Section 10 - Cystic Fibrosis Clinical Care Pathway

Handbook for the Management
of Children with Cystic Fibrosis
Great Ormond Street Hospital for Children
NHS Trust and the Institute of Child Health

Handbook for the Management
of Children with Cystic Fibrosis
Acknowledgements:
This third edition of this handbook has been compiled from
contributions by many members of the Cystic Fibrosis Unit.
Special thanks go to:
Paul Aurora, Chris Benden, Jacquie Burton, Mandy Bryon, Judith Cope,
Bob Dinwiddie, Maureen Ferguson, Adam Jaffe, Gail Norbury,
Tanya Thomas, Mary O’Toole, Ammani Prasad, Sarath Ranganathan,
Denise Sheehan, Helen Spencer, Esta-Lee Tannenbaum, Colin Wallis,
Melissa Watson and Carol Wragg.
Edited by Robert Dinwiddie, Colin Wallis,
Adam Jaffe & Ammani Prasad
March 2004
3

Contents
Introduction
1. The Cystic Fibrosis Service ...................................................................................7
1.1 The unit personnel
1.2 The newly diagnosed patient
1.3 The CF outpatient clinic
1.4 The annual review
1.5 Chest x-ray scoring
1.6 The cystic fibrosis homecare service
2. Pulmonary Management....................................................................................17
2.1 Physiotherapy
2.2 Antibiotic therapy
2.3 Nebuliser therapy
2.4 Totally implanted venous access devices
2.5 Other pulmonary complications
2.6 DNase therapy
2.7 Oxygen therapy and assisted ventilation
3. Gastrointestinal Management...........................................................................39
3.1 Nutritional management
3.2 Pancreatic insufficiency
3.3 Growth and puberty
3.4 Gastrostomy tube feeding
3.5 Meconium ileus
3.6 Distal intestinal obstruction syndrome (DIOS)
3.7 Fibrosing colonopathy
4. Psychosocial Services..........................................................................................54
4.1 Psychological services
4.2 Social services
5. Genetic Services ..................................................................................................61
5.1 Gene typing of the affected individual
5.2 Carrier testing of adult relatives
5.3 Consanguineous marriage
5.4 Carrier testing of siblings
5.5 Prenatal screening
5.6 Population screening
5.7 Neonatal screening
5.8 Essential information
4

6. Lung Transplantation ...................................................................66
6.1 Patient selection
6.2 Surgical aspects and post-operative management
6.3 Survival and complications
7. Additional CF Related Complications..........................................71
7.1 Cystic fibrosis related diabetes
7.2 Liver disease
7.3 Oesophageal varices
7.4 Liver transplantation
7.5 Arthropathy
7.6 Nasal polyps
7.7 Sinusitis
8. Pharmacopoeia .............................................................................80
9. Useful Names and Addresses ......................................................86
10. Further reading.............................................................................89
5

Introduction
Cystic fibrosis (CF) is a life long illness and requires the care of a
multidisciplinary professional team for successful management. A team
approach ensures that the care provided for a patient with CF is both
comprehensive and individualised, and aims to provide as normal a life as
possible for the affected child and their family. The principles of therapy are
to anticipate and minimise any physical, emotional and social problems that
may develop, to prevent progressive lung disease and nutritional deficiency as
far as possible and to achieve optimal growth and psychological development.
However there is no single, ideal regimen of care and controversy still exists in
several areas of management.
This handbook is designed for health care professionals who deal with
children who have CF and comprises the protocols adopted by the Cystic
Fibrosis Unit of Great Ormond Street Hospital (GOSH). It is hoped that
these guidelines will provide a uniformity to the therapy given by the various
team members, both within the hospital and in our shared care clinics. It is
also anticipated that answers to management queries not specifically in one’s
own area of expertise will be available in the absence of the relevant team
member.
Our handbook deals with common management problems in CF and does
not purport to be a comprehensive text on the subject; developments,
advances and consequent changes to protocols are anticipated. Comments
and criticisms regarding omissions and therapies are encouraged.
6

Section One:
The Cystic Fibrosis Service
1.1 Unit Personnel
Cystic Fibrosis Unit
Great Ormond Street Hospital for Children NHS Trust
Great Ormond Street
London WC1N 3JH
CF Clinic:
Tel: 020 7405 9200
Fax: 020 7813 8514
Consultants Robert Dinwiddie Ext 5453
Colin Wallis Ext 0647
Adam Jaffe Ext 5404
Senior Physiotherapist Esta-Lee Tannenbaum Bleep 0464
Dietitian Tanya Thomas Bleep 0300
CF Clinical Nurse Specialist Denise Sheehan Bleep 0581
CF Clinical Nurse Specialist Charlie Dawson Bleep 0154
(homecare) Mob 07979 770292
Clinical Psychologists Mandy Bryon Ext 0501
Melissa Sanchez Ext 0434
Lung Function Laboratory Aidan Laverty Ext 5372
John Rae Ext 5456
Fareeama Subar Ext 5456
Emma Scrase Ext 5456
Secretary & Appointments Carol Wragg Ext 0431
Research / Database Coordinator Ammani Prasad Ext 2328
CF Research Fellow Bleep 0699
CF Staff Grade
Respiratory ward staff:
Bleep 0779
Ward Sister Maureen Ferguson Ext 5402
Registrar Bleep 0635
SHO Bleep 0648
Badger Ward
Transplant Team
Ext 8813
Consultant Paul Aurora Ext 2377
Nurse Specialist Pauline Whitmore Bleep 0600
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1.2 The Newly Diagnosed Patient
The first visit
A diagnosis of cystic fibrosis (CF) can be made at any age. The first contact
between the patient and the members of the CF unit may vary from within
hours of birth to late adolescence. A diagnosis has usually been made on the
basis of clinical suspicion, family history, sweat testing, genotyping, pre- or
postnatal testing, or newborn screening.
The first interview should include both parents and will involve an
introduction to the various members of the cystic fibrosis team. Initial and
long-term management protocols will be introduced and sometimes, if the
child is not already in hospital, an admission is arranged to allow for more
intensive education and treatment of any established disease. Baseline
investigations, including genotyping, will be performed and a repeat sweat
test will often be requested to confirm the diagnosis. Sweat testing on siblings
may also be indicated, even if these children are reportedly asymptomatic.
Although parents will be advised on medical, psychological, social and genetic
issues during this initial visit, it is essential to provide reassurance that
personnel will be available at other times in the near future. There is an
enormous volume of new information to be absorbed at the time of diagnosis
and the facts can be confusing and difficult to retain. There may also be
considerable depression and anxiety following the diagnosis. Hostility toward
the medical profession may be present owing to delays in the discovery of CF
in their child who has been affected by many months of ill health.
Clinic appointments arranged at regular intervals after the first interview will
provide further opportunities to discuss all aspects of CF. A summary of the
CF team’s findings is forwarded to the general practitioner and the referring
hospital consultant. Arrangements will also be made to initiate or continue a
basis of shared care with a local CF clinic if available.
CF is a very variable disorder and the prognosis is unpredictable. The use of
antibiotic therapy regularly or early in pulmonary infections, and careful
attention to nutrition and enzyme supplementation has resulted in a
considerably improved prognosis over the last decade. It is not unreasonable
for all team members to provide an optimistic and hopeful outlook during
these initial interactions with the newly diagnosed patient and their family.
Following discharge from hospital a CF homecare clinical nurse specialist will
visit regularly to provide support, ongoing medical advice and teaching. This
can give the family time to express feelings and concerns in their own
environment whilst being given individualized specialist care and support.
The CF homecare nurse specialist can also perform lung function, blood
sampling, portacath needle flushings and ongoing monitoring of effectiveness
of treatments, including medications, diet and enzymes. These visits can be
8

carried out in conjunction with the community health care team, providing
education and support for these professionals.
The sweat test
The measurement of sodium and chloride levels in sweat remains the most
reliable specific confirmatory test for CF. Levels of chloride greater than 60
mmol/l on an adequate sample of sweat are diagnostic. A sufficient amount
of sweat may be difficult to obtain in neonates. Skilled personnel should
perform the sweat test as false positive and negative results can easily be
obtained and misinterpreted. Values between 40 and 60 mmol/l are equivocal
and should be repeated.
In borderline cases it is worthwhile considering the following points:
1. In normal individuals the sodium is higher than the chloride and their
sum is less than 140 mmol/l.
2. In patients with CF the chloride is usually higher than the sodium and
their sum is greater than 140 mmol/l.
3. Normal sweat sodium levels increase with age: 10% of normal
adolescents may have values greater than 60 mmol/l. Chloride levels are
considered more reliable at all ages.
4. Sweat sodium and chloride levels are also increased in adrenal
insufficiency, hypothyroidism, certain glycogen storage diseases,
mucopolysaccharidoses, ectodermal dysplasia, nephrogenic diabetes
insipidus and may be raised in HIV infection.
5. The test may be negative in the presence of hypoproteinaemia and
oedema.
6. Certain genotypes for CF are associated with borderline or even normal
sweat test results. Although these mutations are rare in the UK, unusual
genotypes may need to be considered, especially in ethnic groups where
CF is generally less common.
1.3 The Cystic Fibrosis Outpatient Clinic
There are currently about 200 children (0-17 years) attending the Out
Patient Cystic Fibrosis Clinic at Great Ormond Street Hospital (GOSH). Of
this group 50% are shared care with the local paediatrician, and 50% directly
with the GP and GOSH.
A number of peripheral clinics are also held with visits to each at least twice a
year. A clinical nurse specialist and a consultant attend each clinic, with a
physiotherapist and dietitian attending for some of these clinics.
The discussion about transferring to an adult team begins around the age of
14, with an invitation to a multidisciplinary transition clinic when they are
9

15 or 16. Young adults are usually transferred to an adult CF clinic in their
16th year. We normally refer to the Royal Brompton Hospital, the London
Chest Hospital and Papworth Hospital, although some children prefer to go
to centres closer to their home. Transition clinics are held at GOSH in the
out patient clinic with each of the above adult centres at least once a year.
These are a multidisciplinary team clinic with both adolescents and parents
invited. Informal visits can be arranged with the clinical nurse specialist at the
adult centre during these clinics.
The CF Clinic is held every Tuesday afternoon in Medical Outpatients (B)
from 2pm onwards for about 12 patients.
Every Clinic is attended by:
Two Consultants
Cystic Fibrosis Fellow
Physiotherapist and Physiotherapy Assistant
Lung Function Technician
Dietitian
Clinical Nurse Specialists (CNS)
Clinical Psychologist
Routine clinic procedure
• Height and weight are recorded by the clinic staff. If there has been any
weight loss urinalysis for glucose should be carried out.
• Physiotherapy assessment including review of technique and sputum or
throat swab is taken (please remember to sign and complete
microbiology request form).
• Spirometry and oxygen saturation (SaO2) are measured on all children
over five years of age and SaO2 alone in those under five.
• Dietary assessment and advice is available to all patients.
• The clinical nurse specialists are available to discuss various issues with all
children and families, including schooling, nebuliser equipment,
disability living allowances, etc.
• Patients’ notes are distributed between the consultants unless a specific
patient request is made. Patients attending for annual review follow up
should be seen by a consultant.
• The assessment by the medical staff pays particular attention to the
control of lung disease, the growth and development of the child, their
nutritional status and to early intervention to minimise complications.
• A clinical psychologist is available to see patients and their families in
clinic.
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Additional services
Compressors - are ordered by the clinic staff. They are available on the
same day.
Portacaths - are flushed in clinic on a monthly basis by the clinical
nurse specialists. If there is no CNS, then they can also be
flushed on the respiratory ward, if the ward staff are given
prior notice.
Information - there is always a variety of literature on aspects of CF
available in the clinic. Ask the clinical nurse specialists if
you need anything specific.
Information dispersal
• A letter is sent to the GP and local hospital paediatrician following each
visit.
• The CF team meets to review patients after each clinic visit. Nutrition,
lung function, microbiological results, psychological problems and
changes in treatment are discussed and plans for future management are
decided. Letters are then sent to GP’s with copies sent to local
consultants, community nurses and other relevant health care
professionals.
1.4 The Annual Review
All CF patients are seen once a year for a detailed clinical review (Tuesdays in
the CF Clinic or Wednesdays on Badger Ward). This annual review provides
a full clinical assessment of an individual’s progress and disease status which
includes the number of hospital admissions, courses of iv and oral antibiotics.
It is also the aim to update the patient and their families on recent
developments and therapeutic modalities and to discuss plans of future
therapy for the forthcoming year. This comprehensive examination is
undertaken against a pre-formatted checklist and includes the parameters
detailed below. All information is entered into a computerised database which
facilitates easy analysis of an individual’s health parameters over the years. All
results obtained are discussed by the CF team and a detailed report sent out
to the shared care centre and/or the GP.
Baseline Data:
• Height and centile
• Weight and centile
• Blood pressure & vital signs
• Oxygen saturation
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• Urine dipstick and analysis
Investigations:
• Full lung function (for children over five years):
Spirometry and plethysmography (expressed as % predicted for height
and sex)
• Bronchodilator response*
• Exercise testing when relevant (GOSH three-minute step test)*
• Infant lung function*
Imaging:
• Chest x-ray - (scored using the original and modified Chrispin-Norman
system, see below)
• Liver and spleen ultrasound* (patients with hepato-splenomegaly,
abnormal LFT’s or clotting profile)
• DEXA scan* (these scans give a measurement of the size and amount of
mineral in the bones, as well as the proportions of fat and muscle)
• CT chest*
Blood tests:
• Haematology: full blood count, clotting profile
• Urea & electrolytes: Na, K, urea, creatinine, Ca, PO4, Mg
• Liver function tests: ALT, Gamma GT, alkaline phosphatase, albumin,
bilirubin
• Blood glucose, HbA1C*
• Fat-soluble vitamins: A and E
• Vitamin D
• Markers of inflammation: immunoglobulins, ESR, CRP
• Total IgE, Aspergillus precipitins & Aspergillus specific IgE*
• Genotype if not previously undertaken
• Pseudomonas antibodies*
Microbiology:
• Sputum or cough swab mc&s
* optional investigations depending on patient requirements
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Review by Team Members:
• Medical examination
• Drug review
• CF Nurse Specialist assessment
• Nutritional advice
• Psychosocial interview
• Physiotherapy assessment
• Equipment review
1.5 Chest X-ray Scoring
The Chrispin-Norman score is used to provide a rating to evaluate the
presence and severity of pulmonary disease on plain and lateral chest x-ray
films and can be used to monitor changes over time. Recently a modified
Chrispin-Norman system has been developed which removes the need for the
lateral film. This has the advantage of less radiation to the patient and cost
savings as only one film is necessary at each evaluation.
The modified score assesses hyperinflation on the basis of chest wall shape,
rounding of the rib cage and spacing of ribs, darkness of the lung fields,
indicative of air-trapping, and descent of the diaphragm below the normal
level of five to six anterior rib ends on the frontal film.
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Chrispin-Norman Chest X-ray Scoring
in Cystic Fibrosis and Modified Chrispin-Norman Score
Feature Not Present but Marked
Chest configuration
Present not marked
Sternal bowing 0 1 2
Diaphragmatic depression 0 1 2
Spinal kyphosis 0 1 2
Modified Score
Chest wall shape 0 1 2
Density of lung fields 0 1 2
Diaphragmatic depression 0 1 2
Bronchial line shadows
Right upper zone 0 1 2
Right lower zone 0 1 2
Left upper zone 0 1 2
Left lower zone 0 1 2
Ring shadows
Right upper zone 0 1 2
Right lower zone 0 1 2
Left upper zone 0 1 2
Left lower zone 0 1 2
Mottled shadows
Right upper zone 0 1 2
Right lower zone 0 1 2
Left upper zone 0 1 2
Left lower zone 0 1 2
Large shadows
Right upper zone 0 1 2
Right lower zone 0 1 2
Left upper zone 0 1 2
Left lower zone 0 1 2
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The frontal and lateral chest x-rays are inspected for forward bowing of the
sternum (lateral film), spinal kyphosis (lateral film), and degree of
diaphragmatic depression (frontal and lateral films); these changes are due to
hyperinflation of the lungs. Each individual item is given a score of: 0-not
present; 1-present but not marked; 2-marked, depending on the degree of
change. The lung fields are then divided into four zones on the PA film; right
upper, right lower, left upper and left lower. Each field is then reviewed for
parenchymal lung changes which are a consequence of bronchial mucus
plugging and infection, and which are seen as bronchial wall thickening,
mottled shadows, ring shadows and areas of confluent consolidation. A score
of 0, 1, or 2 is given according to the severity for each zone in relation to
each of these changes. The increased bronchial line shadowing indicates
thickening of the walls of the airways; these are usually seen as longitudinal
shadows with a straight line branching pattern and also as end-on bronchi
which show as circular shadows - these are best seen in the lateral view.
Mottled shadows indicating sputum collection at the microlobular level show
as small rounded opacities with ill-defined edges which are seen as confluent
areas of increased radio-density. Ring shadows are formed by a central area of
increased lung radiolucency circumscribed by a discrete shadow of lesser
radiancy. These shadows are approximately 0.5cm in diameter and are
predominantly seen in the peripheral lung fields; they represent bronchiectasis
at the lobular level. A score is given for the presence and severity of these
shadows in each quadrant. In clinical practice the score approximates to the
child’s age in years, but scores above 20 indicate advanced lung disease.
1.6 The Cystic Fibrosis Homecare Service
A Clinical Nurse Specialist homecare service is available to all patients and
families. Newly diagnosed patients and those attending GOSH regularly for
intravenous antibiotic admissions are followed up automatically. Any member
of the CF team, community agencies or families, can refer patients to the
service.
The aims of the service are to provide support, guidance and education for
both patients and families regarding diagnosis, physiotherapy, diet, enzymes,
medications, new treatments, transition to adult services, home intravenous
antibiotic therapy and psychosocial issues. Another aim is to decrease the
length of hospital admissions and the number of out patient clinics attended
for some patients.
Patients can be assessed during and after home intravenous antibiotic courses,
providing teaching and monitoring of new treatments. Other clinical services
available to patients include, lung function testing, drug levels, blood
sampling, totally implantable device flushing, weight and dietary monitoring.
Visits can also be arranged to provide education to other agencies such as staff
15

