The cystic fibrosis, is the genetic disease most common. The main manifestations concern the respiratory and digestive tracts, but almost all organs can be affected. Symptoms often appear early in infancy and their severity varies from person to person. This disease causes a thickening of mucus secreted by the mucous membranes of the sinuses, bronchi, intestine, pancreas, liver and reproductive system (see diagram).
The lungs are often the most severely affected. The thick, viscous secretions obstruct the bronchi, making breathing difficult. In addition, the mucus that accumulates in the lungs is conducive to the development of microbes. People with cystic fibrosis are therefore at higher risk for frequent and potentially serious respiratory infections.
The CF also affects the digestive system. Mucus tends to block the thin ducts of the pancreas, preventing the digestive enzymes produced by the pancreas from flowing into the intestine and exerting activity. Foods being only partially digested especially fats and some vitamins, important deficiencies occur. They can lead to stunting.
The disease also has major implications for the liver and reproductive organs, often leading to subfertility in women and infertility in affected men.
Thanks to an earlier diagnosis and better management, the life expectancy and quality of life of people with the disease has been steadily improving in recent decades, especially as new therapies, targeted at genetic abnormality, are beginning to emerge and will change the management of patients in the medium term.
Prevalence of Cystic fibrosis
The cystic fibrosis is genetic disease most common grave in France with nearly 6,000 people with . One in every 4,000 newborns is affected by this disease. It is much rarer among blacks (1 in 13,000) and Orientals (1 in 50,000). It reaches men as well as women. The population of western France test the most affected.
The cystic fibrosis is genetic disease serious most common in Canada. One in 3,600 newborns is a victim. Cystic fibrosis is a little more common in Quebec in the rest of Canada: 3,500 Canadians are affected, including 1,200 Quebecers.
Causes of Cystic fibrosis
The responsible gene, named CFTR (for “Cystic Fibrosis Transmembrane Conductance Regulator”), was only identified in 1989 by Canadian researchers. In sick people, this gene is abnormal (it is said that it is mutated). He is responsible for the synthesis of a chlorine channel to regulate the hydration of mucus. In the event of a defect in the CFTR gene, the mucus produced is too thick and does not drip normally. More than 1,800 different mutations of the CFTR gene involved in cystic fibrosis have been identified is divided into 6 classes according to the different type of dysfunction Of these numerous mutations, the mutation Delta F508, found in 81% of the people affected in France, is the most frequent.
Cystic fibrosis is not a contagious disease. People who have pathogenic mutations of the CFTR gene develop the disease sooner or later but at varying degrees of severity.
Diagnostic of Cystic fibrosis
In general, cystic fibrosis is diagnosed in the first year of life because respiratory symptoms appear very early. In 90% of cases, the disease is detected before the age of 10 years.
To confirm the diagnosis, the doctor conducts a sweat test (or sweat test). In fact, the sweat of people with cystic fibrosis is much more concentrated in salt (from 2 to 5 times more than normal). The genetic tests can identify exactly abnormalities in the CFTR gene. They are essential to consider targeted therapies.
In France, cystic fibrosis has been systematically detected in all newborns since 2002. Early detection has been shown to improve the quality of life and life expectancy of affected children.A blood sample is taken from newborns at 3 days of age after parental consent, before the release of maternity. The test does not give a diagnosis of certainty but will be confirmed or invalidated by specific additional tests (sweat test, genetic study).
In Quebec, there is no systematic screening programof this disease. However, the Canadian Cystic Fibrosis Foundation, supported by several doctors, has been calling for the introduction of neonatal screening for several years. Early detection has been shown to improve the quality of life and life expectancy of affected children.
In the 1960s, the life expectancy of children with cystic fibrosis did not exceed 5 years. Nowadays, according to the latest statistics, the median age of survival is 47 years. The respiratory infections remain the most common cause of death.
Cystic fibrosis is a disease that progressively damages the lungs, pancreas and liver. The medical follow-up, however, reduces the severity and frequency of complications.
