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An inherited
disorder characterized primarily by progressive lung disease, pancreatic
insufficiency, gastrointestinal obstruction, and an excess of sodium and
chloride in the sweat.
Incidence most
commonly is a fatal autosomal recessive disease affecting caucasian
populations (carrier rate is 1/20), and varies between different
populations: Northern Ireland - 1 in 1700 – 1900; USA: Caucasians - 1 in
1900 – 3700; England: Asian - 1 in 10,000; USA: Black - 1 in 17,000. Age
of onset is greater in infancy than adolescence with risk factors:
familial - autosomal recessive
chrom.#: 7q31.2
gene: cystic fibrosis transmembrane conductance
regulator (CFTR) gene
The function of
the CFTR gene is unknown and controversial. There is a defective
transport of anions (Cl) across epithelial cells in the airways,
pancreas, intestine, and sweat glands leads to chronic lung disease,
pancreatic insufficiency, gastrointestinal obstruction, and increased
sodium and chloride in the sweat. Over 400 mutations of the CFTR gene
have been identified with 70% of the mutations in the CFTR being
deltaF508. Those homozygous for this mutation tend to have pancreatic
insufficiency.
Clinically, a
diffuse manifestation of disease processes can occur:
1.
Respiratory
i. Chronic rhinitis/rhinorrhea nasal polyps
(15-20%)
ii. Acute/chronic sinusitis
iii. Middle ear effusions
iv. Culture + for P. aeruginosa
v. Chronic cough (earliest manifestation)
vi. Coarse crackles (RUL)
vii. Obstructive lung disease (hyperinflation,
wheezing)
viii. Exacerbation of respiratory distress
(dyspnea, cough) associated with acute
respiratory infections (later stage)
ix. Hypoxemia, pulmonary hypertension, cor
pulmonale, respiratory failure (end stage)
x. Complications include atelectasis,
pneumothorax, hemoptysis, clubbing, allergic
Aspergillosis, hypertrophic pulmonary
osteoarthropathy, and bacterial infections (s.
aureus, H. influenzae, pseudomonas aeruginosa -
40% of patients are colonized by 5 years of age,
andBurkholderia cepacia)
2.
Gastrointestinal Tract Manifestations
i. Neonates: Meconium ileus and meconium plug
syndrome in the neonate
ii. Infants/Children: Meconium ileus equivalent
(distal intestinal obstruction syndrome);
partial or complete obstruction of the terminal
ileum; rectal prolapse, intussusception,
adhesions (from previous surgury), appendix
(appendicitis, periappendiceal abscess
diverticulosis), and duodenal ulcers.
3.
Pancreatic Diseases
i. Pancreatic enzyme deficiency (blocked ducts);
Decrease absorption of fats, protein, nitrogen
of vitamins D,E,A,K; fecal loss of bile acids,
pancreatitis, diabetes mellitus
4.
Hepatobiliary Disease
i. Biliary cirrhosis, cholelithiasis
5.
Genitourinary Tract Manifestations
i. Males - altered Wolfian duct structures; only
2-3% are fertile
ii. Females - 10% are fertile with a delay in
the onset of puberty and sexual maturation
6.
Sweat Gland Manifestations
i. Failure to reabsorb Cl
ii. Increased Na, Cl, K in sweat (i.e., loose
NaCl through sweat)
iii. Salty taste with salt crystals on skin
iv. Salt depletion, which can lead to profound
hypochloremia, hyponatremia, alkalosis, and/or
hypotension
Investigations
include pulmonary function testing:
Obstructive
Lung Disease
seen
within weeks to months after birth
progresses from peripheral to general involvement
characterized by:
decreased maximal flow rates
decreased FEV/FVC
increase a-A gradient (V/Q mismatch)
reactive airway disease
Restrictive
Lung Disease
late
stage disease
characterized by decreased VC and TLV
End
Stage Disease
FEV1 <30% predicted
(PaO2 <55 mmHg, PaCO2 >50 mmHg)
Malabsorption
see
file on "Malabsorption"
Neonatal Screening
elevated level of trypsinogen in the blood of newborns
Diagnosis can
be made by sweat chloride testing (sweat gain >100 mg with a [NaCl] >60
mmol/L ). As yet there is no correlation between genotype and phenotype.
