Issue 137 Cystic fibrosis an update in research

RESEARCH UPDATE

CYSTIC FIBROSIS: AN UPDATE IN RESEARCH AND RECOMMENDATIONS Jacqui Lowdon Paediatric Dietitian, Leeds Children’s Hospital Jacqui is a Clinical Specialist in paediatric cystic fibrosis at Leeds Children's Hospital. She previously specialised in gastroenterology and cystic fibrosis.

Although her career to date has focused on the acute sector, Jacqui has a great interest in paediatric public health.

REFERENCES Please visit the Subscriber zone at NHDmag.com

Recent research into cystic fibrosis (CF) has brought about recommendations to improve patient outcome measures. At the European Cystic Fibrosis Society Conference held in Belgrade in June this year, further key research studies were presented. Here, Jacqui reports on the hot CF topics.

Respiratory symptoms are the main feature and focus of treatment in cystic fibrosis (CF), however, gastrointestinal (GI) issues, such as constipation and distal intestinal obstruction syndrome (DIOS), are well-recognised complications. They remain two very distinct conditions, although symptoms can be very similar, such as bloating and abdominal pain.

Constipation is when there is a gradual faecal impaction of the colon, whereas DIOS occurs when there is a build-up of faeces and sticky mucus. This forms a mass in the final part of the small intestine (the terminal ileum and caecum), which can either partially block the intestine (incomplete DIOS), or completely block the intestine (complete DIOS). This then becomes connected to the bowel wall and the intestinal villi fix it into position, making it difficult to remove.1 This is potentially a serious symptom, which can affect quality of life and other aspects of care, such as nutritional status, exercise and airway clearance. Clinical practice of treatment of DIOS is inconsistent and there is a lack of consensus.

For these reasons, the Cochrane database of systematic reviews recently evaluated the effectiveness and safety of laxative agents of differing types for preventing DIOS (complete and incomplete) in children and adults with CF.2 Unfortunately, there was only one low-quality, cross-over trial eligible for inclusion, highlighting the need for more research in this area. As the pathophysiology of DIOS is multifactorial, it is highly likely that there will be more than one successful prevention strategy.

GI research is an important research priority in CF as highlighted in the 2017 James Lind Alliance Priority Setting Partnership in CF, a partnership between people with CF and healthcare providers.3 They reached a consensus, listing 10 of the most important research priorities in CF, the second one being, ‘How can we relieve gastrointestinal (GI) symptoms, such as stomach pain, bloating and nausea in people with CF?’ This research priority also emphasised the lack of patient-reported outcome measures (PROMs) for GI problems in CF. PROMs cover areas of particular concern to the patient. It has been recommended that to significantly improve any future research, an agreed consensus on validated GI outcome measures for symptoms should be included. Reliable evidence exists to support the use of PROMs in healthcare. A 2013 systematic review already demonstrated that effective PROMs improve patient-provider communication, patient satisfaction, monitoring of treatment responses and detection of unrecognised problems.4 THE EUROPEAN CF CONFERENCE NEW RESEARCH

Outcome measures The role of PROMs was highlighted at the recent European CF Society Conference.

A group from Nottingham University presented an analysis of outcome measures suggested by a community of patients with CF. They were seeking stakeholder suggestions about how to measure the outcomes in their proposed

www.NHDmag.com August/September 2018 - Issue 137

19

RESEARCH UPDATE Table 1: Nottingham University research - suggested outcome measures Theme

Popular professional outcome measures

Popular lay outcome measures

Diet

Weight, vitamin D levels, BMI, energy levels

Weight, overall wellbeing, nutritional status

Digestive system

Weight, GI symptoms, lung function (LF)

Weight, liver function

Mental health

Anxiety measures, mental health questionnaire

Happiness scale

Treatment burden

Adherence, measurable device, LF

LF, quality of life

Antibiotics

LF, quality of life

LF, frequency of intravenous antibiotics

Genetics

Quality of life, exacerbations

Quality of life

Infection

Culture, LF

Number of infections, LF

Physiotherapy

LF, exacerbations

LF, exacerbations

Respiratory

LF, exacerbations

Number of infections, LF

Table 2: The Clinical Trial Working Group’s questionnaire assessment Group

Suggestions for questionnaire

Adults (N=13)

Focus more on sense of self-identity, future aspirations and fears regarding relationships.

Young people (N=32, 14-20 years)

Questions on amount of time spent on treatments, how peers and family perceive them, potential difficulties with treatment adherence, attitudes towards sport, perceived limits imposed by CF.

Children (N=16, 6-19 years)

This group had problems understanding the questions.

Parents (N=15, of children 6-13 years)

More questions on life organisation, treatment burden, how to help their children cope with the day-to-day challenges of CF, social support from family and friends, future concerns, parental depression and anxiety.

CF research; 513 responded with 787 outcome measures suggested. There were a number of popular suggestions in different categories (see Table 1). It was highlighted that the outcomes suggested from the CF community tended to be more holistic and focused on treatment burden and quality of life, whereas professional responses were more focused on numbers and lung function.

This type of information would be invaluable when developing dietetic outcome measures and could be rolled out to other groups of patients.

