1. Cystic Fibrosis: A Clinical Nutrition Case STudy
Wendy Anderson
February 1, 2013

2. Outline What is Cystic Fibrosis? Overview of Patient
Nutrition Assessment of Patient
Nutrition Diagnosis
Nutrition Intervention
Nutrition Monitoring/Evaluation
Medical Nutrition Therapy for
Cystic Fibrosis
Other Possible Treatments

3. Cystic Fibrosis
Most common life-limiting, autosomal recessive disease in the United States
Defect on chromosome 7 in the area responsible for coding the Cystic Fibrosis Transmembrane Regulator (CFTR) protein
Abnormal transport of ions and water across cells in many organs of the body
Thick, tenacious mucus and organ damage, especially in the respiratory, gastrointestinal, endocrine, and reproductive symptoms

4. Cystic Fibrosis Stats
Incidence of CF is approximately 1:3,500 live births
30,000 people who have CF in the United States, half being older than 18 years of age
CF was first identified in the 1930s, life expectancy was less than 5 years of age
Current median predicted survival of 38.3 years
Mutation of the single gene that encodes for CFTR
identified in 1989
Cystic Fibrosis Foundation. Patient Registry: Annual Data Report Bethesda, MD; 2011

5. Cystic Fibrosis: Life Expectancy

6. What’s the Chance?

7. CFTR: The Gene Associated with CF
Type of protein classified as an ABC (ATP-Binding Cassette) transporter
CFTR transports Cl- Ions across membranes in lungs, liver, pancreas, digestive and reproductive tracts and skin
Made up of 1480 amino acids
Made up of 5 domains
MSD1 and MSD2 (Form Cl- Channel)
NBD1 and NBD2 (Bind and Hydrolyze ATP)
R (Regulates movement of Cl- ions across membrane)

8. CFTR: The Gene Associated with CF

9. 5 Classes of CFTR Mutations: classified by effect on CFTR protein
Pancreatic
Insufficient
Pancreatic
Sufficient

10. Delta F508 Mutation
70% of mutations result from deletion of three base pairs of CFTR’s nucleotide sequence
Loss of AA Phenylalanine located in position 508 in protein: delta F508
Normal CFTR: Protein synthesized/transported to endoplasmic reticulum and Golgi apparatus
CFTR protein with delta F508 reaches endoplasmic reticulum, recognized that protein is folded incorrectly…marked for degredation…delta F508 never reaches cell membrane.

11. Delta F508 Mutation

12. Diagnosis of CF Sweat Chloride test performed
Measures level of Chloride/Sodium in sweat using an electric current
Pilocarpine is a chemical used to stimulate sweat glands
Sweat collected on gauge for 30 minutes, weighed
Positive (>60 mEq/L Cl- in sweat)
CFTR mutation analysis in patients suspected of having CF with normal/borderline sweat chloride value

13. Symptoms of CF Vary depending on severity of disease
Screening of newborns performed in all 50 states
Respiratory symptoms
Persistent cough, production of thick mucus
SOB, wheezing
Decreased ability to exercise
Repeated lung infections
Digestive symptoms
Fowl-smelling greasy stools
Poor weight gain and growth
Intestinal blockage (meconium ileus)
Severe constipation

14. Organs Affected by CF

15. Respiratory Implications
Lungs become colonized with bacteria
Bronchiectasis develops, making infection more difficult to treat
Manifestations
Wheezing
SOB
Persistent cough and excessive mucus
Repeated cases of pneumonia
Digital clubbing

16. GI/Nutritional Implications
Intestinal
DIOS ( Distal Intestinal Obstruction Syndrome)
Blockage of intestines by thickened stool
Pancreatic
Pancreatic insufficiency and recurrent pancreatitis
CFRD
Hepatic
Chronic hepatic disease
Focal biliary cirrhosis/multilobular cirrhosis
Nutritional
Failure to thrive or gain weight (PEM)
Steattorrhea
Abdominal discomfort, gas
Osteoporosis

17. Distal Intestinal Obstruction Syndrome (DIOS)
Complete intestinal obstruction
Abdominal radiography useful to differentiate between Constipation and DIOS
DIOS: Fecal mass in the ileocecum with or without fluid levels in the small intestine
Constipation: Distribution of fecal material throughout the colon
Intensive laxative treatment (oral laxatives and/or enema or polyethylene glycol lavage)
Adequate hydration important!!

