One of the most common autosomalrecessive disorder especially in white people is cystic fibrosis with afrequency of about 1 in 2500 livebirths (Ratjen &Döring, 2003).
This genetic disorder was identified in1989 and is found at 7q31.2, the long arm (q) of chromosome 7 at position 31.2 (Grossman & Grossman,2005). It is associatedwith high rates of premature death (Bethesda, 2013). According to aclinical study conducted by Jane C Davies, Eric W F W Alton, and Andrew Bush (2007), cysticfibrosis used to be a digestive and lung disease of young children but morerecently has become a complex, multisystem disease extending into adulthood;there will soon be more adults than children with the condition. Cysticfibrosis is a progressive disease. In the United States, between the year 2000 and 2010, the number of diagnosed patientsincreased from 21 000 to 26 000 (MacKenzie, et al.
, 2014). The predicted median survival for babies born in the21st century is now more than 50 years. Due to the changes in the standardtreatment given to patients, life expectancy of patients with the disorder has been greatly increased over the past decades. PATHOPHYSIOLOGY Cystic Fibrosis (CF) isconsidered lethal since it affects different organ systems and exhibits a rangeof clinical problems of varying severity. This is most common among Caucasians (Sheppard & Nicholson,2002). Cysticfibrosis is inherited in an autosomal recessive manner, meaning that males andfemales are equally affected and two copies of the faulty CFTR gene arenecessary to have the disease, one from the mother and one from the father.
Ifboth parents carry the faulty gene, there is a 25 per cent chance their childwill have cystic fibrosis, a 50 per cent chance a child will be a gene carrierbut not have cystic fibrosis and a 25 per cent chance they will not have thefaulty gene (Buckland,2016) Approximately 70% of the patients affected by CFhave the commonest mutation which is thedeletion of phenylalanine at codon 508 (phe508del, until recently known as?F508) ((Davies, Alton, & Bush, 2007). According to the book written by James C. Cunningham, M.D and Lynn M. Taussig, M.D (2013), thehealthy version of the gene directs the making of a protein called the CysticFibrosis Transmembrane conductance Regulator (CFTR). This protein forms a channelso that salt (chloride sodium) and water can move in and out of cells (calledion transport). The CF gene mutation changes CFTR so that the protein does notwork properly.
As a result, there is an abnormal ion transport of salt andwater in the cell. The biggest changes are in the sweat and mucous glands. Secreted fluids are normally thin andslippery. But in people with cystic fibrosis, a defective gene causes thesecretions to become sticky and thick.
Patients with thisgenetic disorder which have a mutated gene makes the sweat glands produce amore salty sweat than the normal. Researchshows that abnormal salt transport in cells occurs in all of the exocrineglands in CF. This problem is called the basic defect in CF (Cunningham & Taussig,2013). Since mucous glandsare affected, lungs and intestines are the most vulnerable organs. Lungsdisease is the cause the most number of deaths of about 95% of patients andonly the lung develops a chronic infection phenotype with an associated intenseinflammatory response (Donaldson & Boucher, 2006). Current evidencesuggests that the CF lung is free of infection and not inflamed at the time ofbirth (Armstrong,et al.
, 1997). Over the course of months to years,however, stigmata of first recurrent and then chronic infection begin toappear. Microbiologic studies reveal a fairly typical evolution of pathogens,with respiratory viruses, Haemophilus influenzae and Staphylococcus aureus,predominating early in life.
With time, more problematic and increasinglyresistant pathogens, including Pseudomonas aeruginosa and other Gram-negativebacteria (e.g. Burkhol deria cepacia complex, Stenotrophomonas maltophilia ,Achromobacter xylosoxidans ), often dominate the clinical picture (Dakin, et al.
