What Interventions Are Effective for Managing Dyspnea in People With Cancer?

Introduction and Scope of the Problem

Dyspnea is defined by a consensus panel of the American Thoracic Society (ATS) as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.” Most often termed “shortness of breath” or “breathlessness” by patients and their families, dyspnea is one of the most common symptoms experienced by patients with advanced disease including cancer. The majority of patients with advanced cancer report dyspnea at some point, as do most imminently dying patients. The incidence of dyspnea increases significantly in the last 3 months of life. The symptom is reported by nearly half of all patients receiving palliative care, of whom one-half reported the subjective sensation as being “severe.”

The subjective nature of dyspnea makes clinical assessment challenging for some health care professionals, but it is imperative to believe each patient’s account of the symptom and its impact on their lives. Patients adjust their lifestyles to minimize dyspnea, often having to forego many activities that they may otherwise enjoy and some important aspects of their personhood. Clinicians systematically underestimate the prevalence of dyspnea in their patients and, even when recognizing its presence, undertreat the symptom.

The ATS explains that the experience of dyspnea “derives from interactions among multiple physiological, psychological, social, and environmental factors and may induce secondary physiological and behavioral responses.” The way in which dyspnea manifests and its reported nature and severity are thus defined entirely by patients’ perceptions, rather than physiological measurements with which the perceptions often correlate poorly, especially in the setting of chronic dyspnea (defined as dyspnea persisting despite optimal treatment of the underlying pathophysiology, resulting in disability). Patients’ descriptions of dyspnea vary based on an array of factors such as the individual’s underlying disease, ethnic or racial background, previous experiences, and emotional state. To incorporate the various aspects of dyspnea into a conceptual framework, “total dyspnea” has been described. As a symptom description, total dyspnea involves the interaction of four experiential domains—physical, psychological, interpersonal, and existential—in an attempt to fully capture patients’ experience of this disabling and distressing symptom.

Relevant Pathophysiology

Dyspnea results from one or a combination of three main physiological abnormalities: (1) increased load requiring greater respiratory effort, such as from airway obstruction; (2) increase in the proportion of respiratory muscle required to maintain a normal workload, which may be due to weakening of the relevant muscles; or (3) increase in ventilation requirements resulting from conditions such as fever or anemia. In patients with cancer, the cause(s) of dyspnea may be identified in a specific anatomic condition or associated comorbidity such as pulmonary obstruction (chronic obstructive pulmonary disease [COPD], reactive airways, cough, excess secretions, mass lesions), pulmonary restriction (fibrosis or other interstitial disease, effusions, fibrosis, infections, kyphosis, obesity), mismatch between perfusion and oxygenation (anemia, pulmonary hypertension, heart failure, pulmonary embolism), or fatigue and weakness (cancer-associated anorexia/cachexia syndrome, cancer-associated fatigue and muscle wasting, chemotherapy effect, multiple sclerosis, amyotrophic lateral sclerosis). These specific abnormalities can usually be measured, imaged, or inferred from the patient’s underlying disease to provide clues to the cause(s) of the dyspnea.

Dyspnea often results from systemic effects of illness, instead of or in addition to identifiable localized causes. In a national study, 24% of patients in hospice care with no known cardiopulmonary involvement (e.g., local cancer involvement, pleural effusions, pulmonary infections) reported experiencing dyspnea. In patients in hospice care with no known cardiopulmonary disorder, both prevalence and severity of dyspnea increase significantly as death approaches. Systemic changes such as asthenia and cachexia, both of which affect more than 80% of patients with advanced cancer, are suggested as causes for many people.

In addition to anatomic causes, emotional, spiritual, and existential distress can induce or worsen dyspnea in people with cancer. Anxiety is often present in the development of dyspnea and, in turn, dyspnea is exacerbated by its presence—setting up a perilous spiral of worsening symptoms. Associations between dyspnea and anxiety are well documented. These associations are important given the high prevalence of anxiety in palliative care populations. Patients with underlying anxiety or panic disorders often have an amplified experience of dyspnea when compared with patients who do not have anxiety. The effects of spiritual distress on the experience of dyspnea have been described.

In the key neurophysiological model, dyspnea is thought to begin with the activation of the sensory receptors of respiration; these send afferent impulses to the central nervous system, which then directs an efferent impulse toward the respiratory muscles. Mismatch between these signals and modulation of impulses is therefore central to the perception of dyspnea. Of note, the central processing of dyspnea involves multiple brain structures responsible for physical sensation, emotion, memory, and behavior, which helps to explain the subjective and complex nature of this symptom. Indeed, investigations with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) have added to the knowledge of how dyspnea activates both cortical and cerebellar systems.

Endogenous opioids (endorphins) have been thought to attenuate the sensation of dyspnea in the central nervous system. A recent important investigation conducted in opioid-naïve volunteers has added to the understanding of the mechanisms of efficacy of exogenous opioids, which remain the mainstay of global therapy for dyspnea. In this double-blind, crossover study, levels of β-endorphin were measured at rest and after exercise in 17 patients with COPD undergoing a 10-minute treadmill exercise test. Patients received either intravenous saline or naloxone, an opioid antagonist. A three-fold increase in serum β-endorphin levels was observed from rest to the period immediately after ceasing exercise because the participant’s exercise limit had been reached. Mean self-reported dyspnea scores throughout exercise were significantly higher in patients when they received naloxone, suggesting a need for further studies to identify ways of accentuating the effect of endogenous opioids on dyspnea. This effect is likely modulated only centrally and not through the opioid receptors in the bronchial tree.

Summary of Evidence Regarding Treatment Recommendations

Because of the complex biopsychosocial contributions to the experience of dyspnea, effective management requires a multidimensional and individualized approach. The clinician’s first step is to establish the goals of care in conjunction with the patient, family members, and any other informal caregivers. If dyspnea in a patient with cancer is caused by a modifiable anatomic condition or treatable disease, the initial aim is to reduce the dyspnea by targeting this cause. If the cancer has been optimally treated, no alterable physiological cause is identified, and the patient’s dyspnea persists, the clinical approach shifts to one focused on global symptom management, targeting dyspnea rather than the disease. Treatment options for managing dyspnea in the patient with cancer include nonpharmacological, pharmacological, and other interventions. Regardless of treatment choice, outcomes will be optimized if the clinician addresses as many of each individual’s contributing factors as possible, including anxiety; other symptoms; nonmedical stressors, such as interpersonal, relational, and financial concerns; and spiritual or existential distress. In this context, it is also important to consider the central role of caregivers, who often develop cohesive alliances with patients to help them overcome the limitations associated with dyspnea.