at schools and nurseries, children’s community nurses and staff at shared care
centres.
The service operates Monday to Friday, 9 am to 5 pm and appointments can
be made with the Clinical Nurse Specialist on 0797 9770292 or on bleep
154.
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Section Two:
Pulmonary Management
2.1 Physiotherapy
Chest physiotherapy is an integral part of the management of CF. It is
thought to prevent and reduce pulmonary complications such as atelectasis
and hyperinflation by the removal of bronchopulmonary secretions. Removal
of these secretions reduces the overall proteolytic activity in the lungs, which
could reduce the progression of elastase-mediated damage to the airways and
the mucociliary transport system. The role of the physiotherapist is not
limited to airway clearance but also includes encouragement and advice on
exercise, posture, mobility and inhalation therapy.
Most patients with CF do require some form of chest physiotherapy daily,
however this should be tailored to their individual needs, according to age,
clinical status and social circumstances.
2.1.1 Management of infants
and small children
Traditionally it has been recommended that newly diagnosed infants with CF
begin a twice-daily regimen of postural drainage and percussion undertaken
by a parent or guardian. Postural drainage is carried out in alternate side lying
with a head down tip, supine, prone and in the sitting position. The rationale
for this approach has been based on three arguments. Firstly, early
intervention may prevent the onset of complications and secondly that there
is clear evidence from studies of bronchoalveolar lavage, infant lung function
and radiological imaging that manifestations of lung disease occur at a very
early stage in the disease process. Lastly it is argued that introducing a routine
of chest physiotherapy from an early stage so that it becomes part of the
child’s daily routine will improve compliance with treatment.
With earlier diagnosis and particularly the introduction of neonatal screening
many infants now presenting with CF have very little in the way of
respiratory symptoms and are often well nourished. Although daily treatment
continues to be recommended even in this asymptomatic group of patients
there is as yet no evidence to suggest that routine physiotherapy has an
impact on the course of the pulmonary changes. Furthermore poor adherence
to treatment has been associated with the lack of immediate and obvious
benefit from therapies and daily regimens of chest physiotherapy place a
significant burden on parents and carers. In preference to a routine
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prescription of twice daily chest physiotherapy it is suggested that an
appropriate physiotherapy regimen is formulated depending on the child’s
clinical status and family circumstances. This should include airway clearance
and emphasise the importance of physical activity.
2.1.2 Treatment techniques
In order to maximise therapeutic value and reduce the treatment related
burden on adolescents and older children, a number of independently
performed chest physiotherapy techniques have been developed. The choice
of treatment is made by the physiotherapist in conjunction with the patient
(where age appropriate) and their carer. The physiotherapy treatment
modalities include:
• Postural Drainage and Percussion
• Active Cycle of Breathing Technique (ACBT)
• Autogenic Drainage
• Positive Expiratory Pressure (PEP) Mask:
– High Pressure PEP
– Bubble PEP
• Oscillatory PEP:
– Flutter
– Cornet
• Exercise
• High Frequency Chest Wall Oscillation (HFCWO)
• Intrapulmonary percussive ventilation (IPV)
Postural Drainage and Percussion
Postural drainage or gravity assisted positioning and manual techniques such
as chest percussion are used to assist the clearance of bronchial secretions. A
general regimen of postural drainage would include alternate side lying,
supine and prone positioning with a head down tip. In infants the sitting
position is included to drain the apical segments of the upper lobes. If there is
evidence of a focal area of collapse more specific gravity assisted positioning
may be used. In the presence of proven gastro-oesophageal reflux it may be
necessary to modify the postural drainage regimen to avoid a head down tip
or to use an alternative airway clearance technique.
Active Cycle of Breathing Techniques (ACBT)
The ACBT is a flexible breathing regimen consisting of breathing control,
thoracic expansion exercises and the forced expiration technique. Breathing
control is quiet, gentle breathing at the patient’s own comfortable rate,
keeping the upper chest and shoulders relaxed. It is important to use this in
18

Figure 1:
The active cycle of
breathing
techniques.
between the more active parts of the cycle to prevent any increase in airflow
obstruction or tiredness. Thoracic expansion exercises are deep breathing
exercises emphasising inspiration. Expiration is quiet and relaxed. These
exercises help to loosen bronchial secretions based on the concept of
interdependence and increased collateral flow. Percussion may be performed
during thoracic expansion exercises if it is felt to be helpful. The Forced
expiration technique is one or two huffs interspersed with periods of
breathing control. It is based on the physiological concept of the equal
pressure point. This point is moved more peripherally when a huff is
continued from mid to low lung volume, therefore allowing mobilisation of
more peripheral secretions. The ACBT can be carried out in gravity assisted
positions or in sitting. If there are localised x-ray changes, specific positioning
will be implemented. The cycle is repeated until the huff becomes dry and
non-productive or it is time for a rest. A typical cycle of treatment is shown
in figure 1.
Breathing control
Three or four Thoracic expansion exercises
Breathing control
One or two huffs (mid - low lung volume)
Breathing control
Cough & Expectoration
Positive Expiratory Pressure (PEP)
Positive Expiratory Pressure (PEP) Mask
PEP applied via a face mask or mouthpiece is believed to improve sputum
clearance by its effect on peripheral airways and collateral ventilation. PEP
causes an increase in lung volume enabling air to move behind secretions,
forcing them up the bronchial tree to the more central airways.
The PEP mask consists of a face mask and a one way valve with an
inspiratory and expiratory port (figure 2). A resistor is attached to the
expiratory port to achieve PEP. Patients are assessed by the physiotherapist for
the appropriate resistance - one which gives a steady PEP of 10-20 cmH2O
during mid-expiration. The system and appropriateness of resistance should
19

e reviewed at each clinic visit.
Treatment is performed in the sitting position with elbows on a table and
consists of 10-12 tidal breaths through the mask with slight emphasis on
expiration followed by one or two huffs and coughing. The frequency and
duration of treatment is adapted to the needs of the individual patient
(average 10-20 minutes). The use of gravity assisted positions may also be
helpful in some patients.
High Pressure PEP
The use of high pressure PEP is reported to reduce airway instability,
hyperinflation and airway obstruction, whilst facilitating sputum clearance. It
is a modification of the previously described PEP technique and involves
adding a full forced expiratory manoeuvre through the mask at the end of
each PEP cycle. This usually results in coughing at low lung volume.
Coughing is performed through the mask until secretions are high in the
respiratory tract. Following expectoration, treatment is continued until
maximum clearance is achieved.
Assessment for high pressure PEP requires spirometric lung function
equipment which can be attached to the mask. This should be carried out by
a senior physiotherapist experienced in the technique and meticulous
assessment to choose the appropriate size of resistance, and follow up with
full lung function testing is vital to ensure maximal therapeutic value.
Bubble PEP
Bubble PEP has been developed for use with young patients who require
assistance with clearance of pulmonary secretions. It uses similar physiological
20
Figure 2:
The PEP
mask system

Figure 3: Bubble
PEP
principles to PEP but utilises a bottle filled with a specified level of water and
bubble liquid, and tubing through which the patient blows to create bubbles.
This creative technique provides positive feedback which in turn may assist
the therapist and parent in gaining the cooperation, interest and increased
compliance of the child.
1. TUBING
(wide straw size)
35 - 40 cm long.
2. 2 PINT MILK
OR FRUIT JUICE
CARTON - empty
and washed clean.
3. WATER
+ LIQUID SOAP
(3-4 squirts) with
food colouring
if desired.
4. TRAY OR BOWL
into
child’s
mouth
to catch the bubbles! 2 PINTS
Autogenic Drainage
Water Level
(1 pint or
10cm depth)
Autogenic drainage consists of a three phase breathing regimen performed in
postural drainage or sitting position. Mucus clearance is facilitated by the
adjustment of tidal volume breathing during which the highest possible
expiratory airflow is reached without causing airway closure. The three phases
consist of a period of breathing at low lung volume when secretions are
mobilised from the peripheral areas. This is followed by breathing at mid
lung volume both to collect the mobilised secretions and finally with high
lung volume breaths to clear and expectorate. AD should only be taught by
an experienced therapist, skilled in the technique.
Oscillatory PEP
Flutter VRP1
The Flutter is a pipe shaped hand held device (figure 4a) through which the
patient exhales to generate an oscillatory positive pressure. Altering the
21

inclination of the device from the horizontal can regulate the frequency of
oscillation. The resulting vibratory effect combined with intermittent PEP is
said to maintain airway patency and enhance mucus clearance. Treatment is
carried out in the sitting position or a postural drainage position. The patient
performs approximately 10-12 tidal volume breaths followed by a forced
expiratory manoeuvre (huff) through the device. Following cough and
expectoration this cycle is repeated as necessary.
RC-Cornet
The Cornet consists of a mouthpiece, hose, curved tube, and sound damper
(figure 4b) and is based on similar physiological principles as the Flutter.
Expiration through the device creates an increasing pressure within the hose
until sufficient to cause the hose end to catapult open, thus releasing the
pressure and allowing air to flow through the device. The pressure and flow
rate can be adjusted by rotating the mouthpiece within the tube. The patient
performs 10-12 breaths into the Cornet followed by huffing and
expectoration. The cycle continues as necessary for ten to 20 minutes. The
cornet has been reported to reduce sputum viscosity, however, further studies
of efficacy are required.
a) b)
High Frequency Chest Wall Oscillation (HFCWO) /
Intrapulmonary Percussive Ventilation
High frequency oscillations to the chest wall can be applied using a thoracic
vest or a Hayek oscillator. The application of HFCWO through a range of
frequencies between five and 15 Hz is said to enhance mucus clearance and
alter the viscoelastic properties of secretions. Intrapulmonary percussive
ventilation delivers rapid bursts of air to the airways via a mouthpiece.
Neither of these techniques are currently widely available in the UK.
2.1.3 Exercise
Regular physical activity in the CF population has several positive benefits
including increased cardiorespiratory fitness, increased ventilatory muscle
endurance, decreased breathlessness, enhanced sputum clearance, increased
22
Figure 4:
Diagrammatic
representation of the
a) flutter (left) and
b) Cornet (right)

muscle mass and strength (resulting in improved body image) and an
enhanced quality of life. The positive effects of exercise and its contribution
to maintaining a healthy lifestyle should be emphasised to the whole family
from the time of diagnosis.
Exercise recommendations or programmes need to be individually tailored
and should combine endurance and strength training exercises for the upper
and lower body. Aerobic exercise such as swimming, cycling, skipping and
trampolining aim to improve endurance, allowing longer periods of physical
activity without discomfort. Such weight bearing exercises may also be
beneficial in terms of preventing or delaying the loss of bone mineral density.
Strength training aims to increase muscle strength and mass. While not
discouraged it should be undertaken with care, avoiding repetitive stress on
joints, particularly in children where repetitive strain on the epiphysial plates
can cause injury. Postural deformities, particularly of the thoracic spine, are
common in chronic respiratory disease and careful attention should also be
paid to posture.
Generally those with mild to moderate disease (FEV1>55%)are likely to be
able to exercise to the same level as their healthy peers. Following careful
assessment with exercise testing, those with more severe disease should also be
encouraged to undertake some form of regular exercise. Supplemental oxygen
may be necessary and this should improve performance and reduce
breathlessness during exercise.
2.1.4 Physiotherapy on the ward
On admission to the respiratory ward, the patient is be seen by a
physiotherapist. Physiotherapy treatment is carried out one to four times
daily depending on the severity of the chest disease. Wherever possible one of
the daily treatments comprises exercise interspersed with airway clearance
techniques, either in the physiotherapy gym or hydrotherapy pool. Parents are
also encouraged to participate in their child’s physiotherapy treatments,
usually in the evenings or at weekends.
If a surgical procedure is required, such as nasal polypectomy, insertion of
portacath or gastrostomy, patients may be admitted to the ward for intensive
physiotherapy prior to surgery depending on their respiratory status. When
appropriate the physiotherapist will undertake bronchial lavage techniques
whilst the patient is intubated to help clear secretions.
2.1.5 Intra-operative physiotherapy
If a surgical procedure, such as nasal polypectomy, insertion of portacath or
gastrostomy is required, the patient will usually be admitted to the ward for
23

intensive physiotherapy prior to surgery depending on their respiratory status.
When appropriate the physiotherapist will undertake bronchial lavage
techniques whilst the patient is intubated. This may be to obtain a sputum
specimen for microbiology or to help clear excess secretions from the lungs.
2.2 Antibiotic Therapy
By the age of eight months, almost half of all CF infants will have developed
respiratory symptoms, and the ongoing control of respiratory tract infections
becomes a way of life for the majority of children with this disease. Recurrent
infection leads to disruption of the mucociliary lining of the airways, with
formation of micro-abscesses and the development of bronchiectasis.
The commonest bacterial pathogens are Staphylococcus aureus, Pseudomonas
aeruginosa and Haemophilus influenzae. Staphylococcus aureus is often the
initial infecting organism but is commonly replaced by Pseudomonas
aeruginosa as the child gets older. The prevalence of Stenotrophomonas
maltophilia and other opportunistic pathogens is increasing amongst the CF
population.
The aim of antibiotic therapy initially is to prevent chronic infection by
eradication of the organism. However, once chronic infection occurs,
antibiotic therapy is then aimed at limiting the extent and rate of bacterial
growth and airway damage. Whenever a child is seen in the CF clinic or at
home (with or without a change in respiratory status or symptoms) a cough
swab or sputum sample should be taken for culture and antibiotic
sensitivities. This information provides a useful guide for planning antibiotic
therapy.
2.2.1 Antibiotic Policies
The use of antibiotics in suitable doses via an appropriate route has
contributed significantly to the improvement in both quality and quantity of
life for children with CF.
There are a number of long term regimens currently in use for the
antimicrobial management and CF centres will individualise their therapies
according to local bacterial sensitivities and experience. The guidelines used
by this CF unit are summarised below with the dosage details documented in
the Pharmacopoeia (see Section 8).
Upper respiratory tract infections
The role of viral infections in the progress of lung disease in the young child
is still unclear. All the usual viruses have been implicated but RSV,
Parainfluenza and Influenza A are the most common. A viral infection may
24

predispose CF patients to secondary bacterial infection and therefore oral
antibiotics are used aggressively in presumed viral infections in CF. For mild
upper respiratory tract infections, we recommend anti- Staphyloccocal and
Haemophilus cover for two weeks (e.g augmentin). A two-week course of
ciprofloxacin should be given to patients chronically infected with P.
aeruginosa who have developed an upper respiratory tract infection pending
the results of sputum/cough swab cultures.
Staphylococcus aureus
a) Prophylaxis
In all CF infants under two years of age, we recommend the use of
prophylactic flucloxacillin from diagnosis. Although there have been recent
concerns about the increase in acquisition of P. aeruginosa, most of these
studies reported patients treated with broad spectrum antibiotics (cephalexin).
After the age of two years, flucloxacillin can be stopped in those children who
are not chronically infected with S. aureus. It should be continued in those
children who develop respiratory symptoms after stopping flucloxacillin or
who regularly grow S. aureus. Occasionally infants do not tolerate
flucloxacillin (e.g. vomiting). It is then reasonable to consider alternative antistaphylococcal
treatment (eg. augmentin).
b) Chronic infection
Those children who regularly grow S. aureus in their sputum or whose
symptoms return whenever anti-staphylococcal antibiotics are stopped should
remain on prophylactic anti-staphylococcal medication (usually
flucloxacillin). Any intercurrent respiratory tract infection should be treated
by increasing the prophylactic dosage to a treatment dose and adding a
second anti-staphylococcal agent (e.g. azithromycin) for two weeks. If the
patient fails to respond then intravenous agents for two weeks may be
necessary, either in hospital or at home (see Sections 2.2.4, 2.4). Try and
include an anti-staphylococcal antibiotic with any subsequent IV course of
treatment. Consider a bronchoscopic lavage in patients not responding to IV
treatment.
Hemophilus influenzae
a) Acute infection
Treat with a two-week course of an oral antibiotic (eg. augmentin) if it is
isolated in sputum. If sputum is still positive after two weeks continue
augmentin for a further two weeks and add azithromycin. If still present after
a total of 4 weeks then consider IV antibiotics. Consider a bronchoscopic
lavage in patients not responding to treatment.
b) Chronic infection
In those patients who repeatedly have H. influenzae cultured in their sputum
consider long term prophlaxis (e.g. augmentin).
25

