Breathlessness Patterns in Patients With Cancer, COPD and Heart Failure: an fMRI Feasibility Study

Dyspnea that persists despite optimal pathophysiologic treatment is defined as persistent dyspnea.

Breathlessness, also defined as dyspnea, is a frequent symptom in patients with advanced and progressive diseases such as cancer, chronic obstructive pulmonary disease (COPD) and advanced heart failure (HF). In affected patients, breathlessness causes substantial suffering and is a major contributor to decreased quality of life.

Despite increasingly controversial data on the effectiveness of opioids in advanced disease, they are often prescribed according to expert opinion. It can be hypothesized that breathlessness is conveyed by a variety of different pathophysiologies resulting in various patterns of the central nervous system (CNS) signalling, requiring more than a one-size-fits-all answer to pharmacologic interventions (i.e. opioids).

In recent years, the healthcare industry has seen the development of immersive virtual reality therapies (IVR), also called "digital therapeutics". Immersive virtual reality is an interactive computer simulation that allows a person to be completely immersed within a three-dimensional virtual environment so that it has a real feeling of being in the virtual world. IVR has been used during magnetic resonance imaging (MRI), to reduce stress and anxiety perceived by patients who suffer from claustrophobia.

Functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. Studies conducted to evaluate breathlessness have done so using healthy volunteers, focusing on acute breathlessness or in the context of pulmonary rehabilitation. Little is known about persistent breathlessness patterns and their modulation by different triggers.

Aim of the study:

It is possible that breathlessness is experienced and centrally processed in different ways between different patients, related to: i) the underlying disease, ii) the triggers for breathlessness episodes, iii) differences in patient-reported multidimensional assessment items (i.e. perceived severity vs discomfort vs effort). This study aims to assess whether different patterns of breathlessness can be identified by fMRI technology.

Hypothesis:

The investigators hypothesize that it is possible for patients suffering from persistent breathlessness associated with COPD, heart failure and incurable and life-limiting cancer to undergo an fMRI and associated study interventions.

Primary objective:

To determine the feasibility and acceptability of an observational monocentric study using fMRI and IVR in breathlessness patients with COPD, heart failure and cancer.

Secondary objective:

To identify different breathlessness fMRI signals in different diseases (COPD, heart failure, cancer) and identify different types of breathlessness patterns using fMRI, IVR, and clinical parameters (including patient-reported-outcome measures (PROMs)).

Project design The investigators plan to conduct an observational study that involves the use of an fMRI and IVR. A feasibility study design was chosen because the included patients need particular consideration and the feasibility of the procedure (fMRI) needs to be evaluated.

Total number of participants: four patients with HF, four patients with COPD, four patients with cancer, four healthy volunteers.

Participants will be recruited at the outpatient palliative care clinic of the HUG (single center) on the basis of a screening of medical records of patients and the preverification of the inclusion and exclusion criteria mentioned above.

The healthy controls will be recruited from a convenience sampling of known healthy volunteers meeting the above criteria, from a similar age group, under no hierarchical influence from any member of the research team.

Inclusion criteria

• Age ≥ 18 years and
• Followed by the outpatient palliative care clinic of the Geneva University Hospitals, Switzerland (HUG) and
• Breathlessness at rest > 2 and < 8 on the NRS (numeric rating scale 0 to 10) and
• Persistent breathlessness (persistent dyspnea for > 3 weeks despite adequate and maximal medication according to the pathology) and
• In a stable clinical condition, i.e., without an episode of acute cardiac, respiratory, and/or neurological failure leading to hospitalization in the previous 4 weeks and
• Diagnosis of either HF stage NYHA III-IV, or COPD with dyspnea on the modified MRC scale grade 3-4, or oncological disease with primary or secondary pulmonary involvement

Inclusion criteria

for Healthy Volunteers (Control Group)

• Age ≥ 18 years and
• No respiratory symptoms: dyspnea, cough, wheezing and
• No known pulmonary, cardiac, or oncological disease and
• Smoking status < 10 pack-years and
• No contraindication to fMRI (Appendix 3) and
• Ability to lie flat (supine position) and
• No diagnosed psychiatric illness (severe depression, severe anxiety, psychosis, other) or antipsychotic treatment deemed a contraindication for fMRI based on physician judgement and
• No neurological disorders according to neurological assessment, including diagnosed dementia (frontotemporal dementia, Alzheimer's disease, etc.), brain pathology (tumor, stroke, Parkinson's disease, etc.), or epilepsy and
• No claustrophobia, acrophobia, photophobia, severe hearing loss, and/or severe visual deficit and
• No contraindication to IVR (migraines, photosensitive epilepsy, vertigo)

Exclusion criteria

• Breathlessness at rest ≥ 8 on the NRS (numeric rating scale 0 to 10)
• Contraindication to fMRI
• Inability to lie flat (supine position)
• Diagnosed psychiatric illness (severe depression, severe anxiety, psychosis, other) or antipsychotic treatment deemed a contraindication for fMRI based on physician judgement
• Neurological disorders according to neurological assessment, including diagnosed dementia (frontotemporal dementia, Alzheimer's disease, etc.), brain pathology (tumor, stroke, Parkinson's disease, etc.), or epilepsy
• Presence of claustrophobia, acrophobia, photophobia, severe hearing loss, and/or severe visual deficit
• Contraindication to IVR (migraines, photosensitive epilepsy, vertigo)