Effects of Vibrating Mesh Nebulisation in Patients with COPD During Non-invasive Ventilation (VMN-NIV)

Not Applicable

Not yet recruiting

• Conditions: COPD (Chronic Obstructive Pulmonary Disease); Non-invasive Ventilation

• Registration Number: NCT06884228
• Lead Sponsor: Guy's and St Thomas' NHS Foundation Trust

Brief Summary

Assessment of the effects of vibrating mesh nebulisation versus jet nebulisation on the electrical activity of the muscles involved in breathing (neural respiratory drive), breathing mechanics (respiratory impedance measured by forced oscillation technique), respiratory flow, heart rate and rhythm, spirometry and breathlessness symptoms in patients with chronic obstructive pulmonary disease who require non-invasive ventilation.

Detailed Description

Background Chronic obstructive pulmonary disease (COPD) remains a leading cause of morbidity and mortality in the United Kingdom. Acute exacerbations of COPD (AECOPD) frequently necessitate hospitalisation, with standard treatment comprising nebulised bronchodilators, antibiotics, and systemic corticosteroids. Approximately 20% of patients hospitalised with AECOPD require non-invasive ventilation (NIV) to manage decompensated hypercapnic respiratory failure, often necessitating concurrent administration of nebulised therapy.

Home NIV use is increasing among COPD patients to improve respiratory symptoms, quality of life, reduce hospitalisation frequency, and enhance survival. These patients may also require nebulised bronchodilator therapy during NIV, particularly when managing acute exacerbations not severe enough to warrant hospitalisation.

Currently, two nebulisation modalities are used as standard of care for patients on NIV:

Jet nebulisation (JN) - the conventional delivery method Vibrating mesh nebulisation (VMN) - a newer technology that utilises a mesh membrane oscillating at high frequency to produce drug-carrying droplets of predetermined size

VMN has been developed to optimise drug delivery in various patient populations, including those who are spontaneously breathing, receiving invasive mechanical ventilation, or on NIV. This technology is designed to enhance pulmonary drug deposition while minimising residual drug volume post-nebulisation.

Previous research has demonstrated that VMN achieves superior pulmonary drug deposition during NIV compared to JN in both healthy subjects and stable COPD patients. VMN has also been shown to produce greater improvements in forced expiratory volume in one second (FEV₁) among hospitalised patients. However, the comparative effects of these nebulisation methods on physiological parameters such as neural respiratory drive and respiratory system impedance during NIV in COPD patients with chronic respiratory failure remain unexplored.

Study Objective This pilot randomised crossover trial aims to compare the physiological effects of vibrating mesh versus jet nebulisation of salbutamol during NIV in patients with chronic respiratory failure due to COPD.

Methods Study Design A randomised crossover trial with participants receiving both interventions with a 48-hour washout period between treatments.

Participants We will recruit 12 patients with COPD currently receiving NIV under the care of the Lane Fox Unit. All participants will provide written informed consent prior to study procedures.

Procedures

Following consent, we will record baseline data including:

NIV settings Anthropometric measurements Arterial blood gas analysis Clinical observations

Participants will be randomised to receive salbutamol via either VMN or JN during NIV. We will measure the following parameters at multiple time points within one hour after nebulisation:

Neural respiratory drive via parasternal electromyography Spirometry Respiratory impedance (mechanics of breathing)

Participants will self-report breathlessness using both a numerical scale and a validated scale.

After a minimum of 48-hour washout period, participants will return to repeat the protocol with the alternative nebuliser type.

