Analysis Of Cystic Fibrosis (CF) And CFTR Dysfunction Throughout the Lifespan
Introduction
The clinical manifestation of cystic fibrosis (CF) is a result of mutation in the cystic fibrosis transmembrane conductance regulator (CFTR). At normal functioning, CFTR facilitates water movement and the transport of ions across the epithelial layer. Pulmonary pathogens attacking the lungs of an individual with this mutation are more difficult to eliminate due the defective immune function causing excessive neutrophilic cell airway inflammation that is ineffectual. Pulmonary infection is a greater challenge to prevent as susceptibility is heightened. Around 30,000 individuals in the United States are affected by the disease, and bacterial infection as a result of the inflammation and impaired mucosal immunity is resistant to antibiotics and phagocytic eradication (Cohen & Prince, 2012). The present review will examine current literature investigating cystic fibrosis and CFTR dysfunction across the lifespan.
Childhood
It has been found through longitudinal studies that there is a decline in lung function in infants living with the disease by age 2. Although a bacterial infection will hasten this decline, the deterioration is evident both in the presence and absence of infection. As a current part of care of individuals living with the disease, the anti-inflammatory antibiotic Azythromycin has been effective in inhibiting this loss. Patients in a clinical trial, 6 years of age or older, treated with a drug targeting a specific mutant genotype of the CFTR were found to have improved pulmonary function (Cohen & Prince, 2012). Female patients are diagnosed later than males in childhood, as well as having a significantly decreased life expectancy of approximately 20 years. One study conducted newborn screenings for bronchiectasis in infants with CF to determine if airway inflammation of those who tested positive was more severe. Findings showed that bronchiectasis was indeed common and that the prevalence and level increased in following years. Furthermore, bronchiectasis was associated with neutrophilic cell count and the Pseudomonas aeruginosa infection. The findings proposed that this screening has potential to allow commencement of intervention very shortly after a diagnosis of CF and prevent “respiratory sequelae”.
Exercise and physical activity are shown to be helpful in improving pulmonary function and airway mucus clearance. However, the limited capacity for exercise among the CF population attributed to diminished lung and cardio-respiratory system function can make this a more challenging task. Hence, children with CF are not as physically active as their peers. Several studies have associated lung function with a positive change in aerobic capacity. Parents of children with CF may typically view them as vulnerable, and it is this perception that may precipitate lower activity levels among their children. However, many may be unaware of the benefits of exercise in the prognosis of CF in the pediatric population, including improved muscle strength, cardiovascular endurance, mucus clearance, and quality of life. Wilkes and colleagues also explain the psychological benefits of habitual physical activity for children with CF, including improved self-confidence and perceptions of body appearance, and self-worth. It is true however, that adherence to exercise programs among children is relatively low, and the method to improve regularity entails providing a wider variety of training activities that are fun for these individuals, which will in turn increase their motivation.
Another study administered The Cystic Fibrosis Questionnaire to children and adolescents aged 9-19 years in order to assess associations between nutritional status and quality of life. Results indicated that there was a positive association between nutritional status and physical functioning and body image. It was not significantly associated with emotional or social functioning, however, these results suggest that better nutritional status might enhance physical functioning and allow for greater adherence to exercise programs which in turn, can improve psychological and physical well-being.
Cystic fibrosis in childhood does not only affect parent perceptions of vulnerability amongst their children, it also had strong effects on the family as a whole. In addition to the child living with the disease having to be protected from potential colds or illnesses that may be caught from their siblings or other family members to avoid infection, there may also be a decline in psychological well-being of family members. One study focusing on positive and negative effects of CF found commonalities in affect among several families, including feelings of loneliness, depression, anger, somatic complaints, and low self-esteem.
Adolescents
Another study using The Cystic Fibrosis Questionnaire set out to examine gender and age effects on quality of life in both inpatient and outpatient adolescents with CF. Higher scores represented a better quality of life, with eight examined domains, including emotional state, respiratory symptoms, and treatment burden. Parents of the patients also completed the questionnaire. Results revealed that inpatient adolescents had scores significantly worse than outpatients in emotional state, respiratory symptoms, social, and body image. Younger patients scored higher on body image, emotional state, and treatment burden, and finally, females scored higher on treatment burden than males, with no differences in any other domains. Interestingly, parents found treatment burden to be worse on daily life than their children perceived it to be.
