cystic fibrosis

prevalence

cf is a common life-limiting autosomal recessive genetic disorder that affects ~100k people in the world

highest amounts in europe, NA, australia

what genetic mutation causes cf

mutation in the cf transmembrane conductance regulator (CFTR) gene located on chromosome 7

autosomal recessive genetic disorder

if both parents are carriers what is the probability that their child will have cf

25%

pathophys

cftr regulates chloride, sodium bicarb, + water transport across epithelial cells to maintain salt + water balance in out body

so mutation can lead to absent/insufficient/dysfunctional protein → impaired chloride transport

this causes thick secretions affecting our exocrine glands (sweat, mucus, tears, saliva, digestive juices)

cf clinical care guidelines

standard of care established by cf foundation

• models of care guidelines

• dx care guidelines

• age-specific guidelines

• respiratory care guidelines

• infxn prevention + control care guidelines

• nutrition + gi care guidelines

• cf-related condition guidelines

cf diagnosis

usually diagnosed by 2 yo

use sweat test (gold standard)

cf newborn screening program: immunoreactive trypsinogen (IRT) → mutation panel + full gene sequencing → referral to cf care center for follow up + sweat test

better outcomes w/ early dx!!

how many positive sweat tests are needed for diagnosis

2

sweat test result of ≤29 mmol/L

cf unlikely

sweat test result of 30-59 mmol/L

borderline

sweat test result of ≥60 mmol/L

diagnostic of cf

common CFTR variants

F508del, G542X, G551D, R117H

types of therapy for cf

gi/nutritional care, cf related dm tx, respiratory meds, airway clearance therapy, pulmonary exacerbation tx

gi/nutritional care therapy

pancreatic enzymes, ppis, h2ras, constipation txs, vitamins

cf related diabetes tx

insulin (basal + bolus)

respiratory meds

bronchodilators, mucolytics, inhaled abx, anti-inflammatory, CFTR modulators

airway clearance therapy

airway clearance techniques, high-frequency chest wall oscillator (vest)

pulmonary exacerbation treatment

increase airway clearance, IV/PO abx

gi clinical manifestations

pancreatic insufficiency caused by pancreatic duct obstruction + fibrosis → causes decrease in pancreatic enzymes → decreased absorption, steatorrhea, malnutrition

constipation

gerd

cf-related liver disease caused by bile duct obstruction + resulting liver damage

cf related diabetes

meconium ileus

pancreatic enzymes

exocrine pancreas → digestive enzymes (lipase, protease, amylase)

pancreatic enzyme replacement therapy (PERT) initiated in all newly diagnosed cf pts while waiting for FE-1 results and continued in pts who are pancreatic insufficient

pancreatic enzyme brands

creon, zenpep, pertyze, pancreaze (not interchangable!)

dosing for pancreatic enzymes

determined by weight or fat content of meal, adjusted based on clinical sx of poor wt gain and/or malabsorption

take w each meal or snack (can open)

max dose 10k lipase units/kg/d or 4k lipase units/gm of fat /d (high doses long term → fibrosing colonopathy)

can add h2ra for ppi to prevent acid denaturing enzyme!

pancreatic enzyme starting dose for infants <12 mon

3k lipase units/feed

pancreatic enzyme starting dose for children 1-4

1k lipase units/kg/meal

pancreatic enzyme starting dose for children/adolescents ≥4yo

500 lipase units/kg/meal

vitamins

cf pts cant absorb fat soluble vitamins (ADEK) → give cf specific products that have recommended doses for each

• MVW complete formulation liquid, chew tab

• choiceful chew tab, capsule

• H2-pharma liquid

  • DEKAs liquid

why are pulmonary fxn tests used in cf pts

to establish a clinical baseline (personal best) FEV1

“normal lung fxn is ≥90% predicted, drop of ≥10% predicted baseline means acute pulmonary exacerbation

mechanical airway clearance

guidelines rec airway clearance therapy (ACT) initiated in the first few months of life

usually administered 1-2x daily, 3-4x daily when sick

helps to promote mucus clearance through coughing or huffing

types of mechanical airway clearance

chest physical therapy (CPT)

high frequency chest wall oscillation (vest)

positive expiratory pressure

chest physical therapy (CPT)

rapidly applied to chest wall usually while supine, prone, sitting up, or in another position

rec for age <2yo

percussion → shaking → vibrating

high frequency chest wall oscillation (vest)

vibrates chest at a high frequency

rec for ≥2yo

positive expiratory pressure

increased resistance when breathing out

oscillations create vibrations

pharm respiratory treatments

inhaled bronchodilators → inhaled osmotic → inhaled mucolytic → inhaled antibiotics

in this order!!!

if pt also has asthma what can you give as the last step

inhaled corticosteroids

bronchodilators

relax muscle surrounding the airways → enlarges them, helping w airway clearance

• albuterol: racemic mixture of R-enantiomers and S-enantiomers

• levalbuterol: only has R-enantiomer → more selective for beta 2

prevents hypertonic saline induced bronchospasms

insufficient evidence to rec for or against chronic use!

can admin using a metered dose inhaler or nebulizer ± spacer

albuterol (proair HFA, ventolin HFA) dosing

neb: 3 ml inhaled bid

MDI: 2 puffs inhaled q4h prn

albuterol SEs

tachycardia, tremor, nervousness

what to monitor for bronchodilators

heart rate

albuterol storage

room temp, away from heat

levalbuterol (xopenex) dosing

neb: 0.31-1.25mg qid

mdi: 2 puffs qid + every q4-6h prn

levalbuterol SEs

tachycardia (less than albuterol), tremor, nervousness

levalbuterol storage

room temp, protect from light

inhaled osmotics

hypertonic saline, mannitol

hypertonic saline

restores airway hydration, induces expectoration of sputum, + enhances mucociliary fxn

comes in 3 or 7%

hypertonic saline dosing

4 ml/dose through oral nebulized inhalation bid

hypertonic saline SEs

cough, bronchospasm/chest tightness, pharyngitis, hemoptysis, sinusitis, sneezing

when would you change from 7% to 3% hypertonic saline

if pts develop intolerable adverse effects (sore throat, chest tightness, oropharyngeal irritation)

storage for inhaled osmotics

room temp!

