Follow-up of Mild Eosinophilic Asthma

Clinical Outcome of Mild to Very-mild Asthma With High Sputum Eosinophils and/or High Genetic Risk Score: a Prospective Longitudinal Study

Asthma is a chronic respiratory disease affecting approximately 10% of the population, the majority of patients with very mild to mild asthma. Asthma is characterized primarily by the presence of symptoms clinical variables, reversible airway obstruction and airway hyperresponsiveness. Inflammation is a key factor in the pathophysiology of the disease. Eosinophilic inflammation is the most common type. However, in the literature it is usually associated with more severe and difficult to control asthma. Although mortality associated with asthma has drastically decreased in recent years, several events still occur. Strangely enough, these frequently affect mild asthmatics. Although there is still a misunderstanding in relation to these events, the most recent practice guides have recommended an approach based on the use of inhaled corticosteroids (ICS) in all, including mild asthmatics. This change of therapeutic cap is still debated, but indicates a need for new studies in this population. Recently, the investigators demonstrated that a subgroup of asthma patients with mild asthma had a eosinophilia. The evolution of this subgroup without bronchial obstruction or respiratory symptoms remains unknown. Indeed, it seems imperative to determine the fate of these subjects in comparison with asthma mild non-eosinophilic since it could be a subgroup at risk of poor outcome. The objective of this study will be to examine the course of asthma in very mild to mild asthma patients who exhibit eosinophilic inflammation of the respiratory tract compared to noneosinophilic subjects.

This will be a prospective observational, longitudinal study. Participants for whom a result of induced sputum showing an eosinophil level greater than or equal to 3% was observed at least 1 year ago will be contacted to participate in the study. They will be matched for age, gender and duration of asthma to subjects without eosinophilia. These subjects will not be on bronchial anti-inflammatory medication. They will have a complete evaluation including respiratory function tests, a methacholine challenge and sputum induction. They will also complete questionnaires on controlling their asthma and exacerbations.

Study Overview

• Status: Unknown
• Conditions: Asthma
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V4G5
    • Recruiting
    • Louis-Philippe Boulet
    • Contact: Marie-Eve Boulay, MSc; Phone Number: 2617 4186568711; Email: marie-eve.boulay@criucpq.ulaval.ca
    • Contact: Louis-Philippe Boulet, MD; Phone Number: 4186564747; Email: lpboulet@med.ulaval.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Asthmatic subjects with at least two sputum cell differential results > 1 year before follow-up visit

Description

Inclusion Criteria:

• With a proven diagnosis of asthma
• With very mild or mild asthma at the time of previous assessment
• With at least two sputum cell differential counts > 1 year before follow-up visit
• With stable asthma and asthma medication for at least 4 weeks before baseline assessment and before follow-up visit
• Able and willing to consent to study procedures

Exclusion Criteria:

• Conditions that could affect measurements, such as any active chronic or systemic inflammatory disease, not related to the respiratory system.
• Subjects with a main diagnosis of eosinophilic granulomatosis with polyangiitis (Churg- Strauss syndrome) or hypereosinophilic syndrome.
• Respiratory tract infection in the 4 weeks preceding past assessments and in the 4 weeks preceding follow-up visit.
• Asthma exacerbation in the 4 weeks preceding past assessments in the 4 weeks preceding follow-up visit.
• Current smokers. Ex-smokers must not have smoked for a minimum of 12 months, and should not have a smoking history ≥10 pack years. Subjects who administer nicotine in other forms (patches, chew tobacco, electronic cigarettes, etc.) will also be excluded from the study;
• Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease.
• Pregnant or lactating women at the time of follow-up visit.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with eosinophilic asthma at baseline; Patients showing ≥3% sputum eosinophils at baseline	Other: No intervention; No intervention
Patients with non eosinophilic asthma at baseline; Patients showing <3% sputum eosinophils at baseline	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean annual change in pre bronchodilator forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC) between baseline and follow-up between the two groups	calculated using: (initial value - follow-up value)/number of years between the two tests	At least one year post baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical sub score of the Asthma Control Scoring system (ACSS) at follow-up between the two groups	Score between 20% and 100%	At least one year post baseline
Number of asthma exacerbations in the year preceding follow-up visit between the two groups	Asthma exacerbations defined as a) number of emergency room visits, b) number of hospitalisations, c) number of oral corticosteroid treatments, and d) number of unscheduled medical visits	At least one year post baseline
Airway reactivity at follow-up between the two groups	Airway reactivity recorded as methacholine provocative concentration inducing a 20% fall in forced expiratory volume in one second (FEV1) (PC20)	At least one year post baseline
Prescribed therapy at follow-up between the two groups	Defined as a) daily dose of inhaled corticosteroids (ICS), b) use of second controller therapy	At least one year post baseline
Airway inflammation between the two groups at follow-up	Percentage of sputum eosinophils	At least one year post baseline
Systemic inflammation between the two groups at follow-up	Blood levels of eosinophils (X10^9/ml)	At least one year post baseline

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Louis-Philippe Boulet, MD, IUCPQ-UL

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: October 14, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CÉR21799

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No