NRD to Predict COPD Exacerbations at Home
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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
    

Intervention name(s): Neural respiratory drive measurement
Intervention type(s): Diagnostic Test
Intervention description(s): Neural respiratory drive (NRD) has been validated as an objective physiological biomarker in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Change in NRD during hospital admission has been demonstrated to be a marker of physician-defined clinical deterioration. NRD is a non-invasive measurement that involves skin preparation with a gel and alcohol wipe before placing 3 surface electrodes on the chest wall and collar bone to perform electromyography (EMG) of parasternal muscles. Electrodes are connected to an automated EMG analysis system to derive a measurement of NRD. Measurements take approximately 10 minutes with subject being monitored during normal ("tidal") breathing and performing maximal sniff manoeuvres.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients admitted to hospital with a primary diagnosis of an acute exacerbation of COPD.
      
Keywords: Chronic obstructive pulmonary disease; Acute exacerbation; Neural respiratory drive; Parasternal electromyography; Respiratory physiology; Lung function