Airway Inflammation and Disease Burden in Asthmatic Smokers

Assessment of Airway Inflammation and Disease Burden in Moderate to Severe Asthmatic Smokers

Aim : To compare, among patients with an uncontrolled moderate to severe asthma, the blood eosinophil levels of smokers and non-smokers.

Secondary aims: In uncontrolled moderate to severe asthmatic subjects, to compare between asthmatic smokers and non-smokers: sputum eosinophils counts, fractional exhaled nitric oxide (FeNO), pre and post bronchodilator Forced expiratory volume in one second (FEV1) / Forced vital capacity (FVC), Asthma-related quality of life, asthma exacerbations during the year preceding enrolment in the study, Medical direct and indirect costs related to asthma during the year preceding enrolment in the study, and adherence to asthma treatment during the year preceding enrolment in the study.

Methods: Cross sectional observational study. Never-smoker and smoker asthmatics treated with at least 2 controller medications with a smoking history ≥10 pack/year with a ACQ score ≥ 1.5 points will be identified in the database RESP. Their clinical data will be matched to the Régie de l'assurance médicale du Quebec (RAMQ) and Maintenance et exploitation des données pour l'étude de la clientèle hospitalière (MED-ECHO) administrative databases and reMed (data on medications for patients with private health insurance) in order to access to data on medical services, hospitalisations and medications delivered by pharmacies. T

Study Overview

• Status: Unknown
• Conditions: Asthma
• Intervention / Treatment: Other: Smoking

Detailed Description

Aim : To compare, among patients with an uncontrolled moderate to severe asthma, the blood eosinophil levels of smokers and non-smokers.

Hypothesis: Uncontrolled never-smoker asthmatics (NSA) will have a greater level of blood eosinophils than uncontrolled asthmatic smokers (AS) (difference in blood eosinophil count at least superior to 100 eosinophils per μL).

Secondary aims: In uncontrolled moderate to severe asthmatic subjects, to compare between asthmatic smokers and non-smokers: sputum eosinophils counts, fractional exhaled nitric oxide (FeNO), pre and post bronchodilator FEV1 / Forced vital capacity (FVC), Asthma-related quality of life, asthma exacerbations during the year preceding enrolment in the study, Medical direct and indirect costs related to asthma during the year preceding enrolment in the study, and adherence to asthma treatment during the year preceding enrolment in the study.

Methods: Cross sectional observational study. Never-smoker and smoker asthmatics treated with at least 2 controller medications with a smoking history ≥10 pack/year with a ACQ score ≥ 1.5 points will be identified in the Quebec registry in respiratory health (RESP). Their clinical data will be matched to the "Régie de l'assurance médicale du Quebec" (RAMQ) and "Maintenance et exploitation des données pour l'étude de la clientèle hospitalière" (MED-ECHO) administrative databases and database on medications dispensed in community pharmacies to patients with private drug insurance (reMed) in order to access to data on medical services, hospitalisations and medications delivered by pharmacies. The subjects identified in the RESP database fulfilling the definition of moderate to severe uncontrolled asthma will be contacted. The Asthma Control Questionnaire (ACQ) will be administered to the subjects over the phone. Subjects with an ACQ score ≥ 1.5 points will be invited to come to the research center of Sacré-Coeur Hospital. During a unique visit at the Hospital du Sacré-Coeur de Montréal, after signature of the consent form, 80 asthmatic smokers and 80 non-smoker asthmatic subjects will be asked to complete questionnaires regarding asthma control (if the delay between telephone interview and visit to the hospital exceed one week), quality of life, and asthma impact on daily activities. FeNO will be measured first. They will then perform spirometry. Sputum induction will be performed to obtain sputum cell counts. Blood will be drawn to obtain blood eosinophil count and serum cotinine. We will be able to compare between asthmatic smokers and non-smoker asthmatics: blood eosinophil counts, sputum eosinophils counts, FeNO, pre and post bronchodilator FEV1 / FVC, asthma-related quality of life, asthma exacerbations during the year preceding enrolment in the study, Medical direct and indirect costs related to asthma during the year preceding enrolment in the study, and adherence to asthma treatment during the year preceding enrolment in the study.

