Mechanism and Dynamics of Bronchial Hyper-reactivity to Methacholine in Distal Airway on Obese Patients With Asthma (SCANN'AIR)

New insights of small airway contribution to asthma have been gained. Poor levels of control and recurrent exacerbations were shown to have the phenotypic counterpart of asthma with predominant small airway involvement. Very few pathological specificities were identified at this site: mast cells infiltration was suggested as the specific inflammatory change when compared to the proximal airways.Biomarkers in asthma are still complex to validate, especially in the blood, since compartmentalisation is intense in the lung and the airways, a property attributed to the filtering role of the lung to maintain homeostasis. Over the last few years, Fraction exhaled Nitric Oxide (FENO) was developed as a non-invasive and indirect reflection of airway eosinophilic inflammation]. In the blood, peripheral eosinophil counts were shown as a correct T helper 2 (TH2)-phenotype identifier but not perfectly related to airway eosinophilic infiltration. Club cell secretory protein (SCGB1A1) levels have been shown to have some relevance in asthma, chronic obstructive pulmonary disease (COPD), BOS, sarcoidosis, and lung cancer.A biomarker for small airway disease in asthma may improve the management of the disease, identify areas of therapeutic resistance and constitute a therapeutic guidance tool. In this study, investigators aimed to assess small airway involvement in asthmatic women as far as they could. For this purpose, investigators analysed trends in air trapping by acquiring expiratory CT slices at each dose during a bronchoprovocation test with metacholine. Biomarkers were subsequently tested and confronted to clinical and demographical characteristics in their ability to predict the small airway involvement index obtained at CT.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: metacholine provocation test and CT-scan low dose

Detailed Description

Patients will be recruited in the respiratory department of University Hospital in Montpellier (France) from June 2012 to March 2014. All patients are asthmatics, in order to avoid any gender-related biases, investigators decided to include only women. All participants had normal range spirometry, specifically regarding forced expiratory volume. Each patient will undergo a bronchial provocation test coupled with a thoracic CT scan. Bronchial and alveolar Nitric Oxyde will also be measured, a blood sample will be obtained in order to measure biomarker concentrations, and the patients will be asked to answer the validated Asthma Control Questionnaire in order to quantify asthma control.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Department of respiratory disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients will be recruited in the respiratory department of University Hospital in Montpellier (France) from June 2012 to March 2014. All patients are asthmatics, in order to avoid any gender-related biases, investigators decided to include only women. All participants had normal range spirometry, specifically regarding forced expiratory volume.

Description

Inclusion Criteria:

• Female >= 18 yrs
• Asthma
• Treated with Inhaled Corticosteroid (ICS)
• normal range spirometry

Exclusion Criteria:

• Patients with other respiratory disease
• Patients with myocardial infarction (for 3 month before enrollment)
• Patients with cerebrovascular accident (for 3 month before enrollment)
• Patients with arterial aneurysm known
• Patients in pregnancy
• Patients nursing

Study Plan

How is the study designed?

Design Details

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

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal weight; Included patients with a BMI < 25 will be part of this group.	Other: metacholine provocation test and CT-scan low dose; Investigators perform a metacholine provocation test where expiratory CT slices were acquired at each dose
Overweight; Included patients with a BMI >= 25 and <30 will be part of this group.	Other: metacholine provocation test and CT-scan low dose; Investigators perform a metacholine provocation test where expiratory CT slices were acquired at each dose
Obese; Included patients with a BMI >= 30 will be part of this group.	Other: metacholine provocation test and CT-scan low dose; Investigators perform a metacholine provocation test where expiratory CT slices were acquired at each dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in inspiratory:expiratory mean lung density	Baseline versus post-methacholine challenge	4 hours (after the enrollment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in lung fractal dimension	Baseline versus post-methacholine challenge	4 hours (after the enrollment)
Bronchial morphometry	Analysis of CT imaging	Baseline
CC10 level	Clara cell 10 kD protein levels in blood	Baseline
FeNO	Exhaled nitric oxide level	Baseline
FaNO	Alveolar nitric oxide level	Baseline

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Collaborators: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Arnaud BOURDIN, MD, University Hospital, Montpellier

Publications and helpful links

Helpful Links

• SCANN'AIR on the Open Science Framework
• Derived methods publication.
• Secondary results publication.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 5, 2015
• First Submitted That Met QC Criteria: March 30, 2017
• First Posted (Actual): April 6, 2017

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 2, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: overweight; asthma; Airways
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Bronchial Hyperreactivity
• Other Study ID Numbers: 8836 (CTEP); 2011-A01396-35 (Other Identifier: ANSM)