Cystic Fibrosis

Lee Mei Gie

Group 88
5th course
 Definition
• Cystic fibrosis is an inherited disease of the exocrine
glands affecting primarily the GI and respiratory
systems.
• It leads to chronic lung disease, exocrine pancreatic
insufficiency, hepatobiliary disease, and abnormally
high sweat electrolytes.
 Etiology
• CF is carried as an autosomal recessive trait by about
3% of the white population.
• The responsible gene has been localized on the long
arm of chromosome 7. It encodes a membrane-
associated protein called the cystic fibrosis
transmembrane conductance regulator (CFTR).
• CFTR is a cAMP-regulated Cl channel, regulating Cl
and Na transport across epithelial membranes.
• Mutation of that certain gene leads to cystic fibrosis.
Disease manifests only in homozygotes.
 Epidemiology
• If both parents are heterozygote , there is 25%
possibility of their children are homozygote and
develop cystic fibrosis.
• White population > Black and Asian population
• Ratio male to female is 1:1
• Females with cystic fibrosis have greater
deterioration of pulmonary function with increasing
age and younger mean age at death due to increase
in hormone secretion during puberty may interfere
the defense mechanisms of the immune system.
 Pathophysiology
Nearly all exocrine glands are affected in varying distribution and
degree of severity. Glands may :
• Become obstructed by viscid or solid eosinophilic material in
the lumen (pancreas, intestinal glands, intrahepatic bile ducts,
gallbladder, and submaxillary glands).
• Appear histologically abnormal and produce excessive
secretions (tracheobronchial and Brunner glands).
• Appear histologically normal but secrete excessive Na and Cl
(sweat, parotid, and small salivary glands).
 Signs and symptoms
Specific target organ
1. Gastrointestinal tract
• Meconium ileus
• Abdominal distention
• Intestinal obstruction
• Increased frequency of stools
• Failure to thrive (despite adequate appetite)
• Flatulence or foul-smelling flatus, steatorrhea
• Recurrent abdominal pain
• Jaundice
• GI bleeding
2. Respiratory system
• Cough
• Recurrent wheezing
• Recurrent pneumonia
• Atypical asthma
• Dyspnea on exertion
• Chest pain

3. Genitourinary tract
• Undescended testicles or hydrocele
• Delayed secondary sexual development
• Amenorrhea
 Physical examination

Findings related to the pulmonary system may include the following:

• Tachypnea
• Respiratory distress with retractions
• Wheeze or crackles
• Cough (dry or productive of mucoid or purulent sputum)
• Increased anteroposterior diameter of chest
• Clubbing
• Cyanosis
• Hyperresonant chest upon percussion (crackles are heard acutely in
associated pneumonitis or bronchitis and chronically with
bronchiectasis)
Findings related to the GI tract include the following:
• Abdominal distention
• Hepatosplenomegaly (fatty liver and portal hypertension)
• Rectal prolapse
• Dry skin (vitamin A deficiency)
• Cheilosis (vitamin B complex deficiency)

Examination of other systems may reveal the following:

• Scoliosis
• Kyphosis
• Swelling of submandibular gland or parotid gland
• Aquagenic wrinkling of the palms (AWP)
 Complication
Bronchiectasis
Atelectasis
Pneumothorax
Hemoptysis
Hypertrophic pulmonary osteoarthropathy
Allergic bronchopulmonary aspergillosis (ABPA)
Gastroesophageal reflux
Pulmonary hypertension
Cor pulmonale
Pancreatitis
Cystic fibrosis–related diabetes mellitus
Meconium ileus
Distal intestinal obstruction syndrome
Rectal prolapse
Vitamin deficiency (especially fat-soluble vitamins)
Fatty liver
Focal biliary cirrhosis
Portal hypertension
Liver failure
Cholecystitis and cholelithiasis
Rickets
Osteoporosis
 Diagnosis
The diagnosis of cystic fibrosis (CF) is based on
• Typical pulmonary manifestations, GI tract
manifestations
• Family history
• Universal newborn screening
• Prenatal screening test
• Sweat test results
Requirements for a CF diagnosis include either positive
genetic testing or positive sweat chloride test findings
(>60 mEq/L) and 1 of the following:

• Typical chronic obstructive pulmonary disease

• Documented exocrine pancreatic insufficiency
• Positive family history (usually affected sibling)
Cl concentration for infants Result
(up to 6 months)
0-29 mmol/L CF is unlikely

