Time Course of Respiratory Oscillometry Parameters During Nasal High-Flow Therapy in Stable Chronic Obstructive Pulmonary Disease (NHFlOscillo)

Time Course of Respiratory Oscillometry Parameters During Exposure to Nasal High-Flow Therapy in People With Stable Chronic Obstructive Pulmonary Disease: A Prospective Open-Label Single-Arm Physiological Study

Chronic obstructive pulmonary disease (COPD) can affect the small airways and alter respiratory mechanics. Nasal high-flow therapy delivers warmed and humidified gas through nasal cannulas and may change airway resistance. Respiratory oscillometry is a noninvasive test that measures respiratory resistance and reactance during quiet breathing.

This prospective, single-center study will enroll 20 adults with severe or very severe stable COPD who have never used nasal high-flow therapy. During a single study visit lasting approximately 6 hours, participants will receive individualized nasal high-flow therapy for 4 hours. Respiratory oscillometry will be measured before exposure, immediately after device titration, and after 30, 60, 120, 180, and 240 minutes.

The primary objective is to describe the time course of the difference between respiratory resistance measured at 5 hertz and at 20 hertz (R5-R20), an indirect index of peripheral airway mechanical abnormalities. Secondary objectives are to describe changes in total and proximal respiratory resistance, respiratory reactance, resonant frequency, and area of reactance. The hypothesis is that nasal high-flow exposure will produce measurable, time-dependent changes in respiratory oscillometry parameters.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Device: Heated Humidified Nasal High-Flow Therapy

Detailed Description

NHFlOscillo is a prospective, open-label, single-center, single-arm physiological study involving adults with stable severe to very severe chronic obstructive pulmonary disease (COPD). The study is designed to characterize the time course of respiratory oscillometry parameters during a standardized 4-hour exposure to heated and humidified nasal high-flow therapy.

Participants will attend a single study visit and will be instructed to take their usual medications before the visit. After providing written informed consent, baseline characteristics will be recorded, and participants will complete the modified Medical Research Council Dyspnea Scale (mMRC), the St George's Respiratory Questionnaire (SGRQ), the COPD Assessment Test (CAT), and the Leicester Cough Questionnaire (LCQ). Baseline impulse oscillometry (IOS) will then be performed using a calibrated Vyntus IOS system, with the participant seated and breathing quietly, in accordance with current European Respiratory Society technical standards.

Nasal high-flow therapy will be initiated at a flow rate of 15 L/min and a temperature of 34 °C. After 3 minutes, the temperature will be increased to 37 °C if tolerated; otherwise, it will be maintained at 34 °C. The flow rate will then be increased every 3 minutes to an individualized level consistent with usual clinical practice, up to a maximum of 40 L/min. In participants receiving long-term oxygen therapy, supplemental oxygen will be titrated to maintain an oxygen saturation comparable to that observed under their usual conditions without nasal high-flow therapy.

The exposure will be continued for a total of 4 hours and will be briefly interrupted to perform oscillometry measurements immediately after titration and at 30, 60, 120, 180, and 240 minutes after the start of nasal high-flow therapy.

The target sample size is 20 participants. Changes in oscillometry parameters over time will be analyzed using linear mixed-effects models, with measurement time included as a fixed effect and participant included as a random effect. Each post-exposure time point will be compared with the pre-exposure baseline. Results will be reported as mean differences with 95% confidence intervals and interpreted according to the minimal clinically important difference for each outcome, when available.

Prespecified subgroup analyses will be conducted in participants receiving long-term oxygen therapy and in participants with cough and sputum production. Cough and sputum production will be identified using two alternative operational definitions:

CAT: a score ≥2 on both items 1 and 2; SGRQ: cough on most days or several days per week (response option 1 or 2 to the item "I cough") and sputum production on most days or several days per week (response option 1 or 2 to the item "I bring up sputum").

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tristan Bonnevie, PhD; Phone Number: +33235592970; Email: t.bonnevie@adir-hautenormandie.com

Study Locations

• France
  • Normandy
    • Rouen, Normandy, France, 76000
      • ADIR Association
      • Contact: Tristan Bonnevie, PhD; Phone Number: +33235592970; Email: t.bonnevie@adir-hautenormandie.com
      • Principal Investigator: Tristan Bonnevie, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age >18 years and <85 years;
• Chronic obstructive pulmonary disease classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric grade III or IV;
• Modified Medical Research Council dyspnea score ≥2;
• Completed a pulmonary rehabilitation program at the study center;
• Clinically stable, defined as no exacerbation and no treatment change during the previous 4 weeks;
• With or without long-term oxygen therapy;
• Never previously used nasal high-flow therapy;
• Affiliated with a French social security system;
• Able to read and understand the participant information and provide written informed consent.

