Clinical Practice Guidelines From the Cystic Fibrosis...

SPECIAL ARTICLEPEDIATRICS Volume 137 , number 4 , April 2016 :e 20151784

Clinical Practice Guidelines From the Cystic Fibrosis Foundation for Preschoolers With Cystic FibrosisThomas Lahiri, MD, a Sarah E. Hempstead, MS, b, c Cynthia Brady, DNP, d Carolyn L. Cannon, MD, PhD, e Kelli Clark, BS, f Michelle E. Condren, PharmD, g Margaret F. Guill, MD, c, h R. Paul Guillerman, MD, i Christina G. Leone, MSW, LCSW, j Karen Maguiness, MS, RD, CSP, k Lisa Monchil, RRT-NPS, CCRC, AE-C, l Scott W. Powers, PhD, ABPP, m Margaret Rosenfeld, MD, MPH, n Sarah Jane Schwarzenberg, MD, o Connie L. Tompkins, PhD, p Edith T. Zemanick, MD, q Stephanie D. Davis, MDk

Cystic fibrosis (CF) clinical care guidelines exist for the care of infants

up to age 2 years and for individuals ≥6 years of age. An important gap

exists for preschool children between the ages of 2 and 5 years. This

period marks a time of growth and development that is critical to achieve

optimal nutritional status and maintain lung health. Given that disease

often progresses in a clinically silent manner, objective and sensitive tools

that detect and track early disease are important in this age group. Several

challenges exist that may impede the delivery of care for these children,

including adherence to therapies. A multidisciplinary committee was

convened by the CF Foundation to develop comprehensive evidence-based

and consensus recommendations for the care of preschool children, ages

2 to 5 years, with CF. This document includes recommendations in the

following areas: routine surveillance for pulmonary disease, therapeutics,

and nutritional and gastrointestinal care.

abstract

aPediatric Pulmonology, University of Vermont Children’s

Hospital and Department of Pediatrics, University of

Vermont College of Medicine, Burlington, Vermont; bThe

Dartmouth Institute for Health Policy and Clinical Practice,

Lebanon, New Hampshire; cGeisel School of Medicine

at Dartmouth, Lebanon, New Hampshire; dChildren’s

Respiratory and Critical Care Specialists and Children’s

Hospitals and Clinics of Minnesota, Minneapolis, Minnesota; eTexas A&M Health Science Center, College Station, Texas; fDepartment of Pediatrics, University of North Carolina,

Charlotte, North Carolina; gUniversity of Oklahoma College

of Pharmacy and School of Community Medicine, Tulsa,

Oklahoma; hAllergy and Pediatric Pulmonology, Dartmouth-

Hitchcock Medical Center, Lebanon, New Hampshire; iDepartment of Radiology, Baylor College of Medicine

and Department of Pediatric Radiology, Texas Children’s

Hospital, Houston, Texas; jCystic Fibrosis Center, Children’s

Hospital Colorado, Aurora, Colorado; kSection of Pediatric

Pulmonology, Allergy and Sleep Medicine, Department of

Pediatrics, Riley Hospital for Children, Indiana University

School of Medicine, Indianapolis, Indiana ; lArmond V.

Mascia, MD Cystic Fibrosis Center, Maria Fareri Children’s

Hospital at Westchester Medical Center, Valhalla, New

York; mDepartment of Pediatrics and Cincinnati Children’s

Research Foundation, University of Cincinnati College of

Medicine and Division of Behavioral Medicine and Clinical

Psychology, Cincinnati Children’s Hospital, Cincinnati, Ohio; nDivision of Pulmonary Medicine, Seattle Children’s Hospital

and Department of Pediatrics, University of Washington

School of Medicine, Seattle, Washington; oPediatric

Gastroenterology, Hepatology and Nutrition, University

of Minnesota Masonic Children’s Hospital, Minneapolis,

Minnesota; pDepartment of Rehabilitation and Movement

Sciences, University of Vermont College of Nursing and

Health Sciences, Burlington, Vermont; and qDepartment

of Pediatrics, University of Colorado School of Medicine,

Aurora, Colorado

Drs Lahiri and Davis reviewed selected articles,

drafted the initial manuscript, and revised the fi nal

manuscript; Ms Hempstead performed a literature

Early nutritional intervention and

monitoring for respiratory and

gastrointestinal disease in infants

with cystic fibrosis (CF) is vital to

improve long-term outcomes. Clinical

care guidelines specific to infants with

CF, 1 and nutrition and pulmonary

guidelines for children > 6 years of

age have been published by the CF

Foundation.2, 3 However, a gap exists

in clinical care recommendations

pertaining to preschoolers with CF,

children ages 2 to 5 years.

In addition to typical developmental

milestones, preschoolers with CF and

their families face complex, time-

consuming treatment regimens to

maintain lung health and achieve

optimal growth. It is well established

that airway inflammation, infection,

airway obstruction, and structural

damage exist during preschool years in

children with CF, often in the absence

of overt respiratory symptoms.4–7 For

families of preschoolers with CF, it can

be challenging to institute appropriate

mealtime behaviors, which can lead

to poor nutritional outcomes8–10

and decreased survival at age 18

years when weight-for-age is ≤10th

percentile for age and gender at age

4 years.11 Supporting preschoolers

with CF and their families is critical to

establish habits that promote normal

growth and development and an

active lifestyle (ie, exercise) to prevent

pulmonary decline.

METHODS

In January 2014, the CF Foundation

convened a committee of 16 CF

pediatric experts and parents to

develop clinical care guidelines for

To cite: Lahiri T, Hempstead SE, Brady C, et al.

Clinical Practice Guidelines From the Cystic

Fibrosis Foundation for Preschoolers With Cystic

Fibrosis. Pediatrics. 2016;137(4):e20151784

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LAHIRI et al

preschool-aged children with CF.

The treatment of this population

has become increasingly important,

as earlier diagnoses are made,

primarily through newborn

screening. Committee members

participated in 1 of 3 workgroups.

Each group developed population,

intervention, comparison, and

outcome (PICO) questions, 12 which

were reviewed and approved by

the wider committee. Dartmouth

College investigators conducted a

Medline literature search using PICO

questions and additional medical

search headings provided by the

committee. Committee members

conducted hand searches for

additional literature and existing

guidelines.

In May 2014 the committee convened

to review draft recommendation

statements and supporting evidence.

Unfortunately, the evidence is

lacking for most treatments and

monitoring tools in the 2- to 5-year-

old age group. Whenever possible,

statements were developed and

graded by using the US Preventive

Services Task Force grade

definitions (Supplemental Table

1). The committee decided to make

recommendations for CF care that

would guide both CF clinicians and

primary care providers (PCPs).

Therefore, questions for which

evidence was limited or absent were

then presented and discussed by

committee members. Use of existing

evidence from older children and

adults, as well as clinical experience,

was then used as the basis for

consensus recommendations. An

80% approval by the committee was

agreed on a priori, and required for

all statements. Revisions and voting

were managed by using an online

survey. All recommendations were

approved by the committee, and

had a final consensus rate of at least

87.5%.

A draft manuscript was distributed

by the CF Foundation to all

accredited care centers for a 2-week

public comment period. Feedback

was collected by using an online

survey and the guidelines were

revised accordingly. The committee

recognizes the limitations of these

guidelines, which are the first step

in standardization of preschool

CF care. We fully expect these

recommendations to evolve over

time, as randomized controlled

trials in these younger patients

may provide evidence in favor of or

against consensus recommendations.

