Cystic fibrosis is a heterogeneous autosomal recessive disorder characterized by severe respiratory and digestive problems, salty sweat and infertility. In the UK, over 7500 people are affected with an incidence rate of 1 in 2500 live births.
The condition is usually existent since birth and diagnosed through methods such as prenatal screening, amniocentesis and chorionic villus sampling in unborn babies.
According to the cystic fibrosis foundation (2013), 62% of patients are diagnosed at birth while 72.4% of patients are diagnosed within the first year of life. Yet, although commonly known for its early onset, the cystic fibrosis foundation reports of a class of patients named late diagnosis who are diagnosed after the age of 18 found to be caused by the residual nature of the cystic fibrosis transmembrane regulatory mutations which delays onset (B.Hunat and D.M Geddes ,1985).
According to reports, Canada has an around eighteen late diagnoses annually. The condition is inherited by a recessive allele. An individual needs to inherit two copies of the recessive allele to become affected which is only possible when two carrier parents have a child together.
However, the chance of having a child with cystic fibrosis is one in four- a 25% chance — for each pregnancy. It occurs as a result of the malfunction or absence of chloride transport channels of the exocrine glands caused by a mutation in the cystic fibrosis transmembrane regulator (CFTR) gene located at the 31.2 locus of the q arm (long arm) of the seventh chromosome. There are over 170 identified possible mutations suspected to cause cystic fibrosis (Collins FS,1992)
The most common mutation is a deletion known as DF508 in which the codon located at the 508th position in exon 10 gets deleted. The codon codes for the manufacture of amino acid phenylalanine. As a result, a defective cystic fibrosis transmembrane regulatory (CFTR) protein with a wrong codon sequence producing a cystic fibrosis transmembrane regulatory (CFTR) protein channel which either becomes absent or does not function is produced causing various physiological issues within the individual.
The function of the cystic fibrosis transmembrane regulator gene is to code for a specific protein known as the cystic fibrosis transmembrane regulatory (CFTR) protein whose function is to build chloride channels known as the cystic fibrosis transmembrane regulatory (CFTR) protein channels which align the surface membranes of the cells forming the epithelial lining of various organs and systems. Due to the mutations, the chloride channels fail to function adequately resulting viscous mucus .Cystic fibrosis predominantly affects the respiratory system, the digestive system, the reproductive system and the sweat glands.
In the respiratory system, mucus builds up along the respiratory tubes of the lungs clogging them, reducing the surface area available for gaseous exchange .The amount of oxygen in blood decreases causing breathlessness, a lack of energy, chronic fatigue and coughing fits. Dust particles and pathogens inhaled is often trapped in the thick mucus for prolonged periods providing ideal breeding grounds for bacteria increasing susceptibility to lung infections such as pneumonia ,obstructive pulmonary disorders, emphysema, bronchitis and acute respiratory failures. In the digestive system mucus blocks the pancreatic duct preventing digestive enzymes reaching the duodenum. As a result, digestion does not take place adequately .Trapped digestive enzymes begin digesting the cells around it damaging the cells of the pancreas and often leads to diabetes in cases where the damage reaches the insulin producing cells of the pancreas. Mucus produced along the gut lining forms a barrier between the food contents and the gut lining and clogs the villi reducing the surface area available for absorption. As a result, fail to obtain good nutrition .They suffer from malnutrition, abdominal distress and has a very thin physique. The deficiency of vital vitamins and mineral ions often lead vitamin/mineral related diseases like osteoporosis, rickets, scurvy etc .Other phenotypic features include meconium ileus, the distal intestinal obstruction syndrome, rectal prolapse, hypoproteinemia abnormal bowel movements and edema.
Infertility arise due to complexities associated with mucus in the reproductive tract. In females, mucus assists fertilization by helping the sperm move through the cervix and reach the ovum by acting as a lubricant. Ovaries often produce fertile egg cells but fertilization is less likely because the sperm fail to reach the egg cells due to the obstruction of the cervical canal by mucus. In some instances mucus obstructs the oviducts preventing the release of egg cells making fertilization even less likely. In contrary to female counterparts, affected males lack the vas deferens. Due to the absence of the structure to carry the sperm from the testis into the semen, ejaculation does not occur in men. In some men the vas deferens is present, but is blocked, completely or partially, by mucus releasing only a few sperm into the semen. The low sperm count makes fertilization less probable.
The final overt characteristic is salty sweat. Sweat glands in the human body contains a structural duct along which the produced sweat is passed to the surface of the skin.
As sweat pass through the duct, the cystic fibrosis transmembrane regulatory protein channels move the chloride ions into the cells along a concentration gradient. Sodium chloride is reabsorbed and the loss of important ions is prevented .In cystic fibrosis patients, the cystic fibrosis transmembrane regulatory protein channels fail to move the chloride ions into the cells causing the loss of sodium [Na+] and chloride ions [cl-]. It causes disruptions in the ion balance of the body various health defects such as abnormal intrinsic rhythms of the heart, heart failure, low blood pressure, abnormal nerve signaling etc.