Pseudomonas aeruginosa
The acquisition of P. aeruginosa infection is associated with deterioration in
lung function. An aggressive antibiotic approach may prevent chronic
infection and limit airway disease.
a) Early infection
Continue oral
ciprofloxacin and
nebulised colomycin
for a further three
weeks
Three weeks of oral
ciprofloxacin and nebulised
colomycin
+ve culture
Reculture
Reculture
Stop oral ciprofloxacin
Commence long-term nebulised
colomycin
Consider IV antibiotics
Nebulised colomycin should be
given during IV course
–ve culture
Stop oral ciprofloxacin.
Continue nebulised
colomycin for a total of
three months
+ve culture –ve culture
Stop ciprofloxacin.
Continue nebulised
colomycin for a total
of three months
Follow the above regimen for subsequent isolates of P. aeruginosa.
In those patients in whom P. aeruginosa is suspected but not cultured, do
Pseudomonal antibodies (report available within one to two weeks) and
consider bronchoscopic lavage. Do not blindly treat suspected Pseudomonas
in those not chronically infected with the organism.
b) Chronic infection
Infection with P. aeruginosa is assumed to be chronic after three consecutive
positive cultures have been obtained at least one month apart. Long term
26

nebulised colomycin is then commenced. If patients continue to deteriorate
while on nebulised colomycin then consideration can be given to switching to
preservative free tobramycin (TOBI) alternating with colomycin on a
monthly basis. If patients do not tolerate colistin (eg due to
bronchoconstriction) or they are chronically infected with S. aureus then they
can be switched to phenol free tobramycin or TOBI.
If a child develops a cold or an infective exacerbation then they should be
commenced on two weeks of ciprofloxacin (consider combining with a twoweek
course of azithromycin if very unwell). An infective exacerbation is
characterised by an increase in cough, sputum production, change in sputum
colour, loss of weight and deterioration in lung function. Fever may occur but
is not typical. If there is no response to oral antibiotics then admit for IV
antibiotics. Some children will require regular courses (two to three monthly)
of IV antibiotics depending on clinical status. IV antibiotics should be for at
least ten days with two weeks being the norm. Occasionally patients may
benefit from a further third week of IV therapy.
It is accepted practice to give two antibiotics - usually combining an
aminoglycoside (gentamicin, tobramycin, amikacin) with a third generation
cephalosporin (ceftazadime) in order to minimise the development of
antimicrobial resistance. A combination of piperacillin and tazobactam
extends the sensitivity range of piperacillin to include the beta-lactam
producing organisms and is a useful adjunct to the anti-pseudomonal
armamentarium. The development of a rash or fever may sometimes occur
towards the end of intravenous piptazobactam. Currently we administer
aminoglycosides three times per day but our practice may change following
the results of the TOPIC (once daily tobramycin) study. Nebuliser therapy
can be stopped during intravenous therapy except when a child is admitted in
an attempt to eradicate Pseudomonas following the first isolation.
Other organisms
Burkholderia cepacia
Infection with Burkholderia cepacia may be asymptomatic and can be
associated with a slow decline in lung function or result in the ‘cepacia
syndrome’. This is an accelerated and frequently fatal deterioration in lung
function with fever, necrotising pneumonia and in some cases septicaemia.
Infection with B. cepacia presents a therapeutic problem as it is generally
resistant to the beta-lactams, fluoro-quinolones and aminoglycosides. Patients
with poorer lung function at the time of infection appear to be at greatest risk
of cepacia syndrome but survival cannot be predicted from age, sex, duration
of colonisation, or antibody response.
Recent anxiety has been generated with regard to the epidemiology of the
organism as direct or indirect transmission appears considerably greater than
that observed with P. aeruginosa and other CF pathogens. Based on
genomavar analysis, strains of B. cepacia have been reported to spread in
27

epidemic fashion within individual CF centre patient populations. Thus all B.
cepacia isolates must be sent for genomovar typing. There is circumstantial
evidence that social contact outside of hospital is important in spread of the
epidemic strain within and between clinics.
Fortunately the prevalence of Burkholderia cepacia in the CF clinic at GOSH
remains very low. We do not have many infected patients and have no
evidence for cases of clinic associated transmission. Cross infection is by
coughing and contamination with infected sputum and in keeping with
policies elsewhere, children infected with Burkholderia cepacia are seen in
separate clinics.
The following practical guidelines are in use should an individual, admitted
to the ward, be found to be Burkholderia cepacia positive on sputum culture:
Antibiotic Guidelines
Nebulised and IV colistin should not be used if B. cepacia is the sole
pathogen in the sputum. Consideration can be given to using nebulised
ceftazadime (although the taste is unpleasant). Antibiotic therapy should be
guided by sensitivities. Infective exacerbations may be treated with oral
chloramphenicol, co-trimoxazole or ciprofloxacin.
Nursing Guidelines
• Consideration should be given to admitting patients to a ward other
than Badger.
• Patients with Burkholderia cepacia must sleep in their own rooms.
• Chest physiotherapy must be carried out in the patient’s room only.
• No other patients with CF (including others with cepacia infection)
should go into that room (e.g for lung function testing).
• Equipment (e.g.lung function equipment) must not be shared. If this is
not possible then the Burkholderia cepacia positive child should use the
equipment last, and the cleaning instructions must be followed after use.
• Sputum pots and tissues must be disposed of immediately and hands
must be washed immediately afterwards.
• Staff dealing with all CF patients and coming into contact with sputum
must wear gloves and plastic aprons and pay careful attention to hand
washing before and after each treatment. They should be seen last on
ward rounds.
Social Guidelines
• All children must be encouraged to cover the mouth when coughing.
• Children can mix socially with other non-CF patients as long as they
cough away from patients. Contact with other CF patients should be
avoided.
28

• Intimate contact between patients should be avoided as this carries a
high risk of spread.
• Nursing staff must take responsibility where young children are
concerned with regard to the amount of socialising allowed (e.g. children
who do not cover their mouth when coughing).
Stenotrophomonas maltophilia
This organism is becoming more prevalent among CF patients. There is
conflicting evidence as to whether it is associated with a decline in lung
function. Current opinion is that it does not. Therefore only those patients
who are chronically infected AND have clinical deterioration should be
treated with anti-Stenotrophomans therapy. This is usually with cotrimoxazole
(depending on sensitivities). There is no evidence for cross
infectivity and therefore additional strict isolation protocols are not necessary.
Methicillin-resistant Staphylococcus aureus (MRSA)
A small number of patients will be colonised with MRSA. If sputum is found
to be positive for MRSA then the child must be swabbed according to the
MRSA screening protocol. Nasal carriage is treated with Mupirocin. In
addition, family members should be swabbed and treatment arranged if
found to be positive.
If MRSA is suspected to be causing symptoms then treat according to
sensitivities. Consider nebulised vancomycin preceded by nebulised
salbutamol. For acute exacerbations include either teicoplanin or vancomycin.
Linezolid may become useful in the future but at present experience is
limited.
The hospital policy on MRSA must be followed. Patients should be seen last
on ward rounds and in an isolation area in the outpatient department.
Atypical Myocobacteria
Consider treating the mycobacteria if patients do not respond to conventional
antibiotic therapy. Treatment length should be 6 to 12 months.
Aspergillus Fumigatus
(see Section 2.5)
2.2.2 Macrolides
There is emerging evidence for the beneficial use of azithromycin in children
with CF. In addition to the antibacterial properties it is thought that
azithromycin may work by a variety of anti-inflammatory mechanisms.
29

When should it be prescribed?
a) Infective exacerbation in chronic P. aeruginosa infection
In patients known to be chronically infected with P. aeruginosa, in addition
to nebulised antibiotics, the drug of choice is ciprofloxacin, which is usually
prescribed for two to three weeks. There is in vitro evidence of a synergistic
effect with azithromycin. Therefore consideration should be given to
prescribing azithromycin together with ciprofloxacin at the following dose:
40 kg 500mg once a day for two weeks
Anti-staphyloccocal therapy can be stopped for the duration of azithromycin
treatment if S. aureus is not present in sputum.
b) Declining lung function and clinical state
Long-term azithromycin should be considered for a six-month period in the
following patient groups:
Over eight years of age (may be used in younger children but this has not
been formally studied) with FEV1

Studies to date have used different dosing regimens and it is unclear at
present which dosing interval should be used. This protocol is based on the
current best evidence. Of note, there is no toxicology data for the regular use
of azithromycin for more than six months in patients with CF. It is known
that after four weeks, levels of azithromycin in sputum plateau but because of
the long half-life there is the potential for continued accumulation in tissues.
Important side effects to monitor include; hearing and liver function. Liver
function tests are performed annually. Formal audiological tests are not
routinely performed, unless there are concerns regarding hearing. Changes
caused by azithromycin are usually reversible.
2.2.3 Desensitisation
Occasionally, antibiotic therapy is difficult if patients have become sensitised
to a variety of different classes of antibiotics. In these cases desensitisation
should be considered according to GOSH pharmacy guidelines.
2.2.4 Home IVs
Admission to hospital allows for intensive physiotherapy to be given during
this period as well as providing additional opportunity for attention to dietary
intake and calorie counting. Home therapy, however, is less disruptive to a
child’s routine and may be more appropriate, especially in those older
children requiring frequent courses of intravenous therapy (see Sections 2.4).
Continued attendance at school can often be maintained.
The decision to institute home therapy must be made on an individual basis
after careful consideration of the social situation, expected levels of adherence
and ability to cope with the increased burden of care. Thorough parental and
patient education in the administration of IV antibiotics and other treatment
regimens is essential. Parents should be assessed for competency in
administering IV drugs by nursing staff. The first three doses should be given
in hospital. All home IVs should be co-ordinated with the CF homecare
nurse specialist. Patients must be re-assessed after one week of treatment to
monitor progress and antibiotic levels.
2.3 Nebuliser Therapy
There are three different nebuliser systems and one portable compressor in
use at GOSH. The systems are regularly reviewed and updated and changes
can be expected.
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2.3.1 On the ward
It is unnecessary to use portable compressors on the ward, as wall air and
oxygen is available at all bed spaces. This should be dialled to a flow of six to
eight litres per minute.
Nebulisers:
For bronchodilators or mucolytics:
Sidestream disposable nebuliser with angled mouthpiece. Masks are
available for very young children.
For antibiotics:
Ventstream with filter and mouthpiece (MedicAid) to be used with
System 22 disposable Sidestream nebuliser (with connector for T-piece).
For DNase:
Disposable Sidestream nebuliser with angled mouthpiece.
2.3.2 Outpatients
If a patient requires nebulised medication at home then a Medicaid Portaneb
portable compressor can be loaned by the hospital. It is important that this is
serviced on an annual basis and the patient should bring the compressor with
them to their annual review for this purpose. The portaneb is supplied and
serviced by the Biomedical Engineering Department and is available from
staff during CF clinics.
Nebulisers:
For bronchodilators or mucolytics:
Sidestream (MedicAid) nebuliser with angled mouthpiece.
Masks are available to fit this system for very young children.
For antibiotics:
Pari LC Star (clear pot with maroon insert) with filter value system.
Can be used with a low flow compressor.
Masks are available to fit this system for very young children.
Filters are for single use only.
Used for colomycin and aminoglyocides but not TOBI
or
32

Pari LC Plus (clear pot with clear or blue insert)
Can be used with a low flow compressor.
Masks are available to fit this system for very young children.
Filters are for single use only.
Used for colomycin and other aminoglyocides including TOBI
For DNase:
Pari LC Plus (yellow pot)
Can be used with a low flow compressor.
2.3.3 General comments
1. All nebulised antibiotics should be vented either using a filter system or a
T-piece with wide bore non-corrugated tubing to vent the expired gases
through a window. Venting prevents antibiotic deposition on electronic
appliances, furnishings etc. and reduces the risk of antibiotic resistance.
2. When nebulising any medication the volume should ideally be made up
to three or four mls with normal saline.
3. Bronchodilators and mucolytics can be mixed immediately prior to
nebulisation.
4. DNase should not be mixed with any other medication.
5. All bronchodilators and mucolytics should be given prior to
physiotherapy. Steroids and antibiotics should be given after
physiotherapy. DNase should be administered at least one hour prior to a
physiotherapy session. Recommended regimens of DNase administration
are outlined below (figure 5)
6. A leaflet is available for parents and patients on the care of the nebuliser.
2.3.4 Adaptive Aerosol Delivery System
(AAD)
Improvements to the delivery systems for nebuliser therapy are continually
being made, particularly in terms of efficacy and time required for drug
delivery. AAD technology adapts to individual breathing patterns and targets
antibiotic delivery to the inspiratory phase of the respiratory cycle. It is
electronically programmed to deliver a precise pre set dose of medication.
One type of device that has recently come onto the market is called Prodose
AAD System from Profile Pharma Ltd. It uses this technology to deliver the
company’s own version of colistin (Promixin - colistimethate sodium). It can
33

only be used on children who are able to use a mouthpiece, as there is no
mask attachment. An increase in chest tightness with delivery of antibiotics
using this device has been documented but it is suggested that this may be
due to improved delivery of drug. The use of a bronchodilator prior to
antibiotic inhalation is recommended.
2.4 Totally Implantable Venous
Access Devices (TIVAD)
The totally implantable venous access device (TIVAD) is used for intravenous
antibiotic administration in patients with CF. The Portacath is currently used
at GOSH although there are many other systems available. Suppliers and
ordering instructions can be found in Section 9.
The TIVAD consists of a small metal chamber with a self-sealing silicone
diaphragm. Leading from the chamber is a long thin flexible catheter. At
implantation (under general anaesthesia) the tip of the catheter is positioned
in the superior vena cava, cephalic or jugular vein by cut-down or by
percutaneous introduction into the subclavian vein. A subcutaneous pocket is
then prepared on the lateral chest wall under the arm. The chamber is
connected to the catheter which has been routed subcutaneously to the site
and sutured in place. The system is then flushed with heparinised saline to
check for patency and the skin sutured over the chamber and catheter
insertion site. Special non-coring needles must be used with this device.
TIVADs are offered to patients who are requiring IV antibiotics on a frequent
basis or if there is a problem with repeated intravenous cannulation.
Discussion, planning and initial education is carried out during CF clinic
visits and on the ward. TIVADS are not a solution for needle phobia as
needle insertion is required for monthly flushing.
2.4.1 Hospital admission
for insertion of TIVAD
The admission for insertion of a TIVAD depends on the severity of chest
disease. Occasionally children need to be admitted a few days prior to surgery
for intensive chest physiotherapy and sometimes for IV antibiotics.
Following the insertion of a TIVAD analgesia is very important so that
physiotherapy and daily activities can be continued. A CXR is undertaken to
check the position of the device and ensure there is no pnuemothorax.
Physiotherapy and early mobilisation are important to prevent further
complications. The child is usually ready to go home one or two days
following surgery.
34

The TIVAD can be used immediately if necessary and the surgeons should be
asked to leave the needle in place. From then on the port should be flushed
once a month unless a course of antibiotics is in progress. A no-touch
technique and a straight bevelled needle should always be used. During IV
therapy the needle should be changed every two weeks. Blood should not be
taken routinely from the port.
2.4.2 Complications
If blockage is suspected, position of the needle should be verified first by
gently pressing on the needle. Attempt to flush with normal saline via a 10ml
syringe, if resistance remains a CXR should be done to rule out catheter
malrotation, kinks or port rotation. If the CXR is normal Alteplase
(1mg/1ml) should be given into the catheter tube. This should be left for two
hours and then an attempt is made gently to flush the port.
Line infection usually requires port removal. Following blood cultures, systemic
antibiotics via another line may help. There is risk of thrombus so careful handling
is a priority and injecting into the line should be undertaken with caution. The
child should be referred back to GOSH if a line infection is suspected.
2.5 Other Pulmonary Complications
2.5.1 Wheezing and bronchospasm
Wheezing is a common finding in children with CF and can present as a
symptom in up to 50% of patients. This may occur because of airway
narrowing secondary to infection and localised oedema or as a primary
increase in bronchial hyperreactivity. Allergic bronchopulmonary aspergillosis
should also be excluded in wheezy children with CF (see below).
The response to bronchodilators in CF is variable and a proportion (10 to
15%) of patients may in fact show a deterioration after the use of betaagonists.
Lung function tests to demonstrate a positive bronchodilator
response should be performed whenever possible before bronchodilators are
prescribed long term to ensure that their use is appropriate.
Exercise induced asthma is common and can be demonstrated on exercise
testing. Inhaled Salbutamol or Terbutaline before exercise may significantly
improve the patient’s exercise abilities. The role of the anti-leukotriene agents
such as Monteluekast may also prove useful in the future.
35

