Air Pollution and Inhaled Corticosteroids in COPD
NCT Number: NCT06552364
Acronym: APIC
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: COPD
Interventions: DRUG: LABA+LAMA|DRUG: LABA+LAMA+ICS|OTHER: Filtered Air|OTHER: Diesel Exhaust
Sponsor: University of British Columbia
Collaborators: University of Calgary|University of Ottawa|University of Manitoba|University of North Carolina, Chapel Hill
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 48
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-09-01
Completion Date: 2028-12-31

Summary:
Studies have shown that people with chronic obstructive pulmonary disease (COPD) have worse symptoms after breathing polluted air. People with COPD also often need to go to the hospital if they get a virus or other bug. One of the main drugs taken for COPD treatment (inhaled corticosteroid) may change COPD patients' lungs in ways that make it harder to deal with bugs, especially if they breathe in polluted air. If so, this could cause more frequent hospital visits. On the other hand, the same drug (inhaled corticosteroid) helps some people control symptoms, and may help them avoid hospital visits. The APEL investigators are conducting this study (APIC) to understand if this drug (inhaled corticosteroid), in combination with polluted air, will change the lungs of those with COPD in ways that make it more likely to catch bugs or have other problems.

Primary Outcome Measures: Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on inflammatory cells., Differentially count lung cells., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on exhaled nitric oxide., Measurement of fractional exhaled nitric oxide (FeNO)., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on anti-microbial host defense proteins., Anti-microbial host defense (AMP) matrix, determined from, for example, human neutrophil peptide 1 (HNP1; DEFA1), calprotectin (S100A8/S100A9), cathelicidin antimicrobial peptide/LL-37, Lipocalin-2 (LCN2), and S100 calcium-binding protein A7 (S100A7) in the lungs. And dermcidin (DCD), calprotectin (S100A8/S100A9), cathelicidin antimicrobial peptide/LL-37, and amphiregulin (AREG) in peripheral blood., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on oxidative stress in the lungs., Determine oxidative stress (e.g. H2DCFDA) in the lungs., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on neutrophil extracellular TRAPs (NETs)., Analysis of counts of neutrophil extracellular TRAPs (NETs)., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on lung inflammatory markers., An inflammation matrix will be generated, including data from RNA and proteins (e.g. serum amyloid A (SAA), c-reactive protein (CRP), chemokine ligand 18 (CCL18) and fibrinogen), in the lungs., Comparison of the different arms over the span of 5 months.
Secondary Outcome Measures: Inhaled corticosteroids (ICS) and/or diesel exhaust exposure induced modulation of circulating markers of inflammation., An inflammation matrix will be generated, including data from RNA and proteins (e.g., CRP, CCL18, fibrinogen, CX3CL1, CCL23, CXCL8, SAA, MMP9, MMP12, APOB, APOM) in peripheral blood., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure induced modulation of circulating cells and inflammatory cellular markers., Measurement of cellular inflammation scores from complete cell counts, and cellular markers (e.g. CD80, CD86, HLA-DR, CD283, CD288, CD119, TLR7, CD16, CD64, CD11b, CD206, CXCR2) in peripheral blood., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure induced modulation of lung resistance as assessed by oscillometry., Lung resistance and reactivity from respiratory oscillometry Rrs5, Rrs20, Rrs5-20, Xrs5, AX and Fres., Comparison of the different arms over the span of 5 months.|Inhaled corticosteroid (ICS) and/or diesel exhaust exposure effects on lung function., Lung function as evaluated by spirometry (e.g. FEV1)., Comparison of the different arms over the span of 5 months.|Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on neutrophil function., Neutrophil respiratory burst (Fc-OxyBURST Green) measurement., Comparison of the different arms over the span of 5 months.|Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on phagocytosis., Measurement of phagocytosis (fluorescein isothiocyanate-labelled opsonized S. cerevisiae zymosan-A bioparticles uptake)., Comparison of the different arms over the span of 5 months.|Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the EXACT (and E-RS:COPD) questionnaire., The EXACT (and its derivative instrument E-RS (Evaluating Respiratory Symptoms):COPD) questionnaire (see https://www.evidera.com/what-we-do/patient-centered-research/coa-instrument-management-services/exact-program/exact-content/) will be completed., Comparison of the different arms over the span of 5 months.|Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the mMRC dyspnea scale questionnaire., The modified Medical Research Council (mMRC) Dyspnea Scale (see https://www.pcrs-uk.org/mrc-dyspnoea-scale) will be completed., Comparison of the different arms over the span of 5 months.|Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the Symptoms and Perception questionnaire., The Symptoms and Perception questionnaire (see https://particleandfibretoxicology.biomedcentral.com/articles/10.1186/s12989-022-00506-6#Sec15) will be completed., Comparison of the different arms over the span of 5 months.|Effects of inhaled corticosteroids (ICS) and/or diesel exhaust on the Perceived Stress Scale questionnaire., The Perceived Stress Scale questionnaire (see https://www.das.nh.gov/wellness/docs/percieved%20stress%20scale.pdf) will be completed., Comparison of the different arms over the span of 5 months.