The Effect of Physical Exercise in a Cold Air Environment on Normal Volunteers and Asthmatic Patients
Condition: Asthma, Exercise-Induced
MeSH terms: Asthma, Exercise-Induced
Study type: Interventional

Summary: 
      The purpose of the study is to compare airway physiologic reactions to physical exercise in a
      cold air environment (-5°C, 60% relative humidity) between normal volunteers and subjects
      with mild/moderate asthma. For this purpose, the investigators intend to evaluate the effect
      of a cold air exercise test on the Forced Expiratory Volume in 1 second (FEV1), respiratory
      symptoms, functional airway integrity, local and systemic inflammation and on the airway
      microbiome.

      This study also features as an exploratory study for a subsequent interventional study in
      order to establish the feasibility of the cold air exercise protocol and to determine the
      extent of the effects in subjects with mild/moderate asthma.
    

Detailed description: 
      It is already demonstrated that exercising during cold air exposure and at a high altitude
      may induce asthmatic symptoms, a variable degree of airway obstruction and increased
      neutrophilic airway inflammation in asthmatic patients. Therefore, in this project, the
      investigators want to evaluate the feasibility, of a shorter standardized "cold air exercise
      test" (a submaximal exercise challenge in a controlled cold air (-5°C, relative humidity 60%)
      environment) and to compare the respiratory physiologic reactions to physical exercise during
      cold exposure between healthy volunteers and asthmatic patients. For this purpose, they
      intend to evaluate the effect of a cold air exercise test on FEV1, respiratory symptoms,
      functional airway integrity, local and systemic inflammation and on the airway microbiome.

      This study features as an exploratory study for a subsequent interventional study, that will
      assess the protective effect of azithromycin versus placebo on the cold air exercise induced
      changes in patients with mild/moderate asthma (ALASCAIR2 study). The present preparatory
      study is needed to standardize the cold air exercise test in a controlled environment so that
      it would be possible to use it as challenge test in an interventional study and to identify
      the most appropriate design for such a study.

      The primary objective of this study is to compare the proportional change in FEV1, pre to
      post a 90 minutes submaximal exercise in a cold air environment between healthy volunteers
      versus mild/moderate asthmatics, calculated as a time-weighted average over the 30 minutes
      post-exposure.

      The primary endpoint is the change in FEV1, calculated as a time-weighted average over the 30
      minutes after the cold exercise test. At each time point (pre-exposure, 5' post-exposure, and
      at 15, 25 and 35 minutes post-exposure), FEV1 (L) will be measured in triplicate.

      They want to evaluate whether the exercise test in a cold air environment produces
      respiratory symptoms (such as nasal discharge or obstruction, dyspnea, cough and/or mucus
      production, etc.), has an impact on airway integrity (nasal patency, airflow obstruction,
      lung ventilation inhomogeneity & small airway dysfunction, bronchial hyperreactivity, cough
      reflex hypersensitivity), induces local or systemic inflammatory changes (biomarkers in nasal
      fluid, sputum and blood) or changes to the airway microbiome (in nasal fluid and sputum) in
      healthy volunteers and in mild/moderate asthmatics. The study group also want to compare the
      observed changes induced by the cold air exercise test between the healthy volunteers and the
      mild/moderate asthmatics.

      The secondary endpoints of this study include the observed changes in (respiratory) symptom
      score, Peak Nasal Inspiratory Flow (PNIF), Forced Vital Capacity (FVC), Forced Expiratory
      Flow (FEF25-75), Fraction of Exhaled Nitric Oxide (FeNO), histamine provocative concentration
      causing 20% drop in FEV1 (PC20), cough threshold C2 & C5, sputum differential cell count,
      biomarkers in nasal fluid, sputum and blood, nasal and sputum microbial communities between
      the healthy volunteers and the mild/moderate asthmatics.
    

Intervention name(s): Cold air exercise test
Intervention type(s): Other
Intervention description(s): Subjects will perform a submaximal 90 minutes exercise test in a controlled cold air environment (-5°C, 60% relative humidity) in a climate chamber with evaluation pre§/during*/post§ of heart rate (HR)§* and blood pressure (BP)§*, spirometry§*, PNIF§, FeNO§, electrocardiogram (ECG)§*, body & exhaled air temperature§*, capsaicin cough threshold test§, histamine bronchial challenge test§, and sampling of nasal fluid§, induced sputum§, and venous blood§.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Healthy volunteers will be compared with asthmatic subjects
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Asthma; Exercise; Cold air exposure