Data for PROMs can often be collected by selfadministered questionnaires. The most widely used tool in clinical trials for patients with CF is the Cystic Fibrosis Questionnaire-Revised (CFQ-R). It includes quality of life measures, allowing the patients’ perspective on the pros and cons of a particular treatment. The Clinical Trial Working Group on patient reported outcomes presented their study at the European CF Society Conference, evaluating the CFQ. Their aim was to assess if the tool is relevant and sensitive enough to reflect patients’ daily experiences of living with

CF and the effectiveness of new treatments. The results are summarised in Table 2.

Dietetic outcome measures tool Clinical outcome measures are also being widely developed and the UK CF Dietitians Group (led

by L Cave, Paediatric CF Dietitian, Leeds, UK) presented their final version and evaluation of a dietetic outcome measures (DOMs) tool for adult and paediatric cystic fibrosis patients at the Conference. A working group was set up to develop a core set of outcome measures for routine use, to enable evaluation of the effectiveness of dietetic interventions. It also included identification of common barriers and facilitators, to inform evidence-based practice and enhance patient-centred care. The tool was trialled by 21 UK CF centres with 268 patients. Findings included that, time and practice were needed to become familiar with the tool, but it was easy and quick to use; it was comprehensive and prompted the user to focus on setting SMAART goals (specific, measurable, achievable, appropriate, www.NHDmag.com August/September 2018 - Issue 137

21

RESEARCH UPDATE reliable, timed); it also managed to capture what was important to patients and their families and it assisted identification of gaps in resources.

Body composition Another big topic discussed at the recent CF Conference was the use of body composition (BC) to determine nutritional status in patients with CF. Whilst BMI and BMI percentiles are commonly used as indicators of nutritional status, they do not distinguish deficits, excess stores or changes in weight, fat or fat-free mass (FFM), or both. Assessment of BC can ascertain this information, which encompasses analysis of percent body fat, muscle, water and bone. This will help in identifying the body composition alterations frequently found in patients with CF.5-7 E Owen, Paediatric CF Dietitian at GOSH, London, presented her research, investigating BC changes in pre-pubertal children with CF diagnosed via newborn screening (NBS). Thirty seven children (20 boys), non-meconeum ileus, aged five to eight years were recruited to have their BC measured using dual energy X-ray absorptiometry. The results demonstrated that NBS boys had normal growth, BC and lung function (LF) compared to the reference norms. NBS girls had weight, BMI and fat mass index (FMI) significantly below average, but normal height and LF. Compared to unscreened boys, NBS boys were taller and had higher LF, with significantly lower BMI and fat-free mass index (FFMI). NBS girls were significantly younger with significantly higher LF than unscreened girls and with a trend towards higher weight, height and FFMI. In conclusion, despite normal LF, gender differences in growth and BC were seen in this contemporary cohort of NBS children. This supports BC assessment in girls especially and longitudinal monitoring. Whilst LF was better in the NBS cohort compared to the unscreened cohort, larger numbers are required to better evaluate differences in BC. A Belgium group from Ghent examined changes in body composition of tube-fed patients with CF compared to age and sex-matched controls. Tube feeding (TF) in CF is well recognised to improve BMI, but the influence of TF on BC is not well evaluated. Bio-electrical Impedance (BIA) measures were carried out in patients with CF with (2F, 7M) and without TF (controls). Fat%, body fat mass index (BFMI) and FFMI were examined. The patients were 22

www.NHDmag.com August/September 2018 - Issue 137

matched for age, gender and pancreatic function.

Age at start of TF was 12.8 years (8.7; 15.6). The TF patients were significantly shorter than the controls, but the BMI z score and LF were not significantly different between the two groups. However, BC was significantly different with a higher fat% (p=0.024), a higher BFMI (p=0.019) and a lower FFMI (p=0.04) in the TF patients. The study concluded that the patients in this cohort receiving TF had less FFM. Although TF is often the only remaining method in which to improve nutritional status. However, it can often lead to increased body fat proportions.

As dietitians we need to be aware of this and one option for future interventions would be to work with physiotherapists to incorporate physical activity.

An Australian group from Melbourne examined BC in the first year of treatment with lumacaftorivacaftor in adults with severe CF lung disease.

They defined severe lung disease as an FEV1<40% predicted over 12 months of lumacaftor-ivacaftor treatment. Data was analysed for 20 adults (10 male, mean +/- SD age 33.5 +/- 8.8 years, mean +/- SD FEV1 33.6 +/- 6.5% predicted, mean +/SD BMI 19.9 +/- 2.2kg/m2), who had received lumacaftor-ivacaftor for two months and had BC measured (multifrequency bioelectrical impedance analysis) at six and 12 months. Changes in weight, FFM and FM were measured.

Results demonstrated that at six months, mean +/- SD weight and FM significantly increased (weight 0-6 month; 2.3 +/- 3.9kg (p=0.02); FM 0-6 months 2.1+/- 2.7kg (p=0.003), but with no further increase by 12 months (weight 6-12 months; 0.3 +/- 3.1kg (p=0.66); FM612 months 0.3+/- 2.7kg (p=0.27). No changes were seen in mean FFM. A lower BMI at baseline correlated with greater weight and FM. No one became overweight; 50% gained >5%weight.

In conclusion, weight and FM gains seen at six months plateaued by 12 months. Underweight patients were more likely to have body composition gains. Preservation of FFM contrasts with earlier research that shows declining FFM in association with severe lung disease. Mechanisms underlying these body composition changes require further investigation.

The 2019 European CF Society Conference will be held on 5th to 8th June 2019 in Liverpool. It will be interesting to see what will be presented.