Fig. 1

Schematic depicting of the ELSA trial. Study participants (n = 24, 12 ♀, 12 ♂) complete four study arms after the initial preliminary testing. The purpose of the preliminary testing (2 days) is to determine participants’ general health and physical fitness. Day 1 consists of a medical examination where the individual medical history will be recorded and also anthropometric measurements, measurements of blood pressure (BP) and heart rate (HR), echocardiography and 12-lead electrocardiogram (ECG) at rest, blood and urine collection, respiratory testing, a methacholine bronchial challenge test and a cardio-pulmonary exercise test (CPX). A time trial (TT) for familiarization purposes of the participants on a bicycle ergometer followed by cardiac output measurements will be performed on day 2 of preliminary testing. Each of the four study arms starts with anthropometric measurements, BP and HR recordings at rest, followed by blood and urine collections and respiratory testing. Afterwards, participants inhale the study medication (spray inhalers) and BP and HR are measured and respiratory testing is conducted 10 min after application of the medication. The TT procedure starts 20 min after the inhalation and begins with a 20-min warm-up followed by a 5-min low-intensity interval before the start of the 10-min TT, where participants cycle 10 min at the highest possible workload starting with a load equalling 90–95% of maximum power obtained in the preliminary CPX. During the TT, cardiac output is measured non-invasively. BP, HR, respiratory testing and echocardiography are recorded 15 min after the end of the TT. HR and BP are also measured 1 h, 2 h, 3 h and 24 h after the end of the TT. Blood and urine are collected and respiratory testing is performed at 3 h and 24 h post TT. A muscle biopsy is collected 3 h after the TT. The time between study arms will be 5–8 days. Note: Symbols are placed according to the chronological order of the tests and examinations