the first study to describe the variation of immunological responses in MTX-P with the degree of exposure to MTX. Our findings suggest that MTX-P can be divided into two groups: type 1 MTX-P that occurs early, predominated by neutrophils, lung fibrosis and has a high mortality; and type 2 MTX-P that occurs late, predominated by lymphocytes, has less lung fibrosis and low mortality.

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