Cystic fibrosis (CF) is an autosomal recessive genetic disease affecting multiple organ systems in the body, primarily the hepatic, digestive, reproductive, and respiratory systems (Moola et al., 2011; Swisher & Erickson, 2008). This inherited disorder causes defects in chloride ion transport across the epithelial surfaces in these systems. This results in the accumulation of thick and sticky mucous in these organ systems (Orenstein et al., 2004). This mucous clogs the airways and impedes the pancreas from releasing natural enzymes that break down and absorb nutrients.

CF is the most common life threatening autosomal recessively inherited disorder in the Caucasian population (Savage et al., 2014). CF occurs in every 1 of 2500 births and one in every 25 people is a carrier of the CF gene mutation (Stabb, 2004). Most carriers do not have CF and do not need any special medical attention. However, if both the mother and father are carriers of the CF gene mutation their child has a 25% chance of having CF (Grossman & Grossman, 2005). There is no cure to this fatal disease therefore the treatment is palliative instead of curative (Moola et al., 2011). CF most often results in pre-mature death due to respiratory failure (lung disease) or gastrointestinal complications (Kianifar et al., 2013). When dealing with children, proper disease management is key to preserving optimal quality of life and prolonging symptom severity (Stabb, 2004). Cystic fibrosis is a pertinent issue in contemporary society due to its high prevalence, severity, and the fact that there is no cure for this disease.

Proper disease management is essential for children.

Cause

CF is caused by a mutation in the cystic fibrosis trans membrane conductance regulator (CFTR) gene of chromosome 7 (on the long arm). When the CFTR gene becomes mutated, the CFTR protein that is produced by this gene becomes defective (Grossman & Grossman, 2005). The CFTR protein “allows chloride ions to exit the mucous producing cells” of the body (Grossman & Grossman, 2005). When chloride ions exit the cell, water follows them and dilutes the mucous. When the CFTR protein is defective, the chloride ions are unable to leave the mucous-producing cells, which result in the production of thick and sticky mucous (Grossman & Grossman, 2005). The CFTR protein is involved in controlling the amount of water in sweat, mucous, tears, saliva, and digestive enzymes (Sermet-Gaudelus et al., 2009).

Diagnosis

Newborn screening for cystic fibrosis is conducted using either a genetic test (detecting possible CFTR genes in the newborn) or a blood test (detecting if the pancreas is functioning properly) (Stabb, 2004).

CF is characterized genetically but this disease still needs to be diagnosed clinically by demonstrating an abnormality in the epithelial cells (Orenstein et al., 2002). Often this abnormality is demonstrated by performing a sweat test in a CF center laboratory (Orenstein et al., 2002). This test is conducted if either one’s genetic or blood test shows possible red flags resembling CF. The sweat test is the “Gold Standard Test” for diagnosing CF (Ranganathan, 2003). For this test, a doctor rubs a small area of skin on the leg or arm with a colorless chemical to trigger sweating. An electrode is applied to give the area a slight electrical current for 5 minutes, causing a tingling sensation. Sweat is then collected and examined for high chloride levels. People with CF have elevated chloride concentration levels of 0.60 mmol/l in their sweat. The sweat test can be performed approximately 2 weeks after a child is born (Ranganathan, 2003).

Symptoms and Complications

A CF patient’s symptoms can vary depending on the degree of the mutation to the CFTR gene (Grossman & Grossman, 2005). Complete loss the CFTR gene results in no CFTR protein being produced which can lead to pancreatic disease, severe pulmonary disease, gastrointestinal problems, infertility in men, and fertility problems in women (Grossman & Grossman, 2005). Partial losses of the CFTR gene can cause abnormal production of the CFTR protein which can lead to less severe symptoms (Grossman & Grossman, 2005).

Early Symptoms

The earliest sign of CF is meconium ileus (distal intestinal obstruction) that occurs shortly after birth in 10-15% of children. This results in bowel dilatation, thickened intestinal walls, intestinal atresia, and peritonitis (Stabb, 2004). Research shows that inflammation of airways develops very early in infancy (Ranganathan, 2003). Infants also experience symptoms of decreased mucociliar clearance in the airways that cause bacteria to form in the airways, lung infections, discomfort, wheezing/coughing, and possible lung damage. Other early symptoms include salty skin, constant diarrhea, bulky bowel movements, and a large appetite followed by low weight and lack of growth. In addition, some children develop diabetes at a young age (Stabb, 2004).

