The Mixed Phenotype of Asthma and COPD: the Overlap Syndrome

The Mixed Phenotype of Asthma and COPD: the Overlap Syndrome: A Comparison of Asthma Outcomes in Smoking vs Non-smoking Patients With an Incomplete Reversibility of Airway Obstruction (IRAO)

RATIONALE:

In asthmatic subjects, smoking can lead to several changes in disease characterictics. in smokers of more than 20 pack-years, chronic obstructive pulmonary disease (COPD) can be associated with asthma, also called asthma-COPD overlap syndrome (ACOS). Increasing data support the concept that ACOS is a clinical entity. However, this should be further studied in order to better target therapy.

AIM:

The objective of this study is to evaluate the comparative features of ACOS

METHODS:

This will be a descriptive study comparing the features of the ACOS with the features of asthmatic subjects with an incomplete reversibility of airway obstruction (IRAO).The study will be done over 1 or 2 visits (within a week interval), according to subjects' availability. The visit will include completion of different questionnaires (asthma control asthma quality of life, medical history, exacerbations, etc.), a thoracic examination, allergy skin-prick tests, spirometry and bronchodilator response, lung volumes and compliance measurements, exhaled nitric oxide measurement, blood sampling and a sputum induction.

Study Overview

• Status: Completed
• Conditions: Asthma; COPD

• Study Type: Observational
• Enrollment (Actual): 115

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Asthmatic subjects will be recruited from the asthma outpatient clinic, from participation to past research studies, or from advertisements.

Description

Inclusion Criteria:

ALL SUBJECTS

1. Subjects aged 45 years and older.
2. Free of any other respiratory condition, except for asthma and/or COPD, which may interfere with the tests.
3. Asthma that requires a baseline treatment with inhaled corticosteroids and/or additional asthma medication.
4. Free of respiratory infection in the 4 weeks preceding the study.
5. No changes in the asthma and COPD-related medications in the 4 weeks preceding the study.
6. If female, not pregnant (or lactating).
7. Able to adhere to study procedures.
8. Able and willing to provide written informed consent to participate in the study, in accordance with international conference on harmonization (ICH) good clinical practice (GCP) requirements.

ACOS SUBJECTS

1. Smokers or ex-smokers of at least 20 pack-years. 2. With an IRAO (see definitions section). IRAO SUBJECTS

1. Long-life non-smokers or ex-smokers defined as someone who smoked less than 5 pack-years and who completely stopped smoking for at least 12 months before inclusion in the study.
2. With an IRAO.

Exclusion Criteria:

• ALL SUBJECTS

  1. With COPD without a past diagnosis of asthma.
  2. Unstable respiratory or non-respiratory condition.
  3. Any active chronic inflammatory disease.
  4. Any evidence of malignancy (active and/or treated) within the previous 5 years.
  5. Any significant concomitant illness or injury that would interfere with the subject's participation in the study.
  6. Any history of bronchial thermoplasty. IRAO SUBJECTS
  1. Use of any nicotine containing product within 1 year prior to study entry or a smoking history of > 5 pack-years.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
ACOS smoking history >20 pack-years; Subjects with asthma-COPD overlap syndrome
IRAO smoking history <5 pack-years; Subjects with an incomplete reversibility of airway obstruction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total asthma control questionnaire (ACQ) score	Measurement of asthma control using a 0-6 scale. The questionnaire includes 6 questions. Total score is the mean of the scores from all questions. Total score ranges from 0 to 6. A lower score is better.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spirometry results	Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC	Baseline
Sputum eosinophil percentage	Percentage of sputum eosinophils	Baseline
Concentration of Blood biomarkers	alpha 1 antitrypsine, C-reactive protein (CRP), fibrinogen	Baseline
Asthma quality of life questionnaire (AQLQ) score	Measurement of asthma quality of life using the Mini asthma quality of life questionnaire. It is a 7-point scale questionnaire (where 1 is greatest impairment and 7 is least impairment) containing 15 uqestions divided into 4 domains : symptoms (5 items), activity limitation (4 items), emotional function (3 items), and exposure to environmental stimuli (3 items). during the last 2 weeks. The overall score is the mean of all the responses. Each domain score is calculated from the mean of the items that relate to it.	Baseline
Number of patients with comorbidities	gastro-oesophageal reflux disease (GERD), obstructive sleep apnea (OSA), anxiety, depression	Baseline
Number of asthma exacerbations in the previous year	emergency room (ER) visits, hospitalizations, oral corticosteroids treatment, unscheduled medical visits	Baseline
Change from baseline total Asthma Control Questionnaire (ACQ) score at one-year follow-up	Measurement of asthma control using a 0-6 scale. The questionnaire includes 6 questions. Total score is the mean of the scores from all questions. Total score ranges from 0 to 6. A lower score is better.	Baseline to one-year follow-up
Change from baseline number of exacerbations at one-year follow-up	emergency room (ER) visits, hospitalizations, oral corticosteroids treatment, unscheduled medical visits	Baseline to one-year follow-up

Collaborators and Investigators

• Sponsor: Laval University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: January 13, 2016
• First Submitted That Met QC Criteria: January 24, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): January 25, 2019
• Last Update Submitted That Met QC Criteria: January 24, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: comorbidities; inflammation; pulmonary function; phenotype
• 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: CÉR21047

Drug and device information, study documents

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