31 Cystic Fibrosis and Other Childhood Lung Diseases

Elisabeth Potts Dellon, Jessica Goggin, and Elliot Rabinowitz

Cystic fibrosis (CF) is a well-known disease to many pediatricians and pediatric palliative care (PPC) clinicians. PPC teams may encounter other life-threatening childhood lung diseases, but these are less common than CF. The focus of this chapter is on CF, with a brief overview of other childhood lung diseases. At the same time, readers will find much of the content also applies to these less familiar illnesses. Given the degree of familiarity with CF for the readers of this chapter, this chapter intertwines two goals: to provide an updated view of the rapidly evolving landscape of CF in the past decade and to present a model of primary and specialty palliative care delivery for children and families affected by CF. The typical patterns of care for individuals with CF have historically presented predictable barriers to successful integration of palliative care. Understanding the natural history, changing epidemiology and cultural understanding, and the perceived and actual physical and psychosocial burden of the disease will help palliative care specialists better understand how to integrate their clinical expertise into the established and successful CF model of clinical care. Furthermore, integration of palliative care does not need to disrupt the typically well-established relationships between children and their families with the CF care team.

CF is a life-limiting genetic disorder with an incidence of 1 in 3,200 live births in the United States. CF affects approximately 30,000 in North America and more than 70,000 individuals and their families worldwide.¹ CF is a multisystem disease resulting from mutations in the CF transmembrane regulator (CFTR) gene, causing abnormal chloride ion transport across epithelial cells lining the airways, pancreatic ducts, gastrointestinal (GI) tract, and reproductive organs. This abnormal transport leads to dehydrated and viscous secretions. Clinical manifestations of this defect include recurrent respiratory infections, nutritional deficiencies related to malabsorption from pancreatic exocrine insufficiency, intestinal obstruction, hepatobiliary disease, diabetes, and male azoospermia.² The natural history of CF is a progressive decline in lung function due to recurrent infection, inflammation, and bronchial obstruction leading to bronchiectasis and subsequent ongoing inflammation, infection, and airway damage. Chronic inflammation and infection of the airways accounts for most morbidity in CF, and the vast majority of people eventually die from respiratory failure.³

Once known as a pediatric illness due to short life expectancy, therapeutic advances have transformed CF into a chronic disease, with adults comprising more than half of those with CF in the United States and the United Kingdom.^4,5 Despite increased life expectancy, CF remains life-limiting, and people still die quite young, with a median age at death of approximately 31–32 years in 2018.^4,5 Unfortunately, children with CF and their families still endure the challenges associated with chronic illness, including the burden of numerous therapies and disease exacerbations, the knowledge of a limited life span, the responsibility of complex decision-making regarding lung transplant and other intensive treatments, and the stigma and reproductive choices associated with a genetic disease.

Model of Cystic Fibrosis Care Delivery

The care of individuals with CF involves multiple interdisciplinary clinicians collaborating with parents and caregivers, often following guidelines and recommendations from the Cystic Fibrosis Foundation. While this model provides structure and guidance, the specific care delivered is tailored to each individual’s needs and accessibility of available resources.

Due to its complexity, clinical CF care in the United States is usually received at accredited CF care centers.⁶ Part of a comprehensive network of clinical care, research, support, and quality improvement, accredited care centers were established in 1961 by the Cystic Fibrosis Foundation. There are about 130 accredited care centers across the United States, and people are encouraged to be seen at least quarterly.⁷ Accredited CF care centers must adhere to established guidelines; however, variation may exist related to differences in location, institution, or health systems. For example, children who live a long distance from their closest center may receive primarily consultative care, with much of their day-to-day care provided by a local primary physician. Additionally, children without health insurance may have limited or no access to a CF center at all, especially if the institution does not provide charity care or the child does not have documented status as a US citizen or resident.

Interdisciplinary Teams

An interdisciplinary approach to care is essential to manage this complex illness. Specialized care is provided through interdisciplinary teams with physicians, nurses, social workers, dietitians, and respiratory therapists; disciplines required for CF care center accreditation.⁶ Some teams also include other specialists like pharmacists, gastroenterologists, endocrinologists, psychologists, psychiatrists, physical therapists, or child life specialists. Close relationships often form between children, their families, and CF teams after working together for years and sometimes decades. With outcomes in CF closely linked with adherence to the daily treatment regimen, parents and other caregivers are essential partners in the CF care delivery model.

Palliative Care in Cystic Fibrosis

There are no accreditation requirements or standards for integration of specialty palliative care within CF care in the United States; however, the Cystic Fibrosis Foundation that states palliative care may be useful in symptom management.^8,9,10 Similarly, the European Cystic Fibrosis Society Guidelines call for “attention to communication, symptom control and a multi-disciplinary approach to care, including expertise in palliative care.”¹¹ Access to specialty palliative care varies by institution due to differences in size, scope, and availability of palliative care. For example, some CF centers are in an institution that only provides inpatient palliative care, limiting access for those with CF who could benefit from palliative care but are not hospitalized. Institutions that offer outpatient palliative care may have variable scope of services.

