INTRODUCTION — Palliative care is an interdisciplinary medical specialty that focuses on preventing and relieving suffering and on supporting the best possible quality of life for patients facing serious illness and their families. The primary tenets of palliative care are symptom management; establishing goals of care that are in keeping with the patient’s values and preferences; consistent and sustained communication between the patient and all those involved in his or her care; psychosocial, spiritual, and practical support both to patients and their family caregivers; and coordination across sites of care. Thus, palliative care aims to relieve suffering in all stages of disease and is not limited to end of life care. Palliative services, including setting patient-centered achievable goals for medical care and aggressive symptom management, should be routinely offered alongside curative and disease-modifying treatments for patients with serious illnesses.
Palliative care has been best studied and implemented among patients with cancer, but is also beneficial for patients suffering from chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), interstitial lung disease, pulmonary hypertension, and others. The ultimate goal of palliative care is to improve patients’ quality of life and provide support for patients and their families [1].
Palliative care issues in adult patients with chronic lung disease will be reviewed here. Other aspects of adult palliative care including management of dyspnea and cough, issues related to pediatric palliative care, an overview of patient assessment and symptom management in palliative care, and the palliative care of patients with neuromuscular causes of respiratory failure are discussed separately. (See "Assessment and management of dyspnea in palliative care" and "Palliative care: Overview of cough, stridor, and hemoptysis in adults" and "Pediatric palliative care" and "Approach to symptom assessment in palliative care" and "Overview of comprehensive patient assessment in palliative care" and "Overview of managing common non-pain symptoms in palliative care" and "Palliative care: The last hours and days of life" and "Swallowing disorders and aspiration in palliative care: Definition, pathophysiology, etiology, and consequences" and "Swallowing disorders and aspiration in palliative care: Assessment and strategies for management".)
CLINICAL COURSE AND CAUSES OF DEATH — The disease trajectory of chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, is variable and characterized by considerable uncertainty. While patients typically have a phase of gradual decline, the trajectory can change abruptly due to exacerbations of the underlying lung disease or events caused by a comorbid disease.
The disease trajectories for less common lung diseases such as pulmonary hypertension (PH) or lung transplant recipients differ depending on the cause of the disease, co-morbid conditions, response to treatment or surgery.
Disease trajectory
●COPD – Patients with advanced COPD usually experience a gradual but progressive decline in exercise tolerance and development of oxygen dependence that is typically punctuated by acute exacerbations [2]. Patients with COPD are frequently hospitalized at the end of life, often in the intensive care unit (ICU). However, there is some evidence that over time, fewer patients are dying in acute care hospitals. As an example, one retrospective cohort study examined fee-for-service Medicare beneficiaries who died in 2000, 2005, or 2008 with a diagnosis of cancer, COPD, or dementia [3]. Among the cohort with COPD, between 2000 and 2009, more patients died at home in 2009 than in 2000 (28 versus 24 percent), fewer died in acute care hospitals (32 versus 44 percent) and more patients were under hospice care at the time of their death (39 versus 20 percent).
Every exacerbation of COPD can be life-threatening and is associated with an increased risk of dying. In fact, about 10 percent of patients hospitalized with an acute exacerbation of COPD die during the hospital admission [4]. This proportion increases to about one-fourth for patients who need invasive mechanical ventilation because of respiratory failure [5]. About one-half of the patients admitted for an exacerbation don’t survive four years after discharge [6]. (See "COPD exacerbations: Prognosis, discharge planning, and prevention", section on 'Prognosis after an exacerbation'.)
Importantly, not all patients follow this hypothetical disease trajectory, of a gradual decline with interspersed acute exacerbations. In fact, the progression of COPD is very heterogeneous [7], and the end of the patient’s life is often unanticipated by their loved ones [8]. Despite the heterogeneity in clinical course among patients with COPD, certain parameters predict a greater likelihood of death within 12 months: decrease in six-minute walk distance of 50 meters, change toward a very sedentary lifestyle, change toward feeling upset or downhearted, increase in arterial tension of carbon dioxide of >3 mmHg, or decrease in arterial tension of oxygen by >5 mmHg [9].
●Idiopathic pulmonary fibrosis – Idiopathic pulmonary fibrosis (IPF) is usually characterized by a gradual and inexorable decline in respiratory capacity. However, patients may remain stable for a longer period of time or may be confronted with frequent hospital admissions because of acute worsening of respiratory symptoms [10]. The median survival for IPF is two to three years, although some patients live much longer [11]. Most patients experience a subacute worsening over one or more months, while a minority have an acute deterioration less than one month. (See "Prognosis and monitoring of idiopathic pulmonary fibrosis".)
The majority of patients with IPF die in a hospital setting, and in contrast to the data in COPD, there is no evidence that this number has declined over time or that hospice enrollment has increased [12].
●Pulmonary hypertension – The clinical course of pulmonary hypertension (PH) is highly variable depending on the type, functional class, and comorbidities. For patients with pulmonary arterial hypertension (PAH), the median survival without treatment is three years. Data from the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL registry) reveal one-, three-, five-, and seven-year survival rates of 85, 68, 57, and 49 percent, respectively, from the time of diagnostic right heart catheterization [13]. The prognosis of patients with PH related to chronic lung disease, left heart disease, connective tissue disorders, or portal hypertension varies with the prognosis of the underlying disease, severity of the PH, and response to therapy. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".)
●Lung transplantation – Among patients on the lung transplant waiting list, the one year mortality is approximately 15 percent [14]. Following lung transplantation, the median survival ranges from 4.5 years for patients with IPF to 7.8 years for patients with cystic fibrosis [15]. The median survival for an adult lung transplant recipient is 5.7 years. (See "Lung transplantation: An overview", section on 'Outcomes'.)
Common causes of death — Among patients with chronic lung disease, death may be caused by progressive respiratory failure, an acute exacerbation of the lung disease, intercurrent infection, or a comorbid disease.
●A longitudinal study of patients with COPD showed that approximately 58 percent have a respiratory cause of death [7]. For patients with severe or very severe COPD, respiratory failure from an acute exacerbation of COPD is the primary cause of death [16]. On the other hand, patients with COPD often suffer from multiple comorbidities and a substantial minority (approximately 42 percent) die of non-respiratory diseases [7,17]. The most common causes of death for patients with mild or moderate COPD are cancer and cardiovascular disease [18]. (See "Chronic obstructive pulmonary disease: Prognostic factors and comorbid conditions".)
