Cystic FibrosisVinay Kumar M176312990003A chronic, progressive, and frequently fatal genetic disease of the bodys mucus glands.Affects the respiratory and digestive systems in children and young adults.An average person has a lifespan of 40 years with the right treatment.

Cystic Fibrosis: How Common?Cystic Fibrosis is the most common serious inherited diseaseThe most common cause of exocrine pancreatic insufficiency in childrenThe most common cause of chronic lung disease in childrenAutosomal recessiveIncidence 1:3200 live births (Caucasians)*1:28 Caucasians are carriers

Cloning of the Normal GeneIn 1990, scientists cloned the normal gene, adding it to the CF cells in the laboratory where it corrected the defective transport mechanism.

CausationCystic Fibrosis is caused by a defective CFTR gene which codes for a Na+ and Cl- transporter found on the surface of epithelial cells of lungs and other organs. As many as 1300 mutations in the CFTR gene have been observed worldwide.The severity of the disease is directly related to the characteristic effects of the particular mutations that have been inherited by the individual sufferer.

PathophysiologyCFTR mutations affect epithelial cells, thus affecting:Airways (sinuses, lungs)Pancreas (endocrine and exocrine)GI tract (liver/biliary system, intestines)Reproductive organsSkin

CF LungChloride does not get into airway; more sodium leaves; mucus is thick

CF: Lung lesions

Result from a combination of:Abnormal concentrations of ions and water in the airways. Increased binding of bacteria.Uncontrolled oxidation of fatty acids in the cell membranes.

CF: SymptomsThe 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 ManifestationsRespiratory TractCough is the most constant symptom.WheezingRecurrent chest infectionCyanosis is a late signAtelactasis, hemoptysis, pneumothorax, and cor pulmonaleSinusitis, nasal polyps

Clinical Manifestations.Intestinal TractMeconium ileus 10-20%Meconium plug syndrome (meconium ileus equivalent)more than 85% of patients showed evidence of maldigestion from exocrine pancreatic insufficiency.Intussception

Clinical Manifestations4. Bile or acid reflux with oesophagitis5. Sub acute appendicitis6. Rectal prolapse7. Failure to thrive8. Fat-soluble vitamin deficiency manifestation.

Clinical ManifestationsBiliary TractBiliary cirrhosis symptomatic in 2-3% .Ascitis, Jaundice, hematemesis, esophageal varicesNeonatal hepatitis

Clinical ManifestationsDiabetes Mellitus 8% after the age of 10.95% of males are azoospermic because of failure of development of wolffian duct structure.Secondary amenorrheaCervicitisHypochloremic alkalosis

Presenting features of more than 20,000 CF patients in USA

Feature%Acute or persistent respiratory symptoms50.5Failure to thrive42.9Abnormal stool35.0Meconium ileus, Intestinal obstruction18.8Family history16.8Electrolytes, Acid-base abnormality5.4Rectal prolapse3.4Nasal polyps, sinus disease2.0Hepatobiliary disease0.9Other1-2

Diagnosis of Cystic Fibrosis Sweat test Blood tests Chest x-rays

Sputum cultures Pulmonary function tests Stool evaluations Pancreatic function tests

The Sweat Test

Gold Standard for testing over 40 years - painless - inexpensive - gives definite answers

The Sweat Test

Cl- 60 mEq/L

40-60 mEq/L ?

MANAGEMENTCystic Fibrosis: A Disease for a Multidisciplinary Team

CF Team

Clinic coordinatorSocial workerRespiratory therapistNurseRegistered dietitian

MANAGEMENTThe Principles:To Allow the child and his family, as far as possible, to enjoy a normal lifestyle.To minimize the emotional problems that invariably develop.To prevent, or at least retard as far as possible, progressive lung disease.To achieve optimal nutrition and maintain normal growth

Management of Lung DiseaseThe aim is:Clear secretionsControl infection

Management of Lung DiseasePHYSIOTHERAPY and physical activityChest physiotherapyPostural drainagePositive expiratory pressureAgents to promote airway secretion clearance-Hypertonic saline-DNase I (dornase alfa) -N-acetylcysteine

Management of Lung Disease

ANTIBIOTIC THERAPY

1.IV Antibiotics2.Aerosolized Antibiotics3.Oral Antibiotics

AntibioticsOften unable to eradicate the organismDetermining optimal delivery mode for a drug is difficultCF patients require higher dosesAltered volume of distributionRapid clearance of drugs

IV AntibioticsIndications:Severe exacerbations Bacterial resistance to all orally administered antibiotics Failure of oral antibiotic therapy to resolve symptoms

Management of Lung DiseaseBRONCHODILATOR THERAPYBeta2 agonist

ANT-INFLAMMATORY AGENTSCorticosteroids for Bronchopulmopnary aspergillosis

TREATMENT OF PULMONARY COMPLICATIONS

Management of G.I.T. ManifestationNutrition is closely tied to overall healthMalnutrition in CF associated withStunted growthPubertal delayDeterioration of lung functionEarly death

G.I.T. ManagementPancreatic enzyme replacement (enteric coated granules)Lipase, Amylase, ProteaseNot more than 2500 lipase units/kg/meal

Vitamin and Mineral supplementsFat-soluble vitamins (A, D, E, K)

G.I.T Management Treatment of G.I.T complications-Meconium ileusMeconium ileus EquuivalentGERRectal ProlapseLiver Disease

The most common complications are chronic respiratory infectionsPneumonia, recurrent Pneumothorax Coughing up blood Chronic respiratory failure Cor pulmonale Liver disease Diabetes Osteoporosis and arthritis