Routine care in CF aims primarily to control and/or improve symptoms, prevent or treat respiratory infection, and optimize nutrition.^10,12 This treatment, including airway clearance and medications for respiratory symptoms, pancreatic enzymes to improve GI symptoms and weight, and sometimes other medications to treat complications such as diabetes, forms the foundation of the treatment regimen in CF.

Treatment Burden

Treatment regimens in CF can be time-consuming, sometimes requiring 2–4 hours of therapy daily.¹³ Children with CF require close supervision from caregivers, and even adults often need assistance from caregivers to carry out respiratory therapies and other treatments.¹⁴ Adolescents may be particularly vulnerable if, as they strive to assert independence as part of usual growth and development, they decrease adherence to their CF treatment regimen. The time required is most always burdensome and challenging for both children and their families to maintain. Care should be nonjudgmental, with emphasis on partnering with children and families to focus on making the best decisions they can today and in the future, without blame or guilt related to past decisions.

Infection Control

As more evidence has become available over the past several decades, infection control has become a significant component of treatment. Over time, the lungs become colonized with various organisms, and people with CF risk exposing each other to dangerous respiratory pathogens. Current infection control and prevention guidelines call for people with CF to avoid close proximity to others with CF, staying a minimum of 6 feet apart at all times.¹⁵ An unfortunate consequence of the guidelines is the potential for decreased interaction and social support between people with CF.¹⁶

Mental Health

In addition to physical symptoms, people with CF, including children and adolescents, experience a high rate of depression and anxiety, and an association has also been found with effective management of CF.^17,18 Mental health care in CF has been emphasized through recent requirements for anxiety and depression screening and efforts to facilitate social support for people with CF and their families.¹⁸

Care During Advanced Illness

CF is a lifelong illness that necessitates frequent and never-ending therapies. While intensive therapies aimed at maintaining airway clearance and nutrition may stave off exacerbations, individuals with CF will invariably experience progressive loss of function; live with the unpredictable risk of exacerbations, worsening lung function, and frequent hospitalizations; and, ultimately, suffer a premature death. Unfortunately, even the most experienced CF clinician is unable to predict when these episodes of acute illness and loss may occur, and the disease carries a large degree of uncertainty.¹⁹ Many individuals with CF experience acute decompensations in health, recoveries, and periods of relative stability, usually superimposed on a gradual downward trajectory in lung function (Figure 31.1). An individual’s functional capacity over time often mirrors this course. Most people will have periodic setbacks, and while some of these setbacks will be followed by complete recovery, others may result in a decline of overall function. Lung transplant is a choice for some people with advanced illness but is not curative and comes with a host of burdens and uncertainties along with the potential for life extension and improved quality of life.

Innovative Therapies

When the CF gene was initially described in 1989, many believed a cure was imminent.²⁰ This hope led to great optimism, followed by disappointment when a cure did not readily arrive.²¹ While there is still no cure at this time, new and improved therapies, as well as the possibility of lung transplant, offer hope to many people living with CF.²² Recent development of cystic fibrosis transmembrane conductance regulator (CFTR) modulator medications have led to many in the CF community feeling that the future, long-anticipated following identification of the CFTR gene, is happening now.²³ CFTR modulators address the underlying cause of CF, restoring function to the defective CFTR protein and potentially altering the natural course of the illness.²³ The first CFTR modulator, ivacaftor (Kalydeco), was approved in the United States in 2012, but only about 8–10% of people with CF were eligible to take it. Recent studies report improved clinical outcomes and quality of life in people with CF taking ivacaftor.^24,25 After interim progress with additional modulators, elexacaftor/ivacaftor/tezacaftor (Trikafta) was approved in the United States in late 2019. Close to 90% of adults are now eligible for a CFTR modulator, with hope that approval for children will soon follow. Long-term safety, tolerability, and effectiveness are under study and much has been written about the high cost of these new medications. Ongoing research is already seeking the next generations of CFTR modulators and other innovative therapies.

This is an unprecedented and exciting time, but people with CF, especially those who are ineligible or cannot tolerate CFTR modulators because of drug interactions, hepatic insult, or adverse mental health outcomes, and those with accumulated damage to lungs and other organs will continue to need comprehensive care, including primary and specialty palliative care for years to come.^{26,27,28,29,30} It can be difficult to balance hope and optimism when seeing progress made in CF while at the same time confronted by the reality of disease progression and disappointment when a long-awaited therapy is not available or cannot reverse years of damage and other sequelae of CF.

