Dysfunctional Breathing: Characterisation and Assessment

Dysfunctional breathing (DB) is a respiratory condition characterised by an abnormal breathing pattern, among other complaints, that can occur either in the absence of other pathophysiology (primary DB), e.g. anxiety-related factors, or secondary to cardiopulmonary disease (secondary DB), e.g. asthma. As a consequence, patients may experience breathlessness and present with periods of increased ventilation or erratic breathing, interspersed with episodes of breath holding or deep sighs. In addition to respiratory symptoms, DB also generates non- respiratory symptoms (e.g. dizziness and increased heart rate). It is estimated 1 in 10 people in the United Kingdom (UK) have DB. However, DB remains poorly understood, with no standardised approach to diagnosis and assessment.

The purposes of this study are:

Study 1) To identify physiological, functional and psychological characteristics of participants with DB compared to healthy participants.

Firstly, symptoms, lung function, respiratory gas analysis, exercise capacity, respiratory muscle function, respiratory motion, level of physical activity, quality of life and anxiety \& depression scores will be assessed in 20 participants with primary DB, 20 with secondary DB and compared to 20 healthy participants.

Study 2) To develop an assessment tool based on physiological, functional or psychological variables found to be different between any of the 3 groups in Study 1.

In order to do that, 54 people with DB (between primary and secondary) and 27 people presenting with breathlessness secondary to restrictive lung disease will be assessed. Analysis of these data will determine whether these variables can be used as a diagnostic tool capable of distinguishing DB from restrictive lung diseases characterised by breathlessness.

The recruitment period will be 1-2 years, with an individual participation of 9 days; 1-day on site testing, plus 7-day home activity monitoring, and 1 day to return the activity monitor (which will happen whenever the participant needs to return to the site).

In this research, the aims are: 1) to characterise and compare participants with primary dysfunctional breathing (DB), secondary DB and healthy participants, 2) to develop an assessment and identification tool for the population with DB, 3) to identify subgroups of people with DB based on their functional, physiological and psychological characteristics.

In order to do that, in Study 1, there will be a comparison of many different aspects (described below) between three groups of 20 participants each: primary DB, secondary DB and healthy participants. With the results of these comparisons, it will be possible to know more about the differences people with DB have in relation to the healthy population, and to describe their main characteristics. Based on that, in Study 2, it will be possible to select the variables that are different between groups and replicate those tests in an extra 54 participants DB (primary and secondary) and 27 with breathlessness secondary to restrictive lung disease (DB excluded). The second stage will suggest tests to be used when identifying and evaluating this population, and statistically identify subgroups of people with DB based on their characteristics.

It is important to note why the inclusion of healthy participants and participants with breathlessness secondary to restrictive lung disease is important in this research programme. Firstly, it is essential to know the main characteristics of DB in relation to the healthy population. Secondly, the assessment tool has to be able to suggest probability of negative diagnosis of DB for people who do not have DB, and not only positive diagnosis for those who have.

There are no standardised criteria available to diagnose DB. However, experienced chest physicians at Guy's and St Thomas' Foundation Trust (GSTFT) identify probable DB, and provide a clinical diagnosis (CD) according to the following criteria: patients presenting with symptoms that are not concordant with the severity of the underlying health condition (in case of secondary DB), patients presenting with symptoms that persist despite optimal disease management and/or no objective markers of deterioration/exacerbation (in case of secondary DB), patients presenting with symptoms in the presence of negative tests for organic cause/medically unexplained (in case of primary DB), patients presenting with symptoms that are considered functional (in case of primary DB).

Ability to comprehend and/or perform the procedures of this research, as well as the presence of major orthopaedic, neurological or cardiac conditions will be checked by Leyla Osman and the Chest physicians via medical records and when the possible participant is approached to receive information about the study. For example: health conditions in which patients present with an impairment of mental faculties and/or motor function (inability to cycle with no discomfort).

Healthy participants will be contacted via email list at Brunel University London, and via flyers placed on the University's and Hospital's website and murals (attached). Participants with restrictive lung disease will be reached in person or via telephone call when they are referred to respiratory physiotherapy, or via flyers placed on the Hospital's murals. Because there are not plenty of patients with DB, those who are already registered on the Hospital's system as presenting with DB (assessed by a chest physician) will be called. New patients with DB will be contacted in person or via telephone call by the respiratory physiotherapist of the clinical team (Leyla Osman).

If those contacted about this research are interested in taking part in this study, they will be provided with the participant information sheet, have the opportunity to ask any questions they may have and it will be checked if they meet the inclusion criteria. Before starting the assessments, they will be asked to sign the informed consent.

When signing the informed consent, participants will be asked a few questions:

Please, tick this box if you authorise the researchers of this study to have access to your medical records Please, tick this box if you are aware that your General practitioner will be informed about your participation in this research Please, tick this box if you would like to receive a report with your results of the tests performed in this study (within 30 days from the end of your assessments) Please, tick this box if you would like us to contact you in the future to inform you about the final results of this study Please, tick this box if you are participating in other study/ies at this moment. If yes, please mention below what this/these study/ies is/are about and the contact of the person responsible for it The assessments will be performed by Lais Silva Vidotto (respiratory physiotherapist and researcher) at the Hospital/University over a period of approximately 3 hours. Many of these assessments form part of routine hospital investigations for patients with DB. Duration may vary depending on individual needs and limitations, such as time given to recover from any physical or mental effort. Secondly, a physical activity monitor will be given to all participants, which will be returned to the researchers on the next medical appointment at the Hospital/classes at the University (classes at the University in case of healthy participants). During the 3-hour assessment they will have the opportunity to rest whenever is necessary and snacks and refreshments will be provided in the intervals (caffeine-free ingredients).

