COPD (Chronic Obstructive Pulmonary Disease), Non-invasive Ventilation
Conditions
Keywords
vibrating mesh nebuliser, jet nebuliser
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.
Interventions
DEVICEVibrating 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
DEVICEJet 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.
Sponsors
Guy's and St Thomas' NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
VMN and JN are easily distinguishable due to both their visible and audible signatures. It is therefore not feasible to blind the patient to the delivered intervention. The mode of nebulisation will be known to both the investigator and participant, and the absence of masking is acknowledged to be a potential source of bias. Analysis of NRD and spirometry will be masked as an offline analysis.
Intervention model description
Pilot randomised crossover trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Spirometry - Forced vital capacity | At baseline and during 1 hour after administration of nebuliser on both visits | Spirometry measurements of Forced vital capacity (FVC) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Arterial blood gas | At baseline on first visit | Allows assessment of the persistence and severity of the respiratory failure in addition to being a safety check. |
Countries
United Kingdom
Contacts
Primary ContactEui-Sik Suh, MBBS MChem(Oxon) PhD FRCP
Backup ContactGillian Radcliffe
Outcome results
None listed