Know the clinical features of cystic

fibrosis.

Know how CF is inherited.

Be familiar with criteria to diagnose

CF.

Become aware of the myriad of

treatments used in CF.

A multisystem disease

Autosomal recessive inheritance

Cause: mutations in the cystic fibrosis

transmembrane conductance

regulator (CFTR) gene

➢ chromosome 7

➢ codes for a c-AMP regulated chloride

channel

Very salty-tasting skin

Appetite, but poor

growth & weight gain Coughing, wheezing ,at times

with phelgum &

shortness of breath

Lung infections, e.g.

pneumonia/bronchitis

➢ greasy, bulky stools or

difficulty in bowel movements

6

C Chronic respiratory disease

F Failure to thrive

P Polyps

A Alkalosis, metabolic

N Neonatal intestinal obstruction

C Clubbing of fingers

R Rectal Prolapse

E Electrolyte in sweat

A Aspermia / absent vas deferens

S Sputum – S.aureus/P.aeruginosa

CFTR controls

chloride ion

movement in

and out of the

cell.

The CFTR gene is located on

the long arm of chromosome 7.

There are 1604 mutations in

CFTR listed on the CFTR

mutation database

The most common mutation is

Δ F508---70% CF alleles in

caucasians.

➢ Defects in (CFTR), - encodes for a protein that functions as chloride channel & regulated by (cAMP).

➢ Abnormalities of cAMP-regulates chloride transport

➢ Defective CFTR - decreased secretion of chloride and increased re-absorption of sodium and water

➢ Reduced height of epithelial lining fluid

➢ Decreased hydration of mucus - that is stickier to bacteria

➢ Result in viscid secretions

CF:

Clinical Signs

Cystic fibrosis affects entire body15

• Lungs and sinuses

• GI, liver and pancreas

• Reproductive system

• Nutritional

Endobronchial disease

➢ Cough / sputum production

➢ Air obstruction---wheezing; evidence

of obstruction on PFTs

➢ Chest x-ray anomalies

➢ Digital Clubbing

Sinus disease

➢ Nasal Polyps / sinusitis/ hemoptysis

Hyperinflation

Peribronchial

cuffing

Bronchiectasis

Diffuse fibrosis

Atelectasis

Mucous in the airways cannot be easily cleared from

the lungs.

Presentation of Disease inlung

Benign lesions in nasal

airway(5-20 yrs)

If large - associated with

nasal

obstruction, drainage, heada

ches, snoring

associated with chronic

inflammation

need surgical intervention

High recurrence rate

Intestinal abnormality➢ Meconium ileus (15-20% of newborn with CF)

➢ Distal intestinal obstruction syndrome (DIOS)

➢ Intussusception / Rectal prolapse

➢ Volvulus / atresia / meconium peritonitis

Hepatobiliary disease➢ steatorrhea

➢ Focal biliary cirrhosis

➢ Multilobular cirrhosis

Pancreatic endocrine dysfunction➢ Cystic fibrosis related diabetesCy

stic

Fib

ro

sis

Focal inspissation ofbile

➢ Obstructs biliary ductules

Second leading cause of death inCF

Prevalence 9-37%

Spectrum of disease➢ increased liver enzymes

➢ biliary cirrhosis

➢ portal hypertension

➢ GB stones

Cy

stic

Fib

ro

sis

Pancreatic insufficiency➢ ―cystic fibrosis of the pancreas‖---mucus

plugging of glandular ducts

➢ Chloride impermeability affects HCO3-

secretion and fluid secretion in pancreatic

ducts

Pancreatic enzymes stay in ducts and are activated

intraductally

➢ Autolysis of pancreas

➢ Inflammation, calcification, plugging of ducts, fibrosis

➢ Malabsorption

Failure to thrive

Fat soluble vitamin deficiency(ADEK)

Cy

stic

Fib

ro

sis

Men➢ Abnormal embryologic development of the

epididymal duct and vas deferens-- incomplete

or absent

➢ Congential bilateral absence of vas deferens—

97-98% of men with CF

Women

➢ Lower fertility rate than non-CF women

➢ Viscid mucoid cervical secretions of low

volume in women with CF

Pregnancy and CF:

➢ Goss et al, 2003---no significant difference

in survival in women who became

pregnant with CF compared to women

who did not become pregnant (after

adjusting for disease severity)➢ Fertility is mildly impaired

CF:

Diagnostic Methods

One or more clinical features of CF

OR

A history of CF in a sibling

OR

A positive newborn screening test

Plus

➢ Laboratory evidence for CFTR dysfunction: Two elevated sweat chloride concentrations obtained on separated days

OR

Identification of two CF mutations

OR

An abnormal nasal potential difference measurement

First described by Gibson and Cooke,1950

➢ Chemical that stimulates sweating placed under electrode pad; saline under other electrode pad on arm

➢ Mild electric current is passed between electrodes

➢ Sweat collected(75-100gm)

➢ Positive Sweat chloride: 60-165 meq/L

➢ Borderine sweat chloride: 40-60 meq/L

➢ Normal sweat chloride:

