Cystic fibrosis is a genetic disorder that affects the lungs and digestive system. It is caused by mutations in the CFTR gene that result in abnormal ion transport in epithelial cells. This causes very thick, sticky mucus to build up in the lungs, pancreas, and other organs. The most common mutation is F508del. Symptoms include issues with digestion, lung function decline, and infections. Diagnosis is made through sweat chloride tests, genetic testing, and evaluation of clinical features. Treatment focuses on airway clearance, antibiotics, nutrition support, and newer CFTR modulator drugs that target specific mutations. With advances in care, people with cystic fibrosis now live well into adulthood.

1. CYSTIC FIBROSIS
Dr Jo Martin Kuncheria
Pediatrics

2. Introduction
Family run genetic disorder of epithelial transport affecting
fluid secretion in exocrine glands & epithelial lining of
respiratory , gastrointestinal & reproductive system
Disfunction of CFTR protein (1480 AA ) – epithelial cells of
airways, GIT,sweat glands, genitourinary system)
Most prevalent mutation F508del
Inheritance :AR
Prevalence in western countries 1: 2500 new born
Asians 1: 31000 live birth

3. PATHOPHYSIOLOGY
• CFTR - ion channel that moves chloride and
bicarbonate ions into the extracellular space.
• This adjusts the viscosity of mucous and other
fluids that line the lungs, intestines, pancreas, bile
ducts of the liver, and reproductive tracts.
• In cystic fibrosis , the mucous becomes thick and
hard to move

4. F508 MUTATION
• Mutation in the gene for the CFTR protein. The
mutation deletes three nucleotides that code for
phenylalanine.
• Causes a person to produce CFTR without
phenylalanine
• CFTR protein breaks down because of its
abnormality

5. pathophysiology

6. Organs Affected
• Lungs
• Pancreas
• Liver
• Intestines
• Sinuses
• Sex Organs

7. Clinical manifestations

8. Nutritional S/S
• Failure to Thrive
• Edema
• (hypoproteinemia)
• Chronic pancreatitis
• Cirrhosis
• Pancreatic exocrine
insufficiency
• Steatorrhea

9. New born screening
• Immune reactive trypsinogen / DNA testing on blood
spot- single detected mutation
• Confirmatory sweat analysis
• Screening test is 95% sensitive (median age of
diagnosis 1m)
• Improve early nutritional deficiencies, long term
growth & improve cognitive function

10. Diagnostic criteria
• Two elevated sweat chloride on separate days(≥60 mEq/L) plus
any one
• Presence of typical clinical features including respiratory &
Gastrointestinal
• History of cystic fibrosis in sibling
• Laboratory evidence for CFTR dysfunction
• Identification of 2 CFTR mutations
• An abnormal nasal potential difference measurement

12. Sweat chloride test

13. Diagnosis
• Gold standard for
diagnosis is the
sweat chloride test
(pilocarpine
iontophoresis)
• Test used to induce
sweating then the
sweat electrolytes are
measured

14. Positive Sweat chloride test
• For infants up to 6 months of age
– Chloride levels of:
– Less than 29 mmol/L=CF is very unlikely
– 30-59 mmol/L= CF is possible
– Greater than 60 mmol/L= CF to be diagnosed
• For people older than 6 months of age
– Chloride levels of:
– Less than 39 mmol/L= CF is very unlikely
– 40-59 mmol/L= CF is possible
– Greater than 60 mmol/L= CF to be diagnosed

15. Diagnosis
Other Tests
• Prenatal Screening
– Genetic testing can show if the fetus has CF
– Amniocentesis- removing small amounts of fluid from the sac around the baby
– Tested to see if the CFTR genes are normal
– Chorionic villus testing- removing a tissue sample from placenta to test for CF
• Chest x ray
• Sinus x-ray
• Lung function tests
• Sputum culture
• Trypsin and chymotrypsin in stool

16. Mutation analysis
Gene for cystic fibrosis has been identified on chromosome 7
Caucasian populations the commonest mutation is DF508 and accounts for
approximately 70% of all CF genes
Over 90% of CF mutations can be identified if a patient’s blood is tested for
a panel of 70 mutations in the general population of the United States
The panel of most common mutations for Indian patients is not yet known.
Small studies indicate that the proportion of patients with DF508 may be 19-
44%
Facilities for identification of CF mutations are not readily available in India.
However attempts should be made to identify mutations by sending the
patient or a blood sample to centers carrying out CF mutation testing for
further evaluation where appropriate.

