Joanna Grogono

  • Joanna GrogonoJoanna Grogono joined Oxford Brookes in 2015 as a research student in the Department of Biological and Medical Sciences. Her thesis title is 'Mechanisms of dyspnoea in advanced heart failure'.

    How did you hear about Oxford Brookes University?

    I was a cardiology registrar at John Radcliffe (JR) Hospital and was keen to do clinical research to expand my skill set.  My training programme director informed me of a study that he had been made aware of via one of the cardiology consultants at the JR.  I discussed the study further with Dr Shakeeb Moosavi at Oxford Brookes who had been awarded funding from the British Heart Foundation to investigate the effect of inhaled furosemide in patients with heart failure. This sounded ideal.

    What attracted you to Oxford Brookes University to conduct your research?

    The topic of the research and the fact it had already been awarded funding was the main attraction to study at Brookes,as it is one of the areas I am hoping to specialise in.  I was also impressed by my supervisor and the dynamic cardiorespiratory group.

    What were you doing before?

    I was a cardiology registrar at the John Radcliffe Hospital. I had completed 3 years of cardiology training and applied for an ‘out of programme experience’ for research for 3 years.  I will return to complete my final two years of cardiology registrar training at the John Radcliffe Hospital after completing my research.  

    How easy did you find it to settle into the research environment?

    It initially took a little while to get set up with a computer and desk space but I was able to go to the library within the John Henry Brookes building and work there.  I had a large computer, plenty of desk space and the surroundings were quiet, so I was able to do plenty of background reading around the topic.  I also attended all of the induction sessions during this time.  There was plenty of support and resources available and I was clearly signposted to where to go to get further help/information.

    Tell us about your research project.

    Aims of the investigation:
    •To investigate the effect of inhaled furosemide on experimentally induced breathlessness in healthy volunteers and to determine which specific form of breathlessness (dyspnoea) it relieves (Year 1).  
    •To assess inhaled furosemide on exercise capacity via cardiopulmonary exercise testing or 6 minute walk test (Year 1)
    •To analyse blood biomarkers for heart failure (BNP, NT-proBNP, Troponin) pre and post exercise and to measure the amount of inhaled furosemide that is absorbed into the blood stream.  (Year 1)
    •To characterise key features of the breathlessness relief response to inhaled furosemide in advanced heart failure patients (Clinical trial - Year 2 and 3)

    Background
    The prevalence of chronic heart failure (weak heart pump) is increasing in the UK; over 50% of heart failure patients in the community experience daily breathlessness or tiredness which affects their quality of life by restricting activities. Breathlessness accounts for ≈50% of the symptom burden among hospitalised patients and uncontrolled breathlessness is frightening, degrades quality of life and undermines the will to live. 

    Different forms of breathlessness
    Breathlessness is generally accepted to arise when the brain perceives information reporting when the demand for breathing does not match the signals reporting the amount of breathing – a mismatch.  Analysis of unpleasant sensations evoked by different respiratory stimuli in normal subjects or by different clinical conditions in patients have identified specific distinguishable sensations: 
    Air Hunger (AH) refers to an uncomfortable urge to breathe. Prolonged breath-holds culminate in intense AH.  Increasing the amount of carbon dioxide inhaled with a fixed rate of breathing generates this sensation.
    Work or Effort (WE) refers to an uncomfortable sensation that arises when breathing requires excessive respiratory muscle activity, similar to breathing through a small straw.  This increases the work required to take a breath in.  Patients with weak breathing muscles and interstitial lung disease all report WE.
    Chest Tightness is reported by asthmatics or in subjects who breathe in a substance that results in airway narrowing.

    Inhaled furosemide as a novel treatment for breathlessness
    Furosemide acts in the kidneys to increase urine production. It is used extensively in a tablet and injectable form to relieve breathlessness due to fluid on the lungs and ankle swelling in heart failure.  By relieving excess fluid from the body via increased urine production, the pump function of the heart improves as the filling pressures within the heart are reduced9. In over 1/3 of patients with advance heart failure resistance develops requiring increasing doses of furosemide to provide adequate relief of fluid overload and this can result in kidney failure.  Inhaled furosemide may offer a valuable addition to current heart failure treatment by alleviating breathlessness without significantly raising circulating blood levels of furosemide.  It has also recently emerged as a novel intervention for breathlessness in patients with asthma, Chronic Obstructive Pulmonary Disease (COPD) and cancer with the advantage of not suppressing breathing, eliciting sedation or having extensive side effects.  No study has yet assessed the effect of inhaled furosemide on relief of breathlessness in patients with heart failure, a patient group who are more likely to benefit from inhaled furosemide than any other breathless patients.