Assessments and their approximate duration are as follows: demographic information (10 minutes), health-related quality of life questionnaire (SF-36) (5 minutes), Hospital anxiety and depression scale (HADS) (5 minutes), Nijmegen questionnaire (NQ) (5 minutes), Self-evaluation of breathing questionnaire (SEBQ) (5 minutes), Asthma Questionnaire (only for asthmatics) (5 minutes), lung function test (30 minutes), respiratory muscle function (30 minutes, assessment of the respiratory movements (MARM) (10 minutes), breath-hold test (BHT) (20 minutes), slow-breathing task (15 minutes) and the sub-maximal exercise test (10 minutes) (during the two last tests participants will be wearing small and light-weight devices that monitor heart activity, breathing function and blood pressure and take 15 minutes to be placed all together).

Day 1: Hospital assessments (\~3 hours) The tests will be performed in a private room at St Thomas' Hospital or Brunel University London. Participants will be advised to stay 48 hours without practicing exercise. Also, they will be instructed to take all the medicines they normally use and to report their names and doses to the examiner.

1. Patients will be asked about their medical history, date of birth and symptoms. Also, participants' weight and height will be measured.
2. Chest movements while breathing:

   At this stage, participants are going to stand still while the researcher will place their hands on the back of their chests in order to evaluate its movements while participants are breathing. This is going to take about 10 minutes.
3. Slow-breathing task:

   Participants will be instructed on how to breathe slower (6-10 bpm) for a few minutes (5-15 minutes) and will keep wearing the mask, the heart rate monitor and the arterial blood pressure monitor during this task.
4. Exercise test, breathing and cardiovascular function:

   Light-weight devices will be attached to participants' chest (cardiac monitor), in order to evaluate heart function, to their faces (mask-gas analyser) to assess respiratory function, and to their non-dominant arm (arm and finger), to assess blood pressure. The device used to assess blood pressure continuously measures the pulse of the finger, calibrated by an arm cuff, with no discomfort to the participant. Those assessments will be performed while participants rest for five minutes, while they cycle on a bicycle with moderate resistance for six minutes, and while they rest for five more minutes. Just before the exercise test, at the third minute, and just after it, participants will be asked about any leg or breathing discomfort and how mindful they are in relation to discomfort related to the task. Approximate time of this task: 16 minutes.
5. Questionnaires:

   Participants will be asked to fill in some questionnaires that will ask about their breathing and quality of life and will take about 25 minutes to complete. Participants will be asked to complete these questionnaires after having the opportunity to ask questions about them.
6. Breath hold test:

   Participants will be asked to hold their breath for as long as they can for 3 times, resting for 5 minutes after each one of them, and the researcher will use a stopwatch in order to count the time they are able to do it. The whole task will last in approximately 20 minutes.
7. Lung and respiratory muscle function assessments:

Researchers will use three devices to measure the function of participants' lungs and respiratory muscles. They will be asked to breathe in and out in several different ways, wearing a nose clip, so that researchers can record their general breathing function. This is going to take about one hour to finish.

At the end of the assessment session, participants will be instructed on how to use a device that measures the level of physical activity.

Days 2-8: Physical Activity Monitoring Participants will be asked to wear two small activity monitors attached to their hip for 7 consecutive days, keeping their routine as normal as possible. Participants will have to use the equipment for at least 8 hours/day while they are awake, excluding water activities (e.g. shower) and sleeping, writing down the exact time they put it on and the time they took this off.

Day 9: Return of the activity monitors Participants recruited from Brunel University London will return their physical activity monitors to the researchers on their next visit to the University (for classes, meetings etc.); those recruited from GSTFT will return it on their next hospital appointment.

Although this study requires a cross-sectional design, it may take a long period to be completed, since patients with DB are not easily identified and referred to other health professionals to receive specific diagnosis or treatment. Considering this difficulty in finding participants with DB, justified by the fact that there is no established way of identifying these patients, this research may take 1-2 years to be completed. However, It will enable the researchers to look at every single result and be rigorous with the quality of the data collected. In order to do that, the researchers will not wait for all assessments to be finished to process and plot the data. Every time a participant is evaluated, their results will be organised and plotted within the next few days. It will also enable the data to be statistically analysed when needed.

Eligibility Criteria:
Inclusion Criteria:

* patients with DB (according to the CD)
* healthy people
* aged 18 or over,
* must be able to comprehend and/or perform the procedures of this research
* must be able to consent to participate
* people with signs of breathlessness secondary to restrictive lung disease (DB excluded)

Exclusion Criteria:

* people whose condition is unstable or have experienced an exacerbation of symptoms over the last 4 weeks
* patients who are oxygen-dependant (at rest or during exercise),
* those who are on oral steroids or have completed a course of those medications less than four weeks prior to the assessment day,
* those who have major orthopaedic, neurological or cardiac conditions
* those who received breathing retraining before