Chest
Volume 130, Issue 1, July 2006, Pages 182-189
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Original Research
Immunosuppressive Therapy in Connective Tissue Diseases-Associated Pulmonary Arterial Hypertension

https://doi.org/10.1378/chest.130.1.182Get rights and content

Study objective

Immune and inflammatory mechanisms could play a significant role in pulmonary arterial hypertension (PAH) genesis or progression, especially in patients with connective tissue diseases. Immunosuppressive therapy should be better evaluated in this setting.

Study design

Monocentric retrospective study.

Patients

We reviewed the clinical and hemodynamic effects of immunosuppressants administered as first-line monotherapy to 28 consecutive patients with connective tissue disease-associated PAH.

Interventions

All patients received a monthly IV bolus of cyclophosphamide, 600 mg/m2, for at least 3 months, and 22 of 28 patients received systemic glucocorticosteroids. Responders to immunosuppressive therapy were defined as patients who remained in New York Heart Association (NYHA) functional class I or II with sustained hemodynamic improvement after at least 1 year of immunosuppressive therapy without addition of prostanoids, phosphodiesterase type 5 inhibitors, or endothelin receptor antagonists.

Results

Eight of 28 patients (systemic lupus erythematosus [SLE], n = 5; mixed connective tissue disease [MCTD], n = 3) [29%] were responders. These patients had a significantly improved 6-min walking distance (available in five patients) and a significant improvement in hemodynamic function. No patients with systemic sclerosis responded, while 5 of 12 patients with SLE and 3 of 8 patients with MCTD did respond. Survival analysis indicated that responders had a better survival than nonresponders. Patients with a lower baseline NYHA functional class and better baseline pulmonary hemodynamics (p < 0.05) were more likely to benefit from immunosuppressive therapy.

Conclusion

PAH associated with SLE or MCTD might respond to a treatment combining glucocorticosteroids and cyclophosphamide.

Section snippets

Patients

Between February 1991 and January 2001, 112 patients with connective tissue disease were referred to our institute for PAH management (systemic scleroderma, n = 61; SLE, n = 24; MCTD, n = 17; polymyositis, n = 2; Sjögren syndrome, n = 4; rheumatoid arthritis, n = 4). Among them, 28 patients (25%) were not previously treated with either PAH-specific therapies (IV, subcutaneous, inhaled, or oral prostacyclin derivatives, endothelin receptor antagonists, or phosphodiesterase type 5 inhibitors) or

Baseline Characteristics

Individual baseline demographic and hemodynamic parameters are summarized in Table 1. Most patients were female (82%), with a mean age of 40 ± 17 years. PAH was severe (Table 1), with a mean 6-min walk distance of 256 ± 109 m, and 75% of the patients were in NYHA functional class III (57%) or IV (18%).

Response to Immunosuppressive Therapy

Eight of 28 patients (29%) were responders to immunosuppressive therapy, as defined above. Five of eight responders had SLE (62%), and the remaining three responders had MCTD (38%). Clinical and

Discussion

Pulmonary hypertension is a major complication of connective tissue diseases. In some patients, pulmonary hypertension is due to either significant left-heart disease or chronic respiratory failure with hypoxemia, requiring specific management.2324 However, in many cases, the degree of pulmonary hypertension is not due to pulmonary fibrosis or left-heart disease and corresponds to chronic obstruction of small pulmonary arteries characteristic of PAH.2526 Advances in the understanding of the

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    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    This study was supported by grants from Universite Paris-Sud, Legs Poix, and Institut des Maladies Rares.

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