RES121_Pulmonary Diseases Management

PRELIM: Cystic Fibrosis (Sir Rhen’s PPT) Jardin’s Chapter 15

SANTOS | 3rd Year 1st Semester
CYSTIC FIBROSIS (CF)
Autosomal recessive disorder that affects epithelial
cells of the respiratory, GI and reproductive tracts
and leads to abnormal exocrine gland secretions.
An individual must inherit a defective copy of CF
gene (one from each parent) to have CF.
Although it can affect many organ system, CF is
particularly damaging to the lungs, leading to
COPD in childhood and early adulthood.
Every person inherits 2 CF genes – one from each
parent.
● Children who inherit a faulty gene from each
parent will have CF.
● Children who inherit one faulty gene and
one normal gene will be “CF carriers”.
CF carriers usually have no symptoms of CF, but
they can pass the faulty gene on to their children.

Pathophysiology
CF is due to a mutation in CF gene chromosome 7.
CF gene encodes a protein known as the cystic
fibrosis transmembrane regulator (CFTR)
The abnormal CFTR protein in the patients with CF
leads to disruption of chloride channels on the cells.
Epidemiology Commonest mutation is Delta F508, is a deletion of
The frequency of CF is 1 in 2,000 and 3,000 live three nucleotides that results in a loss of amino
births, and there are ~30,000 children and adults acid phenylalanine at the 508th position of protein.
with this disease in the US (CF foundation).
Although CF was once considered a fatal childhood
disease, ~38% of people living with the disease are
18 y/o or older (CF foundation).
In CF, there is an alteration in the viscosity and
tenacity of mucus produced at epithelial surfaces.
The classical form of the syndrome includes
increased broncho-pulmonary secretion and
infection and pancreatic insufficiency, with a high
sweat sodium and chloride concentration.
RES121_Pulmonary Diseases Management
PRELIM: Cystic Fibrosis (Sir Rhen’s PPT) Jardin’s Chapter 15
SANTOS | 3rd Year 1st Semester
Dehydration of Airway Lining

Clinical Manifestation
Pulmonary manifestations
● Productive cough
● Wheezing hyperinflation of the lung fields on
chest x-ray
● Frequent chest infections, and coughing or
SOB
● PFT results consistent with obstructive
airway disease
CF CXR