Parents of a child with CF should be aware of the symptoms of worsening CF lung disease of their child. They should look for “unilateral chest pain of sudden onset accompanied by shortness of breath” which suggests a pneumothorax (Orenstein et al., 2002).

Chronic Symptoms

a) Endocrine Symptoms

Cystic Fibrosis Related Diabetes (CFRD) (Grossman & Grossman, 2005)

About 13% of all CF patients have CF related diabetes, which is usually diagnosed after the age of 30 (Grossman & Grossman, 2005). These adults have an insulin deficiency due to the obstruction of the pancreatic duct and become insulin dependent. Unlike normal cases of diabetes mellitus patients with CFRD still require a high-energy diet due to their bodies increased energy expenditure. CFTD can lead to liver cirrhosis and periportal fibrosis that cause chronic inflammation

b) Respiratory Symptoms

Phenumothorax (trapping of gas between lung and chest wall)
Chronic Lung Infections
Bronchiolitis (inflammation of the bronchioles)
Bronchitis (inflammation of the mucous membrane of the bronchial tubes)
Bronchiectasis (abnormal widening of the bronchi)
Chronic cough
Pneumonia
Hemoptysis (coughing up blood)
Digital clubbing (enlarged bulbous producing shiny tips of fingers and toes)
Cor pulmonale (enlarged right side of heart)
Sinusitis (nasal inflammation)
Nasal polyps (growths inside the nose)

c) Gastrointestional Symptoms

Poor weight gain and growth
Greasy, foul-smelling stools
Meconium ileus (thick, odorless, green newborn stools)
Distal intestinal obstruction
Hyperglycemia (high blood sugar)
Abdominal discomfort
Rectal prolapse (lining of rectum come out through anus)

d) Reproductive Symptoms

Delayed puberty, mainly because of nutritional factors (Orenstein et al., 2002)
Females: Fertility complications as the thickened, dehydrated cervical mucus can impair sperm activation
Males: Infertility due to mucous damage to the vas deferens

e) Sweat Gland Symptoms

Secretion of salty sweat leading to abnormal heart rhythms

(Wilkes et al, 2009)

Gender Differences

There is a substantial gender difference with the progression of symptoms and complications in cystic fibrosis. The occurrence of CF is equal for both females and males, proving that the chromosome 7 mutation is not influenced by gender (Kianifar et al, 2013). However, the differences appear when analyzing the symptom severity. Females with CF grow at a slower rate and experience more severe symptoms (especially poor lung function) compared to males (Stabb, 2004). They struggle to meet growth milestones and have a 4 to 5 year worse survival rate than males. In addition, females under 20 years of age are at a 60% greater risk of dying of complications caused by CF (Kianifar et al, 2013). Both females and males experience pubertal delay defined by absence of breast development in females before age 12, and absence of increased testicular volume in males before age 14 (Sermet-Gaudelus et al, 2009).

Infertility is compromised in both genders. Due to the damage of the vas deferens (transports sperm to testicles), males have a 98% infertility rate. Females may have irregular menstrual cycles because of mucus blockages in the fallopian tubes, however can become pregnant and have healthy children (if the father didn’t have CF). The child will then become a carrier of the CF gene (Stabb, 2004).

After the onset puberty, gender differences also arise in physical activity. Females have been shown to become much less active compared to males. Additionally, females have a higher resting and working energy expenditure (possibly related to their shortened life expediency) (Ranganathan, 2003).

Nutritional Status

Children with cystic fibrosis often have poor nutritional status due to pancreatic insufficiency causing maldigestion and malabsorption of essential nutrients. The thick mucous characteristic of this disease leads to an inability of the pancreas to supply digestive enzymes to the small intestine (Nixon et al., 2001). The thick mucous secreted by the pancreas also causes the volume of digestive enzymes secreted to be decreased as the mucous can block the pancreatic ducts (Grossman & Grossman, 2005). Both of these factors lead to the impairment of the digestion of fat and protein, and decrease the absorption of vitamins A, D, E, and K (Grossman & Grossman, 2005; Nixon et al., 2001).

