Division of Respiratory Medicine, Nottingham City Hospital, Nottingham NG5 1PB, UK
SIR, We thank Dr Saravanan and colleagues for their interest in our paper [1]. The data we used for our study are derived from general practice records collected as part of routine clinical care, and thus reflect clinical events in the general population. For this reason most cases of fibrosing alveolitis that occur in association with a connective tissue disease in this dataset do so in the presence of rheumatoid arthritis. We agree that median survival times of around 2.5 yr from diagnosis are alarming for patients with fibrosing alveolitis, but these findings are similar to those from other studies [2, 3].
In answer to the specific points raised by Dr Saravanan and colleagues:
First, our study was based on all-cause mortality, which has the advantage of removing bias that may be present when trying to attribute a specific cause of death. In our control cohort (patients without a diagnosis of fibrosing alveolitis) we did find an increase in mortality attributable to rheumatoid arthritis on the borderline of statistical significance; after controlling for age, sex, smoking habit and steroid exposure the hazard ratio was 1.34 (95% CI 0.822.18). This suggests that the mortality rate amongst patients with rheumatoid arthritis who do not have fibrosing alveolitis may be 30% higher than that in the general population. Although this is a clinically important increase, it is far less than the 550% increase present in patients with rheumatoid arthritis and fibrosing alveolitis (hazard ratio 6.47, 95% CI 4.639.04). Thus most of the increase in mortality amongst patients with rheumatoid arthritis with fibrosing alveolitis appears to be due to the fibrosing alveolitis.
Second, we agree that our analyses are only relevant to survival from point of diagnosis. For obvious reasons the same is true for nearly all survival analyses, e.g. lung cancer survival. Our finding that 11% of patients with fibrosing alveolitis also have a connective tissue disease is consistent with other studies [4]. We agree that there is likely to be underdiagnosis of interstitial lung disease in the general practice research database, but the important point is that, if anything, patients with rheumatoid arthritis will be more likely than those with lone cryptogenic fibrosing alveolitis to have their interstitial lung disease diagnosed at an earlier stage, because many patients with rheumatoid arthritis attend a specialist clinic and have a disease known to be associated with lung problems. The impact of this lengthtime bias will be to appear to increase the survival time amongst patients with rheumatoid arthritis and this may explain why other studies have shown an improved survival amongst these patients. This bias may also be present in our study, in which case the median survival we report for patients with rheumatoid arthritis and fibrosing alveolitis may be an overestimate.
Third, Dr Saravanan and colleagues state that the pathological and radiological features of FA associated with RA and CTD are known to be different to those of LCFA and use two papers to support this argument. The first paper, from Rajasekaran et al., includes data for 36 patients, 18 with lone cryptogenic fibrosing alveolitis and 18 with rheumatoid arthritis and fibrosing alveolitis. There were no statistical differences at the 5% level between the HRCT scans of the two groups. The second paper, by Bouros et al., does not include a patient group with lone cryptogenic fibrosing alveolitis at all, although it does show that within patients with systemic sclerosis with fibrosing alveolitis the histological subtype did not appear to influence survival. Studies in this area are difficult to do and most are based on small numbers of highly selected patients. At present we are not convinced that there is evidence to suggest that the natural history of fibrosing alveolitis is different for patients with rheumatoid arthritis compared with those with lone cryptogenic fibrosing alveolitis.
We believe that this is an important area and would like to encourage Dr Saravanan and colleagues with the collection of their cohort. At present their data suggest that the risk ratio for death is 1.6 in patients with lone cryptogenic fibrosing alveolitis compared with patients with rheumatoid arthritis and interstitial lung disease. At least part of this difference will be due to the fact that patients with lone cryptogenic fibrosing alveolitis tend to be older and more often male [1]. We are not surprised that patients have a wide range of disease progression rates, and for this reason their final cohorts will need to be larger and representative of the general population.
Patients with fibrosing alveolitis have a poor prognosis, whether or not they have a coexisting connective tissue disease. Fibrosing alveolitis is an increasingly important cause of mortality in the UK [5, 6], and there is a pressing need for intervention trials to try to improve the outlook for these patients.
Notes
Correspondence to: R. Hubbard. E-mail: richard.hubbard{at}nottingham.ac.uk
References