ESPEN Congress Lisbon 2015

Cystic fibrosisC. Colombo (IT)

ESPEN GUIDELINES

ESPEN GuidelinesCystic fibrosis

Carla Colombo

ESPEN LISBON SEPTEMBER 2015

• Most frequent autosomic recessive disease in the Caucasian population• It is a multisystemic disease affecting lungs, pancreas liver, intestine, sweat glands and reproductive tract• Lung disease is the main cause of morbidity and mortality• Median life expectancy is presently 41.7 yrs (Cystic Fibrosis Foundation Patient Registry, 2013)

CYSTIC FIBROSIS

Pancreatic Enzymes

antistaphylococcal antibioticsantipseudomonal antibiotics

rhDNaseInhaled Tobramycin

Airway clearance

0

5

1015

20

25

30

35

40

1st pathologicdescription

CF geneidentified

Discoveryof high saltin sweat

Sweat chloridetest developed

1st successfulpregnancy

CF proteinidentified

AzithromycinHTS

AZLI

What next?

Age (years)

• Individual benefit is modest but cumulative• Life expectancy greatly increased

Improved Survival with Treatment InnovationIncremental Modest Benefits

Improving outcomes for CF care

• Care delivered by multidisciplinary team in specialized Centers

• Neonatal screening –best care for the screened infant

• Improvement in nutritional status• Effective treatment of infection in the early years• Transition to adult care optimal adult care• New therapies ...the importance of clinical trial networks

Toronto (1970s)

High-fat, high-energy diet

Normal growth and nutritional status

Better survival

1960s-1980s

Low fat diet often prescribed to control abdominal symptoms and maldigestion/malabsorption

As a consequence, most CF patients developed severe malnutrition and stunting due to energy imbalance

Corey et al, J. Clin Epidemiol 1988; 41: 583

Survival Curves of CF patients followed in Boston and in Toronto in 1982

Energy imbalance in patients with CF

Decreased intakeAnorexiaCytokine releaseReflux, oesophagitisBloating, abdominal painSalt deficiencyCoughing, vomitingPsychosocial issues

Increased lossPancreatic insufficiencyBile salt depletion Defective absorptionCF-related diabetes

Increased needBasal metabolic rateRespiratory infectionsWork of breathing

CFF Patient Registry Report 2013

ESPEN Cystic Fibrosis Guidelines Team• Christian P Braegger, MD (Switzerland)• Carla Colombo, MD (Italy)• Dimitri Declercq, MSc (Belgium)• Alison Morton, RD, BSc-Hons (UK)• Ruzha Pancheva, MD, PhD (Bulgaria)• Eddy Robberecht, MD, PhD (Belgium)• Martin Stern, MD (Germany)• Birgitta Strandvik, MD, PhD (Sweden)• Sue Wolfe, RD, BSc-Hons (UK)• Stephane M. Schneider, MD (France)• Dominique Turck, MD (France)• Michael Wilschanski, MBBS (Israel)

Currently under review by ESPGHAN and ECFS

Cochrane Database of Systematic Reviews• Francis DK, Smith J, Saljuqi T, Watling RM. Oral protein calorie

supplementation for children with chronic disease. 2015, Issue 5. • Morton A, Wolfe S. Enteral tube feeding for cystic fibrosis. 2015, Issue 4.• Jagannath VA, Fedorowicz Z, Thaker V, Chang AB. Vitamin K

supplementation for cystic fibrosis. 2015, Issue 1.• Okebukola PO, Kansra S, Barrett J. Vitamin E supplementation in people

with cystic fibrosis. 2014, Issue 12.• Smyth RL, Rayner O. Oral calorie supplements for cystic fibrosis. 2014, Issue

11.• Somaraju U, Solis-Moya A. Pancreatic enzyme replacement therapy for

people with cystic fibrosis. 2014, Issue 10. • Ciofu O, Lykkesfeldt J. Antioxidant supplementation for lung disease in

cystic fibrosis. 2014, Issue 8. • Bonifant CM, Shevill E, Chang AB. Vitamin A supplementation for cystic

fibrosis. 2014, Issue 5. • Ferguson JH, Chang AB. Vitamin D supplementation for cystic fibrosis.

2014, Issue 5• Oliver C, Watson H. Omega-3 fatty acids for cystic fibrosis. 2013, Issue 11

DEVELOPMENT OF GUIDELINES FOR CF NUTRITIONAL CARE TOPICS

• General guidelines statements• Specific guidelines statements• Assessment method and timing• Feeding the newly diagnosed infant• Feeding children and adults• Balancing protein and fat intake• Minerals, trace elements, vitamins• Salt• Treatment of pancreatic insufficiency• Progression and intensified feeding

- Oral nutritional supplements- Tube-fed enteral nutrition- Parenteral nutrition

• CF-related disease with nutritional consequences• Pregnancy• Specialized nutrition-related treatments (essential fatty acids, growth

hormone, appetite stimulants, probiotics, anti-osteoporotic agents)

WHAT ‘S NEW?

