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Cyclophosphamide Is Associated with Pulmonary Function and Survival Benefit in Patients with Scleroderma and Alveolitis

Barbara White, MD; Wendy C. Moore, MD; Fredrick M. Wigley, MD; Hui Qing Xiao, MD; and Robert A. Wise, MD
[+] Article and Author Information

From Veterans Affairs Maryland Health Care System, University of Maryland School of Medicine, and Johns Hopkins University Medical Institutions, Baltimore, Maryland.


Grant Support: By grant 1RO1HL54163 from the National Institutes of Health (Dr. White) and a grant from the Maryland Chapter, Arthritis Foundation.

Requests for Single Reprints: Barbara White, MD, Baltimore Veterans Affairs Medical Center, Research Service, Stop 151, Room 325-A, 10 North Greene, Baltimore, MD 21201.

Requests To Purchase Bulk Reprints (minimum, 100 copies): the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints@mail.acponline.org.

Current Author Addresses: Dr. White: Baltimore Veterans Affairs Medical Center, Research Service, Stop 151, Room 3A-125, 10 North Greene Street, Baltimore, MD 21201.

Dr. Moore: Division of Pulmonary and Critical Care Medicine, Biomedical Research Building, 108 North Greene Street, Suite 119, Baltimore, MD 21201.

Dr. Wigley: Division of Molecular and Clinical Rheumatology, Johns Hopkins University School of Medicine, 1830 East Monument Street, Suite 7300, Baltimore, MD 21205.

Drs. Xiao and Wise: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Room 4B-72, Baltimore, MD 21224.

Author Contributions: Conception and design: B. White, F.M. Wigley, R.A. Wise.

Analysis and interpretation of the data: B. White, F.M. Wigley, R.A. Wise.

Drafting of the article: B. White, W.C. Moore.

Critical revision of the article for important intellectual content: B. White, F.M. Wigley, R.A. Wise.

Final approval of the article: B. White, W.C. Moore, F.M. Wigley, H.Q. Xiao, R.A. Wise.

Provision of study materials or patients: B. White, F.M. Wigley, R.A. Wise.

Statistical expertise: R.A. Wise.

Obtaining of funding: B. White.

Administrative, technical, or logistic support: B. White, F.M. Wigley.

Collection and assembly of data: B. White, W.C. Moore, H.Q. Xiao, R.A. Wise.


Ann Intern Med. 2000;132(12):947-954. doi:10.7326/0003-4819-132-12-200006200-00004
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Interstitial lung disease is the major cause of death in patients with systemic sclerosis (scleroderma) (1). Pathologic studies of early disease show inflammation in the pulmonary interstitium that spills into alveolar spaces (2). Bronchoalveolar lavage fluid obtained from patients with scleroderma who have lung inflammation (alveolitis) may contain increased numbers of total cells, T cells, neutrophils, eosinophils, and mast cells (37). Alveolitis has been associated with subsequent deterioration of pulmonary function in scleroderma (34).

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Figure 1.
Change in forced vital capacity (FVC) (top left and right) and carbon monoxide diffusing capacity (Dlco) (bottom leftandright) over time in patients with scleroderma.

Results of pulmonary function tests done at the time of bronchoalveolar lavage or lung biopsy were compared with those of the last tests done in a patient. “Treated” indicates patients with alveolitis who received cyclophosphamide, and “untreated” indicates patients with alveolitis who did not receive cyclophosphamide. The line in the middle of each box shows the 50th percentile, the limits of the box show the 25th and 75th percentiles, and the limits of the bar show the 5th and 95th percentiles.

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Figure 2.
Survival in patients with scleroderma and alveolitis.dashed linesolid lineP

Survival was better among patients with alveolitis who received cyclophosphamide ( ) than among patients with alveolitis who were not treated ( ) ( = 0.01, Cox–Mantel log-rank test). The numbers above the lines are the number of patients at risk at the indicated time point. The median survival rate was 89% (25th, 75th percentiles, 84%, 94%) in treated patients and 71% (25th, 75th percentiles, 55%, 86%) in untreated patients.

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Summary for Patients

Cyclophosphamide To Treat Patients with Scleroderma Lung Disease

The summary below is from the full report titled “Cyclophosphamide Is Associated with Pulmonary Function and Survival Benefit in Patients with Scleroderma and Alveolitis.” It is in the 20 June 2000 issue of Annals of Internal Medicine (volume 132, pages 947-954). The authors are B. White, W.C. Moore, F.M. Wigley, H.Q. Xiao, and R.A. Wise.

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