    The proposed plan of work
    Year 1:
    Study 1 is performed on healthy volunteers and aims to determine which specific form of breathlessness is relieved by inhaled furosemide. Days 1 and 2 are practice sessions to familiarise participants with the equipment and to ensure participants can identify the different types of breathlessness. Days 3 and 4 include inhalation of a mist, either furosemide or a ‘dummy’ mist of salty water.  The volunteers and the investigator will not know which mist is being inhaled. Before and after the mist inhalation they will perform breathlessness tests to replicate air hunger or work/effort.  This involves two 4 minute periods using a mouthpiece, similar to a snorkel, attached to a breathing circuit of plastic tubing where the level of inspired carbon dioxide can be altered (air hunger) or resistance can be added to the circuit (work/effort).  The degree of breathlessness will be recorded on a visual analogue scale (VAS). This is a 100ml scale with no breathlessness at one end (0mm) and intolerable breathlessness at the other end (10mm). Participants will regularly indicate on the scale the amount of breathlessness they are experiencing.  Also the different sensations of breathlessness will be recorded. Attached is a flow diagram with a brief description in the legend.
    •Sample size n= 20
    Study 2 sets out to determine the feasibility of inhaling furosemide, performing breathlessness tests and exercise test in patients with chronic heart failure and to assess the amount of furosemide that is absorbed into the systemic circulation. This will lead onto a clinical trial. Each patient will attend on 4 occasions and undergo breathing tests of air hunger (as described in study 1) and exercise tests pre and post inhalation of a mist using slow, deep breaths or fast, shallow breaths.  The exercise test will be either the distance the patient walks voluntarily in 6 minutes or cardiopulmonary exercise testing which will be performed on a static bike attached to equipment that enables the peak workload, peak breathlessness, peak oxygen and carbon dioxide levels to be determined. The patient and the investigators will not know whether the mist is furosemide or a ‘dummy’ mist of salty water, in this way they act as their own controls. Blood tests will also be performed looking at established cardiac biomarkers (BNP, NT-proBNP and troponin) to assess their response to inhaled furosemide and exercise.  Blood tests will also be performed to assess how much furosemide is absorbed directly into the blood stream from an inhaled dose.
    •Sample size n = 12
    •Recruitment: Patients from the John Radcliffe Cardiology Clinic identified by the consultant and via the community heart failure nurses.
    •This study is a feasibility study as the primary measures of breathlessness have not been previously used in this patient group. A sample size of 12 patients reflects a conservative estimate of the likely number of suitable advanced heart failure patients that can be expected from the two sources of prospective recruitment over a 1 year period. The data generated will enable power calculations to be made for the follow up clinical trial in Years 2 and 3. Descriptive statistics will be presented for (i) Air hunger (AH) sensitivity during experimentally induced AH (ii) the distance the patient walks voluntarily in 6 minutes or in the case of cardiopulmonary exercise testing, the peak workload, peak breathlessness, peak oxygen and carbon dioxide levels in relation to the mist inhaled (furosemide or saline) and the breathing pattern used (slow, deep breaths or fast and shallow breaths). 

    Year 2 and 3
    A study of 40 patients with a diagnosis of heart failure to assess the effect of breathing in furosemide as a mist to see how it affects their breathing and ability to exercise, similar to study 2.
    •Sample size n = 40
    •The primary outcome measure will be the visual analogue scale (VAS) ratings of breathlessness.  A power calculation was performed to achieve 80% power testing at the 5% significance level stated a sample size of 34 would be required to find a mean difference of 20ml on the visual analogue scale (0 to 10mm scale). 20mm VAS is universally accepted as clinically meaningful.  Allowing for drop-outs we aim to recruit 40 patients.  This sample size determination is based on a 2x2 crossover design, and a standard deviation of 20mm VAS (derived from a the median difference in VAS in 10 patients with advanced heart failure reported in a previous pilot study of breathlessness relief by oral morphine).  

    Novel Contribution

    If successful, this will be the first documentation of the:
    •effect of inhaled furosemide on breathlessness relief and exercise capacity in patients with heart failure
    •specific component of breathlessness that is relieved by inhaled furosemide
    •amount of furosemide absorbed into the systemic circulation from inhalation
    •effect of inhaled furosemide on established cardiac biomarkers

    What do you enjoy about being a research student?

    I enjoy the atmosphere at Oxford Brookes University. There are opportunities to get involved with the running of the university, for example attending committee meetings. There are also excellent courses available to attend relevant to research.  There are also plenty of opportunities to showcase your work, such as on-line conferences, poster presentations and the postgraduate symposium.  

    What do you think about the research training offered at Oxford Brookes?

    Oxford Brookes University offers excellent training opportunities under Professor Susan Brooks. There is plenty of support within and outside your own department for advice.

    What are your future plans?

    After 3 years, I hope to be awarded a PhD.  I will return to my cardiology registrar post at the John Radcliffe Hospital to complete my training. I am planning to sub-specialise in heart failure and devices (e.g. Pacemakers).  I will then apply for a fellowship, followed by a consultant post.  Once established as a consultant I hope to set up a research facility to continue to conduct research in the field of heart failure.