Hope

For individuals with CF and those who care for them, hope and despair are inextricably intertwined. Widespread and consistent application of chronic treatments has led to increasing life expectancy, and new and improved treatments have shown more promise than ever. Understandably, most individuals with CF, family caregivers, and clinicians maintain an attitude of vigorous optimism. Experience suggests that CF teams generally adopt an enthusiastic approach, emphasizing optimistic increases in life expectancy and encouraging hope for improved survival and quality of life. This attitude is in part a response to the outdated image of CF among the general public as a killer of children, in part a strategy to encourage adherence to a time-consuming daily regimen, and in part an antidote to the unpredictable course of the illness.

Despite increasing life expectancy, people with CF still experience significant suffering.^17,31,32,33 In some circumstances, hopeful enthusiasm of CF care team members and parents may crowd out concerns of the child regarding what he or she has heard about limited life expectancy in CF. At other times, optimism may inhibit frank discussion of the reality of life with CF. The same enthusiasm may discourage reporting of bothersome symptoms or concerns about burdens of treatment. In these instances, a CF team’s enthusiastic optimism may worsen the child’s or family’s anxiety, when a quiet but hopeful discussion might have alleviated their concerns. An overly optimistic approach may also prevent the CF care team from recognizing benefits of collaboration with the palliative care team. A rejection of the either/or attitude toward hope and despair encourages recognition that hope can flourish even in the face of the difficult truth of symptom burden and limited life expectancy of CF.

Cystic Fibrosis Illness Trajectory

CF is a lifelong, multisystem, progressive illness characterized by gradual decline in lung function and GI/nutritional difficulties, with worsening symptom and treatment burden over time. In considering when and how to incorporate palliative care into CF care, it is helpful to consider both disease milestones and stage of illness across the life span of individuals with CF, including (1) diagnosis, (2) relative stability, (3) disease progression, and (4) end of life.

CF is an autosomal recessive genetic disorder. Although many older children and adults were diagnosed following onset of symptoms or diagnosis of a sibling, most new diagnoses are now made through newborn screening, resulting in a population of asymptomatic infants diagnosed in the first month of life.^5,34,35 Earlier diagnosis has led to some improved clinical outcomes, but does carry some risks for families, including emotional impact of indeterminate testing results with diagnostic uncertainty and implications of diagnosis of a genetic diseases.^36,37,38,39 Because of their experience with discussing difficult news and helping families manage grief, palliative care teams are in a good position to help CF teams develop a compassionate approach to revealing the diagnosis.⁴⁰

Families must process not only shock of the diagnosis, but also begin a complex care regimen to be followed every day if the benefit of earlier diagnosis via newborn screening is to be realized. CF care teams are accomplished at helping families with this news, but advent of newborn screening brings a new group to light: the largely asymptomatic child with a genetic diagnosis. The change in the experience of diagnosis may offer an opportunity for palliative care teams to approach the CF care team with an offer to help them do the best possible job supporting families affected by CF.

Relative Stability

Two events may provide room for palliative care teams to partner with CF care teams. The first is preparing the team to respond to children and families when they bring up limited life expectancy with CF. Many CF clinicians prefer to minimize this issue by focusing on the progress in CF so far, while many individuals with CF, especially by adolescence, are aware of limited life expectancy and should be offered the opportunity to talk about it.^41,42,43 CF care team members do not want to be surprised when an adolescent asks about mortality, and the palliative care team may be able to help develop an educational approach which explores a range of developmentally appropriate responses to a child’s questions.

Second, palliative care teams may have a window of opportunity to assist CF care teams during the first hospitalization for a pulmonary exacerbation. The first pulmonary exacerbation can be a time of substantial stress for the whole family as they are confronted with the reality of worsening illness.⁴⁴ Habituating the family to a routine of careful surveillance and vigorous treatment of any drop from “baseline” is an important goal. CF care teams may not recognize the increased symbolic meaning of this first exacerbation in an era of newborn screening and highly effective modulator therapy. Although pulmonary exacerbations and their treatment remain routine for CF teams, they are new to people with CF and their families.

Disease Progression and End of Life

There are many opportunities for integration of specialty palliative care within CF as the disease progresses: expert assessment and management of CF-related physical and emotional symptoms; communication augmentation, including assistance with goals of care, advance care planning (ACP), and complex treatment decision-making; caregiver support with shifting burdens and needs; and care coordination. These topics will be addressed in the next section.

With progress in therapies, some of the burden of symptoms and therapies may be lessening for children and adolescents. However, many young people currently living with CF face the challenges of progressive disease and end of life. As such, palliative care specialists should be familiar with the unique needs of children with CF and their caregivers.

