Time Course of Respiratory Oscillometry Parameters During Nasal High-Flow Therapy in Stable COPD

Official title

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

Overview

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 non-invasive 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 one approximately 6-hour visit, participants will receive individualized nasal high-flow therapy for 4 hours. 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 frequency dependence of respiratory resistance (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.

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, the St George's Respiratory Questionnaire, the COPD Assessment Test, and the Leicester Cough Questionnaire. Baseline impulse oscillometry 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 questionnaire: 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").

Interventions

• 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

Primary outcome measures

• Change From Baseline in Frequency Dependence of Respiratory Resistance (R5-R20) [Time frame: 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 (5)

• Change From Baseline in Total Respiratory Resistance at 5 Hz (R5) [Time frame: 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 Hz (R20) [Time frame: 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 Hz (X5) [Time frame: 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) [Time frame: 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) [Time frame: Baseline; immediately after individualized nasal high-flow titration; and 30, 60, 120, 180, and 240 minutes after starting nasal high-flow therapy.]

Eligibility criteria

Inclusion criteria

• Age >18 years and <85 years;
• Chronic obstructive pulmonary disease, GOLD stage 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

France · 1 center

• ADIR Association — Rouen

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. PMID 36758985
• 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. PMID 35484186

Identifiers

NCT: NCT07750613 · NHFlOscillo

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