Cystic Fibrosis Newborn Screening.

Cystic fibrosis (CF) newborn screening (NBS) results in earlier diagnosis of CF and better clinical outcomes. The goal of CF NBS is achievement of a timely, equitable diagnosis for all affected individuals. This article outlines CF NBS processes and algorithms, testing and clinical outcomes, and future needs.

Pediatric Pulmonary Function Testing.

Respiratory disease has a major impact on children's health, and objective measures of lung function are critical for the care and study of pediatric lung disease. Understanding lung development provides a conceptual framework for pulmonary function test (PFT) findings in children. Although the conventional age at which spirometry can be performed in children is 6 y, many children under this age can successfully perform spirometry.

PRenatal mOdulator treatment to PrEvent CF complicaTions (PROTECT) workshop report.

Background: Data from cystic fibrosis (CF) animal models and case studies suggests that in utero administration of CF transmembrane conductance regulator (CFTR) modulators (variant specific therapies, VST) can rescue CFTR-related pathophysiology in the fetus. Use of VST during pregnancy to prevent disease in infants has not been systematically studied. Through stakeholder engagement, we sought to determine if formal research evaluation is warranted.

Elevated serum lipase in infants with cystic fibrosis exposed to prenatal and postnatal elexacaftor/tezacaftor/ivacaftor.

Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction leads to progressive exocrine pancreatic insufficiency, resulting in difficulty in the secretion of digestive enzymes and subsequent malabsorption of nutrients. Case reports have described preserved pancreatic function with prenatal elexacaftor/tezacaftor/ivacaftor (ETI) exposure. However, little is known about pancreatic function and injury as ETI exposure decreases postnatally.

Neonatology Providers Need Education About Cystic Fibrosis Newborn Screening Algorithms.

An essential link in the cystic fibrosis (CF) newborn screening (NBS) process is communication of results. While this is described between NBS programs and primary care providers, data of this occurrence is limited with neonatologists. Neonatology providers represent a group caring for critically ill infants with conditions that can impact their ability to complete diagnostic testing after an abnormal NBS.

Baseline Characteristics and Self-Reported Use of Chronic Daily Therapies of the Home Reported Outcomes With CFTR Modulator Therapy (HERO-2) Cohort.

Background: The HERO-2 study is a prospective, observational study investigating chronic daily therapy (CDT) changes among people with cystic fibrosis (PwCF) ≥ 12 years of age taking elexacaftor/tezacaftor/ivacaftor (ETI). The goal of this analysis was to describe baseline characteristics and patterns of CDT discontinuation reported at study enrollment and identify clinical features associated with CDT discontinuation.

Methods: Study participants were recruited through their CF center, community engagement, or a smartphone application (Folia Health).

Cystic Fibrosis Newborn Screening: A Systematic Review-Driven Consensus Guideline from the United States Cystic Fibrosis Foundation.

Newborn screening for cystic fibrosis (CF) has been universal in the US since 2010; however, there is significant variation among newborn screening algorithms. Systematic reviews were used to develop seven recommendations for newborn screening program practices to improve timeliness, sensitivity, and equity in diagnosing infants with CF: (1) The CF Foundation recommends the use of a floating immunoreactive trypsinogen (IRT) cutoff over a fixed IRT cutoff; (2) The CF Foundation recommends using a very high IRT referral strategy in CF newborn screening programs whose variant panel does not include all CF-causing variants in CFTR2 or does not have a variant panel that achieves at least 95% sensitivity in all ancestral groups within the state; (3) The CF Foundation recommends that CF newborn screening algorithms should not limit variant detection to the F508del variant or variants included in the American College of Medical Genetics-23 panel; (4) The CF Foundation recommends that CF newborn screening programs screen for all CF-causing variants in CFTR2; (5) The CF Foundation recommends conducting variant screening twice weekly or more frequently as resources allow; (6) The CF Foundation recommends the inclusion of a sequencing tier following IRT and variant panel testing to improve the specificity and positive predictive value of CF newborn screening; (7) The CF Foundation recommends that both the primary care provider and the CF specialist be notified of abnormal newborn screening results. Through implementation, it is anticipated that these recommendations will result in improved sensitivity, equity, and timeliness of CF newborn screening, leading to improved health outcomes for all individuals diagnosed with CF following newborn screening and a decreased burden on families.

Impact of CFTR modulator therapy on basic life needs and financial concerns in people with cystic fibrosis: Data from the Well-ME survey.

Background: CFTR modulator (CFTR-M) therapy has led to improved clinical outcomes amongst people with cystic fibrosis (PwCF) eligible for these therapies. However, there is limited data on their impact on the basic life needs and financial concerns of PwCF.

Methods: We used data from the Wellness in the Modulator Era (Well-ME) survey, which includes data from 900 PwCF both taking and not taking CFTR-M.

Clinical features associated with self-reported food insecurity in people with cystic fibrosis.

Background: Food insecurity (FI) is more prevalent in people with cystic fibrosis (PwCF) than the reported national prevalence, but there are limited data on the relationship between FI and health outcomes in PwCF. The objective of this study was to analyze the relationship between FI in PwCF and pulmonary and nutritional status.

Methods: We leveraged an electronic cross-sectional survey that ascertained FI status and gave participants the option to link their survey data to their records in the Cystic Fibrosis Foundation Patient Registry (CFFPR).

Design and implementation of a multicenter protocol to obtain impulse oscillometry data in preterm children.

Importance: Objective measures of lung function are critical for assessing respiratory outcomes of prematurity. Among extremely low gestational age neonates (ELGANs) (< 29 weeks gestational age), high rates of neurodevelopmental impairment may interfere with lung function testing. Impulse oscillometry (IOS) is a noninvasive test of respiratory system mechanics not requiring forced expiration.

