Epidemiology of pediatric pulmonary hypertension

Pulmonary hypertension (PH) is a rare condition. Data on adult PH patients is abundant, but data on pediatric PH are scarce. Nevertheless, in the past decade, increasing data concerning pediatric PH are becoming available, enabling this review of the epidemiology, characterization, and outcome of pediatric pulmonary hypertension.PH is a condition that is associated with a variety of diseases. It is a rare condition in children with a complex and age-specific presentation. Transient forms of pulmonary arterial hypertension (PAH), i.e., potentially reversible PAH, specifically occur in children and form the largest group of pediatric PH. Advanced PAH in children is predominantly idiopathic or associated with congenital heart disease. Other forms of PAH seldom occur in children. WHO PH groups 2-5 are rare in childhood; however, they may be underreported.The clinical presentation of pediatric PH is relatively nonspecific as it is in adults, with dyspnea on exertion as the most common presenting symptom. However, the clinical presentation of pediatric PH includes symptoms specific for children such as syncope. Pediatric PH frequently co-occurs with genetic and syndromal abnormalities, including Down syndrome. Right heart failure is less common in children despite a severe hemodynamic profile.PAH is a detrimental disease with a poor prognosis. Outcome of pediatric PAH differs between patients with different types of congenital heart disease. In the last decades, new PAH-targeted therapies have been developed, which have improved outcome in pediatric pulmonary arterial hypertension. However, currently reported survival rates vary and critical appraisal of patient populations, survival data, and proposed treatment approaches is necessary.</p

Epidemiology of pediatric pulmonary hypertension

Pulmonary hypertension (PH) is a rare condition. Data on adult PH patients is abundant, but data on pediatric PH are scarce. Nevertheless, in the past decade, increasing data concerning pediatric PH are becoming available, enabling this review of the epidemiology, characterization, and outcome of pediatric pulmonary hypertension.PH is a condition that is associated with a variety of diseases. It is a rare condition in children with a complex and age-specific presentation. Transient forms of pulmonary arterial hypertension (PAH), i.e., potentially reversible PAH, specifically occur in children and form the largest group of pediatric PH. Advanced PAH in children is predominantly idiopathic or associated with congenital heart disease. Other forms of PAH seldom occur in children. WHO PH groups 2-5 are rare in childhood; however, they may be underreported.The clinical presentation of pediatric PH is relatively nonspecific as it is in adults, with dyspnea on exertion as the most common presenting symptom. However, the clinical presentation of pediatric PH includes symptoms specific for children such as syncope. Pediatric PH frequently co-occurs with genetic and syndromal abnormalities, including Down syndrome. Right heart failure is less common in children despite a severe hemodynamic profile.PAH is a detrimental disease with a poor prognosis. Outcome of pediatric PAH differs between patients with different types of congenital heart disease. In the last decades, new PAH-targeted therapies have been developed, which have improved outcome in pediatric pulmonary arterial hypertension. However, currently reported survival rates vary and critical appraisal of patient populations, survival data, and proposed treatment approaches is necessary.</p

Prognostic biomarkers in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a progressive life-threatening disease of the pulmonary vasculature. Despite the introduction of targeted therapies, prognosis remains poor. In pediatric PAH, reliable prognostic biomarkers are needed to inform clinicians on disease progression and risk of mortality, in order to be able to assess the need for escalation of medical therapy, consider surgical options such as Pott’s shunt and listing for (heart)-lung transplantation. This review provides an overview of prognostic biomarkers that are considered to carry potential for the clinical management of pediatric PAH. These include conventional physiological biomarkers [resting heart rate, heart rate variability (HRV), a child’s growth], biomarkers of functional status [World Health Organization functional class, 6-minute walk distance (6MWD), parameters derived from cardiopulmonary exercise testing (CPET), daily physical activity level], electrocardiographic biomarkers, circulating serum biomarkers (natriuretic peptides, uric acid, neurohormones, inflammatory markers, and novel circulating biomarkers), and multiple hemodynamic biomarkers and imaging biomarkers [echocardiography and cardiac magnetic resonance (CMR)]. In recent years, many potential prognostic biomarkers have become available for the management of PAH in children. As the available prognostic biomarkers reflect different aspects of the disease process and functional implications, a multi-marker approach appears the most useful for guiding therapy decisions and improve outcome in pediatric PAH

TBX4 variants and pulmonary diseases:getting out of the 'Box'

Purpose of review In 2013, the association between T-Box factor 4 (TBX4) variants and pulmonary arterial hypertension (PAH) has first been described. Now - in 2020 - growing evidence is emerging indicating that TBX4 variants associate with a wide spectrum of lung disorders. Recent findings TBX4 variants are enriched in both children and adults with PAH. The clinical phenotype associated with a TBX4 variant seems to be milder than that in other PAH-associated gene mutations. Further, TBX4 variants have increasingly been associated with a variety of clinical and histopathological phenotypes, including lethal developmental parenchymal lung diseases such as not only acinar dysplasia in neonates, but also less outspoken parenchymal lung diseases in children and adults. Summary The clinical phenotype of a TBX4 variant has recently been recognised to expand from bone disorders to different types of lung diseases. Recent data suggest that variants of TBX4, a transcription factor known to be an important regulator in embryonic development, are not rare in both children and adults with PAH and/or developmental parenchymal lung diseases