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cystic fibrosis
- 2. case • 8 months y/o girl, from Arar, SVD, Full term. • presented to the Ped- ER with SOB, Cough and diarrhea since 4 months Pre time of first admission in KFMC 2011. • Cough was sever inter fir with her sleeping and feeding, increase with breast feeding, with no specific reliving factors. • Diarrhea since birth wax and win, grassy and offensive, frequent 3 time/ day
- 3. • ROS. ▫ Wt loss, decrease appetite. • PMH ▫ Recurrent admission in local hospital due to recurrent chest infection, Mx by Abx. • No PSH • Developmental Hx : ▫ upto her age • Family Hx ▫ 1° consanguinity ▫ The first baby girl dead at age of 4 month with similar presentation. ▫ No family Hx of inherited disease nor congenital. • Socioeconomic status ▫ Fair
- 4. OE • She very thin with loss of adipose tissue , distressed, not cyanotic no dimorphic feature. With good suckling. • Vitally : tackyapnic on 0.25 L O2 nasal cannula. • Wt= 4.6 kg Ht= 60 c.m (below the 3rd percentile) • Heart: S1+S2 no add sound nor murmur • Chest : bilatral crakles • Abd: soft and lax • Neurological : inact
- 5. First Impression • C.F • I° Immunodeficiency • Aspiration syndrome
- 6. Significant finding on paraclinical • CBC WBC = 11.3 lymph = 6.82 % U&E Albumin = 31 g/l Protein = 63 g/l ESR= 19 Ŋ Immunological study within normal Chloride sweat test (61- 80) 1° 102 mmol/l 2° 113 mmol/l Pancreatic enzyme on Faecal < 50 ug/g
- 7. CXR
- 9. Definitive diagnosis C.F • Genetic study done ▫ Homozygous single nucleotide deletion ▫ In chromo 11 of the CFTR
- 10. Cystic Fibrosis Presented by: Sheikah A. Bawazir
- 11. Objective • Genetic aspect • Path physiology • Presentation • diagnosis • Management • Futuer
- 12. • Cystic Fibrosis (CF) is a lifelong, hereditary disease that causes thick, sticky mucus to form in the lungs, pancreas, and other organs . In the lungs, this mucus blocks the airways, causing lung damage, making it hard to breathe, and leading to serious lung infections . In the pancreas, it clogs the pathways leading to the digestive system, interfering with proper digestion . • In 90 percent of cystic fibrosis cases, the airways are affected .
- 13. Epidemiology • Common in Caucasians • 1:2000-3000 live births • M=F • Typically presents in childhood ▫ 7% of CF patients diagnosed as adult • Most common cause of sever ch.lung disease among pediatric group. • Increase life expectancy from 6 months in 1960 to near 40 years now a days
- 14. Genetic aspect • Autosomal recessive • Mutation in the CFTR gene • On q31.2 locus, long arm of chromosome 7 • Most of people have 2 copies . • 1500 mutation that can produce C.F • Most common mutation is ΔF508. • In 66%-70% of C.F cases. • carrier rate =1/25
- 16. Pathophysiology • Disease of exocrine glands cause abnormal transport of Cl and Na across an epithelium , leading to thick, viscous secretions • different mutations cause different defects in the CFTR protein • causing a milder or more severe disease • Other mutations in the CF gene produce fully processed CFTR proteins that are either non- functional or partially functional
- 17. • DF508 mutation leads to improper processing and intracellular degradation of the CFTR protein
- 18. Lung
- 19. • Gastrointestinal ▫ Pancreas Absence of CFTR limits function of chloride-bicarbonate exchanger to secrete bicarbonate Leads to retention of enzymes in the pancreas, destruction of pancreatic tissue. ▫ Intestine Decrease in water secretion leads to thickened mucus and dessicated intraluminal contents Obstruction of small and large intestines ▫ Biliary tree Retention of biliary secretion Focal biliary cirrhosis Bile duct proliferation Chronic cholecystitis, cholelithiasis • Sweat ▫ Normal volume of sweat ▫ Inability to reabsorb NaCl from sweat as it passes through sweat duct
- 20. Manifestation • Common presentations ▫ Chronic cough ▫ Recurrent pulmonary infiltrates ▫ Failure to thrive ▫ Meconium ileus
