The Effect of a Cold Air Eucapnic Hyperventilation Test on Lower Respiratory Airways in Healthy Volunteers and Patients With Asthma

NCT07220928 | Completed FDA Device

• 1 other identifier: S66825
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

In this study, we want to evaluate the feasibility and safety of a CAEH test in healthy volunteers and patients with asthma. We want to develop a CAEH test to differentiate patients with different types of asthma and exercise-induced bronchoconstriction from healthy volunteers and to evaluate whether the respiratory phenotype induced by cold air inhalation differs between subjects with asthma and healthy subjects. Furthermore, we want to evaluate whether the CAEH test is more robust over time compared to the EVH test. Previously, our lab has demonstrated that submaximal exercise at subfreezing temperatures in a climate chamber (-5°C) induces an acute respiratory response in patients with asthma and in healthy subjects who have been exposed to high PM10 (unpublished data). Finally, This study will serve as a preliminary study for a subsequent prospective study in which the results and optimized protocol obtained in this study will be used to further evaluate the feasibility of using this CAEH as a diagnostic tool in asthma compared to EIB (CLARINET2). The present study is required to develop a standardized CAEH test in a safe and feasible manner. This study will also help to identify appropriate endpoints (FEV1, multiple breath washout test, biomarkers…) of the subsequent studies.

Conditions

Asthma (Diagnosis)

Keywords

Cold air hyperventilation; Asthma diagnosis

Outcome Measures

Primary Outcomes (1)

• Proportional change in FEV1 after hyperventilation challenge

  The proportional change in FEV1 after hyperventilation challenges compared to baseline were measured.

  After each hyperventilation challenge: pre, immediately, 3, 5, 10, 15 and 30 minutes after the challenge

Secondary Outcomes (3)

• Changes in symptoms

  From the first hyperventilation challenge until 1 day after the second

• Lung function changes

  After each hyperventilation challenge

• Inflammatory parameters

  At baseline and after each hyperventilation challenge

Study Arms (3)

Healthy volunteers with negative histamine provocation challenge

OTHER

Healthy volunteers with negative histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation

Device: Cold air challenge

Healthy volunteers with positive histamine provocation challenge

OTHER

Healthy volunteers with positive histamine provocation challenge will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation

Device: Cold air challenge

Patients with asthma

OTHER

Patients with asthma will perform the same tests as the other 2 arms. The healthy volunteers are assigned in this group after the histamine provocation challenge. All will perform one hyperventilation challenge at room temperature (EVH) and one with cold air (CACh) with pre- and post-exposure evaluation on FEV1, respiratory symptoms and local and systemic inflammation

Device: Cold air challenge

Interventions

Cold air challenge DEVICE

This intervention consists of a standardized cold air eucapnic hyperventilation test using a device that controls temperature, humidity, and ventilation. Airway responses are measured via spirometry and biospecimens (serum and sputum supernatant). It is distinguished from other studies by its prospective design and inclusion of both healthy and asthmatic participants

Also known as: Cold air hyperventilation test

Healthy volunteers with negative histamine provocation challenge; Healthy volunteers with positive histamine provocation challenge; Patients with asthma

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 65 years old at time of signing informed consent
• BMI between 18 and 28 kg/cm2
• Ability to give informed consent and to comply with study protocol, in the investigator's judgement
• Non-smoking or ex-smokers for at least 12 months with less than 10 pack years
• Normal spirometry
• Group specific:
• Histamine positive healthy controls: histamine bronchial challenge test (\< 8 mg/ml) at screening Healthy controls: histamine bronchial challenge test (≥ 8 mg/ml) at screening
• Patients with asthma:
• Physician-diagnosed asthma for at least 6 months
• Post-bronchodilator FEV1 of ≥ 80% at screening
• Documented airway reversibility either by means of post-bronchodilator reversibility of ≥ 12.% and ≥ 200 ml or in the previous 6 months or by means of documented airway hyperresponsiveness (histamine PC20 \< 4 mg/ml) at screening
• Asthma control questionnaire (ACQ) ≤ 1.5
• Regular treatment with ICS with or without LABA (unchanged dose for at least 30 days) at a low or medium dose of ICS

You may not qualify if:

• Previous history of intubation or admission to ICU due to asthma
• Severe asthma exacerbation within one month prior to screening visit
• Treatment with oral or systemic steroids within one month prior to screening visit
• Previous treatment with biologics for asthma
• Other major concurrent pulmonary (such as COPD, cystic fibrosis, sarcoidosis, interstitial lung disease, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, bronchiectasis) or cardiovascular disease
• Pregnancy

Sponsors & Collaborators

• KU Leuven: lead
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (1)

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

MeSH Terms

Conditions

Asthma; Disease

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lieven Dupont

  KU Leuven/UZ Leuven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Healthy volunteers will be compared to patients with astma

Study Record Dates

• First Submitted: October 23, 2025
• First Posted: October 24, 2025
• Study Start: August 4, 2023
• Primary Completion: November 27, 2024
• Study Completion: November 27, 2024
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)