Cystic Fibrosis PDF

Cystic Fibrosis  Introduction One of the most common recessively inherited life limiting disease in UK. Rare in Chinese, South East Asian and African-Caribbean ethnic groups. 56% of CF patients are adults Median survival is app. 41.4 years.  Introd...

Cystic Fibrosis  Introduction One of the most common recessively inherited life limiting disease in UK. Rare in Chinese, South East Asian and African-Caribbean ethnic groups. 56% of CF patients are adults Median survival is app. 41.4 years.  Introduction Initial symptoms generally develop before 2 years old (occasionally, it may be later). Responsible gene is on chromosome 7 and encodes the protein CFTR (CF transmembrane conductance regulator). Dysfunction in the regulation of salt and water across the cell membranes of secretory epithelial cells and in thickened secretions in all organs with epithelial cells.  Pathophysiology Dysfunction of exocrine glands with disturbances of ion and fluid movement. Thick and dehydrated secretions → multi-organ condition Recurrent Exocrine Intestinal Infertility, IGT/ CFRD respiratory pancreas obstruction especially in infection, insufficiency (meconium males inflammation... with ileus/ bowel Respiratory malabsorption blockage) failure  Pathophysiology Dysfunction of exocrine glands with disturbances of ion and fluid movement. Thick and dehydrated secretions → multi-organ condition Liver diease and Reduced bone Gut motility CF Behavioral portal mineral problems arthropathy and hypertension density psychological pbs  Diagnosis Newborn offered screening on day 5 of life Diagnosis confirmed by sweat test and/or genetic mutations analysis by 4 weeks of age. Early diagnosis → better growth and nutrition  Clinical features Chronic respiratory disease: – Lungs are affected after few weeks of birth. – Obstruction in small airways → progressive and destructive secondary infection. – Common organisms cultured from the lungs are: Staphylococcus aureus, Haemophilus influenzae and subsequently Pseudomonas species. – Damage to the bronchial wall, bronchiectasis and abcess formation. – The child has a persistent, loose cough productive of purulent sputum  Clinical features Chronic respiratory disease: – Objective of respiratory management is to control infection and remove thickened bronchial secretions. Regular surveillance of secretions and prompt and aggressive treatment of infection with ATB. Antibiotic therapy. Regular chest physiotherapy. Use of bronchodilators, anti-asthma treatment and oral steroids. Active lifestyle and physical exercise  Clinical features Gastrointestinal symptoms: Pancreatic insufficiency: – Most common GI problem. – 92% of patients become pancreatic insufficient by 12 m. – Damage begins in utero (replacement of the acini with fibrous tissue and fat/90% of acinar function is lost). – Secretion of digestive enzymes and bicarbonate is disrupted. – Malabsorption of fat, protein, nitrogen, bile, fat-soluble vitamins, vitamin B12… – Treatment: PERT – Diagnosis: fecal elastase  Clinical features Gastrointestinal symptoms: Meconium ileus: – Apparent within the first days of life – Caused by blockage of the terminal ileum by meconium and develops in utero – Management may include surgical intervention  Clinical features Gastrointestinal symptoms: Distal intestinal obstruction syndrome: – Frequent abdominal pain, with complete or partial intestinal obstruction. – Fecal material and mucus gathers in the distal ileum and there is a palpable mass in the right lower abdomen. – Treatment: rehydration + stool softening laxatives or gut lavage → surgery sometimes.  Clinical features Gastrointestinal symptoms: Gastro-oesophageal reflux (GOR): – Mainly caused by inappropriate relaxation of the gastro-oesophageal sphincter. – Improves with increasing age. – Leads to poor weight gain, feeding disturbances, abdominal pain, respiratory symptoms (May adversely affect lung disease by aspiration and reflex bronchospasm). – Treatment: thickening feeds and use of anti-reflux medication.  Clinical features Gastrointestinal symptoms: Abdominal pain: – Occur +++ in children with poorly controlled malabsorption or constipation. – Negative impact on nutritional intake and nutritional status.  