●Among patients with IPF, most deaths are due to progression of IPF rather than comorbid conditions [11]. However, coronary artery disease, heart failure, bronchogenic carcinoma, infection, and pulmonary embolism are additional contributors to mortality. (See "Prognosis and monitoring of idiopathic pulmonary fibrosis".)
●The main cause of death in patients with PAH is right heart failure with circulatory collapse and superimposed respiratory failure. Circulatory collapse can also occur when these patients are placed on mechanical ventilation for ventilatory failure. Patients with PAH who experience cardiac arrest rarely survive. In a retrospective study of more than 3000 patients with PAH who required cardiopulmonary resuscitation (CPR), only 6 percent survived for 90 days [19]. The cause of death for patients with PH varies depending on the course of the underlying disease. (See "Treatment and prognosis of pulmonary arterial hypertension in adults (group 1)".)
●In the first month after lung transplantation, the leading cause of death is graft failure, a form of acute respiratory distress syndrome (ARDS)/diffuse alveolar damage (DAD), which occurs in the early hours to days after transplant. Chronic lung allograft dysfunction (CLAD), which manifests as bronchiolitis obliterans or restrictive allograft syndrome (RAS), is the leading cause of mortality after the first year. Infectious complications remain a major cause of death at all time points after lung transplantation. (See "Lung transplantation: An overview", section on 'Causes of death'.)
USE AND BENEFITS OF PALLIATIVE CARE — The primary goal of palliative care is to improve quality of life for the patient and their family through relief of emotional and physical symptoms. Other key services are establishing goals of care, psychosocial, spiritual, and bereavement support, and coordination of care. (See "Benefits, services, and models of subspecialty palliative care" and "Palliative care and hospice outside of the United States".)
A growing body of evidence supports the effectiveness and positive impact on quality of life and possibly survival of early palliative care consultation for patients diagnosed with advanced malignant diseases, including lung cancer [20-23]. (See "Benefits, services, and models of subspecialty palliative care", section on 'Rationale for palliative care'.)
Fewer studies have specifically examined the benefits of early palliative care consultation in patients with nonmalignant chronic lung diseases, although several have included patients with multi-morbidities including chronic obstructive pulmonary disease (COPD), heart failure, and idiopathic pulmonary fibrosis (IPF):
●In one randomized trial that included patients with refractory breathlessness due to a variety of illnesses (COPD, IPF, cancer, heart failure, and motor neuron disease), usual care was compared with initiation of an interdisciplinary breathlessness support service, which included palliative care specialists [24]. The interdisciplinary support service delivered an intervention focused on assessing patients’ symptoms and teaching mastery skills to manage dyspnea. Patients assigned to the support service reported a 16 percent improvement in breathlessness mastery as compared to usual care. These findings support early integration of palliative care to improve dyspnea control for patients with advanced lung diseases.
●A review of the impact of outpatient palliative care on outcomes that included studies conducted in patients diagnosed with late-stage COPD, heart failure, and cancer concluded that palliative care services improve patient satisfaction, symptom control, quality of life, and reduced health care utilization [25].
●A systematic review of 23 studies that were conducted in the United States, United Kingdom, Sweden, Norway, Italy, Spain, Canada, and Australia and included patients with cancer, heart failure (HF), COPD, HIV/AIDS and multiple sclerosis found that use of expert home palliative care teams more than doubled the odds of dying at home [26]. This review further found that home palliative care reduced the symptom burden for patients, while usual care was associated with an increase in symptoms.
●Similarly, several studies suggest benefit of palliative care consultation services for patients with chronic disease. A study of 524 dying patients at five VA medical centers and affiliated nursing homes in 2006 to 2007 showed that those who received inpatient palliative care consultations had significantly better outcomes in five of six domains studied: information and communication, access to home care services, emotional and spiritual support, well-being and dignity, and care around the time of death [27]. Several studies also suggest that inpatient palliative care consultations are associated with a reduction in costs of care in the hospital [28-30]. Moreover, a study performed in Australia showed that community-based palliative care can reduce hospital costs for patients with multiple conditions, including COPD [31]. (See "Palliative care delivery in the home".)
Despite these benefits, palliative care remains an unmet need for many patients with chronic lung disease, as exemplified by the following data [12,32-44]:
●In one study of adult patients with IPF living in the United States, only 14 percent were referred to palliative care and most referrals occurred in the last month of life [12].
●In a retrospective review of 339 British patients who died of COPD, during the last year of life, 41 percent either left the house less than once per month or never left, 47 percent were hospitalized at least twice, 67 percent died in the hospital, and only 63 percent knew that they could die [32]. Others have also confirmed that patients with COPD are often unaware of the progressive course of their disease and the possibility they could die from COPD [33].
●In a study of patients with oxygen-dependent COPD in the United States, only 32 percent of the patients reported having discussed with their clinician the care they would want if they were too sick to speak for themselves [34]. A Dutch study confirmed that clinicians rarely discuss life-sustaining treatment preferences with their patients with COPD, despite the fact that patients are able to indicate their preferences regarding life-sustaining treatments [35]. Although patients with severe COPD rate their clinicians’ general communication skills highly (eg, listening, answering questions), they rate their clinicians’ skills at discussing end-of-life topics as poor and reported that many topics are not discussed at all (eg, prognosis, what dying might be like, spiritual issues) [36,37]. A systematic review confirmed that advance care planning (ACP) is uncommon in chronic respiratory diseases, despite the willingness of patients to discuss ACP topics [45].
These findings underscore the need for improved palliative care services for patients with chronic lung disease [38]. The World Health Organization lists COPD as one of the most common conditions for which palliative care is an appropriate, yet underutilized service [46].
What is the difference between palliative care and hospice? — While hospice and palliative care share the same principles of providing comfort and support for patients, palliative care differs from hospice care. In the United States, the term hospice is used to describe a model of palliative care that is offered to patients with a terminal disease who are at the end of life (generally with an estimated life expectancy of six months or less) when curative or life-prolonging therapy is no longer the focus of treatment. In contrast, palliative care should be appropriately offered to patients at any time along the trajectory of any type of serious life-threatening illness, even concurrent with restorative, life-prolonging therapies. While all care that is delivered by hospice programs can be considered palliative care, not all palliative care is delivered in hospices.
