A retrospective analysis of 220 cases fulfilling criteria for cryptogenic fibrosing alveolitis (CFA) attending the Brompton Hospital between 1955 and 1973 has been carried out and patients have been followed for between four and 21 years. The frequency of various clinical features confirms previous reports. The 2 :1 male preponderance was similar in all age groups.The mean age at presentation was 54 years ± 12 SD; 202 (92%) of the patients presented with dyspnoea, the severity of which was related to the reduction in vital capacity (p < 0 003) and to the radiographic profusion score (p < 0.01) but not to its duration. Twenty-one per cent of the 220 had joint symptoms, 10% having clinical rheumatoid arthritis. Eleven showed much greater fibrosis and less acute inflammatory cellularity in spite of an interval between onset of symptoms and death of less than four years in 21 of 26 patients. One hundred and fifty-six patients have died (mean survival 3 -2 years). Eleven (5 %) are believed to be alive but have been lost to follow-up. Fifty-five per cent of deaths were attributable directly or indirectly to CFA. There was also an excess of deaths from cardiovascular disease and lung cancer. Using a life-table analysis and a log rank test, longer survival was seen in younger patients (p < 0 001) and women (p < 0.01). After correction for age and sex, lesser grades of dyspnoea (p <0 03) and lesser radiographic abnormality (p < 0-001), absence of right axis deviation (p < 0-001), and a higher Pao2 (p < 0-01) also related to longer survival. Subjects with more cellular histology also survived longer (p <0 02). Factors having no influence on survival included duration of dyspnoea before presentation, degree of reduction of FEV1, FVC, and TLC, the presence of "connective tissue"
Lung cancer was found in 20 (9.8%) of 205 patients with cryptogenic fibrosing alveolitis (CFA) or 12.9% of the 155 patients in this series followed to death. An excess relative risk of lung cancer of 14.1 was found in patients with CFA compared to the general population of comparable age and sex, allowing for the lengths of follow-up of the CFA patients. The relative risk for male smokers was (observed/expected) 15+1.06 = 14.2, and for female smokers (O/E) 2/0.3 = 6.7. Only one male and one female non-smoker had lung cancer. These data suggest that there is an excess risk of lung cancer not wholly accounted for by age, sex, or smoking habit. The distribution of histological types was not obviously different from that found in lung cancer without pulmonary fibrosis. Large opacities suggestive of lung cancer were present at the time of first hospital attendance for symptoms relating to CFA in four of the 20 patients. Finger clubbing was present in 19 (95%) compared with 116/185 (63%) of those so far not developing cancer. There were no other clinical differences at presentation. In particular, cancer was not found especially in those with longer survival from the onset of symptoms of CFA or with a greater initial radiographic change.
In a randomised, controlled study alternate day prednisolone with an initial high dose phase ("prednisolone only series") has been compared with cyclophosphamide plus alternate day low dose prednisolone ("cyclophosphamide-prednisolone series") in 43 patients with previously untreated fibrosing alveolitis (five patients had received prednisolone in minimal dosage). In the prednisolone only series prednisolone 60 mg daily was given for one month and then reduced by 5 mg a week to 20 mg on alternate days or the minimum dose to maintain early improvement. Patients in the cyclophosphamide-prednisolone series received 100, 110, or 120 mg cyclophosphamide daily (depending on body weight) plus 20 mg prednisolone on alternate days. Treatment was continued indefinitely, or changed to the alternative regimen if the patient deteriorated, failed to improve, or developed drug toxicity. For response to treatment (as judged by change in breathlessness score, radiographic appearance, and lung function) patients were classified as improved, stable, or deteriorating. Deaths from cryptogenic fibrosing alveolitis were also analysed.Improvement had occurred at one or more assessments in seven of the 22 patients in the prednisolone only series and in five of the 21 patients in the cyclophosphamide-prednisolone series. At three years, however, only two ofthe 22 patients in the prednisolone only series were still improved and three stable, compared with one and seven of the 21 patients in the cyclophosphamideprednisolone series (three of the seven had stopped treatment because of toxicity).Life table analysis suggested better survival in patients in the cyclophosphamide-prednisolone series but this was not significant. At three years 10 of 22 patients in the prednisolone only series had died compared with three of 21 patients in the cyclophosphamide-prednisolone series. With death or failure of first treatment regimen as outcome there was a significant advantage to the patients having cyclophosphamide-prednisolone. This advantage was explained in part by the better lung volumes in this group on admission. After allowance had been made for total lung capacity (TLC), no other factor was predictive ofoutcome. Analyses ofsubgroups according to TLC on admission showed that patients with a TLC below 60% predicted did badly and those with a TLC of 80% or more predicted did well with both regimens. Patients with an initial TLC of 60-79% predicted did better with the cyclophosphamide-prednisolone regimen. Side effects were uncommon in both series and those due to cyclophosphamide resolved when treatment was stopped. The combination of cyclophosphamide with prednisolone may be an alternative to prednisolone alone with an initial high dose phase. Many patients, however, failed to respond to either treatment.
We have studied retrospectively 220 patients with cryptogenic fibrosing alveolitis (CFA) who were first seen between 1955-73 and had been followed up for at least four years until 1977. Seventy-seven patients had received no treatment and 143 had received corticosteroids. The only clinical difference between the groups was the age at presentation (untreated mean age 61 years± 11 SD; treated mean age 56 years± 11 SD p < 0001). The influence of corticosteroid treatment has been assessed both in terms of the clinical, radiographic, and physiological response after four to eight weeks and in terms of survival, using a log rank method of analysis. Of 143 treated cases 127 had detailed follow-up information. Seventy-two (57 %) had substantial subjective improvement of breathlessness but only 22 (17 %) of the total showed additional objective improvement. The only factors significantly distinguishing the 72 subjective responders from the 55 non-responders, and which therefore might be used as predictors of response, were a younger age at presentation (p < 0 001) and less dyspnoea (p < 0 02). Analysis of survival data demonstrated that treated patients who showed an early good response to steroids had a markedly better survival than non-responders (p <0 0 1). The survival curve for the untreated group lay between the two steroid groups. Analysis of the survival data suggests that steroid responsiveness relates particularly to a subgroup with an inherently better prognosis, which is characterised by a younger age and probably by a cellular histology not however necessarily typical of desquamative interstitial pneumonia. Nevertheless treatment appears to have an additional influence on survival especially in early disease, which is not observed in the untreated cases. A large number of factors are not related either to steroid responsiveness or to survival and these include the presence of associated "connective tissue" diseases, autoantibodies, and the duration of dyspnoea at presentation. It is concluded that biopsy information is valuable in assessment of potential to respond to steroids and that if steroid treatment is to be helpful it must be used at an early stage. The response is very variable and titration of the steroid dose against an individual patient's response is likely to give better results than adherence to arbitrary dose schedules.
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