Asian Cardiovasc Thorac Ann 2000;8:353-356
© 2000 Asia Publishing EXchange Pte Ltd
High-Resolution Computed Tomography and Survival in Fibrosing Alveolitis
Omer S Alamoudi, MD,
Paul M Logan, MD,
Nestor L Muller, MD,
Sverre Vedal, MD,
Raja T Abboud, MD
Respiratory Division
Departments of Medicine and Radiology
Vancouver General Hospital
University of British Columbia
Vancouver, Canada
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For reprint information contact: Omer S Alamoudi, MD Tel: 966 2 640 8272 Fax: 966 2 640 8315 email: oamoudi{at}sbm.net.sa Department of Medicine, King Abdulaziz University Hospital, P.O. Box 80215, Jeddah 21589, Saudi Arabia.
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Abstract
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High-resolution computed tomography findings were reviewed in 32 patients with cryptogenic fibrosing alveolitis and 18 with fibrosing alveolitis associated with connective tissue diseases (other than scleroderma). The percentage of abnormal lung, total ground-glass attenuation, ground-glass attenuation not associated with fibrosis, and fibrosis (reticular pattern and honeycombing) were compared with lung function and survival. In cryptogenic fibrosing alveolitis, 1-year mortality tended to be higher in patients with predominantly fibrotic lesions (39%) compared to mainly ground-glass attenuation (11%). Similar results were obtained in fibrosing alveolitis associated with connective tissue disease (1-year mortality 44% for fibrosis versus 22% for ground-glass attenuation), but the differences were not statistically significant. In cryptogenic fibrosing alveolitis, the extent of abnormal lung on initial computed tomography was 67% ± 20% in survivors at 1 year and 86% ± 8% in nonsurvivors (p < 0.005); this difference was still significant at 4 years. In fibrosing alveolitis associated with connective tissue disease, the degree of lung involvement between survivors and nonsurvivors was different at 1 year only, thus other factors seem to determine survival. Ground-glass attenuation associated with fibrosis adversely affected survival in cryptogenic fibrosing alveolitis, in contrast to isolated ground-glass attenuation.
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Introduction
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Fibrosing alveolitis (FA), or usual interstitial pneumonia, is a diffuse interstitial lung disease of undetermined etiology, characterized by interstitial fibrosis and inflam-mation with a component of alveolitis. It has a progressive course that usually leads to death 3 to 5 years after the onset of symptoms.1–4 FA may be classified into two categories with similar histology: cryptogenic (idiopathic) fibrosing alveolitis (CFA); and FA associated with connective tissue disease (FA-CTD).2 High-resolution computed tomography (HRCT) has become an important tool for diagnosing FA noninvasively, and it provides good evidence of the extent and pattern of lung involvement.5,6 HRCT findings correlate with the histological picture and disease activity.7–11 The presence of a ground-glass (GG) pattern usually indicates an inflammatory process on histology with a favorable response to therapy, while the presence of reticular changes and honeycombing indicates fibrosis with a poor response to therapy.7–15 The purpose of this study was to determine whether HRCT findings could predict the course of the disease and survival in patients with CFA and FA-CTD.
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Patients and Methods
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This was a retrospective study of all patients with FA who were seen at our institution from October 1983 to June 1993, in whom HRCT, pulmonary function tests, and clinical assessments were part of their initial evaluation. Four patients with FA-CTD who had systemic sclerosis were excluded from the study because Wells and colleagues14 found that HRCT did not predict survival in patients with systemic sclerosis. Of the remaining 50 patients, 32 had CFA, their mean age was 66 ± 10 years, duration of disease was 50 ± 42 months, forced vital capacity was 61% ± 25% of the predicted value, and CO transfer factor (diffusing capacity) of the lung was 46% ± 23% of predicted. The other 18 patients had FA-CTD, their mean age was 62 ± 16 years, disease duration was 41 ± 46 months, forced vital capacity was 59% ± 16% of predicted, and CO transfer factor was 42% ± 16% of predicted. The diagnosis of CFA was confirmed in 16 patients by open lung biopsy, whereas diagnosis was based on clinical, functional, and radiological features in the other 16. The criteria for CFA were bibasilar or widespread crackles on auscultation of the chest, pul-monary function tests with restrictive findings or reduced CO transfer factor, HRCT features compatible with fibrosing alveolitis, and absence of other causes of fibrosing alveolitis. Of the 18 patients with FA-CTD, 16 had rheumatoid arthritis diagnosed according to the criteria of the American Rheumatological Association, and 2 had systemic lupus erythematosus.16 Diagnosis of FA-CTD was confirmed by open lung biopsy in 11 patients. Survival information was obtained from hospital records of follow-up carried out by staff of the respiratory division, the most recent follow-up data available was for July 1996. In patients who did not report for follow-up, information regarding survival was obtained from their family doctors and immediate relatives. The duration of follow-up in survivors with CFA ranged from 37 to 124 months with a mean of 64 months, while in FA-CTD, the duration of follow-up ranged from 50 to 135 months with a mean of 55 months.