Clinical features Other clinical problems: CF related diabetes: – Progressive fibrosis and fatty infiltration of the exocrine pancreas lead to destruction of islet architecture → loss of endocrine cells secreting insulin, glucagon and pancreatic polypeptide. – Features of type I and type II DM: non ketotic and insulin dependant. – Gradual onset, preceded by worsening of nutritional status and decline in lung function. – Negative impact on growth in adolescents, on nutritional status, respiratory function and survival. – More common in females.  Clinical features Other clinical problems: CF related diabetes: – Diagnosis and screening: Annual screening through random BG monitoring. All patients over the age of 12 years should be screened annually by performing a OGTT. Result should be considered alongside the clinical picture at the times Abnormal OGTT → higher risk of CFRD HbA1C: not sensitive enough to detect CFRD, possibly because hyperglycemia may be transient or because RBC turnover is elevated due to chronic inflammation in CF.  Clinical features Other clinical problems: CF related diabetes: – OGTT: gold standard to diagnose CFRD, but – CGM important to detect early stage “pre diabetic phase” Present 4 years prior to diagnosis of CFRD Deterioration in lung function, poor growth and weight gain Important for patient receiving overnight enteral nutrition to avoid nocturnal hyperglycemia.  Clinical features Other clinical problems: CF related diabetes: – Treatment: Insulin is the mainstay of treatment Insulin has anabolic effects Control sometimes difficult to achieve because of poor compliance, variable food intake, exercise and growth. Better control achieved with multiple daily injections or short acting insulin given with meals (dose adjusted based on food intake)  Clinical features Other clinical problems: Liver disease: – Multilobular cirrhosis (1st decade of life) → portal HTN & variceal bleeding → liver failure. – Annual screening – Diagnosis: 2 of (abnormal liver functions test, abnormal physical examination, abnormal liver ultrasound) → biopsy – Worsens fat absorption – ESLD → transplantation (but nutritional status does not improve)  Clinical features Other clinical problems: Bone disease: – Low BMD thought osteoporosis or vit D deficiency osteomalacia. – Failure to gain bone mass normally or premature bone loss in ado and adults. – Etiology of low BMD: Overall disease severity Frequency and duration of ATB therapy Corticosteroid use Exercise tolerance and level of physical activity DF508 genotype CFRD Delayed puberty  Clinical features Other clinical problems: Bone disease: – Puberty may be delayed in CF and this is associated with a reduction in bone age and delay in peak height velocity by 9-14 months.  Clinical features Other clinical problems: Bone disease: – Diagnosis: DXA from around 10 years of age (lumbar spine) Repeated every 1-5 years – Recommendations: Goal: achieve normal weight , height, body composition, optimal vit D, Ca, vit K. Weight bearing exercise (20-30 min, 3 times per week ) Glucocorticoid use should be minimized Treat pulmonary complications Recognize and treat pubertal delay Diagnosis  Diagnosis Chloride Concentration for Result Infants (birth to 6 months) 0 - 29 mmol/L Cystic fibrosis is unlikely 30 - 59 mmol/L Intermediate ≥ 60 mmol/L Indicative Chloride Concentration for Infants (older than 6 months) Result children and adults 0 - 39 mmol/L Cystic fibrosis is unlikely 40 - 59 mmol/L Intermediate ≥ 60 mmol/L Indicative of cystic fibrosis  Nutritional management Causes of malnutrition: E losses: – Pancreatic insufficiency → secretions containing less enzymes and bicarbonate, lower pH and smaller V – If untreated → foul smelling frequent loose stools, malabsorption of fat and nitrogen. – CHO malabsorption is minimal – Tx: PERT – Lack of bicarbonate → reduced buffering of HCl in duodenum → dec. efficiency of pancreatic enzymes. – Abnormalities in mucosal ion transport & impaired uptake of nutrients. – Altered motility → affect absorption.  Nutritional management Causes of malnutrition: E losses: – Exacerbated by previous GI surgery for meconium ileus. – Vomiting following cough and GOR. – Glycosuria – CFLD → malabsorption  Nutritional management Causes of malnutrition: Increased E expenditure: – Impaired lung function increases REE. – Associated to declining pulmonary function and subclinical infection, increased O2 cost and work of breathing. – Individual assessment to calculate E needs. – Decreased activity level could compensate Anorexia and low E intake: – During pulmonary exacerbation, E requirements increase but appetite reduces → slow W gain punctuated by weight loss during exacerbations. – Behavioral feeding difficulties.  