RESULTS

In total, 10 427 articles were

retrieved. Review articles, case

reports, letters, nonhuman studies,

and studies not related to the PICO

questions were removed. A total

of 344 articles were retained for

review. Additional details on the

review process can be found in the

Supplemental Information. Guideline

recommendations are summarized in

Table 1.

DISCUSSION

Health Maintenance

Preschoolers with CF should

receive routine well-child care from

a PCP. Collaboration among the

family, PCP, and a CF Foundation

accredited care center is essential,

and information about CF and the

child’s CF care should be provided

to the PCP.1 Children should receive

age-appropriate immunizations and

annual seasonal influenza vaccination

along with family members and

caregivers.13–15 They should receive

the first dose of pneumococcal

polysaccharide vaccine (PPSV23),

given at least 8 weeks after the last

pneumococcal conjugate vaccine

(PCV13) dose. Environmental

tobacco smoke exposure should be

avoided; providers should routinely

assess for environmental smoke

exposure and offer caregivers

information about smoking cessation

and interventions to limit exposure.16

Table 2 outlines routine monitoring

care for preschoolers with CF

including primary care visits. Table 1:

Recommendations 1–5.

Caregiver Engagement

Parenting a preschooler with CF

can be demanding and stressful.

Families can face significant obstacles

accessing CF care, including the high

cost of insurance and prescription

medications, and delays in, or denial

of, coverage. Families may need

guidance to model behaviors to

handle refusals to take medications

and to navigate mealtime struggles.

To promote normal growth and

development, it is essential to

institute and maintain CF care

routines in partnership with families,

especially during preschool-age

development. Parents and CF

providers should collaborate to

develop individualized treatment

goals and plans that address barriers

to care. Supplemental Table 2 lists

some risk factors for poor adherence

and Supplemental Table 3 outlines

questions and topics to help

caregiver engagement with

treatment adherence. Table 1:

Recommendation 6.

SURVEILLANCE FOR PULMONARY DISEASE

Pulse Oximetry

Few studies have evaluated oxygen

saturation levels in CF. In older

children and adolescents with CF,

correlations between nocturnal O2

saturation and lung function indices,

chest computed tomography (CT),

and chest radiograph scores have

been reported17, 18; hypoxia during

sleep has been demonstrated to be

associated with low forced expiratory

volume in 1 second (FEV1).19

In infants and preschoolers, no

significant difference was observed

in nocturnal O2 saturation in those

with CF versus controls.20 Given

the paucity of data in preschoolers

with CF, the committee concluded

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PEDIATRICS Volume 137 , number 4 , April 2016 3

TABLE 1 Recommendation Statements

Topic Recommendation Statement Grade or Consensus Previous Guideline(s)

Health Maintenance 1. For children with CF, ages 2 through 5 y, the

CF Foundation recommends routine well-child

care at PCP following AAP guidelines.

Consensus Recommendation AAP, Preventative Health Care (2014)

Health Maintenance 2. The CF Foundation recommends that children

with CF, ages 2 through 5 y, receive all routine

immunizations, following the recommended

vaccination schedule per the AAP.

Consensus Recommendation AAP, Immunization Schedule (2014)


with CF, ages 2 through 5 y, family members,

and caregivers should receive annual seasonal

infl uenza vaccination.

Consensus Recommendation AAP, Recommendations for Prevention

and Control of Infl uenza in Children,

2013–2014 (2013)

Cystic Fibrosis Foundation Evidence-

Based Guidelines for Management

of Infants with Cystic Fibrosis (2009)

Consensus Recommendation


with CF, ages 2 through 5 y, receive the fi rst

dose of the pneumococcal polysaccharide

vaccine (PPSV23), given at least 8 wk after last

pneumococcal conjugate (Prevnar) vaccine

dose.

Consensus Recommendation AAP Immunization Schedule (2014)

Health Maintenance 5. For children with CF, ages 2 through 5 y, the

CF Foundation recommends that a smoke-

free environment be provided and that all

caregivers are informed that cigarette smoke

exposure harms children with CF.

Consensus Recommendation Cystic Fibrosis Foundation Evidence-




AAP-Tobacco Use: A Pediatric Disease

(2009)

Caregiver Engagement 6. For children with CF ages, 2 through 5 y, the CF

Foundation recommends that parents and a

CF health care professional review treatment

goals and individualized care plans quarterly

to assess and address barriers to CF care.


Screening and Monitoring:

Pulse Oximetry

7. For children with CF, ages 2 through 5 y, the CF

Foundation concludes that there is insuffi cient

evidence to recommend for or against the use

of pulse oximetry routinely as an adjunctive

tool to detect lung disease.

Grade: I; Certainty: Low Cystic Fibrosis Foundation Evidence-



Grade: I, Certainty: Low, Benefi t: Small


Spirometry

8. For children with CF, ages 2 through 5 y, the

CF Foundation recommends that spirometry

should be attempted as early as age 3,

depending on the developmental stage of the

individual child.



Spirometry

9. For children with CF, ages 3 and older, the CF

Foundation recommends the use of spirometry

for identifying pulmonary exacerbations and

monitoring response to therapy in those

children able to perform acceptable and

reproducible maneuvers.



Bronchodilator



evidence to recommend for or against routine

monitoring of bronchodilator responsiveness.

Grade: I; Certainty: Low Cystic Fibrosis Pulmonary Guidelines:

Chronic Medications for Maintenance

of Lung Health (2013) Grade: I

Certainty: Low


Multiple Breath Washout



evidence to recommend for or against routine

monitoring of multiple breath washout.

Grade: I; Certainty: Low


Chest Imaging


CF Foundation recommends chest radiographs

be obtained at a minimum every other year to

monitor progression of lung disease.






LAHIRI et al 4


Cystic Fibrosis Adult Care (2004)



Chest Imaging


CF Foundation recommends consideration of

chest CT as an alternative to chest radiograph

to monitor progression of lung disease. If

chest CT is performed, it should replace chest

radiograph, be performed every 2–3 y, and use

the lowest radiation dose possible.






Microbiology


Foundation recommends routine monitoring of

airway microbiology by oropharyngeal cultures

at least quarterly.



of Infants with Cystic Fibrosis

(2009) Consensus Recommendation,

Certainty: Low, Benefi t: Moderate


Microbiology


Foundation recommends against routine use of

bronchoscopy to obtain lower airway cultures.

Grade: D; Certainty: Moderate;

Benefi t: Negative

Cystic Fibrosis Foundation Pulmonary

Guideline: Pharmacologic

Approaches to Prevention and

Eradication of Initial Pseudomonas

aeruginosa Infection (2014) Grade: D,

Certainty: Moderate, Benefi t: Zero

Therapeutics: Exacerbations 16. For children with CF, ages 2 through 5 y, the

CF Foundation recommends the use of oral,

inhaled, and/or intravenous antibiotics to treat

pulmonary exacerbations.


Therapeutics: Airway

Clearance


CF Foundation recommends the use of daily

airway clearance to improve lung function and

reduce exacerbations.




(2009) Consensus Recommendation

Certainty: Low Benefi t: Moderate

Cystic Fibrosis Pulmonary Guidelines:

Airway Clearance Therapies (2009)

Grade B, Certainty Fair, Benefi t:

Moderate

Therapeutics: Airway

Clearance

18. For children with CF, ages 2 through 5 y,

the CF Foundation recommends increasing

frequency and/or duration of airway clearance

treatments for children diagnosed with

pulmonary exacerbations.