Children with CF have increased energy expenditure due to the “increased caloric demands of fighting infection and greater work of breathing” (Orenstein et al., 2002). This may cause children with CF to have a large appetite and consume sizable meals, but do not grow or gain weight at the same rate as their peers. These symptoms of chronic malnutrition is referred to as “failure to thrive” syndrome (Stabb, 2004). On the contrary, children with CF may consume lower quantities of food due to the severe symptoms of the disease such as stomach pain, coughing, and vomiting. Both children and adults with CF are often “small and have difficulty gaining weight” (Orenstein et al., 2002). Detecting malnutrition in these patients at a young age is crucial for conducting early interventions.

The nutritional status of children with CF has advanced in the past decade. Children take pancreatic enzyme supplements and vitamins before eating to enhance absorption and digestion of essential nutrients. Caregivers should note that pancreatic supplements and vitamins must be taken separately in order to avoid the malabsorption of iron (Grossman & Grossman, 2005). Children with CF are put on a high fat, high calorie diet accompanied by aggressive nutritional supplementation and supervision. Even after these interventions, 100% fat digestion will still never fully occur (Stabb, 2004). Better nutritional status has been associated with improved survival rates in children with CF (Orenstein et al., 2002). In order to have optimal pubertal development and proper bone mineralization, children should take in large quantities of calorie dense foods along with high levels of calcium, vitamin D, and vitamin K (National Heart, Lung and Blood Institute, 2006). Nutritional status plays a key role in exercise capacity. Studies show that poor nutritional status leads to a decrease in aerobic and aerobic activity. Often times, children cannot keep up the calorie requirements needed for high amounts of physical exertion (Wilkes et al, 2009). However, children who are more physically active have shown to be less nutritionally compromised (Sermet-Gaudelus et al, 2009).

Physical Activity

Daily physical activity is recommended for children with CF.

Physical Benefits

Several studies have shown that regular physical activity is essential for the physical and psychological well being of patients with CF (Swisher & Erickson, 2008). It is crucial that CF patients participate in physical activity because research has revealed that CF patients who have high levels of aerobic fitness live longer and have an improved quality of life compared to CF patients who are less aerobically fit (Nixon et al., 1992; Selvadurai et al., 2002). Patients who participate in daily physical activity are able to preserve lung function and slow the progression of the disease. Poor physical fitness has been established as one of the principal factors that is associated with an increased decline of lung function in patients with CF (Orenstein et al., 2002). Quality of life and health status have been reported to increase with aerobic, anaerobic, and strength training in CF patients (Stabb, 2004). Regular aerobic and anaerobic exercise training has been shown to “enhance airway mucous clearance, cardiovascular fitness, and improve fat-free body mass” in CF patients (Swisher & Erickson, 2008). Maintaining a normal body weight through strength and resistance training is important for CF patients because low body mass predicts morbidity and mortality (Swisher & Erickson, 2008). Regular exercise leads to a delayed onset of dyspnea (shortness of breath) and assists in the management of diabetes in those with CF (Bradley & Moran, 2012; Swisher & Erickson, 2008). Aerobic exercise increases one’s breathing rate and heart rate. This increases the carbon dioxide-oxygen exchange, which helps to loosen up sticky mucus lining the airways and promotes coughing (Kianifar et al, 2013).

Bone Health

Physical activity can be protective against a decrease in bone mineral density (BMD) and can help delay the onset of osteoporosis in children and adults with CF (Bradley & Moran, 2012). Patients with CF are at greater risk for low BMD due to their bodies’ decreased ability to absorb vitamin D, which is essential for calcium absorption. Regular participation in daily physical activity during childhood years is important to establish peak bone mass in later life. Puberty is the crucial period when bone mineralization occurs, and children throughout this time should be closely monitored to ensure they are reaching predicted optimal bone-growth milestones (Sermet-Gaudelus et al, 2009). During this critical period, children should be supplementing with calcium and vitamin D, and increase their intake of protein and fats (Stabb, 2004).

