The Present And Future Outlooks For People Suffering From Cystic Fibrosis
Abstract
Cystic fibrosis has traditionally been a dire diagnosis meaning that there would be a shot life full of many complications, frequent hospital appointments and a poor quality of life. Recent medicine however has enabled people with cystic fibrosis to live longer and higher quality lives than ever before. This essay examines the change in quality of life and outlook for cystic fibrosis over time and how this may change in the future.
Introduction
Cystic fibrosis is a genetic condition which affects over 10,400 people in the UK. The disease has no true cure and thus people with the disease suffer throughout their lives with many recurring health issues especially pulmonary illnesses and issues with nutrition. Because of this people that suffer from cystic fibrosis have a much lower quality of life than fully healthy people with individuals having frequent hospital visits and taking large amounts of medication.
Cystic fibrosis is often not the final cause that kills an individual but rather a secondary illness that has developed as a result of the disease this means that many of the drugs and treatments that people diagnosed with cystic fibrosis have are more focused of treating the secondary illnesses rather than directly treating the cystic fibrosis. Because cystic fibrosis is such a serious condition It not only effects those that suffer from the condition but also those that are carriers and the families that surround the condition. For those that carry the defective alleles there is often lots of anxiety and stress around having children to the point at which some people that know they are a carrier refuse to have children. Families surrounding sufferers of the condition, especially parents of children that have the condition, are put under a lot of stress as they have to care for their relatives this can have detrimental effects on the mental and physical health of the individuals concerned.
In this essay I will examine if the outlook for patients with cystic fibrosis has improved and if it has is it still improving. In order to do this, I will first examine what cystic fibrosis is and its symptoms before I move on to examining how it is currently diagnosed and treated and then finally what the future may hold for people with cystic fibrosis.
What is cystic fibrosis
Cystic fibrosis is an autosomal recessive genetic condition that causes a sticky mucus build up in the digestive system and lungs. This can cause lung infections and problems with digesting food. It is estimated that 1 in 25 of us are carriers of a mutation in one of the genes that encodes cystic fibrosis transmembrane conductance regulator (CFTR) protein, however because cystic fibrosis is a recessive genetic disease the mutated gene must be carried by both parents in order for their child to express cystic fibrosis.
Cystic fibrosis is a fatal disease and in 2018 caused 132 deaths in the UK. The median survival time of cystic fibrosis has been slowly climbing from 23 years old in 2004 to 31 in 2017 this is due to new treatments and better care for those suffering from cystic fibrosis. There is also a trend showing that males that live with the disease tend to live slightly longer with the median life expectancy of males being 49. 6 years compared with 43. 1 years in females between 2013-2017.
There are many different mutations that can affect CFTR all of these mutations are found on the 7th pair of chromosomes. In order for cystic fibrosis to be expressed each of the pair of chromosomes must have a mutation on it and since one of these chromosomes comes from each of parent it can easily be calculated using the Punnett square that even if both parents are carriers of cystic fibrosis there is only a 25% chance of the offspring having the disease.
What is the molecular mechanism of cystic fibrosis
Cystic fibrosis is a recessive autosomal genetic disorder where there is a mutation in the gene that encodes cystic fibrosis transmembrane conductance regulator (CFTR) protein, this mutation results in the CFTR protein not functioning properly. CFTR is an ATP-binding cassette transporter consisting of 3 distinct parts, which consist of two membrane-spanning domains, two nucleotide-binding domains and a regulatory domain. The mutation that is responsible for cystic fibrosis can occur in any one or multiple domains and will result in one of two possible defects; firstly, a chloride channel that is the wrong shape and cannot insert into the apical membrane and thus is absent all together or secondly, a channel that cannot open and close properly in the membrane.