17. Abnormality in blood biochemistry
and acid base status
• Low or low normal serum sodium.
• Metabolic alkalosis and hypochloremia.
• Anemia can occur along with hypoalbuminemia and
ascites as a result of vitamin E deficiency and
protein malabsorption.
• Also the routine blood count may show signs
suggestive of bacterial infection

18. Airway bacterial colonization and
infection
• Isolation of P. aeruginosa or Burkholdelia cepacia from
sputum or cough swabs is suggestive of a CF diagnosis
• All children suspected of having CF should have
specimens sent for microbiological culture
• Older children should have sputum specimens sent
regularly for culture.
• Young children and infants secretions from the airways
obtained after saline inhalation and physiotherapy or
a cough swab should therefore be cultured.

19. Pancreatic function tests
• Cystic fibrosis is the commonest cause of exocrine
pancreatic deficiency below 20 years of age
• Measurement of stool pancreatic elastase-1 has been
reported as a sensitive and specific test
• Semi quantitative estimates of intestinal fat
malabsorption can be made using either faecal
microscopy or faecal steatocrit
• Glycosylated hemoglobin, urine glucose levels ,OGTT
are sufficiently sensitive

20. Obstructive azoospermia
• In post pubertal boys, a semen analysis for
azoospermia can be carried out.
• Sperms are absent in up to 98% of men with
cystic fibrosis

21. Radiological imaging
• X-ray films of chest may show hyperinflation, peribronchial
thickening, cystic changes and lobar or segmental collapse.
• The findings on CT include cystic or varicose bronchiectasis,
peribronchial thickening, segmental collapse, mucus
impaction and sub pleural bullae formation.
• The imaging studies of sinuses may show delayed
pneumatization or mucosal thickening.
• These investigations are more useful for monitoring
diagnosed patients.

22. Pulmonary function test
• Primary used for research
• Can be tried from 4y , routinely by age 6.
• FEV1 correlate most
• Gradual decline avg 2-3% per year
• Restrictive changes denoted by declining TLC, VC –
extensive lung injury ,fibrosis and are late findings

23. TREATMENT
• No cure for cystic fibrosis
• Treatment ease symptoms and reduce complications
• Goal :
preventing /controlling lung infection
loosening & removing mucus from lungs
preventing /treating intestinal blockage
providing adequate nutrition

24. MEDICATIONS
• Antibiotics
• Mucous thinning drugs to cough out mucus
• Bronchodilators to keep airway open
• Corticosteroids to reduce inflammation in ABPA,
severe asthma
• Oral pancreatic enzymes for digestion- reduce but
not correct stool fat & nitrogen loss

25. Pulmonary therapy
• Inhalational therapy –
Human recombinant DNAse(25mg) , single daily aerosol dose
Enzymatically dissolves extracellular DNA released by
neutrophils, improves symptoms
Improvement is sustained for 1y or longer with continuous
therapy
Nebulized hypertonic saline – hyperosmolar, draw water into
airway and rehydrate mucus. 2-4 times daily increase mucous
clearance

26. Airway clearance therapy(Chest physiotherapy)
• Inflatable vest: a device worn around the chest that
vibrates at high frequency
• Airway clearance with chest percussion
• Recommended 2- 4 times a day
• Breathing devices: a tube or mask to exhale while
performing breathing exercises
• Cessation of PT results in worsening of lung function
within 3 wks

27. Physical Therapy
• Postural Drainage and Percussion
– 4-5 minutes in 2-3 positions

28. Physical Therapy
• Postural Drainage and Percussion
– 4-5 minutes in 2-3 positions

29. Breathing Techniques
• Positive Expiratory Pressure
– Masks increase force required to exhale

30. Mechanical Devices
• Mechanical Percussor

31. Mechanical Devices
• Inflatable Vest

32. Antibiotic therapy
• Mainstay of treatment to control infection
• To delay lung damage
• Intermittant short course 1 antibiotics to continuous 1 or 2 antibiotics
needed
• Dose may be 2-3 times amount needed for normal infection
• Usual course of therapy 2 wks
• Common organisms – MRSA, MSSA, nontypeable H.influenza, P.
Aeruginosa, other gram negative rods
• Azithromycin 3 times a week improves lung function in chronic P.
aeruginosa