In children, a decrease in BMD loss is caused by both the imbalance of bone formation and bone breakdown (osteoblast and osteoclast activity), and the lack key nutrients the body is able to absorb from food (Mcabe et al, 2011). Low BMD causes complications seen in adolescence and adulthood such as poor bone mineral growth, increased bone demineralization, and bone fragility. These factors lead to osteopenia, osteoporosis, disability, and high fracture rates (Hind et al, 2008). Osteopenia is reported in 85% of patients with CF, and osteoporosis is seen in 10-35% of patients (Sermet-Gaudelus et al, 2009). Pharmaceutical treatments incorporated with daily weight-bearing activities are common strategies to preserve BMD and increase accrual bone growth. Exercise must be continued as children undergo puberty in order to see continuous gains in BMD and bone mineral composition (BMC) (Hind et al, 2008).

Psychological Benefits

CF patients that participate in regular physical activity have been shown to have decreased anxiety, depression, and enhanced feelings of well-being (Bradley & Moran, 2012). Research studies show that improvements in quality of life ratings in CF patients are related to increased peak aerobic capacity (Selvadurai et al., 2002). Physical activity has been shown to improve self-confidence, self worth, and body image in those living with CF. In addition, exercise promotes blood flow throughout the body and releases endorphins to the brain that decrease stress and anxiety, improve sleep, and elevate energy levels.

Parental Influence

At a young age a child’s daily physical activity routine is typically determined by their parents. Parents of children with CF may believe that there are more barriers to their sick child’s ability to exercise than in a healthy child (Swisher & Erickson, 2008). Parents of children with CF may be more protective of their child due to their condition (Moola et al, 2011). However, not allowing one’s child to be physically active because they have CF is inadvertently causing them harm (Orenstein et al., 2002). Getting children with CF to be physically active starts with their parents. Parents of children diagnosed with CF must encourage their child to be physically active and engage in the same activities as other healthy children their age. Involvement of parents in the child’s physical activity intervention is crucial for the children’s exercise compliance (Moola et al., 2011).

Physical Activity Recommendations for children

Clinicians recommend regular participation for children with CF to increase cardiovascular and respiratory efficiency, muscle function, and mucus clearance (Armstrong et al, 2011). It is important that the habit of exercise is started in childhood in children with CF in order to slow the progression of the disease and to allow the patients’ to establish a regular physical activity routine that they can maintain into their adulthood (Tuzin et al., 1998). Physical activity is an important part of management of this disease in children (Swisher & Erickson, 2008). Caregivers and physicians should collaborate to develop an individualized training program for the child with CF that includes fun activities that the child enjoys. These programs should enhance efficacy of the child and promote a mastery environment where success is based upon the child’s personal accomplishments (Moola et al., 2011). Children should be given exposure to many different types of exercise programs and should be given a choice.

Before prescribing an exercise prescription for a child with CF, the child should undergo an exercise tolerance test to determine the functional limitations and ensure the safe prescription of exercise (Rogers et al., 2003). The Association of Chartered Physiotherapists in Cystic Fibrosis state in their guidelines that exercise tolerance tests should be conducted annually for all pediatric patients. The type and application of these tests should be individualized for the patient (Rogers et al., 2003). An exercise tolerance assessment may involve lab tests, field tests, walking tests, step tests, shuttle tests, cycle ergometry tests, or treadmill tests (Hind et al., 2008).

After conducting exercise tolerance tests, a health care team should then design a training program specifically outlining the type, duration, frequency, and intensity of activities the child is cleared to take part in (Wilkes et al, 2009). Aerobic and strength-training protocols improve different areas of the physical and psychological wellbeing of a child with CF (Selvadurai et al., 2002). Therefore when prescribing an exercise program for a child with CF one must combine both aerobic and strength training into the program. These programs need to be aimed to preserve and improve these different areas of fitness (Selvadurai et al., 2002). Aerobic training involves sessions of continuous training for an extended period of time at a target intensity (Bradley & Moran, 2012). Examples of aerobic activities for children that will help increase their aerobic capacity include:

Swimming
Biking
Dancing
Soccer
Basketball
Running games like tag and capture the flag

With the exception of swimming and biking, the activities listed above are examples of regular weight-bearing activities. Pre-pubescent children should participate in various weight-bearing activities a minimum of 2-3 times per week, and progress this activity to a daily affair after a 6-week trial (Hind et al, 2008). Muscle strengthening activities are important to improve a child’s weight gain (total mass and fat-free mass) (Selvadurai et al., 2002). Examples of ways to incorporate strength training into a child’s day include:

Hop-scotch
Jump rope
Jumping jacks
Climbing at playgrounds (ex. Monkey bars)
Push-ups

Children and adolescents with CF should be encouraged to participate in these moderate-to-vigorous intensity aerobic and anaerobic activities often (Nixon et al., 2001). Parents and teachers must remember that children with CF require a longer recovery period between exercise sessions. The main factor when formulating an exercise programs is maintaining compliance to the activity and avoiding discomfort for the child (Armstrong et al, 2011).