Significance: Anti-interleukin 5 have been shown to be very effective in reducing asthma exacerbations in asthmatic subjects with eosinophilic inflammation with frequent asthma exacerbations. However, smokers have been excluded from these studies. It will be important to determine the burden of asthma in this group of subjects in term of healthcare utilization and productivity at work, in order to evaluate whether or not they may benefit from this type of medication. If we show that the direct and indirect cost related to asthma are higher in asthmatic smokers than non-smokers, it will be even more important to characterize the airway inflammation of this group of subjects in order to determine whether they are likely candidates to receive new biologic agents in order to improve asthma control, decrease their healthcare utilization and improve their productivity at work.

• Study Type: Observational
• Enrollment (Anticipated): 160

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montréal, Quebec, Canada, H4J 1C5
      • Recruiting
      • Hopital du Sacre-Coeur de Montreal
      • Contact: Simone Chaboillez, RT
      • Principal Investigator: Catherine Lemiere, MD,MSc

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Never-smoker and smoker asthmatics treated with at least 2 controller medications with a smoking history ≥10 pack/year with a ACQ score ≥ 1.5 points

Description

Inclusion Criteria:

• Participation to the RESP Database.
• Never-smoker and smoker asthmatics (smoking history ≥10 pack/year)
• Treatment with at least 2 controller medications
• ACQ score ≥ 1.5 points will be identified in the database RESP.

Exclusion Criteria:

• Chronic obstructive Pulmonary Disease (COPD)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Asthmatic smokers (AS); Asthmatics will fulfill the following definition of asthma: reversible airflow obstruction and/or a provocative concentration of methacholine inducing a 20% fall in FEV1 (PC20) < 8 mg/ml with a diagnosis of asthma made by a respirologist. Smokers or ex smokers will be defined by a smoking history of ≥ 10 pack/year.	Other: Smoking; Smoking equal or greater than 10 pack/years; never smokers: lifelong history without smoking.
Asthmatic non-smokers (ANS); Asthmatics will fulfill the following definition of asthma: reversible airflow obstruction and/or a PC20 < 8 mg/ml with a diagnosis of asthma made by a respirologist. Never smokers will have a life-long history without smoking.	Other: Smoking; Smoking equal or greater than 10 pack/years; never smokers: lifelong history without smoking.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
blood eosinophil count	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sputum eosinophil count		One year
Fractional exhaled nitric oxide (FeNO)		One year
FEV1		One year
Asthma-related quality of life score	We will use the Asthma Quality of Life Questionnaire (AQLQ). This is a 32-item, self-administered, disease-specific quality of life questionnaire that evaluates asthma quality of life across 4 domains: activity limitation, symptoms, emotional distress, and environmental stimuli. Each item is rated on a 7-point scale (1=maximal impairment, 7=no impairment) to yield a mean score out of 7.	One year
Asthma exacerbations		Two years
Medical direct and indirect costs related to asthma		Two years
Adherence to asthma treatment measured by the proportion of days covered (PDC)(%)	Adherence to controller medications will be measured with the proportion of days covered (PDC), a widely used measure of adherence based on prescription claims data. The PDC will be defined as the sum of the duration of all prescriptions of the medication under study filled in the year preceding the visit, divided by 365 days, expressed in percent. The PDC will be estimated using prescription refills data obtained from the RAMQ and reMed databases in the year preceding enrolment.	Two years

Collaborators and Investigators

• Sponsor: Université de Montréal
• Collaborators: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Catherine Lemiere, MD, CIUSS du nord de l'île de Montréal

Publications and helpful links

General Publications

• Tan NC, Nguyen HV, Lye WK, Sankari U, Nadkarni NV. Trends and predictors of asthma costs: results from a 10-year longitudinal study. Eur Respir J. 2016 Mar;47(3):801-9. doi: 10.1183/13993003.00188-2015. Epub 2015 Dec 2.
• Chaudhuri R, Livingston E, McMahon AD, Thomson L, Borland W, Thomson NC. Cigarette smoking impairs the therapeutic response to oral corticosteroids in chronic asthma. Am J Respir Crit Care Med. 2003 Dec 1;168(11):1308-11. doi: 10.1164/rccm.200304-503OC. Epub 2003 Jul 31.
• Sunyer J, Springer G, Jamieson B, Conover C, Detels R, Rinaldo C, Margolick J, Munoz A. Effects of asthma on cell components in peripheral blood among smokers and non-smokers. Clin Exp Allergy. 2003 Nov;33(11):1500-5. doi: 10.1046/j.1365-2222.2003.01730.x.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 12, 2016
• First Posted (Estimate): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): May 8, 2018
• Last Update Submitted That Met QC Criteria: May 2, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: asthma; smoking; Eosinophils; health care costs
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 2017-1359

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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