lu-208075 and Sarcoidosis

Sarcoidosis associated pulmonary hypertension (SAPH) is associated with significant morbidity and mortality. There is a paucity of information concerning therapy for this condition.. We performed a prospective, open-label, proof of concept trial of ambrisentan for SAPH. 21 subjects with SAPH received 5 mg/day of ambrisentan for 4 weeks and then 10/mg day for 20 subsequent weeks.. No significant change was noted in the 6-minute walk distance over the course of the study (mean change between week 0 and 24: 9.8 +/- 54.6 meters, p: NS). There were also no significant differences between weeks 0 and 24 in terms of dyspnea as measured by the modified Borg scale, serum brain naturetic peptide, diffusing capacity, and quality of life as measured by the Short Form-36. There was a high dropout rate: overall: 11/21, 52%; social reasons: 3/21, 14%; medical reasons: 8/21, 38% because of dyspnea: 6/21, 29% and/or edema: 4/21, 19%. Of those who completed the 24 week study (10/21, 48%), there was an improvement in their WHO functional class and a marked improvement in their health related quality of life as measured by the St. George Respiratory questionnaire (-15.3 +/- 25.0). However both these improvments did not reach statistical significance possibly because of the small sample size.. Although ambrisentan was not well tolerated by many of these subjects with SAPH, in those who remained in this 24-week trial, improvements in WHO functional class and in health related quality of life suggested a possible benefit of this drug in selected patients.

Topics: Adult; Antihypertensive Agents; Exercise Test; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary; Lung; Male; Middle Aged; North Carolina; Phenylpropionates; Prospective Studies; Pyridazines; Quality of Life; Recovery of Function; Respiratory Function Tests; Sarcoidosis; South Carolina; Surveys and Questionnaires; Time Factors; Treatment Outcome

Sarcoidosis is a pleomorphic disease that can present with pulmonary hypertension (PH). What little information is available about the association of these two diseases comes mainly from small series of patients scheduled for transplant. We present 4 cases of mild pulmonary involvement in whom right catheterisation was performed and PH-specific therapy was administered. After obtaining written consent, a genetic study was performed that showed mutations in PH-related genes in 3 of the patients. This is the first study of its kind to yield genetic information for this type of PH.

Topics: Bone Morphogenetic Protein Receptors, Type II; Bosentan; Disease Progression; Epoprostenol; Fatal Outcome; Female; Humans; Hypertension, Pulmonary; Kv1.5 Potassium Channel; Male; Middle Aged; Mutation; Phenylpropionates; Point Mutation; Pyridazines; Respiratory Function Tests; RNA, Messenger; Sarcoidosis; Sildenafil Citrate; Sulfonamides; Tadalafil; Treatment Outcome