Vanzacaftor-tezacaftor-deutivacaftor for children aged 6-11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial.

Background: In phase 2 trials in people with cystic fibrosis aged 18 years and older, vanzacaftor-tezacaftor-deutivacaftor has been shown to be a safe and effective, once-daily cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Restoring normal CFTR function early in life has the potential to prevent manifestations of cystic fibrosis. We aimed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of vanzacaftor-tezacaftor-deutivacaftor in children with cystic fibrosis aged 6-11 years.

Cystic fibrosis newborn screening: the importance of bloodspot sample quality.

Objective: Wales has an immunoreactive trypsin (IRT)-DNA cystic fibrosis (CF) newborn screening (NBS) programme. Most CF NBS false negative cases are due to an IRT concentration below the screening threshold. The accuracy of IRT results is dependent on the quality of the dried bloodspot (DBS) sample.

Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year.

Background: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age.

Methods: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well.

The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial.

Background: Pathogen surveillance is challenging but crucial in children with cystic fibrosis-who are often non-productive of sputum even if actively coughing-because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage.

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.

Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age?

Rationale: Sensitive outcome measures applicable in different centres to quantify and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are needed both for clinical care and interventional trials. Chest CT has been advocated as such a measure yet there is no validated scoring system in infants.

Objectives: The objectives of this study were to standardise CT data collection across multiple sites; ascertain the incidence of bronchial dilatation and air trapping in newborn screened (NBS) infants with CF at 1 year; and assess the reproducibility of Brody-II, the most widely used scoring system in children with CF, during infancy.

Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants.

Rationale: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants.

Objective: To assess changes in pulmonary function during the first year of life in CF NBS infants.

Deaths in childhood from cystic fibrosis: 10-year analysis from two London specialist centres.

Introduction: Death in childhood from cystic fibrosis (CF) is now an uncommon event in the U.K. We wished to assess the circumstances surrounding deaths (and lung transplantation) in the modern era of CF care.

Evaluation and use of childhood lung function tests in cystic fibrosis.

Purpose Of Review: Lung disease begins early in life in cystic fibrosis (CF), yet our understanding of CF lung abnormalities in the first years of life remains limited. By facilitating earlier diagnosis, newborn screening for CF provides the opportunity to understand and characterize presymptomatic lung disease in infants and young children. This could lead to earlier interventions to mitigate disease progression at a time when therapeutic intervention or prevention may be most effective.

New reference equations to improve interpretation of infant lung function.

Rationale: With increasing use of infant pulmonary function tests (IPFTs) in both clinical and research studies, appropriate interpretation of results is essential.

Objectives: To investigate the potential bias associated with "normalising" IPF by expressing results as a ratio of body size and to develop reference ranges for tidal breathing parameters, passive respiratory mechanics (compliance [Crs] and resistance [Rrs]) and plethysmographic functional residual capacity (FRCp ) for white infants during the first 2 years of life.

Methods: IPFTs were measured using the Jaeger BabyBody system and standardized protocols.

Lung function is abnormal in 3-month-old infants with cystic fibrosis diagnosed by newborn screening.

Background: Long-term benefits of newborn screening (NBS) for cystic fibrosis (CF) have been established with respect to nutritional status, but effects on pulmonary health remain unclear.

Hypothesis: With early diagnosis and commencement of standardised treatment, lung function at ∼3 months of age is normal in NBS infants with CF.

Methods: Lung clearance index (LCI) and functional residual capacity (FRC) using multiple breath washout (MBW), plethysmographic (pleth) FRC and forced expirations from raised lung volumes were measured in 71 infants with CF (participants in the London CF Collaboration) and 54 contemporaneous healthy controls age ∼3 months.

Diagnosing allergic bronchopulmonary aspergillosis in children with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) is an important complication of cystic fibrosis. It is a hypersensitivity reaction to Aspergillus fumigatus, leading to a Th2 CD4 response mediated by the release of specific IgE. If ABPA is not treated early, it can cause severe impairment in lung function and long-term lung damage.

Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis.

Aims: To compare continuous positive airways pressure (CPAP) with standard treatment (ST) in the management of bronchiolitis.

Methods: Children <1 year of age with bronchiolitis and capillary PCO2 >6 kPa were recruited and randomised to CPAP or ST and then crossed over to the alternative treatment after 12 h. ST was intravenous fluids and supplemental oxygen by nasal prongs or face mask.