Eligibility for hospice care generally requires that a physician estimate that life expectancy is six months or less. Disease-specific criteria for hospice referral for patients with chronic lung disease as well as non-disease specific criteria are outlined in the tables (table 1 and table 2), and discussed in more detail below.
For patients with a serious, life-threatening illness such as chronic lung disease, palliative care should be offered early in the disease process and should be available throughout the patient’s course if needed to address difficult-to-control symptoms, goals of care, or coordination across sites of care. Palliative care may be delivered in a number of settings across the continuum of health care, including in the home, nursing homes, long-term acute care facilities, acute care hospitals, and outpatient clinics [1]. Moreover, palliative care may include bereavement care for family and loved ones following the death of the patient. (See "Overview of comprehensive patient assessment in palliative care" and "Palliative care delivery in the home" and "Palliative care: Nursing home" and "Benefits, services, and models of subspecialty palliative care" and "Bereavement and grief in adults: Management".)
What is the difference between primary and secondary (subspecialty) palliative care? — Hospice and Palliative Medicine is now recognized as a medical subspecialty by the American Board of Medical Specialties, as well as in Canada, England, Ireland, Australia, and New Zealand. Many other European countries are also in the process of developing certification for palliative care. In most jurisdictions, palliative care is provided by an interprofessional team [47] of specially trained physicians, nurses, social workers, chaplains, and other specialists with advanced training in palliative care who work with a patient’s other clinicians to provide an "extra layer" of support. Clinicians who are specifically trained in palliative care can provide in-depth pain and symptom management, communication regarding goals of care, and care coordination across settings and over time. Subspecialty palliative care services are most available in high-income countries, as exemplified by the United States. The availability of subspecialty palliative care services in low income countries is generally quite limited. (See "Benefits, services, and models of subspecialty palliative care" and "Palliative care and hospice outside of the United States".)
Indications for a formal palliative care consultation are discussed in detail below. (See 'What are the indications for a palliative care consultation?' below.)
In order for the large number of patients with advanced life-threatening illness to benefit from palliative care it is important that supportive services be provided not only by palliative care specialists but also incorporated into the practices of all clinicians who are caring for persons with serious and complex illness such as chronic lung disease. Some term this "primary" palliative care, to distinguish it from "secondary" or "subspecialty" palliative care [48]. This encompasses any type of supportive care that is delivered by all health care professionals caring for patients with serious life-threatening illness. Optimal palliative care for patients with chronic lung disease should ideally incorporate both primary and subspecialty palliative care. Several examples of skill sets that are appropriate for primary versus subspecialty palliative care are provided in the table (table 3). (See "Primary palliative care".)
Clinicians caring for these patients need to attain competence in providing comprehensive supportive care. Several palliative care training options are available for clinicians (table 4).
What are the indications for a palliative care consultation? — While physicians caring for patients with chronic lung disease are able to manage most of their patients' palliative care issues, consultation with a palliative care specialist may be beneficial in certain situations. Indications for a formal palliative care consultation have not been established for patients with chronic lung disease. However, criteria for a palliative care assessment at the time of admission to the hospital are available (table 5). Other criteria that may apply to outpatients with chronic lung disease are summarized in the table (table 6).
Consideration of disease specific criteria (eg, COPD GOLD stage 4 or a decline in forced vital capacity [FVC] for patients with IPF), in addition to the degree of functional impairment, helps guide clinicians on when to consult specialty palliative care. For clinicians who do not integrate primary palliative care into their practice, an early consult to specialty palliative care may help guide subsequent goals of care discussions.
How to introduce palliative care to patients and families — It can be helpful to introduce palliative care as "supportive care" and explain that it focuses on symptom management and team communication about the patients’ goals and care wishes. This description helps to address the general lack of understanding about the meaning of palliative care. A study found that patients and caregivers better understood the meaning of supportive care than palliative care, which is often misperceived as end-of-life care [49]. It is important to emphasize that palliative care is often provided in addition to a patient’s current treatment plan. For example, a patient with COPD can receive palliative care and still choose to receive endotracheal intubation, if needed, in the event of an acute exacerbation with respiratory failure.
When thinking about the language to use to initiate a conversation about palliative care, it may be helpful to focus on aspects of that particular patient’s symptoms or clinical course, such as progressive dyspnea, an increase in oxygen requirement, decrement in pulmonary function tests, increasing dependence on others, or a recent emergency department visit or hospitalization that may have suggested the need for a goals of care discussion or advance care planning (table 7).
It may be beneficial to include family caregivers of patients with advanced lung disease in these discussions as they often need to make specific and urgent treatment decisions about life-sustaining treatment [50]. A systematic review showed the benefits of advance care planning for patients as well as their loved ones [51]. Advance care planning interventions increased the completion of advance directives, the occurrence of discussions about advance care planning, and improved the concordance between preferences for care and care delivered.
What are the important components of palliative care? — Important components of palliative care include exploring the patient’s understanding about their illness and prognosis, assessing and managing symptoms, discussing goals of care and advance care planning, coordinating care, and helping to plan end-of-life care, including determining the need and timing of hospice care (table 8). (See 'Symptom management in chronic lung disease' below.)
Advance care planning — Advance care planning (ACP), defined as "planning for and about preference-sensitive decisions often arising at the end-of-life," is an ongoing process in which patients, their families, and their healthcare providers reflect on the patient’s goals, values, and beliefs, and discuss how they should inform current and future medical care [52]. ACP enables individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and health-care providers, and to record and review these preferences if appropriate [53]. In an ideal ACP discussion, the clinicians, patient, and his or her loved ones think through particular approaches to follow if (or when) the patient’s health declines. This process is iterative and typically occurs longitudinally within the context of an existing and continuing medical relationship [54]. General issues about advance care planning are discussed separately. (See "Advance care planning and advance directives".)
