Outcomes of prenatal use of elexacaftor/tezacaftor/ivacaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis.

As cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies including elexacaftor/tezacaftor/ivacaftor (ETI) have become widely used in eligible patients with cystic fibrosis (CF), the use of these medications in pregnant people has become a critical area of investigation. Since these medications appear generally safe to both mother and fetus when taken by pregnant people with CF, interest has pivoted to the use of ETI in CF carrier mothers to decrease morbidity and mortality from meconium ileus (MI) in fetuses with cystic fibrosis. Here we discuss three infants at our institution with ultrasound findings of MI who were exposed to prenatal ETI through CF carrier mothers for the purposes of treating MI and lowering risk of intestinal complications from this severe manifestation of CF.

Impact of Discontinuing Both Hypertonic Saline and Dornase Alfa after Elexacaftor-Tezacaftor-Ivacaftor in Cystic Fibrosis.

Evaluating approaches to reduce treatment burden is a research priority among people with cystic fibrosis on highly effective modulators, including elexacaftor-tezacaftor-ivacaftor (ETI). We sought to evaluate the impact of discontinuing both hypertonic saline (HS) and dornase alfa (DA) versus continuing both therapies among a subgroup of participants in the SIMPLIFY study who sequentially participated in trials evaluating the independent clinical effects of discontinuing HS and DA. SIMPLIFY participants ≥12 years old on ETI and constituting a subgroup using both HS and DA at study entry were randomized to the HS or DA trial and then randomized 1:1 to continue or discontinue the applicable therapy for 6 weeks.

Implementation and outcomes of a quality improvement project to systematically assess the gross motor skills in school-aged children with cystic fibrosis.

Introduction: Limited data exist on the gross motor abilities of children with cystic fibrosis (CF). The objective of this research project was to implement a systematic gross motor assessment in children with CF ages 4-12 years. Secondarily, we aimed to assess demographic characteristics associated with gross motor delays.

Remote endpoints for clinical trials in cystic fibrosis: Report from the U.S. CF foundation remote endpoints task force.

The COVID-19 pandemic necessitated a rapid shift in clinical research to perform virtual visits and remote endpoint assessments, providing a key opportunity to optimize the use of remote endpoints for clinical trials in cystic fibrosis. The use of remote endpoints could allow more diverse participation in clinical trials while minimizing participant burden but must be robustly evaluated to ensure adequate performance and feasibility. In response, the Cystic Fibrosis Foundation convened the Remote Endpoint Task Force (Supplemental Table 1), a multidisciplinary group of CF researchers with remote endpoint expertise and community members tasked to better understand the current and future use of remote endpoints for clinical research.

Phase 3 Open-Label Clinical Trial of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged 2-5 Years with Cystic Fibrosis and at Least One Allele.

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and effective in people with cystic fibrosis (CF) aged ⩾6 years with at least one allele but has not been studied in younger children. To evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of ELX/TEZ/IVA in children with CF aged 2-5 years. In this phase 3, open-label, two-part study (parts A and B), children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.

Managing cystic fibrosis in children aged 6-11yrs: a critical review of elexacaftor/tezacaftor/ivacaftor combination therapy.

Introduction: Cystic fibrosis is a life-limiting, autosomal recessive genetic disorder resulting in multi-organ disease due to CF transmembrane conductance regulator () protein dysfunction. CF treatment previously focused on mitigation of disease signs and symptoms. The recent introduction of highly effective CFTR modulators, for which ~90% of people with CF are CFTR variant-eligible, has resulted in substantial health improvements.

Case report: Cystic fibrosis with kwashiorkor: A rare presentation in the era of universal newborn screening.

Background: Universal newborn screening changed the way medical providers think about the presentation of cystic fibrosis (CF). Before implementation of universal screening, it was common for children with CF to present with failure to thrive, nutritional deficiencies, and recurrent infections. Now, nearly all cases of CF are diagnosed by newborn screening shortly after birth before significant symptoms develop.

Airway Inflammation in Children with Primary Ciliary Dyskinesia.

The role of airway inflammation in disease pathogenesis in children with primary ciliary dyskinesia (PCD) is poorly understood. We investigated relationships between sputum inflammation measurements, age, lung function, bronchiectasis, airway infection, and ultrastructural defects in children with PCD. Spontaneously expectorated sputum was collected from clinically stable children and adolescents with PCD ages 6 years and older participating in a multicenter, observational study.

