Communication at the Time of Diagnosis
It is difficult for parents and/or patients to obtain more than a general impression of the condition when it is explained for the first time. Not only is CF a very complex disorder but parents are usually shocked and unable to follow detailed explanations at that time. There is a need to consolidate the information they receive at their first visit.
A team approach must be followed. Clinic visits should include consultation with medical personnel, physiotherapists, dieticians, clinic sisters, pharmacists, social workers, psychologists and parent support groups. Information must be made available to general practitioners, caregivers, teachers, relatives and friends. This information should be available in hard copy from the clinic. Additional sites of information, such as the Internet, may be of use.
It may be helpful for relatives to talk to the families of other affected individuals. Mutual support is generally most beneficial. "Remember, you are not alone".
General Management by a NON-CF Specialist
General Facts Discussed at the Time of Diagnosis
- CF remains a serious disorder despite the major advances of recent years.
- The condition of the patient and the long-term outlook depends on the effectiveness
- The outlook continues to improve year by year.
- Individuals who have CF will always need regular follow-up at a hospital. The condition is so complex and advances in treatment so rapid that all patients must be cared for under the guidance of the CF specialist at the regional CF clinic.
- The hereditary aspects of CF.
- Families are told about the Cystic Fibrosis Association. If they agree, their names are forwarded to the relevant CF association.
There are a number of reasonable precautions that should be observed by the CF individual and the family:
- Immunisation is very important (see Section 4.3, p*).
- NO SMOKING (active or passive). Smoking is particularly bad for people with CF.
- Starting nursery school or crèche should be delayed (ideally until 3 years of age).
- Reduction of exposure to friends and relatives who have just started with a "cold" as this is when they are at their most infectious.
- If an infant with CF is admitted to hospital, every effort should be made to provide a cubicle to reduce the risk of acquiring an acute viral infection from other acutely ill children.
- Avoidance of close contact with stables, compost or other forms of rotting vegetation is advised because of the risk of the inhaling Aspergillus spores or infection by Burkholderia cepacia.
CF patients should attend a specialist CF Clinic
- Patients should attend a CF Clinic every one to three months.
- Here the patient's progress must be reviewed by the entire team, if possible.
- At every visit the patient must be weighed and measured.
- At every visit a sputum sample or cough swab should be sent for microscopy, culture and sensitivity.
- Parents should have a sputum container at home to send to the laboratory in the event of new respiratory infection or production of unusually purulent sputum.
- From the age of five years, spirometry should be performed (by experienced personnel).
- Oxygen saturation should be measured using a pulse oximeter.
- To avoid cross infection when using all respiratory function equipment, the use of bacterial filters is advised.
- All staff must wash their hands between patients.
- A comprehensive CF assessment is recommended at diagnosis and annually
Confirmation of diagnosis
Lung status and Tests
Full blood count
Social worker consult
An annual influenza vaccine covering the expected strains for that season should be given as a routine in March/April except if there has been anaphylaxis to egg.
Passive immunisation against the respiratory syncytial virus (Synergis®) for children under the age of 2 years is thought to be useful during epidemics.
Immunisation against chicken pox and hepatitis A is recommended.
A vaccine to Pseudomonas aeruginosa is under trial at present. When/If it becomes available it should be given prior to colonisation with the organism.
Lung status and Tests
Included in the discussions should be:
- Current health status
- Meaning of the changes (if any) over the year reviewed (good and not so good news)
- Adjustments to treatment regimes for the coming year
- Aims of the adjustments
- Discussion of the patient's CF care in general
- Planning for life events in the coming year e.g. school, employment
The secretion of digestive juice from the pancreas is severely reduced in most CF patients from an early age and, unless treated with pancreatic enzyme supplements, the digestion and absorption of food are severely impaired. Inadequate absorption of food from the bowel will lead to unpleasant digestive symptoms, malnutrition, poor growth and specific deficiencies of fat soluble vitamins A, D, E and K.
Well-nourished patients have fewer infections, better quality of life and increased life span. It is, therefore, essential that CF patients be referred to a dietician experienced in the management of CF. Every effort must be made to achieve normal growth in CF as good nutrition promotes good quality of life and longevity.
Feeding of Infants
Pancreatic Enzyme Supplementation
High Lipase Pancreatic Preparations
Pancreatic preparations containing three to five times the quantity of lipase (Creon 25000®) are available for older children. Care should be taken to avoid total daily lipase intake of greater than 10000 U/kg/day.
Use one of the acid-resistant microsphere preparations.
Enzymes are best given at the beginning or early in the meal. Half the dose at the beginning and half in the middle of the meal is recommended.
Capsules should be swallowed whole from as early an age as possible. If removed from the capsule, the microspheres should not be sprinkled on or mixed with the whole meal. Microspheres should be mixed with a little fluid and taken in one swallow. If mixed with food or fruit puree, they should be mixed with one teaspoonful and taken in one or two swallows. Microspheres must not be chewed.
