Understanding the role of acute exercise in modifying eosinophilic airway inflammation in asthma

INTERVENTION: After attending a screening visit to confirm study eligibility, participants will wear an accelerometer on their wrist for one week to record usual physical activity levels. Participants will then attend two study visits on consecutive days. VISIT 1: Participants will be instructed to abstain from moderate‐vigorous exercise for the two days prior to this visit and all physical activity for 12 hours prior to their visit. Participants will be instructed to withhold their asthma medications for 6‐24 hours and anti‐histamine medications for 3 days. Participants will need to fast for at least 2 hours prior to their visit. Upon arrival to the clinic participants will have their accelerometer collected, their weight checked and a venous blood sample collected. Exhaled nitric oxide (eNO) will be measured and spirometry performed. Sputum induction coupled with bronchial provocation will be performed over a standardised 15.5 minutes nebuliser time using 4.5% hypertonic saline. VISIT 2: Visit 2 will be conducted the day following visit 1. The participant will be required to refrain from physical activity and alcohol consumption since before visit 1, caffeine for at least 6 hours and food for 2 hours. Two hours prior to their scheduled visit, participants will be instructed to have their usual breakfast (without caffeine). Participants will be randomised to complete either: a) 40 minutes of moderate‐intensity exercise (50‐55% of heart rate reserve), plus 5 minute warm‐up and 1 minute cool down. b) 25 minutes of vigorous‐intensity exercise (75‐80% of heart rate reserve), plus 5 minute warm‐up and 1 minute cool down; or c) 30‐minutes of rest in a chair All participants will be provided with 400 micrograms salbutamol, inhaled via a valved holding chamber upon arrival for visit 2. Those randomised to complete one of the two exercise interventions will do so on a cycle ergometer, 20 minutes following administration of salbutamol. Vigorous Intensity Exercise: Moderate Intensity Exercise: Following a short break, waist circumference will be measured. Participants will then undergo skin allergy testing and complete questionnaires related to asthma symptoms and characterisation, and exercise levels. Two hours post‐exercise/rest, participants will have a venous blood sample collected and eNO measured. Participants will then be provided with a standardised light lunch. Four hours post exercise/rest, participants will have their blood pressure checked and a venous blood sample collected. eNO will be measured and spirometry performed. Sputum induction will be performed over a standardised 15.5 min CONDITION: Asthma PRIMARY OUTCOME: Induced sputum eosinophil count SECONDARY OUTCOME: Exhaled nitric oxide, measured using an exhaled nitric oxide breath analyser. Plasma interleukin‐10 Plasma Interleukin‐1ra Plasma Interleukin‐6 Plasma nitric oxide Red blood cell glutathione peroxidase Red blood cell superoxide dismutase Sputum 8‐isoprostane Sputum interleukin‐10 Sputum interleukin‐5 Sputum interleukin‐6 Sputum leukocytes INCLUSION CRITERIA: 1. Physician diagnosed asthma 2. Able to provide written informed consent 3. Females 18‐55 years of age or males 18‐45 years of age 4. Body mass index (BMI) <=40kg/m2 5. Not a current smoker (never smoker or quit at least 6 months ago) 6. Post‐bronchodilator forced expiratory volume in 1 second (FEV1) >=50% predicted. 7. Approved for vigorous exercise by the study coordinator, according to the ESSA “Adult Pre‐Exercise Screening Tool”. Participants will complete a 5 minute warm up, where the tension on the bicycle will be set to its minimum load. After the warm up, the tension on the cycle will be gradually increased until the desired heart rate is achieved (75‐80% of heart rate reserve). Every four minutes the participant will stop cycling for 20 seconds but the timer will continue. Participant’s blood pressure, heart rate, SpO2, BORG dyspnoea rating and rating of perceived exertion will be recorded at 4 minute intervals and the values compared to the criteria to terminate the test. After 25 minutes the cycle will be returned to its minimum load for a 1 minute cool down. Immediately following the cool down, blood pressure, heart rate, SpO2, rating of perceived exertion, and dyspnoea rating will be recorded, while blood pressure, heart rate, SpO2, rating of perceived exertion and dyspnoea rating will be recorded again 5 and 10 minutes after completing the test. FEV1 will be measured 5‐10 minutes following the cool down. If there is a >=10% reduction in FEV1 from baseline, or at patient request, the participant will be given 400 micrograms salbutamol, inhaled via a valved holding chamber . Participants will complete a 5 minute warm up, where the tension on the bicycle will be set to its minimum load. After the warm up, the tension on the cycle will be gradually increased until the desired heart rate is achieved (50‐55% of heart rate reserve). Every 10 minutes the participant will stop cycling for 1 minute but the timer will continue. Participant’s blood pressure, heart rate, SpO2, BORG dyspnoea rating and rating of perceived exertion will be recorded at 4 minute intervals and the values compared to the criteria to terminate the test. After 40 minutes the cycle will be returned to its minimum load for a 1 minute cool down. Immediately following the cool down, blood pressure, heart rate, SpO2, rating of perceived exertion and dyspnoea rating will be recorded, while blood pressure, heart rate, SpO2, rating of perceived exertion and dyspnoea rating will be recorded again 5 and 10 minutes after completing the test. FEV1 will be measured 5‐10 minutes following the cool down. If there is a >=10% reduction in FEV1 from baseline, or at patient request, the participant will be given 400 micrograms salbutamo, inhaled via a valved holding chamber .