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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-invasive Ventilation; COPD (Chronic Obstructive Pulmonary Disease)
• Intervention / Treatment: Device: Jet nebuliser; Device: Vibrating mesh nebulisation

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 Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gillian Radcliffe; Phone Number: +442071888070; Email: gillian.radcliffe@gstt.nhs.uk
• Study Contact Backup: Name: Eui-Sik Suh, MBBS MChem(Oxon) PhD FRCP; Phone Number: +44 207 188 7727; Email: euisik.suh@gstt.nhs.uk

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Lane Fox Unit, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust
    • Contact: Gillian Radcliffe; Email: Gillian.Radcliffe@gstt.nhs.uk
    • Contact: Katrina Abernethy, MBBS Mres MRCP
    • Contact: Eui-Sik Suh, MBBS MChem(Oxon) PhD FRCP

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1st Vibrating mesh nebulisation and 2nd jet nebulisation; Participants will receive a single dose of salbutamol whilst on NIV via vibrating mesh nebulisation on their first visit. After a minimum 48-hour washout period, they will receive the same dose of salbutamol via jet nebulisation while on NIV.	Device: Jet nebuliser; Jet nebulisers use the flow of a gas (air or oxygen) to draw medication up through a capillary tube to generate small particles to be inhaled.; Device: Vibrating mesh nebulisation; Vibrating mesh nebulisation (VMN) uses a mesh membrane that oscillates at high frequency (typically 128kHz) to produce a stream of drug-carrying droplets of pre-determined size to be inhaled
Experimental: 1st Jet nebulisation and 2nd vibrating mesh nebulisation; Participants will receive a single dose of salbutamol whilst on NIV via jet nebuliser on their first visit. After a minimum 48-hour washout period, they will receive the same dose of salbutamol via vibrating mesh nebuliser while on NIV.	Device: Jet nebuliser; Jet nebulisers use the flow of a gas (air or oxygen) to draw medication up through a capillary tube to generate small particles to be inhaled.; Device: Vibrating mesh nebulisation; Vibrating mesh nebulisation (VMN) uses a mesh membrane that oscillates at high frequency (typically 128kHz) to produce a stream of drug-carrying droplets of pre-determined size to be inhaled

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in neural respiratory drive	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.	NRD assessed on both visits at baseline and 5, 15, 30 and 60 minutes after nebulisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory System impedence	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	Both visits at baseline, 5 and 60 minutes post nebulisation therapy.
Symptom of Breathlessness (numerical rating scale)	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.	At baseline and at 5, 15, 30 and 60 minutes post nebulisation on both visits
Symptom of Breathlessness (modified Borg Dyspnoea scale)	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.	At baseline and at 5, 15, 30 and 60 minutes post nebulisation on both visits
Transcutaneous CO2 Monitoring	Continuous transcutaneous carbon dioxide levels will be measured	At baseline and for 60 minutes following nebulisation
Spirometry - Forced expiratory volume in 1 second	Spirometry measurements of Forced expiratory volume in 1s second (FEV1)	At baseline and during 1 hour after administration of nebuliser on both visits
Spirometry - Forced vital capacity	Spirometry measurements of Forced vital capacity (FVC)	At baseline and during 1 hour after administration of nebuliser on both visits
Spirometry ratio - FEV1/FVC	Spirometry measurements used to calculate the ratio FEV1/FVC	At baseline and during 1 hour after administration of nebuliser on both visits
Cardiac rate	Assessment of cardiac rate at baseline and following administration of salbutamol via VMN and JN.	At baseline and for 60 minutes following nebulisation
Cardiac rhythm	Assessment of cardiac rate and rhythm at baseline and following administration of salbutamol via VMN and JN.	At baseline and for 60 minutes following nebulisation
Respiratory flow	Assessment of respiratory flow via pneumotrach at baseline and following administration of salbutamol via VMN and JN	At baseline and for 60 minutes following nebulisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial blood gas	Allows assessment of the persistence and severity of the respiratory failure in addition to being a safety check.	At baseline on first visit

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Investigators: Principal Investigator: Eui-Sik Suh, MBBS MChem(Oxon) PhD FRCP, Guy's and St Thomas' NHS Foundation Trust

Publications and helpful links

General Publications

• Brochard L. Non-invasive ventilation for acute exacerbations of COPD: a new standard of care. Thorax. 2000 Oct;55(10):817-8. doi: 10.1136/thorax.55.10.817. No abstract available.
• Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, Church AC, Creagh-Brown B, Dodd JW, Felton T, Foex B, Mansfield L, McDonnell L, Parker R, Patterson CM, Sovani M, Thomas L; BTS Standards of Care Committee Member, British Thoracic Society/Intensive Care Society Acute Hypercapnic Respiratory Failure Guideline Development Group, On behalf of the British Thoracic Society Standards of Care Committee. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016 Apr;71 Suppl 2:ii1-35. doi: 10.1136/thoraxjnl-2015-208209. No abstract available. Erratum In: Thorax. 2017 Jun;72(6):588. doi: 10.1136/thoraxjnl-2015-208209corr1.
• Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet. 2000 Jun 3;355(9219):1931-5. doi: 10.1016/s0140-6736(00)02323-0.

Study record dates

Study Major Dates

• Study Start (Estimated): March 21, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: March 17, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 17, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: vibrating mesh nebuliser; jet nebuliser
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 348845

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
• product manufactured in and exported from the U.S.: No