Hallmark Pathophysiologic Effects of CF

● Excessive mucous production in respiratory
tract with impaired ability to clear secretions
and progressive COPD;
● Atelectasis
● Infection
● Bronchiectasis
● Dilation of distal airway Non Pulmonary Clinical Manifestations
● Acute and chronic damage to the lung and ● GI problems (eg, pancreatic insufficiency,
scarring and fibrosis of lung tissue recurrent abdominal pain)
● Chronic hypoxemia ● Biliary cirrhosis
- When bile ducts become swollen or
Pancreatic Enzyme Deficiency & Impaired
inflamed, this blocks the flow of bile.
Digestion
- These changes can lead to scarring
Pancreatic insufficiency and impaired enzyme
of the liver called cirrhosis
secretion, impaired digestion and absorption of
● Vitamin deficiencies
protein, carbohydrates and fats.
● Recurrent pancreatitis
Degenerative and fibrotic change. ● Weight loss
Small intestine: absence of pancreatic enzymes ● GU problems (male and female infertility)
unable to absorb fats and protein. ● Meconium ileus in newborn babies
● Clubbing of the extremities
Abnormal Elevation Of Na+ And Cl-
● Salty tasting skin
Concentration
● Poor growth and poor weight gain despite
Due to the defect in chloride channels, CF fibrosis
normal food intake
also causes the sweat to become very salty.
RES121_Pulmonary Diseases Management
PRELIM: Cystic Fibrosis (Sir Rhen’s PPT) Jardin’s Chapter 15
SANTOS | 3rd Year 1st Semester
Newborn Clinical Features Nasal Potential Difference
In newborn the period is marked by; The impaired transport of sodium (Na+) and
● Poor weight gain chloride (Cl−) across the epithelial cells lining the
● Intestinal blockage airways of the patient with CF can be measured.
● Accompanied by thick fecces Electrical potential – amount of energy required to
Prenatal Testing move an electrical charge from one point to
The fetus can be tested for CF by amniocentesis another.
after the first trimester. ● In the nasal passages this electrical
● Amniotic fluid is obtained by ultrasound potential difference is called the Nasal
guided needle aspiration of amniotic fluid potential difference.
from around the fetus. NPD can be measured with a surface electrode
● Fetal cells are tested for the presence of CF over the nasal epithelial cells lining the inferior
mutations and identified as CF affected, CF turbinate.
carrier, or normal. ● An increased (more negative) NPD strongly
Genetic counseling is very important in all cases of suggests CF.
pre-natal testing for CF to explain this uncertainty NPD is recommended for patients with clinical
or residual risk to prospective parents. features of CF who have borderline or normal
Infants with positive CF newborn screening sweat test values and nondiagnostic CF genotyping
results Gastrointestinal
- Performed after 2 weeks of age and >2 kg if ● Distal intestinal obstruction (DIOS,
asymptomatic meconium ileus)
Infants with symptoms suggestive of CF ● Malabsorption
● Maldigestion
- Older siblings (including adults) with ● Steatorrhea
symptoms suggestive of CF
- Members of the patient’s family with Stool Fecal Fat Test
confirmed CF. Measures the amount of fat in the infant’s stool and
the percentage of dietary fat that is not absorbed by
the body.
Used to evaluate how the liver, gallbladder,
pancreas, and intestines are functioning.
Under normal conditions the fat malabsorption is
less than 7 g of fat per 24 hours.
Elevated stool fecal fat value (decreased fat
absorption) is associated with a variety of
disorders, including CF.
Fecal elastance is an easier test of pancreatic
function as it only requires a small stool sample for
analysis.
Infants with CF and pancreatic insufficiency will
have a fecal elastance of less than 50 µg/g of stool
(normal is greater than 300 µg/g of stool).
RES121_Pulmonary Diseases Management
PRELIM: Cystic Fibrosis (Sir Rhen’s PPT) Jardin’s Chapter 15
SANTOS | 3rd Year 1st Semester
Reproductive System If the test is positive, it should be confirmed by
● Dysfunctional due to inspissation of mucus mutation analysis (genetic testing) the combination
in reproductive tract of IRT and mutation analysis is sensitive 90% to
● Sterility in males (atrophy or absence of vas 100% all the time.
deferens) Bacterial Presence
Assessment & Diagnostic Findings ● Staphylococcus aureus,
● Sweat test ● Haemophilus influenzae, and
- sweat chloride values of > 60 mEq/L ● Pseudomonas aeruginosa.
● Genetic test Some gram-negative bacteria are also commonly
- to find out what type of CFTR defect associated with CF, such as Stenotrophomonas
is causing CF. maltophilia and Burkholderia cepacia complex.
● Chest X-ray
- inflated lung, lungs fibrosis and The infection stimulates additional mucous
scaring production and further compromises the
● Sinus X-ray mucociliary transport system.
- this test may show signs of sinusitis As the disease progresses, the patient may
● Lung function test develop signs and symptoms of recurrent
● Sputum culture pneumonia, chronic bronchitis, bronchiectasis, and
● Immunoreactive trypsinogen test (IRT) lung abscesses.
Sweat Test Medical Management
Involves application of a medication that stimulates CF has no cure. The goals of CF treatment
sweating (pilocarpine). include;
The resultant sweat is then collected on filter paper ● Preventing and controlling lung infections
or in capillary tube and analyzed for abnormal ● Loosening and removing thick, sticky mucus
amounts of sodium and chloride. from the lungs
People with CF have increased amounts of sodium ● Preventing or treating blockages in the
and chloride in their sweat. intestines
● Providing enough nutrition
In both infants and adults, a sweat chloride ● Preventing dehydration
concentration greater than 60 mEq/L is considered
to be a diagnostic sign of CF. Treatments
● Antibiotic medications
Special diet high in protein and calories for older ● Bronchodilators
children and adults ● Mucus clearance strategies
Pancreatic enzymes to help absorb fats and ● Anti-inflammatory agents may
protein, which are taken with every meal. ● Supplemental oxygen
Vitamin supplements, especially vitamins A, D, E, ● Lung transplantation
and K. ● Gene therapy
● Lifestyle
Your provider can advise other treatments if you ● Lifestyle changes
have very hard stools. ● Pulmonary rehabilitation
Immunoreactive Trypsinogen Test (IRT)
A blood test that involves drawing blood a couple of
days after birth and evaluating the presence of the
protein trypsinogen.