3. INTRODUCTION:
• Cystic Fibrosis is a genetic disorder due to defective CFTR
protein affecting epithelian cells of Respiratory , Gastrointestinal
& Reproductive tracts leading to abnormal exocrine gland
secretion i.e alteration in viscosity & tenacity of mucus produced
at epithelian surfaces.
• It is an Autosomal Recessive Disorder.
• Most common lethal genetic disease in patient with European
ancestry.
• Although CF was once considered a fatal childhood disease ,
approx. of people living with the disease are ≥ 18 years.
4. EPIDEMIOLOGY:
• Approx. 30,000 individuals in US have CF while 70,000
individuals are estimated to have CF globally.
• Highest prevalence is found to be in Europe, North-America, &
Australia.
• Frequency :
- live births Worldwide
- 1 : 377 live births in England
- 1 : 16000 live births in Asians
- live births in Nepal
• CF-Carrier frequency is in Southern Africa.
5. GENETICS:
• INHERITANCE: AUTOSOMAL RECESSIVE DISORDER
• ETIOLOGY: Mutation in CFTR gene on Chromosome 7(deletion:
F508)
have two defective CF genes in which each of two CF
gene is inherited from each parent.
have one defective gene and one normal gene so
that they usually have no symptoms but can pass defective gene
on offsprings.
7. PATHOPHYSIOLOGY:
• CFTR gene encodes an ATP gated Cl- channel which secrets Cl-
in lungs/GI tract & reabsorbs Cl- in sweat glands.
Inheritance causing CFTR Chr.7 Phe508 deletion
↓
Misfolded CFTR proteins
↓
Improper protein trafficking
↓
Protein absent from cell membrane causing disruption of Cl- channel on cells
8. PATHOPHYSIOLOGY:
↓
Decreased Cl- & H2O secretion
↓
Compensatory increase in Na+ reabsorption via ENaC(↑ -ve transepithlial
potential difference) ↓
Increased H2O reabsorption
↓
Abnormally thick & viscous mucus secreted into lungs & GI tracts
↓
Impairs lung function, obstructs airways & increases susceptibility to infections
13. DIAGNOSIS:
1] PRENATAL SCREENING:
CFTR 32 Mutation Panel is used to screen prenatally in CF-Carrier status
parents or with family Hx of CF. The screen is more sensitive among the
Caucasian population at about 78%. Sensitivity is lower in other races
because they could have a mutation not listed on that 32 mutation panel.
2] NEWBORN SCREENING:
A simple heel stick/prick is done at birth. And then one to two weeks
repeated at the pediatric care hospital — which checks over 53 genetic
conditions mainly including IEM.
Mainly done in newborns with clinical signs s/o inherited disease.
15. DIAGNOSIS:
Newborn screen checks for a chemical called ImmunoReactive Trypsinogen
(IRT) which is abnormally high in CF newborns due to clogging of pancreatic
duct.
If the IRT is high, the second step is to look for changes in the gene that
causes CF.
Not all elevated IRT means the baby has CF. Premature birth/Traumatic
delivery can stress out the pancreas, causing it to release a high amount of
IRT into the bloodstream.
3] GENETIC TESTING:
Identifies mutation in the CFTR gene.
16. DIAGNOSIS:
4] SWEAT CHLORIDE TEST:
Gold standard painless diagnostic test measuring elevated Cl- level in the
sweat.
Infants do not sweat much. Sweat glands have to be stimulated by using an
Electrical current, along with a chemical called Pilocarpine.Usually tested on
two sides. Often it is both forearms. After the stimulation, a plastic coil device
the size of a quarter is placed and covered with gauze to collect the sweat &
families are advised to keep babies hydrated and wrapped in a blanket to
obtain enough sweat for the test.
Interpretation:
Normal = <30 mEq
Intermediate = 30-59 mEq → Sweat test repeated then Genetic test done
17. DIAGNOSIS:
Severe = >60 mEq → Indicative but better to confirm with Genetic Testing
False Positive Cases:
Hypothyroidism, Addison's disease & Malnutrition
False Negative Cases:
Pedal edema , Dilution of sample & Milder form of CF
5] CHEST X-RAY:
Hyperinflated lungs with lung fibrosis and diffuse hazziness with
honeycombing.