• Updates (sodium, vitamins, zinc)

• Updated assessment on bone disease, CF-related diabetes, liver disease

• Pregnancy

• Specialized nutrition-related treatments (EFA, anti-osteoporotic agents, GH, appetite stimulants, probiotics)

Screen all newborns for CF, and initiate nutrition care early.

Monitor nutritional status by routine assessment of relevant anthropometric parameters.

Prevent or delay onset of nutrition deficits by nutrition counseling, high-energy intake, supplemental vitamins and minerals, and PERT.

Advise parents/patients on balanced macronutrient intake, especially adequate protein and fat.

Manage under-nutrition by diagnosing inadequacy, treating underlying causes, and compensating specific deficiencies.

General recommendations for 2015 CF nutrition care

We recommend measuring weight and length or height at each clinic visit. GOE=Low

We recommend using these levels to indicate adequate nutritional status: • Infants and children ≤ 2 years: 50th percentile of weight and length for a healthy

same-age population. • Children 2 to 18 years: 50th percentile of the BMI for a healthy, same-age

population• Adults > 18 years – BMI at or above 22 kg/m2 for females and 23 kg/m2 for males

GOE=Low

Assessment of nutritional status

• Infants: weight and length/height at every visit; ideally monthly up to 1 year

• Children and adults: at least quarterly• Plan more frequent monitoring in undernourished patients

Growth/weight/bone measurement

• Annual review with blood tests• Assessment of PERT need or adequacy of treatment bymonitoring growth, nutritional status, and gastrointestinalsymptoms

• Measure pulmonary function (FEV1)

Nutrition monitoring

• Children: every 3 months• Adults every 6 months• Include questions about adherence to dietary adviceDietary review

GOE=Low

Pancreatic enzyme lipase replacement

Age Suggested supplementationInfants (up to 12 months)

2000-4000 U lipase/120 mL formula or estimated breast milk intake and approximately 2000 U lipase/gram dietary fat in food

Children 1 to 4 years 2000 to 4000 U lipase/gram dietary fat, increasing dose upward as needed

Children > 4 years and adults

Consider starting at 500 U lipase/kg BW/meal, titrating upward to a maximal dose of:•1000 to 2500 U lipase/kg BW per meal, or •10,000 U lipase/kg BW per day, or•2000 to 4000 U lipase/gram dietary fat taken with all fat-containing meals, snacks and drinks

The self-management of enzyme replacement in the European cysticfibrosis (CF) patients by means of a mobile application (APP) that allows fora personalised and accurate control and monitoring of pancreaticinsufficiency thanks to the interaction between patients and healthprofessionals.

AIM of the Project

www.mycyfapp.eu

Assess body composition (dual-energy X-ray absorptiometry, DXA), including bone health, for all patients ≥ 8 years old.

Assess calcium intake at least annually

Screen all CF patients ≥ 10 years for glucose tolerance.

For women with CF who are or plan to become pregnant, we recommend increasing the frequency of monitoring and continuing after delivery.

Assess pancreatic function yearly in pancreatic sufficientpatients by fecal elastase-1, with the test repeated if growth is

inadequate.

Specific recommendations for 2015 CF nutrition care

GOE=Low

Energy TargetsAge Energy target Detail

Infants and children ≤ 2 years

110% to 200% of energy requirements for same-age healthy infants and children

Energy intake should be adapted to achieve normal weight- and length-for-age percentiles

Children 2 to 18 years

110% to 200% of energy requirements for same-age healthy children

Energy intake should be adapted to achieve target BMI percentile

Adults > 18 years

110% to 200% of energy requirements for same-age healthy population

Energy intake should be adapted to achieve BMI targets

Curr Opin Clin Nutr Metab Care 2014;17:515-520.

Sodium supplementation Europe vs US

AgeSodium

supplement*Detail

Breastfed infants 0 to 6 months

1–2 mmolper kg bw/day

For infants at risk of sodium deficiency give salt in small portions throughout the day, diluted in water or fruit juice.

For infants with special considerations

Up to 4 mmol per kg bw/day

Increase intake for infants living in hot ambient temperatures; or for those with increased fluid loss due to vomiting, fever, diarrhea, or tachypnea; or infants with ostomies.

