COPD monitoring

Chronic Obstructive Pulmonary Disease (COPD) is a common, preventable disease
that is characterized by persistent respiratory symptoms and airflow limitation
that is due to airway and/or alveolar abnormalities, usually caused by
significant exposure to noxious particles or gases and influenced by host
factors, including abnormal lung development (GOLD 2020 guidelines). COPD is a
disabling respiratory illness that afflicts *10% of individuals over 40 years
of age (O*Donnel et al., 2016), causing chronic morbidity and mortality
throughout the world (Krahnke et al., 2015). The main causes of COPD are
smoking, respiratory infections, air pollution, dust, and chemicals in poorly
ventilated areas. According to the latest World Health Organization (WHO)
estimates (https://www.who.int/respiratory/copd/en/, 2004), currently 64
million people have COPD, and 3 million people die yearly of COPD. WHO predicts
that COPD will become the third leading cause of death worldwide by 2030.
The disease is characterized by gradual deterioration in lung function with
multiple distressing symptoms like dyspnea and fatigue (Park et al., 2013).
Dyspnea is referred to as the sensation of breathlessness, shortness of breath,
or difficulty of breathing and it is often associated with limited physical
activity, increased anxiety and depression, decreased health-related quality of
life (HRQoL), and reduced survival (Anzueto et al., 2017). Scales and
questionnaires are used in the current clinical practice to evaluate this
symptom, that was defined as the *subjective experience of breathing discomfort
that consists of qualitatively distinct sensations that vary in
intensity* (Parshall et al., 2012). Dyspnea assessment, indeed, is achieved by
questioning the patient about the onset, frequency and duration of the symptoms
and its impact on daily activities. According to data from the Clinical
Practice Research Datalink, 82% of patients with COPD had dyspnea of any grade,
as assessed by the Medical Research Council (MRC) breathlessness scale (1-5),
of whom 46% had moderate-to-severe dyspnea (MRC >=3). Moderate-to-severe dyspnea
was also observed in 32% of patients with mild airflow obstruction, indicating
that dyspnea is not limited to patients with more severe COPD (Mullerova et al.
2014). The Borg CR10 Scale, takes into account the patient*s perception. The
scale starts with *Nothing at all" and ends with *Extremely strong* (Borg et
al., 1982).
In COPD patients, dyspnea during exercise reflects an imbalance between the
increased demand to breathe and the ability to meet that demand (Barros de Sà
et al., 2017). A strong correlation between the intensity of dyspnea (measured
through the modified 10-point Borg scale) and the (relative) amplitude of the
surface electromyography (EMG) of the respiratory muscles during exercise
testing was found (Barros de Sà et al., 2017). To our knowledge, the
correlation between dyspnea (BORG) scale and EMG has not been assessed during
exercises that resemble daily activities more closely, such as a constant work
rate test (CWRT), walking on a treadmill and/or cycling.
Another factor that has a major impact on COPD patients is the acute
exacerbations (AECOPD), defined as an acute worsening of the respiratory
symptoms (dyspnea, coughing and sputum) that results in additional therapy
(Wilkinson et al., 2004; GOLD2020) and that typically lasts for several days.
Because exacerbations strongly affect quality of life, disease progression and
health care costs (Guarascio et al., 2013), it is important to enable early
detection and prompt treatment, thereby reducing the risk of hospitalization,
and improving quality-of-life. Exacerbations represent a high economic and
social burden on the health care system (McGuire et al., 2001).
To identify the risk of early readmission among patients hospitalized due to an
exacerbation of COPD and detect inpatient clinical deterioration, parasternal
EMG can be helpful (Suh et al., 2015). Parasternal EMG has been shown to be a
physiological biomarker of worsening dyspnea (Suh et al., 2015).
Patient-reported dyspnea associated with activities of daily living has also
shown to be an important factor for predicting hospitalizations due to AECOPD
(Abascal et al, 2015). Several studies have assessed the value of
telemonitoring of symptoms and/or physiological parameters, of COPD patients.
Some studies suggest that telemonitoring enables early detection of COPD
exacerbations, but this has not been confirmed in large clinical trials (Sink
2018, Fernandez-Granero, 2014, Li 2020). Among the physiological parameters,
breathing rate (at rest), as well as transcutaneous oxygen saturation (SpO2)
and heart rate (both during effort situations), show promise in predicting
exacerbations (Rubio 2017; Galvez-Barron 2019; Buekers 2018).