Issues related to advance care planning for patients with chronic lung disease include the patient’s diagnosis, the expected disease course, and whether the patient would want intubation and mechanical ventilation. If the patient would like a trial of mechanical ventilation, parameters for discontinuing mechanical ventilation should be included. The potential outcomes of intubation/mechanical ventilation should be described to help the patient’s decision-making. While prognostic uncertainty and variable trajectory of illness make communication about these issues difficult [2], it is important to incorporate this uncertainty into advance care planning. (See 'Disease trajectory' above.)
A systematic review demonstrated that advanced care planning was acceptable and desired by most patients with chronic lung diseases and their clinicians, although engaging in advance care planning was rare [45].
Emerging research suggests that advance care planning discussions may be facilitated by nurse-led intervention and the use of specific end of life communication tools.
●A multicenter, open-label randomized trial with preference arm showed that nurse-led facilitated advance care planning is acceptable to patients with advanced respiratory disease and effective in increasing advance care planning discussions and completion of formal documents [55].
●A randomized trial testing an end-of-life communication tool for patients with severe COPD found an increase in the occurrence and quality of these discussions [56]. However, the study was not able to demonstrate a long-term impact on the documentation of goals of care discussions or completion of advanced directives. Further research is needed to develop interventions that ensure repeated assessments of preferences for life-sustaining treatments.
When to begin the discussion — Advance care planning discussions should begin early in the disease process when the patient is well enough to participate. Patients tend to underestimate disease severity and rarely initiate a discussion about palliative care or end-of-life planning [57]. In the month before they died, only 31 percent of patients with advanced COPD estimated their life-expectancy to be less than one year [58]. Concerns about dying and fears of breathlessness or suffocation are highly prevalent, but are scarcely discussed with their clinicians [33]. Preferably, these discussions should occur when the patient is relatively stable, rather than at a time of acute illness. Studies suggest most patients and their families prefer to have these conversations in a stable medical state when they are able to make clear decisions [59].
Several transition points in chronic lung disease have been identified that should serve to prompt a discussion about goals of care and advance care planning [59-61]:
●The start of new or different treatments, eg, initiation of oxygen therapy
●Lack of further life-prolonging treatment options
●Functional decline
●Frequent exacerbations
●Frequent hospitalizations/emergency room visits
●Referral for lung transplantation
Once a transition point is identified, the clinician can choose the appropriate time and place to broach the topic, determine who should be present, and hold a meeting with the patient and family.
One barrier to initiating a discussion of palliative care is the lack of precision in determining prognosis, particularly among patients with COPD. (See 'Disease trajectory' above.)
What topics should be discussed? — While all of these topics may not be discussed at a single visit, topics that are important for patients to address during advance care planning conversations include the following [62,63]:
●Diagnosis and expected disease process
●Treatment options
●Prognosis
●Patient’s goals of care (eg, longer survival, more time at home, control of symptoms)
●Values and beliefs
●The process of dying
The discussion should be patient-centered, balancing hope with reality with sensitivity. Eliciting information about the patient’s perception of the impact of the disease in their life, disease severity and prognosis will guide the clinician in achieving this balance. Sensitivity to the individual patient’s response to a discussion of these issues is essential due to the broad variation in patient responses. Discussions about prognosis can be especially difficult. Issues related to communication of prognosis in patients with advanced life-threatening illness and practical guidance for discussing prognosis are addressed elsewhere. (See "Communication of prognosis in palliative care" and "Discussing serious news".)
Many patients with advanced lung disease fear dyspnea crisis and suffocation. So, it is important for patients to discuss palliative care options for dyspnea and how to manage dyspnea crisis. Reassurance about a clear plan to deal with dyspnea may alleviate unspoken fears. Other relevant palliative care topics are the role of advance directives and surrogate decision-makers, preferences for location of end-of-life care and spiritual beliefs [63,64]. (See 'Anticipating and managing "dyspnea crisis"' below and "Advance care planning and advance directives" and "Palliative care: The last hours and days of life".)
Patients with chronic lung disease are particularly likely to develop respiratory failure in the setting of acute exacerbations or relatively mild intercurrent illnesses. Thus, understanding a patient’s preferences for life-sustaining treatments early in the disease course is particularly relevant. When given the opportunity, patients with chronic lung disease are able to indicate their preferences regarding life-sustaining treatments based on their expected burden of treatment and expected outcome of treatment [35]. Thus, it is important to include a discussion of prognosis after resuscitation or mechanical ventilation and potential withdrawal of life support.
●Prognosis after resuscitation or mechanical ventilation – Patients with COPD tend to have a poor prognosis for returning home and living independently after in-hospital resuscitation or, to a lesser extent, mechanical ventilation for an exacerbation. A study found that among patients with COPD who received in-hospital resuscitation, only 15 percent of patients survived to hospital discharge and, among survivors, they had a median survival of only five months [65]. Furthermore, less than 2 percent were discharged home after the hospitalization and were alive at six months [65]. A retrospective cohort study of 4791 patients with COPD receiving long term oxygen treatment examined the outcomes of patients who received invasive mechanical ventilation for an exacerbation [5]. In total, 23 percent of these patients died during the hospital admission, and an additional 45 percent died in the subsequent 12 months. Two-thirds of the patients surviving hospitalization were readmitted at least once in the year following the hospital admission and more than a quarter were discharged to a nursing home or skilled nursing facility.
For patients with IPF, prognosis after mechanical ventilation for respiratory failure is also poor. In one review that included 135 patients, the mortality was 87 percent in the intensive care unit and 94 percent at three months [66]. Other smaller studies have reported a similar 85 percent in hospital mortality rate for invasive mechanical ventilation [67,68].
●Withdrawal of ventilatory support – Making an "all-or-nothing" decision about ventilatory support may be difficult in the early stage of an illness. The possibility of a time-limited trial of ventilatory support may allow treatment of a process like pneumonia, which is expected to be curable, but enable clinicians to withdraw ventilatory support if the patient does not improve in a reasonable amount of time as guided by the patient. Thus, it is prudent to establish the goals of care and the situations in which mechanical ventilation would be discontinued. Alternatively, patients may agree to noninvasive ventilation, but not intubation with invasive ventilation. (See 'How to establish goals of care' below and "Withholding and withdrawing ventilatory support in adults in the intensive care unit".)
