Cystic fibrosis


    • Severely life-shortening genetic disease

    • Results from abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR)

      • Chloride channel found in cells lining the lungs, intestines, pancreatic ducts, sweat glands, and reproductive organs.

    • There are over 1500 known disease-causing mutations that interrupt various stages of CFTR synthesis and function

    • The most common clinical manifestations are:

      • pancreatic dysfunction, resulting in calorie malabsorption

      • lung disease, resulting from a cycle of mucus retention, infection, and inflammation

Risk Factors

    • FHx

    • Carrier status of parents

Differential diagnosis

    • Primary ciliary dyskinesia

      • Ciliary biopsy will demonstrate ultrastructural abnormalities of respiratory cilia.

    • Primary immunodeficiency

      • Measurement of lymphocyte number and function, neutrophil function, and immunoglobulin levels.

    • Chronic aspiration

      • Modified barium swallow or gastric emptying studies may be useful

      • May also be positive in patients with CF.

  • Failure to thrive

      • Sweat test should be negative if CF is not the cause

      • However, severe malnutrition causes a falsely elevated sweat test.

  • Coeliac disease

      • Intestinal biopsies.

    • Protein-losing enteropathy

      • Intestinal biopsies.


    • There are about 8500 cases in the UK, 30,000 cases in the US and 70,000 worldwide. [4] [5]

    • The incidence among white people is about 1/3000

    • The incidence is lower among people of African, Hispanic, and Asian descent.

    • It is most common among people of European descent. [6]

    • One study suggests that the incidence may be decreasing since the institution of newborn screening. [7]

    • Lung disease is the most common cause of morbidity and mortality.


    • Genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR)

      • An anion channel found in the apical membrane of epithelial cells.

    • Patients may be either homozygous or heterozygous with respect to CFTR mutations.

      • Carriers of one CFTR mutation and one normal CFTR allele do not demonstrate disease in most cases.

Clinical features

    • Key Findings

      • Common

        • presence of risk factors

        • positive newborn screen

        • failure to pass meconium

        • failure to thrive

        • voracious appetite

        • wet-sounding cough

        • recurrent infection

        • chronic sinusitis

        • genital abnormalities in males

      • Uncommon

        • Haemoptysis

    • Other diagnostic factors

      • Common

        • malabsorptive stool steatorrhoea

        • wheeze

        • digital clubbing

        • gastro-oesophageal reflux

      • Uncommon

        • increased anteroposterior (AP) diameter of the chest

        • hx of pancreatitis (uncommon)

        • hx of acute appendicitis (uncommon)

        • enlarged liver or spleen (uncommon)


    • Mutations in CFTR result in abnormal salt (chloride and bicarbonate) transport by epithelial cells

      • Results in thick, sticky secretions.

    • In the pancreas, this leads to:

      • blockage of exocrine ducts

      • early activation of pancreatic enzymes

      • eventual autodestruction of the exocrine pancreas

      • Therefore, most patients require supplemental pancreatic enzymes.

    • In the intestine, bulky stools can lead to intestinal blockage.

    • In the respiratory system, the absence of CFTR function results in:

      • hyperabsorption of sodium from the airway surface liquid to the blood

      • depletion of airway surface liquid

      • Leads to:

        • mucus retention

        • chronic infection

        • inflammation

        • eventuate to destruction of lung tissue. [2]

      • Lung disease is the most common cause of morbidity and mortality.


    • Sweat test

      • Generally considered the most conclusive test for diagnosis.

      • Sweat tests may be performed in children of any age.

      • Some children may not produce enough sweat to give accurate results.

        • If this occurs, the child should be retested within a week.

      • A sweat chloride measurement of <40 mmol/L (<40 mEq/L), essentially rules out the diagnosis.

      • A positive sweat test (>60 mM) is consistent with CF and requires immediate referral to a CF centre.

      • For those with a sweat test falling within 40 and 59 mmol/L, further investigations may be required.

    • Immunoreactive trypsinogen (IRT) test (newborn screening)

      • A positive IRT test, defined differently by each laboratory, is not diagnostic.

      • Each positive result should be followed by confirmatory testing.

      • All patients with a positive IRT test should be referred to a CF centre. [10]

    • Genetic testing

      • Most laboratories will perform an initial 'screen' for the most common CFTR mutations.

      • If two common mutations are not found, most laboratories have an option for sequencing more of the CFTR gene

    • Sinus x-ray

      • May show pansinusitis

    • Deep throat swab

      • Presence of respiratory pathogens


a) conservative

    • monitoring

    • chest physiotherapy

      • manual chest physiotherapy

      • high-frequency oscillatory vest device (VEST therapy)

      • flutter valve

      • positive expiratory pressure mask

    • fat-soluble vitamin supplementation

b) medical

    • pancreatic enzyme replacement

      • Enzyme replacements consist of lipase, protease, and amylase

    • H2 antagonist or proton-pump inhibitor

      • Used to provide a more alkaline environment for pancreatic enzyme supplemental therapy, improving enzyme function

      • Also to treat GORD

    • ursodeoxycholic acid

      • If liver disease present

    • inhaled bronchodilator

      • Salbutamol

    • inhaled mucolytic

      • Dornase alfa

    • inhaled tobramycin

      • Used in patients with chronic infection with Pseudomonas aeruginosa

    • anti-inflammatory agent

      • macrolide, NSAID, corticosteroid

    • inhaled corticosteroid

      • Fluticasone

    • oral osmotic agents

      • For meconium ileus

c) surgical

    • Relief of blockage in meconium ileus/partial distal intestinal obstruction

    • Lung transplantation


    • This is a genetic disease for which there is no cure.

    • However, the outlook for patients with this condition has greatly improved.

    • In the past 50 years, the mean age of survival has risen from infancy/school age to almost 38 years old.

    • Many new, beneficial therapies have emerged over the past 5 decades.