Effects of ivacaftor on systemic inflammation and the plasma proteome in people with CF and G551D.

Background: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator for people with CF and the G551D mutation. We aimed to investigate the biology of CFTR modulation and systemic effects of CFTR restoration by examining changes in circulating measurements of inflammation and growth and novel proteins with ivacaftor treatment.

Methods: Blood samples from 64 CF subjects with G551D-CFTR were analyzed for inflammatory and growth-related proteins at baseline, 1 and 6 months after ivacaftor initiation.

Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study.

Background: A previous phase 3 study showed that lumacaftor-ivacaftor was generally safe and well tolerated over 24 weeks of treatment in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation. In this study, we aimed to assess the long-term safety of lumacaftor-ivacaftor in a rollover study of children who participated in this previous phase 3 study.

Methods: In this multicentre, phase 3, open-label, extension study (study 116; VX16-809-116), we assessed safety of lumacaftor-ivacaftor in children included in a previous multicentre, phase 3, open-label study (study 115; VX15-809-115).

Detection of bacterial pathogens using home oropharyngeal swab collection in children with cystic fibrosis.

Background: Collection of respiratory cultures for airway microbiology surveillance is an essential component of routine clinical care in cystic fibrosis (CF). The COVID-19 global pandemic has necessitated increased use of telehealth, but one limitation of telehealth is the inability to collect respiratory specimens. We initiated a protocol for at-home collection of oropharyngeal (OP) swabs from children with CF.

Oral antibiotic prescribing patterns for treatment of pulmonary exacerbations in two large pediatric CF centers.

Introduction: Oral antibiotics are frequently prescribed for outpatient pulmonary exacerbations (PEx) in children with cystic fibrosis (CF). This study aimed to characterize oral antibiotic use for PEx and treatment outcomes at two large US CF centers.

Methods: Retrospective, descriptive study of oral antibiotic prescribing practices among children with CF ages 6-17 years over 1 year.

Highlights from the 2019 North American Cystic Fibrosis Conference.

This review briefly summarizes presentations in several major topic areas at the conference: pathophysiology and basic science of cystic fibrosis lung disease, clinical trials, clinical quality improvement, microbiology and treatment of infection, and transition, advanced lung disease and transplant, mental health and psychosocial concerns. The review is intended to highlight several areas and is not a comprehensive summary of the conference. Citations from the conference are by the first author and abstract number or symposium number, as designated in the supplement.

Characteristics and outcomes of oral antibiotic treated pulmonary exacerbations in children with cystic fibrosis.

Background: Pulmonary exacerbations (PEx) in children with cystic fibrosis (CF) are frequently treated in the outpatient setting with oral antibiotics. However, little is known about the characteristics of PEx managed on an outpatient basis and the effectiveness of oral antibiotic therapy. We sought to prospectively evaluate clinical and laboratory changes associated with oral antibiotic treatment for PEx.

Pulmonary exacerbations and clinical outcomes in a longitudinal cohort of infants and preschool children with cystic fibrosis.

Background: Pulmonary exacerbations (PEx) in school aged children and adults with cystic fibrosis (CF) lead to increased morbidity and lung function decline. However, the effect of exacerbations in young children with CF is not fully understood. We sought to characterize the frequency and clinical impact of PEx in a pilot study of infants and pre-school aged children with CF.

Sputum induction improves detection of pathogens in children with cystic fibrosis.

Background: Sputum induction is a safe, well tolerated means of obtaining lower airway secretions from children with cystic fibrosis (CF), particularly for assessment of airway inflammation but the clinical value in diagnosing outpatient infections has not been extensively studied.

Objectives: Investigate the success rate and microbiologic yield of induced sputum (IS) compared to oropharyngeal swabs (OP) and expectorated sputum (ES) samples in children with CF, and determine if IS culture results impact treatment.

Methods: Two cohorts were included in this prospective, longitudinal comparative study.

Advances in the diagnosis and treatment of cystic fibrosis.

CF is a genetic, life-shortening, multisystem disease that is most commonly diagnosed through newborn screen performed in all 50 states in the United States. In the past, therapies for CF lung disease have primarily targeted the downstream effects of a dysfunctional CFTR protein. Newer CFTR modulator therapies, targeting the basic defect in CF, are available for a limited group of people with CF, and offer the hope of improved treatment options for many more people with CF in the near future.