Cystic fibrosis

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Stages
Symptoms
Causes And Risk Factors
Prevention
Diagnosis
Treatment
Lifestyle/management
Prognosis And Complications
References

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Cystic fibrosis is a chronic genetic disease affecting both the lungs and the gastrointestinal system. It is caused by a gene defect that is passed on to children having parents who carry a defective gene. The defective gene codes for a protein that causes the lungs to produce a sticky, dense mucus. Gradually, the mucus clogs the lungs and causes multiple lung infections that might be fatal. Moreover, it affects the normal functioning of pancreas by obstructing the production of certain substances (enzymes) required by the body to digest and absorb food. Cystic fibrosis is known to be the most common cause of fatality because of end-stage lung disease.

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Stages

There are five classes of the pathogenesis of cystic fibrosis:

Class 1 - In this class, dysfunction is an effect of splice site mutation, frameshift mutation or a nonsense mutation. This leads to the premature termination of mRNA sequence; 2%–5% of cystic fibrosis is caused by class 1 dysfunction.

Class 2 - In this type of this function, CFTR protein undergoes abnormal post-translational processing because of which CFTR protein loses its mobility to a particular cellular location.

Class 3 - This type of dysfunction protein activity is diminished because of intracellular signal signaling.

Class 4 - Protein introduced and correctly located on the cell surface; however, the rate of channel activation after stimulation and chloride ion flow decreases from the average.

Class 5 - Because of rapid degeneration, CFTR channels decrease in the cellular membrane concentration. These mutations alter the mRNA’s stability.

Symptoms

The clinical symptoms of cystic fibrosis are similar to many of the symptoms reported in asthma, whooping cough, tuberculosis, chronic diarrhoea and conditions related to the immune system and digestive system. Hence, during their first visit to the doctor, patients with cystic fibrosis are never suspected to have this condition.

Usually, in India, cystic fibrosis patients suffer from malnutrition along with respiratory and digestive problems. A specific characteristic of these patients is the presence of high salt concentration in their sweat.

Respiratory problems because of a dense, sticky mucus include:

Persistent cough

Difficulty in breathing

Choked nasal passage

Wheezing

Increased tendency to develop sinusitis and nasal polyps (swelling on the walls of nasal cavity or sinuses)

Digestive problems include:

Poor digestion

Constipation

Foul-smelling stools

Blocked intestine

Undernourishment because of the lack of absorption of nutrients

Weakness

Difficulty in gaining weight

Diabetes may develop in people with cystic fibrosis because of damaged pancreas. Moreover, older children or adults may show signs of arthritis or osteoporosis (weakness in bones and joints) as the disease develops. Older adults with cystic fibrosis are infertile.

Causes And Risk Factors

Causes

This condition is caused by a genetic defect, and the severity of disease is variable depending on the defect site in the gene. Moreover, there are >1000 identified mutations in the gene causing cystic fibrosis. There are five types of mutations that can cause systemic fibrosis:

Disordered regulation

Accelerated channel turnover

Defective chloride conductance

Defective protein synthesis

Defective protein processing

Studies reported that symptoms and profile of patients with cystic fibrosis in India are considerably different than patients in other countries, thus making diagnosis even more difficult.

Risk Factors

There is a risk of developing cystic fibrosis-related genetic mutations, excessive inflammatory response, and abnormal composition and secretion of mucus.

Prevention

Cystic fibrosis cannot be prevented. Carrier testing is the only option that can prevent the incidence of cystic fibrosis. Couples who are either planning or expecting a baby should consider taking the test.

For this test, blood samples of the couple are used to detect the presence of defective gene or mutation in the gene that causes cystic fibrosis. If both partners are positive, additional prenatal screening is performed to examine chances that their baby has or may develop cystic fibrosis.

Diagnosis

Suspecting cystic fibrosis is a complicated task. With the detailed study of patients’ symptoms and a look at their family history, cystic fibrosis can be suspected. Usually, the suspected cystic fibrosis cases are confirmed by detecting the salt concentration in the patient’s sweat. A chloride concentration of >60 mmol/L indicates cystic fibrosis. As part of diagnosing cystic fibrosis, physical examination should be performed on new-borns.

In certain cases, cystic fibrosis is diagnosed during the prenatal ultrasound. This may demonstrate meconium peritonitis, absence of gallbladder or bowel dilation.

