COPD (Chronic Obstructive Pulmonary Disease), Chonic bronchitis, Emphysema Chronic Obstructive Pulmonary Disease
Conditions
Interventions
Sponsors
Eligibility
Inclusion criteria
Inclusion criteria: Asymptomatic smoking age- and sex-matched controls (40-75 years, n=50) Patients with usual COPD (postbronchodilator FEV1/FVC ratio <0,7 40-75 years, n=50) without exacerbations Patients with usual COPD (postbronchodilator FEV1/FVC ratio <0,7 40-75 years, n=50) and frequent exacerbations (=1 moderate exacerbations and/or >=1 severe exacerbation with ER-visit/hospitalisation in the past year)Patients with COPD related to alpha-1 antitrypsin deficiency (AATD-COPD) (postbronchodilator FEV1/FVC ratio <0,7 40-75 years, n=50), genotype Pi*ZZ, without exacerbations.
Exclusion criteria
Exclusion criteria: • Incompetence to provide informed consent prior or during study • History of severe nose bleedings • Diagnosed with chronic rhinosinusitis, allergic rhinitis and or allergic asthma • Use of oral corticosteroids or antibiotics in the past 6 weeks (unless a patient is prescribed antibiotics due to a persistent bacterial colonization in the lung) • Symptoms of a respiratory tract infection or common cold in the past 2 weeks • Immunocompromised individuals (with primary immune deficiency or secondary immune deficiency) and individuals using methotrexate. • Bronchiectasis, lung cancer or other forms of cancer. • Life expectancy <28 days in the opinion of study physician • Vaccination in the last month
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare Type I and III interferons (IFNs) and IFN-stimulated genes (ISGs) IFN-beta gene expression in nasal secretions, as a proxy for nasal anti-viral defence readiness, in COPD patients with and without frequent exacerbations under steady state conditions. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. In depth (gene) profiling of innate immune cells in nose and blood of asymptomatic smokers, and in COPD patients with or without frequent exacerbations. 2. Analysis of secreted immune mediators (e.g. cytokines, antimicrobial defence molecules, immunoglobulins and metabolites) in nasal lining fluid and blood of each group. 3. Determine the interferon score in each group through collective analysis of the expression of interferon-stimulated genes and IFN protein levels, and other relevant downstream signalling molecules. 4. Assess the responsiveness of nasal epithelium to viral infections in ex vivo cultured nasal cells (through expanded organoid cultures). 5. Associate nasal and systemic factors (e.g. cytokines, immunoglobulins and metabolites) with innate immune cells. | — |
Countries
Netherlands
Contacts
Leids Universitair Medisch Centrum