Mechanism and Dynamics of Bronchial Hyper-reactivity to Methacholine in Distal Airway on Obese Patients With Asthma

Completed

• Conditions: Asthma
• Interventions: Other: metacholine provocation test and CT-scan low dose

• Registration Number: NCT03102749
• Lead Sponsor: University Hospital, Montpellier

Brief Summary

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.

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 Timeline

• Study Start: 2012-06
• Primary Completion: 2013-03
• Study Completion: 2014-12
• Study First Submitted: 2015-06-05
• Study First Submitted QC: 2017-03-30
• Study First Posted: 2017-04-06
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-02
• Last Update Posted: 2019-07-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 35

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Overweight	metacholine provocation test and CT-scan low dose	Included patients with a BMI \>= 25 and \<30 will be part of this group.
Obese	metacholine provocation test and CT-scan low dose	Included patients with a BMI \>= 30 will be part of this group.
Normal weight	metacholine provocation test and CT-scan low dose	Included patients with a BMI \< 25 will be part of this group.

Primary Outcome Measures

Name	Time	Method
Change in inspiratory:expiratory mean lung density	4 hours (after the enrollment)	Baseline versus post-methacholine challenge

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Department of respiratory disease; 🇫🇷 Montpellier, France