The clinical manifestations of cystic fibrosis are typically categorized as pulmonary and non-pulmonary.

Pulmonary manifestations

The pulmonary manifestations of cystic fibrosis are encountered in the majority of the cases. They are often the presenting complaints of the patient.

• Recurrent pulmonary infections are very characteristic of cystic fibrosis. The most common pathogen responsible for pulmonary infection in cystic fibrosis is Staphylococcus aureus. Other pathogens commonly encountered in this disease include Pseudomonas aeruginosa, Hemophilus influenza and Burkholderia cepacia.
• The patient also suffers from persistent (or recurrent) productive cough. In addition, dyspnea and wheezing are also present.
• With time, the damage resulting from these recurrent infections and coughing accumulates and leads to progressive bronchiectasis. There is also scarring of the airways which may result in airflow obstruction.

Other manifestations

The non-pulmonary manifestations of cystic fibrosis cover several organ systems and are summarized below.

• General physical manifestations: A number of findings will be seen in the advanced cases of cystic fibrosis upon general physical examination. Clubbing of the fingernails is often present. The anteroposterior diameter of the chest is also increased and upon percussion, the chest is found to be hyper-resonant.
• Upper respiratory tract manifestations: The patients of cystic fibrosis often suffer from sinusitis. The upper respiratory tract may produce purulent secretions in large amount. Nasal polyps also occur frequently in cases of cystic fibrosis.
• Gastrointestinal tract manifestations: In newborns, the distal gastrointestinal tract can become filled with thick, sticky intestinal secretions, causing meconium ileus and obstruction of the small intestine. The meconium also contains a higher amount of carbohydrates and proteins [5]. Although much less pronounced in adults, advanced cases can present with similar findings.
• Pancreatic insufficiency: Both the exocrine and endocrine functions of the pancreas can be affected. Dysfunction of the exocrine part can cause some degree of indigestion. This mostly comes to notice as steatorrhea due to the high undigested lipid content in the stool. Pancreatic insufficiency also leads to decreased levels of insulin. As a result, insulin dependent diabetes mellitus can occur.
• Reproductive system manifestations: Almost all the male patients suffering from cystic fibrosis are infertile. This is due to the inability of the vas deferens to develop on both sides.

Diagnosis of cystic fibrosis can easily be made on clinical grounds but a number of examinations are still very useful for confirming the diagnosis. Investigations can also be performed routinely in patients with an affected first degree relative. The following investigations are of diagnostic importance in cystic fibrosis.

Sweat sodium or chloride concentration

The amount of salt in the sweat is increased in the patients suffering from cystic fibrosis. Values of sweat sodium or chloride greater than 60 mmol/L are diagnostic of cystic fibrosis.

DNA analysis

The patient’s DNA can be analyzed in order to locate defects in the gene corresponding to this disease.
Pulmonary function tests: Pulmonary function tests may indicate an obstructive and/or restrictive disease pattern. There may be hypoxemia and in advanced stages, respiratory acidosis.

Imaging

Features of cystic fibrosis can be identified on imaging. Common findings in cystic fibrosis include hyperinflation of the lungs, peribronchial cuffing, mucus plugging, bronchiectasis and peripheral opacities.

Treatment of cystic fibrosis focuses on the removal of respiratory tract infections, reduction of secretions and reversal of bronchoconstriction coupled with interventions to combat pancreatic and nutritional insufficiency.

• In cases of respiratory tract infections, the sputum should be cultured and appropriate antibiotics are then administered. Short term antibiotics are used against the infections caused by Staphylococcus aureus, Hemophilus influenza, Burkholderia cepacia and Stenotrophomonas maltophilia. Long term antibiotics are required against Pseudomonas aeruginosa [6].
• Inhaled bronchodilators are effective in reducing respiratory symptoms in most patients.
• Mucolytics are given to reduce the viscosity of the secretions.
  Pancreatic enzyme supplements are given in order to make up for pancreatic insufficiency.
• Nutritional supplements and multivitamins are required.
• A new oral drug named ivacaftor has recently become available for 5% of the cystic fibrosis patients with G551D mutation. This drug reverses the dysfunction of the chloride membrane channel [7]. This treatment is therefore referred to as CFTR corrector therapy.
• Lung transplantation is the most definite treatment in severe respiratory disease [8].
• Adopting an exercise regimen can improve the quality of life of the patient [9].