2.5.2 Haemoptysis
Occasional streaking of the sputum with blood is common and signifies
underlying infection or mucosal trauma associated with severe coughing
spells. In this situation, mucolytics should be stopped. Haemoptysis also
occurs with Aspergillus infection especially when accompanied by wheezing.
Larger episodes of haemoptysis can be sudden in onset and dramatic. These
generally follow a localised infection of the bronchial wall and rupture of an
adjacent arteriole. This rare complication is mainly seen in adolescents or
adults with extensive lung disease. In severe cases it requires invasive
haemostasis using catheter placed plaques of gel foam or metal coils inserted
into bronchial arteries supplying the region of bleeding. Acute surgical
resection of the affected lobe is required if other more conservative measures
fail. Attention to oxygenation, blood replacement and vitamin K
administration should be carried out before any of the above procedures.
2.5.3 Pneumothorax
A pneumothorax may occur following increased transpulmonary pressure on
hyperinflated lungs. This is most commonly seen in adolescents with
advanced lung disease and presents with the acute onset of pleuritic chest
pain and respiratory distress, the diagnosis is confirmed on chest x-ray.
A large acute pneumothorax requires intercostal drainage (ICD). A small
pneumothorax can be closely observed and treated conservatively with high
inspired oxygen for 48 hours to aid resolution. Intercostal drains are not
without complication in the CF patient. Immobilisation interferes with
effective physiotherapy and persistent air leaks are common.
Pneumothoraces can be recurrent and troublesome and in these circumstances
a pleurodesis may be indicated following consultation with the thoracic
surgeons. Limited pleurodesis is preferred as generalized pleurodesis in this
situation can complicate future lung transplantation.
2.5.4 Aspergillosis
Aspergillosis fumigatus is not uncommonly seen in the sputum of patients
with CF and many have positive skin tests, demonstrating an immediate
hypersensitivity to the organism. Despite this, allergic bronchopulmonary
aspergillosis (ABPA) is uncommon.
ABPA presents with recurrent wheezing in association with deteriorating
chest symptoms. Investigations include a positive early and late reaction on
skin testing, elevated total and specific IgE and the presence of serum
36

precipitins, eosinophilia on full blood count and a positive culture of the
organism from the sputum. The chest x-ray commonly shows bilateral fluffy
shadows.
Patients who are symptomatic, generally respond to oral Prednisolone one to
two mg/kg/day for two weeks with a gradual reduction in dose thereafter over
four weeks. Patients who develop signs of invasive bronchopulmonary
aspergillosis should be treated with anti-fungal agents such as oral
itraconazole or inhaled amphotericin. Lung function tests and CXR are used
to monitor progress. Recent studies have shown a high incidence of adrenal
suppression in CF children treated simultaneously with inhaled cortosteriods
and itraconazole. Combined treatment with itraconazole and inhaled or oral
corticosteroids should therefore be used with caution and the patient closely
monitored.
2.5.5 Segmental bronchiectasis
The place for lung resection in CF is limited because the pulmonary
involvement is invariably generalised. Sometimes, however, segmental
bronchiectasis acts as a focus for infection, haemoptysis and ill-health in a
patient whose other lobes are normal or only minimally diseased. In such
circumstances, local resection can improve the child’s general health and
protect the other lobes from danger of ‘spill-over’ damage.
2.6 rhDNase Therapy
CF sputum contains large amounts of DNA derived from neutrophils.
Aerolised rhDNase (Pulmozyme) is a synthetic enzyme that cleaves DNA and
is used as a mucolytic to decrease sputum viscosity and aid expectoration.
Clinical trials have shown that it is safe and effective with an improvement in
lung function of about ten percent initially, with a plateau improvement over
a year of approximately six percent and a decrease by one third in the number
of respiratory exacerbations. Apart from some transient hoarseness and
alteration in voice quality, there have been no serious adverse reactions.
Currently rhDNase (Pulmozyme) is licensed for use in children over the age
of five years. A trial of therapy is recommended in children who are chronic
sputum producers with difficult expectoration or lung function that is
deteriorating below 70% predicted.
Pulmozyme (2.5mg) can be administered once daily or on alternate days via
nebuliser. It has been shown that alternate day can be as effective as daily
treatment in individual cases. Pulmozyme should be given at a time
convenient to the family at least one hour prior to the next physiotherapy
session. If benefit is documented by an improvement in lung function,
subjective criteria or improved weight gain over a trial period of four to six
37

weeks then long term maintenance therapy may be warranted. The cost of
DNase long term is not insubstantial and for this reason the responsible
purchaser must be made aware of its use at the beginning of the trial period
and be willing to continue funding should benefit be proven. Shared care
guidelines for the use of DNase are available from the CF clinic.
2.7 Oxygen Therapy
and Assisted Ventilation
Oxygen therapy can be used acutely or long term when chronic hypoxia has
been established. Oxygen may first be required during a chest exacerbation
when oxygen saturations fall below 92% and is delivered by nasal cannulae or
face mask. Frequently, with antibiotic therapy and increasing sputum
clearance, the saturations will return to normal and oxygen supplementation
is no longer required. As lung disease advances children may become
chronically hypoxic. The commonest symptoms are early morning headache
and daytime drowsiness. Exercise tolerance will also be severly curtailed.
Overnight oxygen saturation measurement is required to determine the level
of hypoxia and to document correction with supplemental oxygen delivery.
The use of overnight oxygen usually improves the quality of sleep and
eradicates morning headaches. Patients may also find oxygen useful in the
daytime during physiotherapy, during or after exercise and with meals. It can
allow patients to continue attendance at school. Oxygen can be supplied by
various fixed and portable systems; cylinder, via a concentrator or liquid
oxygen system.
Oxygen may also be required during aircraft flights or on holidays at high
altitude. Evaluation of the effects of altitude can be performed by the ‘fitness
to fly’ test. Patients breathe an inspired oxygen of 15% in the laboratory and
the level of hypoxaemia is assessed. A useful predictor of desaturation during
flight is an FEV1 of less than 50%. Should oxygen be required a charge is
often made by the airline and arrangements should be made well in advance
of travel.
The use of assisted ventilation in cystic fibrosis is controversial. Most centres
would consider it inappropriate to intubate and ventilate a child with CF and
terminal lung disease. Ventilation would be considered in the presence of
potentially reversible factors or a severe chest infection in a young child. Such
decisions need to be made individually by the CF team in conjunction with
the family.
Non-invasive ventilation can be a useful bridge to transplant. It can also be
used for the treatment of acute decompensation during a treatable chest
exacerbation. The role of long term non-invasive ventilation for chronic
respiratory failure in CF is still unclear.
38

Section Three:
Nutritional Management
3.1 Nutritional Management
Importance of nutritional status
Malnutrition is not an inevitable consequence of CF and can be prevented or
corrected. Poor nutritional status can lead to:
• Stunted growth, delayed onset of puberty/sexual development.
• Weight loss due to loss of adipose tissue and muscle wasting (including
the respiratory muscles). This can eventually impair the ability to cough
leading to an increase in respiratory infections and decline in lung
function. Appetite may be further affected by the large amounts of
mucus swallowed due to inadequate coughing.
• Poor body image, leading to depression and school absenteeism.
• Decreased immune function.
• Specific signs of certain nutrient deficiencies (e.g. of fat soluble vitamins
or essential fatty acids).
Patients with CF may have altered nutritional requirements as a consequence
of three interrelated factors: malabsorption, increased energy expenditure and
poor intake.
a) Malabsorption
Increased stool losses of fat, fat soluble vitamins and protein often occur in
CF due to one or more of the following:
• Pancreatic enzyme deficiency (affecting >85% of patients).
• Low intestinal pH, secondary to lack of pancreatic bicarbonate and over
production of gastric acid. Some patients with persistent malabsorption
may benefit from H2 receptor antagonists such as ranitidine taken 30
minutes before meals or proton pump inhibitors such as omeprazole
once daily.
• Excessive, viscous intestinal mucus presenting a physical barrier to
nutrient absorption.
• Bile salt abnormalities (both quantitative and qualitative) due to
decreased ileal bile reabsorption and increased stool losses.
39

) Increased energy expenditure
There is still controversy in the literature over whether the primary cystic
fibrosis defect is an energy requiring one. Assessments of resting and total
energy expenditure suggest that elevated energy expenditure in CF may only
accompany advancing lung disease and possibly particular genotypes (e.g.
homozygous (∆F508). Other contributions to energy expenditure include the
energy cost of laboured ventilation and the presence of infections which can
impose an increased energy demand. Pyrexia increases calorie requirements by
13% per °C rise in body temperature.
c) Poor intake
Despite many young, untreated patients presenting with a voracious appetite,
the converse is seen in a large proportion of older children with CF. The
reasons for this include:
• Gastro-oesophageal reflux in many patients with CF, leading to
oesophagitis and dysphagia.
• Avoidance of food because of an association with nausea, flatulence and
abdominal distension.
• Rebellion against continual pressure to eat.
• Peer group/media pressure to be slim and on a ‘healthy’ diet.
• Timing difficulties with physiotherapy.
• Depression.
• Refusal of food because of embarrassment at passing offensive stools.
• Poor appetite (further exacerbated by malnutrition).
The help of the team’s clinical psychologist can be useful in establishing the
importance of psychological factors.
3.1.1 Nutritional priorities
a) Energy and protein
Daily energy requirements may be between 100-150% of the Estimated
Average Requirements (EAR) for age (see table below). The higher energy
needs may only be necessary as pulmonary disease progresses and/or a child
has recurrent infections. The dietitian can assist with estimation of an
individual child’s requirements. However, in practice the only proof of an
adequate energy intake is weight gain and growth.
Restriction of dietary fat is not appropriate as this would limit a concentrated
source of energy, fat soluble vitamins and essential fatty acids. Children with
40

iliary cirrhosis, intractable steatorrhoea or repeated distal intestinal
obstructive syndrome (DIOS) may require some degree of fat restriction.
Protein malnutrition is rarely a problem in CF as most children take in excess
of normal requirements so counteracting stool losses. However, some infants
fed on breast milk may require protein supplementation using a powdered
infant formula. Serum albumin is an indicator of protein status but because
of its long half life is not a very reliable indicator.
Table: Range of Daily Energy Requirements
for Cystic Fibrosis (%EAR)
Age
Male & Female
100% 120% 150%
0-3 months 100-115 kcal/kg 120-140 kcal/kg 150-170 kcal/kg
4 months-3 years
Male
95 kcal/kg 115 kcal/kg 140 kcal/kg
4-6 years 1715 2000 2600
7-10 years 1970 2400 3000
11-14 years 2220 2700 3300
15-18 years 2755 3300 4100
Female
4-6 years 1545 1800 2300
7-10 years 1740 2100 2600
11-14 years 1845 2200 2800
15-18 years 2110 2500 3200
Adapted from Dietary Reference Values HMSO, 1991 (DoH publication report no 41).
b) Vitamins
Malabsorption of fat soluble vitamins (A, D, E and K) is common in patients
with CF and deficiency states have been reported. Poor appetite may also
result in inadequate intake of water soluble vitamins (B & C) and these are
commonly included in the oral supplements. Children with CF should
receive a multivitamin preparation containing vitamins A and D, together
with a separate vitamin E supplement. (See Pharmacopoeia for suggested
doses).
The multivitamin preparation Dalivit is used for infants and toddlers. Older
children should take an appropriate multivitamin tablet or capsule. The more
comprehensive vitamin supplement Ketovite (tablets and liquid) is useful for
children on very limited diets.
41

Vitamin K is not routinely given as a supplement but may be necessary for
those with underlying liver disease, extensive bowel resection or a prolonged
clotting time. Contributory factors to vitamin K deficiency in CF include
malabsorption, decreased bacterial synthesis (due to long term antibiotics)
and poor intake.
Annual monitoring of vitamin levels should be carried out for A, D and E
and dosage altered as indicated. If a patient is unwell at the time of the blood
test, serum levels of vitamin A may not be reliable. Care should be taken to
prevent overdosing with fat soluble vitamins as oral nutritional supplements
and enteral feeds are fortified.
c) Salt
Salt supplements may be necessary in any situation that increases sweat
production such as during very hot or humid weather, high fever or vigorous
periods of exercise. For patients with signs and symptoms of salt depletion
(cramps, lethargy and dehydration), extra salt can be added onto foods or
(more rarely) sodium chloride tablets prescribed.
3.1.2 Practical dietetics
a) In infancy
Infants with CF can either be breast fed or fed an infant formula. Breast
feeding provides immunological protection and some natural lipase and
amylase along with psychological benefits for mother, so should be
encouraged. Breast fed infants still require appropriate pancreatic enzyme
supplementation (see section 3.2).
If infants fail to thrive despite the use of pancreatic supplements, the feeding
regimen may need to be modified. For breast fed infants, an increase in
frequency of feeding may be all that is required to achieve adequate weight
gain; or expressed breast milk can be fortified with an infant formula or
glucose polymer. Energy supplements (glucose polymers ± a fat emulsion) can
be added to a standard infant formula. In hospital, pre-pack feeds of Low
Birth Weight SMA (SMA Nutrition) have a high energy density and can be
used at ward level. Sometimes a high-energy infant formula such as Infatrini
(Nutricia) is indicated. Further modifications to standard feeds can be
prepared in the hospital milk room and parents instructed on their
preparation prior to discharge home.
Solids can be started between the ages of four and six months with
appropriate enzyme supplementation. Extra energy as fat and/or carbohydrate
may be added to these solids if weight gain is poor. An infant formula should
be used in preference to cow’s milk until at least one year to ensure a good
nutrient intake.
42

) In older children
Many children with CF require high-energy meals and frequent snacks to
achieve their energy requirements and maintain weight gain. Supermarket or
prescribable energy supplements (drinks and powders) can be used and a list
of suitable products is available from the dietitian. Milk based energy
supplements will require pancreatic enzymes to aid digestion.
At GOSH, CF in-patients have their energy intakes estimated each day by
the nursing staff and compared to a target set for their requirements. The
following high energy drinks are available from the milk room in addition to
proprietary supplements:
GOSH shakes - Milkshakes providing 1.2kcal/ml in vanilla, chocolate,
banana or strawberry flavours.
Maxijul - a glucose polymer made into 10, 15 or 20% solutions
(providing 40, 60 or 80kcal/100ml). This can be used in place of water
to prepare squash or Ribena and is tasteless so can also be added to other
drinks.
Children who fail to gain height and weight (despite dietetic advice) should be
given the option of supplementary tube feeding (see section 3.4). Gastrostomy
is the preferred route for older children.
c) CF related diabetes mellitus (see Section 7.1)
A strict carbohydrate controlled, low fat, high fibre diet is inappropriate for
diabetes accompanying CF as this would compromise energy intake. The
main principles of dietary management are as follows:
• To limit sugary drinks or supplements to mealtimes only, choosing sugar
free varieties at other times. High sugar foods such as cakes, biscuits and
chocolate are best taken at the end of a meal or prior to exercise. It is
preferable that sugary foods be eaten together with starch or fat to delay
its absorption e.g. a chocolate bar and a glass of milk.
• Starchy foods should be included with every meal/snack e.g. bread,
breakfast cereal, crackers, biscuits, crisps, potato, rice, pasta, noodles.
• A regular daily pattern of three meals and three snacks should be
followed. The bedtime snack is particularly important and should not be
missed.
• A high energy/high fat diet should be continued.
• Patients can treat hypoglycaemia by the immediate use of quick acting
carbohydrate such as fruit juice, fizzy drink or glucose tablets; followed
by longer acting carbohydrate e.g. bread or toast, biscuits, yogurt, cereal.
43

d) Post-Intestinal Surgery
Infants who have undergone surgery for meconium ileus may develop
temporary disaccharide intolerance. As a precaution the use of a hydrolysed
protein feed post surgery is sometimes indicated. Pregestimil (Mead Johnson)
or Pepdite (Scientific Hospital Supplies) are both suitable infant formulae,
being sucrose and lactose free and having a proportion of the fat in the form
of medium chain triglycerides (MCTs). These feeds are prepared in the milk
room at GOSH, and do require appropriate enzyme supplementation
Infants may be discharged home on these products and the dietitian will
advise the parents on feed preparation and prescription (via the General
Practitioner). Thriving infants should be challenged with a standard infant
formula within three months of the surgery. If this fails, sucrose and lactose
free weaning advice may need to be given.
e) Liver and Biliary Problems (see section 7.2)
Tolerance of dietary fat and protein may be reduced in patients with liver or
biliary involvement. If dietary restrictions are necessary, energy intake must
still be maintained and adequate fat soluble vitamin status ensured.
Introduction of ursodeoxycholic acid may aid absorption in these patients.
3.1.3 Hospital dietetic service
The CF Unit at GOSH has a dietitian who specialises in the care of infants
and children with cystic fibrosis. Her role is to plan dietary management,
assess and monitor nutritional status and offer advice on the use of pancreatic
enzyme and vitamin supplements. The dietitian visits the respiratory ward
daily, routinely reviews CF patients attending the outpatient clinic and takes
part in the assessment of CF patients attending for annual review.
The following patient advice sheets are available from the dietitian
• CF Trust booklets: Nutrition: Eating well with Cystic Fibrosis. A guide for
feeding infants.
• Getting the balance right between fat intake and enzymes
• Calcium. Are you getting enough?
• Information Sheet on Dietary Management of CF Related Diabetes
• Ways to increase calories in your diet
• Increasing the energy content of your diet
44

3.2 Pancreatic Insufficiency
Pancreatic insufficiency is present in about 85-90% of the CF population.
Patients who are homozygous for the common ∆F508 mutation have a 99%
chance of being pancreatic insufficient. This can lead to a variety of
manifestations, including steatorrhoea, malnutrition, fat-soluble vitamin
deficiency, growth failure and rectal prolapse. Distal intestinal obstruction
syndrome (DIOS) can also occur.
Pancreatic elastase can be measured on a 1 cubic centimeter stool sample, at
any age. Specimens are sent to virology (for the attention of David Cubbitt)
at GOSH for analysis. Normal levels are in excess of 500µg/g. CF patients
usually have levels below 200µg/g. In pancreatic insufficient CF patients
undetectable levels are frequently reported.
The gold standard for assessing pancreatic insufficiency is by direct sampling
and measurement of the pancreatic juices in the second part of the
duodenum after stimulation. In practice, this is rarely done and is restricted
to specialist paediatric gastroenterology centres.
3.2.1 Pancreatic enzyme supplementation
There is no standard enzyme dose. The correct dose is that which
symptomatically corrects steatorrhoea, abdominal pain and decreases
frequency and mass of stools. More enzymes may be needed with a fatty meal
or if stools are loose, frequent, offensive, pale and oily. Completely normal
stools may never be achieved in some cases.
Infants: Enteric coated mini microsphere enzyme preparations (Creon 10000,
Solvay) are started in young infants. The starting dose is usually a quarter
capsule per feed. The gelatine capsule is opened and the granules mixed with
a little soft food such as fruit puree and given at the start of the feed.
Alternatively, it can be mixed with some breast or formula milk on a spoon
but should not be added to the baby’s bottle.
Children: patients either swallow the capsules whole (over five years) or
empty the granules directly into their mouth. The granules should not be
chewed or crushed as this destroys the enteric coating. High doses of enzyme
have been linked to the occurrence of colonic strictures (fibrosing
colonopathy, see section 3.7). The use of high strength preparations is now
discouraged in children and an upper limit of 10,000 international Lipase
Units/Kg body weight/day has been suggested.
45