In School

Children with CF should be encouraged to fully engage in school and extracurricular physical activities (Orenstein et al., 2002). As a child’s quality of life is impacted by their ability to take part in physical activity and be a “normal” child who can run around with their friends (Rogers et al, 2003). Children should be pushed to participate in their usual school gym class and gym excuses should be denied (Orenstein et al., 2002). Parents should inform the child’s teacher that the child will have to take medicine during school hours and will have to have unlimited bathroom privileges due to their medical condition.

Barriers

In today’s society there has been a drop in child physical activity participation rates. This trend of physical inactivity is amplified in those children with CF. Children and adolescents with CF are less physically fit then their healthy peers (Orenstein et al., 2002; Swisher & Erickson, 2008). Swisher & Erickson (2008) organized the reasons for CF patients decreased participation in physical activity into two categories, internal barriers and external barriers. Internal barriers include disease related physical factors like general discomfort (ex. Muscle soreness, fatigue, joint pain, increased heart rate) and increased lung symptoms (Swisher & Erickson, 2008). External barriers include disinterest in the activities prescribed and boredom (Swisher & Erickson, 2008). Patients with CF often develop a shortness of breath (dyspnea) when exercising which is a major barrier to their exercise tolerance (Bradley & Moran, 2012). This abnormal respiratory response during exercise is usually due to progressive respiratory disease (Bradley & Moran, 2012). Children with CF blood lactate levels during and post exercise are more elevated than in healthy children due to their heightened need for oxygen supply and carbon dioxide removal. Therefore children with CF experience higher levels of perceived exertion and fatigue in shorter amounts of time compared to healthy children (Armstrong et al, 2011). As well CF causes sweat to become very salty, causing large amounts of sodium to be lost during exercise. Often times, high-salt diets are recommended for active children with CF (Wiedemann et al, 2007).

Children with CF are constantly battling infection and illness causing them to undergo harsh treatment or go into hospital. Time-consuming routine doctor and therapist appointments often impact exercise adherence. Additionally, the physical, mental, and emotional impacts of chronic illness create barriers for activity participation (Stabb, 2004).

Parents pose as another barrier to exercise adherence. They often worry about placing their child at risk or having their child “stand out” in a group of healthy children. This phenomenon is referred to as ‘vulnerable child’ syndrome, which blurs a parents’ awareness of their child’s physical capabilities and causes them to become overprotective when allowing their child to participate (Wilkes et al., 2009).

All of these factors strongly diminish activity participation, thus putting children at an even poorer health status due to the combined effects of CF and lack of physical activity (Mcabe et al., 2011). Unfortunately, with the progression of this disease, lung function inevitability declines, and the aptitude to partake in physical activity is reduced (Rogers et al., 2003).

Management

There is no cure for CF, however proper management of this disease is essential for preserving quality of life and reducing the severity of the symptoms (Mcabe et al., 2011). Common management treatments include chest physiotherapy for airway clearance, nutritional supplementation, and medicine. Chest physical therapy (CPT) loosens up the thick and sticky mucus in the airways so it can be coughed up and cleared from the lungs (also referred to as chest clapping or percussion). CPT is the action of pounding over the chest and back with the palm of the hand. Though this technique is uncomfortable, simple devices have been invented to assist in the pounding action. Basic breathing techniques, such as forcing out short or deep breaths followed by normal breathing, are also used to loosen the mucus. CPT is usually done while the child lies on their stomach or is seated, thus using gravity to draw out mucus from the lungs (Kianifar et al., 2013).