18. CF-related liver disease
~ 24% CF adults have hepatomegaly or abnormal LFTs
Ultrasound of right upper quadrant
Gallstones, common bile duct stones, nodules of liver (suggest cirrhosis), steatosis (retention of lipids within cells)
Cholestasis
Flow of bile from liver is slowed/blocked
Ursodeoxycholic acid (UDCA)
Improves bile flow
Stimulate bicarbonate secretion into bile

19. Overview of patient

20. Patient Background
IM is a 27 year old Caucasian Female admitted on 12/6/12
Diagnosed at 8 months (Sweat test: 113 mEq/L Cl-)
First JHH CF clinic visit was in November, 2010
Current Medical History
CF; unknown genotype
Complicated by Burkholderia cepacia
Pancreatic insufficiency
Past Medical History
Gerd
Sinus problems
Hx of asthma
Anxiety/ADD

21. Social History
Previously lived in San Diego, CA (lost job in TV production in wardrobe during writer’s strike)
Moved home to live with parents in Southern MD, 2010
Has a boyfriend
Works as a waitress in Annapolis, MD
Does not smoke
ETOH 3-4x/month
Occasional illicits (marijuana)
Twin brother in excellent health

22. Hospital Course Seen in JHH CF Clinic on 12/3/12
Admitted on 12/6/12 with one week history of worsening of pulmonary symptoms
Last admission was in August 2012
Diagnosis: CF exacerbation
CXR on 12/6/12 revealed improved minimal mucous plugging in right lower lobe since 8/13/12
Automatic nutrition consult for CF patients (within 48 hours)

23. Nutrition Assessment

24. Why WAS Nutrition consulted?
Monitor energy and protein intake
Address pancreatic enzyme and vitamin regimen
Provide education to promote achieving and maintaining a healthy body weight

25. Nutritional Assessment
Height: 63”
CBW: 49 kg
UBW: 50 kg
%UBW: 98%
Weight History: 8/2012 (50.8 kg); 3/2012 (49.2 kg); /2011 (52.7 kg)
BMI: 19.1
%FEV1 upon admission: 44%
%FEV1 baseline: ~80%

26. Interview IM was extremely tired
Experiencing nausea and decreased appetite
No breakfast; last meal was nachos and cheese she shared with her mother
Endorsed AquADEKS and CREON 24
**Reports taking AquADEKS after enzymes
Not taking Vitamin D… “I forget”
Prepares her own food and is a huge snacker
Prior snacks preferences on previous admissions:
Ensure CS, pretzels, yogurt, Sierra Mist, potato chips, orange, Oreos, fruit cocktail, etc.

27. Common Nutrition Diagnosis/ PES Statement
Increased energy expenditure (NI 1.2)
Inadequate oral intake (NI 2.1)
Unintentional weight loss NC 3.2)
Altered GI function (NC 1.4)
PES Statement
“Inadequate oral intake (NI 2.1) related to increased energy expenditure as evidenced by pancreatic insufficiency, poor lung function and a BMI < 22 (ideal for female with CF to promote optimal lung function)”.

28. Nutrition Assessment Goals Intervention/Monitoring Recommendations:
Increase PO intake
Maintain weight
Preserve lean body mass
Intervention/Monitoring
Supplements and snacks (increased calorie and fat intake), monitor labs, weights
Follow up in 5-7 days
Recommendations:
Continue with regular diet and provide snacks per patient preference
Ensure Clinical Strength TID
Order Cholecalciferol 50,000 IU q7 (IM not taking at home)

29. Home Medications Medications Functions Possible GI Side Effects
Adderall
Anti-ADHD
Dry mouth, N/C/D, stomach pain, metallic taste
Pristiq
Antidepressant
taste changes, N/V/C/D
Abilify
N/V/C, dry mouth, dyspepsia
Cogentin
Controls movement related side effects
Advair
Bronchodilator
Candidiasis, N/V/D
Pulmozyme (Dornase alfa/DNase)
Decreases viscosity of secretions
Laryngitis
Hypertonic Saline Nebs
Decreases viscosity
Increases coughing, chest tightness
Albuterol Nebs
Sore throat, diarrhea
Creon 24
Pancreatic enzymes
N/V, abdominal pain, diarrhea
Ergocalciferol
Vitamin D supplement
N/V/C/D, metallic taste
AquADEKS
MVI w/ minerals
Overdose can cause GI issues
Subuxone
For opioid addiction
N/V, dry mouth
Azithromycin
Antibiotic
Miralax
Laxative
N, bloating, cramps, flatulance
Lansoprazole
Proton Pump inhibitor
N, abdominal pain, diarrhea