Delivering Palliative Care to Children with Cystic Fibrosis

Palliative care is ideally a partnership, whereby CF care team members provide continuous monitoring and support for palliative needs, or primary palliative care, while palliative care specialists support the CF care team with expert management of complex or severe concerns.^45,46 Long-term, trusting relationships often exist between CF care teams and individuals with CF and their caregivers, thus facilitating CF care teams in addressing primary palliative care needs. CF care team members endorse the need for focused training in primary palliative care skills, including basic pain and symptom management, communication about goals of care, prognosis, and treatment decisions.^8,46,47,48 Palliative care specialists can offer expert management of complex or intractable distress that is beyond the scope or skill set of the CF care team (i.e., specialty palliative care) and can provide training and support around primary palliative care skills.

Historically, there has been no standard for incorporating specialty palliative care within CF care. Not unlike the general public and even some healthcare clinicians, many CF care teams inappropriately regard specialty palliative care as associated only with end of life. As a result, specific palliative interventions, including therapies directed at managing symptoms in those with mild to moderate disease, are often not introduced until the person is clearly dying—often too late to derive the benefits of specialty palliative care. A palliative care approach, clearly differentiated from end-of-life care and integrated with disease-directed and restorative measures from the time of diagnosis, may limit the burden of disease, maximize quality of life at all stages of illness, and provide effective support to individuals with CF and their families.⁴⁵ The intensity of palliative care should match the unique needs of each individual, including but not limited to physical and emotional symptom management, addressing existential and spiritual suffering, communicating about prognosis and treatment options, eliciting goals of care, engaging children with CF and caregivers in ACP, and, when relevant, offering support during lung transplant evaluation and following transplantation.

The remainder of this section will emphasize the role of the palliative care specialist in caring for individuals with CF, complementing primary palliative care offered by the CF care team. While consultation is more likely to occur in later stages of disease, it is important to recognize the value that specialty palliative care could bring throughout the life span. For examples of how palliative care teams can partner with CF care teams in providing palliative care to children with CF throughout the life span, please refer to Box 31.1 and the Family Reflection at the end of this chapter. Table 31.1 highlights examples of primary and specialty palliative care within the domains of palliative care.

Symptom Assessment and Management

Distressing physical and emotional symptoms are common in individuals with CF throughout the life span.^{49,50,51,52,53} While clinicians typically expect both physical and emotional symptoms to worsen as lung disease progresses, they are not as clearly associated as one might expect.^{10,51,52,53,54,55} Little research describes the impact of symptoms on quality of life or on the end-of-life experience for individuals with CF, but existing literature and clinical practice suggest much room for improvement in both care delivery and support for CF team members in managing symptoms.^47,56 General principles of symptom management can be applied in CF, and the multidisciplinary nature of CF care should allow for regular attention to symptoms with input from palliative care specialists for complex and/or severe symptoms and spiritual/existential distress. Because other chapters focus on assessment and management of symptoms, this section covers issues specific to symptom management in CF.

Respiratory Symptoms

Respiratory symptoms such as cough and dyspnea may be only minimal or intermittent in younger people, but worsen as lung disease progresses, with periods of increased cough and dyspnea occurring during respiratory exacerbations. Basic CF respiratory care, directed at reducing respiratory symptoms, involves a combination of airway clearance techniques, aerosolized therapies, antimicrobials, anti-inflammatory medications, and exercise.⁵⁷ Devices like percussive vests are used several times daily to help loosen and dislodge thick, sticky mucus. Daily airway clearance therapies are essential to maintain lung health and quality of life in CF. Respiratory exacerbations of CF manifest in many ways, with symptoms including increased cough and sputum production, dyspnea, fatigue, fever, chest pain, hemoptysis, sleep disturbance, and weight loss.

Cough is necessary for clearance of thick respiratory secretions, but excessive cough may be distressing and disruptive. Aerosolized therapies and airway clearance techniques facilitate cough and are routinely recommended for maintenance of health and are intensified during respiratory exacerbations. While these treatments are intended to reduce chronic respiratory symptoms, they are also burdensome due in part to the extensive amount of time required for treatments, but also the discomforts associated with respiratory therapies, such as pain, dyspnea, sleep disturbance, and urinary incontinence.^58,59 Treatment of increased cough includes aerosols and airway clearance therapies, antibiotics for infection, and specific treatments for other common causes of cough in CF, including gastroesophageal reflux disease, sinus disease, asthma, and allergies. Antitussives are typically avoided due to their negative impact on airway clearance. For severe exacerbations, hospitalization may be necessary. Intravenous antibiotics are commonly used, often in combination given the challenges of combating virulent and often drug-resistant respiratory pathogens, along with intensified airway clearance therapies.³

Hemoptysis may occur in association with cough, particularly in the setting of lower respiratory infections. Small volume hemoptysis is generally managed with antibiotics, correction of bleeding disorders, and cautious use of or temporary suspension of aerosols and airway clearance therapies. Massive hemoptysis (more than 240 milliliters in 24 hours or recurrent bleeding of more than 100 milliliters per day) occurs in approximately 1% of children with CF and is unrelated to severity of lung disease, is associated with other respiratory complications, and has a high likelihood of recurrence.⁶⁰ Bronchial artery embolization is utilized for acute treatment, but recurrent and unremitting end-stage hemoptysis may require sedation and measures such as the use of dark towels and linens to reduce visualization of bright red blood and help lessen anxiety.