30-59 mmol/L intermediate

≥ 60 mmol/L Indicative of CF

Cl concentration for Result

infants older than 6
months, child and adult

0-39 mmol/L CF is unlikely

40-59 mmol/L intermediate
≥ 60mmol/L Indicative of CF

*The sweat test must be performed at least

twice in each patient, preferably several
weeks apart.
 Other examinations
• Imaging test (X-ray, US, CT, MRI)
• Genotyping
• Pulmonary function test
• Bronchoalveolar lavage and sputum microbiology
• Immunoreactive trypsinogen
• Contrast barium enema
Hyperinflation and predominantly upper lobe bronchiectasis.
Complete right lung
atelectasis with
extreme bronchiectasis.
Marked hyperinflation
of the left lung is noted.
High-resolution CT image shows bronchial wall thickening (tram
lines), predominantly in the upper lobes.
String-of-pearls sign in the
left lower lobe in a patient
with cystic fibrosis. The
soft tissue surrounding
each "pearl" indicates focal
atelectatic, fibrotic lung.
Meconium ileus- Marked abdominal distension at 3 days of life.
Dilation of bowel loops. No air is seen in the colon or rectum.
Progression to
perforation, with overt
free air under the
diaphragm and a
double air-contrast of
bowel.
There is also free air in the scrotum, from tracking of air into the
processus vaginalis. At laparotomy, a meconium plug was found.
Raised volume rapid thoracic compression
(RVRTC)
Sputum microbiology
The most common bacterial pathogens in the sputum of patients
with cystic fibrosis are as follows:

• Haemophilus influenzae
• Staphylococcus aureus
• Pseudomonas aeruginosa
• Burkholderia cepacia
• Escherichia coli
• Klebsiella pneumoniae
Immunoreactive trypsinogen (IRT)
• is a pancreatic enzyme that can help with diagnosing CF in
neonates with meconium ileus when IRT relative ratios are
elevated greater than the 99th percentile.
• IRT plus sweat test was shown to increase sensitivity and
specificity in screening.
 Management
The primary goals of CF treatment include the following:

• Maintaining lung function as near to normal as possible by

controlling respiratory infection and clearing airways of mucus
• Administering nutritional therapy (ie, enzyme supplements,
multivitamin and mineral supplements) to maintain adequate
growth
• Managing complications
Mild acute pulmonary exacerbations of cystic fibrosis can be
treated successfully at home with the following measures:

• Increasing the frequency of airway clearance

• Inhaled bronchodilator treatment (especially if bronchial
hyperresponsiveness is present or as part of airway clearance
[inhaled bronchodilator followed by chest physical therapy
and postural drainage)
• Chest physical therapy and postural drainage
• Increasing the dose of the mucolytic agent dornase alfa
(Pulmozyme)
• Use of oral antibiotics (eg, oral fluoroquinolones)
Medications used to treat patients with cystic fibrosis may
include the following:

• Pancreatic enzyme supplements

• Multivitamins (including fat-soluble vitamins)
• Mucolytics
• Nebulized, inhaled, oral, or intravenous antibiotics
• Bronchodilators
• Anti-inflammatory agents
• Agents to treat associated conditions or complications (eg,
insulin, bisphosphonates)
• Agents devised to potentially reverse the abnormalities in
chloride transport (eg, ivacaftor)
Pancreatic enzyme supplements
• Pancrelipase (Creon, Pancreaze, Ultresa, Zenpep)

Mucolytics
• Dornase alpha (Pulmozyme)

Bronchodilators
• Inhaled beta2-agonist : Albuterol (AccuNeb, ProAir, Proventil
HFA, VoSpire ER, Ventolin HFA)

Vaccination
• Vaccination against Pertussis, Haemophilus influenzae,
Varicella, Streptococcus pneumoniae, and measles and annual
influenza vaccination.
Airway clearance
• Postural drainage, percussion, vibration, and assisted coughing are
recommended at the time of diagnosis and should be done on a
regular basis

Antibiotics (oral, intravenous, or inhalation)

• Aerosolized form : gentamicin, aztreonam, colistin, and preservative-
free high-dose tobramycin especially formulated for inhalation.
• First-generation to third-generation cephalosporins gives increasing
gram-negative coverage and less gram-positive coverage, effective
against Staphylococci and Haemophilus influenza
• Fluoroquinolones are effective against most gram-positive and gram-
negative organisms, effective against P aeruginosa.
• Gentamicin is usually combined with one of the penicillins used to
treat pseudomonad infections in patients with CF.
• Aztreonam is a monobactam antibiotic that elicits activity in vitro
against gram-negative aerobic pathogens, including P aeruginosa.
Vitamins
• Fat soluble vitamins A, D, E, and K and water soluble biotin,
folic acid, niacin, pantothenic acid, B vitamins (ie, B-1, B-2, B-
6, B-12), and vitamin C.

CFTR Potentiators
• Cystic fibrosis transmembrane conductance regulator (CFTR)
potentiators are the first available treatment that targets the
defective CFTR protein.
• Ivacaftor (Kalydeco) - facilitates increased chloride transport
by potentiating the channel-open probability (or gating) of
certain CFTR gene mutations.
Surgical therapy may be required for the treatment of the
following respiratory complications:
• Pneumothorax
• Massive recurrent or persistent hemoptysis
• Nasal polyps
• Persistent and chronic sinusitis

GI tract complications requiring surgical therapy are as follows:

• Meconium ileus
• Intussusception
• Gastrostomy tube placement for supplemental feeding
• Rectal prolapse

*Lung transplantation is indicated for the treatment of end-stage

lung disease
Thank you!