Enzymes are required with all meals and drinks that contain fat. Start with or ½ capsule (i.e. 3000 to 5000 units) in infants and one or two capsules per meal in older patients. Increase gradually until the bowel symptoms are controlled. Increase the dose with more fatty meals. It is advisable not to exceed a dose of 3000 units of lipase/kg body weight/meal or 10 000 units of lipase/kg body weight/day. Some patients may require higher doses.
Changes in dose should be made gradually to avoid constipation.
Insufficient pancreatic enzyme will cause symptoms of malabsorption e.g. abdominal pain, pale, loose, fatty, offensive stools, and will eventually lead to growth failure.
A diet that is high in both energy and protein is required to achieve normal weight gain and growth. Individual requirements vary but most patients need 20 to 80% more energy than an unaffected individual of the same age. The food intake of most patients does not meet this increased energy requirement.
Patients are encouraged to take foods rich in energy such as fried foods, crisps and chocolate and those rich in protein such as milk, cheese and meat as part of their total balanced diet. Dietary sources of fat such as butter, margarine, cream or mayonnaise can be added to food to increase the energy density.
Dietary fat intake should never be restricted as this nutrient is essential to achieve a high energy intake and a normal nutritional state with growth. If foods with a high fat content cause abdominal pain or more frequent and paler stools, the dose of pancreatic enzymes should be increased whenever that food is taken. The dose is gradually increased until the food is tolerated and the steatorrhoea resolves.
It is very important that children are given frequent meals and snacks (5-6 per day) from a young age to maximise daily energy intake. Toddlers should get into the habit of regular eating. This habit will stand them in good stead as they grow up.
Psychological factors may play a major role in poor food intake patterns in some children and adolescents.
A booklet by Dr. Tony Westwood of the Red Cross Children's Hospital in Cape Town provides useful recipes and advice on CF nutrition (available from SACFA or CF centres)
There is excessive loss of salt in sweat in CF. Most South African diets contain sufficient salt to compensate for this. There are two circumstances under which excess salt loss may cause clinical problems for someone with CF.
All infants with CF lose about 0.5 mmol/kg more sodium than non-CF infants. Salt deficiency can contribute to poor weight gain and must be sought where other explanations (e.g. inadequate pancreatic supplementation) are not present. Hyponatraemic dehydration may be a presenting feature of CF. In these circumstances, 0.5-1mmol/kg of salt per day in a 3% solution should be given until the age when solids constitute most of the child's diet.
Older children who live in and all who exercise in conditions of high environmental temperature should take salt tablets (1-3 per day) or increase their dietary salt and also increase their fluid intake.
Salt intake should not be restricted but excessive salt intake is dangerous.
All CF individuals should receive supplements of the fat soluble vitamins A, D and E. The recommended daily supplements that usually achieve normal plasma levels are considerably greater than the usual daily recommended intake. The plasma fat soluble vitamin levels should be checked annually and the dose adjusted depending on the levels. Dosages are given in Appendix 8.
Vitamin A deficiency may cause night blindness in older patients. Clinical progress improves when low levels of vitamin A detected at assessment are corrected.
Vitamin D deficiency may cause rickets (which is rare) and osteomalacia. Osteoporosis and low levels of vitamin D metabolites are well documented, particularly in older patients.
Vitamin E deficiency may cause haemolytic anaemia in infants. In older CF individuals Vitamin E deficiency may cause neurological problems. Vitamin E appears to be important as an anti-oxidant in CF.
Vitamin K may be low, particularly if there is an associated liver problem, and supplements of Vitamin K, 10mg daily, may be required if the INR is abnormal or if elective surgery is planned. Vitamin K is also important in bone disease.
Iron supplements are not routinely needed. Full blood count should be monitored annually. Patients with moderate to severe lung disease require iron supplementation.
Many CF patients take insufficient dietary calcium. Calcium supplementation is recommended to maximise bone mineral accretion.
Assessment of Growth and Nutritional status
Growth and nutritional status need to be assessed at a specialised CF clinic every 1 to 3 months
Weight, length/height and head circumference
These must be measured and plotted on growth charts at regular intervals, looking at the pattern of growth. Current standards used in South Africa are the WHO z-score charts of weight and length/height for age and weight for height. Body mass index (BMI) is a useful index and plotted on WHO charts for children and standard tables for adults. Children under 5 years of age should have their head circumference measured every 6 months.
Mid arm muscle circumference and triceps skinfold thickness are useful indicators of lean body mass and body fat.
Growth velocity is an important measure and can assist in identifying sub-optimal growth.
Many CF patients do not eat enough. Dietary intakes must be assessed regularly to ensure that energy requirements are being met. As part of their annual assessment, patients should record a 3-day dietary diary from which their nutritional intake is analysed and advice is given accordingly.
Nasogastric & Enterstomy Feeds
- Children less than 5 years: weight/height less than 85% expected; weight loss or plateau in weight gain over 4 months.