Consensus Recommendation Cystic Fibrosis Pulmonary Guidelines:

Airway Clearance Therapies (2009)

Grade B

Therapeutics: Bronchodilators 19. For children with CF, ages 2 through 5 y, the

CF Foundation concludes that the evidence

is insuffi cient to recommend for or against

the chronic use of inhaled bronchodilators

to improve lung function and quality of life or




of Lung Health (2013), Grade: I,

Certainty: Low

Therapeutics: Hypertonic

saline


CF Foundations recommends that hypertonic

saline be selectively offered to patients based

on individual circumstances.

Grade C; Certainty: Moderate;

Benefi t: Low



of Lung Health (2013) Grade: B,

Certainty: Moderate, Benefi t:

Moderate

Therapeutics: Dornase alfa 21. For children with CF, ages 2 through 5 y, the

CF Foundation recommends that dornase alfa

be selectively offered to patients based on

individual circumstances.

Grade C; Certainty: Moderate;

Benefi t: Low



of Lung Health (2013) Moderate to

severe disease: Grade: A, Certainty:

High, Benefi t: Substantial. Mild

disease: Grade: B. Certainty: High,

Benefi t: Moderate




In symptomatic infants: Consensus

Recommendation, Certainty: Low,

Benefi t: Moderate

TABLE 1 Continued




Therapeutics: Inhaled

Corticosteroids


and without asthma or recurrent wheezing,

the CF Foundation recommends against the

routine use of inhaled corticosteroids to

reduce exacerbations, airway infl ammation, or

improve lung function or quality of life.

Grade: D; Certainty: High; Benefi t:

Low



of Lung Health (2013) Grade: D,

Certainty: High, Benefi t: Zero. Cystic

Fibrosis Foundation Evidence-Based

Guidelines for Management of

Infants with Cystic Fibrosis (2009)

Consensus Recommendation,

Certainty: Low, Benefi t: Zero/Negative

Therapeutics: Corticosteroids 23. For children with CF, ages 2 through 5 y,

and without allergic bronchopulmonary

aspergillosis, the CF Foundation recommends

against the chronic use of systemic

corticosteroids to reduce exacerbations, or

improve lung function, or quality of life.

Grade: D; Certainty: High; Benefi t:

Low




Certainty: High, Benefi t: Negative

Therapeutics: Ibuprofen 24. For children with CF, ages 2 through 5 y, the CF


evidence to recommend for or against

chronic high-dose ibuprofen use to slow rate

of decline of FEV1, reduce exacerbations and

hospitalizations, or improve quality of life.



of Lung Health (2013), Grade B,

Certainty: Moderate, Benefi t:

Moderate

Therapeutics: Leukotriene

Modifi ers


CF Foundation concludes that the evidence is

insuffi cient to recommend for or against the

routine chronic use of leukotriene modifi ers

to improve lung function or quality of life or




of Lung Health (2013), Grade: I,

Certainty: Low

Therapeutics: Azithromycin 26. For children with CF, ages 2 through 5 y, the CF


evidence to recommend for or against the

chronic use of azithromycin.



of Lung Health (2013), Grade: C,

Certainty: Moderate, Benefi t: Small

Therapeutics: Chronic

Pseudomonas Infection


CF Foundation recommends that children who

remain persistently infected with P aeruginosa

be treated chronically with alternate-month

inhaled antipseudomonal antibiotics.

Grade B; Certainty: Moderate;

Benefi t: Moderate



of Lung Health (2013) Inhaled

Tobramycin Moderate to Severe:

Grade A, Certainty: High, Benefi t:

Substantial Inhaled Tobramycin

Mild Disease: Grade B, Certainty:

Moderate, Benefi t Moderate

Inhaled Aztreonam Moderate to

Severe Disease: Grade: A Certainty:

High, Benefi t: Substantial Inhaled

Aztreonam Mild Disease: Grade

B, Certainty: Moderate, Benefi t:

Moderate Other Inhaled Antibiotics:

Grade I: Benefi t: Low.




Consensus, Certainty Low, Benefi t

Moderate

Therapeutics: S aureus 28. For children with CF, ages 2 through 5 y,

the CF Foundation recommends against the

prophylactic use of oral antistaphylococcal

antibiotics.

Grade: D; Certainty: Moderate;

Benefi t: Negative




Certainty: Moderate, Benefi t: Negative

Therapeutics: S aureus 29. For children with CF, ages 2 through 5 y, the CF


evidence to recommend for or against active

attempts to eradicate Staphylococcus aureus,

including methicillin-resistant S aureus, in

asymptomatic patients.

Grade: I; Certainty: Low Cystic Fibrosis Foundation Evidence-



Grade: I, Certainty: Low, Benefi t:

Unknown.

TABLE 1 Continued


LAHIRI et al 6


Therapeutics: Staphylococcus

aureus

30. For children with CF, ages 2 through 5 y, and

with Staphylococcus aureus persistently

present in cultures of the airways, the CF

Foundation concludes that the evidence is

insuffi cient to recommend for or against

the chronic use of oral antistaphylococcal

antibiotics to improve lung function or quality

of life or reduce exacerbations.



of Lung Health (2013) Grade: I,

Certainty: Low

Therapeutics: Ivacaftor 31. For children with CF, ages 2 through 5 y, the

Preschool Guidelines Committee recommends

the routine use of ivacaftor in those with

specifi c gating mutations* and a consideration

for those with a confi rmed diagnosis of CF and

a R117H mutation.

Consensus Recommendation Chronic Medications (2013) Grade: A,

Certainty: Substantial, Benefi t: High

*The mutations are G551D, G1244E, G1349D, G178R,

G551S, S1251N, S1255P, S549N, and S549R.

Nutrition, Behavior, and

Gastrointestinal: Nutrition


Foundation recommends that weight-for-age be

maintained at ≥10th percentile.

Grade: A; Certainty: High; Benefi t:

Substantial




CF Foundation recommends weight-for-stature

assessments use the BMI% method on the

Centers for Disease Control and Prevention

growth charts and a BMI ≥50th percentile be

maintained.

Grade: B; Certainty: High; Benefi t:

Moderate

Evidence-Based Practice

Recommendations for Nutrition-

Related Management of Children

and Adults with Cystic Fibrosis and

Pancreatic Insuffi ciency: Results of

a Systematic Review (2008) Registry

Data-based Recommendation



34. For children with CF, ages 2 through 5 y, who

are meeting optimal nutritional thresholds, the

CF Foundation recommends ≥90–110 kcal/kg

per day and protein intake based on dietary

reference intakes and dietary guidelines

recommendations: ≥13 g protein/d 2–3 y old,

≥19 g protein/d 4–5 y old.


Substantial


Gastrointestinal: Nutritional

Risk


the CF Foundation recommends evaluation

and more intensive management of children

demonstrating any of these criteria of

nutritional risk:

Grade: B; Certainty: High; Benefi t:

Moderate

• BMI <50th percentile, or rate of weight gain

<50th percentile expected for age (≥6

g/d), or weight-for-age <10th percentile, or

inappropriate weight loss



Risk


and at nutritional risk, the CF Foundation

recommends patients be seen in 8 wk or

sooner. These visits should include medical,

behavioral, and nutritional assessment;

education; and intervention. Nutritional

intervention should aim at achieving the

patient’s target goal for both weight-for-age

and BMI.

