Correspondence

Treatment of Pulmonary Arterial Hypertension

N Engl J Med 2005; 352:308-309January 20, 2005

Article

To the Editor:

In their review of treatment for pulmonary arterial hypertension, Humbert et al. (Sept. 30 issue)1 discuss therapeutic strategies with the use of prostacyclin and endothelin-receptor antagonists. Potential future therapies focus on other vasodilators and combination therapy. However, in addition, on the basis of pathophysiological mechanisms, there might be a role for immunosuppressive therapy. Several case reports show that in patients with systemic lupus erythematosus, the use of immunosuppressive drugs in the absence of disease activity results in an improvement of severe pulmonary arterial hypertension.2,3 Recently, the role of inflammation in pulmonary arterial hypertension has been described.4 Moreover, endothelin-receptor antagonists work not only because of their vasodilating effects, but also because of their blockade of the proliferation of smooth-muscle cells. In that respect, they are disease-modifying drugs.5 The combination of vasodilating, antiproliferative, and immunosuppressive therapies might be the most effective approach. Further studies are warranted to elucidate the role of immunosuppressive therapy in pulmonary arterial hypertension.

Anne-Margriet Huisman, M.D.
Sint Franciscus Gasthuis, 3045 PM Rotterdam, the Netherlands
m.huisman@sfg.nl

Simone A. Vreugdenhil, M.D.
Erasmus Medical Center Rotterdam, 3000 DR Rotterdam, the Netherlands

Henk C. van Paassen, M.D.
Sint Franciscus Gasthuis, 3045 PM Rotterdam, the Netherlands

5 References

1. 1

   Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351:1425-1436
   Full Text | Web of Science | Medline

2. 2

   Karmochkine M, Wechsler B, Godeau P, Brenot F, Jagot JL, Simonneau G. Improvement of severe pulmonary hypertension in a patient with SLE. Ann Rheum Dis 1996;55:561-562
   CrossRef | Web of Science | Medline

3. 3

   Morelli S, Giordano M, De Marzio P, Priori R, Sgreccia A, Valesini G. Pulmonary arterial hypertension responsive to immunosuppressive therapy in systemic lupus erythematosus. Lupus 1993;2:367-369
   CrossRef | Web of Science | Medline

4. 4

   Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J 2003;22:358-363
   CrossRef | Web of Science | Medline

5. 5

   Mayes MD. Endothelin and endothelin receptor antagonists in systemic rheumatic disease. Arthritis Rheum 2003;48:1190-1199
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Dr. Huisman and colleagues that inflammatory mechanisms may play an important role in pulmonary arterial hypertension of various origins.1 Considerable improvements have been reported with the use of antiinflammatory drugs in cases of pulmonary arterial hypertension associated with systemic lupus erythematosus.2 In addition, patients with idiopathic pulmonary arterial hypertension also have immunologic disturbances, suggesting a possible role of inflammation in the pathophysiology of the condition. However, most, if not all, of such patients have no clinical response to antiinflammatory agents, and current therapeutic guidelines therefore do not consider these drugs.3,4 Nevertheless, it is widely accepted that antiinflammatory agents should be proposed for patients with pulmonary arterial hypertension and active inflammatory diseases such as systemic lupus erythematosus.2 Currently approved therapies (endothelin-receptor antagonists and prostacyclin derivatives) have antiinflammatory effects, possibly contributing to the efficacy of these drugs, which do not act as pure vasodilators.4,5 Further developments in the management of pulmonary arterial hypertension may indeed involve the use of a combination of drugs with different targets and effects in order to maximize their action on the vasoconstrictive, proliferative, and inflammatory components of the disease process.4

Marc Humbert, M.D., Ph.D.
Olivier Sitbon, M.D.
Gérald Simonneau, M.D.
Hôpital Antoine Béclère, 92140 Clamart, France
marc.humbert@abc.aphp.fr

5 References

1. 1

   Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J 2003;22:358-363
   CrossRef | Web of Science | Medline

2. 2

   Sanchez O, Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary hypertension secondary to connective tissue diseases. Thorax 1999;54:273-277
   CrossRef | Web of Science | Medline

3. 3

   Badesch DB, Abman SH, Ahearn GS, et al. Medical therapy for pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004;126:Suppl:35S-62S
   CrossRef | Web of Science | Medline

4. 4

   Humbert M, Sitbon O, Simmoneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351:1425-1436
   Full Text | Web of Science | Medline

5. 5

   Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med 2004;351:1655-1665
   Full Text | Web of Science | Medline