Cystic Fibrosis

A chronic, progressive inherited

disease
which may lead to the development of
very thick, easily dried out mucous in
nose, lungs, and intestines …
life-limiting disorder
Average life expectancy has increased
from a few years to 40 years with the
right treatment.
 Cystic Fibrosis: How Common?
Autosomal recessive
It is the most common life-limiting inherited
condition in Caucasians.
Incidence 1:2500 live births (Caucasians)*
1:25 Caucasians are carriers
 much less common in other ethnic groups
 Etiology
• Genetically transmitted
disease
– Genes (DNA)
– From parents
• Gene located on 7th
chromosome
– 2 copies of genes needed to
inherit disease
– Carrier states

(National Institutes of Health, n.d.)

 Cystic fibrosis gene mutations
. As many as 1900 mutations in the CFTR gene have been
observed worldwide.

• the most Common mutation – Delta F508

UK Caucasians - 75%
UK Asians - 29%

The severity of the disease is directly related to the

characteristic effects of the particular mutations that have
been inherited by the individual sufferer
Molecular Genetics and Gene Function
• Locus: 7q31.2 - The CFTR gene
is found in region q31.2 on the
long (q) arm of human
chromosome 7.

• Protein CFTR called cystic

fibrosis transmembrane regulator
(CFTR)
• The normal CFTR protein
product is a chloride channel
protein found in membranes of
cells that line passageways of the
lungs, liver, pancreas, intestines,
reproductive tract, and skin.
 Protein Function and
Biochemistry
•
• Protein Function:
• CFTR is a cyclic AMP-
dependent chloride channel
blocker
• CFTR controls chloride ion
movement in and out of the
cell.
 Pathophysiology
• Body produces thick,
sticky mucus
– Clogs the lungs
• Stagnant mucus
– Obstructs the pancreas
• Malabsorption &
malnutrition

(MedlinePlus, 2006)
Presentation of Disease

Mucous in the airways cannot be easily cleared from the lungs.

 Presentation of Disease
Colon

Pancreas

Sticky mucus secretion

Ducts are filled with sticky mucus. Scaring of tissue.

 CF: Symptoms

 The body produces thick, sticky mucus in the

lungs which becomes a breeding ground for
infection.
 The pancreas becomes blocked by mucus,
unable to release digestive enzymes into the
intestines needed for digestion and
absorption of nutrients.
 Excess mucus production impairs
reproductive organ functions in both males
and females.
 Clinical Manifestations
• Respiratory Tract
• Cough is the most constant symptom.
• Wheezing
• Recurrent chest infection
• Cyanosis is a late sign
• Atelectasis, hemoptysis, pneumothorax,
and cor pulmonale
• Sinusitis, nasal polyps
 Clinical Manifestations….
• Intestinal Tract
1. Meconium ileus 10-20%
2. Meconium plug syndrome (meconium
ileus equivalent)…
3. more than 85% of patients showed
evidence of maldigestion from exocrine
pancreatic insufficiency.
4. Intussception
 Clinical Manifestations…
4. Bile or acid reflux with oesophagitis
5. Sub acute appendicitis
6. Rectal prolapse
7. Failure to thrive
8. Fat-soluble vitamin deficiency
manifestation.
9. Fingers clubbing
10.steatorhea
 Clinical Manifestations…
• Biliary Tract
• Biliary cirrhosis symptomatic in 2-3% .
• Ascitis, Jaundice, hematemesis,
esophageal varices
• Neonatal hepatitis
 Clinical Manifestations…
• Diabetes Mellitus… 8% after the age of
10.
• 95% of males are azoospermic because of
failure of development of wolffian duct
structure.
• Secondary amenorrhea
• Cervicitis
• Failure to thrive
• Clubbing fingers
 Diagnosis of Cystic Fibrosis

• neonatal screening
 Sputum cultures
• Sweat test
 Pulmonary
• Blood tests
function tests
• Metabolic alkalosis
FEV1
• Chest x-rays  Stool evaluations
 Pancreatic
function tests
 Screening
. Screening of all newborn infants for CF is
routinely performed throughout the UK.
Immunoreactive trypsin (IRT) is raised in CF
patients.
Those samples are then screened for
common CF gene mutations.
Infants with two mutations have a sweat
test to confirm the diagnosis.
.
 Screening

Identifying cases in the neonatal period

allows the early treatment & ↑ Average life
expectancy

It enables early genetic counselling for the

parents about the 1 in 4 risk of recurrence
and the possibility of prenatal diagnosis in
future pregnancies.
 The Sweat Test

“Gold Standard” for testing over 40 years

- painless
- inexpensive
- gives definite answers
 The Sweat Test
essential diagnostic procedure
• Cl- ≥ 60 mEq/L

• 40-60 mEq/L ?
 The Sweat Test
• False positives • False negatives
– adrenal insufficiency – severe malnutrition
– nephrogenic DI with edema
– hypothyroidism – too little sweat
– mucopolysaccharidosis – inexperienced tester
– G6P deficiency
– hypoproteinemia
– anemia from poor
nutrition
 MANAGEMENT
Cystic Fibrosis: A Disease for a
Multidisciplinary Team
• Clinic coordinator
• Social worker
• Respiratory therapist
• Nurse
• Registered dietitian
 Management of Lung Disease
• The aim is:
1. Clear secretions
2. Control infection
3.PHYSIOTHERAPY and physical activity
Chest physiotherapy
Postural drainage
Positive expiratory pressure
Agents to promote airway secretion clearance
-Hypertonic saline
-DNase I (dornase alfa)
-N-acetylcysteine
Management of Lung Disease…

ANTIBIOTIC THERAPY

1. IV Antibiotics
2. Aerosolized Antibiotics
3. Oral Antibiotics
 Antibiotics
• Often unable to eradicate the organism
• Determining optimal delivery mode for a
drug is difficult
• CF patients require higher doses
– Altered volume of distribution
– Rapid clearance of drugs
 IV Antibiotics
Indications:
1.Severe exacerbations
2.Bacterial resistance to all orally
administered antibiotics
3.Failure of oral antibiotic therapy to resolve
symptoms
 G.I.T. Management…
• Pancreatic enzyme replacement (enteric
coated granules)
– Lipase, Amylase, Protease
– Not more than 2500 lipase units/kg/meal

Vitamin and Mineral supplements

Fat-soluble vitamins (A, D, E, K)
 G.I.T Management …
• Treatment of G.I.T complications
• Meconium ileus
• Meconium ileus Equuivalent
• GER
• Rectal Prolapse
• Liver Disease
 Gene Therapy
• Gene therapy is the use of
normal DNA to "correct" for
the damaged genes that
cause disease.
• In the case of CF, gene
therapy involves inhaling a
spray that delivers normal
DNA to the lungs.
• The goal is to replace the
defective CF gene in the
lungs to cure CF or slow the
progression of the disease.