Consensus Recommendation Consensus Report on Nutrition for

Pediatric Patients with Cystic

Fibrosis (2002) Defi nition of

Nutritional Failure and Patients at

Risk



Risk



recommends energy intake 10% to 20% above

baseline with continued incremental upward

adjustments of 10% to 20% as needed up to

200% to achieve weight gain.

Grade: B; Certainty: Moderate;

Benefi t: Moderate





Pancreatic Insuffi ciency: Results of a

Systematic Review (2008) Grade: B

TABLE 1 Continued






Risk



recommends the use of oral nutrition

supplements, in addition to usual dietary

intake, to improve rate of weight gain.


Benefi t: Moderate









Risk


at nutritional risk who do not respond to

previously described nutritional interventions,

see Figure 2, the CF Foundation recommends

an expanded evaluation to consider

other causes of poor growth, including

gastrointestinal, endocrine, behavioral, and

social causes. Subspecialty consultation may

be considered.




Risk


at nutritional risk who do not respond to

standard nutritional intervention and who

have not responded to the evaluation and

management plan of the multidisciplinary

team, the CF Foundation recommends the

use of enteral nutritional supplements via a

feeding tube to improve the rate of weight

gain. The concept of enteral feedings should be

introduced early as a component of CF care.


Benefi t: Moderate


Gastrointestinal: Vitamins


CF Foundation recommends standard, age-

appropriate non–fat-soluble vitamins and the

recommended levels of vitamins A, D, E, and

K by using a fat-soluble vitamin supplement

formulated for children with CF and if indicated

based on levels, additional supplementation of

vitamins A, D, E, and K.









CF Foundation recommends that blood levels

of fat-soluble vitamins be measured annually.

If values are abnormal, more frequent

measurements after dose adjustment are

recommended.








CF Foundation recommends that management

of vitamin D defi ciency follow the treatment

outlined in the CF Foundation Vitamin D

guidelines: An Update on the Screening,

Diagnosis, Management, and Treatment of

Vitamin D Defi ciency in Individuals with Cystic

Fibrosis: Evidence-Based Recommendations

from the Cystic Fibrosis Foundation, 2012.



Gastrointestinal: Salt


CF Foundation recommends adding additional

salt to meals and snacks, especially during

the summer months and for those who live in

warm climates.







Gastrointestinal: PERT

45. For children with CF and PI, ages 2 through 5

y, the CF Foundation recommends that PERT be

adjusted up to a dose of no greater than 2500

lipase units per kg per meal with a maximum

daily dose of 10 000 lipase units/kg.

Consensus Recommendation Evidence-Based Practice





Systematic Review (2008) Consensus

Recommendation

TABLE 1 Continued


LAHIRI et al

that there is insufficient evidence to

recommend for or against routine use

of pulse oximetry as an adjunctive

tool to detect lung disease. Table 1:

Recommendation 7.

Spirometry

Spirometry is the most important

and widely used tool to assess lung

function in CF. Several studies have

demonstrated that spirometry

is feasible in preschoolers with

CF, and has the potential to

detect pulmonary exacerbations

and airway obstruction despite

minimal symptoms.6, 21, 22 In a

cross-sectional, multicenter

study, FEV in 0.5 second and flow-

related volumes were found to

be more sensitive than FEV1 for

identifying abnormal lung function

in asymptomatic, preschool-

aged children.23 Another study

demonstrated improvement of

spirometric indices in both

school-aged children and 10

preschoolers who were treated

for pulmonary exacerbations.24

Because there is no risk to

performing spirometry in

preschool-aged children, and

they benefit from practicing

with technicians, the committee

concluded that spirometry should

be attempted as early as 3 years

of age, depending on the child’s

8



Gastrointestinal: Behavior


CF Foundation recommends that the CF team

members, working in concert with the family,

set energy-intake goals and assess progress

on a regular basis.


Benefi t: Substantia




CF Foundation recommends that all families

are regularly assessed for the presence

of mealtime behavior challenges and are

provided with proactive behavioral assistance

when needed.


Substantial




are at nutritional risk, or exhibiting challenging

mealtime behaviors, or not meeting energy-

intake goals, behavioral therapy provided

by knowledgeable team members should

accompany nutritional therapy.


Substantial








Gastrointestinal:

Gastrointestinal

49. The CF Foundation recommends that

all providers be aware of the presenting

symptoms of the following gastrointestinal

tract disorders: constipation,

gastroesophageal refl ux disease, small bowel

overgrowth, distal intestinal obstruction

syndrome, and celiac disease.



Gastrointestinal:

Gastrointestinal


CF Foundation recommends that children

and their parents be questioned regarding

abdominal pain at each visit, and that pain is

investigated if persistent or recurrent.



Gastrointestinal:

Gastrointestinal

51. For children with CF, ages 2 through 5 y, and

who are PS, the CF Foundation recommends

that children are reevaluated annually for

the conversion to PI with fecal elastase

measurement, particularly if genetic testing

reveals 2 mutations potentially associated

with PI.

Consensus Recommendation Consensus Report on Nutrition for

pediatric Patients with Cystic

Fibrosis (2002) Issues Related to

Pancreatic Insuffi ciency: Identifying

Pancreatic Insuffi ciency


Gastrointestinal:

Gastrointestinal


and who are PS with severe abdominal pain,

particularly if associated with vomiting, the

CF Foundation recommends measurement of

lipase and amylase to determine if pancreatitis

is present.



Gastrointestinal:

Gastrointestinal


had terminal ileal bowel resection, the CF

Foundation recommends annual measurement

of serum vitamin B12 concentration.


AAP, American Academy of Pediatrics;

TABLE 1 Continued


PEDIATRICS Volume 137 , number 4 , April 2016

developmental level. Table 1:


Bronchodilator Responsiveness

Three articles demonstrated

bronchodilator responsiveness

in <20% of children with CF.

Bronchodilator responsiveness

may be associated with certain

polymorphisms.25–27 Although there

is insufficient evidence to recommend

for or against routine monitoring

of bronchodilator responsiveness,

evaluation may be considered if there

are concerns or symptoms suggestive

of airway hyperreactivity. Table 1:

Recommendation 10.

Multiple-Breath Washout

Multiple-breath washout (MBW)

testing measures regional ventilation

heterogeneity and appears to be

more sensitive than spirometry

in detecting pulmonary function

abnormalities in young children

with CF. Two prospective studies

9

TABLE 2 Routine Monitoring and Care

Age at Visit 2 y 3 y 4 y 5 y

Intervention

Visit Done 1 2 3 4 1 2 3 4 1 2 3 4 1 2 3 4

Care issues

Continue high-salt diet, supplement

additional salt in hot weather.

