The challenges in paediatric pulmonary arterial hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a rare, progressive disease affecting both adults and children. While overall survival has improved in recent years, the need for improved therapeutic approaches remains. Treatments for paediatric PAH have not yet been sufficiently examined, particularly regarding potential toxicities and optimal dosing, and there is a lack of appropriate clinical trial end-points and validated treatment goals that might enable a goal-oriented therapeutic approach. Adult randomised controlled trials in PAH are demonstrating a shift towards more long-term designs, focusing on mortality and morbidity end-points rather than changes in 6-min walking distance. However, such trial designs may not be feasible within the paediatric setting due to challenges such as sufficient recruitment and retention of paediatric patients. Consideration should, therefore, be given towards identifying optimal end-points for the paediatric population, allowing sufficient duration to evaluate efficacy and safety of potential treatments. Herein we consider some of the complexities involved in the management of paediatric PAH, specifically presenting diagnostic challenges as well as reflecting on the lack of evidence currently available to support various therapeutic approaches within the paediatric population.

Figure 1.

Multifactorial causes of paediatric pulmonary hypertensive vascular disease. Reproduced from [9] with permission from the publisher.

Figure 2.

The recently proposed paediatric idiopathic/hereditable pulmonary arterial hypertension treatment algorithm. In Europe, the use of all agents is considered off-label in children, aside from sildenafil. CCB: calcium channel blocker; ERA: endothelin receptor antagonist; PDE-5i: phosphodiesterase type-5 inhibitor. Reproduced from [18] with permission from the publisher.