Air Pollution and Inhaled Corticosteroids in COPD (APIC)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: COPD
• Intervention / Treatment: Other: Diesel Exhaust; Drug: LABA+LAMA; Other: Filtered Air; Drug: LABA+LAMA+ICS

Detailed Description

APIC will involve 48 volunteer participants (24 of each biological sex assigned at birth) with mild-to-moderate COPD where the researchers will look at what (if any) are the differences between breathing in fresh air (filtered air - FA) or polluted air (diesel exhaust - DE) while taking the drug (Inhaled corticosteroid - ICS) or not (no ICS), both in combination with two standard COPD medicines that make it easier to breath (a long-acting beta-agonist and a long-acting muscarinic antagonist). The participant will take an inhaled medication daily throughout the study. This study will use a controlled amount of diesel exhaust to model traffic-related air pollution (TRAP), a commonly encountered form of polluted air.

Each participant will act as their own control, as they will experience all four combinations: 1) FA-ICS, 2) FA-no ICS, 3) DE-ICS, and 4) DE-no ICS. These combinations will be randomized in what researchers call a double-blinded crossover study, so that every participant will get these combinations in a different order. However, only the engineer on the team will be allowed to know which participant gets what. Blinding will prevent everyone else, including the participant, from being biased against the conditions and affecting outcomes based on this perception.

The study will span over five months (approximately 121 days of active commitment), which includes ten in-person visits to a research office at the Vancouver General Hospital, for a total of approximately 40 hours. While the participant is on-site, the investigators will supervise a series of questionnaires, sample collection (blood, urine, bronchoscopy lung samples), and lung function tests. The investigators will evaluate multiple endpoints as detailed in the Outcome Measures section. For each applicable endpoint, the investigators will evaluate stratified analyses and effect modification by biological sex, participant age, gene score, and microbiomes.

The investigators do not expect that the participant's responses to either the corticosteroid or diesel exhaust will be noticeable to them. Any responses that may occur will probably only be detectable through careful examination of their cells and tissues (e.g., blood, urine, bronchial samples). However, understanding the subtle changes that may occur could help reduce or prevent health problems associated with TRAP exposure in the future.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: PJ (Parteek) Johal, BCS; Phone Number: 604-875-5132; Email: p.johal@ubc.ca
• Study Contact Backup: Name: Agnes Yuen, BSc; Phone Number: 66455 604-875-4111; Email: agnes.yuen@ubc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Between the ages of 40 to 80
• Mild-to-moderate COPD diagnosis (Global Initiative for Chronic Obstructive Lung Disease stage 1-2) as confirmed by medical history, questionnaires, and spirometry (a test that measures the amount of air one can breathe in and out of the lungs) results
• Spirometry results will be assessed by the study physician to determine eligibility

Exclusion Criteria:

• Currently smoking or have been smoking within six months of your screening visit for this study
• Have had an acute exacerbation of COPD (AECOPD) diagnosis within 365 days of the screening visit
• Have a history of asthma or asthma-COPD overlap syndrome
• Existing medical condition or other health concerns as assessed by the study physician
• Pregnant, plan to be pregnant, or breastfeeding during your enrolment in the study. Participants of childbearing potential will be required to have a negative pregnancy test prior to study inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Filtered Air with LABA/LAMA; Participants will inhale a ultra Long-Acting Beta-Agonist (LABA; vilanterol (25mcg)) + Long-acting Muscarinic Antagonist (LAMA; umeclidinium (62.5mcg)) combination medication once daily for 28+ days before sitting in a booth and being exposed to high-efficiency particulate air (HEPA) filtered air for 2 hours.	Drug: LABA+LAMA; 1 dose per day (AM); Other Names: Anoro Ellipta; Other: Filtered Air; Exposure to HEPA filtered air, as a control
Active Comparator: Filtered Air with LABA/LAMA + ICS; Participants will inhale a LABA (vilanterol (25mcg)) + LAMA (umeclidinium (62.5mcg))+ Inhaled Corticosteroid (ICS; fluticasone furoate (100mcg)) medication once daily for 28+ days before sitting in a booth and being exposed to HEPA-filtered air for 2 hours.	Other: Filtered Air; Exposure to HEPA filtered air, as a control; Drug: LABA+LAMA+ICS; 1 dose per day (AM); Other Names: Trelegy Ellipta
Active Comparator: Diesel Exhaust with LABA/LAMA; Participants will inhale a LABA (vilanterol (25mcg)) + LAMA (umeclidinium (62.5mcg)) medication once daily for 28+ days before sitting in a booth and being exposed to diesel exhaust (standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5)) for 2 hours.	Other: Diesel Exhaust; Diesel exhaust standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5).; Other Names: Traffic Related Air Pollution; Drug: LABA+LAMA; 1 dose per day (AM); Other Names: Anoro Ellipta
Experimental: Diesel Exhaust with LABA/LAMA + ICS; Participants will inhale a LABA (vilanterol (25mcg)) + LAMA (umeclidinium (62.5mcg))+ Inhaled Corticosteroid (ICS; fluticasone furoate (100mcg)) medication once daily for 28+ days before sitting in a booth and being exposed to diesel exhaust (300ug/m3 of PM2.5) for 2 hours.	Other: Diesel Exhaust; Diesel exhaust standardized to 300µg/m³ of particulate matter with a diameter of 2.5 micrometers or less (PM2.5).; Other Names: Traffic Related Air Pollution; Drug: LABA+LAMA+ICS; 1 dose per day (AM); Other Names: Trelegy Ellipta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: University of Manitoba; University of North Carolina, Chapel Hill; University of Calgary; University of Ottawa
• Investigators: Principal Investigator: Neil Alexis, PhD, University of North Carolina, Chapel Hill; Principal Investigator: Christopher Carlsten, MD, MPH, University of British Columbia; Principal Investigator: Neeloffer Mookherjee, PhD, University of Manitoba; Principal Investigator: Shawn Aaron, MD, FRCPC, University of Ottawa/Université d'Ottawa; Principal Investigator: Janice Leung, MD, FRCPC, University of British Columbia; Principal Investigator: Christopher F Rider, PhD, University of British Columbia

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: August 8, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Air Pollution; LABA/LAMA; Inhaled Corticosteroid; Triple Therapy (LABA/LAMA/ICS)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration
• Other Study ID Numbers: H22-03008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No