X X X X

History and physical with weight and

height

X X X X X X X X X X X X X X X X

Teach and assess airway clearance,

review airway clearance techniques

X C C C X C C C X C C C X C C C

Assess weight gain, caloric intake, and

PERT dosing


Continue vitamins designed for patients

with CF


Introduce chronic dornase alfa and/

or HS

C C C C

Seasonal infl uenza vaccination X X X X

Pneumococcal polysaccharide

vaccination

X

Diagnostic testing

Sweat test and genotyping confi rmed

documentation

X C C C

Pancreatic functional status testing C C C C

Respiratory culture X X X X X X X X X X X X X X X X

Chest radiograph or CT X C X C

Vitamin levels A, D, E, prothrombin time X X X X

Serum electrolytes, SUN, creatinine,

glucose

X X X X

Complete blood count X X X X

AST/ALT/GGT/bilirubin, albumin, ALP X X X X

Spirometry A A A A A A A A X X X X

Abdominal pain questioning X X X X X X X X X X X X X X X X

Education

Teach and assess infection control X C C C X C C C X C C C X C C C

Document CF Foundation patient

registry consent

X X X X

Discuss clinical research C C C C

Referrals to community resources C C C C

Tobacco smoke exposure avoidance

education

X X X X

Patient and caregiver engagement

assessment

X C C C

Set energy goals and assess progress X C C C X C C C X C C C X C C C

Assess for presence of mealtime

behavior challenges and provide

proactive behavioral assistance

X C C C X C C C X C C C X C C C

Annual health supervision visits with

PCP

X X X X

ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyltransferase; SUN, serum urea nitrogen.

A single letter under one of the 4 yearly headings indicates the task should be performed, considered or attempted once a year. Further letters appear under quarterly visits when the

task should be performed, considered, or attempted at >1 visit per year: A, attempt this task; C, consider this task; X, perform this task.


LAHIRI et al

that included preschool-aged

children reported that MBW indices,

specifically lung clearance index

(LCI), was more sensitive than

spirometry in detecting abnormal

lung function5, 28 and was generally

abnormal in preschoolers with CF

compared with healthy controls.20

The utility of MBW in the clinical

setting and what constitutes a

clinically significant change in the

LCI has not yet been determined.

The committee concluded that there

is currently insufficient evidence

to recommend for or against the

routine use of MBW in CF. Table 1:

Recommendation 11.

Chest Radiographs

Chest imaging can be performed at

all ages and can identify structural

changes that may be regional,

early, and presymptomatic. Chest

radiographs are relatively insensitive

and nonspecific compared with CT

scans, but require less radiation

exposure, expense, and patient

cooperation. Chest radiographs have

been shown to detect the existence

and progression of CF lung disease

in infants, 29 and preschool-aged30

and school-aged children.31 Chest

radiographs demonstrate a higher

correlation than FEV1/forced

vital capacity with Pseudomonas

acquisition in young children with

CF.32 Chest radiograph scores

are superior to FEV1 in detecting

concurrent abnormalities on chest

CT scans, 33 and in predicting future

FEV1 and chest radiograph scores.34

To monitor disease progression,

chest radiographs should be obtained

at a minimum of every other year

following a baseline radiograph at

diagnosis. Use of a scoring system, such

as Brasfield, 35 Chrispin-Norman, 36

or Wisconsin37 scores, should be

considered to monitor changes over

time. Chest radiographs also should

be considered in preschoolers with

CF with a change in respiratory

status that does not respond to

appropriate interventions. Table 1:

Recommendation 12.

Chest CT

Chest CT is a sensitive tool for

monitoring early CF lung disease, as

it detects early airway wall thickening,

bronchiectasis, and gas trapping in

infants and preschoolers, 4, 38, 39

without symptoms or abnormal

pulmonary function.40, 41

Bronchiectasis in this age group

often persists or progresses.42

The rate of structural lung disease

progression on CT in preschoolers

with CF is not well defined; however,

CT scans have revealed progressive

bronchiectasis in older children

over a 2-year period, despite stable

pulmonary function testing.40 In

children <4 years of age experiencing

a pulmonary exacerbation, CT

detected regional differences in

airway inflammation and scores

improved after treatment.43 Although

the carcinogenic risk of radiation

exposure is small and continues

to decrease with technological

innovations, 44 concerns remain

regarding the risk of radiation

exposure and expense. Controversy

also persists regarding the

significance of early changes seen on

CT45 and the preferred methodology

and reproducibility of scoring

systems, especially in early or mild

disease.46 There are currently no

valid surrogates to replace CT. In a

cohort of patients 5 to 19 years of

age, a normal LCI almost excluded

CT abnormalities41; in a younger

cohort (mean age 7.8 years), LCI

and high-resolution CT had similar

sensitivity to detecting CF lung

disease but provided complementary

information.47 If routine monitoring

is performed, it should replace chest

radiographs, be performed every 2 to

3 years, and use the lowest radiation

dose possible needed to obtain

diagnostic-quality images. If used,

consideration should be given to

using a scoring system to standardize

interpretation of repeated scans over

time. Table 1: Recommendation 13.

Microbiology

Quarterly respiratory cultures are

the standard of care for patients

with CF.48 For infants1 and other

nonexpectorating patients, an

oropharyngeal (OP) swab is the usual

respiratory sample, despite limited

diagnostic accuracy compared with

bronchoalveolar lavage (BAL).49

BAL is the only means by which to

directly sample the lower respiratory

tract and provides measures of

lower airway inflammation that

may have important prognostic

value, 4 but is invasive and costly. A

randomized controlled trial in infants

and preschoolers with CF50, 51 found

no difference in outcome at age 5

years when therapy was directed

by OP culture as opposed to BAL.

Induced sputum may have greater

yield than OP culture, 52–54 but it is

time-consuming and impractical in

standard clinic settings. Respiratory

microbiology monitoring by OP

cultures should be performed at

least quarterly and routine airway

monitoring by bronchoscopy is

not recommended. However,

bronchoscopy with BAL should be

considered in patients with a change

in respiratory status that does not

respond to antibiotics directed

toward pathogens isolated from OP

swabs. Table 1: Recommendations

14–15.

PULMONARY THERAPEUTICS

Pulmonary Exacerbations

Based on our current understanding

of early disease progression,

the association of pulmonary

exacerbations with worse outcomes,

and evidence of improvement

with antibiotic treatment, 43,

55–66 the recommendation for

preschoolers with CF experiencing

an exacerbation is oral, inhaled,

and/or intravenous antibiotic

treatment. Defining a pulmonary



exacerbation is beyond the scope of

this article; however, Fig 1 outlines

the recommended approach to

preschool-aged children with

increased respiratory symptoms.

There are no randomized clinical

trials of pulmonary exacerbation

treatment in preschool-aged children

with CF; thus, these guidelines

for management were based on

consensus recommendations, and

management decisions should be

individualized. Oral antibiotics

targeting bacteria detected on

airway cultures are recommended

for mild to moderate pulmonary

exacerbations, whereas intravenous

antibiotics are recommended for

moderate to severe pulmonary

exacerbations or mild exacerbations

unresponsive to oral antibiotics.

Inhaled antibiotics are recommended

based on standard guidelines for

treatment of new and chronic

Pseudomonas aeruginosa infection.2, 67

Table 1: Recommendation 16.

Airway Clearance Therapy

Airway clearance therapy (ACT)

is an important maintenance

treatment and is recommended for

all individuals with CF.1, 68 With early

airway disease noted in the youngest

population, ACT has the potential to

prevent development of irreversible

disease. Continuing ACT through

preschool years will encourage

maintenance throughout childhood.

An active lifestyle consisting of

vigorous physical activity and

exercise, important components

of maintaining lung health, should

be encouraged and initiated in this

age group. In preschoolers with

CF, daily ACT is recommended

and increased frequency and/or

duration is recommended during

pulmonary exacerbations. Table 1:


Bronchodilators

No studies were found that

address bronchodilator efficacy

in the absence of asthma or

bronchial hyperresponsiveness

in CF; therefore, the evidence is

insufficient to recommend for or

against the chronic use of inhaled

bronchodilators in preschoolers.