How to establish goals of care — Discussing goals of care is an important component of advance care planning, and this starts with exploring what is important to the patient. Exploring what "living well" means to patients can help start this discussion [69]. Some patients feel that living as long as possible is most important even if it means that they have to undergo highly burdensome interventions, such as prolonged mechanical ventilation, that impair their quality of life. Other patients may want to spend their remaining time at home with their loved ones without having to go to the hospital, even if this compromises their survival. The best possible care should support patients to live the rest of their lives according to their informed wishes. (See "Discussing goals of care".)
Asking about the experience of living with advanced lung disease as well as previous experiences with hospital admissions is important during goals of care and advance care planning discussions [69]. The narrative of these experiences can help the clinician understand the patient’s day-to-day disease burden, and also their expectations, hopes, and fears about their future disease experience. Once the goals have been defined, the clinician may then describe the potential burden of future treatments, possible outcomes, and the likelihood of these outcomes in the context of the patient’s goals. Doing so will greatly facilitate decision-making for specific treatments. Hopefully, such discussion will also lead to a realistic understanding of the limits of therapy and avoidance of requests for treatments that are considered futile or medically inappropriate. (See "Ethics in the intensive care unit: Responding to requests for potentially inappropriate therapies in adults" and "Palliative care: Medically futile and potentially inappropriate therapies of questionable benefit".)
Gaining insight to patients’ perspectives on what is important to their quality of life not only serves as the foundation for making decisions about treatments, but can improve patients’ overall satisfaction with clinicians’ communication skills [70]. Thus, it is important to avoid the common mistake of asking patients to make specific treatment choices, such as cardiopulmonary resuscitation or mechanical ventilation, prior to ascertaining the patient’s overall values and goals for care. (See "Discussing goals of care", section on 'REMAP: A stepwise approach'.)
Some patient have advanced directives stating their preferences for care that were established long before the terminal stage of the illness. Importantly, preferences for life-sustaining treatments may change during the course of the disease. In one study, more than one-third of the outpatients with COPD changed their preferences regarding cardiopulmonary resuscitation and/or invasive mechanical ventilation at least once during one year [35]. Preferences are more likely to change when patients with COPD experience a change in health status, mood status, mobility, or marital status [35]. (See "Advance care planning and advance directives", section on 'Stability'.)
Finally, it is of major importance to stress that a decision to forego life-sustaining treatments doesn’t mean that a patient won’t receive the best possible care to meet their needs and individual goals of care, including optimal management of dyspnea, pain, and other symptoms to alleviate suffering.
Helpful exploratory questions that can be used in discussing goals of care in the advance care planning process are outlined in the table (table 9).
End-of-life care — End-of-life care refers to the processes of addressing the medical, social, emotional, and spiritual needs of people who are nearing the end of life. It may include a range of medical and social services, including disease specific interventions (eg, noninvasive ventilation, supplemental oxygen) as well as hospice care [1]. (See "Palliative care: The last hours and days of life" and "Hospice: Philosophy of care and appropriate utilization in the United States" and "Palliative care and hospice outside of the United States".)
An important component of end-of-life care planning is to determine whether the patient and their caregivers would be most comfortable spending their last days to weeks at home or in a hospital setting. For patients with lung disease, the management of dyspnea and hypoxemia at home should be discussed, if the patient’s preferences and goals of care are in keeping with dying at home. Palliative care can be delivered at home; one of the best known models is home hospice care, although hospice care can also be delivered in acute care hospitals and in nursing homes. (See "Palliative care delivery in the home" and "Palliative care: Nursing home".)
Hospice referral guidelines for chronic lung disease — In general, referral for hospice care is appropriate for patients with an estimated life expectancy of six months or less. In the United States, hospice referral guidelines are largely determined by the Medicare hospice eligibility guidelines, which are divided into those criteria that are disease-specific and non-disease specific (table 1 and table 2) [71]. (See "Hospice: Philosophy of care and appropriate utilization in the United States".)
Unfortunately, patients with non-neoplastic advanced lung disease face a number of difficulties in getting referred to hospice [71]:
●The prognosis of noncancer patients with advanced lung diseases (eg, COPD or interstitial lung disease) is more difficult to determine than it is for malignancy.
●Some physicians may be reluctant to discuss hospice because of their lack of skill or training in acknowledging or communicating to patients that death is near.
●Physicians may fail to recommend hospice care at home or in another setting for noncancer patients because they are unaware of its availability or unaware of the published criteria for hospice eligibility.
SYMPTOM MANAGEMENT IN CHRONIC LUNG DISEASE — Patients with advanced lung disease are frequently troubled by dyspnea, but are also prone to other symptoms that may benefit from palliative care [72]. Discussions of the assessment of respiratory symptoms (ie, dyspnea, cough, stridor, and hemoptysis) in the palliative care setting, including when to do further testing or choose empiric symptom-based management, are provided separately. (See "Assessment and management of dyspnea in palliative care", section on 'Testing to determine underlying cause'.)
Refractory dyspnea — Dyspnea is a central symptom in most advanced lung diseases. As an example, dyspnea is the most frequently reported symptom of patients with advanced chronic obstructive pulmonary disease (COPD) with 94 percent reporting moderate to severe dyspnea and most patients reporting insufficient treatment [73]. Dyspnea has significant impact on the patient, as well as family caregivers, and is a major determinant of health status [74,75].
Alleviation of dyspnea has many components, including addressing any specific treatable causes of dyspnea (eg, bronchoconstriction, pleural effusion, excess secretions), nonpharmacologic management (eg, relaxation exercises, fan, energy conservation, optimal positioning, supplemental oxygen), and medications (predominantly opioids) [76]. Consensus-based concepts for chronic dyspnea explanations provide a starting point for conversations with patients and caregivers [77]. The general assessment and management of dyspnea in palliative care are discussed separately, but aspects related to patients with advanced lung disease are reviewed in the sections that follow. (See "Assessment and management of dyspnea in palliative care".)
Pharmacologic management of refractory dyspnea — For patients with advanced lung disease, pharmacologic management of dyspnea includes optimizing disease-specific treatments, such as bronchodilator therapy for COPD, systemic glucocorticoids for acute exacerbations of COPD, idiopathic pulmonary fibrosis, and other interstitial lung diseases, and also antibiotics for comorbid lung infection or bronchiectasis, unless these interventions are not consistent with the goals of care (table 10). The management of these diseases is discussed separately. (See "COPD exacerbations: Management", section on 'Home or office management of COPD exacerbations' and "Acute exacerbations of idiopathic pulmonary fibrosis" and "Management of refractory chronic obstructive pulmonary disease", section on 'Pharmacologic agents'.)
For patients with refractory dyspnea despite optimal treatment of their underlying condition, international guidelines recommend the use of opioids [71,76,78,79]. Several, but not all, studies support using opioids to relieve dyspnea in patients with COPD, as discussed separately [80-84]. (See "Assessment and management of dyspnea in palliative care", section on 'Opioids'.)
Despite the recommendations in practice guidelines [71,78], clinicians are often reluctant to prescribe opioids to patients with chronic respiratory diseases due to concerns about hypoventilation. In fact, only one-fourth of the patients with COPD received opioids in their last six months of life, while half of the patients with lung cancer received opioids [85]. Clinicians report fear of adverse respiratory effects as important barriers towards opioids prescription [86] despite studies showing no evidence for significant adverse effects among patients receiving palliative care [78,87-91]. In particular, a systematic review found no evidence for clinically relevant respiratory adverse effects of opioids used for chronic breathlessness [91], and a randomized trial found no evidence for respiratory depression with 20 to 30 mg per day of sustained-release morphine in patients with COPD [82]. (See "Assessment and management of dyspnea in palliative care", section on 'Opioids'.)
Opioids should always be accompanied by laxatives to prevent constipation (table 11). The use of opioids to alleviate dyspnea is discussed separately. (See "Assessment and management of dyspnea in palliative care", section on 'Opioids' and "Prevention and management of side effects in patients receiving opioids for chronic pain", section on 'Opioid bowel dysfunction'.)
Anxiolytics have also been recommended to treat dyspnea [71]; however, the literature is conflicting about the effectiveness of anxiolytics for palliative treatment of dyspnea [92-94]. On the other hand, when dyspnea is accompanied by anxiety, treatment with anxiolytics can be considered with careful evaluation of effects and adverse effects. (See "Overview of anxiety in palliative care", section on 'Treatment approach' and "Assessment and management of dyspnea in palliative care", section on 'Management of anxiety'.)
A randomized trial found no evidence for a benefit of sertraline on dyspnea [95]. Although a case series and small trial suggest a role for mirtazapine for patients with chronic dyspnea in advanced disease [96,97], large randomized trials supporting this role are lacking.
Supplemental oxygen — For patients with advanced interstitial lung disease or pulmonary hypertension, hypoxemia may be refractory. As a patient’s oxygen requirement increases, the type of interface (eg, nasal cannula, reservoir, mask), need for humidification, type of portable oxygen, and the capacity of oxygen concentrator may need adjustment. Some patients may feel more in control if they have a finger oximeter to assess their oxygen saturation at home.
●Interfaces that can improve oxygen delivery include use of a reservoir cannula (eg, mustache or pendant), simple face mask, or nonrebreathing mask. (See "Portable oxygen delivery and oxygen conserving devices", section on 'Reservoir cannulas' and "Continuous oxygen delivery systems for the acute care of infants, children, and adults".)
●Encouraging the patient to breathe slowly and deeply may improve oxygenation as less room air is entrained during slow inspiration.
●As the oxygen flow rate increases, humidification should be added to the inspired oxygen to avoid excessive drying of the airway mucosa.
●Portable sources with oxygen conserving devices may not provide an adequate pulse of oxygen during exertion. Using continuous flow and an oxygen cylinder rather than liquid oxygen may enable better oxygenation during exertion (eg, walking).
●Patients with advanced disease may require 6 L/min supplemental oxygen. Many home oxygen concentrators are limited to delivery of 6 L/min, so the concentrator would need to be changed to one that can deliver up to 10 L/min.
Noninvasive ventilation in the setting of palliative care — Noninvasive ventilation (NIV) is the mode of ventilator support of choice for some groups of patients with acute respiratory failure, such as patients with an acute exacerbation of COPD. Use of NIV in patients who have chosen to forego endotracheal intubation for mechanical ventilation has been controversial, but may be appropriate in selected patients [98-100]. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)
Two international professional society statements have promoted the conceptualization of the use of NIV for patients with chronic lung disease and acute respiratory failure into one of three categories:
●NIV as life-sustaining treatment when there are no preset limitations on life-sustaining treatments
●NIV as life-sustaining treatment when patients and families have decided to forego endotracheal intubation and invasive mechanical ventilation
●NIV as a palliative measure when patients and families have chosen to forego all life support and receive comfort measures only [98,99]
Therefore, NIV should only be applied after careful discussion of the goals of care. To help clarify the goals of care, clinicians should consider which of these three categories apply to specific patients. These three categories underscore the need to elicit patient preferences and goals, communicate the rationale for NIV, and outline parameters for success and failure of NIV. Importantly, goals of care may change during the treatment of an episode of acute respiratory failure.
Studies suggest that NIV is the treatment of choice for some patients with acute respiratory failure in category 1 (such as acute exacerbations of COPD). For category 2, studies suggest that in some subgroups of patients (such as patients with COPD or heart failure) hospital survival after use of NIV for a patient who has opted to forego endotracheal intubation can be acceptable, in the 50 to 75 percent range [98,99]. For patients with COPD and hypercapnia who have benefitted from NIV during hospitalization for an acute exacerbation of COPD, nocturnal NIV may be used after discharge. (See "Nocturnal ventilatory support in COPD".)
Data to support the use of NIV in category 3, exclusively as a comfort measure, are limited [98,99,101,102]. However, one randomized trial that included patients with a malignant disease suggests that some patients may benefit with reduced time to control of dyspnea and reduced opioid use [101]. Another smaller trial suggests a similar improvement in dyspnea scores between NIV and high-flow oxygen in patients with dyspnea related to advanced cancer [102]. Despite the limited data, 2017 recommendations from the European Respiratory Society and American Thoracic Society (ERS/ATS) support offering NIV to dyspneic patients for palliation in the setting of terminal cancer or other terminal conditions [100].
