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

Study Status: Completed
Recruit Status: Completed
Study Type: Observational

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

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 Summary: 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.
Sponsor: University Hospital, Montpellier

Current Primary Outcome: Change in inspiratory:expiratory mean lung density [ Time Frame: 4 hours (after the enrollment) ]

Baseline versus post-methacholine challenge


Original Primary Outcome: Same as current

Current Secondary Outcome:

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


Original Secondary Outcome: Same as current

Information By: University Hospital, Montpellier

Dates:
Date Received: June 5, 2015
Date Started: June 2012
Date Completion:
Last Updated: March 30, 2017
Last Verified: March 2017