Cystic Fibrosis

Dr. K Venugopal

Consultant Pulmonologist
Sooriya Hospital
Chennai
India

Beware the salty child

for they will surely die
(German folklore)

BACKGROUND
Cystic fibrosisCystic fibrosis is an inherited disease that
causes thick, sticky mucus to build up in the lungs
and digestive tract. It is the most common type of chronic
lung disease in children and young adults, and may result in
early death.

CYSTIC FIBROSIS
The most common lethal inherited disease affecting
Caucasians (not uncommon in Asians)
Autosomal recessive
Incidence 1:2500 Caucasian populations
Carrier frequency 4%
Single gene disease (CFTR 7q)
Gene discovered 1989

CFTR MUTATIONS
> 1000 mutations described
F508 accounts for 70%
Certain mutations occur more frequently in
particular ethnic groups
Commercially available genetic tests screen for the
31 most common mutations(accounts for 85% of the
mutations).

WHAT IS CF?
Cystic Fibrosis is a
genetic disease that
affects a number of
organs in the body
(especially the lungs and
pancreas) by clogging
them with thick, sticky
mucus

Overview
Millions of Americans carry the defective CF gene, but do not
have any symptoms. That's because a person with CF must inherit
two defective CF genes -- one from each parent. An estimated 1 in 29
Caucasian Americans have the CF gene. The disease is the most
common, deadly, inherited disorder affecting Caucasians in the
United States. It's more common among those of Northern or
Central European descent.

CF IN INDIA
CF was thought to be extremely rare in India
It is uncommon in non-whites (Fraser & Pare, Diseases of
the chest) Teaching
CF is probably far more common in people of Indian
origin than previously thought Reality

CF is under diagnosed or missed in majority of cases

CF MAGNITUDE OF
PROBLEM
Caucasian 1:2000 1:2500
African 1:784 1:13924
Asian 1:10000 40,000

Facts
Most children are diagnosed with CF by their 2nd birthday. A
small number, however, are not diagnosed until age 18 or older.
These patients usually have a milder form of the disease.

Chance of Occurrence
Both parents carriers of CF
1 out of 4 having a child with CF

Punnett Square

Punnett Square
C
C

CC

Cc

Cc

cc

Cystic Fibrosis=c

CF CLINICAL FEATURES
(LUNG)

Thick viscid secretion

in respiratory tract
Bacterial
colonization
Mucosal inflammation
Mucosal hypertrophy
Recurrent LRTI
Bronchiectasis

CF CLINICAL FEATURES (PANCREAS)

Thick viscid secretions in

Pancreas
Pancreatic insufficiency
Meconium ileus
Meconium peritonitis
Steatorrhea
Failure to thrive

CF Clinical Features

Increased chloride
content in sweat
Salty taste on kissing
Increased salt wasting
Dehydration in hot
weather
Salt craving

Salties and Wrinklies

Beware the salty child for they will
surely die (German folklore)

Beware the wrinkly child as well.

Classical Clinical Features

ENT:

Chronic Sinusitis
Nasal Polyps

Lungs:

Cough and sputum

Airflow obstruction
Recurrent infection (Pseu, S. aureus)

GI:

Pancreatic insufficiency (malnutrition)

Pancreatitis (PS)
Meconium ileus and DIOS
Biliary cirrhosis and portal hypertension

Sex organs: Obstructive azoospermia (CBAVD)

Adapted from Welsh and Smith. Sci Am. 1995;273:52-59.

Lung Damage

Meconeum Ileus

Rectal Prolapse

Unusual Manifestations
Severe hypokalemia, hyponatremia with
alkalosis: pseudobarter syndrome

Meconium ileus equivalent

Sterility in males: Azoospermia alone

CF RADIOLOGY
Chest Skiagram

Hyperinflation
Peribronchial thickening
Mottled shadows
Ring shadows
Large shadows Lung collapse
Hilar adenopathy

Chest CT

Cystic Bronchiectasis
Peribronchial thickening
Mucoid impaction
Areas of centrilobular opacities
Sub pleural Bullae

Cystic fibrosis reported in Indian literature

Authors

No. of patients

Diagnosis

Ref

Bhakoo et al.1968

01

Histopathology

13

Mehta et al. 1968

13

Sweat test

14

Mehta et al.1969

06

Sweat test

15

Devi et al.1969

04

Sweat test

16

Gupte et al.1970

06

Sweat test

17

Reddy et al.1970

12

Autopsy

18

Goodchild1974

03

Sweat test

10

Maya PP et al. 1980

03

Sweat test

22

Deivanayagam CN et al. 1990s

64

Sweat test

24

Bowlers 1993

09

Sweat test

11

Spencer et al. 1994

13

Sweat test

Powers et al. 1996

20

Sweat test

Kabra et al. 1996

15

Sweat test, Mutations

Kabra et al. 1996

13

Sweat test

Kabra et al. 1999

62

Sweat test, Mutations

12

Kabra et al. 2000

24

Sweat test, Mutations

CF reported from India

CYSTIC FIBROSIS CHENNAI STUDY

1985 - 2011
Total number of sweat test performed 4900

Total number of cases with elevated sweat chloride

170
Male 98
Female 72
Mean age at diagnosis 46 months

CF IN INDIA
Total diagnosed till 2011:
470
Died
110
Adult CF
60
Oldest patient:
40 years

