Current Trends in Cystic Fibrosis

Interview with Theresa Lowry- Lehnen (PhD), CNS, GPN, RNP, South East Technological University.

Cystic fibrosis (CF) is an inherited chronic disease, primarily affecting the lungs and digestive system of over 1,300 children and adults in Ireland and 70,000 people worldwide. 1 Between 2008 and 2016, an average of 38 individuals in Ireland were diagnosed with CF each year, with 22 diagnosed in 2016. 5 Ireland has the highest incidence per head of population of CF in the world, with three times the rate of the United States and the rest of the European Union. 1

We spoke with Theresa Lowry Lehnen, Clinical Nurse Specialist and Associate Lecturer Institute of Technology Carlow to learn more about this lifelong condition.

The symptoms and severity of cystic fibrosis vary from person to person. The majority of people have both respiratory and digestive problems. There is no cure for cystic fibrosis, however, life expectancy has increased steadily over the past 20 years, and today cystic fibrosis is no longer exclusive to childhood.

At the beginning of each year, the CF Registry of Ireland (the ‘registry’) conducts a survey of hospitals known to provide care to people with CF in the Republic of Ireland. The registry has gathered information on people with CF since 2002. The annual hospital census carried out by the registry in 2016 showed that 1,339 people were living with cystic fibrosis (PWCF) in Ireland. Most patients attended one hospital for CF care (n=1,107, 82.7%), whereas 17.3% (232) shared care at two or more hospitals. 2016 was also the first time that the median age for PWCF reached 20 years (half of the population over 20 years and half under) while 8.9% of the PWCF population in Ireland was recorded as over 40 year’s old. There were 1,266 individuals (565 children and 701 adults) with CF on the registry on the last day of 2016, representing 94.5% of people living with CF in Ireland in that year.

Theresa told us, “About 2,000 CFTR gene mutations have been identified to date. Genetic testing provides important information to assist the diagnosis and treatment of cystic fibrosis. F508del is the most commonly detected CFTR mutation in Irish people living with CF.

“In 2016, 91.6% of the CF population had at least one copy, 15.2% at least one copy of G551D, and 5.8% at least one copy of R117H. All other CFTR mutations affect less than 5% of the CF population. Fifty-five percent of patients (55.6%) living with CF in Ireland in 2016 had two copies of the F508del mutation (F508del homozygous). This compares with 46.1% in the United States and 50.3% in the United Kingdom in 2015. Thirtysix percent (36.0%) of people had just one copy of the F508del mutation (F508del heterozygous). The F508del homozygous mutation is the most common CFTR gene mutation in people under 40 years. In those over 40, F508del heterozygous mutations are most common.” 5

Cystic fibrosis affects multiple organ systems including the lungs, pancreas, upper airways, liver, intestine, and reproductive organs to varying degrees. Early diagnosis provides opportunities for earlier medical intervention.

Providing infants with the best possible care results in better nutritional and lung function outcomes later in life, says Theresa. “Optimised treatment prolongs the lives of people with cystic fibrosis, improving their quality of life,” she says.

“Improved diagnosis and symptomatic treatments have increased the survival rates of people with the condition, from a life span of only a few months in the 1950s to a global median age of 40 years today. The predicted median age of survival for a person in Ireland with CF is early to mid-30’s.”

Cystic fibrosis is caused by a gene mutation leading to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel of exocrine glands. The defect leads to diminished chloride secretion which, in turn, leads to increased sodium absorption through epithelial sodium channels and removal of water from secretions, which become abnormally viscous. “The effects cause obstruction, inflammation, infection in the lungs and upper airways, tissue reorganisation and loss of function. The severity of the disease in the individual depends on variable organ sensitivity and on the genetically determined residual function of the CFTR protein. 99% of affected male patients are infertile because of obstructive azoospermia, and 87% of patients have exocrine pancreatic insufficiency. Disease severity particularly the degree of pulmonary involvement, also depends on other diseasemodifying genes and a number of factors including socioeconomic background,” says Theresa. 2, 3

Diagnosis

Most cases of cystic fibrosis are diagnosed through screening tests, which are carried out early in life. However, some babies, children and even young adults are diagnosed later following unexplained illness.

Symptoms

Theresa explains, “People with cystic fibrosis present with a variety of symptoms, including, very salty-tasting skin, persistent coughing with phlegm, frequent lung infections, wheezing or shortness of breath, poor growth/ weight gain despite a good appetite and frequent greasy, bulky stools or difficulty in bowel movements. 1

“Symptoms usually appear in the first year of life, although occasionally they can develop later. The thick, viscous mucus in the body affects a number of organs, particularly the lungs and digestive system. Typical respiratory symptoms include cough and wheeze. Recurring chest and lung infections are caused by the continual buildup of mucus in the lungs, which provides an ideal breeding ground for bacteria. 7 Organisms detected in the airways of individuals with CF in Ireland in 2016 included Staphylococcus aureus (54.7%) and Haemophilus influenza (29.0%) found most frequently in children. Pseudomonas aeruginosa was detected in at least one respiratory sample of 60.3% of adults. 5 Two strains of bacteria that commonly infect people with cystic fibrosis are Pseudomonas aeruginosa and Burkholderia cepacia complex. They multiply in the thick mucus inside the lungs and may cause serious health problems and repeated chest infections. As more and more people with cystic fibrosis become infected with these bacteria, the bacteria become resistant to antibiotic treatment, which is why cross infection is such a problem. Lung infections caused by Pseudomonas aeruginosa and Staphylococcus aureus can become chronic, and cause an irreversible reduction in lung function. 5, 7