Management
includes the following:
For the pancreatic-sufficient type there may be no need
for pancreatic enzymes
Management with pancreatic enzymes in the
pancreatic-insufficient type
Management of respiratory manifestations in all patients
Goals of
Therapy
no
cure for cystic fibrosis and thus management goals
revolve around the amelioration of the respiratory and
gastrointestinal manifestations
Management Strategies
Supportive
CF is a chronic and progessive illness that
needs close monitering and thus regular
follow-up is important 0
the patient and family should be linked to a CF
support group within the community
Psychological support - living with CF, dying with CF
funding for medical therapy is provided through
the government and the distribution of
medications is through regional centres
throughout Canada
the Pediatrician coordinates a team approach
involving pharmacists, dieticians,
psychologists, & physiotherapists
Follow-up
clinical assessment every 3-6
months with sputum samples and
pulmonary function tests with
each visit
chest x-ray every 6-9 months
SMA11 and CBC with differential every 12
months
Chest Physiotherapy
performed at least 3
times per day to relieve
mucous obstruction in
the lungs
postural drainage of the
17 segments may take up
to 20-30 minutes per
session
autogenic drainage -
breathing at different
lung volumes to increase
release of mucous from
the lower airways
Diet
Newborn
Provide 150% of normal
caloric requirements
Follow clinically -
stooling pattern,
abdominal distension,
weight gain
Breast Feeding
Encourage but may not be
tolerated
Supplement with formula
(see below)
upplement formula to
27 kcals/oz. with
Polycose and MTC Oil
if taking elemental
formulas by mouth,
may switch over to
milk-based formula
when infant gaining
weight (i.e., by 6
weeks of age)
Elemental feeds -
Alumentum or
Nutramigen
Supplementations
Pancreatic Enzymes
Cotazym
supplements
needed for all
breast and
formula-fed
infants
may add cotazym
powder to apple
sauce prior to
feed
always wash
mouth after
enzymes given to
prevent
autodigestion
Vitamins
Poly-Vi-Sol 0.6 cc po od
Vitamin E 100 mg
po tid for 1st
year then 400 mg
po od
Children to Adulthood
Meals
High calorie meals high in salt
Supplementations
Ensure drinks or
puddings
Pancrelipase
Preparations
Cotazym and Cotazym ECS
Take as much is
needed to
control diarrhea
and
malabsorption
must take with
each meal and
snack
Multiple Vitamins
poly-vi-sol (tablets or
drops)
vitamin E (capsules or
drops)
NaCl
snacks high in
salt (chips,
cheezies, salt
pills)
particularly in
hot weather
Birth Control
liver function tests should be
monitered carefully for hepatits
in women on the birth control
pill
lung function declines after
pregnancy
Pharmacologic
Antibiotics
Prophylaxis (Continuous)
Staph. aureus
Keflex
(Cephalexin)
50-70 mg/kg/d po
tid-qid
Cloxacillin 100
mg/kg/day po qid
Pseudo. aeruginosa
Tobramycin
(Nebulized)- 2cc
(80mg) tid after
physiotherapy
Acute Exacerbations - positive sputum
H. flu
Amoxicillin 25-50 mg/kg/day po
tid x 2 weeks
P. aeruginosa
add
Ciprofloxacin 40
mg/kg/day po bid
x 2 weeks to
Tobramycin
therapy
B. cepacia
Ciproflaxacin 40
mg/kg/day po bid
or Septra po bid
x 2 weeks to
Tobramycin
therapy
Hospitalization
Tobramycin
80 mg nebulized tid and 3-3.5
mg/kg/dose IV q8h
Ceftazidime
150 mg/kg/day IV tid (max.
2g/dose)
Keflex or Cloxacillin po
Ventolin by mask bid
Surgery
For Complications
pneumothorax, hemoptysis
meconium ileus + equivalent, meconium plug syndrome,
rectal
prolapse, partial or complete obstruction,
appendicitis, cholethiasis, etc.
For Lung Transplantation
for end stage lung disease (when FEV1 is <25%
normal)
about 10% of patients reach transplantation
with a 50% mortality within two years of
transplant
Experimental Therapies
Amiloride (decreases NaCl and water absorption
(diuretic); inhibits bacterial growth (gram +); enhances
the activity of tobramycin; given by mask
Dnase decreases the viscosity of sputum and
thins out lung secretions: increases mucociliary
transport; digests the DNA released by
inflammatory cells found in the lung secretions;
given by mask bid
2. Trials
§ 2.5 mg Pulmozyme od has a minimal
effect (2-4%) on pulmonary function
tests and is reported to show
clinical improvement (decreases
dyspnea, CF-related symptoms, and
hospitalized days)
§ side effects: anaphylaxis,
hemoptysis
§ disadvantages: $26,000/yr/patient
Gene Transfer Therapy (adenovirus vectors with
normal CFTR gene inserted into the genome
administered to patients via an aerosol mist)
Prognosis is
dependent on severity of illness.
This edited version is
being used with the permission of its original author, Dr.
Alan Gandy.
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