Assessment of growth and nutritional status W , H and head circumference: – Patients with CF often have a delayed puberty. This can lead to overestimation of malnutrition (drop from the growth centiles before demonstrating catch-up during pubertal growth spurt). BMI. W/A, H/A, W/H. – Interpret with care in case of delayed puberty. – % wt/ht, %wt/age and % ht/age – No single accurate measurement. SFT→ poor reproducibility, not recommended in routine practice. Mid upper arm circumference: used in organomegaly and fluid retention (advanced CFLD). Bone age: assessed in any child with stunting (%ht/age < 90%, or height < 0.4th centile) or pubertal delay. BMD: after 10 y and repeated every 1-5 years.  Assessment of growth and nutritional status Definition of growth failure: – Children < 5 years: W/H < 85% W loss or plateau in W gain over 2 clinic visits (max 4 months). – Children from 5-18 years: W/H < 85% W loss or plateau over 2 clinic visits (max 6 months).  Nutritional management Energy: – In general: 120-150% of the requirements for age and sex. High fat diet is recommended (+++ MUFA and PUFA) Increase refined CHO intake Encourage snacks between meals but without affecting appetite at main meals. Attention to media influence about healthy diets.  Nutritional support Oral supplementation Supplements may be considered if dietetic counseling to improve E and protein intake has been given and there is persistent: – W/H is 85-89% – No weight gain for 4 months in children < 5y – No weight gain for 6 months in children > 5y – Plateau in weight for 4-6 months Nutritional support  Nutritional support Enteral feeding Considered if nutrition and supplements have failed: – Child is persistently less than 85% expected weight for height. – Height and weight are below the second percentile. This will improve: – Weight gain and nutritional status – Respiratory function – Height for age and BMI NG (short term) or gastrostomy (long term) Given overnight.  Nutritional support Route of feed Nasogastric feeding: – Short term duration during respiratory exacerbations or as a trial prior to gastrostomy – Preferred in patients with oesophageal or gastric varices in whom gastrostomy placement may be contraindicated. – Disadvantages: coughing, difficulties passing the tube, nasal irritation, swallowing enzymes which becomes uncomfortable. Percutaneous endoscopic gastrostomy (PEG): – Preferred route in children for long term feeding. – Feeding may be more comfortable +++ during exacerbations.  Nutritional support Types of enteral feed: – Whole protein polymeric feeds: 1.5 kcal/ml are generally tolerated, cheap, prescribable, low osmolarity, sterile ready to hang packs. – Elemental feeds (a.a. based feeds): Lower in fats than polymeric feeds Mixture of MCT and LCT → reduce amount of PERT required Expensive, high osmolality, low E density. – High fat feeds: contradictions about its benefits. Theoretical advantage in patients with severe lung disease as they result in less CO2 production and lower respiratory quotient. Not routinely used in clinical practice  Nutritional support Pancreatic enzymes with feeds: – Optimum fat absorption when enzymes were given in a divided dose, at the start of the feed (1/2 dose) and part way through the feed or at the end (1/2 dose). – Initial dose of enzymes based on the fat content of the feed titrated against the number of enzymes required for a fat containing meal or snack is used, and then adjusted based on GI symptoms. – Should be taken orally (impossible in ventilated patients) → choose an a.a. based, MCT containing feed given continuously over 24 h If still malabs., give powdered enzyme preparations mixed with water via the feeding tube.  Vitamin and mineral supplements Fat soluble vitamins Frequent in CF +++ in case of pancreatic insufficiency and altered bile salt metabolism. Patients with PI should receive vit A, D, E (recheck levels every 3-6 m). – Taken with or just prior to meal times to coincide with PERT supplementation Patients without PI should be monitored for supp. needs.  