mannitol dosing

≥18: 400mg (10 capsules) inhaled bid

mannitol SEs

bronchospasm, cough, hemoptysis, arthralgia, increased bronchial secretions, fever

mannitol administration

admin bronchitol 2-3 hr before bedtime

admin short acting bronchodilator 5-15 mins before every dose

what test is required for mannitol

bronchitol tolerance test

inhaled mucolytic

dornase alfa! (pulmozyme) → cleaves extracellular DNA of mucus + decreases the viscosity

is used long term in pts ≥6yo

• condition use for those 2-5

• can be used in symptomatic infants <2yo

dornase alfa dosing

2.5 mg/2.5ml oral nebulized inhalation 1-2x daily

dornase alfa SEs

chest pain, congestion, pharyngitis, hoarseness/voice alterations

why should dornase alfa not be mixed/diluted w other drugs

cause it may inactivate it!

dornase alfa storage

refrigerated, protect from light

which bacteria are inhaled abx usually targeting

P.aeruginosa

inhaled abx

inhaled tobramycin solution or powder

aztreonam inhalation solution

colistimethate inhalation solution

amikacin inhalation solution

inhaled tobramycin moa

inhibition of protein synthesis by binding to aminoacyl site of 16s ribosomal rna in 30s subunit

aztreonam inhalation solution moa

inhibits cell wall synthesis by binding to pbp and preventing crosslinking

colistimethate inhalation solution moa

disrupts cell membrane by binding to phospholipids + makes it highly permeable

amikacin inhalation solution moa

inhibits protein synthesis by binding to 30s ribosomal subunits

tobramycin inhalation powder brand name

TOBI podhaler

tobramycin inhalation powder dosing

4 × 28mg capsule (112mg total) inhaled bid

tobramycin inhalation powder admin time

2-7 mins

tobramycin inhalation powder storage

at room temp in a dry place

tobramycin inhalation powder counseling

rinse mouth w water after!

tobramycin inhalation solution brand name

TOBI nebulizer

tobramycin inhalation solution dosing

300mg/5ml inhaled bid

tobramycin inhalation solution admin time

15 mins

tobramycin inhalation solution storage

refridgerated, protect from light

important dosing for tobramycin

take as close to 12h apart as possible, and no less than 6h apart

cycled 28d on and 28d off (28d eradication course)

ADRs for tobramycin

cough! (podhaler >neb), sob, sore throat, hemoptysis, ototoxicity, nephrotoxicity, bronchospasm

aztreonam inhaled solution brand name

cayston

aztreonam inhaled solution dosing

75 mg nebulized tid

cycle 28d on, 28d off

aztreonam inhaled solution preparation

reconstitute w 1 ml of sterile diluent prior to use

aztreonam inhaled solution admin

only use w altera nebulizer system!!!!, give over 2-3mins, dose should be given at least 4h apart

aztreonam inhaled solution storage

refridgeration recommended but can be kept at room temp for 28d, protect from light

aztreonam inhaled solution ADRs

cough, nasal congestion, wheezing, pharyngolarygeal pain, chest discomfort, bronchospasm

colistimethate inhalation solution brand name

colistin

colistimethate inhalation solution dosing

75 mg or 150 mg in 3ml sterile water nebulized bid

cycle 28d on and 28d off

colistimethate inhalation solution preparation

mix vial w 3 ml sterile water prior to use

colistimethate inhalation solution administration

via nebulized immediately following preparation to decrease possibility of high concentrations of colistin from forming

admin immediately!!!!, discard after 24h

colistimethate inhalation solution storage

room temp

colistimethate inhalation solution ADRs

bronchospasm, cough, chest tightness, life-threatening lung toxicity, + apnea d/t neuromuscular blockage

amikacin brand name

arikayce

amikacin dosing

1 vial (590 mg daily)

cycled 28d on, 28d off

amikacin preparation

vial should be at room temp prior to use, shake well before opening

amikacin administration

using lamira nebulizer system only!!, inhaled over 14-20 mins

amikacin storage

refridgerated

amikacin adrs

diarrhea, nausea, asthenia, fatigue, voice disorder, ototoxicity, bronchospasm, cough, pulmonary exacerbation, hemoptysis, URI

amikacin care

aerosol head should be replaced every 7d, disinfect w boiling distilled water

anti-inflammatory therapy

azithromycin, high dose ibuprofen, inhaled corticosteroids

azithromycin moa

suppresses proinflammatory cytokine production, potentiates macrophage phagocytosis + anti-inflammatory cytokine expression

azithromycin dosing

<40kg: 250 mg TIW (MWF)

≥40kg: 500mg TIW

who is azithromycin recommended for

pts ≥6 yo w chronic p.aeruginosa colonization

azithromycin SEs

diarrhea, nausea, vomiting

azithromycin monitoring

screen for nontuberculosis mycobacterium b4 initiation + at 6-12 mon intervals (withheld in present of infxn)

when is ibuprofen used

in children 6-17 yo w FEV1 > 60% but not routinely used d/t nephrotoxicity + gastric ulcers

when is inhaled corticosteroids used

only in presence of asthma or allergic bronchopulmonary aspergillosis (if needed given as last step!!)