“Chronic disease of the lungs and paranasal sinuses varies among patients with cystic fibrosis and can be difficult to distinguish from frequent recurrent bouts of bronchitis and/or pneumonia, especially in young children. Children with cough, sputum production, or wheezing of more than three months’ duration, persistently abnormal radiological findings, persistently positive bacterial cultures of respiratory secretions, or clubbing of the fingers should undergo diagnostic testing for cystic fibrosis even if their neonatal screening test was negative. The same applies for children with bilateral chronic rhinosinusitis with frequent exacerbations, with or without nasal polyps. 2

“Cystic fibrosis causes mucus to block the ducts in the pancreas leading to malnutrition, steatorrhoea and diabetes. People with cystic fibrosis who develop diabetes may find it difficult to gain weight or may lose weight and see a decline in their lung function. Cystic fibrosis-related diabetes is usually controlled by regular injections of insulin. Diabetes rarely occurs in children with cystic fibrosis. 6

“Pancreatic insufficiency (PI) is manifested by voluminous, fatty, shiny, malodorous, pulp like stools, abdominal symptoms, dystrophy, and deficiencies of fat-soluble vitamins (e.g., hemolytic anemia due to vitamin E deficiency) and trace elements (e.g., zinc dermatosis). The diagnosis can be established by a low fecal elastase measurement. Patients with primary pancreatic insufficiency are at increased risk of chronic and/or recurrent pancreatitis.” 4

In addition, Theresa reveals that people with cystic fibrosis are also prone to sinusitis and hay fever. She continues, “Older children with cystic fibrosis can develop a form of arthritis in joints such as the knee which improve with time and treatment. Older children and adults are prone to osteoporosis due to, repeated infection, poor growth or weight, lack of physical activity and lack of vitamins and minerals due to digestive problems. People with cystic fibrosis are more at risk of developing osteoporosis if they are taking steroids to help with lung infections. Osteoporosis as a result of cystic fibrosis may cause joint pain and cause bones to fracture more easily. Bisphosphonates are taken to help maintain bone density. 6

“One in ten babies with cystic fibrosis is born with meconium ileus and an operation to remove the blockage will probably be required. 6 In nearly all men with cystic fibrosis, the spermatic tubes do not develop correctly, making them infertile. Women with cystic fibrosis may find their menstrual cycle becomes absent or irregular if they are underweight. There is also an increased thickness of cervical mucus, which may reduce fertility. However, most women with cystic fibrosis can conceive without any difficulty. 6

If the bile ducts in the liver become blocked by mucus as the disease progresses, this can be serious and in some cases a liver transplant may be necessary.” 6

Treatment

There is no cure for cystic fibrosis. The aim of treatment is to clear and control infections in the lungs and digestive system, and reduce long-term damage caused by infection and organ complications.

Talking about current treatments, Theresa says, “Inhaled bronchodilator drugs are treatments used to relax the muscles surrounding the airways and help the person breathe more easily. Antibiotics are prescribed to treat infections in the lungs. All young children diagnosed with cystic fibrosis are started on a course of oral antibiotics to protect them from certain bacteria, which will be continued until they are three years of age. The number of days spent on IV antibiotics for pulmonary exacerbation for all people with CF in Ireland in 2016 came to a total of 14,084. The mean duration of pulmonary exacerbation treatment was 16.4 days and median duration was 14 days. 5 Steroids are used to help reduce the swelling of the airways, which can help with breathing and DNase an enzyme, which is usually inhaled, is used to help thin and break down the viscous mucus in the lungs, so it is easier to expectorate. 6

“Pancreatic enzyme replacement therapy (PERT) is required by almost all individuals with CF, due to pancreatic insufficiency. When the exocrine pancreas no longer functions adequately, the production of pancreatic enzymes is reduced, leading to fat malabsorption. The consequences of this include steatorrhoea, malnutrition, and fat-soluble vitamin deficiencies. Ninety-one percent of patients with CF in Ireland received PERT in 2016. Supplementary feeding can be required due to continued weight loss. Nearly 38% of individuals with CF required supplemental feeding in 2016. Approaches to supplemental feedings included oral supplementation, gastrostomy tube/button feeding, nasogastric tube feeding and total parenteral nutrition. 5

“Pancreatic enzymes are taken before and during every meal and fat-containing snack or drink helping the digestive system break down food so that it can be digested and absorbed. The number of enzyme capsules taken needs to be adjusted depending on the amount of fat in the meal, snack or drink. The enzymes should be taken with the meal and the timing may vary depending on the age of the person with cystic fibrosis. It is essential that people with cystic fibrosis receive advice about enzymes from a specialist cystic fibrosis dietitian. Fat-soluble vitamin supplements (A, D, E and K) are taken to help replace lost vitamins and to prevent deficiencies. Because people with cystic fibrosis lose fat in their stools, they also lose the fat-soluble vitamins. Nutritional supplements can help compensate for poor digestion and provide additional energy and nutrients.” 5, 6

People who have diabetes as a result of their cystic fibrosis, need to take insulin and manage their diet to control blood glucose levels.