Exercise has been shown to be an effective alternative or an additional aide to chest physiotherapy (Tuzin et al., 1998). It has been shown that CF patient’s compliance is better with exercise than with CPT but the act of starting an exercise routine still proves to be difficult (Tuzin et al., 1998). Exercise programs focused on maintaining and improving aerobic fitness are considered a fundamental part of pulmonary rehabilitation in patients with CF (Selvadurai et al., 2002). Exercise increases ventilatory muscle endurance, pulmonary function, immune function, and cardiopulmonary fitness (Tuzin et al., 1998).

Other CF management protocols include:

Ensuring adequate nutrition, consuming nutritious, high calorie foods
Preventing dehydration, drinking ample amounts of fluids
Medication: Antibiotics, bronchodilators, anti-inflammatories, and other mucus-clearing medications aid to prevent lung infections, thin mucus, and open up the airways (Wiedemann et al, 2007).
Stretching: Mobilize muscles and joints supporting chest, spine, and shoulders (Stabb, 2004).

Most importantly, the child should be closely monitored by a CF specialist and a team of health care professionals consisting of doctors, nurses, physical therapists, dietitians, and social workers (Kianifar et al, 2013).

Future Research

Detection of decline in lung function is imperative at a young age so that preventative measures can be taken. Researchers are working to create a brighter future for CF patients (Rogers et al, 2003).

As CF worsens and treatment options have been exhausted approximately one-third of patients undergo lung transplantation (Sermet-Gaudelus et al, 2009). Bilateral lung transplants are usually performed because CF affects both left and right lungs. Transplantation extends survival time and increases quality of life (Rogers et al, 2003). Patients with pre-existing low BMD levels or a high prevalence of fractures are at ‘high risk’ and are advised against surgery (Sermet-Gaudelus et al, 2009).

Growth hormone treatment has shown to produce good results with other catabolic conditions such as HIV, cancer, polytrauma, and burns. However, in CF, more research is needed of the effects of growth hormone on improving or preserving lung function (Stabb, 2004).

Gene therapy is also appearing on the horizon for treatment of CF and is currently the only potential ‘cure’ for the disease to date. The process involves constructing a healthy version of the damaged CFTR gene and putting it into lung cells in the body via viruses or liposomes. However, this method only corrects the illness and fails to treat the current symptoms. It has been conducted on animals and in several clinical trials, yet has not proven itself effective in curing CF in humans (Ranganathan, 2003).

References

Movement Experiences for Children
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KIN 366
Section:
Instructor:	Dr. Shannon S.D. Bredin
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Important Course Pages
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12. Ranganathan, S. C. (2003). The Evolution of Airway Function in Early Childhood Following Clinical Diagnosis of Cystic Fibrosis. American Journal of Respiratory and Critical Care Medicine. 169(8), 928-33. Retrieved from http://www.atsjournals.org.ezproxy.library.ubc.ca/journal/ajrccm

13. Rogers D, Prasad SA, Doull L. (2003). Exercise testing in children with cystic fibrosis. Journal of the Royal Society of Medicine. 96(43), 23-29. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1308784/?tool=pmcentrez&report=abstract

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15. Selvadurai, H. C., Blimkie, C. J., Meyers, N., Mellis, C. M., Cooper, P. J., Van Asperen, P. P. (2002). Randomized Controlled Study of In-Hospital Exercise Training Programs in Children With Cystic Fibrosis. Pediatric Pulmonolgy, 33, 194-200. doi: 10.1002/ ppul.10015

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18. Swisher, A., & Erickson, M. (2008). Perceptions of Physical Actvity in a Group of Adolescents with Cystic Fibrosis. Cardiopulmonary Physical Therapy Journal, 19 (4), 1-07-113. Retrieved from http://www.cardioptjournal.com/

19. What Is Cystic Fibrosis? (2006). National Heart, Lung and Blood Institute. Department of Health and Human Services, Retrieved Feb 8, 2014 from, http://www.nhlbi.nih.gov/health/dci/Diseases/cf/cf_what.html

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21. Wilkes, Donna L., Jane E. Schneiderman, Thanh Nguyen, Liane Heale, Fiona Moola, Felix Ratjen, Allan L. Coates, and Greg D. Wells. (2009). Exercise and Physical Activity in Children with Cystic Fibrosis. Pediatric Respiratory Reviews. 10 (3), 105-09. Retrieved from http://www.sciencedirect.com.ezproxy.library.ubc.ca/science/article/pii/S1526054209000396