Cryptogenic Fibrosing alveolitis. 97/1

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Introduction

Cryptogenic fibrosing alveolitis (CFA) is a serious interstitial lung disease, and although relatively rare, is becoming increasingly common. It is characterised by increased numbers of inflammatory cells in the alveoli and surrounding tissues, resulting in progressive fibrous scarring of the lung. The causes are largely unknown, although clues are emerging.

The disease is usually diagnosed on clinical grounds on a basis of a combination of:

• inspiratory crackles at the lung bases;
• bilateral radiographic shadowing predominantly in the lower zones of the chest x-ray;
• restrictive lung function abnormalities

in the absence of an alternative cause of pulmonary fibrosis such as a connective tissue disorder or exposure to fibrogenic agents, such as asbestos or silica, or certain drugs. The diagnostic 'gold standard' is still lung biopsy, but this is only performed in about 12% of cases in the UK. More recently, it has been recognised that the appearances on high resolution CT scanning, which is much more accurate diagnostically than the chest X-ray, may avoid the need for invasive procedures in many cases.

Epidemiology and natural history

The incidence and prevalence of the disease are poorly understood, due in part to difficulties in diagnosis and ascertainment. The incidence was recently estimated at 11 (males) and 7 (females) per 100,000 per year in New Mexico, whilst in Nottingham, a prevalence estimate of 6 per 100,000 was made. It is a disease of the elderly. In the British Thoracic Society Study of nearly 600 cases, the mean age at presentation was 67.4 years; in another study in the Trent region of over 200 cases, the mean age of incident or newly presenting cases was 69.8 years. Both these studies showed a male predominance: 1.7:1 for all cases in the BTS study and 3.5:1 in the Trent study for incident cases. At presentation, patients have usually been symptomatic with breathlessness and cough for about a year. The standard treatment is oral steroids, although other immunosuppresives may be used. The response to treatment is normally poor with only a quarter of patients responding objectively. Earlier studies found a mean survival of 4 to 5 years from diagnosis, but more recently, the survival in unselected patients has been shown to be considerably worse, with about half dying by 3 years in both the BTS and Trent studies.

Mortality

Figure 1:Deaths attributed to fibrosing alveolitis

The majority of deaths attributed to CFA in England and Wales occur in those aged over 55, and there are more deaths among males than females. Recorded mortality due to CFA is increasing both in the UK and elsewhere (Australia and Canada).

Figure 2:Deaths attributed to fibrosing alveolitis, males and females

The number of deaths in England & Wales ascribed to CFA has increased steadily, with the total number trebling since the early 1980s. Figures 3 & 4 show the age-specific rates for males and females. The increase in mortality has been particularly marked in the elderly, although it is seen in all ages above 55.

However, the study of mortality is complicated by problems in coding. A specific ICD code for CFA (516.3) was introduced for the first time in 1979. An examination of the records of patients whose death certificates were coded 516.3 shows that a high proportion (83%) were likely to have had the disease. However, a substantial proportion (45%) of cases coded 519.9 (post-inflammatory pulmonary fibrosis (PIF)) were also considered to have had the disease. Nevertheless, diagnostic transfer between these codes is unlikely to account for the rise in mortality since there have been increases in deaths due to both CFA and PIF, and changes in the annual ratio of CFA to PIF deaths have been small. Recorded mortality from the disease is thought to underestimate total deaths with the disease by about half.

Cause

It is likely that CFA is due to a variety of causes. Genetic influences are suggested by familial clusters, although these are rare, and no convincing evidence for an HLA (tissue-type) association has yet been produced. Auto-antibodies (rheumatoid and antinuclear factors) are about twice as prevalent in patients with CFA as in the general population. Several recent studies have shown that CFA is about twice as common among cigarette smokers than non-smokers. There are also case reports of fibrosing alveolitis following severe specific lung infections and evidence of Epstein-Barr virus replication is found in lung tissue much more commonly in cases than in controls. A recent large case-control study concluded that up to 20% of cases might be attributable to metal and wood dust exposure. Finally, studies of GP prescribing records suggest that use of anti-depressants and certain other drugs might also be associated with the disease.

Summary

• CFA is a serious interstitial lung disease with a poor response to treatment and a poor prognosis.

• The mean age at presentation is almost 70 years and the disease is twice as common in men.

• Mortality due to CFA is steadily increasing.

• The causes of CFA are likely to be multiple and varied. It is associated with smoking and with exposure to metal and wood dust. Infection and drugs may also be important.

References

British Thoracic Society Study of cryptogenic fibrosing alveolitis: current presentation and initial management. Johnston IDA, Prescott RJ, Chalmers JC, Rudd RM. Thorax 1997, 52:38-44.

Occupational exposure to metal or wood dust and aetiology of cryptogenic fibrosing alveolitis. Hubbard R, Lewis S, Richards K, Johnston I, Britton J. Lancet 1996, 347:284-89.