Dyspnea is commonly reported as CF lung disease progresses.^10,51,61 This complex symptom is related to increased ventilatory demand due to increased dead space in abnormal CF lungs, increased respiratory effort to move air through dilated and obstructed airways, and increased muscle force required for maintenance of normal ventilation because of abnormal airway resistance and flattening of the diaphragm by hyperinflated lungs.⁶² Notably, the interplay between dyspnea and anxiety can be complicated.^63,64 Enhanced airway clearance and treatment of infection and inflammation with standard CF therapies may reduce acute or subacute dyspnea. With disease progression, dyspnea may become less responsive to such treatments.

For those with chronic dyspnea and more advanced lung disease, physical therapy to improve conditioning may be helpful. The use of oxygen to support gas exchange with exertion, during sleep, and on a continual basis later in the course of disease may reduce the sensation of dyspnea. Oxygen is usually administered by nasal cannula, although some people prefer to use face masks during periods of acute illness. Noninvasive positive pressure ventilation for management of dyspnea, hypoxemia, and hypercapnia was often avoided in the past because of concern for applying positive pressure to airways which are abnormally dilated and impacted with thick mucus, making airway clearance more difficult, but it has gained favor over time for those with sleep disturbance and daytime fatigue and as a bridging therapy for those with respiratory insufficiency awaiting lung transplantation.^65,66 Intubation with mechanical ventilation, and even extracorporeal life support (ECLS), may also be considered for some people with “reversible” causes of respiratory failure and for lung transplant candidates.^67,68 Ventilator modes and settings that combat hypercapnia in advanced CF lung disease are uncomfortable and typically necessitate the use of sedative medications which interfere with the ability to communicate. ECLS as a bridge to lung transplantation is intended to be provided to people who are awake and ambulatory, but the risk for complications is not insignificant.^68,69 The decision to use these interventions must be made with the knowledge that, while they may provide relief of severe dyspnea and possibly prolong life, their use has many associated risks which must be understood by individuals with CF and caregivers, along with continued exploration of goals of care.

Decreasing the sensation of dyspnea using opioids and benzodiazepines may be considered for use in advanced CF lung disease.^70,71 However, despite evidence that these medications can be used safely in people with respiratory diseases, concerns about respiratory depression in advanced CF lung disease have been described and may act as barriers to effective palliation of dyspnea.^{9,55,67,70,72,73} Aerosolized opioids have not been found to be efficacious.⁷⁴ Concerns about the use of opioids to relieve dyspnea may be alleviated by starting with very low doses and titrating to effect, monitoring closely for undesirable secondary effects and managing constipation proactively. This strategy also allows everyone the time to become more comfortable with the use of opioids to treat dyspnea. Other supportive and adjunctive therapies, including blowing cool air with fans, maintaining cooler ambient temperatures, positioning, relaxation techniques, and psychotherapy may be beneficial for some people. Clusters of symptoms like dyspnea and anxiety require thoughtful management.

Pain

Pain, including headache and sinus, chest, back, abdominal, and joint pain, is common in individuals with CF throughout the life span and negatively affects adherence, emotional symptoms, quality of life, and survival.^33,52,75 Headache may be due to cough, sinus disease, or hypercapnia in addition to the numerous other causes of headache in people without CF, and treatment should reflect the cause. Sinus pain may respond to treatment for infection with systemic or nasally instilled antibiotics or use of intranasal steroids and saline to facilitate drainage of secretions. Surgical intervention by an otolaryngologist for severe or persistent pain may be warranted.⁷⁶ Chest pain that originates from the lung may be due to infection, mucus plugging, hemoptysis, or pneumothorax; it is often localized and may be pleuritic and/or associated with symptoms like cough and dyspnea. Musculoskeletal chest pain may result from frequent cough and increased thoracic volume.⁷⁷ Individuals with CF may also be at increased risk of rib and vertebral compression fractures in the setting of osteoporosis related to chronic vitamin D deficiency and/or systemic steroid use.^78,79 Physical therapy, pharmacologic agents, and orthopedic referral can be considered depending on the etiology of the pain. Joint pain may be due to typical injuries or causes of arthritis in the non-CF population and to fluoroquinolone antibiotic use, but CF arthropathy, a diagnosis of exclusion, affects a small proportion of people with CF.⁸⁰ Symptoms are typically episodic and present at times of illness and stress. Treatment may involve analgesics and anti-inflammatory medications, sometimes including disease-modifying anti-rheumatic drugs.⁸¹ Caution should be given to concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients who are treated with nephrotoxic antibiotics for pulmonary exacerbations or with known comorbid kidney or liver disease; acetaminophen should be used carefully in those with CF-associated liver disease.

