Computed tomography assessment of early structural lung disease in young children with cystic fibrosis

Lauren Mott

    Research output: ThesisDoctoral Thesis

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    Abstract

    [Truncated] Background and rationale

    Progressive lung disease remains the leading cause of morbidity and mortality in cystic fibrosis. Despite widespread implementation of newborn screening programs, the rate of decline in pulmonary function in adolescents with cystic fibrosis has remained unchanged over successive cohorts, suggesting that current standards of management for cystic fibrosis are doing little to prevent progressive lung disease. Several exciting developments in the cystic fibrosis therapeutic pipeline have the potential to alter the disease trajectory in children with cystic fibrosis. The ability to confirm that these therapeutics can prevent progressive lung disease if commenced early in life is hindered, however, by a lack of suitable pulmonary endpoints for clinical trials in early childhood. Chest computed tomography (CT) is a promising endpoint that reflects altered lung structure in infants with cystic fibrosis, assessing key components of early structural lung disease, including bronchiectasis, mucous plugging, and air trapping. Before the widespread adoption of chest CT as a clinical marker of disease severity, and as an endpoint for clinical trials commencing in infancy, the ability of chest CT to reflect progressive lung disease must be demonstrated, and chest CT acquisition protocols must be standardised for use in multicentre studies.

    Research objective and aims

    The global objective of the research presented in this thesis was to contribute to the development of chest CT as a suitable endpoint for cystic fibrosis clinical trials commencing in infancy, by demonstrating the ability of chest CT to reflect progressive lung disease, and to contribute to standardisation of chest CT acquisition protocols for this population. The latter objective was addressed through a series of studies focussing on volumetric acquisition protocols, confirming the heterogeneous distribution of early lung disease, and determining whether assessment of early bronchiectasis is dependent on lung volume.

    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2013

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    Cystic Fibrosis
    Lung Diseases
    Thorax
    Tomography
    Lung
    Bronchiectasis
    Clinical Trials
    Research
    Multicenter Studies
    Biomarkers
    Air
    Newborn Infant
    Morbidity
    Mortality
    Therapeutics
    Population

    Cite this

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    title = "Computed tomography assessment of early structural lung disease in young children with cystic fibrosis",
    abstract = "[Truncated] Background and rationale Progressive lung disease remains the leading cause of morbidity and mortality in cystic fibrosis. Despite widespread implementation of newborn screening programs, the rate of decline in pulmonary function in adolescents with cystic fibrosis has remained unchanged over successive cohorts, suggesting that current standards of management for cystic fibrosis are doing little to prevent progressive lung disease. Several exciting developments in the cystic fibrosis therapeutic pipeline have the potential to alter the disease trajectory in children with cystic fibrosis. The ability to confirm that these therapeutics can prevent progressive lung disease if commenced early in life is hindered, however, by a lack of suitable pulmonary endpoints for clinical trials in early childhood. Chest computed tomography (CT) is a promising endpoint that reflects altered lung structure in infants with cystic fibrosis, assessing key components of early structural lung disease, including bronchiectasis, mucous plugging, and air trapping. Before the widespread adoption of chest CT as a clinical marker of disease severity, and as an endpoint for clinical trials commencing in infancy, the ability of chest CT to reflect progressive lung disease must be demonstrated, and chest CT acquisition protocols must be standardised for use in multicentre studies. Research objective and aims The global objective of the research presented in this thesis was to contribute to the development of chest CT as a suitable endpoint for cystic fibrosis clinical trials commencing in infancy, by demonstrating the ability of chest CT to reflect progressive lung disease, and to contribute to standardisation of chest CT acquisition protocols for this population. The latter objective was addressed through a series of studies focussing on volumetric acquisition protocols, confirming the heterogeneous distribution of early lung disease, and determining whether assessment of early bronchiectasis is dependent on lung volume.",
    keywords = "Cystic fibrosis, Computed tomography, Imaging, Bronchiectasis, Trapped air, Early childhood, Paediatrics, Pulmonology",
    author = "Lauren Mott",
    year = "2013",
    language = "English",

