Clinical study
Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival,

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Abstract

PURPOSE: We evaluated the risk and potential benefit of high-dose corticosteroid therapy in patients with idiopathic pulmonary fibrosis.

SUBJECTS AND METHODS: We prospectively studied 41 patients with previously untreated, biopsy-proven idiopathic pulmonary fibrosis. Before treatment, we calculated clinical, radiographic, and physiologic severity-of-illness scores for each patient. We scored high-resolution computerized tomographic (CT) scans for ground glass and interstitial opacity. We determined the extent of cellular infiltration, interstitial fibrosis, desquamation, and granulation in open lung biopsy samples. Patients were monitored monthly for steroid-related side effects, response to therapy at 3 months, and mortality.

RESULTS: All patients experienced at least one steroid-induced side effect. Eleven (27%) patients were nonresponders, 11 (27%) were responders, and 19 (46%) remained stable. Of the 19 patients who died during a mean (± SD) follow-up of 3.3 ± 2.3 years, 8 (42%) lost weight during the initial 3 months of steroid therapy; only 3 (14%) of the 22 patients still living (P = 0.08) experienced weight loss. In a multivariate analysis, greater fibrosis (hazard ratio [HR] = 1.4 per unit increase; 95% confidence interval [CI]: 1.0 to 1.9; P = 0.03) and cellularity (RR = 1.9 per unit increase; 95% CI: 1.3 to 2.8; 3, P <0.001) in the biopsy sample and whether a patient was classified as a responder (RR = 0.4 versus nonresponder; 95% CI: 0.2 to 1.0; P = 0.05) or stable (RR = 0.2 versus nonresponder; 95% CI: 0.1 to 0.6, P <0.001) after steroid therapy were associated with mortality.

CONCLUSION: Corticosteroid treatment for idiopathic pulmonary fibrosis is associated with substantial morbidity. Patients who remain stable or respond to corticosteroid therapy have better survival than those who fail to respond. Whether this difference reflects an effect of treatment or less severe disease can be determined only in a randomized trial.

Section snippets

Sample

We included all patients referred to the University of Michigan for enrollment in the specialized center of research protocol for idiopathic pulmonary fibrosis, as diagnosed by symptoms, physiologic abnormalities, and radiographic findings. No patient had undergone previous surgical lung biopsy or received therapy. We excluded patients with other medical problems, and those who were unable or unwilling to undergo surgical lung biopsy.

Physiologic assessments

We measured pulmonary flows and volume, and the diffusing

Results

There were similar numbers of men and women in the sample (Table 1). When we compared the initial 24 patients who were treated with somewhat higher doses of prednisone with the subsequent 17 patients, we found that the mean total pathology scores (26 ± 2 versus 20 ± 2, P = 0.02) and the interstitial disease score on the CT scan (1.8 ± 0.2 versus 1.3 ± 0.2, P = 0.05) were somewhat greater in the patients who had been in the initial group.

Discussion

The corticosteroid dosage regimens that were used during the study period were chosen based on reports in the literature 6, 7, 20. Given the high incidence of side effects during the early phase of our study, we reduced the dose (from about 100 mg to 60 mg per day) in 17 patients. Nevertheless, we observed that steroid-related side effects occurred in all 41 patients with idiopathic pulmonary fibrosis. However, survival was better in patients who remained stable or responded to initial

Acknowledgements

We are grateful for the assistance and expertise provided by Phillip Cascade, MD, and David Spizarny, MD, while scoring CT scans associated with this investigation.

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    Supported in part by the National Institutes of Health (HL46487, RR00042, AG08808, HL04212).

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