Distressing and/or debilitating pain from any source warrants careful evaluation. Appropriate management involves identifying and, if possible, eliminating underlying causes. Establishing goals of treatment and selection of medications and other treatments, and monitoring response to therapies and treatment side effects, should follow standard approaches to pain management addressed in previous chapters. Concerns about opioid use are often amplified in CF due to concerns about respiratory depression and severe constipation in addition to the societal concerns about misuse, abuse, and addiction. Additionally, lung transplant eligibility may affect opioid prescribing given concerns from transplant centers about perioperative management and long-term outcomes. There is not enough evidence to either support or refute withholding opioids from individuals with CF who have appropriate indications, including moderate to severe acute or chronic pain, painful therapies, dyspnea in severe lung disease, or pain/dyspnea at end of life.^82,83 As such, consideration around opioid prescribing must be individualized, with lung transplant not being an absolute contraindication.

Gastrointestinal Symptoms

Gastrointestinal manifestations of CF are numerous and include steatorrhea and malnutrition related to pancreatic exocrine insufficiency (present in approximately 85% of individuals with CF), gastroesophageal reflux, and obstructive biliary tract disease.⁵ Symptoms related to these problems include abdominal pain, constipation, anorexia, and, for a small percentage of people, symptoms of progressive hepatobiliary disease.⁸⁴ Abdominal pain associated with an increase in bowel movements, urgency, or distension should prompt optimization of pancreatic enzyme replacement. Constipation may be acute or chronic in nature and may be treated with oral electrolyte solutions and/or stimulant laxatives. Distal intestinal obstruction syndrome may occur when excessively viscid intestinal contents become impacted in the distal small intestine and proximal colon and should be suspected when pain and obstipation occur concomitantly. Treatment involves intestinal lavage and close monitoring for progression to frank bowel obstruction, which warrants surgical intervention.⁸⁵ Gastroesophageal reflux is managed with standard therapies, including histamine receptor antagonists and proton pump inhibitors. Surgical treatment of reflux does not appear to confer benefit but is considered in some cases.⁸⁶ Other causes of GI symptoms which are not specific to or more common in CF must not be overlooked.

Because of malabsorption and increased metabolic demands, individuals with CF require greater caloric intake to achieve and maintain adequate nutritional status. As lung disease progresses, cough and increased work of breathing may make eating laborious and maintenance of weight difficult or impossible without medical intervention. Behavioral interventions around feeding, calorie-dense oral supplements, and appetite stimulants are typically offered in a stepwise fashion as other causes of and contributors to anorexia, including gastroesophageal reflux disease, sinus disease, depression, and anxiety are addressed.^87,88 For those who are unable to maintain acceptable nutritional status, feeding tubes may be recommended.⁸⁸ Individuals with advanced disease who choose to pursue lung transplantation may be required to pursue intensive nutritional interventions in order to reduce operative and recovery-related risks. Those for whom transplantation is not desired or not an option may be offered more choices about the ongoing use of nutritional interventions.

Psychological Symptoms

Depression and anxiety are known to be more prevalent in CF compared to the general population.⁸⁹ They may adversely impact health outcomes and quality of life. Screening for depression and anxiety and guiding those affected to appropriate interventions and support are recommended as a routine part of CF care.¹⁸ For patients and families affected by any chronic illness, disease-specific social support plays a vital role in coping with stress and managing depression and anxiety. In contrast to past extensive social support available through cohorting of children with CF on hospital wards and summer camps, strict guidelines for infection control have led to physical isolation of individuals with CF and thus often their families. This has led to social networking and support via the internet and other media which allow for indirect contact.⁹⁰ For some, this is extremely effective, but for others this isolation leads to loneliness which may theoretically impact disease-related coping.^91,92

Treatment of depression in CF does not differ from standard treatment, apart from the recognition of chronic illness as a provocative factor.¹⁸ Anxiety about disease progression is common, suggesting the need for ongoing attention to this symptom throughout the life span. Symptom clusters may occur, such that anxiety may be perpetuated by dyspnea, cough, pain, and fatigue; thus, addressing these symptoms may reduce and indirectly treat anxiety. Medications commonly used to treat CF, such as beta-agonists and steroids, may also contribute to anxiety symptoms. Treatment of anxiety may involve cognitive-behavioral therapy, psychotherapy, and complementary techniques such as biofeedback and relaxation. Pharmacologic agents may be added in select cases, with favor given to selective serotonin reuptake inhibitors (SSRIs) and selective-norepinephrine reuptake inhibitors (SNRIs), noting potential for drug interactions in those using CFTR modulators or antimicrobial drugs with shared hepatic metabolism; this is most commonly the case with SSRIs.⁹³ Oral benzodiazepines are considered for short-term treatment of acute anxiety but otherwise reserved for those with severe and unremitting symptoms or advanced lung disease as per Cystic Fibrosis Foundation guidelines.^18,83