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    TY - THES

    T1 - Computed tomography assessment of early structural lung disease in young children with cystic fibrosis

    AU - Mott, Lauren

    PY - 2013

    Y1 - 2013

    N2 - [Truncated] Background and rationale Progressive lung disease remains the leading cause of morbidity and mortality in cystic fibrosis. Despite widespread implementation of newborn screening programs, the rate of decline in pulmonary function in adolescents with cystic fibrosis has remained unchanged over successive cohorts, suggesting that current standards of management for cystic fibrosis are doing little to prevent progressive lung disease. Several exciting developments in the cystic fibrosis therapeutic pipeline have the potential to alter the disease trajectory in children with cystic fibrosis. The ability to confirm that these therapeutics can prevent progressive lung disease if commenced early in life is hindered, however, by a lack of suitable pulmonary endpoints for clinical trials in early childhood. Chest computed tomography (CT) is a promising endpoint that reflects altered lung structure in infants with cystic fibrosis, assessing key components of early structural lung disease, including bronchiectasis, mucous plugging, and air trapping. Before the widespread adoption of chest CT as a clinical marker of disease severity, and as an endpoint for clinical trials commencing in infancy, the ability of chest CT to reflect progressive lung disease must be demonstrated, and chest CT acquisition protocols must be standardised for use in multicentre studies. Research objective and aims The global objective of the research presented in this thesis was to contribute to the development of chest CT as a suitable endpoint for cystic fibrosis clinical trials commencing in infancy, by demonstrating the ability of chest CT to reflect progressive lung disease, and to contribute to standardisation of chest CT acquisition protocols for this population. The latter objective was addressed through a series of studies focussing on volumetric acquisition protocols, confirming the heterogeneous distribution of early lung disease, and determining whether assessment of early bronchiectasis is dependent on lung volume.

    AB - [Truncated] Background and rationale Progressive lung disease remains the leading cause of morbidity and mortality in cystic fibrosis. Despite widespread implementation of newborn screening programs, the rate of decline in pulmonary function in adolescents with cystic fibrosis has remained unchanged over successive cohorts, suggesting that current standards of management for cystic fibrosis are doing little to prevent progressive lung disease. Several exciting developments in the cystic fibrosis therapeutic pipeline have the potential to alter the disease trajectory in children with cystic fibrosis. The ability to confirm that these therapeutics can prevent progressive lung disease if commenced early in life is hindered, however, by a lack of suitable pulmonary endpoints for clinical trials in early childhood. Chest computed tomography (CT) is a promising endpoint that reflects altered lung structure in infants with cystic fibrosis, assessing key components of early structural lung disease, including bronchiectasis, mucous plugging, and air trapping. Before the widespread adoption of chest CT as a clinical marker of disease severity, and as an endpoint for clinical trials commencing in infancy, the ability of chest CT to reflect progressive lung disease must be demonstrated, and chest CT acquisition protocols must be standardised for use in multicentre studies. Research objective and aims The global objective of the research presented in this thesis was to contribute to the development of chest CT as a suitable endpoint for cystic fibrosis clinical trials commencing in infancy, by demonstrating the ability of chest CT to reflect progressive lung disease, and to contribute to standardisation of chest CT acquisition protocols for this population. The latter objective was addressed through a series of studies focussing on volumetric acquisition protocols, confirming the heterogeneous distribution of early lung disease, and determining whether assessment of early bronchiectasis is dependent on lung volume.

    KW - Cystic fibrosis

    KW - Computed tomography

    KW - Imaging

    KW - Bronchiectasis

    KW - Trapped air

    KW - Early childhood

    KW - Paediatrics

    KW - Pulmonology

    M3 - Doctoral Thesis

    ER -