Treatment of small as well as large declines in lung function enhances recovery to baseline in people with CF.

Background: The benefit of antibiotic treatment of acute drops in FEV percent predicted (FEVpp) has been clearly established, but data from the early 2000s showed inconsistent treatment. Further, there is no empirical evidence for what magnitude of drop is clinically significant.

Methods: We used data from the CF Foundation Patient Registry (CFFPR) from 2016 to 2019 to determine the association between treatment (any IV antibiotics, only oral or newly prescribed inhaled antibiotics, or no antibiotic therapy) following a decline of ≥5% from baseline FEVpp and return to 100% baseline FEVpp days using multivariable logistic regression including an interaction between the magnitude of decline and treatment category.

Lung T1 MRI assessments in children with mild cystic fibrosis lung disease.

Rationale: Lung T1 MRI is a potential method to assess cystic fibrosis (CF) lung disease that is safe, quick, and widely available, but there are no data in children with mild CF lung disease.

Objective: Assess the ability of lung T1 MRI to detect abnormalities in children with mild CF lung disease.

Methods: We performed T1 MRI, multiple breath washout (MBW), chest computed tomography (CT), and spirometry in a cohort of 45 children with mild CF lung disease (6-11 years of age).

Pediatric pulmonology year in review 2023: Physiology.

Application of the principles of pulmonary physiology and lung development to the care and management of respiratory disease in children is a distinguishing feature of pediatric pulmonology. In 2023, this was evident in numerous publications in Pediatric Pulmonology and other journals. This review will highlight some of the papers in this area.

Decreased vascular reactivity associated with increased IL-8 in 6-month-old infants of mothers with pre-eclampsia.

Background: Offspring born to mothers with pre-eclampsia (Pre-E) suffer higher risks of adult cardiovascular diseases, suggesting that exposure to an antiangiogenic environment in-utero has a lasting impact on the development of endothelial function. The goal of this study is to test the hypothesis that in-utero exposure to Pre-E results in alterations of angiogenic factors/cytokines that negatively impact vascular development during infancy.

Methods: Infants born from mothers with and without Pre-E were recruited and followed up at 6 months.

Clinical outcomes at 9-10 years of age in children born with cystic fibrosis transmembrane conductance regulator related metabolic syndrome.

Background And Objectives: There are limited data on cystic fibrosis (CF) transmembrane conductance regulator-related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to analyze outcomes of infants with CRMS up to the age of 9-10 years using the CF Foundation Patient Registry (CFFPR).

Methods: We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020.

Clinical features associated with pulmonary exacerbation diagnosis in infants and young children with cystic fibrosis.

Rationale: Diagnosing cystic fibrosis (CF) pulmonary exacerbations (PEx) in very young people with CF <3 years (VY-PwCF) is challenging because of the frequency of respiratory viral infections in this age group, and there are limited data on the clinical features associated with the diagnosis of PEx in this age group. The goal of this study was to identify clinical features associated with the diagnosis of PEx in VY-PwCF.

Methods: We reviewed the medical records of VY-PwCF followed at the Children's Hospital of Philadelphia born between 2013 and 2019.

Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis.

Newborn screening for cystic fibrosis was fully implemented in the US by 2010, but delays in timeliness of evaluation for infants with positive newborn screening tests persist. Through evaluation of national patient registry data, we determined that late initiation of cystic fibrosis care is associated with poorer long-term nutritional outcomes.

Antibiotic Regimen Changes during Cystic Fibrosis Pediatric Pulmonary Exacerbation Treatment.

Antibiotic selection for in-hospital treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) is typically guided by previous respiratory culture results or past PEx antibiotic treatment. In the absence of clinical improvement during PEx treatment, antibiotics are frequently changed in search of a regimen that better alleviates symptoms and restores lung function. The clinical benefits of changing antibiotics during PEx treatment are largely uncharacterized.

Pediatric pulmonology year in review 2021 and 2022: Physiology.

Pulmonary physiology is a core element of pediatric pulmonology care and research. This article reviews some of the notable publications in physiology that were published in Pediatric Pulmonology in 2021 and 2022.

Variation in cystic fibrosis newborn screening algorithms in the United States.

Rationale: Cystic fibrosis (CF) newborn screening (NBS) algorithms in the United States vary by state. Differences in CF NBS algorithms could potentially affect the detection rate of CF newborns and lead to disparities in CF diagnosis amongst different racial and ethnic groups.

Objectives: Generate a database of CF NBS algorithms in the United States and identify processes that may potentially lead to missed diagnoses or lead to healthcare disparities.

Detection of disease-causing CFTR variants in state newborn screening programs.

Background: Newborn screening (NBS) algorithms for cystic fibrosis (CF) vary in the United State of America and include different cystic fibrosis transmembrane conductance regulator (CFTR) variants. CFTR variant distribution varies among racial and ethnic groups.

Objective: Our objectives were to identify differences in detection rate by race and ethnicity for CFTR variant panels, identify each US state detection rate for CFTR variant panels, and describe the rate of false-negative NBS and delayed diagnoses by race and ethnicity.

Real-world Associations of US Cystic Fibrosis Newborn Screening Programs With Nutritional and Pulmonary Outcomes.

Importance: Newborn screening (NBS) for cystic fibrosis (CF) has been universal in the US since 2010, but its association with clinical outcomes is unclear.

Objective: To describe the real-world effectiveness of NBS programs for CF in the US on outcomes up to age 10 years.

Design, Setting, And Participants: This was a retrospective cohort study using CF Foundation Patient Registry data from January 1, 2000, to December 31, 2018.