For cases of persistent steatorrhoea the following should be checked:
• Is the child actually taking their enzymes with all meals and snacks?
• Check stated dose per meal and snack against the reported daily total.
• How are they taken?
• Ideally, the dose should be split through a meal (half at the start, half in
the middle) but failing this they can be taken at the beginning of the
meal. The enteric coated preparations should not be crunched or mixed
in with the whole feed.
• Is the amount of enzyme altered with the fat content of the meal?
• Has a previous increase in enzyme dose improved digestion?
If not, has an H2 receptor antagonist (e.g. ranitidine) or proton
pump inhibitor (e.g. omeprazole) been tried?
• Are the enzymes stored correctly?
Enzymes should be stored away from heat as this denatures the
enzyme. Are the enzymes used still in date?
• Are the enzymes taken with large volumes of fluid?
Although it is important that children with cystic fibrosis drink
plenty of fluids, taking enzymes with large volumes of fluid can
result in the enzymes being washed too quickly through the gut
leaving food but little enzyme for digestion.
Stool microscopy can be undertaken to check for the presence of unabsorbed
fat (stool elastase levels are unaffected by exogenous enzyme administration).
Foods not requiring enzymes include:
• Fruit (except avocado)
• Vegetables (except potatoes, beans, peas and olives)
• Sugar, jam, honey or syrup
• Fruit juice, fizzy drinks, squash or water
• Sorbet or fruit lollies
• Special products such as glucose polymer powders and liquids and fruit
juice based supplements e.g. Fortijuce.
46

3.3 Growth and Puberty
Close monitoring of linear growth and weight should be carried out at each
clinic visit. Measurements should be plotted on appropriate centile charts and
height velocity calculated from measurements made over six monthly
intervals.
Infants with CF often grow poorly in the first year of life, particularly before
the diagnosis is made. Catch-up growth usually occurs once treatment is
established so that expected height for age is reached by five years. Growth
during middle childhood is usually normal but a period of slow growth is
often noted in the pre-pubertal period, leading to a decline in the centile rank
around this age. The majority of patients with CF show some delay of growth
in late childhood and this problem is exacerbated by the late onset of puberty
that is commonly associated with CF. Children do tend to keep growing for
longer than normal so they often regain their original height centile. The final
height in the majority of patients therefore tends to fall within the normal
range although often less than that expected from mid-parental height.
Pubertal development should also be monitored. Patients with delayed
puberty should be referred to the growth clinic. Estimation of bone age (x-ray
of left hand and wrist) is best performed at the endocrine clinic itself rather
than before referral. Depending on individual circumstances, some patients
will be offered hormone therapy to aid onset of puberty. This is usually of
great psychological benefit and does not appear to reduce final height.
CF itself does not involve a primary abnormality of growth hormone
secretion. Growth problems are usually related to poor nutrition, recurrent
infections and disturbed lung function. Optimising CF therapy is therefore
very important in the management of those with a falling height centile for
age.
Bone density (DEXA) scans should be performed at annual review in those
with delayed onset of puberty and any patient on long term oral steroids.
3.4 Gastrostomy Tube Feeding
Long term supplementary tube feeding may be necessary for some children
with CF. At GOSH a gastrostomy is preferred to nasogastric feeding for the
following reasons:
• Nasogastric (NG) tubes may be dislodged with physiotherapy and
coughing.
• The presence of an NG tube may irritate the nose and throat and can be
difficult to pass in individuals with nasal polyps.
47

• Children may be reluctant to go to school with an NG tube in situ.
• Gastrostomy tubes are less obtrusive.
The indication for gastrostomy feeding is a documented period of inadequate
growth (height and weight) secondary to an inability to meet energy
requirements. Oral intake should first be optimised by regular discussions
with the dietitian and, if indicated, the psychologist. If weight gain remains
static for a further six months, gastrostomy feeding should be considered. The
CF team will discuss any social, psychological and clinical factors that may
influence this decision.
3.4.1 Gastrostomy techniques
Currently GOSH uses two gastrostomy techniques. These are outlined below.
a) Percutaneous endoscopic gastrostomy (PEG)
This gastrostomy tube is introduced percutaneously with an endoscope under
a general anaesthetic. At GOSH the standard PEG set used is made by
Fresenius (see Section 9). Feeding can commence 24 hours after insertion.
The tube should be changed at the discretion of the CF team, but can remain
in situ for several years. Changing of the tube requires a general anaesthetic
with a one to two night stay in hospital. It has been recommended by
Fresenius that removal of the tube should be performed endoscopically to
prevent bowel obstruction. However, this may not happen in practice.
48
Figure 6:
PEG device

Figure 7:
MIC-KEY
gastrostomy
button
b) Gastrostomy Button
The button is a skin level, silicone anti-reflux feeding device. In practice there
may be problems with leaking around the button site and repeated local skin
infections leading to granuloma formation. However, some children will
prefer this less obtrusive device even with the associated problems. The
button can only be inserted into a previously established stoma and this can
be performed as an outpatient. The initial stoma is formed under general
anaesthetic and a replaceable gastrostomy tube inserted (Corpack). This is left
in position for six to eight weeks before being replaced with the button
device. The stoma nurse specialist or one of the surgical registrars should
carry out the first change of this tube.
3.4.2 Admission procedure
Planning an admission for a gastrostomy must include liaison with the Cystic
Fibrosis Clinical Nurse Specialist to establish links with the local community
children’s nursing team before admission. This must be set up before
discharge to ensure that long term supplies of pumps and equipment is
established. The duration of admission will depend on the severity of chest
disease (e.g. requiring intravenous antibiotics and intensive physiotherapy
prior to surgery) and the tolerance of feeds.
3.4.3 Feeding regimen
Feeds can be started 24 hours after the insertion of a PEG if bowel sounds are
present. Continuous overnight feed administration via a feeding pump over
seven to ten hours (as practical) is the approach preferred by most children. A
one to two hour break off tube feeds before morning physiotherapy can
reduce nausea. Most children will thrive if about two-thirds of their estimated
energy requirements are provided from an overnight tube feed.
Hyperglycaemia has been reported in some older children following initiation
of overnight feeds and so blood sugars should be monitored first thing in the
morning during the hospital admission.
49

The type of feed chosen will depend on the age of the child and their current
malabsorbtive problems.
Under one year of age: Infant formulas (fortified if appropriate) or
High Energy Formula e.g. Infatrini (Nutricia)
One to ten years of age: A complete whole protein based liquid feed
with an energy density of 1kcal/ml e.g. Nutrini
(Nutricia) or Paediasure (Abbott) or
1.5kcal/ml e.g. Nutrini Extra (Nutricia) or
Paediasure Plus (Abbott)
Over ten years of age: A complete whole protein based liquid feed
(1.5kcal/ml) e.g. Ensure Plus (Abbott)
For some children with poor absorption or who are unwilling to take
enzymes or who already take a large dose of enzymes, an elemental tube feed
Emsogen (Scientific Hospital Supplies) may be helpful. This has protein in
the form of amino acids, carbohydrate as glucose syrup and 83% of the fat as
MCT. It is produced in 100g sachets of powder and can be reconstituted to
provide up to two kcal/ml if necessary.
For all feeds, initial delivery rates should be slow (e.g. 30ml/hour) but the
rate can be increased by 20-30ml/hour each night. In some cases it may be
beneficial for a child to stay in hospital until the final feeding regime is
established. However, in practice many parents feel confident to continue the
planned changes at home. Children with diabetes require careful titration of
their insulin to the feed and should remain in hospital until their blood
sugars have been stabilised.
At this hospital, enzymes are given before and after the feeding period. The
dose chosen is based on that taken with a typical meal but this may need
adjusting.
3.5 Meconium Ileus
Ten to fifteen percent of newborn babies with cystic fibrosis present with
symptoms of intestinal obstruction within 24 hours of birth. Inspissated
meconium, often containing air bubbles on X-ray, fills a varying length of the
intestine particularly the ileum. The bowel is collapsed distal to the
obstruction and dilated proximally. The degree of obstruction may vary from
delay in the passage of meconium to complete occlusion of the bowel lumen.
Additional complicating sequelae can occur in the form of bowel perforation,
volvulus or atresia.
50

The diagnosis of CF should be confirmed by genotyping or by a sweat test.
Meconium ileus on rare occasions can occur in infants who do not have CF.
Serum immunoreactive trypsin is only useful as a screening test and is not
diagnostic. A recent blood transfusion is not a contraindication to attempted
genotyping on the infant. If in doubt gentyping can also be performed on the
parents.
Management
1. If clinical or radiological evidence of a surgical complication such as a
perforation, volvulus or atresia is present:
• Attend to fluid and electrolyte replacement and acid-base balance.
• Seek a surgical opinion: the current surgical procedure involves an
end-to-end or end-to side anastamosis following resection of the
necrotic bowel. Ileostomy is now only undertaken in exceptional
circumstances.
• Physiotherapy, prophylactic antibiotics and enzyme replacement will
need consideration immediately post-operatively.
• Some infants may be troubled by post-operative malnutrition and
will require special formulae feeds such as Pregestimil (see Section
3.1) or TPN
2. If there is no evidence of surgical complications consider conservative
management under the primary care of a surgical team.
• Attend to fluid and electrolyte replacement.
• Consider a diluted Gastrografin enema, preferably under
fluoroscopic control. Additional intravenous replacement may be
necessary. This procedure may need to be repeated and is best
undertaken in a specialised paediatric surgical unit as urgent
operative intervention may still be required if it fails.
Post operative feeding regimens are discussed under section 3.1.
3.6 Distal Intestinal Obstructive
Syndrome (DIOS)
This term describes the accumulation of tenacious, muco-faeculent masses in
the distal ileum or caecum which may become adherent and calcify. The
cause is unclear but appears to be associated with dehydration, fever, the
reduction of enzyme supplementation, liver disease and the use of anticholinergic
and opiate drugs. Although it occurs most frequently in those
over 15 years, it can occur at any age.
51

Other conditions which should be considered in the differential diagnosis
include:
• Constipation
• Intussusception
• Acute appendicitis
• Acute pancreatitis
• Volvulus
• Strictures of colon or ileo-caecal junction
• Obstruction due to adhesions or strictures
DIOS presents acutely with signs of abdominal obstruction or more
commonly, sub-acutely with cramping abdominal pain and relative
constipation. A palpable mass is often palpable in the right iliac fossa. The
management varies accordingly to severity (see table)
In all patients:
• Check dose of pancreatic enzymes
• Check compliance with medications
• Ensure adequate dietary roughage
• Ensure adequate fluid intake
• Ensure patient has a well-established toilet routine
• Consider adding ranitidine or omeprazole if ongoing malabsorption
• Check timing of enzymes and consider possible mismatch in gastric
emptying between food bolus and pancreatic enzymes
3.7 Fibrosing colonopathy
This form of colonic stricture is unique to cystic fibrosis, was first described in
five cases in 1994 and incriminated certain high strength enzyme preparations
in the aetiology. Doses of 24,000 to 50,000 units of lipase per kilogram per
day are associated with an increased risk of developing the disease.
The lesion usually involves the ascending colon and consists of submucosal
fibrosis which causes long segment stenosis. This can lead to partial or
complete bowel obstruction and the need for resection of a length of colon.
The early clinical picture can be similar to DIOS. Diagnosis is by contrast
enema. There is some evidence that early withdrawal of high strength
enzymes can lead to reversal of the bowel wall thickening in the early stages
of the disease. Following the occurrence of fibrosing colonopathy the current
recommendation for daily lipase use is less than 10,000 - 15,000 units/kg,
however in some cases this may need to be exceeded with caution.
52

Table: Management of DIOS
Acute presentations Investigation Treatment
Mild Episodes
Mild abdominal pain Nil Rehydration
No obstruction Lactulose 10-20 ml BD
May be recurrent Acetylcysteine 100 mg 3 times daily (Fabrol)
(out-patient management) Consider adding oral gastrografin
Severe Episodes
Abdominal pain with Full blood count Rehydration
distension and constipation Urea & Electrolytes Lactulose 20ml 3 times a daily
No obstruction Abdominal X-ray (classically, speckled Oral gastrografin: 7 years 100ml 3 times daily
(consider admission) quadrant with dilated small bowel loops) Klean-Prep via NG tube until clear fluid passed PR (see section 8)
Consider gastrografin enema (under radiological guidance)
Obstruction present
(admit to ward) Full blood count Rehydration
Urea& Electrolytes ‘Drip and suck’
Abdominal X-ray Inform surgeons
Consider oral gastrografin
Consider gastrografin enema (under radiological guidance)
1 Monitor for hypoglycaemia in those with diabetes or liver disease
53

Section Four:
Psychosocial Services
4.1 Psychological Services
4.1.1 Hospital clinical psychology service
Clinical psychologists are available to all children with CF attending GOSH
as outpatients or inpatients. As a member of the CF team the psychologists
attend the weekly ward based psychosocial meeting and the outpatient CF
clinic. Individual appointments for children and families are provided when
necessary. The psychologists will meet all families at the annual review to
conduct a brief assessment.
4.1.2 Hospital psychiatry service
Appointments with a child psychiatrist are available when necessary. These
can be made through the clinical psychologists by contacting the Department
of Psychological Medicine (ext 8679), or in an emergency by requesting the
psychiatrist on-call via the hospital switchboard (ext 5000). The clinical nurse
specialists in CF also offer counselling and support for children and families,
including school liaison.
4.1.3 Need for psychological intervention
CF is a chronic illness with a shortened life expectancy. There are daily
dietetic and physiotherapy requirements. Regular medical monitoring is
necessary with the need for antibiotic therapy and inpatient care. Associated
illnesses can result in additional daily medical management and other
outpatient attendance. All of these therapeutic burdens can interfere with
psychological adjustment, development of self esteem and routine family
functioning. The psychological service aims to be preventative as well as
responsive to particular problems. The aim is to enable the family to reach an
adaptive balance between CF treatment and normal life experiences. All
members of the family, not just the child with CF, may feel the effects of the
chronic illness. The psychological service is therefore, available for all family
members if required.
54