30. What labs do we check in CF Patients?
Vitamins A, D 25-OH, and E checked annually
Vitamin K
Indirectly assessed by evaluating prothrombin time
CBC
Hemoglobin/Hematocrit levels
Zinc
Liver enzymes checked annually
Casual glucose levels annually (monitor for CFRD)
Sputum sample

31. IM’s Lab Values Parameter Ref. Range Value Date Indication Vitamin A
38-98 mcg/dL
37 (L)
8/4/12
Malabsorption
Vitamin D
ng/dL
23 (L)
12/7/2012
Vitamin E
5.7-19,9 mg/dL
6.2
7/30/12
Prothrombin
10-14 sec
10.2
12/7/12
Albumin
g/dL
4.1
Total Bilirubin
mg/dL
0.2
12/14/12
Alk Phos
U/L 71
AST
0-31 U/L 20
ALT 21
Glucose
60-99 mg/dL
117(H)
HbA1c %
5.8 (H)
Impaired glucose tolerance
WBC
,000
13,000 (H)
Infection
Hemoglobiin
12-15 g/dL
11.2 (L)
Low Iron stores
Hematocrit
36-46%
36.4
Indicator of Iron status
MCV fL
87.2
Lipase
16-23 U/L
3 (L)
Chronic disease

32. Pulmonary Function Tests… What is FEV1%???
FEV1 definition
Volume of air that can forcibly be blown out in one second, after full inspiration
Measure lung functionality and need for and response to antibiotic therapy
IMs FEV1 History
11/18/10 (64%)
10/12/11 (80%)
8/27/12 (64%)
12/3/12 (44%)

33. Nutritional status & pulmonary Function in Adult CF Patients
Journal of Physiology and Pharmacology, 2008
39 CF patients (21 females and 18 males)
Mean age years
BMI used to single out groups:
Normal weight (n=28) w/ BMI > 18.5 kg/m2
Malnourished (n=11) w/ BMI < 18.5 kg/m2
Pulmonary function abnormal if FEV1 < 80%
Statistical analysis revealed significant differences btw malnourished and not malnourished pts concerning FEV1%
Poor clinical outcome associated with significant loss of body weight (Malnutrition , or risk of malnutrition remains a frequent complication of CF)

34. Medical Nutrition Therapy for CF

35. Nutrition Goals in CF Control adequate maldigestion and malabsorption
Provide adequate nutrients
Promote optimal growth
Maintain weight for height
Support pulmonary function
Prevent nutritional deficiencies
PERT (Pancreatic Enzyme Replacement Therapy)
Fat-soluble vitamins

36. What Nutritional Indicators should be evaluate?
Decreased Oral Intake
Diarrhea, steatorrhea, or changes in stool
Diet quality (macro and micronutrient quality)
Abdominal pain
Weight loss or lack of weight gain
Inadequate growth
Reduced skeletal muscle mass
** Patients with weight loss = HIGH nutritional risk!

37. General Dietary Guidelines
3 meals, 2-3 snacks per day
Pancreatic enzyme and vitamin supplementation
Unrestricted diet (including high fat foods)
Supplements
Encourage variety of whole grains, fruits and vegetables
Counseling to provide ideas for calorie boosters
Extra salt especially during hot weather/exercise/febrile
Adequate calcium, vitamin D, vitamin K

38. Energy Requirements for CF Patients
Calorie and protein requirements are usually 1.2-2x the DRI for age
Factors to consider
Age
Gender
Physical Activity
Respiratory Infections
Severity of lung disease
Severity of malabsorption