The respiratory complications are the most frequent, including bronchiectasis, causing bronchitis , pneumonia repeatedly. There are periods of worsening respiratory symptoms, where the patients are very “congested”, are more breathless, lose weight, often because of an infection. Respiratory disease can be life threatening.
With regard to the digestive system, the obstruction of the bile ducts that allows the evacuation of bile to the digestive tract can lead to cirrhosis of the liver. The obstruction and progressive sclerosis of the pancreas can cause malabsorption of nutrients and the onset of diabetes . These disorders often lead to significant nutritional deficiencies and chronic diarrhea . In general, deficiencies can be corrected by a special diet. Conversely, significant constipation , or intestinal obstruction, can also occur.
In general, puberty occurs later in boys and girls with cystic fibrosis. Finally, fertility is decreased, especially in men who are almost all (95%) infertile due to obstruction of vas deferens. These channels carry sperm from the testes to the seminal vesicles. In women, the increased viscosity of the vaginal mucus slows the movement of the spermatozoa. The disease can also alter the regularity and frequency of ovulation. Fertility decreases, but pregnancy is still possible.
Symptoms of Cystic Fibrosis (Cystic Fibrosis)
The symptoms of cystic fibrosis appear most often before the age of 1 year, but sometimes later (including in adulthood). In general, the earlier the disease appears, the more important the symptoms are. On the other hand, there is a great variability between the people affected. Some are very embarrassed and weakened by the disease; others live normally in everyday life. Be that as it may, cystic fibrosis is a disease that is not “visible” and does not result in intellectual disability.
Respiratory tract damage
Generally, respiratory symptoms dominate. They appear during the first year of life in more than 80% of cases with:
- In infants, repetitive bronchitis.
- A chronic fatty cough with expectoration of a large amount of mucus, and sometimes blood (especially in adults).
- Shortness of breath on exertion (dyspnoea) with worsening of the respiratory function. This is explored and followed by a regular breath measurement (Functional Respiratory Exploration)
- Frequent respiratory infections called “bronchial exacerbation” will enmesh the lives of people who can progress to respiratory failure.
- Different microbes colonize the bronchi with dangerousness depending on the species. In infancy, haemophilus and staphylococcus aureus are the most common, and with age the frequency of colonization with Pseudomonas aeruginosa or other gram-negative bacilli increases. These last germs aggravate the respiratory function more quickly. Other pathogens such as fungi or mycobacteria may also be present in the sputum, which regular analysis is essential.
- Frequent sinusitis and the appearance of nasal polyps that can cause nasal obstruction, discharge, headache and sometimes loss of sense of smell
Achievement of the digestive tract
The symptoms are varied with:
- A low weight gain despite a big appetite, due to malabsorption of fat.
- An inflated belly, at children
- Abnormal stools (bulky, frequent, greasy, and smelly).
- Frequent diarrhea or constipation (even intestinal obstruction, called meconium ileus in the newborn).
- Gases that result from incomplete digestion of food.
- Abdominal pain.
- A puberty delay of 2 years on average.
- Gastroesophageal reflux
- Joint pain in some affected adults.
- Diabetes affects about half of people who are 30 years old
- Osteoporosis often early
People at risk for cystic fibrosis (cystic fibrosis)
If parents have had a child with cystic fibrosis, there is a risk that future children will also be affected. In fact, cystic fibrosis is a genetic disease, transmitted by parents to their child in the recessive mode. This means that both parents carry the abnormal gene, but the disease does not manifest in them. It is when the child inherits both the abnormal gene from his father and that of his mother that he develops the disease. Thus, both copies of the CFTR gene must carry a mutation for cystic fibrosis to occur.
People who have a single mutated copy of the gene (and a normal copy) are “healthy carriers” of the disease, which they mostly ignore. Cystic fibrosis will never appear in them, and they will never show the symptoms, but they can transmit the anomaly to their offspring. If their spouse has the same anomaly, it is possible that their child suffers from the disease with a risk of 4 births on average. In France, one in 25 is a healthy carrier.
When both parents (each possessing a healthy gene and an affected gene) decide to have a child, there is for each newborn of the same family:
- 50% of possibilities that the child is not reached, but that he carries the gene of the disease (a healthy gene and a diseased gene healthy carrier);
- 25% of possibilities that he is neither carrier nor affected by the disease (two healthy genes);
- 25% of possibilities that the child has the disease (two sick genes).
Prevention of cystic fibrosis (cystic fibrosis)
|Can we prevent?|
|Unfortunately, it is impossible to prevent cystic fibrosis in a child whose two CFTR genes are mutated. The disease is present from birth, even if the symptoms may appear later.|
|Couples with a family history of the disease (cystic fibrosis in the family or the birth of a first child with the disease) can consult a genetic counselor about their risks of giving birth to a child with the disease. The genetic counselor will be able to inform parents about the various options available to help them make an informed decision.
Screening in the future parents. In recent years, we can detect the genetic mutation in future parents, before the conception of the baby. This test is generally offered to couples with a family history of cystic fibrosis (for example, an affected sibling). The test is performed on a sample of blood or saliva. The goal is to detect a possible mutation in the parents, which would make them likely to transmit the disease to their future child. However, it should be noted that tests can detect only 90% of mutations (because there are multiple kinds of mutations).
Prenatal screening. If the parents have given birth to a first child with cystic fibrosis, they can benefit from a prenatal diagnosis for subsequent pregnancies. Prenatal diagnosis can detect possible mutations of the cystic fibrosis gene in the fetus. The test involves taking placental tissue after the 10 week of pregnancy. If the result is positive, the couple can then choose according to the mutations, to interrupt the pregnancy or to continue it.
Preimplantation diagnosis. This technique uses in vitro fertilization and allows implantation into the uterus only embryos that do not carry the disease. For “healthy carrier” parents who do not wish to take the risk of giving birth to a child with cystic fibrosis, this method avoids the implantation of an affected fetus. Only certain reproductive health centers are authorized to use this technique.
Screening in the newborn. The goal of this test is to identify newborns with cystic fibrosis to provide the required treatments as soon as possible. The prognosis and quality of life are better. The test consists of the analysis of a drop of blood at birth. In France, this test has been performed systematically at birth since 2002.
|Measures to prevent complications|
Medical treatments for cystic fibrosis (cystic fibrosis)
Cystic fibrosis requires multidisciplinary care and very regular medical follow-up. It is a real team effort that involves the patient, his family and the health professionals. In addition to the occasional workers, the multidisciplinary team consists of a doctor, a nurse, a dietician, a physiotherapist, a social worker, a pharmacist, a psychologist. Affected individuals consult at least every 3 months in the CRCM (Center for Resources and Competence for Mucoviscidose created in 2001). Thanks to an efficient organization of care, people can, in most cases, lives an almost normal life: going to school, playing sports, traveling…
The treatments have hitherto been symptomatic, making it possible to reduce the symptoms and to live better with the disease. Research aimed at restoring the activity of the defective CFTR protein is very active and since 2012 are emerging therapies improving the functioning of CFTR. For each mutation variety of the CFTR gene it is necessary to find a specific and adapted solution. This is specific therapy focused on mutation. To date 2 drugs are marketed. One can treat patients with the G551D mutation or 8 other “gating” mutations with good results and the other patients with 2 DF508 mutations. Several clinical trials are underway with the hope of new targeted treatments.
The goal of the respiratory treatments is twofold:
– to help the patient to drain the mucus which obstructs the bronchi – to avoid and treat early the pulmonary infections.
The daily exercises of respiratory physiotherapy are the basis of the treatment. They constitute a kind of “toilet” of the lungs. By draining the excess mucus contained in the bronchi, they greatly improve the quality of life of those affected and reduce the risk of infections.
In the child, these breathing exercises are in the form of games: laugh or sigh deeply, blow in a straw, on small papers, on ping – pong balls or candles. The physiotherapist or the parent also conducts postural drainage sessions, which can evacuate a large amount of mucus. Gradually, he can do them alone in self-draining. Antibiotics are used to treat infections. They are administered orally, intravenously or inhaled depending on the type of germ and the severity of the infection. They are chosen according to the antibiogram results of the bacteria found in the cyto-bacteriological examination of sputum (ECBC) done regularly. Intravenous antibiotic therapy is instead reserved for Pseudomonas aeruginosa or other gram-negative bacilli for which the choice of antibiotics administered orally is usually very limited. Aerosolized antibiotics reduce bronchial bacterial load and may reduce the frequency of exacerbations.