0-40

False positives:➢ Hypothyroidism

➢ Addison disease

➢ Ectodermal dysplasia

➢ Glycogen storage disease

➢ Edema

➢ Malnutrition

➢ Lab error (evaporation or contamination of sample)

False negatives:➢ Edema

➢ Malnutrition

➢ Some CF mutations

➢ Sample diluted

DNA testing- 30–80 of CFTR mutations.This identifies ≥90% who carry 2 CF

mutations

increased potential differences across

nasal epithelium with reference to

forearm

loss of potential

difference with topical amiloride

application is more in CF

Pancreatic function

➢ Fat estimation in stool

➢ OGTT

Pulmonary radiologic finding

Pulmonary function

Microbiologic studies

➢ More than 1604 mutation identified

➢ 2 CFTR mutations in association with

symptom is diagnostic

Goal: early diagnosis may be

associated with better nutritional

outcome

➢ Immunoreactive trypsinogen usually first followed by

either sweat or DNA testing

CF:

Treatment

Pulmonary Therapy

Inhalation Therapy

Airway Clearance Therapy

Infection-Antibiotic Therapy—

➢ Oral

➢ Aerosolized

➢ IV

Bronchodilator

Antiinflammatory

Endoscopy & lavage

Nutrition➢ Diet

➢ Pancreatic enz replacement

➢ Vitamins

Gastrointestinal & Rx of complication

Infertility

Others-

➢ Nasal polyp

➢ Rhinosinusitis

➢ Salt depletion

➢ Growth & maturation

Social Issues

Atelactasis

Hemomptysis

Pneumothorax

Allergic aspergilosis

Nontuberculous mycobactria infection

Bone & joint complication

Sleep-Disordered Breathing

Acute Respiratory Failure

Chronic Respiratory Failure

Heart Failure

Nutritional therapy.

➢ Follow nutrition parameters closely

➢ Pancreatic enzymes

➢ Vitamin supplementation

➢ Other nutritional supplementation

➢ Tube feedings

➢ High calorie supplemental shakes,

formulas

Meconium Ileus.

Distal Intestinal Obstruction Syndrome

Gastroesophageal Reflux

Rectal Prolapse

Heptobiliary Disease

Pancreatitis

Hyperglycemia.

Nasal Polyps

Rhinosinusitis.

Salt Depletion

Growth and Maturation Surgery.

Follow nutrition parameters closely

Pancreatic enzymes

➢ Porcine extract, 2000U/kg/meal

➢ TheraCLEC-Total, micro derived under

Vitamin supplementation-➢ ADEK

Other nutritional supplementation➢ Tube feedings

➢ High calorie supplemental shakes, form

Microsurgical epididymal sperm aspiration coupled plus in vitro

technology

Percutaneous epididymal sperm

aspiration

Testicular sperm extraction

Maternal genetic testing

Quality of life

➢ Frequent hospitalizations

➢ Time spent on therapies

➢ Morbidity from disease

➢ Restrictions secondary to disease

Adherence to therapies

Family planning

End of lifeissues

Mucolytic-

➢ Pulmozyme -to thin mucus

➢ Dornase alfa- enzyme hydrolyse DNA-

improve airway clearance

Antibiotics- Inhaled TOBI

➢ Cayston- Aztreonam, monobactem AB

inhaled for p. aeruginosa

Antioxidant

ACTs loosen thick, sticky lung mucus➢ move mucus from small to large airways to be coughed or huffed

out.

Coughing is the most basic ACT.

Huffing is a type of cough. involves taking a

breath in and actively exhaling. It is more like

―huffing‖ onto a mirror or window to steam it up

Chest Physio Therapy

Oscillating Positive Expiratory Pressure (Oscillating

PEP) an ACT where the person blows all the way out

many times through a device named

FlutterTM, AcapellaTM, CornetTM and Intrapulmonary

Percussive Ventilation (IPV). Breathing with devices

vibrate & dislodge.

High-frequency Chest Wall Oscillation

Positive Expiratory Pressure (PEP)

Active Cycle of Breathing Technique

(ACBT) It gets air behind

mucus, lowers airway spasm and clears

mucus.

Thoracic expansion exercises – deep breaths in.

➢ done with chest clapping or vibrating,

followed by breathing control.

Forced expiration technique – huffs of varied

lengths with breathing control.

Autogenic Drainage (AD) means ―self-

drainage.‖

➢ uses varied airflows to move mucus.

➢ aims to reach very high airflows in different

lung parts. This moves mucus from small to

large airways.

Lung Transplant

➢ 900 LT /year in USA

➢ 1600 received LT from 1991

➢ 2003– 17 pts received from living donor & 126 from cadaveric lung transplant

Gene therapy is the use of normal DNA to "correct" for the damaged genes that cause disease.

In the case of CF, gene therapy involves inhaling a spray that delivers normal DNA to the lungs.

The goal is to replace the defective CF gene in the lungs to cure CF or slow the progression of the disease.

ThankYou!