Pathogenesis Of PAH Research Articles

Thyrotoxicosis as a Risk Factor for Pulmonary Arterial Hypertension

Letters7 February 2006Thyrotoxicosis as a Risk Factor for Pulmonary Arterial HypertensionLewis J. Rubin, MD and David B. Badesch, MDLewis J. Rubin, MDForm the University of California, San Diego, La Jolla, CA 92093, and the University of Colorado Health Sciences Center, Denver, CO 80262.Search for more papers by this author and David B. Badesch, MDForm the University of California, San Diego, La Jolla, CA 92093, and the University of Colorado Health Sciences Center, Denver, CO 80262.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-3-200602070-00023 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Drs. Ma and Chow that there is some justification for screening patients with PAH for thyroid dysfunction. We were among the first to make the observation that thyroid abnormalities might occur with increased frequency in patients with PAH (1). In that report, we speculated that there might be a common underlying autoimmune disorder. The concept that antithyroid antibodies could play a role in the pathogenesis of PAH is indeed quite intriguing, and there have been several subsequent reports of hypothyroidism and hyperthyroidism occurring in patients with pulmonary hypertension (2-5), although a causal relationship has not ...

Present and Future Treatment Strategies for Pulmonary Arterial Hypertension

Idiopathic pulmonary arterial hypertension (IPAH) is a rare progressive disorder historically associated with mortality in <3 years post-diagnosis. The etiology of PAH is complex, multifactorial, and likely involves the interplay between genetic and environmental factors. These are reviewed with emphasis on the nitric oxide pathway. Use of treatment modalities including vasodilator therapy have resulted in improved symptoms, hemodynamics, and survival in these patients. Vasodilators, including the calcium channel antagonists, prostanoids, and endothelin receptor antagonists, have been used to counteract potential imbalances in vasoactive mediators in PAH patients; all have produced improved long-term symptomatology and hemodynamics. Only the prostanoid epoprostenol has improved survival in IPAH patients. Although these medications have worked well in many patients with PAH, each of them has limitations. The phosphodiesterase-5 (PDE-5) inhibitors are a relatively new form of treatment for PAH. They are designed to potentiate the effects of cyclic guanosine monophosphate, thereby mimicking endogenous nitric oxide within the vasculature. PDE-5 inhibitors are selective pulmonary vasodilators effective in animal models of pulmonary hypertension. The published clinical studies evaluating their use have been small in size to date but appear to demonstrate benefit. The recently completed 12-week randomized placebo-controlled Sildenafil Use in Pulmonary Hypertension (SUPER-1) trial demonstrated improvement in 6-minute walk distance and hemodynamics in patients receiving sildenafil. These data suggest that the PDE-5 inhibitors are effective in treating PAH and that it is likely that their usage will increase over time. The purpose of this review is to present a current view of the pathogenesis and treatment of PAH, with an emphasis on the use of PDE-5 inhibitors in these patients.

RECENT ADVANCES IN THE TREATMENT OF PEDIATRIC PULMONARY ARTERY HYPERTENSION

As our understanding of the pathogenesis of PAH evolves, newer strategies for its treatment are being developed and implemented. Based on studies with adult PPH patients, anticoagulation is now regarded as a mainstay of therapy and is associated with prolonged survival. Before the era of vasodilator therapy, which began in the late 1970s, most children with PPH died within 1 year of diagnosis. Now with chronic calcium channel blockade, survival and QOL are improved in children who acutely respond to vasodilator drug testing. In the author's experience, the 5-year survival rate for patients treated with chronic oral calcium channel blockade who respond acutely to vasodilator testing is 97% versus 35% for those who do not respond acutely. Continuous i.v. prostacyclin has also been used successfully, with a 5-year survival rate of 92% in children in whom oral calcium channel blockade failed (although in some patients the prostacyclin therapy was used as a bridge to transplantation) versus 29% in children in whom oral calcium channel blockade also failed and for whom chronic prostacyclin was unavailable. Before the availability of long-term prostacyclin therapy, 30% to 40% of patients with PPH died while waiting for transplantation. Prostacyclin has virtually eliminated this situation. The results of lung transplantation for adult patients with PPH at 3 years are similar to the results of those on continuous i.v. prostacyclin. Ultimately, the best therapy for an individual child depends on the results of longer follow-up studies. Inhaled nitric oxide has also been used to treat PAH in newborns and other forms of acute and chronic PAH. Although less experience exists with long-term inhaled nitric oxide than with long-term prostacyclin, the preliminary results of long-term inhaled nitric oxide are promising and await further study. The "optimal" vasodilator for long-term therapy, (e.g., calcium channel blockade), prostacyclin, nitric oxide, or potential future therapies, such as prostacyclin analogs, endothelin receptor blockers and thromboxane synthase inhibitors or receptor blockers, must be based on a thorough evaluation with acute vasodilator testing and overall risk-benefit considerations for the various therapeutic regimens. Further clarification of the mechanisms of the development and perpetuation of the PAH process will undoubtedly lead to a refinement in treatment strategies for patients with PAH, which not too long ago was often considered untreatable and fatal. By increasing our understanding of the pathogenesis and pathophysiology of primary and secondary PAH disorders, one day we may be able to prevent or cure these diseases as opposed to providing only palliative therapy. Despite this, therapeutic advances have significantly improved the outcome for children with PAH.