39. Estimated Needs: Energy/Protein
Not defined in literature at this time
Energy equation: JHH
(DBW x 35 x FEV1 factor) to (DBW x 40 x FEV1 factor)
FEV1 Factors:
FEV1 > 90% predicted = FEV % predicted = 1.5
FEV % predicted = FEV1 33% predicted = 1.75
FEV % predicted = FEV1 25% predicted = 2.0
FEV % predicted = 1.4
Protein:
18-20% of caloric needs or ~2.2g/kg

40. IM’s Estimated Needs (JHH Formula)
Energy needs
IM’s IBW (BMI 22 for women, 23 for men)
56.3 kg
Promotes optimal lung function
(DBW x 35 x FEV1 factor) to (DBW x 40 x FEV1 factor)
(56.3 kg x 35 x 1.5) to (56.3 x 40 x 1.5)
= kcals/day
Protein needs
2.2 x 56.3kg
= 124g/day

41. Energy Requirements Calculation from the AND Nutrition Care Manual
Step 1: Calculate BMR
Age in years
Females
Males
10-18
12.2 (kg) + 746
17.5 (kg) + 651
18-30
14.7 (kg) + 496
15.3 (kg) + 679
30-60
8.7 (kg) + 829
11.6 (kg) + 870

42. Step 2: BMR x (Activity Coefficient + Disease Coefficient)
Energy Requirements
Step 2: BMR x (Activity Coefficient + Disease Coefficient)
Activity Level
Activity Coefficients (AC)
Confined to bed
BMR x 1.3
Sedentary
BMR x 1.5
Active
BMR x 1.7
Disease Severity
Disease Coefficients
FEV1 > 80%
(BMR x [AC + 0])
FEV %
(BMR x [AC + 0.2])
FEV1 < 40%
(BMR x [AC ])

43. Energy Requirements
Step 3: Calculate Daily Energy Expenditure, taking into account the degree of steatorrhea
For Pancreatic Sufficient Patients: (including pts with a coefficient of fat absorption [CFA] > 93%)
Daily energy requirement equals the daily energy expenditure
For Pancreatic Insufficient Patients:
Daily energy requirement equals the daily energy expenditure times (0.93/CFA)
If a stool fat collection is not available to determine fraction of fat intake, use approximate value of 0.85

44. IM’s Energy Requirements (AND Formula)
BMR = 14.7 (49kg) + 746
= 1216 kcals
Daily Energy Expenditure = 1216 kcals x ( )
= 3891 kcals
Total Daily Energy Requirement
= 3891 kcals (0.93/0.85)
= 4257 kcals
** JHH formula = 3378 kcals

45. Macronutrients Protein: 15–20% calories Fat: 35–40% calories
Levels are increased due to malabsorption
Fat: 35–40% calories
Carbohydrates: Varies

46. CF Sample Meal Plan Meal Menu Breakfast
1-2 large eggs scrambled in 1 tablespoon butter
2 slices whole wheat toast with butter
6 oz orange juice
Morning snack
Instant pudding made with evaporated milk
Lunch
Tuna salad (tuna canned in oil, hard-cooked egg, onion, pickle relish and mayonnaise
6 club crackers
2 canned peach halves with 2 Tbsp cottage cheese and 4 walnut halves
Afternoon snack
Fruit smoothie (apple juice, banana, frozen strawberries, ¼ c whole milk)
Evening meal
3 oz ground beef pattie with gravy
Baked potato with butter
Broccoli with cheese sauce
2 slices bread with butter
Evening snack
1 scoop ice cream with chocolate syrup
Approximate Nutritional Analysis: Calories: 3,094; Protein:129g (16% of calories); CHO:362g (46% of calories); Fat: 129g (37% of calories); Cholesterol: 750 mg; Sodium: 4,250 mg; Fiber 23g
SOURCE: AND Nutrition Care Manual

47. Fat Soluble Vitamin Supplementation
Vitamin A: 4, ,000 IU
Vitamin D: 800 – 2,000 IU
Vitamin E: 150 – 300 IU
Vitamin K: No recommendation
IM takes AquADEKS x1 tablet BID
Also recommended: Cholecalciferol 50,000 IU
q7 days; (IM has forgotten to take)

48. Pancreatic Insufficiency
85-90% of pts with CF
Definition: Elevated fecal fat excretion and presence of steatorrhea (fecal fat excretion > 7%)
Pancreatic enzyme supplements (enteric coating)
Prevents inactivation in acidic environment
Hyperacididty of upper GI tract in CF patients
Inadequate bicarbonate secretion by pancreas
H2 blockers and proton pump inhibitors (decrease gastric acid production)