The results of this study suggest that as patients age and the disease advances, physical functioning weakens further, resulting in increased limitations and need for therapy, and a lower perceived quality of life. Another study identified barriers to treatment adherence among the adolescent population. Participants were administered a questionnaire that inquired about self-perceptions of physical health and functioning, as well as what treatments they were using, and main barriers to adherence to this treatment. Younger patients reported having better health more than the older patients did.
Primary barriers for most participants were time management, having too many treatments to keep track of, and forgetting treatments. Airway clearance therapy was the treatment that most thought had the least consequences if missed, which was agreed to be uncomfortable and tedious. Many adolescents also felt embarrassed about treatment and isolated from their peers. These results indicate that to improve adherence in the future, technological developments including treatments that may be done at the same time or in a more discrete manner might be beneficial.
Another challenge experienced by adolescents with CF is the transition from pediatric to adult care. Due to advancements in treatment, survival rates of individuals with the disease have improved significantly, leading to lifelong treatment being required by an increasing number of patients. However, this increase in life expectancy also comes with additional health complications with age. Several steps are undergone in the transition process including facilitating self-management skills and “feedback between pediatric and adult health care teams”. Adolescent development is often disrupted by CF, with many individuals feeling out of place with the desire to be “normal”. This anxiety provoking thought may also be exacerbated by possible delays in puberty as a result of the disease.
Adult care for these patients now has to consider issues such as sexual health, lifestyle issues, and ongoing education and/or employment issues and provide assistance in these areas to ensure progress in all areas of life for these adolescents. Considerable focus is placed upon parental support and family care in the transition process in order to make it easier for adolescents to adapt to the changes. Challenges include moving to an unfamiliar environment in an adult hospital, ongoing health insurance issues after 18 years of age, and facilitating their independence. It is integral for health care providers to assist adolescents in preparing for emerging adulthood and in gaining a sense of control in their lives.
One study examining coping strategies of adolescents with CF who also may be experiencing pain found that problem-solving, acceptance, and self-encouragement were the skills that were the most effective and frequently exercised. In addition to these coping mechanisms, another study found that parental guidance was one of the most conducive factors in helping adolescents move forward through their disease progression and treatment, especially with comfort from their mothers.
Emerging Adulthood
As adolescents move toward emerging adulthood, concern for the psychosocial and psychiatric factors of their lives rises. Although many living with the disease show similar psychological health as their counterparts without the disease, there is evidence supporting the higher rates of depression and lower rates of quality of life and daily functioning among this population. One study assessed anxiety and depression through administration of a 14-item questionnaire to 59 outpatient adolescents and young adults with CF. The findings of this study revealed low rates of depression among this population which could have been attributed to treatment advances.
However, anxiety symptoms highlighted previous literature in that 32% reported signs of anxiety. The study explains the possibility of anxiety preceding later depression as the disease tends to progress with age with a subsequent decline in health, therefore, screening for depression is still warranted. Finally, females exhibited higher anxiety symptoms than males in this study which may be due to their decreased life expectancy. Cruz et al. , (2009) discuss the exacerbation of medical complications as a result of anxiety and depression among the CF population, as well as the worsening of the chronic lung disease and functional impairment among those who experience a comorbidity of these symptoms.
As aforementioned, sexual health becomes a concern as adolescents become young adults. A study conducted by Traci and colleagues (2016) concluded that both providers and patients of CF care agreed that sexual and reproductive health care education should be a critical inclusion of CF care. Ongoing communication between the patient and CF provider can reduce barriers of discomfort, contributing to the necessity for these providers to be trained and capable of providing the appropriate resources for sexual health specific to CF.
Working with young families in the presence of a chronic illness is now a more frequent occurrence, as successful pregnancies among women with the disease have become a more realistic possibility. There have been findings regarding the CFTR in the cervix and hypothalamus, and how this may affect cervical mucus consistency and possibly lead to infertility.
Additionally, women with CF who already have a severely compromised physiology, may experience an increased with for health decline as they may not adjust to the bodily changes that pregnancy precipitates as well as their non-CF counterparts would. In a woman with CF, variations in pulmonary function as a result of pregnancy may negatively affect gas exchange which may induce hypoxia and lead to pulmonary decompensation. Furthermore, cardiovascular demands of pregnancy may also lead to cardiac failure in this population. This risk is particularly heightened if pulmonary hypertension is present, a condition in which the maternal mortality rate is approximately 50% when coupled with pregnancy. Thorpe-Beeston (2009) also discusses the consequences of changes in weight and glucose tolerance associated with pregnancy for women with CF. These consequences include a likely necessity for supplemental feeding for these women to reach the caloric requirements to facilitate fetal growth, as well as the already impaired glucose tolerance among these women, leading to an increased risk for gestational diabetes.