, 2002). On the other hand, gastrointestinalproblems in patients with cystic fibrosis are due to the inability of thepancreas to supply digestive enzymes to the intestine. Because the volume ofpancreatic enzymes secreted decreases, the pancreas secretes thick mucus thatobstructs the pancreatic ducts and the volume of enzymes that can be secretedbecomes even smaller (Stites, Plautz, Bailey, et al., 1999). The types ofcomplications in patients with cystic fibrosis differ depending on the degreeof mutation of CFTR. Also, some patients do not experience pathological changesin all the systems usually affected by cystic fibrosis. Respiratory,hematopoietic, gastrointestinal, endocrine and reproductive organ systems are onesthat are vulnerable to diseases if a person is affected by this geneticdisorder(Grossman & Grossman, 2005).
CLINICAL MANIFESTATION Based on the Report of the Canadian Patient DataRegistry (2001),Cystic Fibrosis primarily manifest in childhood. Diagnosis ofCF is made by sweat testing when there is elevation of sweat chloride by > 60mmol/l in a patient with one or more clinical features consistent with the CFphenotype, a positive neonatal screening test, or history of CF in a sibling (Smyth, 2005). Diagnosed cysticfibrosis adult patients often manifest pancreatic sufficiency, inconclusive sweat test results, and a highprevalence of mutations that are not commonly seen in childhood. Although most patients have lung disease of variabledegrees, single-organ manifestations such as congenital bilateral absence ofthe vas deferens and pancreatitis are seen. Repeated sweat tests and extensivemutation analysis are often required. Nasal PD may aid the diagnosis, but hasnot been standardized for clinical diagnosis. Patients with CF diagnosed in adulthood present with a wide spectrum ofsymptoms and severity of disease that does not resemble the characteristicfeatures at presentation in childhood.
(Gilljam, Zienlenski, Durie, & Tullis, 2004). Diseaseprogression is reported in infancy and throughout childhood. The youngest age at which disease progression was reported was bythe age of 6 months in both digestive (pancreatic sufficiency decline) andrespiratory systems (lung function decline). Accumulation of lung damage wasreported by 1 year of age, and lung structure and function worsenedsignificantly each year of life in young children, with potentiallyirreversible lung damage reported by the age of 2 years (VanDevantera, Kahleb,O’Sullivan, Sikirica, & Hodgkins, 2016).
MEDICAL MANAGEMENT Danny Buckland (2016)reported that there is no cure forcystic fibrosis but due to the advancement of technology and new discoveredtreatments for cystic fibrosis, successful therapy regimens are available,which combine medication, physiotherapy, exercise and nutrition can be of greathelp to patients suffering from this genetic disorder. A multidisciplinaryapproach, combined with new inhaled therapies, mucolytics and antibiotics, hasvastly improved both longevity and quality of life. Exciting advances are beingmade with genetic research but there is still concern about wrinkles in serviceprovision and that new medicines are struggling to win approval from NICE andthe Scottish Medicines Consortium (SMC) because they are costly.
A recent negativeruling from National Institute for Health and Clinical Excellence (NICE) on thegene mutation-specific lumacaftor/ ivacaftor (Orkambi) – a twice dailycombination drug treatment that improved lung function in clinical trials –sparked consternation among patients (Wainwright, etal., 2015). Up until recently, the drug treatments available for cystic fibrosisonly controlled symptoms or prevented and reduced complications. Suchtreatments include antibiotics for chest infections and bronchodilators andsteroids for airway inflammation, as well as the mucolytics dornase alfa andmannitol, which are specifically licensed for cystic fibrosis. However, in thepast few years, medicines that target the underlying cause of the disease byimproving the functioning of CFTR ion channels have become available. There areseveral that could be taken up by patients such as, Dornase alfa (Pulmozyme),Ivacaftor (Kalydeco), Mannitol and Lumacaftor/ ivacaftor (Orkambi) (Buckland, 2016).
Each drug has their own corresponding purposes, treatments, methodof delivery, mode of action, and side effects. Patients are advised to visittheir attending physicians to ask for what treatment or drug they shouldtake.