Methacholine Challenge Test (MCT) in Healthy Adults

Methacholine Challenge Test (MCT) in Healthy Adults: Oscillometry Measured Alone Compared to Oscillometry and FEV1 During the Same Test

Knowledge of Methacholine Challenge Test (MCT) and impedance Oscillometry (IOS) is limited. Only three studies have included adult patients, and none of these with healthy controls. The three studies have combined IOS and spirometry in the same test, although it is not recommended to perform IOS after a test that requires deep breathing, e.g. FEV1 measurement. Deep breathing is considered to affect the impedance via reduced tone in the smooth muscle.

Study Overview

• Status: Recruiting
• Conditions: Hyperreactive Airway Disease
• Intervention / Treatment: Diagnostic test: Methacholine Challenge Test

Detailed Description

Asthma is a common chronic disease that is characterized by a history of variable respiratory symptoms and variable expiratory airflow limitation, and usually associated with airway hyperresponsiveness.

In general, FEV1 is used to test for airway hyperresponsiveness (AHR), and a 20% decrease after methacholine challenge test (MCT) is considered a positive test.

There is increasing recognition that the small airways are involved in 40-80% of patients with asthma, and the function of these airways is overlooked (the "silent zone") when measuring FEV1, which mainly reflects the function of the central airways.

Small airway dysfunction (SAD) can be assessed by IOS where pressure applied to the airways at a range of frequencies, and components of respiratory resistance and reactance are measured. Resistance at 5 Hz (R5) and 20 Hz (R20), respectively, represent total airway resistance and proximal airway resistance. The difference between these two values can be calculated (R5-R20). High R5-R20 and low reactance at 5 Hz (X5) indicate the presence of SAD.

Knowledge of MCT and IOS is limited. Only three studies have included adult patients, and none of these with healthy controls. These studies have combined IOS and spirometry in the same test, although it is not recommended to perform IOS after a test that requires deep breathing, e.g. FEV1 measurement. Deep breathing is considered to affect the impedance via reduced tone in the smooth muscle.

The investigators have the following objectives for these studies:

1. To determine the IOS response to MCT in healthy adults.
2. To investigate whether spirometry (FEV1) carried out in relation to MCT influences IOS by comparing the IOS response to MCT performed with and without spirometry in healthy adults.

• Study Type: Observational
• Enrollment (Estimated): 25

Contacts and Locations

• Study Contact: Name: Thomas Ringbæk, MSci; Phone Number: 21969087; Email: thomasringbaek@gmail.com
• Study Contact Backup: Name: Lars Frolund, MSci; Email: lars.froelund@dadlnet.dk

Study Locations

• Denmark
  • Helsingør, Denmark, 3140
    • Recruiting
    • Thomas Ringbæk
    • Contact: Thomas J Ringbæk, MSci; Phone Number: 21969087; Email: thomasringbaek@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy adults

Description

Inclusion Criteria:

• Forced expiratory volume in the 1. second (FEV1) >80%
• FEV1/FVC-ratio >0,7
• FeNO <25 pbb
• Oxygen saturation (SatO2) >95%
• Negative methacholine Challenge Test = drop in FEV1 less than 20%

Exclusion Criteria:

• Any lung disease
• Lung symptoms
• Medicine for lung disease
• Tobacco smoking
• Ex-smokers with more than 5 package years
• BMI (body mass index) >40 kg/m2

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls; No lung disease or symptoms. Negative methacholine Challenge Test.	Diagnostic test: Methacholine Challenge Test; MCT with IOS alone versus MCT IOS and FEV1 combined; Other Names: FEV1 measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oscillometry; R5	Resistance at 5 Hz; kPa/L/s with FEV1 measurement	baseline (carried out with FEV1 measurement)
Oscillometry; R5	Resistance at 5 Hz; kPa/L/s change from baseline	1-10 days from baseline and carried out without FEV1 measurement
Oscillometry; R20	Resistance at 20 Hz; kPa/l/s with FEV1 measurement	baseline (carried out without FEV1 measurement)
Oscillometry; R20	Resistance at 20 Hz; kPa/L/s change from baseline	1-10 days from baseline and carried out without FEV1 measurement
Oscillometry; X5	Reactance at 5 Hz; kPa/l/s with FEV1 measurement	baseline (carried out without FEV1 measurement)
Oscillometry; X5	Reactance at 5 Hz; kPa/L/s change from baseline	1-10 days from baseline and carried out without FEV1 measurement
Oscillometry; AX	Area of reactance; kPa/L with FEV1 measurement	baseline (carried out without FEV1 measurement)
Oscillometry; AX	Area of reactance; kPa/L change from baseline	1-10 days from baseline and carried out without FEV1 measurement
Oscillometry; Fres	Resonant frequency; Hz with FEV1 measurement	baseline (carried out without FEV1 measurement)
Oscillometry; Fres	Resonant frequency; Hz change from baseline	1-10 days from baseline and carried out without FEV1 measurement

Collaborators and Investigators

• Sponsor: Allergi- og Lungeklinikken, Elsinore
• Investigators: Principal Investigator: Thomas J Ringbæk, Allergy and Lung Clinic Elsinore

Publications and helpful links

General Publications

• Coates AL, Wanger J, Cockcroft DW, Culver BH; Bronchoprovocation Testing Task Force: Kai-Hakon Carlsen; Diamant Z, Gauvreau G, Hall GL, Hallstrand TS, Horvath I, de Jongh FHC, Joos G, Kaminsky DA, Laube BL, Leuppi JD, Sterk PJ. ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests. Eur Respir J. 2017 May 1;49(5):1601526. doi: 10.1183/13993003.01526-2016. Print 2017 May.
• Cottini M, Lombardi C, Passalacqua G, Bagnasco D, Berti A, Comberiati P, Imeri G, Landi M, Heffler E. Small Airways: The "Silent Zone" of 2021 GINA Report? Front Med (Lausanne). 2022 May 23;9:884679. doi: 10.3389/fmed.2022.884679. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2024
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): December 23, 2024

Study Registration Dates

• First Submitted: April 7, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 19, 2024

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: spirometry; oscillometry; bronchial hyperreactivity; IOS
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Cholinergic Agonists; Respiratory System Agents; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Methacholine Chloride
• Other Study ID Numbers: Elsinore_Healthy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No