Novel views on endotyping asthma, its remission, and COPD

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    Abstract

    The chapters presented in this thesis provide an overview of what is known about asthma remission, further characterize of complete asthma remission, elaborate on the asthma- obesity complexity, apply cutting edge techniques to endotype asthma and COPD as well as novel devices to analyze airway remodeling and small airways dysfunction.
    Various conclusions have been made:
    I. In order to elucidate the pathophysiological state of asthma remission, future studies should focus on complete asthma remission, since this phenomenon is likely to yield superior prognostic and scientific impact. This is of interest, since elucidation of the pathophysiology of asthma remission could potentially lead to new treatment options for asthma.
    II. To clearly predict asthma remission later in life, we need to integrate biomarkers with clinical features at asthma-onset.
    III. Measuring particles of exhaled air correlates with large, and indirectly, small airways parameters, in asthmatics, clinical-, complete asthma remission subjects, and healthy controls.
    IV. Transcriptomic bronchial cell typing (e.g. single-cell RNA-sequencing) characterizes the landscape of lung-resident structural and inflammatory cells and their interactions, enabling us to identify differences in proportions and transcriptional output of cells between asthmatics and healthy.
    V. Optical coherence tomography enables us to quantify extracellular matrix components in the airway wall, such as collagen. This now allows for future studies ‘in vivo’ to explore the clinical characteristics and the underlying pathobiology related to airway remodeling in asthma and asthma remission.
    VI. The asthma-obesity syndrome is a common combination of diseases with its own distinct pathophysiological processes.
    VII. There will presumably be no room for serum periostin in COPD clinical decision- making.
    VIII.Transcriptomic profiling can be implemented as a biomarker for COPD patient prognosis.
    Unavoidably, aforementioned conclusions lead to new questions and recommendations for future studies. These recommendations include:
    I. To expand our knowledge on asthma remission by implementing single-cell RNA-sequencing on blood samples, bronchial- and nasal brushes, and bronchial biopsies of subjects with clinical and complete asthma remission, while comparing to asthmatics and healthy controls.
    II. To test single-nucleus RNA-sequencing in the ARMSTRONG study. This method enables sequencing of frozen biopsy samples of former datasets, consequently extending the number of subjects.
    III. To analyze exhaled, aberrant proteins linked to asthma, instead of merely counting exhaled particles.
    IV. To compare metabolomic breathprints of various asthma severities.
    V. To introduce novel methods in small airways disease-phenotypes in asthma, which
    enable visualization of airtrapping and gas exchange, such as functional MRI. VI. To study the effects of leptin and adiponectin in the asthma-obesity syndrome. Specifying the eligibility for bariatric surgery in patients with severe asthma and
    morbid obesity, in order to treat this phenotype more safely.
    VII. To analyze the presence of airway remodeling – defined by optical coherence tomography and histological parameters - in complete and clinical asthma
    remission, compared to asthmatics and healthy controls.
    VIII.To correlate optical coherence tomography-defined airway wall remodeling
    parameters with both fixed airway obstruction and single-cell RNA sequencing inflammatory cell types or proportions.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Kerstjens, Huib, Supervisor
    • van den Berge, Maarten, Co-supervisor
    • Nawijn, Martijn, Co-supervisor
    • Pavord, I., Assessment committee, External person
    • Sterk, P. J., Assessment committee, External person
    • Gosens, Reinoud, Assessment committee
    Award date9-Nov-2020
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978-94-6375-586-3
    DOIs
    Publication statusPublished - 2020

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