PROBLEMS IN DIAGNOSIS
Teaching in Medical schools
Awareness Physician
Parents
Sweat Testing only few centers in India
Delayed Diagnosis
Advanced Disease
Poor Resources

WHEN WE SUSPECT ?
Child presenting with recurrent pneumonia
Meconium ileus
Malabsorption: pancreatic origin; significant
steatorrhoea, oil droplets in stools
Metabolic alkalosis, hyponatremia, hypokalemia,
hypochloremia
Pseudomonas in sputum or respiratory secretions
Child treated as asthma; develops clubbing

WHEN WE SUSPECT ?
Syndrome complex
Bronchiectasis
Sinusitis
Difficult wheeze
Abdominal pain
Signs of malabsorption
Male infertility

CASE SCENARIO I
A 2 day old, healthy term baby was noticed
to have abdominal distention at 24 hrs of life.
This was followed by bile stained vomiting.
What are your thoughts?

POSSIBILITIES INCLUDE..
Imperforate anus
Gi malformations-Atresia, webs, bands, volvulus,
duplications
Hirchsprungs disease
Sepsis
Small left colon (IDDM)
Meconium ileus

Meconium not
passed
Anus patent
P/A- Doughy
abdomen, firm
palpable mass freely
mobile

A contrast study
shows :

A specimen of intestine opened showing a thick, inspissated,

long, meconium plug

MECONIUM ILEUS (MI)- HARD

FACTS
10-15% Of CF have Ml, 90% of MI have CF
Antenatal diagnosis possible
Uncomplicated(60%) relieved by diagnostic contrast
enema (Gastrograffin) which also reveals microcolon
Complicated(30-40%) surgical intervention
Complications - perforation & electrolyte imbalance
Mortality -10-20%

NEONATAL JAUNDICE IN CF
Occurs in < 5% of patients
Associated with MI in 50% .
Conjugated jaundice + / - hypoalbuminemia.
Median duration of jaundice-7 months.
Consider investigations to exclude biliary atresia.
Treatment - ursodeoxycholic acid.
Good medium term prognosis, if no co-existent
problems.

MORAL OF THE STORY

Every time you see a newborn with
meconium ileus or with neonatal hepatitis

Think CF !

CASE SCENARIO - II
Kabir, a 3 year old is brought for fever and a
rapid respiratory rate since 3 days.
On examination he has a grunt and a respiratory
rate of 44/min.
On auscultation he has an increased vocal
resonance in the right mammary and infra
mammary area.

What are your thoughts?

His X ray shows

Not again,says his mother. He had a pneumonia three months ago .

Here are his X rays .

RECURRENT PNEUMONIADIFFERENT LOBES

Aspiration
Asthma
Left to right shunts
Immunodeficiency
CF
ABPA

On review, in the month of October, Kabir had been

admitted to hospital with dehydration
His baseline investigations were:

Hb 10.2 TC 15300 P70 L30.

S Na-124meq/L , K 2.8meq/L, Cl 86meq/L

This is pseudo Bartters syndrome

In a setting of pneumonia with
hyponatremic, hypokalemic hypochloremic
metabolic alkalosis
Think CF !

HOW WE CONFIRM DIAGNOSIS

Demonstration of raised sweat chloride is the
primary diagnostic test for CF

Sweat chloride > 60 mEq/l on two occasions with

clinical findings suggestive of CF

Demonstration of two mutations of CF

SWEAT TEST
Gibson & Cooke Method:
Pilocarpine iontophoresis is the only acceptable sweat
test procedure (Gibson & Cooke 1959)
Sweat glands stimulated for 15 mins with electrical
current 0.5mA to 4mA
Positive electrode charged with 2% soln: of pilocarpine
nitrate.
Sweat collection time 30 mins, on to 5cmX 5cm filter
paper. Minimum Sweat 75 to 100 mg
Indigenously made equipment is available.

SWEAT TEST
< 40mmol/L
- Normal
40 60 mmol/L
- Borderline
60 mmol/L
- Consistent with CF
>150mmol/L
- ?Contamination
? Error

TREATMENT OPTIONS..
Physiotherapy and Bronchodilators are
important components of care
Antibiotic therapy.

Pancreatic enzyme replacement therapy

Vitamins and minerals

Oral corticosteriods/macrolides.
Hypertonic saline
Immunization

Expectations
Disease registries now show that 40% of patients with cystic fibrosis are
over age 18.
Today, the average life span for those who live to adulthood is
approximately 35 years, a dramatic increase over the last three decades.
Death is usually caused by lung complications.

IMPROVING OUTCOMES IN CF
PATIENTS
Creating Awareness

Early diagnosis New born screening

Preserve the lung function

Nutritional support

Infection control/ Physiotherapy airway clearance

Transition from pediatric to adult care

CONCLUSION
CF does occur in India
Precise Magnitude not known needs documentation
Clinical features are similar, few atypical features
High colonisation with resistant Pseudomonas,
multiple morphotypes in some patients
Diagnosis is missed / delayed
Indigenous sweat testing is reliable method
Genotype is different
Screening strategy for mutations costly
Awareness creation through teaching module