- 21. GenitourinaryGastrointestinalRespiratory tract Pseudo bartter’s Late onset puberty Due to chronic >95% of male patients with CF have azoospermia 20% of female patients with CF are infertile >90% of completed pregnancies produce viable infants Meconium ileus distal intestinal obstruction syndrome Exocrine pancreatic insufficiency Found in >90% of CF patients decreases with age Increased incidence of GI malignancy Chronic sinusitis Nasal obstruction Rhinorrhea Nasal polyps in 25% Chronic cough Persistent Viscous, purulent, green sputum
- 22. Diagnosis • DNA analysis not useful due to large variety of CF mutations • Sweat chloride test >80 mmol/l 1-2% of patients with clinical manifestations of CF have a normal sweat chloride test • 72 hr. fecal fat determination • Sputum culture (to ID infective organisms)
- 23. Diagnosis • Criteria ▫ One of the following Presence of typical clinical features History of CF in a sibling Positive newborn screening test ▫ Plus laboratory evidence for CFTR dysfunction Two elevated sweat chloride concentrations on two separate days Identification of two CF mutations
- 24. Treatment • Major objectives ▫ Promote clearance of secretions ▫ Control lung infection ▫ Provide adequate nutrition ▫ Prevent intestinal obstruction
- 26. Interrupting the Vicious Cycle
- 27. Treatment • Lung ▫ Antibiotics Early intervention, long course, high dose Staphylococcus- Penicillin or cephalosporin Pseudomonas treated with two drugs with different mechanisms to prevent resistance e.g. cephalosporin + aminoglycoside Use of aerosolized antibiotics Oral cipro for pseudomonas Rapid emergence of resistance Intermittent treatment (2-3 weeks), not chronic IV antibiotics for severe infections or resistant to orals
- 30. Interrupting the Vicious Cycle AIRWAY CLEARANCE TECHNIQUES
- 31. Treatment • Lung ▫ Breathing exercises ▫ Flutter valves ▫ vest machine ▫ Chest percussion ▫ Hypertonic saline aerosols
- 32. Interrupting the Vicious Cycle AIRWAY CLEARANCE TECHNIQUES
- 33. Treatment • Lung ▫ Increasing mucus clearance Sulbetamole + HTS + CPT Long-term DNAse treatment increases time between pulmonary exacerbations ▫ Anti-inflammatory Flixotide
- 34. Treatment • Lung ▫ Atelectasis Chest PT + antibiotics ▫ Respiratory failure and cor pulmonale Vigorous medical management Oxygen supplementation Only effective treatment for respiratory failure is lung transplantation 2 year survival >60% with lung transplatation
- 35. Treatment • Nutrition ▫ Pancreatic enzyme replacement ▫ Calories ranging from normal to 150 % ▫ Replacement of fat-soluble vitamins- especially vitamin E & K
- 36. Treatment • Gastrointestinal ▫ Insulin for hyperglycemia ▫ Intestinal obstruction Pancreatic enzymes + osmotically active agents Distal- hypertonic radiocontrast material via enema ▫ End-stage liver disease- transplantation 2 year survival rate >50% ▫ Hepatic and gallbladder complications treated as in patient without CF
- 37. Back to Our case • Gentamicin and tazocin • Pancreatic enzyme • Ventolin + HTS+ CPT • ADEK • Vit.D • Nacl and Kcl oraly • Follow up app. 2 month
- 38. Pt readmitted multiple time due to pul. Exacerbation ,pseudo bartter's FTT. 5.8 6.6 7.5 8.4 10.3 10.7 6.5 7.2 7.8 9.33 10.8 11.8 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10 10.5 11 11.5 12 17 month 21 month 22 month 34 month 42 month 48 month weight on discharge NGT over night feeding Omeprezole started GT tube
- 39. Last admission
- 40. C.F. Future • Journal of Cystic Fibrosis Volume 10 Suppl 2 (2011) S114–S128 Gene and cell therapy for cystic fibrosis: From bench to bedside • Ivacaftor ▫ is approved for use in cystic fibrosis patients in the US and across some European countries. The US Food and Drug Administration approved Ivacaftor in January 2012 ▫ During Phase 3 clinical trials, the STRIVE study demonstrated a 10.6% mean absolute improvement in baseline lung function (FEV1) over a 24 week period and a 10.5% mean absolute improvement in lung function over 48 weeks among those who had the G551D mutation and were treated with Ivacaftor ▫ Cystic Fibrosis Trust Research Strategy 2013–2018 in UK
