Related Experiment Video
Updated: Apr 3, 2026
The WinCF Model - An Inexpensive and Tractable Microcosm of a Mucus Plugged Bronchiole to Study the Microbiology of Lung Infections
Published on: May 8, 2017
Evolution of cystic fibrosis lung function in the early years
1aImperial College bNational Heart and Lung Institute cRoyal Brompton Harefield NHS Foundation Trust London, UK dThe University of Queensland eQueensland Children's Medical Research Institute fDepartment of Children's Health and Environment gWHO Collaborating Centre for Children's Health and Environment, Brisbane, Australia.
Insights
Early cystic fibrosis lung disease shows abnormal lung function by 3 months but improves or stabilizes in the first two years. Lung function is not a reliable endpoint for clinical trials in infants with cystic fibrosis.
Area of Science:
- Pediatric Pulmonology
- Clinical Trials
- Cystic Fibrosis Research
Background:
- Most cystic fibrosis (CF) treatments lack evidence from randomized controlled trials (RCTs).
- Novel therapies for CF necessitate early intervention, requiring RCTs in infants.
- Understanding the natural history of early CF lung disease is crucial for designing effective RCTs.
Purpose of the Study:
- To review findings from two large prospective infant cohorts (LCFC and AREST-CF) to understand early CF lung disease.
- To assess the feasibility of using lung function as an endpoint in early CF clinical trials.
Main Methods:
- Prospective cohort study analysis of infants diagnosed with CF via newborn screening.
- Review of lung function, nutritional status, bronchoalveolar lavage (BAL), and high-resolution computed tomography (HRCT) data.
Main Results:
- Excellent nutritional status was maintained in both cohorts.
- Abnormal lung function was detected at 3 months, with varying trajectories in preschool and school-age years.
- HRCT showed mild abnormalities in one cohort, while the other reported high prevalence of elastase-related changes.
Conclusions:
- Lung function is not a suitable primary endpoint for RCTs in the first two years of life for CF.
- Routine BAL and HRCT are not clinically justifiable in this age group.
- While newborn screening improves outcomes, novel point-of-care biomarkers are needed for better monitoring.
Purpose Of Review:
Most treatment of newborn screening-diagnosed cystic fibrosis is not evidence-based; there are very few randomized controlled trials (RCTs). Furthermore, the advent of novel molecular therapies, which could be started at diagnosis, mandates performing RCTs in very young children. However, unless the natural history of early cystic fibrosis lung disease is known, RCTs are impossible. Here, we review the results of two large prospective cohorts of these infants - London Cystic Fibrosis Collaboration (LCFC) (London, UK) and Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST-CF) (Australia).
Recent Findings:
Nutritional status remained excellent in both the cohorts. Both cohorts reported abnormal lung function aged at 3 months. AREST-CF, which previously reported rapidly declining preschool lung function, now report good conventional school-age spirometry. LCFC reported improvement between 3 months and 1 year, and stability in the second year. AREST-CF also reported a high prevalence of high resolution computed tomographic abnormalities related to free neutrophil elastase in bronchoalveolar lavage; LCFC reported high resolution computed tomographic changes at 1 year, which were too mild to be scored reproducibly.
Summary:
At least in the first 2 years of life, lung function is not a good end-point for RCTs; routine bronchoalveolar lavage and HRCT cannot be justified. Newborn screening has greatly improved outcomes, but we need better point-of-care biomarkers.
More Related Videos
07:38Design and Development of a Model to Study the Effect of Supplemental Oxygen on the Cystic Fibrosis Airway Microbiome
Published on: August 3, 2021
08:00Generation of Human Nasal Epithelial Cell Spheroids for Individualized Cystic Fibrosis Transmembrane Conductance Regulator Study
Published on: April 11, 2018
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:24Cystic Fibrosis: Management
Sinus disease and chronic...
01:20Chronic Obstructive Pulmonary Disease-I: Introduction
01:27Chronic Obstructive Pulmonary Disease-IV: Assessement and Diagnostic Studies
Medical History
01:25Pulmonary Function Tests
Pulmonary Function Tests are crucial diagnostic tools for assessing respiratory function, particularly in patients with chronic respiratory disorders. They comprehensively evaluate lung volumes, ventilatory function, breathing mechanics, diffusion, and gas exchange. These tests help diagnose pulmonary diseases and play a significant role in monitoring disease progression, evaluating disability, and assessing response to therapy.
PFTs involve using a spirometer, a...
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation