WHAT IS CYSTIC FIBROSIS?
Cystic Fibrosis Life Expectancy: CF Disease Diet, Treatment, Diagnosis, Symptoms: Cystic fibrosis, also known as CF, is one of the most common congenital metabolic diseases. The cause is a defect in the CFTR gene (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator), which is responsible for the production of an ion channel on the surface of body cells.
The cystic fibrosis inheritance is autosomal recessive, is therefore independent of sex and the disease only breaks out if both copies of the CFTR gene are defective.
In healthy individuals, the ion channel produced from the CFTR gene regulates the salt balance of the cells by allowing salt and water to flow through it. If the CFTR gene is defective, tough mucus forms in the body, which can clog various organs and thus impair their function. This results in typical cystic fibrosis symptoms. Affected are Below all
- the lung,
- the pancreas,
- the liver,
- the reproductive organs and
- the intestine.
Due to the many mucus can easily be located in the respiratory tract viruses, bacteria and fungi, which is why often pneumonia and infections occur that can be life-threatening.
Cystic Fibrosis Cause: The CFTR gene
The CFTR gene responsible for cystic fibrosis has been known since 1989. It is located on chromosome 7 and serves as a blueprint for a transport channel through which chloride and bicarbonate ions are transported out of the mucosal cells.
In healthy people, the cells secrete chloride ions via this channel, which combine with sodium to form common salt (sodium chloride, NaCl) outside the cell. In order to balance the increasing salt concentration outside the cell and reconcile it with the concentration in the cell, water flows out of the cells and moisturizes the mucous membranes.
In people with cystic fibrosis, the function of the ion channel is disturbed by errors in the CFTR gene. Outside the cell, an acidified, water-poor environment is formed. As a result, the mucus formed by the mucosal cells is viscous, clumped and can only be removed with difficulty. As it progresses, it clogs the fine branches of the bronchi in the lungs , the ducts of the pancreas, and the bile ducts. This leads to severe respiratory and digestive disorders (intestine, pancreas, liver, kidneys).
Many genetic manifestations of cystic fibrosis have already been identified, which may lead to new therapeutic approaches.GOOD TO KNOW
To date, more than 2,000 different changes in the CFTR gene are known. However, only a small part of it actually leads to the onset of cystic fibrosis.
The most common mutation in the United State is the so-called Phe508del mutation. The mutation lacks three base pairs in the sequence of the CFTR gene and thus the amino acid phenylalanine at position 508 of the CFTR protein. The protein cannot be properly folded by this defect and degrades even before it reaches the cell surface.
What are the Symptoms of Cystic Fibrosis?
Due to the broken ion channel and the disturbed salt balance of the cells, many people with cystic fibrosis experience many typical complaints that affect different organs. Many cystic fibrosis symptoms, however, are similar to the symptoms that can also occur in other diseases such as bronchitis, asthma and celiac disease. Therefore, it may initially come to misdiagnosis.
Cystic Fibrosis Symptoms of the lungs
Patients with cystic fibrosis often suffer from respiratory complaints due to the viscous mucus. This includes
- persistent chronic cough,
- increased mucus production,
- whistling breath sounds,
- Clubbed fingers,
- chronic sinusitis and
- recurrent pneumonia.
Dysfunction of the digestive Tract
The digestive system is also affected by the mucus because it blocks the pancreas and liver and prevents digestive enzymes from entering the intestine. Cystic fibrosis symptoms can already be felt in babies. Frequently, the first chair, the so-called child’s bladder (meconium), causes problems that can lead to intestinal obstruction (ileus).
Stand with age:
- stubborn diarrhea,
- foul-smelling chair,
- Underweight and
- growth retardation
in the foreground, because the food can not be processed properly. The diet and nutritional supplements are therefore a central issue in the treatment of CF.
Salt Balance in People with Cystic Fibrosis
The disturbed salt balance in people with cystic fibrosis also causes them to lose a lot of salt through sweat. This electrolyte disorder can manifest as symptoms of increased thirst, headache, dizziness, or muscle spasms.
Cystic fibrosis is a progressive disease in which metabolic processes continue to worsen. In the course of the disease can therefore follow-on diseases such as diabetes, osteoporosis, inflammation of the pancreas (pancreatitis) or fertility disorders occur.
Different disease course
All forms of cystic fibrosis are based on a defect in the same gene. However, the clinical course of the disease and the organs affected, as well as the severity of the symptoms, can be very different and greatly affect the survival of patients.
The various forms of disease are caused not only by the error in the CFTR gene, but also by so-called modifier genes. Modifier genes are involved in the expression of the cystic fibrosis genes and lead to different disease processes despite the same original genetic defect.
The severity of the disease is individually very different, and the number of affected organs may vary.
On average, those affected now reach the age of over 40 years. The share of adult patients is currently well over 60 percent.
Cystic Fibrosis Risk Factor
Autosomal recessive means that the disease is inherited regardless of gender and only occurs when the genome of a human has two identical copies of a particular gene.
Children can only develop cystic fibrosis if
- both parents are carriers of the defective allele, so are the gene severity and
- both defective genes are passed to the child.
In Germany, about one in every 25 healthy German citizens carries the cystic fibrosis gene and can pass it on, usually without knowing it.
If both parents are carriers of characteristics – so they each have a broken CFTR gene – there is a risk of 25 percent of every pregnancy that the child is going to contract cystic fibrosis. If one parent suffers from cystic fibrosis and the other parent is a healthy trait – a very rare combination – then the likelihood of having cystic fibrosis offspring increases to 50 percent.
On the other hand, if one parent suffers from CF and the other parent is healthy and not a carrier of signs, all the children are healthy and become only carriers of signs.
Couples with a desire to have children, in which both partners each carry only one defective allele, can contact a genetic counseling center in advance.
CYSTIC FIBROSIS DIAGNOSIS
The earlier the cystic fibrosis diagnosis takes place, the better the patients can be treated. Basically, cystic fibrosis (CF) is present as a hereditary disease from birth, but in the past it was often diagnosed late.
Since 2016, all newborn babies in Germany have been tested for cystic fibrosis as part of their newborn screening. This test can give first clues to the disease. But the family history and symptoms can also provide clues, for example in older children.
According to the guideline, there must be at least one diagnostic indication for a confirmed cystic fibrosis diagnosis and a functional disorder of the CFTR gene mustbe detected (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator).
As diagnostic information apply:
- Positive newborn screening
- Siblings with cystic fibrosis diagnosis or
- at least one clinical indication of cystic fibrosis
Evidence of dysfunction of the CFTR gene is provided by:
- Increased salt content in sweat during sweat test or
- Detection of two mutations in the CFTR genes that cause cystic fibrosis or
- Electrophysiological examinations, such as intestinal short-circuit current measurement (ICM) or nasal potential difference measurement (NPD)
The diagnosis of cystic fibrosis is therefore quite complex and takes place gradually.
Newborn screening for cystic fibrosis
In 2016, newborn screening for cystic fibrosis was introduced in Germany . The screening is a screening in the first days of life of a child, with which many congenital metabolic diseases can already be detected. An early diagnosis has the advantage of being able to start as early as possible with appropriate treatment and thus to support the development of a child as well as possible.
For neonatal screening for cystic fibrosis, no additional blood sample is needed. Usually, on the third day of life, one drop of blood is taken from the child’s heel, which is sufficient for all tests.
New cystic fibrosis screening includes the IRT (= immunoreactive trypsinogen) test and the PAP (= pancreas-associated protein) test and the genetic test for the most common cystic fibrosis-inducing mutations.IN A NUTSHELL
For the detection of cystic fibrosis, the so-called IRT (= immune-reactive trypsinogen) test is used in the first step: In the pancreas, trypsinogen is formed as the precursor of a digestive enzyme. In cystic fibrosis, the viscous mucus, which affects the function of the pancreas, can cause more trypsinogen to enter the bloodstream than in healthy people. Increased levels of trypsinogen in the blood may therefore be a first sign of the disease.
If the IRT test has not been sufficiently conclusive, the second step is the PAP (= pancreas-associated protein) test and a genetic test for the most common CFTR mutations. PAP, a stress protein, is produced in the diseased pancreas. Its content in the blood of babies with cystic fibrosis is also increased.
If there is a suspicion of cystic fibrosis due to the neonatal screening tests, a sweat test should then be performed to confirm the diagnosis. The sweat test is also recommended for children born before 2016 who show symptoms of cystic fibrosis.
Cystic Fibrosis Test
In people with cystic fibrosis, the salt content in the sweat is increased by the CFTR mutation. As early as 1959, this finding was used as a diagnostic option. And even today, the sweat test is the gold standard used to substantiate the suspicion of cystic fibrosis.
The painless test can be performed from the third day of life of the child, optimally from the 14th day of life. However, its informative value depends crucially on the quality of the performance and its interpretation. The danger of both false-positive and false-negative findings exists.
Dysfunction of the CFTR gene is considered to be established if at least two independent measurements of sweat chloride exceed 60 mmol / L (millimoles per liter). At 29 mmol / L or less, cystic fibrosis is unlikely. If the value lies in the intermediate range, further diagnostic methods must be used.
If the result of the sweat test is unclear, but also if the result is positive, then a genetic test for CFTR mutations should be carried out. Especially with regard to mutation-specific therapies that have been available for some time.
