title: Circulating endothelial cells in refractory pulmonary hypertension in children: markers of treatment efficacy and clinical worsening.
abstract: BACKGROUND
  Pulmonary vasodilators in general and prostacyclin analogues in particular have improved the outcome of patients with pulmonary arterial hypertension (PAH). Endothelial dysfunction is a key feature of PAH and we previously described that circulating endothelial cell (CEC) level could be used as a biomarker of endothelial dysfunction in PAH. We now hypothesized that an efficient PAH-specific vasodilator therapy might decrease CEC level.
  
  
  RESULTS
  CECs were prospectively quantified by immunomagnetic separation with mAb CD146-coated beads in peripheral blood from children with idiopathic PAH (iPAH, n = 30) or PAH secondary to congenital heart disease (PAH-CHD, n = 30): before, after treatment and during follow up. Controls were 23 children with reversible PAH. Oral treatment with endothelin receptor antagonists (ERA) and/or phosphodiesterase 5 inhibitors (PDE5) significantly reduced CEC counts in children. In 10 children with refractory PAH despite oral combination therapy, subcutaneous (SC) treprostinil was added and we observed a significant decrease in CEC counts during the first month of such treatment. CECs were quantified during a 6 to 36 month-follow-up after initiation of SC treprostinil and we found that CEC counts changed over time, with rising counts always preceding clinical deterioration.
  
  
  CONCLUSIONS
  CECs might be useful as a biomarker during follow-up of pediatric iPAH and PAH-CHD to assess response to treatment and to anticipate clinical worsening.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Levy
authors.forename: Damien
authors.initials: D
authors.lastname: Bonnet
authors.forename: Laetitia
authors.initials: L
authors.lastname: Mauge
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D042783:Endothelial Cells / Q000473:pathology*; D065128:Endothelin Receptor Antagonists; D004730:Endothelium, Vascular / Q000473:pathology*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000627:therapeutic use; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D018189:Immunomagnetic Separation; D007223:Infant; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use; D011446:Prospective Studies; D012720:Severity of Illness Index; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D058986:Phosphodiesterase 5 Inhibitors; D014665:Vasodilator Agents; D011464:Epoprostenol; C427248:treprostinil