Study Timeline

• Study First Submitted: 2025-02-27
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-17
• Last Update Submitted: 2025-03-17
• Study First Posted: 2025-03-19
• Last Update Posted: 2025-03-19
• Study Start: 2025-03-21
• Primary Completion: 2026-05-01
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Patients with COPD receiving home non-invasive ventilation for chronic respiratory failure under the Lane Fox Respiratory Service at Guy's and St Thomas' NHS Foundation Trust
• Tolerating home non-invasive ventilation for at least 4 hours/24 hours
• Aged 18-80 years old
• Able to communicate symptom burden to the research team
• Able to give informed consent for participation in the study
• Clinical stability, with no acute exacerbations of COPD for 2 weeks prior to enrolment

Exclusion Criteria

• Severe, non-respiratory organ dysfunction including, but not limited to:

  • Congestive cardiac failure
  • Significant cardiovascular disease
  • End-stage malignancy
  • End-stage renal failure

• Acute pulmonary pathology requiring emergency treatment including, but not limited to:

  • Pneumonia
  • Pneumothorax
  • Pulmonary embolism

• Severe cognitive impairment

• Psychosocial factors that would preclude completion of the study protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Change in neural respiratory drive	NRD assessed on both visits at baseline and 5, 15, 30 and 60 minutes after nebulisation	Change in neural respiratory drive (NRD) 30 mins following vibrating mesh or jet nebulisation with a bronchodilator (2.5mg salbutamol) during NIV. This will be measured using surface second intercostal space parasternal muscle EMG. This reflects the load-capacity relationship of the respiratory system and will likely decrease with more effective bronchodilation and secretion clearance.

Secondary Outcome Measures

Name	Time	Method
Spirometry - Forced vital capacity	At baseline and during 1 hour after administration of nebuliser on both visits	Spirometry measurements of Forced vital capacity (FVC)
Cardiac rhythm	At baseline and for 60 minutes following nebulisation	Assessment of cardiac rate and rhythm at baseline and following administration of salbutamol via VMN and JN.
Respiratory flow	At baseline and for 60 minutes following nebulisation	Assessment of respiratory flow via pneumotrach at baseline and following administration of salbutamol via VMN and JN
Respiratory System impedence	Both visits at baseline, 5 and 60 minutes post nebulisation therapy.	Change in respiratory system impedance 5 and 60 minutes after vibrating mesh or jet nebulisation therapy with 2.5mg salbutamol during NIV. Respiratory system impedance will be assessed using the forced oscillation technique (FOT).; Change in the difference in within-breath respiratory reactance at 5Hz (ΔXrs,5Hz) 5 and 60 minutes after vibrating mesh or jet nebulisation therapy with 2.5mg salbutamol during NIV, as measured by FOT
Symptom of Breathlessness (numerical rating scale)	At baseline and at 5, 15, 30 and 60 minutes post nebulisation on both visits	Breathlessness numerical rating scale: This will allow patients to report their dyspnoea and how it may change with treatment. The scale ranges from 0 to 10, where 0 indicates no breathing difficulty and 10 represents maximal breathing difficulty.
Symptom of Breathlessness (modified Borg Dyspnoea scale)	At baseline and at 5, 15, 30 and 60 minutes post nebulisation on both visits	Patient perception of breathlessness will be assessed using the modified Borg dyspnoea scale (mBorg). The scale ranges from 0 to 10 (whole numbers plus 0.5), where - indicates no breathing difficulty and 10 represents maximal breathing difficulty.
Transcutaneous CO2 Monitoring	At baseline and for 60 minutes following nebulisation	Continuous transcutaneous carbon dioxide levels will be measured
Spirometry - Forced expiratory volume in 1 second	At baseline and during 1 hour after administration of nebuliser on both visits	Spirometry measurements of Forced expiratory volume in 1s second (FEV1)
Spirometry ratio - FEV1/FVC	At baseline and during 1 hour after administration of nebuliser on both visits	Spirometry measurements used to calculate the ratio FEV1/FVC
Cardiac rate	At baseline and for 60 minutes following nebulisation	Assessment of cardiac rate at baseline and following administration of salbutamol via VMN and JN.

Trial Locations

Locations (1)

Lane Fox Unit, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust; 🇬🇧 London, United Kingdom