- 41. Summary
- 42. Reference • Yankaskas JR, Marshall BC, Sufian B, Simon RH, Rodman D. (2004). "Cystic fibrosis adult care consensus conference report". Chest 125 (90010): 1– 39.doi:10.1378/chest.125.1_suppl.1S. PMID 14734689 • U .S . Census Bureau . The 2010 Statistical Abstract . Population: Estimates and Projections by Age, Sex, Race/Ethnicity . Table 6 . Available at http://www .census .gov/compendia/statab/cats/population/estimates_and_projections_by_age_sex_raceethnicity .html . Accessed January 7, 2010 . • Centers for Disease Control and Prevention . National Center for Health Statistics . CDC Wonder On-line Database, • compiled from Compressed mortality File 1999-2006 Series 20 No 2L, 2009 . Accessed January 11, 2010 • Cystic Fibrosis Foundation . Patient Registry 2007 Annual Report . September 2009 . Available at http://www . • cff .org/research/ClinicalResearch/PatientRegistryReport/ . Accessed January 11, 2010 • http://www.uptodate.com/contents/cystic-fibrosis-antibiotic-therapy-for-lung-disease#H13 • http://www.uptodate.com/contents/cystic-fibrosis-overview-of-the-treatment-of-lung- disease?source=see_link&anchor=H12#H12 • Long-term daily high and low doses of azithromycin in children with cystic fibrosis: A randomized controlled trial.S.K. Kabra, , R. Pawaiya, Rakesh Lodha, Arti Kapil, Madhulika Kabra, A. Satya Vani, G. Agarwal,,S.S. Shastri,DOI: 10.1016/j.jcf.2009.09.001, http://www.sciencedirect.com/science/article/pii/S1569199309001234 • http://www.uptodate.com/contents/cystic-fibrosis-nutritional-issues
Editor's Notes
- known as mucoviscidosis, also.
- The most common mutation,ΔF508, is a deletion (Δ signifying deletion) of three nucleotides[40]that results in a loss of the amino acid phenylalanine (F) at the 508th position on the protein. This mutation accounts for two-thirds (66–70%[18]) of CF cases worldwide and 90% of cases in the United States; however, there are over 1500 other mutations that can produce CF.[41] Although most people have two working copies (alleles) of the CFTR gene, only one is needed to prevent cystic fibrosis. CF develops when neither allele can produce a functional CFTR protein. Thus, CF is considered an autosomal recessive disease. the CFTR gene, found at the q31.2 locus of chromosome 7, is 230,000base pairs long, and creates a protein that is 1,480 amino acids long. More specifically the location is between base pair 117,120,016 to 117,308,718 on the long arm of chromosome 7, region 3, band 1, sub-band 2, represented as 7q31.2. Structurally, CFTR is a type of gene known as an ABC gene.[19] The product of this gene (the CFTR) is a chloride ion channel important in creating sweat, digestive juices andmucus. This protein possesses two ATP-hydrolyzing domains, which allows the protein to use energy in the form of ATP. It also contains two domains comprising 6 alpha helices apiece, which allow the protein to cross the cell membrane. A regulatory binding site on the protein allows activation by phosphorylation, mainly by cAMP-dependent protein kinase.[19] The carboxyl terminal of the protein is anchored to thecytoskeleton by a PDZ domain interaction.[42]
- The CFTR protein Single polypeptide chain, 1480 amino acids Cyclic AMP regulated chloride channel Regulator of other ion channels Found in the plasma membrane of normal epithelial cells IN CF the abnormal ion transport across the epithelial cells of the exocrine glands of the respiratory tract and pancreas results in increased viscosity of secretions. Abnormal function of the sweat glands results in excessive concentrations of sodium and chloride in the sweat. This forms the basis of the sweat test.