It is also important to ensure that NIV is applied with monitoring and staff who are experienced with initiating and trouble-shooting NIV. A qualitative study of patients with COPD, caregivers, and health care professionals identified important issues to be considered prior to initiating palliative NIV, such as the effectiveness of NIV in providing symptom relief and improved energy, patients’ and caregivers’ perceptions of the usefulness of NIV to manage dyspnea, burden of therapy and effects on quality of life (eg, discomfort of mask and pressure sores, dryness in mouth, loss of intimacy if bed partner bothered by noise of machine), and socioeconomic issues (eg, greater burden and dependence on caregivers; expense of machine, tubing, replacement masks) [103]. (See "Noninvasive ventilation in adults with acute respiratory failure: Practical aspects of initiation".)
Anticipating and managing "dyspnea crisis" — "Dyspnea crisis" is defined as a "sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers’ ability to achieve symptom relief" [104]. Dyspnea crisis is very common, can be overwhelming and debilitating to the patient and caregiver, may result in over-utilization of health care resources, and requires individual and system-based approaches directed at prevention and early management [105]. The ATS statement provides an approach defined in the table (table 12), in addition to a mnemonic "COMFORT" that can be used by caregivers to remember the steps to managing a dyspnea crisis: Call for help; Observe the degree of respiratory difficulty; Medications such as inhaled bronchodilators or morphine may help; Fan or other measures to create air movement; Oxygen can be administered or increased; Reassure; Take your time (figure 1). (See "Assessment and management of dyspnea in palliative care".)
Investigators have characterized various aspects of "episodic breathlessness" in patients with advanced cancer and nonmalignant diseases including COPD and heart failure [106]. One hundred and twenty-nine patients described episodes of acute breathlessness as mainly short in duration (lasting <10 minutes); severe, with mean rating of 6.5 on a 0 to 10 modified BORG scale (table 13); and occurring daily. Another study conducted by the same investigators compared characteristics of episodic breathlessness among 82 patients diagnosed with either COPD or lung cancer [107]. Patients with COPD perceived significantly higher peak severity of dyspnea, compared with patients with lung cancer and the duration of the episodes were longer in the COPD group, by approximately two minutes. The frequency of the dyspnea episodes was similar and often daily in both groups. Collectively, these findings describe acute breathlessness episodes and help guide effective management and coping strategies to improve acute symptom relief.
Cough, sputum production, and hemoptysis — Cough, sputum production, and hemoptysis can be bothersome symptoms for patients with advanced lung disease and their caregivers [108,109]. If it is consistent with the goals of care, the first step in the management of chronic cough is to determine the etiology, as it is not necessarily due to the primary lung disease. As examples, among patients with interstitial lung disease, cough may be caused by etiologies such as angiotensin converting enzyme inhibitors, upper airway cough syndrome, gastroesophageal reflux, or bronchiectasis [110,111]. Alternatively, if a diagnostic evaluation is not consistent with the goals of care, symptom-based management is appropriate.
Systemic opioids are the most effective treatment for refractory cough. No one agent appears superior. Initial doses in opiate-naïve patients are usually small, such as codeine 15 to 30 mg orally every four hours or the equivalent dose of hydromorphone or morphine. Further control of cough may be derived from adding benzonatate to the opioid regimen, although data are limited.
For patients with bronchiectasis, control of purulent sputum production can often be achieved with antimicrobial agents. Depending on the prior antibiotic usage and current sputum cultures, antipseudomonal antibiotics may need to be administered intravenously.
Hemoptysis, even of small amounts, may be extremely frightening for the patient and those who watch. The distress from expectoration of a small amount of blood-flecked sputum may be relieved by reassurance. At the other extreme, if hemoptysis is massive, it may herald a life-ending event, and witnessing what may be exsanguination requires urgent attention to all who are witnesses. Patients with massive hemoptysis should be immediately placed into a position in which the presumed bleeding lung is dependent. The roles of invasive and palliative management of hemoptysis are discussed separately. (See "Palliative care: Overview of cough, stridor, and hemoptysis in adults", section on 'Management'.)
Other symptoms in chronic lung disease — Several studies have demonstrated that patients with chronic lung disease experience high symptom burden in addition to dyspnea and cough, including symptoms such as anxiety, depression, fatigue, insomnia, muscle weakness, and pain. (See "Overview of managing common non-pain symptoms in palliative care".)
●In a systematic review comparing symptom prevalence among patients with cancers, AIDS, heart disease, and renal disease and COPD, multiple symptoms were common among all five diseases including depression, pain, and fatigue [112]. In addition, patients with COPD experienced high rates of anxiety.
●In a systematic review, the prevalence of pain among patients with moderate to severe COPD was 66 percent (95% CI 44 to 85 percent) [113].
●A subsequent review conducted on patients with end-stage chronic organ failure including COPD, heart failure, and chronic renal failure found that many patients experience a significant daily symptom burden of fatigue, pain, and insomnia [114].
●A study comparing symptoms among patients with advanced COPD or heart failure identified that many patients suffered from high levels of fatigue, muscle weakness, coughing, low mood, and insomnia [73]. Only a minority of these patients received symptom treatment.
These studies illustrate that patients with COPD and other chronic lung diseases experience a high and diverse symptom burden, supporting the need for both primary and specialized palliative care. The palliative management of common non-respiratory symptoms is discussed separately. (See "Approach to symptom assessment in palliative care" and "Overview of managing common non-pain symptoms in palliative care" and "Insomnia in palliative care".)
Patients in the last days/hours of life often have unrelieved physical suffering, as well as significant emotional, spiritual, and social distress. Recognizing that a person is entering the imminently dying or terminal phase of their illness is critical to appropriate care planning and a shift to comfort care. Issues surrounding care during these last days and hours are discussed separately. (See "Palliative care: The last hours and days of life".)