- Children 5-18 years: weight/height <85% expected; weight loss or plateau in weight gain over 6 months
- Adults: a BMI of <19; weight loss of >5% body weight for more than 2 months duration
- Fine nasogastric tube left in permanently or replaced every morning (not usually well tolerated in the long term).
- Percutaneous endoscopic gastrostomy (PEG) with gastrostomy button.
- Traditional surgical placement.
- Feed for 10-12 hours at night (stop 2 hours before morning physiotherapy session).
- Eat normally during the day. At least 40-50% of the total daily energy requirement should be given at night.
- Ideally use a peristaltic pump to avoid the tube blocking.
- Use Ensure® as food source (not semi-elemental expensive preparations).
- Take two thirds of enzymes at beginning and one third in morning on wakening or half on starting and half on going to sleep. Dosage to be adjusted according to usual enzyme requirement per gram of fat for the patient.
- Patients tolerate smaller volumes of higher concentration feeds (1 or 1.5kcal/ml) better than larger volumes of less concentrated formulae.
- Prokinetic agents may be required. Patients should be encouraged to sleep with the head elevated (30%).
- Vomiting, aspiration and increase in gastro-oesophageal reflux.
- Hyperglycaemia. Baseline oral GTT should be done before this type of feeding is commenced. Some patients will require insulin supplementation during feeding at night (see Diabetes mellitus Chapter 8 page *)
- Leakage, bleeding or ulceration at the gastrostomy site.
Management of cystic fibrosis-related diabetes in children and adolescents
Factors specific to CF that cause fluctuations in glucose metabolism include:
- respiratory infection and inflammation,
- increased energy expenditure,
- malnutrition, glucagon deficiency and
- gastrointestinal abnormalities
- altered gastric emptying and intestinal motility
- liver disease.
Abnormal chloride channel function in CF results in thick viscous secretions causing obstructive damage to the exocrine pancreas with progressive fibrosis and fatty infiltration. This result in disruption and destruction of islet architecture leading toloss of endocrine beta, alpha and pancreatic polypeptide cells. Beta-cell dysfunction is not related to autoimmune disease in CF, outside of isolated case reports of autoantibody positive individuals with CFRD.
The role of insulin deficiency
The primary defect in CFRD is severe but not absolute insulin deficiency. Virtually all exocrine insufficient patients with CF, with and without diabetes, show evidence of beta-cell dysfunction . Fasting insulin and C-peptide concentrations are normal, but there is delay and blunting of peak insulin secretion during a standard OGTT. This effect is more pronounced with worsening glycemic status. Delayed insulin secretion during the OGTT is related to loss of first phase insulin secretion, which is found even in CF patients with normal glucose tolerance. Secretion of other islet hormones is also impaired in CF, in particular loss of glucagon responses.
The role of insulin resistance
In CF patients without diabetes, insulin sensitivity is variable. While most of these patients are sensitive to insulin in their baseline state of health, infection and inflammation increase insulin resistance. CF patients with diabetes are insulin resistant, due to both decreased peripheral glucose uptake and poor insulin suppression of hepatic glucose production. Insulin resistance can become acutely severe during infectious exacerbations.
- Unexplained polyuria or polydipsia
- Failure to gain or maintain weight despite nutritional intervention
- Poor growth velocity
- Delayed progression of puberty
- Unexplained chronic decline in pulmonary function
Diagnosis of CFRD
- Oral glucose tolerance test
- Random and fasting glucose levels - while hyperglycemia is diagnostic for diabetes, normal fasting or random glucose levels do not exclude a diagnosis of diabetes in CF
- Continuous glucose monitoring - this may aid the diagnosis of CFRD when considered in conjunction with the OGTT result and the clinical scenario.
- HbA1c has been shown to be unreliable in the diagnosis of CFRD.
Insulin is the only recommended medical therapy for CFRD. Insulin therapy may help to stabilise lung function and improves nutritional status in patients with CFRD. There are no definitive data to date on the benefits of insulin therapy for CF children and adolescents with milder forms of abnormal glucose tolerance, although a small case series has demonstrated similar benefit. Choice of the insulin regimen depends on individual needs and characteristics of the patient. The standard basal bolus regimen provides background insulin and a continuous anabolic effect. The short acting insulin controls postprandial hyperglycaemic episodes and provides flexibility for variable eating patterns. Alternatively, effective basal-bolus therapy can be accomplished with insulin pump therapy.
Oral diabetes agents
Oral diabetes agents are currently not recommended in CFRD.
CFRD without fasting hyperglycemia and CF with impaired glucose tolerance
While insulin treatment of CFRD with fasting hyperglycemia has been the accepted standard-of-care for several years, treatment of less severe glucose tolerance
Routine annual testing for diabetes should be performed in CF patients aged 10 years and older during a time when they are clinically well. The decision to treat should be based on consideration of blood glucose levels and the impact of treatment on the individual's overall condition.