Hereditary pulmonary arterial hypertension burden in pediatrics: A single referral center experience.

Introduction: Hereditary pulmonary arterial hypertension (HPAH) is a rare yet serious type of pulmonary arterial hypertension (PAH). The burden in the pediatric population remains high yet underreported. The objective of this study is to describe the distribution of mutations found on targeted PAH panel testing at a large pediatric referral center. Methods: Children with PAH panel administered by the John Welsh Cardiovascular Diagnostic Laboratory at Texas Children's Hospital and Baylor College of Medicine in Houston, Texas between October 2012 to August 2021 were included into this study. Medical records were retrospectively reviewed for clinical correlation. Results: Sixty-six children with PAH underwent PAH genetic testing. Among those, 9 (14%) children were found to have pathogenic mutations, 16 (24%) children with variant of unknown significance and 41 (62%) children with polymorphism (classified as likely benign and benign). BMPR2 mutation was the most common pathogenic mutation, seen in 6 of the 9 children with detected mutations. Hemodynamic studies showed higher pulmonary vascular resistance among those with pathogenic mutations than those without (17.4 vs. 4.6 Wood units). All children with pathogenic mutations had severe PAH requiring triple therapy. There were tendencies for higher lung transplantation rate but lower mortality among those with pathogenic mutations. Conclusions: Abnormalities on genetic testing are not uncommon among children with PAH, although majority are of unclear significance. However, children with pathogenic mutations tended to present with more severe PAH requiring aggressive medical and surgical therapies. Genetic testing should be routinely considered due to consequences for treatment and prognostic implications. Larger scale population studies and registries are warranted to characterize the burden of HPAH in the pediatric population specifically.

Corrigendum: Case report: Selexipag in pediatric pulmonary hypertension: initiation, transition, and titration.

[This corrects the article DOI: 10.3389/fped.2023.1050508.].

Case Report: Selexipag in pediatric pulmonary hypertension: Initiation, transition, and titration.

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient's and caregiver's quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited to case reports in older adolescent patients and selexipag is not approved for use in the pediatric pulmonary hypertension population, many pediatric centers are expanding the use of this therapy to this population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children under 10 years of age, between 10 and 30 kg. Seven patients were initiated on selexipag therapy including de novo initiation and transition from intravenous treprostinil to oral selexipag. All patients were on stable background therapy with phosphodiesterase-5 inhibitor and endothelin receptor antagonist therapies at baseline. All patients reached their planned goal selexipag dose during admission without the need for changes to the titration schedule and without hemodynamic deterioration. In our experience, oral selexipag is safe and well-tolerated in young pediatric patients with pulmonary hypertension. Based on our favorable experience, we developed an institution-specific selexipag process algorithm for continued successful use in the pediatric population.

Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients.

Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.

Easy Breathing: A Review of the Impact of Air Quality on Pediatric Health Outcomes.

Preventable environmental factors such as exposure to poor air quality are predicted to affect 23% of all global deaths. Although there have been efforts to reduce air pollution through federal guidelines for vehicle and industrial emissions, the air in the United States remains far from clean. Children and pregnant women have been identified as high-risk populations who are particularly susceptible to the negative effects of poor air quality. This paper provides an overview of health concerns related to poor air quality, pediatric considerations from pregnancy through childhood, the importance of increased awareness of air quality assessment and prevention in patient encounters, and current advocacy efforts and legislation.

Building a dedicated pediatric pulmonary hypertension program: A consensus statement from the pediatric pulmonary hypertension network.

Pediatric pulmonary hypertension (PH) is a severe, life-threatening disease associated with diverse cardiac, pulmonary, and systemic disorders, which generally requires expertise from multiple disciplines for management. Unfortunately, expert centers are limited, often due to inadequate resources or unfamiliarity with needed components for success. The Pediatric Pulmonary Hypertension Network (PPHNet) includes expert centers in North America specifically dedicated to advancing the field of pediatric PH through research and excellent clinical care. PPHNet member sites were queried for valuable program components and these findings were discussed for consensus. Here we provide a collective overview of key elements of an optimal pediatric PH program: team composition, access to services, and commitment to education. It is our intention that this document will assist newer and/or smaller programs identify avenues and resources for growth and provide avenues for collaboration.

The role of a multidisciplinary team in a pediatric pulmonary hypertension center.

The multidisciplinary team in a pediatric pulmonary hypertension (PH) center can improve the delivery of care to the PH patient by helping them address the different challenges that correlate to a PH diagnosis. Currently, there are a limited number of accredited pediatric PH centers nationwide, and many healthcare facilities have little experience managing patients with this complex and rare disease. Patients with PH may see providers from multiple medical specialties, inherit a high-cost burden from their PH medications, and have little community backing due to unfamiliarity of the disease. The multidisciplinary team can embrace these challenges. Through the delineation of tasks and roles within the composition of the team, patients can experience the support, resources, and care they need. The composition of the team can vary from center to center, but it may include an attending physician, advanced practice provider, nurse, dietitian, physiologists, respiratory therapists, social workers, research coordinators, and subspecialty collaboration including cardiology, pulmonology, genetics, psychology, and palliative care. When composing a multidisciplinary team, consider the heterogeneity of the patient population being served. Look at the resources available and overall community familiarity with PH. It is important to know the center's limits and refer to an expert PH center as necessary. The goal for every patient with pulmonary hypertension is to maximize their quality of life and outcomes, and the use of the multidisciplinary team is one approach to reaching this goal.

Outcomes of COVID-19 infection in pediatric pulmonary hypertension: A single-center experience.

BACKGROUND: The global COVID-19 pandemic was particularly concerning for the pediatric pulmonary hypertension (PH) population due to immature immune systems and developmental comorbidities. This study aims to describe a single-center experience of pediatric PH patients diagnosed with COVID-19 disease. METHODS: A retrospective cohort study of all pediatric patients followed by the PH Center at Texas Children's Hospital diagnosed with COVID-19 infection from April 2020 to February 2021. RESULTS: We identified 23 patients with a median age of 58 months (interquartile range [IQR]: 25-75th, 21-132 months), 48% being Hispanics. Eight patients (35%) required hospitalization; median length of stay was 6 days (IQR: 25-75th, 5-8 days). Only three of these eight patients required increased respiratory support. Targeted PH therapy was escalated in four patients (two in dual and two in triple therapy). There was one mortality in a patient with failing Fontan physiology. Ninety-one percent of patients have had post-COVID outpatient follow-up, median of 101 days (IQR: 25-75th, 50-159 days) from diagnosis. Of the five patients with 6 min walk test (6MWT) data, three (60%) children walked less distance, median of -12 m (IQR: 25-75th, -12 to +49 m) compared to pre-COVID testing. Postinfection pulmonary function testing (PFT) was notable for decrease in predicted forced vital capacity (FVC; median -6%, range -11% to +6%) and forced expiratory volume in one second (FEV1; median -14%, range -12% to -18%) in 75% of the patients with PFT data. CONCLUSION: In our institution, COVID-19 was found more frequently in Hispanics and associated with low mortality.