Although uncommon, cystic fibrosis manifests various psychological reactions among its victims. Lawler, Nakielny and Wright (1966) conducted a psychological and psychiatric study on 11 children with cystic fibrosis. The findings implied depression to predominate all psychological problems which the participants displayed through interesting methods such as elaborative drawing, preoccupation with sad music along with noticeably intense anxiety throughout the study period. The patients also showed signs of the excessive use of defense mechanisms , the most common ones being denial, excessive use of fantasy, hostility towards self and others, progressive depression, regression and repressed aggression. The study indicates the incidence of moderate psychopathology among the participants. Affected individuals usually experience negativity in mood due to limited social interaction and restricted daily activity due to treatments and physical complications.
According to Beinke (2011), adolescent boys seem less confident in their bodies due to the lack of a well-built physique. Both genders are reported to have psychosexual problems associated with infertility. Men often feel impotent while females feel unattractive. Factors like parental overprotection /rejection along with a less peer network which accompanies by is associated with the poor development of self-concept (Beinke,2011)
There is no cure for cystic fibrosis. Hence, health professionals focus on minimizing the effects of the symptoms by confronting them with a range of different systematic treatment methods such as antibiotics, physiotherapy, diet management, enzymes, drug therapies, transplant surgeries, infertility treatments and gene therapy. Physiotherapy includes a spectrum of physical therapies, typically, motivated to amputate mucus from the respiratory system and improve breathing whilst the management of other physical complications. The airway clearance techniques (ACT) such as the active cycle of breathing technique (ACBT) and the Positive expiratory pressure (PEP), inhalation therapy, Weight bearing exercises, physical exercises are few of the physical therapies involved in physiotherapy. According to Elbasan B et.al (2012), chest physiotherapy along with active breathing techniques share a positive correlation with aerobic performance, thoracic mobility and physical fitness along with an increase in chest circumference among.
Due to lack of adequate nutrition affected individuals are advised to consume a balanced diet for regular meals along with high-fat, high-protein and high-carbohydrate foods.
As a result of the difficulties in digestion and absorption, they also need to eat about twice more than unaffected individuals to make up for what they are unable to digest. They essentially also need to take in enzymes together with the meals to replace the blocked pancreatic enzymes and help digestion. As a result of the extensive symptom-count expressed by the condition, treatment methods always entail the prescription of several countless drugs, also called drug therapy. The most commonly prescribed are antibiotics, vaccines, mucolytic drugs, asthma drugs, DNAase enzymes and insulin. Antibiotics destroy the bacteria trapped in the mucus along the airways reducing the likelihood of lung infections. They are usually breathed in, rather than orally consumed, using aerosols to transport them to the internal tissues where they are needed. Affected adults are injected ’flu vaccines and pneumonia vaccines annually. Asthma drugs and mucolytic drugs are essentials. Asthma drugs such as salbutamol and steroids lessen the impact of the condition by reducing inflammation and clearing the airway while mucolytic drugs such as acetyl cysteine and ambroxol breaks down mucus making it runny so that it can be easily coughed off. Insulin is a provided in a regular basis to control blood sugar levels if the affected individuals are diabetic.
Heart and lung transplant surgeries are performed when the damage to the organs are severe and the organs fail to function adequately. Patients who has undergone organ transplants need to consume immunosuppressive drugs for great lengths of time to suppress the immune system from rejecting the new tissue. These patients are usually under specialized care to prevent secondary infections that arise as a result of the weakened immune system. Patients often do well after the surgery.
Another common treatment is infertility treatment. There are not many available though. The most common method is in vitro fertilization (IVF) where the sperm cells and egg cells are extracted from the parents, fertilized in a laboratory and returned to the mother’s uterus or a surrogate mothers uterus where the fertilized zygote can develop into a healthy human child.
Gene therapy is the sole treatment method which focus on eliminating the symptoms entirely and curing cystic fibrosis instead of minimizing the effects of the symptoms.
Gene therapy attempts to replace the defective cystic fibrosis transmembrane regulatory gene with a healthy cystic fibrosis transmembrane regulatory gene using a vector. In detail, the functional cystic fibrosis transmembrane regulatory gene sequence is cut using the restriction endonuclease enzyme. An mRNA copy is transcribed from the healthy DNA sequence and reversed using the reverse transcriptase enzyme. The prepared healthy gene is then attached to the DNA of a vector which will carry it to the target cells. The most commonly used vectors are plasmids, harmless viruses and liposomes. Once the vectors reach the target cells and insert the modified DNA into the target cells, special enzymes called DNA ligase help it pass through the nuclear membrane and stick into the host DNA. Once joint with the host DNA, the healthy gene will produce the functional cystic fibrosis transmembrane regulatory protein and relieve the symptoms. Though gene therapy is a potential relief for patients it is not much practical in conductance due to limitations of the procedure. Limitations include intra/extracellular membranes making it difficult for the vectors to reach host DNA, loss of restored cells due to constant shedding of the epithelial linings and the short lifespan of the gene expression.
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