33. Aerosolized antibiotic therapy
• Tobramycin, Aztreonam- 1m then off 1m
• Liposomal amikacin, levofloxacin
• All effective against P . Aeruginosa
• For eradication of organism, reduce symptoms,
improve pulmonary function, decrease the
occurrence of pulmonary exacerbation

34. Intravenous antibiotic therapy
• Not responding to oral antibiotics
• Ideal duration of treatment unknown
• Shows response in 1wk , extent treatment to min 2 wks
• 2 drug therapy
• Infection control in health setting to prevent spread of resistant bacterial
organisms
• H. influenza,P.Aeruginosa,Burkholderia- mox ciprofloxacin, azithro, erythromycin
• S. aureus- vancomycin , naficillin, dicloxacillin, clindamycin,linezolid
• P.Aeruginosa- tobra, amikacin,piperacillin,Meropenem

35. Bronchodilator therapy
• Reactive airway obstruction occurs in association
with frank asthma , ABPA
• Reversible obstruction – improvement ≥ 12% in
FEV1 or FVC after inhalation of bronchodilator
• 5-10%(physiologic response)

36. Antiinflammatory agents
• Corticosteroids useful for ABPA & severe asthma
• Ibuprofen with peak serum concentration 50-
100mcg – slowing of disease progression
• Macrolide antibiotics have antiinflammatory effect-
3 days / wk reduce pulmonary exacerbation
especially with pseudomonas infection

37. CFTR modulator therapies
• Ivacaftor:
– Activates CFTR G551D mutant protein , a class 3
CFTR mutation
• Ivacaftor & Tezacaftor indicated for ≥ 12y with 1 or 2
phe F508 del mutation
• Ivacaftor with Lumocaftora connector , stabilise
misfolded F 508
Available for > 6y old with F508 mutation

38. Surgical procedures
• Endoscopy & Lavage : Mucus suctioned from
obstructed airway by endoscope
• Bowel surgery: may need surgery to remove
blockage in bowel.

39. • Aerobic training is essential to increase VO2
peak
• Median survival after lung transplantation is
2.84 years, last resort

40. MNT in Cystic Fibrosis
• Monitor ongoing nutrition status
• Supply pancreatic enzyme replacement therapy
(PERT)
• Meet increased energy requirements
• Provide vitamin/mineral supplements

41. Pancreatic Enzyme Replacement Therapy..... (PERT)
• PERT is first step taken to correct maldigestion
/malabsorption.
• Microspheres are taken orally, designed to
withstand the acidic stomach, and release
enzymes in the duodenum for digestion of
macronutrients.
• Monitoring fecal elastase, fecal fat, or nitrogen
balance may help evaluate adequate enzyme
dosage and efficacy.

42. Macronutrient needs
• CHO needs:
 needs change as disease progresses
 CF patients may develop lactose intolerances
• Protein needs:
 Slightly increased, but 15--20% should meet DRI for protein
requirements
• FAT needs:
 CF patients have increased fat needs; 35-40% of total kcals
(especially sources of EFA)
 Check for EFA deficiencies in regular lipid profiles
 Also watch for fat-soluble vitamin deficiencies since there is likely
fat malabsorption.
 Fat intolerances found in stool samples.

43. Specific Vitamin Recommendations
• Water soluble vitamins:
 Adequately absorbed; requirements are met by diet and
multivitamin/mineral supplement.
• Fat soluble vitamins:
 Usually inadequately absorbed (fat malabsorption)
 Low serum vitamin A - impaired mobilization and transportation from
liver.
 Decreased vitamin D - related to decreased bone mineral content
 Low vitamin E - hemolytic anemia and abnormal neurologic findings.
 Vitamin K deficiency - secondary to antibiotics or liver disease.

44. Mineral needs
• Intake should meet CF patients gender / age
recommendations.
• Minerals to watch:
• Na requirements increase because increased
losses in sweat..

45. Minerals to watch (cont)
• Calcium - watch for decreased bone mineralization
during childhood esp.
• Iron - check yearly in children, and monitor hgb
and hct
• Zinc - decreased absorption and increased zinc in
stools (esp in children and infants). Also related to
vitamin A levels.

46. PROGNOSIS
• Remains life limiting disorder
• Survival dramatically improved – remain relatively
healthy into adolescence and adulthood
• Median cumulative survival 40y
• Should not restrict their activities
• Anxiety and depression are prevalent – both is now part
of comprehensive care
• With appropriate medical & phychosocial support
children with CF cope well

47. Thank you