The evidence for CFTR dysfunction is the presence of two diseases causing CFTR mutations, elevated sodium chloride levels of 60 mEq/L at instances and the abnormal nasal potential difference. The sodium chloride test is a diagnostic pathway to diagnose cystic fibrosis.

A pancreatic enzyme test is performed to screen new-borns with meconium ileus for cystic fibrosis immunoreactive trypsinogen (IRT). The severity of cystic fibrosis can be compared with IRT monitoring.

To identify hyperinflation, bronchiectasis, atelectasis or abscesses, radiographic chest tests are performed. The pan opacification of paranasal sinuses can be diagnosed with sinus radiography. Bronchoalveolar lavage provides help for analysing the level of neutrophils in the blood. Moreover, bronchoalveolar lavage can be tested for microbiological culture, which can help detect Haemophilus influenza, Pseudomonas aeruginosa, Escherichia coli, Burkholderia cepacia or Klebsiella pneumonia.

To evaluate the progression of cystic fibrosis, a pulmonary function test is important. Spirometry is a type of pulmonary function test used to monitor the disease state of cystic fibrosis.

Sweat-testing centres in India are not widely available. New born screening tests can detect the presence of the defective CF gene in the child. Genetic screening test is really helpful for the early detection of condition, improving the quality of life and increasing the life span of the individual.

Treatment

Cystic fibrosis cannot be cured. The treatment’s aim is to ease the symptoms and improve the quality of life of patients. Previously, only a few children diagnosed with cystic fibrosis survived to attend school.

At present, because of developments in treatments and research, individuals with cystic fibrosis can expect to live up to their 40s and even beyond with proper management and care.

Medication

Medicines are primarily prescribed to clear the blocked nasal passage and treat infections. However, other conditions related to cystic fibrosis can be managed with drugs.

Bronchodilators, aerosols, and liquid medicines are given to relax muscles and open up airways.

Mucolytics are thus given to thin the mucus.

Antibiotics may be given orally, intravenously or in the form of inhalers to fight respiratory infections. Tobramycin is extensively used to treat infections caused by Pseudomonas bacteria. Azithromycin is another antibiotic that is effective for treating infections.

In case of nasal polyps, corticosteroids are prescribed to reduce the swelling.

Bisphosphonates can also be prescribed to treat weak both bones and joints.

There are a few breathing devices and devices that help in removing mucus from lungs.

Physical therapy

Physical therapy is important in patients with cystic fibrosis to improve their lung function. Usually, pulmonary rehabilitation is considered, which includes exercise techniques and techniques to minimize energy expenditure on a daily basis. Breathing techniques may help patients manage their condition well. Physiotherapy is also another option, particularly for people having bone and joint problems.

Surgery

Surgical removal of nasal polyps may be recommended if medication does not resolve obstructed breathing.

Endoscopy may be performed to remove excess mucus and clear airways.

A bowel surgery is usually performed to remove or repair the bowels in case of complete blockage.

Lung transplant may be performed in patients who have severe breathing problems or when infections do not respond to antibiotics, leading to life-threatening complications. However, transplants are rare and involve many complications.

Lifestyle/management

Because cystic fibrosis is associated with problems in absorption of nutrients, special care for diet and nutrition should be taken. The diet of patients with cystic fibrosis should be high in calories and should include simple carbohydrates. Because of digestive problems, semi-solid foods or foods that are easily digestible may be given. Liquids such as fruit juices and milkshakes should also be included in the diet. Sometimes, dietary supplements may be required.

Prognosis And Complications

Prognosis

Patients with cystic fibrosis eventually require lung transplantation. Progressive lung disease is the most common cause of mortality for patients with cystic fibrosis. Moreover, the lifespan of an individual with cystic fibrosis ranges around 40 years.

Complications

Cystic fibrosis progression is accompanied by the involvement of other organs that often lead to complications. Liver complications vary from steatosis to hepatic fibrosis to secondary biliary liver cirrhosis. Moreover, 32% of patients are affected by liver complications. Other complications associated with cystic fibrosis are arthropathy, comorbid mental illnesses such as depression and anxiety, type 3 diabetes mellitus, and osteoporosis. Note that additional complication called distal intestinal obstruction syndrome can occur.