Other drugs are sometimes used:
– Mucolytics to thin the mucus. These can be given before a respiratory physiotherapy session to facilitate the evacuation of mucus (eg, hypertonic saline and dornase alfa or Pulmozyme). They are administered as an aerosol.
– The bronchodilators can improve in some patients the opening of the bronchi (eg, salbutamol or Ventolin and Atrovent).
In case of respiratory failure, oxygen therapy (at home or in hospital) is used. This measure makes it possible to compensate for the poor extraction of oxygen by the sick lung. To compensate for poor ventilation (retention of carbon dioxide or CO 2), non-invasive assisted ventilation using a nasal or naso-oral mask is proposed. The machine then takes the relay to rest the patient who makes much less effort to breathe; it is restrictive but can allow waiting for transplantation.
When the bronchi and lungs are overly damaged by the disease and the patient needs oxygen and non-invasive ventilation to help them breathe, a lung transplant may be considered. It helps to remove diseased lungs and replace them with healthy lungs taken from a deceased donor. The transplant helps to find the breath and resume a more active life. However, this is a risky operation that is reserved for the most serious cases. The transplant recipient must follow an immunosuppressive treatment very seriously for the rest of his life. Finally, it should be known that the lung transplant does not make the cystic fibrosis disappear: the digestive problems and the other symptoms remain always present.
Pulmonary transplantation is mainly used in adults. Nowadays, it is rare that a transplant is needed before the age of 18 years. The survival rate 1 year after the intervention is 80% of cases. 5 years after a lung transplant it is 60% the main cause of death is the chronic rejection of the transplanted organ.
Despite a good appetite, children with cystic fibrosis lose weight. This is due to the poor digestion of food, caused by the pancreas. Respiratory disorders can also affect growth and weight gain. Sufferers therefore need a special diet, established by a nutritionist. Their diet must be richer in protein and calories, to reach 120% to 130% of the usual caloric intake of children of the same age. This diet compensates for the poor absorption of lipids in the small intestine and corrects nutritional deficiencies. It helps to minimize growth delays.
Often, taking various oral supplements is often necessary.
- Of pancreatic enzymes help better digest fat and replace natural enzymes that are “blocked” in the pancreas. These medications should be taken at the beginning or during meals.
- Some supplements soluble vitamins (A, D, E and K) and carotenoids, as they are less well absorbed are needed. Of the mineral supplements are recommended, such as sodium chloride (salt), s urtout AC s fever or significant sweating (when it is hot, for example). In fact, sufferers lose a lot of sodium by sweating. Some calcium supplements are also available because of the increased risk of osteoporosis.
If the special diet and dietary supplements are not enough to gain weight, enteral nutrition will be required either by gastric tube or gastrostomy.
Psychological and social support
A help from relatives, but also discussions with other parents of children with or meetings with a psychologist are invaluable for the patient and family members.
Patient and parent associations dedicated to cystic fibrosis offer all sorts of practical information about treatments and daily life with the disease. For more information, see the Support Groups section below.
Advice to parents
Here are some tips offered by Mayo Clinic to parents of children with cystic fibrosis 10
- Encourage your child to be active. Sport is not inadvisable, quite the contrary. It improves the lung function and the well-being of the child, and strengthens the respiratory muscles. Talk to your doctor.
- Be sure to follow a special diet, as recommended by the doctor or nutritionist or dietician. If the child is too hungry or has no appetite, tell the doctor.
- Be very rigorous about taking daily supplements of vitamins and digestive enzymes.
- Encourage your child to drink a lot: water liquefies mucus and facilitates bronchial drainage.
- Do not smoke in the presence of the child since second-hand smoke aggravates breathing disorders.
- Establish the habit of frequent hand washing for all members of the family to prevent infections.
- Be up to date in the schedule of vaccinations