4.1.4 Common psychological problems
Early Childhood
Following diagnosis parents often experience emotional reactions connected
with ‘grieving the loss of a normal child’, e.g. shock, denial, guilt, blame,
feelings of being overwhelmed and of incompetence. Their plans and dreams
for their child become painful. Often the need to nurture becomes the need
to nurse. Along with the fear of death the parent-child relationship can
become detached and ‘professional’.
As the child approaches the ‘terrible two’ stage, which results from a
developing sense of self and competence, the parents may face noncompliance
with treatment for the first time. Additionally, parents and
extended family often feel the temptation to avoid upsetting the child as
compensation for having the illness. This often results in the failure to gain
positions of authority, draw effective and appropriate family boundaries and
set limits on the child’s behaviour. The consequences of such management
styles can be continued non-compliance with medical regimens and a general
insecurity in the child who may never have experienced a sense of parental
control.
Middle Childhood
Issues during this phase tend to concern the children themselves. There is an
ability to understand the nature of their illness and a need to incorporate CF
into their personal identity. They need permission to be themselves rather
than the illness taking priority. Providing accurate, honest information is
essential with this age group. Parents who lie will have great difficulty
maintaining trustworthy relationships as the child discovers the truth.
Particular problems often concern adherence to diet, co-operation with
physiotherapy, needle/procedure phobia, how to inform school and dealing
with being teased.
Nutrition
The chapter on nutrition (Section 3.1) explains the consequences of poor
intake. The children often face the dilemma of requiring a large calorie intake
but having no interest in food - one child described “never being excited by
food like other people”. Each meal time can be aversive and akin to force
feeding; food, rather than a source of pleasure, is seen as part of a medical
regimen.
Physiotherapy
Physiotherapy takes time away from other preferred activities and is a
reminder of the illness. It also involves parents and so requires timetabling for
the family and co-operative relationships. As described in the section of
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physiotherapy, self managed techniques such as a PEP mask will not
necessarily solve the problem.
School Entrance
School entrance involves exposure to a wider audience for the illness. It
requires explanations, understanding and, in some cases, unsolicited adverse
reactions. The child can be made to feel different when the normal drive is to
be like their peers. A sense of isolation and loneliness can lower self esteem. A
child can become withdrawn and watchful or alternatively, boisterous and
aggressive as a means of compensation. Helping the child to feel positive
about their CF, to be confident in providing explanations and aiding the
child to participate in normal life experiences are essential.
Procedure Phobia
Needle phobia and other fears associated with hospital admissions are
common. The fear has a rational basis to avoid pain and incomprehensible
procedures. Parents often find themselves in an uncomfortable position as
they cannot fulfil their protective role but must force the child to comply. It
is essential that parents help to reduce the child’s anxiety in anticipation of a
painful procedure. If parents themselves are anxious then they will be unable
to fulfil their role. Parents who experience procedure related anxiety must
receive some help themselves from the clinical psychologist. There are many
successful strategies to desensitise a child to such procedures but notice to the
psychologist must be given of an impending admission, so work can be done
in advance.
Adolescence
In addition to the previously mentioned difficulties, there may be particular
psychosocial concerns during adolescence. Often the psychological phase of
adolescence begins early in children with CF. It appears that the daily
management of chronic and terminal illness brings premature self
responsibility and opinions irrespective of intellectual level. The beginning of
secondary education can often result in a change of personality and poor
adherence to treatment. During adolescence most children are expanding
their experience, planning a future career and actively seeking opportunity,
whereas children with CF may be contemplating their own mortality. The
strength of peer pressure at this stage often introduces potential problems
such as pregnancy, cigarettes, alcohol and drug abuse. The psychologists are
often called upon to help families with such concerns.
Particular problems occurring during adolescence in CF concern body image,
a possible delayed puberty, sexual relationships and the likely infertility of
males. The age at which infertility should be raised with the boy concerned is
often difficult for parents. The CF team recommends informing the boy at an
early age rather than later in adolescence. This issue must be discussed with
the young man before transfer to the adult clinic.
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Our aim is to promote a collaborative relationship between the adolescent,
family and CF team in order to reflect the increasing independence of the
teenager and prevent a rejection of medical recommendations.
4.1.5 Bereavement Support
Fortunately, childhood death from CF is now very rare. During the terminal
illness specific work is done to help the family and child with appropriate
guidance but minimal intrusion. When death occurs in the hospital, close
collaboration with the ward staff is ensured.
Continued support for the family can be given by offering follow-up
appointments. The aims are not to forget the child and get on with life but to
feel comfortable remembering the child and to dispel myths and reduce
regrets.
4.2 Social Services
If help or support is required during a hospital stay parents or carers can ask
to see a social worker or family support worker. The department is on Level 2
close to the main entrance and is open every weekday between 9am and 5pm.
4.2.1 Guide to government help
1. Disability Living Allowance (DLA)
The DLA is payable on top of earnings, it is tax-free and not means tested. It
consists of the care component payable at three different rates; and the
Mobility component is payable at two different rates. Each component has a
different qualifying entry and both are available at the same time.
Applications should be made by completing claim pack DLA1 or DLA1A
(for children under 16), obtainable by phoning Freephone 0800 882200.
Further information is available from the Family and Adult Support Services
at the CF Trust or from the clinical nurse specialists.
2. Invalid Care Allowance
Invalid Care Allowance (ICA) is a benefit for people of working age who
spend at least 35 hours a week caring for someone who receives the care
component of DLA at the middle or higher rate. Carers do not have to be
related to, or even live with the disabled person and can receive ICA even if
they have never worked.
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ICA does not depend on contributions; but it is taxable. The claimant must
not be earning more than £75.00 per week (2002). The partners earnings are
not taken into account. Apply by using claim pack DS700. The pack and a
free SAE are available from your local Benefits Agency or from the social
work department.
3. Families receiving income support
The award of Disability Living Allowance and Invalid Care Allowance will
entitle families receiving Income Support to extra premiums as follows:
Disability Living Allowance - Disabled Child Premium
Invalid Care Allowance - Carer Premium
Although invalid care allowance counts as income and is deducted from
income support, the award of a carers premium leaves the family better off.
4. Motability
Motability is a voluntary organisation set up on the initiative of the
Government and intended to help people with disabilities use their Mobility
Component of the Disability Living Allowance to buy or hire a car.
Full details are available from Motability, 2nd Floor, Gate House, Westgate,
The High, Harlow, Essex, CM20 1HR.
5. Blue Badge Scheme
The Blue Badge Scheme allows a vehicle displaying a Blue Badge, and driven
by a disabled person or with a disabled person as passenger a number of
parking concessions. Blue Badges are available from the local authority.
In order to qualify for a Blue Badge the patient must be aged 2 or over and:
i) receive the Mobility Component of the Disability Living Allowance; or
ii) use a vehicle supplied by a government department or be receiving a
grant towards running their own car; or
iii) be registered blind; or
iv) have a “permanent and substantial disability which causes inability to
walk or have very considerable difficulty in walking”.
6. Help with Equipment
Health authorities, as part of their community health services, may provide
nursing equipment such as special beds, commodes, urinals, incontinence
pads, etc.
Because some items may serve a dual purpose, for nursing and daily living,
most health and social service authorities have a jointly agreed procedure for
deciding who supplies which item. In the first instance, apply for any item via
the GP, district nurse, health visitor, occupational therapist or social worker.
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General Practitioners may prescribe only the equipment which is included on
an approved list called the Schedule of Appliances and Devices in the Drug
Tariff.
However, an NHS consultant may prescribe any item of equipment which
s/he considers is necessary as part of a patient’s treatment, e.g. nebulisers.
4.2.2 The Family Fund Trust
The Family Fund Trust is financed by the Government. Any family caring for
a severely mentally or physically disabled child under the age of 16 and living
at home with them may apply for help. The diagnosis of CF is not a
sufficient criterion unless the child is severely affected by it.
The Fund is discretionary but works within general guidelines agreed with
the Government. The purpose is to relieve stress arising from the day to day
care of a disabled child. It can help families whose gross income is not more
than £21,000 (2002) and who have savings of £8000 or less. There is no set
list of items or needs covered by the Fund, except that it is not designed to
replace help available from the health or local authority.
Application forms are available from: The Family Fund Trust, PO Box 50,
York, YO1 2ZX, Telephone: 01904 621115 or from the social work
department.
4.2.3 Travel to hospital
Patients and parents may be entitled to assistance with fares or other travel
expenses to a hospital where they receive treatment if they are receiving
Income Support or Family Credit or they are covered by the low income
scheme (see below). Visiting parents who receive Income Support or meanstested
Job Seekers Allowance may receive a community care grant from the
Social Fund. The social work department can sometimes help with visiting
fares for parents on a low income.
4.2.4 The low income scheme
Parents may qualify for full help if their ‘income resources’ are less than, or
the same as their requirements. If they are more than their requirements they
may still qualify for some help but their capital must not exceed £8,000.
If possible parents should apply for help with travel to the hospital
beforehand. To do this send off Form AG1 (obtainable from Benefits Agency
or a post office or the social work department). The Benefits Agency will
decide whether they are entitled to full or partial help and, if they are, will
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send them a certificate (Form AG2 or AG3). This certificate is valid for six
months.
If parents are unable to send off Form AG1 in advance, they can obtain a
refund but their claim must be made within one month of paying for the
travel expenses. Apply on Form AG5 (from the Benefits Agency or post
office).
4.2.5 Social fund (discretion)
The discretionary element of the Social Fund is intended to help meet certain
expenses. Help may be provided in the form of grants or as repayable interestfree
loans. Decisions are taken by the social fund officers based in local
Benefits Agency offices and are made within the fixed framework of
directions, and the more flexible framework of guidelines. However, different
Benefits Agency offices are likely to operate the social fund in different ways.
Three types of help are available:
i) Community Care Grants: These are payments to help families cope with
exceptional pressures and to cover certain travel expenses in the UK.
Parents must also be in receipt of Income Support or means-tested Job
Seekers Allowance.
ii) Budgeting Loans: These are available only to people who have been
receiving Income Support or means-tested Job Seekers Allowance for 26
weeks. If parents cannot afford to repay a loan, they won’t get one.
iii) Crisis Loan: Crisis loans can be given to help meet short-term needs in
an emergency or after a disaster (such as a fire or burglary). The loan
must be the only means to prevent serious risk to the health or safety of
any member of the family.
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Section Five:
Genetic Services
5.0 Genetic Services
Introduction
CF is inherited as an autosomal recessive disease. The incidence of CF is
highest in individuals of European origin and in the British population is
about 1 in 2,500. Approximately 1/25 of the population are carriers of the
disease. This means that although they themselves are not affected by the
disease, in their genetic make-up, one of the two copies of the CF gene
contains an alteration (mutation). Affected individuals carry mutations in
both copies of their CF genes. The parents of a child with CF are both
carriers but are healthy. Each time two carriers have children there is a one in
four chance that the child will be affected.
The disorder arises from mutations in the gene called the CF transmembrane
conductance regulator (CFTR). There are a very large number of recognised
mutations and the laboratory offers routine screening for 31 mutations which
together account for approximately 90% of CF mutations in the UK
population. Some additional alterations or variants in the gene have a less
certain effect and the spectrum of CFTR-related disorders is now recognised
to be quite wide. This in conjunction with other factors means that it is not
always possible to predict directly the precise clinical outcome from the
genetic analysis for individuals who carry two mutated copies of their CF
gene.
5.1 Gene typing of the affected individual
Mutation detection in affected individuals is useful to both confirm the
diagnosis at a genetic level, to facilitate phenotype-genotype correlations and
to provide the opportunity for other relatives to determine their personal
carrier risk and, if appropriate, seek prenatal diagnosis. Because of the
sensitivity of the test and the variable effects of some mutations, the diagnosis
of patients affected with CF should be made on clinical grounds. Genotyping
can be used as part of the diagnostic process in neonates with suggestive
histories (meconium ileus for example), although it must be remembered that
a negative test does not necessarily exclude the diagnosis. Routine genotyping
includes screening for 31 mutations (which account for approximately 90%
of CF mutations in the UK population). For individuals of Asian origin an
additional six mutations specific to this population may be tested. The
interpretation of the analysis and subsequent risk calculation is dependent
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upon a clinical assessment, the family history and ethnic origin. For example,
an individual who screens negative may carry no mutations, or, one or two
undetectable mutations and an individual with one detectable mutation may
be a healthy carrier or an affected compound heterozygote (with one
detectable and one undetectable mutation). In families where it is not
possible to identify the mutation, carrier detection may be possible using
highly informative markers within the CFTR gene.
In certain instances a more comprehensive mutation analysis of the CFTR
gene may be undertaken. Such analysis that may take several months and
should be by prior arrangement with the referring clinician.
5.2 Carrier testing of adult relatives
Once a child has been diagnosed as having CF, it is important to offer genetic
counselling to the parents and to other adult relatives. The parents may wish
to consider the option of prenatal diagnosis in future pregnancies.
The aunts and uncles of an affected individual each have a 50:50 risk of
being a carrier of CF. Clearly this is of no importance to them, unless their
partner is also a carrier. However, we know that one in 25 of the white
Northern European population is a carrier so the risk to the aunt/uncle of a
child with CF is one in 200 ( 1 /2 x 1 /2 x 1 /4) of having a child with CF
themselves. At this level of risk we consider screening all adult relatives of an
affected case to be worth offering, so that they can be aware of whether of not
they are at high or low risk of having an affected child.
In many cases, an adult relative requests screening but no information is
available about the affected child - they may have died or be living in another
country. It is still possible to screen that person but the accuracy of the test
will be reduced without the information about the mutations present in the
index case. A positive test means the person is definitely a carrier; a negative
test reduces the risk that they are a carrier, but does not exclude it completely.
5.3 Consanguineous marriages
As the carrier frequency in the white population of the UK is one in 25, and
cousins have an increased risk of carrying the same abnormal genes given
their common ancestors, we usually offer CF carrier screening to couples who
are related (first cousins, etc.) even in the absence of a history of CF in their
family.
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5.4 Carrier testing of siblings
The healthy siblings of a child with CF each have a two in three risk of being
a carrier of CF. As a general rule, the appropriate time to arrange for brothers
or sisters to be tested is in the mid to late teenage years when they can
understand the implications of the test. At the present time, CF carrier
testing is not offered to minors in this clinic, as it is not considered to be
ethically acceptable to do genetic testing on individuals without their
informed consent.
Occasionally, parents who do not wish to have prenatal diagnosis, request
that a new baby is tested immediately after delivery, so that they can start
appropriate treatment early and not be kept in suspense for some weeks
awaiting the results of a sweat test. The parents are informed as to whether
the baby is affected, unaffected or a carrier.
5.5 Prenatal screening
Parents of a child with CF have a one in four risk of recurrence. Some may
opt to have prenatal diagnosis, and a termination of pregnancy (TOP) if the
baby is predicted to be affected. Many couples find this a very difficult
subject, especially with the improvements in treatment and life expectancy.
Some feel that having a TOP implies that they would not have had their
affected child had they been aware of the diagnosis during pregnancy. Other
couples do not agree with termination on religious or personal grounds, and
may wish to discuss their risks and other possible options (e.g. donor
insemination, pre-implantation diagnosis, etc.) in order to avoid having a
further affected child. For this reason, all parents who are considering having
further children should be offered genetic counselling.
During pregnancy, a mother may have a routine fetal ultrasound scan which
may reveal an anomaly that increases the risk that the fetus may be affected
by CF. In these cases, both partners are offered prenatal screening. The results
of this will allow further evaluation of the risk that their baby may be affected
and provide information regarding possible prenatal diagnosis.
Prenatal diagnosis is usually carried out by testing a chorion villus sample
(CVS) not before 11 weeks’ gestation. The test has about a one percent risk
of causing a miscarriage. The result usually takes about a week to process so
that a first trimester termination can be performed if necessary.
It is always best if the preliminary gene typing has been carried out on the
family prior to pregnancy, so that the laboratory knows precisely which
mutations they are testing for in the CVS. Even if the affected child has an
undetectable mutation, it is still possible to do a prenatal diagnosis (using
gene tracking), providing the work-up has been done prior to pregnancy.
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5.6 Population screening
There has been much debate about introducing some kind of mass screening
programme so that people can know, prior to starting their families, whether
they are at high risk of having a child with CF. The fact that the screening
would not detect all mutations, that some mutations may be of variable
significance, the consequences of results to other relatives and the complexity
of communicating all this information has made uncertain the overall benefits
of such programmes. At present families at risk are only identified following
the birth of an affected child. Some areas are carrying out routine newborn
screening by a biochemical test on a blood spot.
5.7 Neonatal screening
Neonatal screening is possible using immunoreactive trypsin followed by gene
testing of positive samples on the Guthrie card. Such a national screening
programme is expected to be introduced in the near future following
agreement of the testing strategy.
5.8 Essential Information
1. Sample required for genotyping -
EDTA tube (preferably plastic)
Two to five ml (child), ten ml (adult)
Send to:
North East Thames Regional Molecular Genetics Laboratory
Level 1, Camelia Botnar Laboratories
Great Ormond Street Hospital
Great Ormond Street
London
WC1N 3JH
Mouthwash and buccal scrape samples are now accepted but a blood
sample may be requested for further work after initial testing. Blood
samples are preferred on neonates for diagnostic tests and pregnant
women and their partners for urgent carrier screening. Neonates who
have had a blood transfusion can be tested within 48 hours of the
procedure.
Mouthwash - 10mls sterile saline swirled in the mouth for one minute.
Collect in a 20ml sterilin tube, clearly labelled.
Buccal scrape - scrape the inside of the cheek with a plastic spatula. Drop
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into 10 mls sterile saline in a 20ml sterilin bottle, clearly labelled. Mix to
free cells from spatula.
2. The laboratory will receive samples from any patient at GOSH and
patients living within the North East Thames Region. For patients living
outside this contact the Department of Genetics for name and address of
local geneticist and clinic.
3. Contacts
Director of Laboratory Gail Norbury
Administrator Tony Young
Telephone 020 7905 2223
Fax 020 7813 8196
Email cmg@gosh.nhs.uk
Clinical Genetics Unit
Institute of Child Health,
30 Guilford Street, London.
WC1N 1EH
Telephone 020 7905 2647
Fax 020 7813 8141
Lead Clinician Dr Elisabeth Rosser
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Section Six:
Lung Transplantation
6.1 Patient Selection
Introduction
Transplantation of the lungs or the heart and lungs has been employed in the
management of end stage CF since 1985 and has been performed in children
at GOSH since 1988. Improved survival and quality of life have been
demonstrated following the procedure and this has precipitated an increase in
the number of potential recipients referred. Selection criteria and clinical
parameters to evaluate short-term prognosis have been developed to identify
appropriate candidates, while expertise in the post transplant management
has rapidly expanded. The development of new, more effective anti-rejection
agents continues with exciting prospects for improved results and fewer
associated complications. Measures to increase the donor pool are also being
sought to enable a greater number of patients to benefit from this therapy.
Patient selection/referral
Selection criteria for transplantation include a limited life expectancy and a
severely impaired quality of life. A prognosis of less than two years has
generally been considered appropriate in view of the current recipient waiting
times and post transplant survival. A number of studies have shown that
children with an FEV1 of 30% predicted usually have a prognosis of less than
two years, though girls, younger children and children deteriorating rapidly
may have an even worse prognosis. We prefer children to be referred just
before they reach this point, as this then allows the child and family some
time to come to terms with the severity of their condition and decide whether
they wish to have a transplant. It also allows us to see the child more than
once, so that we can make some estimate of their rate of decline.
Contraindications continue to reduce in number in line with increasing
surgical and medical expertise. Previous thoracic procedures including
pleurodesis and even pleurectomy are no longer absolute contra indications,
nor are diabetes mellitus, steroid therapy or hepatic involvement. Established
cirrhosis of the liver may however necessitate a triple (i.e. combined heart,
lung and liver) transplant. Major contraindications include severe
psychosocial disorder of the child and/or family, or irreversible damage to
other organs, such as renal failure. Chronic infection with Burkholderia
cepacia genomovar III appears to be associated with a very poor post
transplant outcome and we consider this an absolute contra indication.
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Chronic infection with other Burkolderia cepacia genomovars, multi-resistant
Pseudomonas, MRSA or mycobacteria do not represent an absolute contra
indication. If a referring centre has any uncertainty about whether a child
would be considered, it is worth contacting us to ask advice.
Transplantation assessment
The aims of the transplant assessment are multiple. Firstly, to assess the child’s
likely prognosis without transplant and to determine whether there are any
contra indications to transplant. Secondly, to determine the child’s quality of
life (a child with an FEV1 of 30% who reports a good quality of life is
unlikely to be listed for transplant). Thirdly, it is essential that we educate the
child and family about what transplant involves. The child and family are
admitted for between three to five days, during which time they spend the
night sleeping in our patient hotel, with the days having investigations or
discussions with members of the transplant team. The following tests are
performed:
24 hour urine collection X-rays
Fasting blood tests ECG
Liver ultrasound Echocardiogram
Sputum collection CT scan
Dental assessment ENT assessment
Lung function tests Dietary assessment
Exercise tests
Many of these tests are performed in order to estimate prognosis and to identify
contra indications. Research performed at our own centre suggests that the best
way to estimate prognosis in children with CF is to use a combination of lung
function measurement, exercise tolerance, nutritional status, sex, age and rate of
deterioration.
Education is an essential component of this transplant assessment. We are
very honest with the child and family about the current donor shortage,
about the limited post transplant survival (see below) and about the need for
life-long medication and close monitoring post transplant. For most families,
this is a very difficult time and we do not rush these sessions.
Children who are being considered for the active waiting list are discussed at
a multidisciplinary meeting and will also meet with one of the consultant
surgeons. If a child is listed for transplant, their families are issued with a
pager and continue to live at home. Their care will continue to be provided
by the CF team, but the transplant team are also available to provide
whatever support is necessary. The current waiting list time is an average of
ten months. However, the waiting time may be much less or much more than
this. Due to donor shortage, just over half the children who are listed for
transplant die before receiving organs. For the families and for those involved
in the service, this is the most difficult aspect of paediatric lung
transplantation.
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6.2 Surgical Aspects
and Post-Operative Management
Surgical aspects
Donor and recipient are matched by ABO blood group compatibility and
size. Donor lungs should ideally be in pristine condition, demonstrating good
gas exchange (with PaO2 of 40 kPa in 100% oxygen), a normal chest X-ray
and clear aspirate from the endotracheal tube. Lungs do not tolerate
ischaemia well and it is usual to limit total organ retrieval time to a maximum
of four hours. The shortage of donors has forced many transplant centres to
consider lungs from so called marginal donors, such as donors who were light
smokers, or lungs that have minor chest X-ray changes. Early results suggest
that post-transplant outcome using marginal donors is usually acceptable.
With the successful development of bilateral lung transplantation for adults
with cystic fibrosis, thus avoiding transplantation of the native heart, there
has been a trend to perform this procedure in children rather than heart-lung
transplantation and subsequent domino heart transplantation. Results for
both techniques are comparable and choice of procedure lies mainly with the
surgeon’s preference. However, bronchial anastomoses may be at greater risk
of ischaemic complications in the smaller child and therefore combined heartlung
transplantation with the tracheal anastomosis and associated intact
coronary-bronchial circulation may be a more suitable and less hazardous
procedure.
Post-operative management
Surgery does not imply cure. Post operative management entails careful
immunomodulation to prevent and treat acute rejection of the pulmonary
allograft whilst minimising the risk of intercurrent infection with pathogenic
and/or opportunistic organisms. The child will usually remain an inpatient
for four to six weeks.
Cyclosporin A, a specific suppressor of T-cell activation, is a potent inhibitor
of cell-mediated immune function and hence the rejection response and is
taken for life. The dose of cyclosporin is determined by whole blood level
(one ml EDTA sample by EMIT assay; therapeutic range: 200-400µg/l) and
renal function. Tacrolimus (previously known as FK506) is a very similar
drug to cyclosporin A and is often used as an alternative. These drugs remain
the cornerstone of current immunosuppressive regimens for cardiopulmonary
transplantation and are usually combined with azathioprine and
prednisolone to form ‘triple therapy’. Peri-operative induction protocols may
also comprise an anti-lymphocyte preparation to deplete circulating T-cells,
thus allowing time for cyclosporin A to reach effective blood levels.
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Routine monitoring of the pulmonary allograft for rejection and/or infection
incorporates twice-daily spirometry and regular bronchoscopy,
bronchoalveolar lavage and transbronchial biopsy. Acute rejection is treated
by augmentation of immunosuppression with high dose intravenous
methylprednisolone, while further anti-lymphocyte therapy is occasionally
required. Infections are treated according to culture and/or serology and are
most prevalent in the early post-operative period (first three months)
associated with the highest incidence of rejection and, accordingly, most
intense immunosuppression.
The majority of pulmonary infective episodes are due to Pseudomonas species
which often colonise the lung allograft, presumably seeded from the diseased
upper airways and sinuses. Attempts to prevent this colonisation have ranged
from the use of nebulised antibiotics to more aggressive therapy including
regular antral washout and antrostomy.
Management of the non-pulmonary facets of the CF patient must be
maintained, particularly the preservation of gastrointestinal function and a
satisfactory absorptive surface for the essential immunosuppressive drugs.
Adequate pancreatic enzyme replacement, and when indicated aperients and
enteral acetylcysteine are required to satisfy these objectives.
6.3 Survival and Complications
Survival
Survival following lung transplantation for CF is 80% at one year and 60%
at five years. Data from the International Registry suggests that these survival
figures are slowly improving and we suspect this is the case at our centre also,
however, the small number of transplants performed in children in the UK
do not allow us to confirm this as yet. The majority of survivors enjoy a
markedly improved quality of life afforded them by increased pulmonary
function. This enables return to school or college and other age related
activities.
Complications
Mortality in the early post operative period is often associated with episodes
of acute pulmonary rejection and infection, in addition to other
complications related to surgery. After the first three post operative months
the major cause of morbidity and mortality is due to the development of
obliterative bronchiolitis, a progressive obstructive airway disease which may
eventually be associated with a central bronchiectasis and chronic infection.
Its aetiology remains obscure but appears to be immunologically mediated.
Efforts to reverse the pathology with augmented immunosuppression have
been attempted, but once established, the only effective ‘cure’ is retransplantation,
which presently produces poor results and is not practised at
GOSH.
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Other complications following heart-lung transplantation include tracheal
stenosis at the anastomotic site, which may be associated with a more
generalised bronchomalacia process proceeding to obliterative bronchiolitis.
Diabetes mellitus may be precipitated by the use of glucocorticoids but is
usually well controlled with insulin therapy. Other major drug side effects
include systemic hypertension, renal dysfunction and neurological
abnormalities - all associated with cyclosporin A toxicity or tacrolimus.
Another longer term post transplant concern is the increased incidence of
lymphoma and other malignancies. The former frequently appears to be
related to infection with the Epstein-Barr virus and has been termed
‘lymphoproliferative disease’. This disorder may respond to reduction of
immunosuppressive therapy and high dose acyclovir. Although not a major
medical concern in itself, alteration in body appearance including
hypertrichosis, gingival hypertrophy and Cushingoid features may induce
non-compliance to therapy and result in serious graft dysfunction as
witnessed with other organ transplants.
Lung replacement for children with end-stage pulmonary complications of
CF offers improved life expectancy and quality of life, although not all
patients referred and/or undergoing the procedure will reap these benefits.
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Section Seven:
Additional CF Related Complications
7.1 Cystic Fibrosis-Related Diabetes
(CFRD)
Although impaired glucose tolerance is common among patients with CF
(estimates vary but average at 40%), the prevalence of overt diabetes mellitus
(DM) is estimated at between 2.5-12% and seems to be increasing with
improved survival. Incidence increases with age and CFRD is predominantly
a condition of adolescents and young adults (mean age at diagnosis 18-20
years). However it can occur in younger children and is commoner amongst
females. CFRD shares certain features of both type one insulin-dependent
DM and type two adult-onset DM, but is sufficiently different from both to
warrant a category of its own. CFRD is commoner among those homozygous
for the ∆F508 allele than the heterozygous ∆F508 CF patients, possibly due
to the way genetic factors influence the degree of pancreatic disease.
Destruction of exocrine tissue with concomitant pancreatic fibrosis is thought
to lead to gradual destruction of insulin-producing islet cells.
Presenting features
CFRD has a slow insidious onset and rarely presents with ketoacidosis. Usual
presentation is with weight loss, fatigue and poor appetite; with polyuria and
polydipsia being much less common. However urine should be tested for
glycosuria in the clinic whenever there has been weight loss. Liver disease may
also disturb glucose metabolism. Onset may be precipitated by treatment
with corticosteroids (particularly post-transplant), or by the introduction of
overnight enteral feeding regimes. At the time of diagnosis, many of the
patients will have a decrease in weight, deteriorating lung function, increase
in chest exacerbations and an increase in daily intake of pancreatic
supplements when looking retrospectively over preceding years. It is likely
that the pre-diabetic state leads to an overall insidious decline in CF clinical
status.
Survival figures for CF patients with DM are worse than for those without
(25% vs 60% survival to 30 years). It had previously been thought that
complications of DM were not encountered in patients with CF. However,
due to increasing longevity, microangiopathy has now been reported
(including neuropathy, retinopathy and nephropathy); it is generally found in
those who have had CFRD for more than five years and those who are poorly
controlled. For this reason, yearly ophthalmological and neurological
examination is advisable, as well as measurement of urinary protein and
creatinine clearance.
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Diagnosis
In the presence of glycosuria, a random blood sugar should be done
immediately, if it is less than seven mmol/l no action is required. If it is over
seven mmol/l then a fasting blood sugar and a HbA1c should be organised as
soon as possible. If the fasting blood glucose is less than seven mmol/l and
the HbA1c is 6.4%, with or without a positive urinalysis then an oral glucose tolerance
test (OGTT) needs to be organised. The OGTT is considered the gold
standard in the diagnosis of CF related diabetes. Please refer to flow diagram
overleaf.
Management
Nearly all patients require insulin therapy although some adults may be
managed for a time using oral hypoglycaemic agents (such as glibenclamide).
In general, insulin requirements are not high and management is relatively
simple, usually with twice daily injections of short and medium/long-acting
insulin. Some patients prefer to use a QDS regimen with three mealtime
doses of an actrapid insulin with a pre-bed dose of a mixture of medium/long
acting insulin. Patients are particularly prone to hypoglycaemic episodes so
need to carry a source of glucose with them at all times. BM stix are
recommended two to three times daily before meals. The aim is for a premeal
glucose of four to seven mmol/l. Glycosylated haemoglobin (HbA1c)
should be measured in clinic when control is in question, and should be
under ten percent, and preferably under 8.5%. Insulin requirement must be
adjusted during exacerbations of infections and patients must take a
concentrated carbohydrate snack prior to strenuous exercise. Intravenous
insulin infusions are usually necessary to cover surgery. Insulin dosage will
also need to be adjusted if a patient starts on night time enteral feeding.
The dietary aims are the same as for CF in general (see Section 3.1). Patients
with CFRD are encouraged to eat what they can rather than undergo the
restrictions placed on non-CF diabetics. They should continue to aim for a
high calorie input and it is best for them to have three meals per day with
mid-meal and pre-bedtime snacks. Insulin intake can be adjusted to cover the
food eaten. Restriction on sugar intake is not necessary although they should
avoid snacks containing simple sugars alone. Patients must continue to take
pancreatic enzyme supplements with all food.
Compliance is often poor, particularly in adolescents. The burden of two
chronic diseases may well mean extra psychosocial support is necessary.
72

