NRD to Predict COPD Exacerbations at Home
NRD to Predict COPD Exacerbations at Home
COPD is a common, serious disease and is a major burden on patients and the National Health
 Service. Patients with COPD can develop worsening of their symptoms, known as an
 exacerbation, which can be severe enough to warrant hospital admission. There are currently
 no objective measurements available to patients and clinicians to predict exacerbation and
 monitor recovery. Detection of exacerbation by both patients and physicians is known to
 correlate poorly with onset of respiratory deterioration.

 Measurement of neural respiratory drive (NRD), or drive to breathe, using respiratory muscle
 electromyography (EMG) correlates with changes in patients' symptoms and physician defined
 deterioration during hospital admissions.

 This pilot study aims to identify whether daily measurement of NRD at home following
 admission to hospital with exacerbation of COPD can detect an exacerbation within 30 days of
 discharge (20% of patients are readmitted within this period). This technique could enable
 early detection of deterioration at home, facilitating earlier treatment compared to current
 practice, potentially avoiding hospital readmission.

 30 patients admitted to St Thomas' Hospital because of an exacerbation of COPD aged 40-80,
 with a body mass index <35kg/m2, who can follow English instructions and give informed
 consent, who are discharged home will be recruited. If patients consent to participate, they
 will have assessments as inpatients and for 30 days at home following discharge, or until
 hospital readmission, whichever is sooner. Assessments include vital observations (heart
 rate, blood pressure, respiratory rate and oxygen saturations), NRD, and a symptom
 questionnaire. At the baseline assessment, age, height weight, a brief medical history,
 results of tests already taken by the clinical team (blood tests and chest x-ray) and lung
 function tests will be recorded. This study will take 12 months. Philips and its Affiliates
 are providing the NRD measuring equipment.
Introduction

 COPD is a common and serious disease, and is a major burden on patients and the National
 Health Service. Current markers to detect and monitor exacerbations and response to treatment
 are based on symptoms reported by patients, clinical assessment and Early Warning Scores,
 which are a composite measurement of standard observations, including heart rate, blood
 pressure, respiratory rate and oxygen saturations. However these scores have been validated
 on general populations and there is concern regarding their application to COPD patients.
 There is currently no objective biomarker to predict and monitor COPD exacerbations in
 routine clinical use.

 NRD is measured using parasternal intercostal EMG measurements. Daily NRD measurements during
 hospital admission with exacerbation of COPD has been demonstrated to be a reproducible
 non-invasive measurement which is acceptable to patients. Importantly, it can reliably detect
 clinical deterioration and worsening in patient reported breathlessness more reliably than
 current standard assessments.

 This observational pilot feasibility study is designed to identify whether NRD can be
 measured reliably at home following discharge from hospital with exacerbation of COPD, and
 whether it can detect respiratory deterioration within 30 days. This technique thus has the
 potential to allow early detection of deterioration at home, which can facilitate early
 treatment in the community and potentially avoid hospital readmission, which would have a
 profound impact on both patients and the NHS.

 Study objectives

 Primary: The primary objective of the study is to investigate whether home measurement of NRD
 can detect an exacerbation of COPD (symptom based definition) within a 30-day post hospital
 discharge period.

 Secondary

 Clinical:

 -  To validate NRD as an advanced physiological biomarker of clinical respiratory
 deterioration and a re-exacerbation of COPD

 -  To analyse NRD trajectory as it relates to standardly subjective measurements of
 respiratory symptoms e.g. COPD Assessment Test (CAT) and Modified Borg Scale (mBorg), or
 symptoms as assessed by the EXACT-PRO questionnaire

 -  To determine positive and negative predictive value of NRD, and/or a combination of
 clinical features, to detect clinical respiratory deterioration

 -  To assess correlation of change in NRD, physical activity and symptom resolution

 Feasibility:

 -To investigate quality of parasternal EMG measurements performed in the home environment

 Technical:

 -To use the data collected during the study to tune, refine, optimise the automated NRD
 calculation algorithm

 Study end-points Primary end-point: Change in NRD from baseline to day prior to an acute
 exacerbation of COPD.

 Secondary outcomes

 -  Change in NRD from peak exacerbation (hospital) to recovery baseline (home)

 -  Correlation of time to recovery as measured by NRD and EXACT-PRO

 -  Correlation of NRD to EXACT-PRO from hospital discharge to recovery

 -  Correlation of NRD to physical activity from hospital discharge to recovery

 -  Physician-assessed exacerbation within 30-day post-discharge

 -  Self-treated exacerbation within 30-day post-discharge

 -  All cause hospital readmission within 30-day post-discharge

 -  Mortality within 30-day post-discharge

 -  Recovery as defined by the EXACT-PRO within 30-day post-discharge

 -  Medication change within 30-day post-discharge

 -  Unplanned healthcare contacts

 -  Attendance of emergency department (without admission)