Older children through adults

Salty foods or sodium chloride capsules or vials

Supplement in stress situations when excessive sweating is expected (i.e., fever, exercise/sports, hot weather).

We recommend assessing infants’ needs for sodium supplementation on an individual basis, taking climate and sodium losses into consideration, by measuring fractional excretion of sodium (FENa) or urinary sodium: creatinine ratio

Daily zinc supplementation

AgeRecommended

supplementationRecommended dosing

period

Infants and children < 2 years and at risk of zinc insufficiency

1 mg/kg/day(max 15 mg/day)

6 months

Children 2 to 18 years andat risk of zinc insufficiency

15 mg/day 6 months

Adults > 18 years andat risk of zinc insufficiency

25 mg/day 6 months

We suggest zinc supplementation for people with CF who are at risk of zinc insufficiency (e.g., growth retardation, increased susceptibility to infections, delayed sexual maturation, eye problems, and anorexia).GOE=Low

Fat Soluble Vitamins

Vitamin A

Vitamin D

Vitamin E

Vitamin K

Vitamin D supplementation for pancreatic-insufficient patients

Vitamin SupplementationSerum reference values

and monitoring frequency

Vitamin D Dependent on serum values, which vary with dietary intake and sun exposure:•Starting dose of D3 (cholecalciferol)

- Infants 400 IU/day (advance to upper limit of 1000 IU/day)

- All others 800 IU/day (advance to upper limit of 2000 for children 1-10 years, and 4000 IU/day for older)

•Maintenance dose: adapt to annual serum values, preferably measured at the end of dark months

Serum-25 (OH) Dminimum 20 ng/mL (50nmol/L)

Monitor annually, and check 3 to 6 months after a dosage change

Supplementation of vitamins E and K for pancreatic-insufficient patients

Vitamin SupplementationSerum reference values and

monitoring frequency

Vitamin E (tocopherols)

α-tocopherol dosing:100 to 400 IU/day 50 IU/day for infants < 12 mos(1mg = 1.49 IU)

Plasma α-tocopherol:cholesterol ratio > 5.4 mg/g Monitor annually, and check 3 to 6 months after a dosage change

Vitamin K Vitamin K1•Infants: 0.3 to 1.0 mg/day•Older children and adults: 1 to 10 mg/day

Routine biochemical measurement not widely available

Vitamin A supplementation for pancreatic-insufficient patients

Vitamin SupplementationSerum reference values and

monitoring frequency

Vitamin A Amounts dependent on serum values, and supplement form:Retinol (preformed):•Start low•Adapt rapidly to target normal serum reference range Beta carotene (provitamin A):•Prescribe 1 mg/kg BW/day (maximum 50 mg/day) for 12 weeks•Follow with maintenance dose (maximum 10 mg/day)

Normal reference range provided by the laboratory processing the sample

Monitor annually and 3 to 6 months after a dosage change. Also test when pregnancy is considered.

Guidelines: Nutrition intervention

• We recommend nutrition intervention based on a full review of nutrition status, including a detailed review of pancreatic enzyme replacement therapy (PERT), and correction of any underlying medical conditions.GOE=High

• We recommend using age-appropriate BMI-related thresholds for deciding when to advance nutrition intervention. GOE=High

• We recommend a progressive approach to intensification of nutrition interventions as needs increase: preventive nutritional counseling, dietary modification and/or oral nutrition supplements, and enteral tube feeding. GOE=Low

Nutritional status and Intervention

Decision point for intensified nutritional support

Infants ≤ 2 years Children 2 to 18 years Adults > 18 years

Normal nutritional status: Preventive nutritional counseling

Weight and length ≤ 50th percentile

BMIp ≤ 50th percentile • BMI:19 to 22 (for females)19 to 23 (for males), or

• No weight loss

Special nutritional support: Diet modification and/or oral nutrition supplements

Failure to thrive:weight and length 10th to 50th percentile

• BMIp 10th to 50th, or• Weight loss in previous

2 to 4 months, or• No weight gain

in previous 2 months

• BMI < 19, or• Weight loss of 5% in previous 2

months

Persistent undernutrition:Enteral tube feeding

Persistent failure to thriveweight and length < 10th

percentile

• Persistently low BMIp (BMIp < 10th), or

• Weight loss of 2 percentile points since last visit

• Persistently low BMI(BMI < 19), or

• Continuing weight loss

Feeding undernourished people with CF

Acknowledgements• The systematic review and grading of the evidence were

performed by Prof Leonard Leibovici and DrVeredZarezky from Rabin Medical Centre, Beilinson Hospital and Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel.

• We thank Cecilia Hofmann, PhD, for her valued assistance with compilation of the medical literature and with editing this English-language guideline.