Bisphosphonates are taken to treat osteoporosis, which can occur as a result of cystic fibrosis to help maintain bone density and reduce the risk of fractures. “It is important that people with cystic fibrosis are up to date with all the required vaccinations and should have the flu vaccine annually, as they are more susceptible to complications as a result of infection,” she adds. 6

Daily physiotherapy is usually required and, if the person with cystic fibrosis has a chest infection the amount of airway clearance will need to be increased. Physiotherapy is tailored to the individual’s needs. While physiotherapy for cystic fibrosis mainly focuses on airway clearance, the role of physiotherapy in cystic fibrosis has expanded to include daily exercise, inhalation therapy, posture awareness and in some cases for the management of incontinence. 6

“A specialist CF physiotherapist will assess a person with cystic fibrosis and recommend the most appropriate techniques to use. Techniques may change as the person gets older or as their disease progresses. Some airway clearance techniques are done without the need for equipment and focus on specific breathing exercises, such as the active cycle of breathing techniques (ACBT) and autogenic drainage. Other techniques use devices to help with the clearance of mucus. These devices use positive pressure to hold open the airways while some create vibrations. Techniques include positive expiratory pressure (PEP), oscillating positive expiratory pressure and high frequency chest wall oscillation (HFCWO). 6

“In severe cases of cystic fibrosis, when the lungs stop working properly and all medical treatments have failed, a lung transplant may be required. Lung transplantation for cystic fibrosis has a good success rate: 70% of patients survive one or two years after transplantation and the longest surviving patients had their transplant operation over 15 years ago. 6

“Hospitalisations recorded by ‘the registry’ reflect admission for a variety of reasons, both CF and non-CF related. In 2016, 954 hospitalisations were recorded in 497 individuals. Over seventy percent of hospitalisations (71.3%) were for the purpose of treating a pulmonary exacerbation. 363 individuals, 32.1% of individuals attending CF centres/clinics in that year were hospitalised for treatment of a pulmonary exacerbation; 20.8% of children (n=106) and 41.1% of adults (n=257). Of those hospitalised for treatment of a pulmonary exacerbation in 2016, 44.4% (n=161) were admitted to hospital two or more times in the year. The cumulative total number of days spent in hospital by individuals with CF for treatment of a pulmonary exacerbation in 2016 was 9,278 days; 1,689 days for paediatric patients, 7,589 for adult patients. The CFRI recorded 6,792 outpatient visits to CF specialist centres and CF clinics across the country by 1,133 individuals with CF in 2016, however, CF day-unit and drop-in visit statistics are thought to be underestimated,” Theresa says. 5

“The number of deaths from CF in Ireland varies from year to year. Since 2000, an average of 18 individuals died annually (range: 7 to 31). The deaths of 13 people with CF occurred in 2016 (9 female, 4 male). These individuals died between the ages of 11 and 59 years, with the median age of death 32.5 years. Deaths were due to respiratory/ cardio-pulmonary causes (n=9), transplant-related issues (n=2) and the cause of death in two individuals was not known to the registry at the time of reporting. 5

“Cystic Fibrosis Ireland (CFI) is a voluntary organisation, initially set up by parents in 1963 to improve the treatment and facilities for people with CF in Ireland. CF Ireland supported by fundraising and voluntary contributions, co-operates with medical professionals to provide maximum assistance to both parents and children/ adults with cystic fibrosis. They provide: Funding towards new cystic fibrosis units around the country, including dedicated inpatient, day care and out-patient facilities: Advocacy to shape government policy, through the ‘Pollock Report’ on cystic fibrosis services and campaigning to improve lung transplantation rates in Ireland: Funding for medical and scientific research aimed at understanding, managing and treating cystic fibrosis: Funding for specialist cystic fibrosis multidisciplinary posts in hospitals throughout Ireland: Advice, information and advocacy services: Exercise, transplant and fertility grants: Support for public awareness about cystic fibrosis and information updates on new treatments and developments in CF, especially through their website and bimonthly newsletter ‘Spectrum’.” 1

Theresa concluded, “Better treatment strategies improve the duration and quality of life of people living with CF by controlling their symptoms. Improved treatments can be developed using patient registries. One of the CF registry’s founding principles is to promote and facilitate the use of clinical data in approved research projects. The CFRI participates alongside other European countries in a long-term safety study of CF therapy ivacaftor. Cystic fibrosis registries gather information on all aspects of a patient’s condition acting as information databases for infection and treatment statistics. Detailed analysis of this information yields significant findings about the most effective treatments for CF. Through this analyses, better management and improved outcomes for individuals with CF can be achieved.” 5

References available on request

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