 Methods

 30 consecutive patients admitted to St Thomas' Hospital with a primary diagnosis of
 exacerbation of COPD will be enrolled within 16 hours of admission who fulfil inclusion and
 exclusion criteria (listed below). Baseline assessments will include recording of age,
 height, weight, pack year smoking history, exacerbation frequency, pre-admission lung
 function and breathlessness score, co-morbidities, regular medications, chest x-ray, venous
 and arterial blood test results already taken by the medical team, symptom questionnaires
 (CAT, mBorg and EXACT-PRO), vital observations (heart rate, blood pressure, respiratory rate,
 oxygen saturation and use of supplementary oxygen), lung function and NRD. Participants will
 receive inpatient assessments by an investigator to receive an update from the clinical team
 and measure standard observations, NRD and complete the EXACT-PRO questionnaire. On the day
 of discharge, participants' updated medical history and blood tests will be documented and
 vital observations, symptom questionnaires (CAT, mBorg and EXACT-PRO), lung function and NRD
 will be measured. Participants will be issued with a physical activity monitor which will be
 worn for the remaining duration of the study. Participants will then receive home visits from
 an investigator, who are experienced in the management of COPD, to measure NRD, complete the
 EXACT-PRO symptom questionnaire and review participants' daily symptom diary. Lung function
 and the CAT symptom questionnaire will be performed weekly at home. Participants will be
 followed up for 30 days following hospital discharge or until they are readmitted to
 hospital, whichever is sooner.

 Study design: Observational cohort design

 Inclusion criteria

 -  Age 40-80 years

 -  Patients hospitalised with a primary diagnosis of an acute exacerbation of COPD

 -  Body mass index (BMI) ≤ 35 kg/m2

 -  Cognitively and linguistically able to follow instructions given in English and provide
 informed consent

 -  To be discharged to home following the hospitalisation

 -  Patient lives in the catchment area served by the Integrated Respiratory Team at Guy's
 and St Thomas' NHS Foundation Trust in a home environment deemed safe by the
 investigators to perform home assessments

 Exclusion criteria

 -  Previous home PAP (CPAP or NIV) therapy use within the past year, or post-discharge

 -  Allergies to latex, metals or local anaesthetic agents

 -  Wound or inflamed skin at parasternal location (2nd intercostal space)

 -  History of skin allergies or sensitivity to cosmetics and lotions

 -  Psychological and social factors that would impair compliance with study protocol and
 schedule

 -  Any major non-COPD chronic disease or condition, such as severe heart failure
 (LVEF<30%), malignancy (active treatment and palliation), end stage renal
 failure/dialysis, significant neuromuscular disease (eg. NMD, MD) determined by review
 of medical history and / or patient reported medical history that may contribute
 significantly to risk of readmission, as determined by PI

 -  Length of stay < 6 hours

 -  Planned travel away from home within the 30 day post discharge period

 Consent:

 Patient will be provided with a patient information sheet and have a minimum of one hour to
 consider trial participation. A longer period for consideration of trial participation can be
 provided if required by the patient, however baseline assessments must be made within 16
 hours of hospital admission.

 Risk and benefit:

 Sticker placement for the EMG electrodes may require participants to shave their chest. The
 adhesive stickers and the skin preparation gel may cause minor skin irritation. Participants
 are required to perform sniff manoeuvres as part of NRD measurement which may feel
 uncomfortable. Participants will be advised to breath normally should they feel light headed
 or breathless.

 There will be no direct benefit to individual participants. However the study aims to develop
 a technique that can be used to predict and prevent hospital readmission following admission
 with exacerbation of COPD, which will have benefits for the wider community of patients and
 the NHS.

 Confidentiality:

 Participants' name, date of birth and other identifiable information will be collected during
 the study phase. All stored data will be in line with the Caldicott principals, data
 protection and REC guidelines.

 Conflicts of interest:

 There are no perceived conflicts of interest. Participants' supervising consultants will
 remain responsible for clinical care and will not be involved in the collection or
 interpretation of the research data, which will be performed by a dedicated research team.

 Tissue and biological samples:

 No tissue or biological samples will be obtained for the study protocol outside of routine
 care.

 Protocol amendments:

 In September 2018, the following amendments were made to the protocol which were approved by
 the London-Westminster Research Ethics Committee:

 -  Addition of the Modified Borg Score to daily assessments to measure subjective
 breathlessness intensity

 -  Inclusion criterion six was amended so that participants must live in the catchment area
 served by the Integrated Respiratory Team (not the "Lane Fox Respiratory Unit") at Guy's
 and St Thomas' NHS Foundation Trust for clinical, safety and practical purposes.

 -  Collection of hospital admission, healthcare utilisation and mortality data following
 study participation from electronic medical records
Inclusion Criteria:

 -  Age 40-80 years

 -  Patients hospitalized with a primary diagnosis of an acute exacerbation of COPD

 -  Body mass index (BMI) ≤ 35 kg/m2

 -  Cognitively and linguistically able to follow instructions given in English and
 provide informed consent

 -  To be discharged to home following the hospitalization

 -  Patient lives in the catchment area served by the Integrated Respiratory Team at Guy's
 and St Thomas' NHS Foundation Trust in a home environment deemed safe by the
 investigators to perform home assessments

 Exclusion Criteria:

 -  Previous home PAP (CPAP or NIV) therapy use within the past year, or post-discharge

 -  Allergies to latex, metals or local anaesthetic agents

 -  Wound or inflamed skin at parasternal location (2nd intercostal space)

 -  History of skin allergies or sensitivity to cosmetics and lotions

 -  Psychological and social factors that would impair compliance with study protocol and
 schedule

 -  Any major non-COPD chronic disease or condition, such as severe heart failure
 (LVEF<30%), malignancy (active treatment and palliation), end stage renal
 failure/dialysis, significant neuromuscular disease (e.g. NMD, MD) determined by
 review of medical history and / or patient reported medical history that may
 contribute significantly to risk of readmission, as determined by PI

 -  Length of stay ≤ 24 hours

 -  Planned travel away from home within the 30 day post discharge period