- airway surface liquid (ASL) Lung Raised trans-epithelial electric potential difference Absence of cAMP-dependent kinase and PKC-regulated chloride transport Raised sodium transport and decreased chloride transport Alternative calcium-regulated chloride channel in airway epithelia which is a potential therapeutic target High rate of sodium absorption and low rate of chloride secretion reduces salt and water content in mucus, depletes peri-ciliary liquid Mucus adheres to airway surface, leads to decreased mucus clearing Predisposition to Staph and Pseudomonas infections
- \ Lung function Small airway disease is first functional lung abnormality Progresses to reversible as well as irreversible changes in FEV1 Chest x-ray may show hyperinflation, mucus impaction, bronchial cuffing, bronchiectasis Meconium ileus Abdominal distention Failure to pass stool Emesis Meconium ileus equivalent or distal intestinal obstruction syndrome RLQ pain Loss of appetite Emesis Palpable mass May be confused with appendicitis Exocrine pancreatic insufficiency Found in >90% of CF patients Protein and fat malabsorption Frequent bulky, foul-smelling stools Vitamin A, D, E, K malabsorption Sparing of pancreatic beta cells Beta cell function decreases with age Increased incidence of GI malignancy
- Pseudomonas aeruginosa is a gram-negative, aerobic rod measuring 0.5 to 0.8 µm belonging to the bacterial family Pseudomonadaceae. Like other Pseudomonads, P. aeruginosa secretes a variety of pigments, including pyocyanin (blue-green), fluorescein (yellow-green and fluorescent), and pyorubin (red-brown). P. aeruginosa is often preliminarily identified by its pearlescent appearance and grape-like odor in vitro. Early dx of pseudo swabs every three months during routine clinic visits. When P. aeruginosa is first detected, we recommend treatment with inhaled tobramycin alone (300 mg in 5 mL, administered twice daily) for 28 days rather than a regimen including ciprofloxacin or other antibiotics. The therapy is repeated only if surveillance cultures show recurrence of P. aeruginosa. Chronic oral antibiotics Long-term administration of azithromycin (AZM) in children with cystic fibrosis (CF) has improved outcomes. However, the doses and schedule of administration There was increase in exacerbations after stopping azithromycin in both the groups. Our results also suggest that the decrease in the incidence of LRTI persists only till 6 months after discontinuing azithromycin. Azithromycin has been implicated in fewer drug-drug interactions than other macrolide antibiotics[114]but has had a strong inhibitory effect on the actions of dornase alfa in vitro, possibly by binding to human DNA and/or to dornase alfa itself.[115] The suggested interaction between azithromycin and dornase alfa was observed clinically in one randomized controlled study.[106] However, a subsequent study reported a benefit in lung function associated with azithro-mycin therapy even though 75% of patients in the active treatment group were concomitantly treated with dornase alfa.[107] Azithromycin appears to be a well-tolerated and clinically efficacious antiinflammatory treatment modality for maintenance of lung function in children and adults with cystic fibrosis.[105–107 ]Most experience with azithromycin has been with patients older than 13 years with a history of chronic P. aeruginosacolonization; it has not been studied in children younger than 6 years. Azithromycin 250 mg 3 times/week in patients weighing less than 40 kg and 500 mg 3 times/week in those weighing 40 kg or more may be recommended in patients aged 6 years or older with chronic P. aeruginosa colonization. Azithro-mycin may benefit patients without a docu-mented history of P. aeruginosa with suspected infection, although supporting literature is lacking. The beneficial effects of azithromycin in patients with cystic fibrosis are generally observed as early as 1 month after the start of treatment but may be delayed for 4–6 months in some patients.[106, 107] Both caregivers and patients should be informed of this variability in response time. Azithromycin therapy for up to 6 months appears to be safe; nausea, diarrhea, and wheezing are the predominant adverse effects.