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

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

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

Abstract

Background: Lung inflammation (alveolitis) may cause lung fibrosis in scleroderma.

Objective: To determine whether cyclophosphamide treatment is associated with retention of lung function and improved survival in scleroderma patients with alveolitis.

Design: Retrospective cohort study.

Setting: Johns Hopkins and University of Maryland Scleroderma Center.

Patients: 103 patients with scleroderma who had bronchoalveolar lavage or lung biopsy.

Intervention: Cyclophosphamide therapy.

Measurements: 1) Serial measurement of forced vital capacity [FVC] and carbon monoxide diffusing capacity and 2) survival.

Results: During a median follow-up of 13 months after bronchoalveolar lavage or biopsy, patients with alveolitis who did not receive cyclophosphamide therapy experienced a decrease in FVC (mean difference, −0.28 L [95% CI, −0.41 to −0.16 L] and −7.1% of the predicted value [CI, −10.9% to −4.0%]). Carbon monoxide diffusing capacity also decreased in these patients (mean difference, −3.3 mmol · min ⁻¹ · kPa ⁻¹ [CI, −4.6 to −2.1 mmol · min ⁻¹ ·kPa ⁻¹] and −9.6% of the predicted value [CI, −16.7% to −2.4%]). During a median follow-up of 16 months, patients with alveolitis who received cyclophosphamide were more likely to have a good outcome (stabilization or improvement) in FVC (relative risk, 2.5 [CI, 1.5 to 4.1]) and diffusing capacity (relative risk, 1.5 [CI, 1.0 to 2.2]). These patients also had improved survival; the median survival rate was 89% (25th, 75th percentiles, 84%, 94%) compared with 71% (25th, 75th percentiles, 55%, 86%) in untreated patients (P = 0.01, log-rank test).

Conclusions: The presence of lung inflammation identifies patients with scleroderma who are more likely to have worsening lung function. Lung function outcomes and survival are improved in patients with alveolitis who receive cyclophosphamide.

Article and Author Information

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.
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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.