Normally the CFTR protein becomes a chloride ion channel in the apical membrane of epithelial cells, however in people with cystic fibrosis the mutation can result in this ion channel being either absent or dysfunctional. The result in this channel not functioning is that chloride ions are not pumped out of the cell, normally these chloride ions would attract sodium ions and this would in turn result in the flow of water to the outside of the cell and mucous being hydrated and thinned so that it can be cleared. Since the mucous cannot be thinned it cannot be cleared by normal ciliary action and it begins to build up in organs.
The built up mucous in patients with cystic fibrosis provides an ideal environment for bacteria to grow in this allows for the development of further complications specifically chronic pulmonary infections, degradation in lung function and issues in other organs that mucous builds up in.
What are the symptoms of cystic fibrosis
Cystic fibrosis can show multiple symptoms including recurring chest infections, shortness of breath, wheezing, coughing and bronchiectasis due to the buildup of mucous within the lungs. There are also other symptoms that are associated with the mucous building up in other organs such as the pancreas. When the pancreas has a buildup of mucous there is difficulty in enzymes reaching the gut for digestion, this results in food being not fully digested therefore patients with cystic fibrosis often struggle to put on weight and can easily become malnourished. Patients with cystic fibrosis can also exhibit abnormalities with their stool or suffer from constipation or diarrhoea as a result of food not getting fully digested. Patients with cystic fibrosis also often develop a number of related illnesses due to the cystic fibrosis such as diabetes, osteoporosis, infertility in males and liver problems. These secondary illnesses can all be attributed to the buildup of mucous causing blockages in different organs such as the pancreas, sperm ducts or liver. These secondary illnesses often provide complications that further reduce the quality of life of individuals.
How is cystic fibrosis diagnosed
In the UK most new born babies are screened a few days after birth by having a heel prick test also known as the newborn blood spot test however this program does allow parents to opt out this can result in some people not finding out that they have cystic fibrosis until later in life. The heel prick test is a test for 9 serious conditions including cystic fibrosis. If the result of the heel prick test indicates that a baby may have a gene for cystic fibrosis more tests will be done to indicate if that individual is a carrier or they are expressing the gene. If an individual has not been diagnosed with cystic fibrosis at birth or their heel prick test indicates that they may have cystic fibrosis, then two further tests are performed. Firstly, a sweat test is done, this test shows the amount of salt in the sweat and if it is unusually high then this is an indication that the patient could have cystic fibrosis. Secondly a genetic test is done by taking a sample of blood or saliva which is then sequenced to check for any faulty genes.
How is cystic fibrosis treated
The outlook for people that suffer from cystic fibrosis worsens with time and although there is no true treatment for cystic fibrosis there are treatments that can control the symptoms and make the condition easier to live with however regular hospital appointments for check-ups to monitor the condition are still required. To treat lung problems people with cystic fibrosis may have to take a variety of medicines to treat and prevent lung related complications, these may include antibiotics to treat bacterial infections, and medicines to reduce production of and thin mucous that builds up in airways. There are also medicines available to increase the diameter of the airways in order to allow for easier breathing and steroids to treat small growths that can develop in the nose. These drugs are administered in three ways: orally, via inhalation or by injection. Air way clearance techniques are also employed by people with cystic fibrosis this can include active cycle of breathing techniques and autogenic draining which is a series of gentle breathing techniques. There are also away clearance devices which are small handheld devices that use vibration and air pressure in combination with controlled breathing techniques in order to loosen and remove built up mucous deposits within the airways. Physical exercise is also recommended to people that suffer from cystic fibrosis as this can help to loosen mucus as well as improve overall health.
Cystic fibrosis also requires a carefully controlled diet as because the pancreas does not function properly is difficult to digest and absorb nutrients. This means that cystic fibrosis sufferers often have to attend appointments with dietitians to discuss methods to obtain extra calories. Diets that are recommended are often high calorie and will include mineral and vitamin supplements as well as enzyme capsules to aid in digestion. Patients with severe cystic fibrosis and those where other treatments have proven ineffective and the lungs have failed can be recommended lung transplants, however as organs are in short supply there are often long waiting lists with an estimated 6,300 people awaiting an organ transplant at any one time with around 70 of those being patients with cystic fibrosis. All patients are with cystic fibrosis are advised to keep up to date with vaccinations and are also advised to get the annual flu vaccination in order to try to reduce any possibilities of complications caused by preventable illnesses.
