Ventilatory Responses to Hypercapnic and Hypoxic Conditions in Hyperventilants

For almost a century, many hypotheses have converged on the idea of altered chemosensitivity in patients suffering from hyperventilation syndrome (HVS).

Given the evolution of current technical equipment and the ability to maximise true positives in HVS ( using the revised hyperventilation provocation test), it seems reasonable to investigate central and peripheral chemosensitivities in HVS subjects.

Study Overview

• Status: Completed
• Conditions: Hypoxia; Hypercapnia; Hyperventilation Syndrome
• Intervention / Treatment: Diagnostic test: Hypercapnic hyperoxic ventilatory response; Diagnostic test: Hypoxic eucapnic ventilatory response

Detailed Description

In the inter-war period, many medical investigators who studied the hyperventilation syndrome (HVS) had already questioned the chemosensitivity to CO2 in HVS patients, without being able to explore it for all intents and purposes.

It was subsequently observed that although HVS is not systematically linked to manifest resting hypocapnia, it is nevertheless systematically correlated with significant variability and complexity of ventilation.

This is consistent with the observations of an increased plant gain in HVS, to be related to an increased loop gain (due to instability of controller gain feedback).

On the other hand, some authors already noted that, when capnia is chronically compromised in HVS, it can be greatly altered by small, transient and barely perceptible increases in VE: a 10% increase in VE could indeed halve PetCO2, while a sigh would be able to decrease PetCO2 by up to 15mmHg.

More recently, teh assumption was made that peripheral chemosensitivity may be impaired in HVS patients.

For all these considerations, it seems reasonable to investigate central and peripheral chemosensitivities in identified HVS subjects on the basis of an objective test, such as the induced hyperventilation test.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brabant
    • Bruxelles, Brabant, Belgium, 1000
      • Chu St Pierre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A plethysmography within subject's predicted values
• A negative metacholine test (no documented allergy)
• A hyperventilation provocation test result that is consistent with the Nijmegen questionnaire score, confirming either group classification (HVS+ or HVS-)

Exclusion Criteria:

• Each of the following known or documented conditions: chronic bronchitis (COPD), emphysema, asthma, cardiac disorder, neurological disorder, gastrointestinal disorder, thyroid disorder or psychological/psychiatric disorder
• Suspicious cardio-pulmonary exercise testing (CPET) with cardiac or respiratory limitation
• Pregnant women or women in the process of becoming pregnant
• Persons with a diving practice (amateur or professional),
• High-level athletes,
• Active smokers and
• persons using morphine, and/or barbiturates, and/or anxiolytics and/or sleeping pills

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HVS-; subjects with no complaint AND a Nijmegen questionnaire score of < 23/64 AND a negative hyperventilation provocation test (criteria revised in 2021) (HVS-)	Diagnostic test: Hypercapnic hyperoxic ventilatory response; The hypercapnic ventilatory response (HCVR) described by Read in 1967 (Read's rebreathing method) is a clinical way to assess the central and peripheric sensitivity to CO2, using a small bag (4-6 l) to achieve prompt equilibrium between the apparatus compartments and the lungs. By rebreathing a hyperoxic mixture with an initial composition of 70% O2, 7% CO2 and 23% N2, this equilibrium is assumed to be achieved after 15 seconds of rebreathing, when the relationship between VE and PetCO2 has become linear.; Diagnostic test: Hypoxic eucapnic ventilatory response; The hypoxic eucapnic ventilatory response (HOVR) is a clinical way to assess the peripheric chemosensitivity to O2, using a small bag (4-6 l) to rebreathe a gas mixture initially composed of 20% O2, 0% CO2 and Δ% N2. Eucapnia is achieved by the activation of a CO2 reabsorption cell during the course of the test.
Other: HVS+; subjects with complaints AND a Nijmegen questionnaire score of ≥23/64 AND a negative hyperventilation provocation test (criteria revised in 2021) (HVS+)	Diagnostic test: Hypercapnic hyperoxic ventilatory response; The hypercapnic ventilatory response (HCVR) described by Read in 1967 (Read's rebreathing method) is a clinical way to assess the central and peripheric sensitivity to CO2, using a small bag (4-6 l) to achieve prompt equilibrium between the apparatus compartments and the lungs. By rebreathing a hyperoxic mixture with an initial composition of 70% O2, 7% CO2 and 23% N2, this equilibrium is assumed to be achieved after 15 seconds of rebreathing, when the relationship between VE and PetCO2 has become linear.; Diagnostic test: Hypoxic eucapnic ventilatory response; The hypoxic eucapnic ventilatory response (HOVR) is a clinical way to assess the peripheric chemosensitivity to O2, using a small bag (4-6 l) to rebreathe a gas mixture initially composed of 20% O2, 0% CO2 and Δ% N2. Eucapnia is achieved by the activation of a CO2 reabsorption cell during the course of the test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The slope of the ventilatory response to hypercapnia (HCVR)	Ventilation increase (litres/min) per unit increase in PetCO2 (mmHg) using Read's method	baseline - during the test
The slope of the ventilatory response to hypoxia (HOVR)	Ventilation increase (litres/min) per unit decrease in SpO2 (%) using Read's method	baseline - during the test
Ventilatory recruitment threshold (VRT) of the HCVR	From the average baseline ventilation and PetCO2, the VRT id the PetCO2 level at which the ventilatory response is activated	baseline - during the test
Ventilatory recruitment threshold (VRT) of the HOVR	From the average baseline ventilation and SpO2, the VRT is the level of SpO2 at which the ventilatory response is activated	baseline - during the test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Extrapolated apnoeic threshold of the HCVR	PetCO2 level above which apnoea (zero ventilation) is disrupted, obtained from the extrapolation of the HCVR at the X-axis intersection (when VE=0 l/min)	baseline - during the test
Dyspnea	Visual analogic scale (VAS) of dyspnea, from 0 (no dyspnea) to 10 (maximal dyspnea)	baseline, end of the test

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre
• Collaborators: Université Libre de Bruxelles

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Actual): October 15, 2021
• Study Completion (Actual): October 15, 2021

Study Registration Dates

• First Submitted: October 18, 2021
• First Submitted That Met QC Criteria: December 22, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): January 12, 2022
• Last Update Submitted That Met QC Criteria: December 22, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Hypoxia; Hypercapnia; Hyperventilation
• Other Study ID Numbers: B076201836758 -2

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