In the past few decades, the prognosis of patients with cystic fibrosis has significantly improved. The life expectancy of these patients averages 40 years [10].

Modern treatment strategies enable more than 80% of the cystic fibrosis patients to reach adulthood. Deaths in these patients usually result from complications related to the lungs.

Cystic fibrosis is primarily a genetic disease and is inherited in an autosomal recessive pattern. The underlying genetic defects involve only a single gene on chromosome 7.

Currently, a total of 1965 different mutations have been identified in the aforementioned gene and up to 230 genes have been proven to cause clinical manifestations of cystic fibrosis [3].

The most common mutation in cystic fibrosis is ΔF508. It is characterized by a deletion of three nucleotides that code for the amino acid phenylalanine at position 508. It is present in over 65% of the clinical cases of cystic fibrosis worldwide [4].

Other common mutations of clinical significance include G542X, G551D, N1303K and W1282X.

Cystic fibrosis seems to be a rare disease on paper but practically, it is the most common fatal disease in the white population [1]. As expected from this statement, the disease is much more common in the western world, particularly in Europe; and much less common in the Asian and African countries.

In the United States, the prevalence of the disease varies among various races. The highest prevalence (one case per 3200 population) is present in the population of European descent. On the other hand, the lowest prevalence (one case per 31,000 population) is present in the Asian Americans. Hispanics and African Americans (at one case per 9200 and 15000 population, respectively) lie between these two extremes.

Ireland has the highest worldwide incidence of this disease with 1 new case per 1353 individuals per year [2].

The defective gene in this disease encodes a membrane chloride channel and regulatory protein known as Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). This membrane chloride channel is normally found in the apical epithelia of several organs of the body including the lungs, pancreas, stomach, intestines, endocrinal and reproductive organs.

Cystic Fibrosis Transmembrane Conductance Regulator encoded from the mutated gene has several functional defects. There is an abnormal transport of chloride ions and water molecules across the apical surface of the epithelia in the respective organs. The transport of sodium, bicarbonate and other ions may also be affected in some mutations.

As a result, the mucus produced at these epithelial surfaces is unusually thick, viscous and sticky causing clinical manifestations. In the respiratory tract, this viscid sputum prevents the adequate hydration of the mucociliary epithelium and also predispose the epithelium to recurrent infections. The surface epithelium starts acquiring damage and chronic inflammation results. Sloughing of the epithelium into the mucus causes the production of viscid sputum.

In endocrinal organs, the thick, sticky mucus gathers in the duct and causes obstruction. Similar pathologies occur in the gastrointestinal tract and reproductive organs. The salt content in sweat is also increased due to defects in Cystic Fibrosis Transmembrane Conductance Regulator.

There are no guidelines for prevention of cystic fibrosis.

Cystic fibrosis is an autosomal recessive disease resulting from mutations in the gene encoding a membrane chloride channel called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) that is present in the epithelia of various tissues of the body, including the lungs, pancreas, stomach, intestines, endocrinal and reproductive organs.

Dysfunction of this channel causes the production of abnormal secretions in these organs, which ultimately leads to a multitude of pulmonary and extra-pulmonary manifestations.

With proper management, the life expectancy of most patients exceeds 40 years.

Cystic fibrosis results from a genetic defect that causes a malfunction in a protein present in tissues in many organs of the body including the lungs, pancreas, stomach, intestines, endocrinal and reproductive organs.

This causes the production of abnormal secretions and symptoms related to these organs result.

The management of cystic fibrosis has improved in recent years and the prognosis is fairly good.

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