Non-inclusion Criteria:

• Under legal guardianship or curatorship;
• Confirmed or suspected pregnancy;
• Unable to provide informed consent;
• Primary diagnosis of another chronic obstructive respiratory disease, such as asthma or primary bronchiectasis;
• Severe or unstable cardiovascular disease, including uncontrolled cardiac arrhythmia, severe heart failure, recent myocardial infarction, or unstable angina;
• Hemodynamic instability.

Exclusion Criteria:

• None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Nasal High-Flow Therapy; Participants receive individualized, heated and humidified nasal high-flow therapy (myAirvo 3, Fisher & Paykel Healthcare, New Zealand) for 4 hours during a single study visit, with repeated respiratory oscillometry assessments.

Device: Heated Humidified Nasal High-Flow Therapy; Therapy is initiated at 15 L/min and 34 °C. After 3 minutes, the temperature is increased to 37 °C if tolerated; otherwise it is returned to or maintained at 34 °C. Flow is increased every 3 minutes to an individualized clinically used level, up to 40 L/min. In participants receiving long-term oxygen therapy, supplemental oxygen is titrated to maintain a saturation comparable to the usual saturation without nasal high-flow therapy. Total exposure duration is 4 hours. The intervention is briefly interrupted for respiratory oscillometry immediately after titration and at 30, 60, 120, 180, and 240 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Frequency Dependence of Respiratory Resistance (R5-R20)	Frequency dependence of respiratory resistance is calculated as respiratory resistance measured at 5 hertz minus respiratory resistance measured at 20 hertz (R5-R20). It is measured by impulse oscillometry using the Vyntus impulse oscillometry system (IOS) and expressed in kilopascals per liter per second (kPa/L/s). Percent-predicted values will also be reported when appropriate reference equations are available. The outcome is the change from the pre-exposure baseline at each post-baseline assessment during the exposure period. The registered measure is the repeated change from the pre-exposure baseline across the exposure period.	Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Respiratory Resistance at 5 Hertz (R5)	Total respiratory resistance at 5 hertz (R5) is measured by impulse oscillometry and expressed in kPa/L/s. Percentage of predicted values will also be reported when reference equations are available.	Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.
Change From Baseline in Proximal Respiratory Resistance at 20 Hertz (R20)	Respiratory resistance at 20 hertz (R20), reflecting predominantly proximal airway resistance, is measured by impulse oscillometry and expressed in kPa/L/s. Percentage of predicted values will also be reported when reference equations are available.	Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.
Change From Baseline in Respiratory Reactance at 5 Hertz (X5)	Respiratory reactance at 5 hertz (X5) is measured by impulse oscillometry and expressed in kPa/L/s. Percentage of predicted values will also be reported when reference equations are available.	Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.
Change From Baseline in Resonant Frequency (Fres)	Resonant frequency (Fres) is measured by impulse oscillometry and expressed in hertz. Percentage of predicted values will also be reported when reference equations are available.	Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.
Change From Baseline in Area of Reactance (AX)	Area of reactance (AX) is measured by impulse oscillometry and expressed in kPa/L. Percentage of predicted values will also be reported when reference equations are available.	Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.

Collaborators and Investigators

• Sponsor: ADIR Association
• Collaborators: Fisher and Paykel Healthcare; University of Rouen Normandie
• Investigators: Principal Investigator: Tristan Bonnevie, PhD, ADIR Association

Publications and helpful links

General Publications

• Abdo M, Kirsten AM, von Mutius E, Kopp M, Hansen G, Rabe KF, Watz H, Trinkmann F, Bahmer T; ALLIANCE study group. Minimal clinically important difference for impulse oscillometry in adults with asthma. Eur Respir J. 2023 May 5;61(5):2201793. doi: 10.1183/13993003.01793-2022. Print 2023 May.
• Kuo YL, Chien CL, Ko HK, Lai HC, Lin TL, Lee LN, Chang CY, Shen HS, Lu CC. High-flow nasal cannula improves respiratory impedance evaluated by impulse oscillometry in chronic obstructive pulmonary disease patients: a randomised controlled trial. Sci Rep. 2022 Apr 28;12(1):6981. doi: 10.1038/s41598-022-10873-x.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 29, 2028
• Study Completion (Estimated): February 29, 2028

Study Registration Dates

• First Submitted: August 3, 2026
• First Submitted That Met QC Criteria: August 3, 2026
• First Posted (Actual): August 6, 2026

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 6, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Respiratory mechanics; Impulse oscillometry; Small airways; High-flow nasal cannula; Respiratory oscillometry; Nasal high-flow therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: NHFlOscillo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available upon reasonable request for research purposes after publication. This includes de-identified data related to demographic characteristics, as well as endpoints published either in the main manuscript or any supplemental data. Requests should be sent to t.bonnevie@adir-hautenormandie.com
• IPD Sharing Time Frame: Data will be made available after publication.
• IPD Sharing Access Criteria: Data will be made available upon request for research purposes. Requests should be sent to t.bonnevie@adir-hautenormandie.com.

Drug and device information, study documents

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