Fatigue

Fatigue is a highly prevalent but often underappreciated symptom in childhood chronic disease and is a common symptom in CF.^49,64,94 Fatigue is reported to impact adherence to treatment and quality of life.^94,95,96 This complex symptom is often unresponsive to rest, limits functioning, and affects physical, cognitive, and emotional stamina.⁶⁴ The interaction between fatigue and other symptoms such as cough, dyspnea, pain, and depression may be substantial.⁹⁵ Treatment for fatigue is also complex and not well studied in CF, but interventions including exercise, psychotherapy and disease-specific support networks, complementary and alternative therapies, improving sleep hygiene, and the use of stimulants are possible options.^64,97 Management of sleep disturbance, either on its own or as a contributor to fatigue, centers on improving nocturnal hypoxemia or sleep-disordered breathing. If present, treatment with supplemental oxygen or noninvasive positive pressure ventilation and avoiding use of hypnotics in favor of nonpharmacological strategies may be beneficial, with melatonin felt to be safe and efficacious for children with CF.^98,99

Role of the Palliative Care Team in Symptom Management

While CF clinicians and other care team members are aware of the high symptom burden in CF, many lack specific training in thorough assessment and management of symptoms. Additionally, the focus of routine CF care is often on preservation of “baseline” health and lung function rather than on chronic management of symptoms, even for those symptoms which are more likely to progress than to remit. Concerns about medication side effects and long-term implications of certain symptom-specific treatments, as well as a lack of clinical decision support, may lead to under-prescribing of medications and other symptom-specific treatments, particularly in the late stages of CF lung disease. Palliative care clinicians may use their expertise to bring attention to and offer relief from distressing symptoms experienced by individuals with CF as their disease progresses.

Communication: Goals of Care, Advance Care Planning, and Decision-Making

Most individuals with CF will live into their adult years, necessitating a transition of decision-making from surrogates to autonomous decisions. Often, in this transition, adults with CF may defer decision-making to the parent who has carried that responsibility all their lives.¹³ For this reason, special care should be taken to assess the role of each individual in the decision-making process, and effort should be made to actively include the adolescent and young adult.¹⁰⁰

While few people give no thought at all to the life-threatening nature of their disease, some adolescents and young adults develop certain fantasies or beliefs about their life span and may develop symbolic meaning to living past a certain age.^43,101,102 These expectations and perceptions may directly influence planning for the future, adherence to the therapeutic regimens, and quality of life. Prognostic uncertainty and discussions about life expectancy lead to anticipatory grief in children with CF. This grief may intensify during hospitalization and when health declines, as well as through observation of serious illness and death in CF peers. Children, caregivers, and clinicians should be encouraged to see grief as an expected part of life with CF. Much like other children with chronic life-threatening illnesses, children with CF are often aware they are dying even if never told directly, and they have concerns about impending death and separation from caregivers, family, and friends.¹⁰³ They may also grieve the loss of function, lack of interaction with family and peers, and changes in body image. Palliative care specialists and others with expertise in psychosocial support can help children communicate these concerns and find meaning and control as illness progresses. They can also be helpful in educating caregivers and members of the CF care team in how to provide appropriate supports to the child and how best to involve children in planning and decision-making, which could help mitigate anxiety and grief around serious illness and disease progression.

While ACP for children does not carry legal weight, the American Academy of Pediatrics recommends that children, adolescents, and young adults with a life-limiting illness be involved in ACP.¹⁰⁴ As such, children with CF should be included in medical decision-making in a culturally and developmentally appropriate way with an effort of transition from assent to autonomy.^41,105,106 Information about ACP in CF is limited, especially in children. A study of adults with CF revealed that most recognized the life-threatening nature of their disease and have considered the type of care they would want to have if unable to decide for themselves, and many even developed specific plans about end-of-life care.¹⁰⁷ While these adults discussed their plans with family members and said they would be comfortable discussing them with the CF care team, only one-third had in fact discussed ACP with any member of the team. Subsequent studies suggest greater rates of ACP, but this is not universal among adults with this known life-limiting illness.^48,105,108 Reasons for lack of communication include perceptions that these discussions will hinder hope, optimistic expectations of treatment outcomes, denial of disease severity, delaying conversations until patients themselves are too ill to participate, and beliefs that they only need to occur when death is imminent.^109,110