[107] Continuing therapy seems necessary to maintain the benefits associated with azithromycin therapy. An evaluation of the safety and efficacy of this agent for treatment periods longer than 6 months is in progress. Inhaled aztreonam lysine — Following the success of inhaled tobramycin, investigators have considered a number of other antibiotics for administration by inhalation to treat CF lung disease. Aztreonam, a monobactam antibiotic with antipseudomonal activity that was approved for intravenous use in 1986, became a likely candidate. Because inhalation of the IV preparation of aztreonam induces airway inflammation, a lysine salt formulation was developed that circumvents this problem. This preparation has undergone large scale clinical trials. chronic pseudomonal lung infection were given either inhaled aztreonam lysine (75 mg) or placebo either two or three times daily for 28 days. All patients were older than 6 years, had had FEV1 between 25 and 75 percent predicted, and had received 28 days of inhaled tobramycin prior to the trial [112]. The group treated with inhaled aztreonam had a longer time before needing additional antipseudomonal antibiotics (92 days) as compared with those given placebo (71 days). Furthermore, patient-reported respiratory symptom scores, FEV1, and pseudomonas density in sputum samples also improved in the group given aztreonam. There were no differences between two and three times a day aztreonam dosing. Periodic hospitalization — Periodic hospitalizations for preventive therapy, including intravenous antibiotics (referred to as "clean outs"), were utilized more in the past than at the present in the United States , for 2 weeks / 3-4 months
- Although pancreatic dysfunction is the major gastrointestinal contributor to malnutrition in CF, several other factors may contribute to the problem. These include CF-related liver disease, bile salt abnormalities, CF-related diabetes mellitus, altered gastrointestinal motility, and small bowel bacterial overgrowth. Gastroesophageal reflux, distal intestinal obstructive syndrome, and constipation can also negatively affect nutrition. (See "Cystic fibrosis: Overview of gastrointestinal disease".) In addition to malabsorption and gastrointestinal dysfunction, two other mechanisms contribute to nutritional deficiencies and growth failure in patients with CF: chronic, progressive pulmonary infection with bronchiectasis leads to increased work of breathing and higher than expected nutrient needs [5], and chronic infection may reduce appetite and cause cytokine-induced catabolism ASSESSING AND MONITORING NUTRITION — The most effective way to maintain good nutrition status in CF, as in other chronic diseases, is to prevent suboptimal nutrition from occurring. Growth — The nutritional status of individuals with CF tends to decline during childhood. Data from the Cystic fibrosis Foundation (CFF) shows that the body mass index (BMI) percentile For children with CF, the BMI target range is above the 50th percentile [1,8]. Children with BMIs between the 10th and 50th percentiles are generally considered at nutritional risk, and those with BMIs below the 10th percentile are in need of nutritional rehabilitation. Children with BMIs above the 85th percentile are considered overweight [9]. There are rare CF patients who are overweight and even obese [9]. For children younger than two years of age, the same percentile criteria are applied to weight-for-height rather than BMI. For adults with CF, the target is a BMI at or above 22 for women, and 23 for men Patients with CF have the following multiple risk factors for developing bone disease [19]: ●Failure to thrive ●Delayed pubertal development ●Malabsorption of calcium, magnesium, vitamin D, and vitamin K ●Hepatobiliary disease ●Reduced weight-bearing activity ●Chronic corticosteroid use ●Inadequate intake of nutrients CF-related diabetes mellitus — Approximately 25 percent of individuals with CF develop CF-related diabetes (CFRD) by 20 years of age; the risk increases with age and varies with CF genotype and severity . The CFF and American Diabetes Association recommend annual screening for CFRD beginning at age 10 years, carried out at a time of clinical stability [29]. An oral glucose tolerance test (OGTT) should be used for screening because either fasting plasma glucose or hemoglobin A1C has low sensitivity in this patient group. Recommendations from the UK Cystic Fibrosis Trust are similar, except that routine screening begins at 12 years of age Pulmonary function testing — Pulmonary function testing (PFT) is not a measure of nutritional status, but there is a close correlation between PFT results and nutritional status Small intestine bacterial overgrowth — Individuals with CF may be susceptible to small intestine bacterial overgrowth (SIBO), primarily because of decreased intestinal motility. The disorder can contribute to malnutrition by decreasing appetite, and by interfering with fat absorption. SIBO should be considered in patients with suggestive clinical symptoms and/or deterioration in nutritional status Calories — In the past, the caloric requirement of a CF patient was estimated to be 130 percent of recommended dietary allowance (RDA) for calories [33]. This is now considered an unwarranted simplification. A number of recent studies used open and closed indirect