However, viral-triggered wheezing or

asthma in preschoolers may respond

to bronchodilator therapy. Table 1:

Recommendation 19.

Hypertonic Saline

Several studies have demonstrated

safety and tolerability of 7%

hypertonic saline (HS) in infants

and young children.69–71 Unlike a

study in older individuals with CF, 72

a randomized controlled trial of

344 children <5 years failed to

show a reduction in the primary

endpoint of pulmonary exacerbation

rate.73 However, in 2 small studies

that were part of this larger trial,

infant lung function and the LCI

did demonstrate improvement in

subjects receiving 7% HS.73, 74 Given

these findings, the CF Foundation

recommends that HS be offered

to patients based on individual

circumstances, either for chronic

use or during acute pulmonary

exacerbation. Further studies may

alter this recommendation. Table 1:

Recommendation 20.

Dornase Alfa

Routine use of dornase alfa is

associated with reduced pulmonary

exacerbations, improved lung

function, and decreased rate of

lung function decline among older

children and adults with CF.75–81

Dornase alfa has been shown to have

positive effects on CT changes and

LCI82–84 and improved health-related

quality-of-life scores in children >6

years.85 Safety and tolerability of

dornase alfa has been demonstrated

in children ages 3 months to 5

years.86, 87 Potential benefits include

its effect on mucous plugging, air

trapping, and lung health in CF that

may result in delayed pulmonary

disease progression. Based on

moderate evidence that dornase

alfa is safe and effective, and the

potential benefit is at least small,

the CF Foundation recommends

that dornase alfa be offered to

patients based on individual

circumstances, either for chronic

use or during acute pulmonary

exacerbation. Further studies may

alter this recommendation. Table 1:

Recommendation 21.

Systemic and Inhaled Corticosteroids

With the exception of treatment

of allergic bronchopulmonary

aspergillosis, systemic

corticosteroids are not recommended

for routine use in children with CF,

as potential harm outweighs any

benefit. Inhaled corticosteroids are

not recommended for management

of CF lung disease, as no clear

benefit has been identified.2 Table 1:

Recommendation 22–23.

Ibuprofen

High-dose ibuprofen is recommended

for chronic use in individuals with

CF older than 6 years with mild lung

disease.2 We found no prospective

trials that support its use in children

younger than 6 years and conclude

there is insufficient evidence to

recommend for or against its use

in preschoolers with CF. Table 1:

Recommendation 24.

Leukotriene Modifi ers

In the absence of comorbid

conditions, such as asthma

or recurrent wheezing, there

is insufficient evidence to

recommend for or against the

chronic use leukotriene modifiers

for preschoolers with CF. Table 1:

Recommendation 25.

Azithromycin

Routine use of azithromycin is

recommended for individuals with CF

>6 years with persistent P aeruginosa

infection.2 Azithromycin is safe,

reduces lower airway inflammation

and exacerbations, and improves


LAHIRI et al

lung function and weight gain in

older children with mild CF lung

disease.88, 89 There are conflicting

data regarding the potential for

higher nontuberculous mycobacterial

infection rates in individuals with

CF on chronic azithromycin.60, 90–92

There is insufficient evidence to

recommend for or against the chronic

use of azithromycin in preschoolers

with CF. Table 1: Recommendation

26.

Chronic P aeruginosa Infection

The use of cycled inhaled tobramycin

for the management of infants,

children, and adults with persistent

P aeruginosa infection has been

12

FIGURE 1Approach to preschool-aged children with increased respiratory symptoms.



previously recommended.1, 2

Additional inhaled antibiotics, such as

aztreonam, also have been effective

and safe in improving lung function

and reducing exacerbations outside

of the infant and preschool age

range.93–96 Microbiologic efficacy and

safety of inhaled tobramycin has been

demonstrated in infants and young

children.97–100 The use of alternate-

month inhaled antipseudomonal

antibiotics for preschoolers with

persistent P aeruginosa infection

is recommended. Table 1:

Recommendation 27.

Staphylococcus aureus Prophylaxis and Eradication

In keeping with previous guide-

lines, 4, 42, 43, 101 the prophylactic use

of oral antistaphylococcal antibiotics

is not recommended given the

risk of increased P aeruginosa

isolation.2, 102–106 Several studies have

addressed the utility of eradication

attempts after first acquisition of

S aureus, particularly methicillin-

resistant isolates, but none have been

randomized or focused on young

children with CF.107–110 Prophylactic

use of oral antistaphylococcal

antibiotics is not recommended;

evidence is insufficient to

recommend for or against attempts

to eradicate S aureus and for chronic

use of oral antistaphylococcal

antibiotics in preschoolers with CF

who persistently culture S aureus.

Table 1: Recommendations 28–30.

Ivacaftor

Ivacaftor has been shown to improve

lung function, sweat chloride

values, weight gain, and quality

of life in people 6 years and older

with at least 1 copy of the G551D

mutation.2, 111–113 This therapy has

recently been approved for use

in patients with additional cystic

fibrosis transmembrane conductance

regulator (CFTR) gating mutations:

G1244E, G1349D, G178R, G551S,

S1251N, S1255P, S549N, S549R,

and R117H. A forthcoming study

in preschoolers has demonstrated

safety of ivacaftor in the preschool-

aged child.114, 115 The availability

of oral granules now allows for

appropriate dose adjustment in

young children. Monitoring of liver

function abnormalities will be

important. Based on data in older

subjects, forthcoming safety data, and

recent Food and Drug Administration

approval for this age group, the use

of ivacaftor for preschoolers with

specific gating mutations and R117H

is a consensus recommendation

of this committee. Table 1:

Recommendation 31.

CLINICAL AND BEHAVIORAL NUTRITION AND GASTROINTESTINAL CARE

Nutrition

Normal ranges of weight-for-age,

height-for-age, and BMI percentile

are associated with better pulmonary

function, height closer to the 50th

percentile for age and gender,

and survival.3 A recent study

demonstrated that weight-for-age

≥10th percentile for age and gender

at age 4 years was associated with

superior survival at 18 years.11

Therefore, it is recommended that

weight-for-age of preschoolers with

CF be maintained at ≥10th percentile.


Measurement of height and weight,

with calculation of BMI percentile

using Centers for Disease Control and

Prevention growth charts, should

be performed to assess weight-for-

stature.116, 117 Weight-for-height and

BMI must be evaluated in the context

of the child’s height. Stunting is a risk

in CF and can obscure nutritional

risk in a child. Preschoolers

with CF should maintain a BMI

≥50th percentile. Recommended

monitoring of growth and nutrition

in this age group is found in Table 3.

Table 1: Recommendations 33.

Energy and protein requirements

should be assessed in preschoolers

with CF.118, 119 Energy and protein

recommendations of ≥90 to 110

kcal/kg per day, and protein intake

based on dietary reference intakes120

and dietary guidelines recommend

≥13 g protein per day for children

aged 2 to 3 years and ≥19 g protein

per day for children aged 4 to 5

years to meet optimal nutritional

thresholds. Table 4 outlines general

energy guidelines by age and gender

for preschoolers with CF. Table 1:

Recommendation 34.