With regards to nutritional status, it is important to consider intestinal malabsorption as a result of pancreatic insufficiency. The weakened nutritional status as a result of this warrants close observation and the need to optimize nutrition and vitamin intake to improve the outcome of pregnancy. Furthermore, the various medications taken by women with CF must be reviewed and managed to ensure there are none with “teratogenic potential”. Women with severe pulmonary disease and hypertension are at a heightened risk for maternal morbidity, therefore, regular pulmonary function tests are necessary to enhance patient outcomes. Regular evaluation of fetal growth in the third trimester is should be carried out as approximately 25% of pregnancies result in preterm labor.
This may be associated with the complex issues discussed in this section, such as nutritional status and lower maternal weight gain. The findings of a retrospective study of pregnancies among women with CF are as follows: the forced expiratory volume in 1 second (FEV1) dropped for most women during pregnancy but was later recovered within six months post-partum, there was a high rate of gestational diabetes, preterm births were induced due to risk for maternal respiratory deterioration, and adverse fetal outcomes were primarily associated with considerably lower FEV1 and BMI before pregnancy. It is evident that women who are contemplating pregnancy should be aware of the increased risk of mortality associated with factors including diabetes and pulmonary decline. Offspring of women with CF will be obligate heterozygotes, underscoring the need for genetic counseling to be undergone to assess for the carrier gene in the partner in an attempt to safeguard against having an infant afflicted with the disease. Despite the progress in CF care, it is important that these women note that having this life-shortening disease means that they may not be able to raise their children for a long period of time; the mortality of the mother must be discussed openly when planning for a child, and the implications for the family and child that will follow.
Adulthood and Ageing
Studies have indicated skeletal muscle weakness and low bone mineral density and among adult patients with CF. Analysis of several studies indicated that osteopenia and osteoporosis are common among this population. Vertebral fractures at the thoracic level are also common, but the prevalence decreased with a higher body mass index (BMI). Risk factors for this low bone mineral density might include low BMI, malabsorption of calcium and vitamin D, and malnutrition, among others. Using a multi-sensor arm band with 64 adults with CF and 20 adults without CF, intensity of physical activity over 5-7 days was able to be measured. The arm band also assessed variables such as bodyweight and height. The findings indicated that those with CF were indeed smaller and lighter than those in the control group, and peripheral muscle force was significantly lower among both men and women with CF, specifically in hand-grip and quadriceps force.
A significant relationship between lung function impairment and hand-grip force was found, but not for quadriceps force. Physical activity of moderate intensity was also much lower for patients with CF; an important finding as this level of intensity has significant long-term protective effects on health. The prevalence of exercise intolerance among adult patients with CF stresses the need for increased focus to be placed on physical activity and training recommendations in treatment regimen of this population. Increased muscle development might also be a protective factor against vertebral fractures in this population in addition to a higher BMI which showed lower incidence of these fractures. The presented literature discussing the benefits of habitual physical activity among patients with CF suggests that it should be implemented into their daily lives to potentially improve survival.
Improvements in clinical care leading to an increase in the survival rates of individuals with CF (>30 years) has prompted studies of strategies to improve this rate. Cymberknoh and colleagues (2011) discuss the developments responsible for these improvements, indicating that they include timely nutritional support, improved mucous clearance, effective hygienic methods inside and outside of CF centers, such as the prevention of cross-contamination between patients, and the commencement of “antimicrobial and anti-inflammatory therapy as soon as possible”. This study also emphasizes the importance of the therapeutic alliance with the patient and their loved ones to promote patient empowerment and motivation to adhere to therapy and treatment.
To ensure “optimum functioning for the maximal period of time”, active and health ageing should be initiated early on, with one study suggesting a holistic approach for the treatment and management of cystic fibrosis as the comorbidities increase with age. One study assessing employment among patients with CF found that more than half of the participants felt that their disease impacted their ability to work. The study also concluded, however, that employability seemed to be most affected by educational achievements than the diagnosis itself, and that higher education levels led to the attainment of skilled jobs which may be more flexible to the changes that accompany long-term health degradation. These difficulties in employment may be reflected later on in the financial stability of individuals with CF as they grow older and approach retirement age. Finally, in terms of independence as individuals with CF age, possible loss of parents and family members, and children who may no longer live with the individual, will lead to the need for greater support in order to maintain stable health, prevent deterioration, and balance factors such as treatment needs and family and social life.
