The Role of HNHF to Improve Clinical Outcomes Following Severe AECOPD

The Role of Humidified Nasal High-flow to Reduce 30-day Hospital Re-admissions Following Severe Exacerbations of Chronic Obstructive Pulmonary Disease: a Mixed Methods Feasibility Study

Chronic Obstructive Pulmonary Disease (COPD) is a common lung disease, affecting 1.2 million people in the United Kingdom (UK). COPD patients suffer with episodes of worsening breathing symptoms called acute exacerbations (AECOPD). Exacerbations occur more often as the disease progresses and are a leading cause of emergency hospitalisation. Patients recovering from exacerbations are at high risk of deteriorating, with one quarter readmitted to hospital within thirty days. COPD thus imposes immense burdens on the National Health Service and patients.

This research will investigate the effects of using humidified nasal high-flow (HNHF) during recovery from severe COPD exacerbations. HNHF delivers warmed, humidified air under flows of up to 60 litres per minute through a nasal interface. This has been shown to improve clinical outcomes, including exacerbation frequency, hospitalisations, breathlessness and quality of life amongst COPD patients with respiratory failure. It is thought to achieve this by improving secretion clearance and providing positive airways pressure which supports the breathing system.

Patients admitted to St Thomas' Hospital, London with COPD exacerbations will be recruited. Prior to discharge, participants will be randomised to receive either usual care alone or usual care plus a HNHF device, which they will be trained to use for a regular period daily. Usual care includes inhalers, steroids and may include antibiotics.

Participants will be followed up for 30-days after hospital discharge using weekly assessments, daily symptom diaries and wrist-worn watch-like devices that detect physical activity. This will enable evaluation of the clinical effects of HNHF on re-exacerbations, readmissions, breathlessness, physical activity and quality of life. Device usage will also be quantified. Participants who receive devices will be interviewed to explore their experiences. After the 30-day home follow-up period, a sub-group of participants will undergo detailed breathing tests during and after exercise to explore the effects of HNHF on the respiratory system.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Device: Humidified nasal high-flow device

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

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Guy's and St Thomas' NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Emergency hospital admission with a primary diagnosis of AECOPD
• Aged 40-80 years
• ≥10 pack year smoking history
• Body mass index ≤ 35kg/m2
• Cognitively and linguistically able to follow English instructions, provide informed consent and complete the study protocol
• To be discharged home following the hospitalisation in a home environment deemed safe by the investigator to perform home assessments
• Patient lives in the catchment area served by the Integrated Respiratory Team at Guy's and St Thomas' NHS Foundation Trust

Exclusion Criteria:

• Chest radiograph excludes pneumothorax
• Requirement for acute non-invasive ventilation (NIV) during index hospitalisation or established on home positive airway pressure (PAP)
• Significant chronic respiratory failure (PaCO2 >7.0)
• Clinically significant obstructive sleep apnoea requiring treatment
• Allergies to latex, metals or local anaesthetic
• Broken or inflamed skin at the second intercostal space parasternal chest wall areas
• Psychological or social factors that would impair compliance with the study protocol
• Any major non-COPD chronic co-morbidity that may contribute significantly to risk of readmission, including (but not limited to) severe heart failure (left ventricular ejection fraction <30%), malignancy (active treatment or palliation), end stage renal failure and significant neuromuscular disease
• Planned travel away from home in the 30-day post-discharge period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; HNHF device (intervention) + usual care	Device: Humidified nasal high-flow device; Humidified nasal high-flow device which delivers warmed, humidified air at flow rates of up to 60 litres per minute via a nasal cannula interface. Intended delivery at 30 L/min at 37 degrees Celsius, if tolerated.
No Intervention: Control; Usual care alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 30-day hospital readmission following index hospitalisation with AECOPD	30-day readmission	30 days following hospital discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment rate of eligible patients	Feasibility outcome measure: assessed by proportion of patients who fulfil eligibility criteria who consent to participate.	30 days following hospital discharge
Adherence with completion of clinical outcome measures (symptom diary)	Feasibility outcome measure: assessed by completion of symptom diaries. Progression criterion = participant diaries completed by >70% of participants. Assessed at 30-days following hospital discharge.	30 days following hospital discharge
Adherence with completion of clinical outcome measures (physical activity monitor)	Feasibility outcome measure: assessed by usage of physical activity monitors. Progression criterion = usage >70% of participants. Measured from physical activity monitor computer downloads at 30-days following hospital discharge.	30 days following hospital discharge
Adherence with completion of clinical outcome measures (spirometry)	Feasibility outcome measure: assessed by completion of spirometry. Progression criterion = spirometry measured at every study assessment for >70% of participants.	30 days following hospital discharge
Participants' HNHF device usage	Feasibility outcome measure: usage hours accessed from the device at completion of participants' study participation for those participants allocated to the intervention arm.	30 days following hospital discharge
Acceptability of HNHF at home: semi-structured interviews	Qualitative evaluation: Use of semi-structured interviews after 30 days post-discharge following index hospitalisation to explore barriers and facilitators to device usage in intervention arm participants.	30 days following hospital discharge
Non-readmission AECOPD	Clinical outcome measure: the number of acute exacerbations of COPD that do not require hospitalisation will be recorded using symptom diaries.	30 days following hospital discharge
Breathlessness	Clinical outcome measure: breathlessness severity will be assessed using the modified Borg scale (minimum score = 0, indicating no breathlessness, maximum score = 10 indicating maximal intensity of breathlessness).	30 days following hospital discharge
Breathlessness	Clinical outcome measure: breathlessness severity will be assessed using the Multidimensional Dyspnoea Profile.	30 days following hospital discharge
Physical activity	Clinical outcome measure: daily physical activity (measured in counts per minute) will be quantified using a wrist-worn physical activity monitor which uses a triaxial accelerometer.	30 days following hospital discharge
Health-related quality of life: COPD Assessment Test	Clinical outcome measure: assessed using the COPD Assessment Test.	30 days following hospital discharge
Health-related quality of life: Clinical COPD Questionnaire	Clinical outcome measure: assessed using the Clinical COPD Questionnaire. Scored from 0 to 60, with higher scores indicative of worse disease-specific health-related quality of life.	30 days following hospital discharge
Inspiratory capacity	Proof of concept study outcome: measured during the physiological sub-study involving incremental exercise using a pneumotachograph.	30 days following hospital discharge
Breathlessness	Proof of concept study outcome: measured during the physiological sub-study involving incremental exercise using the modified Borg scale. This zero to ten scale measures breathlessness intensity, with higher scores representing more intense breathlessness. The score will be measured before exercise, at 2 minute intervals during exercise, at exercise cessation and during exercise recovery.	30 days following hospital discharge
Neural respiratory drive	Proof of concept study outcome: measured during the physiological sub-study involving incremental exercise using a parasternal and diaphragm electromyography using surface and nasogastric electrodes, respectively.	30 days following hospital discharge
Pulmonary pressures and flow	Proof of concept study outcome: measured during the physiological sub-study involving incremental exercise using a pressure transducer connected to a nasogastric catheter and a pneumotachograph.	30 days following hospital discharge
Time to recover from maximal breathlessness	Proof of concept study outcome: time from maximal breathlessness at peak exercise to pre-exercise modified Borg scale.	30 days following hospital discharge

Collaborators and Investigators

• Sponsor: Guy's and St Thomas' NHS Foundation Trust
• Investigators: Principal Investigator: Nicholas Hart, PhD, Guy's and St Thomas' NHS Foundation Trust

Publications and helpful links

General Publications

• Suh ES, Mandal S, Harding R, Ramsay M, Kamalanathan M, Henderson K, O'Kane K, Douiri A, Hopkinson NS, Polkey MI, Rafferty G, Murphy PB, Moxham J, Hart N. Neural respiratory drive predicts clinical deterioration and safe discharge in exacerbations of COPD. Thorax. 2015 Dec;70(12):1123-30. doi: 10.1136/thoraxjnl-2015-207188. Epub 2015 Jul 20.
• Murphy PB, Kumar A, Reilly C, Jolley C, Walterspacher S, Fedele F, Hopkinson NS, Man WD, Polkey MI, Moxham J, Hart N. Neural respiratory drive as a physiological biomarker to monitor change during acute exacerbations of COPD. Thorax. 2011 Jul;66(7):602-8. doi: 10.1136/thx.2010.151332. Epub 2011 May 19.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2019
• Primary Completion (Actual): March 24, 2021
• Study Completion (Actual): March 24, 2021

Study Registration Dates

• First Submitted: March 21, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (Actual): April 2, 2019

Study Record Updates

• Last Update Posted (Actual): April 12, 2021
• Last Update Submitted That Met QC Criteria: April 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Ventilation; Physiology; Neural respiratory drive; Respiratory muscles; High-flow nasal cannula; COPD exacerbation; Nasal high-flow
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 242147

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