Vitamin and mineral supplements Fat soluble vitamins Vitamin K: – Inconclusive results. – Risk factors: CFLD, ATB use, short gut syndrome. – Suggestion: vit K supplementation should be considered in patients with low BMD, liver disease or prolonged prothrombin time  Vitamin supplementation usually given in CF Vit D: 75 nmol/l. May reach 2000 IU in adolescents. For vit K: 300 µg/kg/d for infants 5 mg for children 2-7 y 10 mg for children > 7 years  Vitamin and mineral supplements Minerals Calcium: – Should be optimized to reduce the risk of low BMD – 1300-1500 mg/d in children > 8 y +++ in those who dislike dairy foods.  Vitamin and mineral supplements Minerals Sodium: – Breast milk and infants formulas have relatively low Na content. – Deficiency confirmed by urinary Na → sup: 1-2 mmol/kg/d in divided doses mixed with feeds. – In hot weather, supplement all age groups. 1-7 y: 1 g Na/d (600 mg NaCl) > 7 y: 2-4 g Na/d  Supplements EFA: +++ omega 6 and DHA May benefit CF patients because of their AI effect on lungs No evidence to advocate routine supplementation Probiotics: Some evidence that probiotics reduce intestinal inflammation and severe respiratory infection in CF. Need more research  Appetite stimulants Considered in case of severe anorexia Megestrol acetate: improves appetite, but leads to adrenal suppression and glc intolerance Cyproheptadine: antihistamine with 2dary effect of appetite stimulation / transient drowsiness GH: stimulates growth, anabolic agent (increases W and LBM). Pancreatic enzyme replacement therapy Enteric coated better than non enteric powders Enzymes should be titrated according to the fat content of the meal or snack. Requirements vary from 400 IU lipase/g fat to 5000 IU lipase/g fat. Most patient require 50-100 IU lipase/g fat/kg/d Enzyme preparations must not be crushed or chewed and should be given at the start, midpoint and end of a meal. No harm if enzyme is given and food not eaten Pancreatic enzyme replacement therapy Doses should be individualized based on; – Clinical symptoms – Appearance and frequency of stools – Presence of abdominal symptoms – Weight gain. Maximum dose: 10000 IU lipase/kg/d Administration: – Infants should be given enzymes in a granular form on a spoon, mixed with a small amount of milk or fruit puree. – Given at the start and throughout the feed if the feed takes in excess of 30 min to complete. – Older children should be changed to a capsule preparation usually around 4-5 y. they should be encouraged to swallow the enzymes capsules whole. Split the dose throughout the meal so that adjustments can be made according to the amount of food eaten.  Breast milk Advantages of BF over formulas: – Amylase and lipase content partially compensate for reduced pancreatic secretion – Optimal FA profile. – Immunological protection against infections. – Nutrients highly bioavailable – Better psychologically for the mother. Recent studies have shown a decline in nutritional status in infants who are breastfed beyond 2 months of age → supplementary high E feeds may be required if there is evidence of faltering growth.  Infant feeding in CF Infant formulas: – Standard formulas: infant whey based formulas. – High E formulas: necessary if W gain is inadequate (Infatrini…) – Protein hydrolysate formula: used if the infant develops a disaccharide intolerance after meconium ileus or cow’s milk protein allergy. Otherwise, no advantage  CFRD – Insulin should be tailored to the dietary intake of each individual (< 6 g NaCl/d)  CFRD – Patients are encouraged to eat regularly and to aim to eat a similar amount of CHO each day. – Refined CHO recommended to be given with meals rather than eaten ad lib between meals. – Patients using oral nutritional supplements → use polymeric supp. rather than CHO only – In case of EN → long acting insulin to cover increased CHO load overnight  CFLD – E requirements may increase as a result of fat malabsorption and up to 150% requirement may be needed. – MCT are useful – Salt supplementation may need to be restricted to avoid ascites – Fat soluble vit required – If not taking vitamin K already, supplement 10 mg daily – Patients are prone to develop significant anorexia → overnight supplementary feeding may be necessary to prevent worsening malnutrition – Gastrostomy CI in case of advanced disease or varices (risk of gastric bleeding) – Liver transplantation is an effective intervention.