Random blood glucose (RBG)
Results checked over
following week
RBG is equal to or
greater than 7 mmol/l
Fasting blood glucose (FBG),
HbA1c
Repeat urinalysis
FBG is equal or greater
than 7 mmol/l
(HbA1c greater
than 6.4%)
And/or
urinalysis positive
to glucose
Oral glucose tolerance
test must be arranged
as soon as possible
If RBG is less than 7mmol/l
and urine negative no further
action needs to be taken
If FBG is less than 7mmol/l
and urine negative no further
action needs to be taken
Urinalysis
Urinalysis positive
Finger prick
blood glucose
must be
checked
immediately
7mmol/l
Admit child
for FBG
± OGTT
All children with CF related diabetes must have an HbA1c checked at every
annual review.
73

7.2 Liver Disease
Introduction
Pathological changes of liver disease such as bile plugging of the smaller
biliary ducts and scattered areas of fibrosis, pericholangitis and dilatation of
the ductules occurs in the liver of many young children with CF and may
even be present to a minor degree at birth. These changes progress slowly,
variably and unpredictably towards focal biliary cirrhosis. Eventually portal
hypertension often with oesophageal varices and hepatic failure intervenes.
Ascites, hypersplenism and gall stones are additional manifestations of hepatic
disease. Symptomatic liver disease is seen in 4% of patients only, it peaks at
16-20 years of age (9%) and is twice as common in males.
Hepatic failure is only occasionally seen in the paediatric clinic but post
mortem studies have found that over 50% of patients have liver cirrhosis. CFrelated
liver disease is an increasingly important cause of portal hypertension
and multilobular cirrhosis in the young adult.
Screening for liver disease
• Clinical examination:
Hepatomegaly - is likely to represent fibrosis/cirrhosis if hard
and irregular especially if the left lobe is
prominent in the epigastrium.
- is likely to be due to fatty infiltration if the
liver enlargement is smooth, regular and
both lobes are equally involved, especially
if present in a malnourished child.
- beware of apparent liver enlargement due
to hyperinflated chest, especially in
younger children.
Splenomegaly - almost all patient with varices will have
splenomegaly and documentation of its
presence is essential in screening for portal
hypertension.
• Liver function tests: Mild biochemical abnormalities are often
detected early in life but are of little
clinical significance and bear no relation to
portal pressure especially with normal
clinical findings. Elongation of the
prothrombin time is more likely to
represent vitamin K malabsorption than
hepatic malfunction. There may be some
74

• Ultrasound:
importance in documenting early enzyme
elevations when planning the introduction
of ursodeoxycholic acid therapy (see
below). Grossly abnormal liver function
tests (elevated transaminases four times
above normal range) are mostly seen with
biliary disease.
Is valuable in demonstrating portal vein
dilatation, gall stones, and a heterogeneous
texture of liver enlargement. Doppler
studies can demonstrate splenic venous
retrograde flow. Liver and spleen
ultrasound should be performed when
significantly abnormal liver function tests
and abnormal clinical findings are
detected. Pathological ultrasound results
should be followed up once a year at the
annual review assessment.
• CT scan: Will confirm the heterogeneous texture of
the liver enlargement but adds little to the
clinical examination and ultrasound.
• Barium swallow: Useful to confirm the presence and size of
oesophageal varices if splenomegaly is
present.
• Endoscopy: To visualise varices and plan sclerotherapy
if indicated.
• Scintigraphy: The DISIDA scan will show normal
uptake but delayed excretion in CF liver
disease and is likely to be abnormal when
serum ALT is twice normal. Correlation
with serum GGT is not as good.
• Liver biopsy: May be indicated in selected cases but is
not routine in this clinic.
• ERPC Endoscopic retrograde cholangiopancreatography
may be useful in
outlining bile and pancreatic ducts in those
with severe disease.
Management
General supportive therapy is required as for any patient with significant liver
disease. The need for vitamin K administration will be determined by the
prothrombin time. Vitamin K is given if prothrombin time is more than four
seconds greater than control. Haematemesis from oesophageal varices can be
75

a catastrophic event and may require sclerotherapy, often in a patient in
whom severe chest disease adds considerably to the anaesthetic risk (see
Section 7.3). Aspirin and related compounds should not be used in patients
with liver cirrhosis. Patients with significant splenomegaly should also avoid
contact sports. Surgical measures such as porto-systemic shunting procedures
or liver transplantation should be approached with caution and will require a
team consideration with special appraisal of the patient’s long term respiratory
outlook.
Ursodeoxycholic acid
Ursodeoxycholic acid is a highly hydrophilic bile acid and choleretic agent
and its flushing effect has shown promise in the stabilisation of cystic fibrosis
related liver disease.
The early results of ursodeoxycholic acid administration (10-20 mg/kg/day)
have been promising with reduction in elevated enzyme levels and
improvements in scintigraphy studies. Whether it can stop the development
of cirrhosis at the stage of focal biliary fibrosis has yet to be determined but
once cirrhosis has developed then administration of this agent is probably
futile.
Further studies are underway to document the optimal time for its
introduction. Our current practice is to commence ursodeoxycholic acid
when there is palpable enlargement of the liver and/or spleen, or if liver
enzymes are elevated to twice normal or above.
7.3 Oesophageal Varices
All children with CF liver disease should be monitored carefully for the
development of portal hypertension (see Section 7.2). Oesophageal varices
occur secondary to a rise in portal pressure and are often present even when
liver function tests are relatively normal. Varices can be detected on hepatic
ultrasonography, outlined with a barium swallow and confirmed by
endoscopy.
Prophylactic sclerotherapy
Varices may be obliterated by injection of a sclerosing agent. Often three to
six sclerotherapy sessions may be required for complete eradication of the
lesions with follow-up endoscopies at approximately six monthly intervals to
exclude recurrences. Ligation therapy has also been of significant benefit.
There are two schools of thought regarding prophylactic sclerotherapy:
- Some would claim that the benefits obtained from obliterating
potentially life threatening varices before they bleed outweighs the
respiratory complications of a general anaesthetic and the regular
monitoring required thereafter.
76