Nutritional Risk

Nutritional risk is defined as a BMI

<50th percentile, or rate of weight

gain <50th percentile expected for

age (≥6 g per day), or weight-for-age

<10th percentile, or inappropriate

weight loss. Families of preschoolers

with CF at nutritional risk and CF

13

TABLE 3 Routine Monitoring and Nutritional Care of Preschoolers with CF

Every visit

Measure and evaluate weight and height by using standard guidelines (American Academy of

Pediatrics).

Assess rate of weight gain in g/d since the last encounter.

Assess PERT dose for lipase units/kg per meal and lipase units/kg per day.

Assess for any issues that impede PERT administration as prescribed.

Encourage a well-balanced diet, with emphasis on calorically dense food sources.

Inquire if any eating behaviors need to be addressed.

Inquire if any changes in routine are expected to occur (preschool, daycare, baby sitter) for

anticipatory guidance.

Yearly

Serum levels of fat-soluble vitamins.

As appropriate

Referrals to community food resources (Supplemental Nutrition Program for Women, Infants,

and Children; food stamps; food pantries).

Information on nutrition resources via enzyme assistance programs.


LAHIRI et al

health care professionals should

establish a multifaceted care plan

that addresses medical, behavioral,

and nutritional issues and schedule

more frequent follow-up to ensure

rapid establishment of normal

growth. Interventions to improve

nutritional status can be guided

by the algorithm in Figs 2A, 2B,

2C, and 2D. Collaboration with a

PCP or a visiting nurse to obtain

weight and height measurement is

an option for preschoolers needing

more frequent evaluation. Table 1:


Increased energy intake results in

improved weight gain3; however,

fewer data support improved height

with increased energy intake.121, 122

There is conflicting evidence

regarding the use of nutritional

supplements to increase energy

intake.122, 123 Oral supplements may

be beneficial to preschoolers with

CF at nutritional risk. Supplements

may increase protein and energy at

a time when eating behaviors may

interfere with daily food intake.

The use of supplements should be

integrated with other nutritional

and behavioral approaches for this

age group. Families and CF health

care professionals should be aware

of the substantial impact of behavior

on optimal nutrition.124–127 Children

who continue to be at nutritional

risk despite having addressed

pulmonary, social, and dietary factors

should be referred to pediatric

gastroenterologists, endocrinologists,

and behavioral specialists for

further evaluation and management.

Gastrostomy tube feedings have

been shown in older children and

adults with CF to improve weight and

pulmonary function.128–131 Table 1:


Vitamins

CF-specific multivitamins are

recommended, in a form that

the child will best accept, and at

recommended doses based on

manufacturer guidelines.1 Patients

with low serum levels of a specific

fat-soluble vitamin(s) should

continue to receive CF-specific

multivitamins in addition to

supplementation of the specific fat-

soluble vitamin associated with low

serum levels. Serum levels should

be remeasured to ensure adequate

response to therapy. Frequency

of remeasurement should depend

on the level of deficiency, the

dose used for treatment, and the

risk associated with deficiency or

toxicity of the vitamin. Specific CF

guidelines for vitamin D management

are published132; there has been

limited evaluation of the efficacy

of these guidelines.133 Table 1:


Salt

Preschoolers with CF are advised to

continue a high-salt diet, especially

in the summer, and for those who

live in warmer climates. For those

who may not select foods with a

high salt content, supplementation

with at least one-quarter teaspoon

of salt per day (581 mg sodium) may

be necessary. Caregivers should be

advised to avoid overuse of salt.134


Pancreatic Enzyme Replacement Therapy

For preschoolers with CF who

are pancreatic insufficient (PI),

consistent administration of the

appropriate doses of pancreatic

enzyme replacement therapy (PERT)

is essential. Recommendations for

PERT follow previous guidelines to

ensure adequate digestion and avoid

risk of fibrosing colonopathy.135

Evaluation of PERT dose and

adherence should occur at each visit

(Supplemental Table 4). Table 1:

Recommendation 45.

Behavior

To meet growth goals, families of

preschoolers with CF and health care

professionals should establish individ-

ualized energy-intake goals and

routinely monitor progress.10, 136–139


In multiple studies, families

consistently reported challenges with

mealtime energy-intake goals due to

demanding mealtime behaviors,

leading to significant stress.8, 9, 124–127

These mealtime behavioral

challenges can predict calorie

intake and weight gain.140 Regular

assessment for mealtime behavior

challenges should be performed

and proactive behavioral assistance

should be provided when needed

Table 5.10, 136, 137, 141–143 Table 1:

Recommendation 47.

CF health care professionals with

appropriate training should provide

behavioral therapy for preschoolers

with CF at nutritional risk, exhibiting

challenging mealtime behaviors, or

not meeting energy-intake goals.

Behavioral and nutrition treatment

can lead to improvements in

attaining energy-intake

goals.10, 136–140, 143, 144 Table 1:

Recommendation 48.

Gastrointestinal

Conditions associated with abdominal

pain may contribute to malabsorption,

14

TABLE 4 General Calorie Guidelines for Age and Gender: The Recommendations Are a Consolidation

of 3 References118–120

Age, y Boys Girls

2–3 1290–1430 kcal/d 1200–1250 kcal/d

100–105 kcal/kg/d 95–100 kcal/kg/d

3–4 1430–1520 kcal/d 1285–1290 kcal/d


4–5 1520–1655 kcal/d 1285–1505 kcal/d


5–6 1655–1780 kcal/d 1505–1605 kcal/d




FIGURE 2ANutrition algorithm: Tier One Initial Evalutaion.


LAHIRI et al

impaired quality of life, reluctance to

perform airway clearance therapies,

and loss of appetite in children with

CF. In a large retrospective study of

children with CF, abdominal pain

frequency in children <6 years

of age was no different from the

general population.145 Abdominal

pain should not be attributed to

pancreatic enzyme dosing.145 If

pain persists after assessment for

common causes of abdominal pain in

CF, or “red flag” symptoms, listed in

Supplemental Table 5, are present,

refer to pediatric gastroenterology.

16

FIGURE 2BNutrition algorithm: Tier Two Consultation and In-depth Diagnostic Evaluation. (continued)



Studies of preschoolers with CF have

shown that constipation, 146 distal

intestinal obstruction syndrome, 147

gastroesophageal reflux disease, 148

small bowel overgrowth, 149 and

celiac disease150 can occur. Providing

parents with a questionnaire directed

at gastrointestinal symptoms can

assist in detecting disease.151, 152 CF

health care professionals unfamiliar

with the diagnosis and management

of these conditions should refer the

child to a pediatric gastroenterologist.

Table 1: Recommendations 49–50.

Children with CF who are

pancreatic sufficient (PS) do

not necessarily have normal

17

FIGURE 2CNutrition algorithm: Tier Three Consideration of G-Tube. (continued)


LAHIRI et al 18

FIGURE 2DNutrition algorithm: BMI and Weight for Age.



pancreatic function.153 Over time,

they may develop PI. Diarrhea is

an unreliable indicator of PI. Poor

weight gain or growth may be a late

indicator of PI, and micronutrient

deficiency may be present. Fecal

elastase, 72-hour stool for fecal

fat, and cholecystokinin/secretin-

stimulated pancreatic function

testing may be used to diagnose PI.

Fecal elastase is the simplest, most

available screening test. Table 1:

Recommendation 51.