Existing ACP tools may not fit the clinical characteristics of CF given the unique aspects of the CF illness trajectory and disease-specific therapies. In an attempt to improve ACP, some CF care centers have developed CF-specific tools or have adapted programs such as Voicing My Choices and Five Wishes for use in CF clinical care.¹¹¹ Do not attempt resuscitation (DNAR) and do not attempt intubation (DNAI) orders appear to be perceived as having limited practical use in ACP in CF in the United States because a DNAR order is not in place for most people with CF until very late in the course of illness.¹¹² In practice, DNAR and DNAI orders should not be used as the sole document regarding appropriate interventions near the end of life, particularly as the roles and outcomes of advanced therapies like extracorporeal membrane oxygenation (ECMO) to support respiratory failure evolve.⁶⁸ Instead, these orders should be used as part of meeting the goals of care of the individual and family and should be consistent with the anticipated outcome of the intervention.

Lung Transplantation for Advanced CF Lung Disease: Special Considerations

Lung transplantation is the most intensive treatment available for advanced CF lung disease and is considered when one’s functional status and quality of life are significantly impaired, with listing occurring when anticipated survival with a transplant is greater than without.¹¹³ Transplant may improve survival and quality of life for selected patients. Length of survival after transplant is unpredictable for an individual, and shorter on average in children than adults: median survival is currently 9.9 years for adults with CF versus 5.6 years for children.¹¹⁴ While some people have relatively benign operative and post-transplant courses, complications are unfortunately difficult to predict and count as the second leading cause of death among people with CF.⁵ Quality-of-life outcomes are variable throughout the transplant course, often affected by medical complications, and accompanied by anxiety and depression.^115,116 With advances in therapies, the time frame for transplant consideration may be shifted away from childhood, but, at this time, many children and adolescents/young adults with CF still face this decision.

The pursuit of lung transplantation may inherently change the focus of care from restorative and palliative to “curative” in the eyes of individuals with CF, caregivers, and medical providers.^9,117 It is important to recognize that the additional stress of waiting for a transplant may have great emotional impact, with candidacy for transplant always at risk because of development of disease complications that might preclude it and the risk of dying before transplant.¹¹⁸ Discussions about transplant provide a natural opportunity to address wishes for ongoing medical care, including hopes for survival, goals and expectations for palliation of symptoms, and desired roles of caregivers. While meeting new clinicians and teams may be an additional stressor, palliative care consultation during the transplant decision-making process and after transplant—ideally with continuity throughout—may have many benefits.

It is important that individuals with CF and their caregivers fully understand the risks and benefits of transplant as well as alternative treatment options. Earlier referral for transplant evaluation is recommended to allow people time to process information and make a truly informed decision in the context of their goals and values.¹¹³ Discussions about transplant often take place with various clinicians, including members of the CF care team, lung transplant team, and palliative care team. Input from different parties may help individuals with CF and caregivers decide whether transplant falls within the context of their goals and values. Open communication among clinicians and teams is essential so that decisions can be supported.¹¹⁹ In addition, offering peer decision-support by means of support groups and mentoring programs may be helpful. Issues of caregiver stress and fatigue should be acknowledged and addressed.¹²⁰

For those considering or awaiting lung transplantation, decisions to limit life-sustaining treatments can be particularly complex. Challenges exist in simultaneously managing end-of-life care/ACP and candidacy for lung transplantation. As previously discussed, transplant eligibility may limit or preclude use of opioids and benzodiazepines for severe symptoms or when end of life may be near but hope for transplant remains. This is primarily because of perceptions, despite lack of evidence, that perioperative management and long-term outcomes might be negatively affected by use of these classes of medications.^73,82,83 CF and transplant care clinicians are encouraged to engage people in honest conversations about implications and anticipated outcomes of treatments like mechanical ventilation and/or ECLS as a bridge to lung transplantation and decisions to forego or limit symptom-relieving medications in the face of this uncertainty. Palliative care specialists can be helpful to individuals with CF, their families, and CF clinicians as they balance these often conflicting choices. Regardless of transplant eligibility or candidacy, preferences may change as one’s condition changes, and clinicians should invite ongoing conversations about ACP.

Individuals with CF who pursue lung transplant but are deemed ineligible for transplant because of medical or psychosocial contraindications deserve thoughtful discussion of their goals for ongoing medical care, which may include continuation of standard CF therapies, incorporation of palliative treatments, and/or transition to hospice care. Palliative care consultation for discussion of treatment options and further planning may be beneficial for individuals with CF, caregivers, and the CF care team.

Related posts:

Quality in Pediatric Palliative Care Program Development The Language of Pediatric Palliative Care Relationships with Children and Ensuring Their Voices in Decision-Making Advanced Heart Disease Children’s Voices: The Experience of Patients and Their Siblings

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