49. Pancreatic Enzyme Replacement Therapy (PERT)
Pancreatic Enzymes
Effects
Lipase
Lipase works with bile from the liver to break down fat molecules
Protease
Protease breaks down proteins
Amylase
Amylase breaks down CHO into sugars
Also found in saliva
** IM takes Creon 24: 4 tabs with meals and 3 tabs with snacks
**24,000 USP units of lipase; 76,000 USP units of protease;
120,000 USP units of amylase capsules
**CF Foundation recommends 500 to 2,500 units lipase per kilogram
body weight per meal

50. Cystic Fibrosis-Related Diabetes (CFRD)
> 15% patients that are > 35 years old
OGTT or fasting glucose >126 mg/dL when confirmed by second fasting blood glucose
Marker of advanced disease
Treatment
Insulin therapy
Oral diabetes agents not as effective as insulin
Check blood sugars TID
Check HbA1c on regular basis
Moderate aerobic exercise
IM’s HbA1c was 5.8 (slightly increased) on 7/30/12 but does not have CFRD at this time

51. Enteral Feeding
If initial nutrition interventions are not effective and BMI < 19, consider enteral feedings
Usually G-tube, or J-tube
Usually nocturnal feedings
Caloric-dense formulas, > 1 kcal/ml
Enzyme replacement
If nocturnal feedings: pre and post feeding
Enzyme powder can also be added directly to the formula

52. Medical Treatment Variety of airway clearance techniques
Antibiotics- oral, IV, and aerosolized
Lung transplantation (end-stage CF)

53. Airway Clearance Techniques
Chest physiotheapy (CPT)
PEP devices
The Vest
Physical activity augments airway clearance

54. Antibiotics/Mucolytic agents
Tobramycin (TOBI)- chronic suppressive therapy
Improves lung function (490 mg IV daily)
Decrease density of Pseudomonas aeruginosa in sputum
Antimicrobial resistance?
Ceftazadime (2 gram IV q8)
Acute exacerbations of P. aeruginosa
Azithromycin
Recommendation: Consider for CF patients > 6 of age chronically infected with P. aeruginosa
Pulmozyme (Recombinant human DNase)
Nebulized Hypertonic Solution
Bronchodilators

55. Lung Transplantation End-stage CF
Became viable option > 10 years ago
5-year post transplant survival rate ~50%
Considered if have limited survival/ exhausted conventional therapies
Still prone to common transplant complications
Graft dysfunction
Acute and chronic rejection
Variety of infections and malignancies
Renal failure

56. Hospital COurse Pseudomonas Aeruginosa & B. Cepacia
Tobramycin at 10mg/kg/day
Ceftazadime 2mg q8
Benadryl and Prednisone (prophylactic)
Miralax PRN
Increased appetite, denies N/V/D/C
CPT/Acapella valve
Hypertonic saline nebs, albuterol nebs
FEV1 %: 73%
Discharged on 12/14/12 to complete
antibiotic course

57. Since IM’s Discharge of 12/14/12…
Clinic visit (12/21/12)
IM confused Tobramycin with Ceftazadime and took 3 doses of Tobramycin
Tinnitus (toxicity 2/2 Tobramycin toxicity)
PFTs: FEV1% of 59% (Decreased)
Clinic visit (1/7/13)
Repeat PFTs FEV1 % of 55% (Decreased)
CBW: 48.6 kg (decreased)
No GI issues at this time
Readmitted for IV antibiotics

58. Kalydeco (Ivacaftor)
New treatment approved by US Food and Drug Administration on January 31, 2012
First drug to TARGET a CAUSE of CF
G551D mutation in CFTR gene (~4% of CF in US)
Defective protein moves to the right place at the surface of the cell but does not function correctly
Acts like a locked gate, preventing the proper flow of salt and fluids in and out of the cell.
Oral medication taken BID
Improves lung function and increases weight gain

59. Questions?

60. References
Mahan LK, Escott-Stump S, and Raymond JL. Krause’s Food and the Nutrition Care Process. St. Louis, MO: Elsevier, 2012.
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