calorimetry and doubly-labeled water to determine energy expenditures. These studies consistently show that energy expenditure is directly associated with the severity of the CF gene mutation and inversely associated with pancreatic function [34-36]. A wide range of energy expenditures are reported in individuals with CF, ranging from normal to 150 percent of normal, depending on the CF mutation, the patient's age and current state of health. Each patient should have a nutritional regimen tailored to his or her needs [37]. Ideally, energy expenditure should be measured for each individual; however, techniques of determining energy expenditure can be difficult, especially in patients with CF. Measurement of resting energy expenditure requires either endotracheal intubation or a tight fitting hood to collect expired gases. CF patients do not tolerate either method well. A handheld apparatus for measuring resting energy expenditure is available [38]. To date, this device has not been tested in CF patients, and its use could be limited by chronic cough and by problems with contamination. However, if the technique proves feasible and accurate in this population, it could allow more exact matching of patients' needs with nutritional recommendations. Fat soluble vitamins — CF liver disease and pancreatic dysfunction lead to fat malabsorption that predisposes patients to deficiencies of the fat-soluble vitamins: A, D, E, and K [39] Fluoride — Infants and children with CF require fluoride for dental health at the same levels as healthy children [13]. Vitamins formulated for CF do not generally include fluoride. Fluoride supplements should be supplied separately beginning at 6 months of age, if the fluoride concentration of the water supply is not adequate. (See"Preventive dental care and counseling for infants and young children", section on 'Fluoride'.) Zinc — For infants with CF under two years of age who are not growing well despite adequate energy intake and pancreatic enzyme supplementation, the CF foundation suggests a trial of zinc supplementation (1 mg elemental zinc/kg/day in divided doses for six months). This suggestion is based on expert consensus, inferred from the positive effects of zinc on growth in some other clinical settings. (See "Zinc deficiency and supplementation in children and adolescents", section on 'Enhancement of growth'.) Rarely, infants with undiagnosed CF may present with a dermatitis caused by zinc deficiency, often in combination with EFA deficiency and/or protein-energy malnutrition. The dermatitis resembles acrodermatitis enteropathica. (See "Zinc deficiency and supplementation in children and adolescents", section on 'Other'.) NUTRITION SUPPORT Oral — All individuals with CF should be given dietary advice about a balanced diet with adequate calories to ensure growth at or above the 50th percentile for age. Caloric goals will often be higher than those for the general population. Pancreatic enzyme replacement therapy should be provided for those with pancreatic insufficiency. (See 'Growth' above and 'Calories' above and "Cystic fibrosis: Assessment and management of pancreatic insufficiency".) For infants with cystic fibrosis, human milk feeding is specifically encouraged [13]. If infants are fed formula, a standard infant formula may be used; formulas containing extensively hydrolyzed protein are not helpful unless the infant has a milk protein intolerance in addition to CF. If weight gain is inadequate, the energy content of the formula or human milk should be increased using standard methods. (See "Failure to thrive (undernutrition) in children younger than two years: Management", section on 'For infants'.) Parents should be educated to use behavioral techniques to promote positive feeding behaviors [13]. These include: ●Providing attention and praise for positive eating behaviors ●Gentle persistence when offering new foods (offer a new food 10 or more times before giving up) ●Ignoring negative eating behaviors such as food refusal ●Offer meals and substantive snacks on a regular schedule ●Keep mealtimes relaxed and time-limited; do not enforce specific goals for intake at each meal For patients with suboptimal growth, the initial intervention is to provide more intensive dietary advice to increase caloric intake [13]. A number of studies support this approach and show nutritional benefit through counseling with the use of behavior modification strategies to support dietary change [57-61]. As an example, a small randomized trial found that a behavioral intervention substantially increased caloric intake in toddlers and preschool-aged children with CF as compared with standard care, and that these effects persisted 12 months after the intervention [62,63]. The behavioral techniques included differential