Children with PS and CFTR mutations

associated with milder disease are at

risk for acute pancreatitis, which may

lead to episodes of acute, recurrent,

or chronic pancreatitis.154 Specific

CFTR mutations cannot reliably

predict which children will get

pancreatitis.155 Acute pancreatitis is

a potentially life-threatening disease

associated with severe pain, nausea,

and vomiting. Although infrequent

in preschoolers, providers should be

aware that pancreatitis can occur in

preschoolers who are PS. Table 1:

Recommendation 52.

Vitamin B12 is absorbed exclusively

in the terminal ileum. Individuals

with resection of the terminal ileum

will become vitamin B12 deficient,

which may take 1 to 3 years to

develop.156, 157 These individuals

should be screened by using serum

B12 levels or urinary methylmalonic

acid. Providers should not wait for

the development of hematologic

signs to screen for deficiency. Table

1: Recommendation 53.

UNANSWERED QUESTIONS

With few clinical trials evaluating

monitoring, therapeutics, and

nutritional care, determining

care pathways for preschoolers

with CF is challenging. Additional

research on monitoring for lung

disease in preschoolers to advance

early detection and potentially

improve outcomes is needed. MRI

and other imaging modalities that

avoid radiation exposure may

hold promise for evaluation of

early CF lung disease. MBW, after

further validation, may become

incorporated into clinical care.

Therapeutic trials evaluating efficacy

of chronic respiratory medications,

including dornase alfa and HS, are

important; increasing treatment

complexity with additional therapies

must be weighed against the

potential of preventing irreversible

damage. CFTR modulators

are a potentially life-changing

therapeutic strategy for CF. The

recent approval of ivacaftor for

preschoolers will hopefully allow

for early disease prevention. As

modulators and correctors are

developed for other mutations,

it is important to recognize the

substantial benefits for the youngest

patients. Gaps in nutritional,

behavioral, and gastrointestinal

studies in this age group remain.

Additional research on timing of

nutritional interventions and of the

conversion from PS to PI is needed.

Determining the prevalence of key

gastrointestinal disorders is needed

to assist providers with testing and

diagnostic decisions.

CONCLUSIONS

The care of the preschool-aged child

with CF includes complex, time-

consuming treatment regimens

and overcoming behavioral

challenges common in this age

group to maintain lung health and

optimize growth. We hope that these

guidelines will help CF care teams

and families make informed decisions

regarding care of the 2- to 5-year-old

children with CF.

ACKNOWLEDGMENTS

The authors acknowledge Elaine

Skopelja, Indiana University, for

her assistance with the literature

review.

19

ABBREVIATIONS

ACT: airway clearance therapy

BAL: bronchoalveolar lavage

CF: cystic fibrosis

CFTR: cystic fibrosis

transmembrane

conductance regulator

CT: computed tomography

FEV1: forced expiratory volume

in 1 second

HS: hypertonic saline

LCI: lung clearance index

MBW: multiple-breath washout

OP: oropharyngeal

PCP: primary care provider

PERT: pancreatic enzyme

replacement therapy

PI: pancreatic insufficiency

PICO: population, intervention,

comparison, outcome

PS: pancreatic sufficiency

TABLE 5 Behavioral Assessment and Management of Mealtimes

Assessment of behavior at mealtimes

It is important to assess for a regular schedule of meal and snack times, for mealtime duration, and

for child behaviors and family stress related to diffi culties in meeting energy-intake goals and a

balanced variety of foods.

Setting energy-intake goals

For families of preschoolers to succeed with meeting growth goals, it is important that energy-intake

goals individualized to the child are set and then monitored in terms of progress.

Inclusion of behavioral expertise when evaluating concerns about growth

Whenever concerns with growth and/or family stress related to mealtimes (and with meeting energy-

intake goals) are present, it is critical to consider a multidisciplinary approach to understanding

the problem, developing a treatment plan, and assessing the success (or need to further modify)

the plan. Inclusion of expertise in child behavior management and knowledge of the evidence-based

behavioral and nutrition treatment is strongly recommended whenever possible.

Recommending behavioral and nutrition treatment to improve energy intake and growth

A treatment plan focused on increasing energy intake and improving growth in preschoolers with

CF will likely be more successful with inclusion of evidence-based interventions that are part of

behavioral and nutrition treatment.


LAHIRI et al

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20

review and assisted with manuscript preparation and revision; Drs Brady, Schwarzenberg, and Rosenfeld reviewed selected articles, and each compiled and

edited contributions for major sections of the manuscript and drafted sections of the manuscript; Drs Cannon, Condren, Guill, Guillerman, Powers, Tompkins, and

Zemanick and Ms Clark, Ms Leone, Ms Maguiness, and Ms Monchil reviewed selected articles and contributed written sections to the manuscript; and all authors

reviewed and approved the fi nal manuscript as submitted

DOI: 10.1542/peds.2015-1784

Accepted for publication Dec 29, 2015

Address correspondence to Thomas Lahiri, MD, Director, Pediatric Pulmonology, University of Vermont Children’s Hospital, Smith 571, 111 Colchester Ave,

Burlington, VT 05401. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2016 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they have no fi nancial relationships relevant to this article to disclose.

FUNDING: Funding was provided by the Cystic Fibrosis Foundation.

POTENTIAL CONFLICT OF INTEREST: Dr Cannon's institution has received funding from Vertex Pharmaceuticals, Gilead Sciences, Insmed, and Novartis

Pharmaceuticals for running the studies supported by Cystic Fibrosis Therapeutics funds. Dr Cannon is an inventor on a patent for an antimicrobial licensed to

Akron Research Commercialization Corporation, DBA Nebusil. Dr Guillerman has consulted for PTC Therapeutics, Inc, received funding from the Cystic Fibrosis

Foundation Therapeutics, Inc, and compensation from Vertex Pharmaceuticals. Dr Rosenfeld has received grant funding from Vertex Pharmaceuticals. Dr Davis

has served as a board member for Vertex Pharmaceuticals and served as an unpaid consultant for Eli Lilly. The other authors have indicated they have no

potential confl icts of interest to disclose.



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DOI: 10.1542/peds.2015-1784 originally published online March 23, 2016; 2016;137;Pediatrics

Schwarzenberg, Connie L. Tompkins, Edith T. Zemanick and Stephanie D. DavisKaren Maguiness, Lisa Monchil, Scott W. Powers, Margaret Rosenfeld, Sarah JaneMichelle E. Condren, Margaret F. Guill, R. Paul Guillerman, Christina G. Leone,

Thomas Lahiri, Sarah E. Hempstead, Cynthia Brady, Carolyn L. Cannon, Kelli Clark,Preschoolers With Cystic Fibrosis

Clinical Practice Guidelines From the Cystic Fibrosis Foundation for

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DOI: 10.1542/peds.2015-1784 originally published online March 23, 2016; 2016;137;Pediatrics

Schwarzenberg, Connie L. Tompkins, Edith T. Zemanick and Stephanie D. DavisKaren Maguiness, Lisa Monchil, Scott W. Powers, Margaret Rosenfeld, Sarah JaneMichelle E. Condren, Margaret F. Guill, R. Paul Guillerman, Christina G. Leone,

Thomas Lahiri, Sarah E. Hempstead, Cynthia Brady, Carolyn L. Cannon, Kelli Clark,Preschoolers With Cystic Fibrosis

Clinical Practice Guidelines From the Cystic Fibrosis Foundation for

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