20. DIAGNOSIS:
6] PULMONARY FUNCTION TEST:
Consistent with Obstructive airway disease.
7] SINUS X-RAY:
Shows signs of sinusitis.
8] SPUTUM CULTURE:
Rule outs other infective chronic conditions.
21. DIAGNOSIS:
9] RENAL FUNCTION TEST:
Can present with contraction alkalosis & hypokalemia as ECF effects
analogous to loop diuretic effect due to ECF H2O/Na+ losses via sweating &
concomittant renal K+/H+ wasting.
10] ARTERIAL BLOOD GAS ANALYSIS:
Done if severe respiratory clinical presentation to diagnose T2RF.
22. COMPLICATIONS:
Meconium Ileus
Recurrent Pulmonary Infections(S.aureus in infancy & early childhood and
P.aureginosa in adults)
Allergic Bronchopulmonary Aspergillosis(ABPA)
Chronic Bronchitis & Bronchiectasis
Failure To Thrive
Fat Soluble Vitamin Deficiencies
Endocrine Dysfunctions(CF related DM)
Biliary Cirrhosis
Infertility
Atelectasis/T2RF
23. MANAGEMENT:
• Cystic fibrosis (CF) has no cure. So,the goals of treatment includes
multidisciplinary approach by Pulomonologists , Dieticians , Physiotherapists ,
Psychologists & Paediatricians to :
1. Prevent and control lung infections
2. Loosen and remove thick, sticky mucus from the lungs
3. Prevent or treat blockages in the intestines
4. Provide enough nutrition
5. Prevent dehydration
6. Depending on how severe of the disease child is treated in a hospital
24. MANAGEMENT:
1. Airway Clearance : help loosen and get rid of the thick mucus that can build up in the
lungs which can be done with =
• Coughing or huffing - a gentle cough
• Chest Physiotherapy (CPT)- which involves lying in various positions and clapping on the
chest & back
• Positive expiratory pressure (PEP) device
• Flutter device - also known as oscillating positive expiratory pressure
• CPT vest
• Exercises, Percussion & Vibration
2. Bronchodilators : To alleviate the respiratory symptoms.
3. Mucolytics : Inhaled hypertonic saline(3%&7%) / N-acetylcysteine /
Bromohexine /Aerosolized Dornase Alfa(DNase)
25. MANAGEMENT:
4. Antibiotic Therapy : IV Azithromycin & Inhaled Tobramycin
prevents acute exacerbation
5. Anti-Inflammatory Agents : Steroids and Ibuprofen can be given IV
6. CFTR Modulators : can be used alone or in combination.Efficacy depends
on pharmacogenomics.They are either potentiators(Ivacaftor) or
correctors(Lumacaftor & Tezacaftor)
7. Supplemental Oxygen : depending on the saturation level
8. Pancreatic Enzyme Replacement Therapy : Pancrealipase can be used in
Pancreatic Insufficiency
9. Approptiate Nutrition : High calorie diet, Fat soluble vitamin supplementation
with restricted oily diets
26. MANAGEMENT:
For Infants =
Standard infant formula and breastmilk have 20 calories per ounce. We can
concentrate or fortify both formula and breastmilk up to 30 calories per ounce.
For Children and Adults =
Scandishakes
Carnation Instant Breakfast
Pediasure, Boost Kid Essentials (both 1.0 and 1.5 versions)
Boost, Ensure (regular and Plus version)
Resource Breeze, Glucerna
27. MANAGEMENT:
10. Lifestyle Changes : Chest excercises & avoiding dust/cold/smoke.
11. Gene Therapy : Done at molecular level ,costly.
12. Pulmonary Rehabilitation: may be required frequently in severe cases
13. Lung Transplantation : last option for severe stage of obstructive airway
disease
PROGNOSIS & QUALITY OF LIFE :
• Improved Life expectancy = advances in treatment modality has
significantly increased life expectancy.
• Challenges = Daily management , Frequent hospitalization & Potential
complications impacts quality of life.
• Supportive Care = Multidisciplinary approach required with different
specialist.
