Clinical trial NCT02833727: Airway Inflammation and Disease Burden in Asthmatic Smokers
Official title: Assessment of Airway Inflammation and Disease Burden in Moderate to Severe Asthmatic Smokers
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthma
Keywords: asthma; smoking; Eosinophils; health care costs
Lead sponsor: Université de Montréal
Sponsor class: OTHER
Collaborators: name: Teva Pharmaceuticals USA
First posted: 2016-07-14
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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

Brief summary: 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

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.

Eligibility criteria: 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)

Primary outcomes:
measure: blood eosinophil count
timeFrame: one year
Secondary outcomes:
measure: Sputum eosinophil count
timeFrame: One year
measure: Fractional exhaled nitric oxide (FeNO)
timeFrame: One year
measure: FEV1
timeFrame: One year
measure: Asthma-related quality of life score
timeFrame: One year
measure: Asthma exacerbations
timeFrame: Two years
measure: Medical direct and indirect costs related to asthma
timeFrame: Two years
measure: Adherence to asthma treatment measured by the proportion of days covered (PDC)(%)
timeFrame: Two years
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
Study officials:
affiliation: CIUSS du nord de l'île de Montréal
name: Catherine Lemiere, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.