W E N D Y A N D E R S O NF E B R U A R Y 1 , 2 0 1 3

CYSTIC FIBROSIS: A CLINICAL NUTRITION CASE STUDY

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

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

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 2010. Bethesda, MD; 2011

CYSTIC FIBROSIS: LIFE EXPECTANCY

WHAT’S THE CHANCE?

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)

CFTR: THE GENE ASSOCIATED WITH CF

5 CLASSES OF CFTR MUTATIONS: CLASSIFIED BY EFFECT ON

CFTR PROTEIN

Pancreatic Insufficient

Pancreatic Sufficient

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.

DELTA F508 MUTATION

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

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

ORGANS AFFECTED BY CF

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

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

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!!

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

OVERVIEW OF PATIENT

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

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

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)

NUTRITION ASSESSMENT

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

NUTRITIONAL ASSESSMENT

• Height: 63”• CBW: 49 kg• UBW: 50 kg• %UBW: 98%• Weight History: 8/2012 (50.8 kg); 3/2012 (49.2

kg); 6/2011 (52.7 kg)• BMI: 19.1• %FEV1 upon admission: 44% • %FEV1 baseline: ~80%

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.

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)”.

NUTRITION ASSESSMENT

• Goals• 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)

HOME MEDICATIONSMedications Functions Possible GI Side Effects

Adderall Anti-ADHD Dry mouth, N/C/D, stomach pain, metallic taste

Pristiq Antidepressant taste changes, N/V/C/DAbilify Antidepressant N/V/C, dry mouth, dyspepsiaCogentin Controls movement

related side effectsAdvair Bronchodilator Candidiasis, N/V/DPulmozyme (Dornase alfa/DNase)

Decreases viscosity of secretions

Laryngitis

Hypertonic Saline Nebs Decreases viscosity Increases coughing, chest tightnessAlbuterol Nebs Bronchodilator Sore throat, diarrheaCreon 24 Pancreatic enzymes N/V, abdominal pain, diarrheaErgocalciferol Vitamin D supplement N/V/C/D, metallic tasteAquADEKS MVI w/ minerals Overdose can cause GI issuesSubuxone For opioid addiction N/V, dry mouthAzithromycin Antibiotic N/V, abdominal pain, diarrheaMiralax Laxative N, bloating, cramps, flatulanceLansoprazole Proton Pump inhibitor N, abdominal pain, diarrhea

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

IM’S LAB VALUESParameter Ref. Range Value Date IndicationVitamin A 38-98 mcg/dL 37 (L) 8/4/12 MalabsorptionVitamin D 32-100 ng/dL 23 (L) 12/7/2012 MalabsorptionVitamin E 5.7-19,9 mg/dL 6.2 7/30/12Prothrombin 10-14 sec 10.2 12/7/12Albumin 3.5-5.3 g/dL 4.1 12/7/12Total Bilirubin 0.1-1.2 mg/dL 0.2 12/14/12Alk Phos 30-120 U/L 71 12/14/12AST 0-31 U/L 20 12/14/12ALT 0-31 U/L 21 12/14/12Glucose 60-99 mg/dL 117(H) 12/7/12

HbA1c 3.5-5.5 % 5.8 (H) 7/30/12 Impaired glucose tolerance

WBC 4500-11,000 13,000 (H) 12/14/12 InfectionHemoglobiin 12-15 g/dL 11.2 (L) 12/14/12 Low Iron storesHematocrit 36-46% 36.4 12/14/12 Indicator of Iron

statusMCV 80-100 fL 87.2 12/14/12Lipase 16-23 U/L 3 (L) 7/30/12 Chronic disease

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%)

NUTRITIONAL STATUS & PULMONARY FUNCTION IN ADULT CF PATIENTS

• Journal of Physiology and Pharmacology, 2008• 39 CF patients (21 females and 18 males)• Mean age 23.9 + 3.7 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)

MEDICAL NUTRITIONTHERAPY FOR CF

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

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!

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

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

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 = 1.0 FEV1 40-50% predicted =

1.5• FEV1 70-90% predicted = 1.2 FEV1 33% predicted =

1.75• FEV1 60-70% predicted = 1.3 FEV1 25% predicted = 2.0• FEV1 50-60% predicted = 1.4

• Protein:• 18-20% of caloric needs or ~2.2g/kg

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)• = 2955-3378 kcals/day

• Protein needs• 2.2 x 56.3kg• = 124g/day

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

ENERGY REQUIREMENTS

Step 2: BMR x (Activity Coefficient + Disease Coefficient)

Activity Level Activity Coefficients (AC)

Confined to bed BMR x 1.3Sedentary BMR x 1.5Active BMR x 1.7

Disease Severity Disease CoefficientsFEV1 > 80% (BMR x [AC + 0])FEV1 40-79% (BMR x [AC + 0.2])FEV1 < 40% (BMR x [AC + 0.3 - .05])

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

IM’S ENERGY REQUIREMENTS (AND FORMULA)

• BMR = 14.7 (49kg) + 746• = 1216 kcals

• Daily Energy Expenditure = 1216 kcals x (1.5 + 1.7)• = 3891 kcals

• Total Daily Energy Requirement• = 3891 kcals (0.93/0.85)• = 4257 kcals

• ** JHH formula = 3378 kcals

MACRONUTRIENTS

• Protein: 15–20% calories• Levels are increased due to malabsorption

• Fat: 35–40% calories

• Carbohydrates: Varies

CF SAMPLE MEAL PLAN Meal Menu

Breakfast 1-2 large eggs scrambled in 1 tablespoon butter2 slices whole wheat toast with butter6 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 mayonnaise6 club crackers2 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 gravyBaked potato with butterBroccoli with cheese sauce2 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

FAT SOLUBLE VITAMIN SUPPLEMENTATION

• Vitamin A: 4,000 -10,000 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)

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)

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 sugarsAlso 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

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

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

MEDICAL TREATMENT

• Variety of airway clearance techniques

• Antibiotics- oral, IV, and aerosolized

• Lung transplantation (end-stage CF)

AIRWAY CLEARANCE TECHNIQUES

• Chest physiotheapy (CPT)

• PEP devices

• The Vest

• Physical activity augments airway clearance

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

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

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

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

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

QUESTIONS?

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