attention (parents praised children for desired eating behaviors and ignored non-eating behaviors) and contingencies (rewards to motivate children to meet energy goals). A larger multicenter trial of children aged 4 to 12 years assessed the efficacy of a similar behavioral intervention designed to promote energy intake [64,65]. The group receiving the behavioral intervention achieved improved energy intake and weight gain at the end of a nine-week intervention, and a slower rate of decline in BMI z-score over the subsequent two years, as compared with control patients receiving nutritional education alone. In addition to nutritional and behavioral counseling, patients with suboptimal growth should also be assessed for the possibility of emerging pancreatic insufficiency or inadequate replacement therapy. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency".) For infants with CF under two years of age who are not growing well despite adequate energy intake and pancreatic enzyme supplementation, the CF foundationsuggests a trial of zinc supplementation. (See 'Zinc' above.) If dietary counseling is not successful, a liquid supplement that is high in calories and protein can be added to the diet. A variety of supplements are available and are appropriate for use by patients with CF (table 8). These supplements are often less efficacious than expected because the supplements tend to displace ordinary food rather than being taken in addition to a usual diet [66], and patients often complain of taste fatigue with oral supplements. As an example, a systematic review found that calorie-protein supplements do not confer benefits above dietary advice and monitoring in CF patients who have moderate malnutrition [67]. Enteral feedings — When oral nutrition support fails, enteral nutrition (EN) (tube feeding) should be employed. Aspects of enteral nutrition that are specific to patients with CF are outlined here. An overview of enteral nutrition in children is presented separately. (See "Enteral nutrition in infants and children".) EN is widely used for patients with CF and perceived as helpful [68-70]. This practice is supported by a number of observational studies that suggest improved nutritional status and stabilization of lung function in CF patients receiving EN, as illustrated by the following examples [69,71,72]: ●A series of 14 patients with moderate to severe lung disease were compared with age- and disease-matched contemporary controls, with a mean follow-up of 1.1 years [73]. The patients receiving EN experienced a weight percentile increase, while growth percentiles declined in the comparison group. The FEV1 in the EN group did not change, while the FEV1 of the comparison group worsened. ●A series of 53 patients with CF, ten of whom were children, showed an increase in expected weight and stabilization of lung function, but these outcomes were not compared to a control group [69]. No randomized studies of EN have been performed in patients with CF. Therefore, the clinical benefits and potential adverse consequences, including effects on quality of life, have not been rigorously addressed [71]. Route — EN is usually provided to patients with CF via gastrostomy tube (G-tube), because nasogastric tubes are usually poorly tolerated due to chronic cough, nasal polyps, and the sensation of suffocating. Gastrojejunostomy and jejunostomy feeding may also be used, but these tubes are more difficult to place and maintain in position. Additionally, jejunal feeds must be given continuously rather than in boluses, making the route inconvenient for ambulatory patients. G-tubes can be placed surgically, endoscopically, or by an interventional radiologist, with minimal risk. If general anesthesia is not advisable for a particular patient, the procedure can be performed under sedation and local anesthesia. A skin-level device (or "button") can be used so that the patient can disconnect from all tubing between feeds, to optimize mobility and cosmesis. Schedule — Schedules for tube feeding vary and should take into account the patient's activities and other therapies. Feeds can be instilled continuously, as boluses, or a combination of these two regimens. For the school-age child, a frequently employed schedule supplies approximately 40 percent of daily requirements via a slow infusion overnight, and the remainder of the requirement is supplied through food taken by mouth during the day. If the child is unable to meet the daily caloric requirements, the nighttime infusions can be lengthened or the rate of infusion increased so that a greater percentage of the requirements are delivered overnight. For the younger patient who is at home during the day, nutritional requirements can be supplied through a combination of nighttime continuous