Genetic test for cystic fibrosis
In the genetic test, it is examined whether the CFTR gene is in the correct or altered (mutated) form. A mutation affects the function of the CFTR ion channel and, depending on the nature of the defect, different types of cystic fibrosis may occur. If the result of the genetic test is established, a genetic counseling of the patient or the guardian takes place.
Not all mistakes lead to the onset of the disease; The cystic fibrosis-inducing gene alterations are now divided into six classes, which can be used as an approach for various therapeutic procedures.
However, in some patients, the diagnosis of cystic fibrosis cannot be clearly established even after sweat and gene tests. It is then recommended to check the function of the CFTR channel by electrophysiological measurements. This is done either by means of the so-called intestinal short-circuit current measurement (ICM) or the nasal potential difference measurement (NPD).
CYSTIC FIBROSIS Treatment And Therapy
Cystic fibrosis, or cystic fibrosis, is still not curable. Because the causative defect in the CFTR gene (CFTR = Cystic Fibrosis Transmembrane Conductance Regulator) can not be repaired so far. Attempting to correct the broken gene using gene therapies is currently experimental.
Cystic fibrosis is a progressive disease in which the metabolic functions continue to worsen. Although this process can not be stopped, there is the possibility to do something against the various symptoms, such as to facilitate the expectoration of viscous mucus and to improve the digestive functions. The sooner the therapy starts and the more consistently it is performed, the higher is the life expectancy.
Cystic Fibrosis Medications
In 2012, the first mutation-specific drug for cystic fibrosis therapy was approved in Europe – the active ingredient ivacaftor.
In patients with certain mutations, Ivacaftor, as a so-called “potentiator,” can restore or enhance the function of the defective CFTR ion channels by supporting the opening of the channel. Thus, the salt and water balance of the mucosal cells can be normalized. Ivacaftor is effective in approximately four percent of all cystic fibrosis patients.
In addition, there are two other active ingredients in Germany, Tezacaftor and Lumacaftor, which can be used in combination with ivacaftor to treat certain patient groups. These patients carry the most common mutation Phe508del on one chromosome and the Phe508del mutation on the other chromosome, or a mutation in which the CFTR ion channel still works a bit.
Lumacaftor and Tezacaftor are so-called correctors, which prevent in patients with a Phe508del mutation that the flawed CFTR protein is already degraded before installation in the cell membrane. This allows more ion channels to be placed in the right place, which can then be activated by Ivacaftor.
Symptomatic Therapy Options
The most important pillar of the symptomatic treatment of cystic fibrosis is the inhalation therapy. With the inhalation of various expectorant or bronchodilator substances one tries to mobilize the mucus, so that the coughing easier. By inhalation, however, various other medications such as anti-inflammatories or antibiotics can beaccurately administered into the lungs.
Cystic fibrosis is associated with adult patients with diabetes. Early detection via regular glucose tolerance tests from the age of 10 years and diabetes therapy with insulin have a positive effect on the further course of the disease.GOOD TO KNOW
Intensive respiratory physiotherapy with breathing exercises such as autogenous drainage and the use of various respiratory therapy devices can measurably improve lung function.
It is also important to increase overall performance with personalized physical training. As the duration of the disease increases, the heart and lungs become increasingly strained.
In the advanced stage of the disease, it may be necessary to administer oxygen and to supply the chronically congested heart with medication. If the lung is too damaged, a lung transplant may be required.
Antibiotics in cystic fibrosis
Antibiotics are used to treat bacteria that like to stick to cystic fibrosis in the viscous mucus of the bronchi . Inhaled antibiotics can be delivered directly to the site of action, the lungs, without burdening the whole body. A combination with orally taken antibiotics as a tablet or juice is possible. However, resistance of bacterial pathogens such as Pseudomonas aeruginosa is a major problem.
The chronic colonization of the respiratory tract with the bacterium Pseudomonas aeruginosa requires many patients with cystic fibrosis several times a year an intravenous pseudomonas therapy over two weeks, which can usually be performed at home.
Diet in cystic fibrosis
In addition to respiratory ailments, nutritional deficiencies and low caloric intake are the main problems of cystic fibrosis therapy. Patients are often affected by deficiencies. They are missing
- essential fatty acids,
- fat-soluble vitamins,
- Trace elements and
A very high calorie diet and the absorption of fat-soluble vitamins – vitamins A, D, K and E – are therefore particularly important. In addition, the supply of digestive enzymes is necessary so that the food can be better unlocked. The dose of these preparations must be supplemented with dietary fat. A care by specialized dietitians is highly recommended.
Since 2018 it is possible for people with cystic fibrosis to take advantage of nutritional therapy at the expense of the statutory health insurance . This was decided by the Federal Joint Committee (GB-A) on 16 March 2017.
Because CF patients today have significantly longer life expectancies than they did twenty years ago, those affected are confronted with new problems and need support in the past. Because it raises new questions in connection with education, work and life planning with chronic illness.