CAREGIVER BURDEN AND SUPPORT FOR CAREGIVERS — As lung disease progresses, patients with chronic obstructive pulmonary disease (COPD) may experience increasing impairment in performing normal daily tasks [115,116]. Patients may, for example, need assistance with instrumental activities of daily living, like grocery shopping, house work, laundry, and travel, but also with basic activities of daily living, like bathing and dressing [116]. Therefore, patients often receive help from family caregivers [32,117]. Almost half of the outpatients with advanced COPD require help with personal care; family caregivers provide care to over 80 percent of the patients with advanced COPD; professional caregivers also provide in-home support [118,119]. Caregiver burden is common in family caregivers of patients with advanced COPD [120]. Family caregivers report schedule burden (ie, disruption of daily tasks), financial burden, and family burden. As patients approach the end of life, schedule burden increases [121]. (See "Palliative care delivery in the home", section on 'Role of caregivers'.)
Moreover, health status and emotional well-being of family caregivers can be impaired [119]. A recent study showed that 64 percent of the family caregivers of patients with COPD experience clinically relevant symptoms of anxiety and 34 percent of the caregivers experience clinically relevant symptoms of depression [122]. This study also showed that family caregivers were more likely to develop anxiety or depression as the severity of dyspnea of the patient increased. Nevertheless, family caregiving may also be a positive experience for family caregivers [118,123]. A study among loved ones of patients with COPD, chronic heart failure or chronic renal failure showed relatively high scores for caregiving appraisals and family well-being [118]. Therefore, healthcare providers of patients with chronic lung disease should pay attention to caregiver burden and also the positive aspects of family care giving. (See "Palliative care delivery in the home", section on 'Burden of caregiving'.)
High quality palliative care also includes bereavement support [124]. Recent studies show evidence for positive outcomes of bereavement care [125-127]. Loved ones of deceased patients with chronic lung disease may be at risk for the development of complicated grief, but only a minority received bereavement care [128]. Development of bereavement care as part of palliative care for patients with chronic lung disease and their loved ones may be important to reduce the important consequences of complicated grief for the loved ones as well as for the society. Indeed, complicated grief is associated with significant distress, work impairment, impaired social functioning, negative health outcomes, depression, and suicidality risk [127,129,130]. (See "Prolonged grief disorder in adults: Epidemiology, clinical features, assessment, and diagnosis", section on 'Clinical features'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dyspnea" and "Society guideline links: Palliative care for advanced lung disease" and "Society guideline links: Subacute and chronic cough in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Medical care during advanced illness (The Basics)" and "Patient education: Advance directives (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Palliative care is important for people suffering from chronic lung diseases such as chronic obstructive pulmonary disease (COPD), interstitial lung diseases (ILD), and pulmonary hypertension. (See 'Introduction' above.)
●The primary goal of palliative care is to improve the quality of life for the patient with a serious illness and their family through relief of emotional and physical symptoms. Thus, eligibility is based on the diagnosis of advanced, life-threatening illness requiring management of serious symptoms, social or emotional needs, or a goals-of-care discussion. (See 'Use and benefits of palliative care' above.)
●Palliative care differs from hospice in the United States, where the term "hospice" describes a model of care focused primarily on comfort that is offered only toward the end of life, generally the last one to six months of life. Criteria for hospice eligibility are described in the tables (table 1 and table 2). (See 'What is the difference between palliative care and hospice?' above.)
●Optimal palliative care for patients with chronic lung disease incorporates both primary and secondary (subspecialty) palliative care. Basic aspects of primary palliative care can be provided by the patient’s usual clinicians, while secondary palliative care is provided by clinicians with specialty training in palliative care. Individual patients in different stages of their illness require different services depending on their needs and preferences, as well as the palliative care skills of their clinicians. (See 'What is the difference between primary and secondary (subspecialty) palliative care?' above.)
●While patients with serious lung disease typically have a phase of gradual decline, the trajectory can change abruptly. Thus, advance care planning, including patient-clinician communication about end-of-life care, is of major importance for patients and their loved ones. (See 'Clinical course and causes of death' above and 'Advance care planning' above.)
●Topics that are important to address during advance care planning discussions include diagnosis, prognosis, patient’s goals of care, and values and beliefs. Only after discussing these issues, should clinicians discuss treatment preferences. In particular, it is important to avoid the common mistake of asking patients to make specific treatment choices, such as cardiopulmonary resuscitation or mechanical ventilation, prior to discussing their values and goals. (See 'What topics should be discussed?' above.)
●Dyspnea is a central symptom in most advanced lung diseases. For patients receiving palliative care who have dyspnea that is refractory to specific therapies for their underlying disease, systemic opioids are the first-line agents. The usual initial dose is sustained-release morphine 10 mg daily with gradual individual dose titration while monitoring for adverse effects. The use of opioids for dyspnea is not associated with excess mortality. Early integration of palliative care can improve dyspnea mastery for patients with COPD and probably for patients with other chronic lung diseases. (See 'Refractory dyspnea' above and "Assessment and management of dyspnea in palliative care".)
●"Dyspnea crisis" is defined as sustained and severe resting breathing discomfort that occurs in patients with advanced, life-limiting illness and often overwhelms the patient and caregivers’ ability to achieve symptom relief. The mnemonic "COMFORT" can be used by caregivers to remember the steps to managing a dyspnea crisis: Call for help; Observe the degree of respiratory difficulty; Medications such as inhaled bronchodilators or morphine may help; Fan or other measures to create air movement; Oxygen can be administered or increased; Reassure; Take your time (table 12 and figure 1). (See 'Anticipating and managing "dyspnea crisis"' above.)
●Noninvasive ventilation (NIV) is sometimes used in patients with chronic lung disease to avoid intubation and mechanical ventilation and occasionally used to reduce dyspnea or treat chronic hypercapnia. Defining the goals of care before implementing NIV, either as a life-sustaining treatment or as a palliative measure, is particularly important in the care of patients with chronic lung disease. (See 'Noninvasive ventilation in the setting of palliative care' above.)
●The palliative treatment of other respiratory symptoms, such as cough, sputum production, and hemoptysis, and also extrapulmonary symptoms (eg, anxiety and insomnia) can improve the patient’s experience of their illness. (See 'Cough, sputum production, and hemoptysis' above and 'Other symptoms in chronic lung disease' above and "Palliative care: Overview of cough, stridor, and hemoptysis in adults" and "Overview of anxiety in palliative care" and "Insomnia in palliative care".)
21 : Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial.
66 : Outcome of patients with idiopathic pulmonary fibrosis (IPF) ventilated in intensive care unit.