There is often a need for mental health to be monitored as people with cystic fibrosis are more likely to develop mental health issues such as depression and this in turn can interfere with people’s ability to take care of themselves. If this goes untreated then patients can become less likely to manage their treatment plans which can then further lead to increased hospitalisation and a lower quality of life. Researchers have also found that those who look after people with cystic fibrosis are also at a significantly higher risk of developing mental health issues specifically depression. This problem is addressed by counselling and by charities working with families and sufferers of the condition to try to treat the depression, in cases that this does not work then antidepressants can be prescribed in addition to the support that is given. Future possibilities Although modern medicine as already dramatically increased the quality and length of life for sufferers of the condition there is still a lot of research to be done to fully understand the it. There is also no current cure for cystic fibrosis, A cure for cystic fibrosis will be the ultimate goal however this seems to be a long way off.
Current research
I focused on three main groups of drugs: potentiators, correctors and read-through agents. Potentiators increase the activity of correctly positioned CFTR channels. Correctors alter defects in the folding of F508del the protein which is responsible for the vast majority of cystic fibrosis cases. Read- through agents enable ribosomes to ignore stop codons that appear too soon in the genetic code as a result of a mutation. Potentiators are one of the most significant development of recent times in the treatment of cystic fibrosis. One particular potentiator called ivacaftor in particular has showed a lot of promise with trials confirming the ability of the drug to increase the activity of CFTR in Asp551Gly (G551D), the most common mutation of this type, and was proven to be safe in a clinical trial in children between 2-5 years old. This drug has recently reached approval in the UK and is now available to everyone over the age of two who is eligible. F508del is the most common cystic fibrosis causing mutation worldwide with it occurring in 89. 5% of cases in the UK, it results in CFTR not being folded correctly and thus the channel is ineffective. New developments into correctors have generated a number of new drugs that can be used as a stand-alone or in combination with other drugs, one such drug is Lumacaftor (VX-809) this has been shown to restore CFTR function to ~15% of that of normal levels in vitro. When Lumacaftor was combined with vacaftor there was significant improvement in FEV1.
Ataluren allows ribosomes to read-through of premature termination codons resulting in the formation of a full length CFTR instead of a shortened non-functioning version. In a large-scale phase III trial, there was little difference seen between patients that were given the drug and those that received a placebo however there was noted benefits to patients not receiving inhaled aminoglycoside antibiotics. This led researchers to theorise that that aminoglycoside antibiotics was inhibiting the effect of Ataluren this prompted a second Phase III trial to be carried out to investigate this with an estimated completion date of June 2019. Gene therapy has been a promising area of research for treatment or even a cure for cystic fibrosis for many years research. There is lots of work that is currently happening that is working towards using gene therapy to treat cystic fibrosis, some examples of this are Liposomal CFTR gene therapy which has completed phase IIb clinical trials, pseudotyped lentivirus and QR010 is currently in phase I trials. These trials are providing hope for future treatments for cystic fibrosis.
Conclusion
In recent times there have been many developments that have aided in the improvement of quality of life for sufferers of cystic fibrosis be it providing better care plans for patients through to new medicines that can extend life and reduce complications. This gives hope to families, carriers and sufferers of cystic fibrosis around the world that treatment will continue to improve their outlook and quality of life and perhaps one day find a cure. In terms of future developments there appears to be many new roads which are providing promising new treatments that are being entered in to new medical trials continually, however, there appears to be still a long way to go before a total cure for the disease meaning that it is likely to be many years until cystic fibrosis can be eradicated. To answer the question posed at the beginning of this essay I believe that the outlook for patients with cystic fibrosis has improved and furthermore I believe that there is enough evidence to say that the current research will continue to improve the outlook for sufferers of cystic fibrosis.