feeds, daytime meals, and daytime bolus feeds. If the child fails to ingest the prescribed amount at any daytime meal, a bolus feed is added to compensate. CF patients often have a complex care schedule because of their need for multiple medications and frequent pulmonary therapies. Feeding schedules should take these other elements of therapy into account. Formula — No one class of formula has been shown to be superior to another. Some formulas supply protein that is either elemental (free amino acids) or semi-elemental (table 9). The protein in a semi-elemental formula may be extensively hydrolyzed (containing short peptides) or partially hydrolyzed (containing longer peptide chains). However, more extensive protein digestion does not have a clinical advantage as long as pancreatic enzyme replacement is given, and it may have the disadvantage of increasing the osmolarity of the formula. In one study, a non-elemental formula plus pancreatic enzyme replacement was as well absorbed as a semi-elemental formula without pancreatic enzymes [74]. Concentrated formulas with 1.5 to 2 Kcal/mL have the advantage of delivering more calories in a smaller volume. Since nighttime urination is a problem when using high-volume overnight feeds, a smaller volume can make the feeding schedule more tolerable. When using the more concentrated formulas, care must be exercised to avoid carbohydrate overload and possible inadequate supply of free water. Use of formulas with concentrated carbohydrates may uncover CF related diabetes (CFRD). Similarly, in established diabetics, these formulas may complicate diabetes treatment. The complications encountered because of CFRD are surmountable and should not preclude the use of EN. Enzyme replacement — As with other aspects of EN in CF, there is little information on the best way to administer pancreatic enzyme replacement therapy (PERT) in conjunction with EN. (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency", section on 'Pancreatic enzyme replacement therapy'.) In the absence of evidence-based guidelines, we suggest the following approach: ●Start by calculating the grams of long chain triglycerides (LCT) being administered. LCT is the main determinant of the lipase requirement, because medium chain triglycerides (MCT) require relatively low concentrations of lipase to hydrolyze the fatty acids from the glycerol backbone. Therefore, MCT accounts for little of the fat malabsorption in CF. ●Supply 1600 to 2000 lipase units per gram LCT (table 10). See Pancrelipase drug information. •For cycled and continuous overnight feeds, administer three-fourths of the enzymes at the beginning of the feeding and one-fourth of the enzymes at the end of the feeding. •For bolus feedings, administer the calculated amount of enzymes just prior to the feeding. •For continuous 24-hour feedings, divide the total calculated lipase into six doses, and give each dose at four hour intervals. Parenteral nutrition — Parenteral nutrition (PN) should be prescribed for CF patients when GI function is inadequate to supply complete nutrition. This could occur during times of extreme metabolic stress, such as post-transplantation or following GI surgical procedures. The PN solution should contain a balance of amino acids, dextrose, lipids, vitamins, and trace elements to provide appropriate nutrition. (See "Parenteral nutrition in infants and children", section on 'How to prescribe PN'.) One study observed that PN promoted weight gain in patients with CF but was also associated with higher rates of sepsis [75]. Moreover, after PN was discontinued, weight decreased again, and no long-term gain was achieved. PN should not be a part of palliative care ________________________________________________ Dosing of pancreatic enzymes is based upon the units of lipase determined as a function of patient weight or dietary fat intake. ●The weight-based method can generally be used at any age. The starting dose for children less than four years of age is 1000 lipase units/kg body weight per meal, and for children older than four years of age is 500 lipase units/kg body weight per meal [24,27,28]. Smaller doses usually are offered with fat-containing snacks eaten between meals. Dosing is increased based upon symptoms of pancreatic insufficiency to a maximum of 2500 lipase units/kg body weight per meal to avoid fibrosing colonopathy. ●The fat-based method is useful for infants who take a known amount of formula or in patients who receive tube feedings. The dose starts at approximately 2000 lipase units/120 ml of formula or per breast feeding (about 1600 lipase units/gram of fat ingested per day). The dose can be adjusted up to no more than 2,500 lipase units per kg body weight per feeding, with a maximum daily dose of 10,000 lipase units per kg