HRCT scans were obtained with a GE 9800 scanner (GE Medical Systems, Milwaukee, IL, USA). All patients underwent HRCT of the chest at the time of diagnosis and before starting any therapy. HRTC was performed using 1.5-mm collimating scans at 10-mm intervals, images were reconstructed using a high-spatial-frequency algo-rithm. Each scan was obtained during a breath-hold at end-inspiration. The lungs were divided into 3 zones (upper, middle, and lower); each zone was evaluated separately for the presence and extent of areas of GG attenuation, reticular pattern, and honeycombing. Each of the 3 zones corresponded to approximately one-third of the images from the lung apex to 1 cm below the dome of the diaphragm. HRCT was evaluated by 2 observers (PML, NLM) who reached a consensus and graded the HRCT of each lung zone according to: % of lung involve-ment (both GG and fibrosis); % of lung involvement by GG attenuation; % of lung involvement by fibrosis (reticu-lar pattern and honeycombing); and % of involvement by GG attenuation in areas without fibrosis, since GG attenuation in areas of fibrosis often represents microscopic fibrosis below the resolution of the scanner rather than active alveolitis.11 From these data, the overall extent of abnormal lung and the extent of lung involvement for each pattern could be calculated, as in previous studies.14,16 We also calculated the % area of GG pattern associated with fibrosis, from the difference between total GG and isolated GG areas. On the basis of HRCT, cases were classified as predominantly fibrotic when the area of lung with fibrosis was greater than the total area with GG pattern, or predominantly GG when lung involvement with GG pattern 
fibrosis.
Statistical analyses were performed using SPSS software (SPSS Inc, Chicago, IL, USA). Student's t test was used to compare means of 2 continuous distributions. Chisquared analysis or Fisher's exact test when expected values were low, were used to compare proportions across 2 groups. Survival was defined as the time in months from HRCT scan to either death or the end of the period of observation. The adequacy of the model was assessed by determining whether the proportional hazards assump-tion was met; continuous variables were dichotomized at the mean value for examining model adequacy.
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Results
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There were no significant differences in age, duration of disease on presentation, lung function results, or HRCT findings between patients with CFA and those with FA-CTD. In patients with CFA, 23/32 (72%) had a predominantly fibrotic pattern compared with 9/18 (50%) patients with FA-CTD (p > 0.10). Survival was similar in both the CFA and FA-CTD groups (Table 1
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Table 1. Survival in 32 Patients With Cryptogenic Fibrosing Alveolitis and 18 With Fibrosing Alveolitis and Connective Tissue Disease
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The relationship between survival and the extent of abnormal lung determined by HRCT in CFA and FA-CTD patients is shown in Table 2. Surviving patients at 1 year in both groups had a significantly lower percentage of abnormal lung on initial HRCT than those who died. Late survivors in the CFA group also had significantly less lung involvement than non-survivors, in contrast to the FA-CTD group where late survival was not related to the extent of abnormal lung (Table 2). Mortality according to predominant HRCT pattern is shown in Table 3. In both CFA and FA-CTD groups, mortality increased during 4 years of follow-up, but it was similar in the predominantly GG and predominantly fibrotic subgroups.
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Discussion
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Fibrosing alveolitis has a poor prognosis with no effective curative therapy available at present; the 5-year survival rate is less than 50%.1–4 Diagnosis of FA can be suspected by the clinical presentation and physical examination, and it may be supported noninvasively by the findings on chest radiography, pulmonary function testing, and bronchoalveolar lavage.1–3,17–20 Open or thoracoscopic lung biopsy is the definitive procedure to confirm the diagnosis, assess disease activity, and provide useful information about prognosis. However, open lung biopsy is an invasive procedure associated with some morbidity, which may not be tolerated by every patient. The need for a noninvasive investigation to confirm the diagnosis and aid prognosis has made HRCT an important tool in evaluating pulmonary fibrosis. HRCT also helps to determine the extent of disease, pattern of distribution, and presence of disease activity.5–11
The results of our study indicate a significant correlation between the extent of lung involvement and survival in CFA. In FA-CTD, factors other than the extent of lung involvement seem to determine survival. Previous studies have shown HRCT to be useful for differentiating between predominantly inflammatory and predominantly fibrotic disease.8–11 Reticular changes and honeycombing indicate fibrosis that tends to have a worse prognosis, while GG attenuation usually indicates an inflammatory component of alveolitis, which usually responds favorably to corti-costeroids.12–14 However, areas of microscopic fibrosis may also appear as GG attenuation on HRCT.8,10,11 Therefore, we quantified areas of GG attenuation isolated from fibrosis, in addition to the total extent of GG attenuation. Thus, we could analyze the relationship of duration of survival to the total GG attenuation, to isolated GG attenuation, and to GG attenuation associated with fibrosis.
A significant negative correlation was found in CFA between duration of survival and both the extent of fibrosis and the extent of GG attenuation associated with fibrosis, but not with the total area of GG attenuation or the extent of isolated GG attenuation, suggesting that GG attenuation in such a location is at least partly due to microscopic fibrosis rather than alveolitis. A predominantly GG pattern in CFA appears to be associated with a lower mortality rate at 1 year (but not subsequently) than a predominantly fibrotic pattern. Our findings suggest that the extent of lung involvement, fibrosis, and GG pattern associated with areas of fibrosis may be more important than the overall HRCT pattern (fibrotic versus GG) in determining survival. In contrast, Wells and colleagues14 in a study of 76 patients with CFA, reported that patients with a predominantly GG pattern survived longer than those with a predominantly fibrotic pattern, however, they did not correlate duration of survival with HRCT-determined extent of disease. The difference between the two studies regarding the relationship of the predominant HRCT pattern to survival may be due to differences in patient populations and to the smaller numbers in our study.
Our study confirms that use of HRCT to determine the pattern and extent of lung involvement is helpful in assessing prognosis in CFA. Although the results were significant, there were some limitations: it was a retrospective study in which the data was extracted from patients' files; and a relatively small number of patients were studied, particularly in FA-CTD. However, we concluded that the extent and pattern of lung involvement on HRCT predicted prognosis in CFA, but not in FA-CTD (other than scleroderma). Short-term survival may be better in patients with a predominantly GG pattern than those with a predominantly fibrotic pattern. Moreover, the extent of lung involvement affected survival in CFA but not in FA-CTD.
Presented in part, at the American Thoracic Society 1995 International Conference, Seattle, Washington, USA, May 20–24, 1995.
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Abstract
Introduction