The purposes of this feasibility study are:
• to evaluate the correlation between COPD-related dyspnea and the EMG of
respiratory muscles when simulating daily activities, to assess the dyspnea
symptom in a more objective (measurable) way;
• to characterize changes in EMG, respiration rate and SpO2 while simulating
daily activities, associated with exacerbations of COPD.
• to characterize SpO2 and respiration rate when simulating daily activities;
The above-mentioned points serve together the aim of detecting exacerbations
earlier and to provide better treatment, to improve patients* quality of life.

this is a prospective, non-randomized, single-arm, feasibility study.
Up to 31 subjects with a clinical diagnosis of COPD and referred for
rehabilitation at the rehabilitation center for respiratory pathologies (CIRO,
The Netherlands) will be enrolled. The point of enrollment is the time when
subjects sign and date the Informed Consent Form (ICF), once verified all the
Inclusion/Exclusion (I/E) criteria. At that point, the subject is considered
included in the study.
The I/E criteria of the subjects will be reviewed during a standard of care
Pre-rehabilitation visit (not part of the study visits) performed by the
attending physician. At the Pre-rehabilitation visit, the attending physician
will ask eligible subjects if they are interested in participating in a
clinical study and -if so- ask their permission to be put in contact with the
Principal Investigator (PI) or his designee.


If they agree, the PI or his designee will deeply discuss the present study
with the subjects and provide them the Subject Information Letter and Informed
Consent at the end of the Pre-rehabilitation visit. Once the rehabilitation at
the rehabilitation center has been planned by the attending physician and not
earlier than 7 days after the pre-rehabilitation visit, the Investigator or his
designee will contact the subject by phone to answer any further question the
subject might have on the study. The admission visit will be scheduled after
this phone call, to have ample time to reflect and decide whether or not to
participate in the present study. At the admission visit, the
Inclusion/Exclusion (I/E) criteria will be checked by the PI or his designee
who will enroll eligible subjects by having them sign the Informed Consent Form
(ICF). During the Admission visit, the PI or his designee will also
retrospectively collect data, which have been previously recorded at the Pre-
rehabilitation visit, as part of the site standard of care. At time of the
Admission visit, once the informed consent process is completed, clinical data
assessed at time of standard of care Pre-rehabilitation visit will be collected
retrospectively for enrolled subjects. The Admission visit will take place at
the beginning of the rehabilitation program, then 8 Follow-up visits (once per
week) will be planned during their rehabilitation program.
Additional Exacerbation-triggered visit(s) may be performed during acute
exacerbations, diagnosed by a physician in accordance with the GOLD guidelines,
occurring while subjects are at the rehabilitation center.
Finally, before Study Exit, a Pre-discharge visit will be scheduled at the end
of subject*s rehabilitation program (refer to section 9 for additional details
on the procedures).
Physiological parameters will be collected during the Admission, Follow-Up and
Exacerbation-triggered visits and Pre-Discharge visit.
Data analyses are expected to be completed for internal review approximately 6
months after the last subject*s Pre-discharge visit will occur.

Please see study design above.

The participants will perform an exercise (cycle) test during the admission
visit, during which various physiological parameters (such as EMG; complete
list provided in the CIP) will be measured.
During 8 follow-up visits, possible exacerbation-triggered visits and 1
pre-discharge visit, physiological parameters (EMG, oxygen saturation and
respiration rate) will be measured while the subjects perform their regular
exercises / tests.
Wearable, non-invasive devices will be used for the measurement and data
collection. Wearing the measurement devices, i.e. the electrodes (for the EMG
of the respiratory muscles) and the chest strap (for the respiration rate)
during the study visits may cause mild skin irritation.
Subjects will be also provided with a paper diary, which they will be asked to
complete daily before going to sleep, during their stay at Ciro (from the day
of the admission until the day before the study exit).
The potential risks associated with the study were identified, assessed,
evaluated and effectively controlled. Medtronic has reduced the residual risk
to as low as possible prior to starting the clinical study. Any potential risks
associated with this study are further minimized by selecting a qualified
investigator. Moreover, the investigator and respective study site personnel
will be trained on Clinical Investigation Plan. Therefore, it was concluded
that the overall benefits outweigh the risks.