- Others argue that the complications of sclerotherapy (oesophagitis,
necrosis, ulceration, stricture formation, dysphagia and perforation)
outweigh the risks of bleeding and sclerotherapy should be delayed until
evidence of bleeding is documented. Prophylactic sclerotherapy may also
result in variceal formation at other sites and once a programme of
prophylactic sclerosis has been initiated, regular endoscopic examination
(often requiring anaesthesia in children) is required.
Endoscopic appearances seem to be the best guide as to the risk of bleeding:
large varices are more likely to bleed than small ones, tense lesions at greater
risk than flaccid and thinly covered veins more vulnerable than those with a
thicker overlying layer. Commonly, the final decision lies with the consultant
surgeon based on personal experience and practice.
At the CF clinic at GOSH, prophylactic sclerotherapy is not usually
recommended. Those who have had a variceal bleed should be referred for
urgent assessment for liver transplantation.
7.4 Liver Transplantation
Liver transplantation offers the only potentially curative treatment for
advanced CF related liver disease. It is an effective therapy in young CF
patients with portal hypertension and hepatic dysfunction and is indicated
before a critical stage of deteriorating lung function is reached. Pre-emptive
liver transplant in younger CF patients not only has a better outcome but
improves lung function. CF constitutes an indication for less than five
percent of paediatric liver transplants.
Evaluation and transplantation for end-stage liver disease associated with CF
should be undertaken at an early stage. Transplant assessments are carried out
at King’s College Hospital. Certain criteria are used to indicate when a child
should be referred to the liver transplant team. As all patients with significant
portal hypertension have splenomegaly, liver transplantation need not be
considered if this finding is absent on physical examination and abdominal
ultrasound. The criteria for liver transplant include indices of the severity of
the portal hypertension (frequency and severity of variceal bleeding, ascites),
of liver function (liver enzymes, albumin and prothrombin time), of
haematological signs of hypersplenism (low white cell count and platelet
count) and of nutritional status.
There are some specific contraindications to liver transplantation which may
be subject to change over time with the availability of new treatment options
in the future. These contraindications currently include longstanding history
of severe lung involvement with regular pulmonary exacerbations, colonization
with certain genomovars of the B. cepacia complex or other multiresistant
organisms, extensive lung fibrosis and evidence of severe pulmonary
hypertension with impairment of right ventricular function.
77

7.5 Arthropathy
Cystic fibrosis arthropathy (CFA) normally presents with episodic pain and
swelling of the large joints such as knees, ankles and wrists. It is often
accompanied by a low grade fever and there may be an erythematous or
purpuric rash or erythema nodosum. CFA may occur in up to 10% of
children with CF, with a mean age of onset between 13 to 20 years. It is
thought to be immune-mediated and related to chronic pulmonary infection
and inflammation. Joint x-rays are usually normal. Episodes of arthritis tend
to settle spontaneously after three to four days and respond well to nonsteroidal
anti-inflammatory drugs (e.g. ibuprofen). Intensification of chest
therapy may also help control joint symptoms.
Hypertrophic pulmonary osteoarthropathy (HPOA) may complicate
advanced lung disease that is associated with CF, resulting in severe joint
pain, joint effusions and early morning stiffness. It occurs in two to seven
percent of patients with a median onset of 20 years. X-rays can show
periosteal elevation and these changes may also be seen on an isotope bone
scan. Symptoms are mainly controlled by non-steroidal anti-inflammatory
drugs, intensification of chest therapy and on occasions oral steroids.
Refractory HPOA has also been treated with iv Pamidronate with some
effect.
7.6 Nasal Polyps
Nasal polyps occur in about 10% of children with CF and in up to 40% of
adults. They are uncommon under the age of five and onset is generally
between eight and ten years. Aetiology is uncertain but may be related to
infection, allergy, immune factors, altered secretions and abnormal ciliary
function. There is also an association with chronic sinus infection.
Polyps are usually asymptomatic but can result in chronic nasal obstruction,
which increases airways resistance and can lead to mouth breathing and
snoring. They can also cause headaches and impair smell and taste. Diagnosis
is made by direct visualisation.
If symptomatic, initial treatment is usually a steroid nasal spray such as
fluticasone (Flixonase) or beclomethasone (Beconase). Anti-histamines are of
limited value. If unsuccessful, surgery should be considered, but due to the
high recurrence rate (60 - 90%), multiple procedures may be necessary. Oral
steroids are occasionally used for severe multiple recurrent polyps.
78

7.7 Sinusitis
Although almost all children with CF have chronic paranasal sinusitis, only
one percent are symptomatic. X-ray of the sinuses is of little value as over
92% of all children with CF will have opacification of the maxillary, ethmoid
and sphenoid sinuses. Initially, opacity is due to retention of thick secretions
but later it may be due to polyposis within the sinuses. The frontal sinuses
may be underdeveloped in children with CF, probably due to early onset of
sinusitis which prevents pneumatisation. Chronic sinusitis is commonly
associated with nasal polyposis.
Sinusitis may cause headaches, particularly on tilting the head forwards.
Other symptoms are related to chronic nasal obstruction (mouth-breathing,
snoring, olfactory loss) and purulent drainage (postnasal drip, constant
throat-clearing, halitosis). Long-term oral antibiotics may be of value (three
to six weeks), and we have found oral metronidazole may improve halitosis.
Sinus wash-out is rarely successful as the secretions are thick and tenacious;
occasionally, more radical surgical drainage procedures are necessary to
alleviate symptoms.
79

Section Eight:
Pharmacopoeia
Drug Information
The following drug information is intended as a guide for prescription of
drugs commonly used in cystic fibrosis. For additional information or
confirmation please consult the GOSH formulary or the GOSH Antibiotic
Policy (2003).
Antibiotics Individual Doses Doses
Oral

Antibiotics Dose per Nebulisation Nebs
Nebulised 2 mnths: 90 mg/kg (18 g) 4
Tobramycin 1 - once daily 10mg/kg (550mg) 1
1 Infuse over 30 minutes. Monitor serum levels (before 2nd and 8th dose):
Trough (pre-dose)
Amikacin < 10 mg/l
Tobramycin < 1 mg/l
Gentamicin < 1 mg/l
Colistin Levels not recommended outside of neonatal period.
Levels must be taken in presence of renal failure.
81

Gastrointestinal Individual Oral Dosage Doses
Per Day
Acetylcysteine (Fabrol) 100-200 mg (available as granules in a sachet) 1-3
Cisapride 0.2 mg/kg (maximum 10 mg/dose) 3
(Named patient use)
Gastrografin 1 < 7 years: 50 ml } with 4 times the volume 3
> 7 years: 100 ml } of water 3
Klean Prep 2 20-30 ml/kg/hour Maximum
(start slowly, details below) 1 l/hour
Lactulose 5-20 ml (depending on age and response) 2-3
Lansoprazole 30 kg: 30 mg (max 60 mg) 1
Omeprazole 1-3 mg/kg 1
Ranitidine < 6 mnths: 1 mg/kg 3
> 6 mnths: 2-4 mg/kg 2
Ursodeoxycholic acid 10 mg/kg 2
1 Monitor intravascular fluid volume carefully 2 Hypoglycaemia has been reported
Klean-Prep
5-10 kg weight 1st 1 /2 hour: 50 ml/hour, then for
1 hour 100 ml/hour, then at
200 ml/hour until bowel is emptied
10-20 kg weight 1st 1 /2 hour: 100 ml/hour, then for
1 hour 200 ml/hour, then at
300 ml/hour until bowel is emptied
20-30 kg weight 1st 1 /2 hour: 200 ml/hour, then for
1 hour 300 ml/hour, then at
500 ml/hour until bowel is emptied
> 30 kg weight 1st 1 /2 hour: 200 ml/hour, then for
82
1 hour 400 ml/hour, then at
600 ml/hour until bowel is emptied

Vitamins and Minerals
DOSAGE: < 1 year > 1 year
Vitamin A 1200 µg/4,000 IU 1,500 µg/5,000 IU
Vitamin D 10 µg/400 IU 15 µg/600 IU
Vitamin E 50 mg/75 IU 100 mg/150 IU
Vitamin K 12yrs 10 mg/day
- water soluble)
Product Usual Fat soluble vitamin content
Dalivit
Multivitamins (BPC or equivalent)
Daily Dose A D E
0.6 ml 1500 µg 10 µg
1.2 ml 3000 µg 20 µg
Capsules/tablets 2 /day approx approx
Vitamin E
Sodium chloride
1500 µg 15 µg
- Suspension 0.5-1 ml – – 100 mg/ml
- Tablets 1 /2-1 tablet – – 100 mg/tablet
< 2 yrs: additional 2 mmol/kg
2-7 yrs: 10-20 mmol/day (600-1200 mg)
> 7 yrs: 2-4g/day
83

Mucolytics Individual nebulised dosage Doses
< 5 years > 5 years Per Day
3% Saline 3-5 ml 3-5 ml Pre-physiotherapy
Parvolex (n-acetylcysteine) 0.5 ml 1 ml
or + + Pre-physiotherapy
Mistabron (mesna) 3 ml NaCl 2.5 ml NaCl
DNase (Pulmozyme) 2.5 mg 2.5 mg Once daily / alternate days
Non Enteric-Coated
Enzymes Per Capsule (BP Units)
(for tube feeders & those unable to swallow)
(>1 hour before physiotherapy)
Protease Lipase Amylase Appearance
Pancrex V Capsules 160 2950 3300 Clear capsules
‘125 (Paines & Byrne)’ containing powder.
Enteric Coated
Standard Preparations
Nutrizym GR (Merck) 650 10000 10000 Olive green/yellow
opaque capsules
Pancrease (Cilag) 330 5000 2900 White opaque capsules.
Containing microspheres.
Creon 10000 600 10000 8000 Brown/translucent capsules
84
containing microspheres

Prescribable Nutritional Supplements Used in Cystic Fibrosis
Product Manufacturer Comments
Glucose polymer powders
Caloreen Nestlé
Maxijul Scientific Hospital All provide about 4kCal/g powder.
Supplies (SHS) Can be made into a solution with
Polycal Nutricia water or mixed in with food
Polycose Abbott
Glucose polymer liquids
Maxijul liquid SHS Flavoured concentrated glucose polymer
Polycal liquid Nutricia solutions. Can be drunk neat, diluted
Milk shakes
1kCal/ml:
Ensure Abbott
Fresubin Fresenius
with a fizzy drink or used to make jelly
or instant puddings
1.5kCal/ml: Liquid in cans or cartons with a straw
Ensure plus Abbott Various flavours (savoury and sweet)
Entera Fresenius
Fortisip Cow & Gate
Powder:
Calshake Fresenius
Scandishake SHS 600 kCal (1 sachet + 240ml milk)
Yogurt style Fortifresh Nutricia 1.5kCal/ml
Non-milk based supplements
Fortijuce Nutricia 1.5 kCal/ml
Enlive Abbott 1.25 kCal/ml
Provide Xtra Fresenius 1.25 kCal/ml
This list is not comprehensive but mentions the most commonly used
products
85

Section Nine:
Useful Names and Addresses
9.0 Useful Names and Addresses
ADULT CF CENTRES
Royal Brompton National Heart & Lung Hospital
Department of Cystic Fibrosis
Sydney Street
London SW3 6NP
Tel: 020-7352-8121
Professor M Hodson - Consultant
Dr Sarah Elkin - Consultant
Professor D Geddes - Consultant
Su Madge - Nurse Consultant
Jacquie Francis CNS (paeds)
London Chest Hospital
Bonner Road
Bethnal Green
London E2 9JX
Tel: 020-8980-4433
Dr D Empey - Consultant (adults)
Anne-Marie McCormack CNS
Mark Butler - CNS
Papworth Hospital
Papworth Everard
Cambridge CB3 8RE
Tel: 01480-830541
Dr D Bilton - Consultant
Dr C Haworth - Consultant
Angie Lyons - CNS
86

ASSOCIATIONS
Cystic Fibrosis Trust
11 London Road
Bromley, Kent BR1 1BY
Tel: 020 8464 7211
www.cftrust.org.uk
PHYSIOTHERAPY EQUIPMENT
PEP Masks:
Order: PEP-RMT masks and sets Astratech
71001 (child) PO Box 13
71002 (adult) Gloucester GL5 3DL
Pressure gauges 71040 Tel: 01453 791763
Postural Drainage:
Chesham Postural Drainage Frame: Chesham Engineering Co Ltd
217 Berkhampstead Road
Chesham
Bucks HP5 3AP
Tel: 01494 783599
Foam wedges: For postural drainage Pentoville Rubber Products Ltd
48-50 Pentoville Road
London N1 9HF
Tel: 020 7837 4582 / 0238
Becki beds: 25 Garston Crescent
Calcott
Reading
Berks
Tel: 01734 428791
Parents can ask for VAT exemption forms from the CF Trust when
purchasing equipment.
NEBULISERS & COMPRESSORS
Nebulisers:
For antibiotics order Ventstream nebuliser: Medic-Aid
For others order Sidestream nebuliser: Hook Lane
Pagham
West Sussex PO21 3PP
Tel: 01243 267321
87

OR
For antibiotics order Pari LC Plus with Pari Medical Limited
filter-valve set (white pot): London House
For DNase order Pari LC Plus (yellow pot): 243-253 Lower Mortlake Rd
Surrey TW9 2LL
Tel: 020 8332 6513
Compressors:
Porta nebs are ordered via out-patients and are serviced on a yearly basis
by biomedical engineering. Multi-voltage and freeway-lite compressors are
available for loan by the CF Nurse Specialists ext 2328.
GASTROSTOMY TUBES
As there are many types on the market they can be ordered via the
Clinical Nurse Specialist in Stoma Care (bleep 609).
Buttons:
MIC-KEY Vygon UK Ltd Vygon UK Ltd
skin level gastrostomy feeding set Bridge Road
Cirencester
Glos GL7 1PT
Tel: 01285657051
Peg Tubes: Order Freka – PEG
Standard gastric set 7901 051 Fresenius Ltd
Christleton Court
Stuart Road
Manor Park
Runcorn
Cheshire WA7 1 ST
Tel: 01928 579444
TIVAD
Portacaths:
Order Low profile titanium, Sims Portex Ltd
venous access device: New Universal House
Gripper needles 22 g 303 Chase Road
Straight huber needles 22 g 1” Southgate
London N14 6JB
Tel 020 8882 9535
Fax: 020 8886 7757
88

Section 10:
Further Reading
General
• Aurora P, Whitehead B, Wade A, Bowyer J, Whitmore P, Rees PG, Tsang
VT, Elliott MJ, de Leval M: Lung transplantation and life extension in
children with cystic fibrosis. Lancet 1999;354:1591-1593
• Bluebond-Langer M, Lask B, Angst D. Psychosocial aspects of cystic
fibrosis. Arnold, London 2001
• Borowitz D, Baker RD, Satllings V. Consensus report on nutrition for
paediatric patients with cystic fibrosis. J Pediatr Gastroenterol Nut 2002;
35(3): 246-259
• Davis PB. Cystic Fibrosis. Pediatric Reviews 2001; 22(8): 257-264
• DiWakar V, Pearsn L, Beath S. Liver disease in children with cystic
fibrosis. Paediar Resp Rev 2001; 2(4): 340-349
• Hodson ME, Geddes DM. Cystic Fibrosis (2nd ed). Arnold, London
2000
• Lanng S. Glucose intolerance in cystic fibrosis patients. Paediatr Resp
Rev 2001; 2(3): 253-259
• Prasad SA, Tannenbaum E, Mikelsons C. Physiotherapy in Cystic
Fibrosis. J Royal Soc Med 2000; 93 (suppl 38): 27-35
• Ratjen F, Doring G. Cystic Fibrosis. Lancet 2003 Feb 22; 361: 681-689
• Roskin BJ, Cutting GR. The diagnosis of cystic fibrosis: a consensus
statement. J Pediatr 1998; 132(4): 589-595
• Saiman L, Siegel J, and the Cystic Fibrosis Foundation Consensus
Conference on Infection Control Participants. American Journal of
Infection Control 2003; 31: 55-552
• Sokol RJ, Durie PR. Recommendations for management of liver and
biliary tract disease in cystic fibrosis. Cystic Fibrosis Foundation
Hepatobiliary Disease Consensus Group. J. Pediatr Gastroenterol Nutr
1999; 28 (Suppl 1): S1-13
• Stevens DA, Moss RB, Kurup VP et al. Allergic bronchopulmonary
aspergillosis in cystic fibrosis - state of the art: Cystic Fibrosis Foundation
Consensus Conference. Clin Infect Dis 2003; 37 (Suppl 3): 225-64
89

Cystic Fibrosis Trust Booklets
• Antibiotic treatment for cystic fibrosis (2nd edition). Sept 2002
• Standards of care. May 2001
• National consensus standards for the nursing management of cystic
fibrosis. May 2001
• Clinical guidelines for the physiotherapy management of cystic fibrosis.
Jan 2002
• Nutritional management of cystic fibrosis. April 2002
• Pseudomonas infection in cystic fibrosis. May 2001
Internet sites
• Cystic Fibrosis Trust (UK)
www.cftrust.org.uk
• Cystic Fibrosis Foundation (USA)
www.cff.org
• Canadian Cystic Fibrosis Foundation
www.cysticfibrosis.ca
90

© GOSH Trust 2004
Produced from donations to the Badger Ward Trust Funds
Great Ormond Street Hospital for Children NHS Trust
Great Ormond Street
London WC1N 3JH