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Purpose of Review: Loss of skeletal muscle mass and cachexia are important manifestations of chronic obstructive pulmonary disease and have been associated with breathlessness, functional limitation and poor prognosis. A number of other life-limiting illnesses, including cancer and chronic heart failure as well as acute conditions seen in ICU such as sepsis, are characteristically associated with cachexia and sarcopenia. These conditions may have respiratory muscle atrophy of sufficient magnitude to contribute to the development of breathlessness and associated functional limitation. The purpose of this review is to summarize findings related to a direct role for severe respiratory muscle wasting in the etiology of breathlessness in advanced, life limiting illness., Recent Findings: Localized wasting of respiratory muscles appears to be part of systemic wasting of skeletal muscles, driven by deconditioning, nutritional insufficiencies and inflammation, and because of disease-specific factors (tumor factors and exacerbations), anabolic insufficiency, autonomic dysfunction, drugs (such as corticosteroids and chemotherapy agents), mechanical ventilation and comorbidities. Marked morphological and biochemical abnormalities have been noted in diaphragm muscle biopsies., Summary: Older patients with multiple comorbidities associated with muscle loss and cachexia are likely to be at elevated risk of respiratory muscle atrophy and functional loss, because of the presence of multiple, interacting etiologic factors.

Exertional dyspnea is an important symptom in cancer patients, and, in many cases, its cause remains unexplained after careful clinical assessment. To determine mechanisms of exertional dyspnea in a variety of cancer types, we evaluated cancer outpatients with clinically important unexplained dyspnea (CD) at rest and during exercise and compared the results with age-, sex-, and cancer stage-matched control cancer (CC) patients and age- and sex-matched healthy control participants (HC). Participants (n = 20/group) were screened to exclude clinical cardiopulmonary disease and then completed dyspnea questionnaires, anthropometric measurements, muscle strength testing, pulmonary function testing, and incremental cardiopulmonary treadmill exercise testing. Dyspnea intensity was greater in the CD group at peak exercise and for a given ventilation and oxygen uptake (P < 0.05). Peak oxygen uptake was reduced in CD compared with HC (P < 0.05), and breathing pattern was more rapid and shallow in CD than in the other groups (P < 0.05). Reduced tidal volume expansion during exercise correlated with reduced inspiratory capacity, which, in turn, correlated with reduced inspiratory muscle strength. Patients with cancer had a relatively reduced diffusing capacity of the lung for carbon monoxide, reduced skeletal muscle strength, and lower ventilatory thresholds during exercise compared with HC (P < 0.05). There were no significant between-group differences in measurements of airway function, pulmonary gas exchange, or cardiovascular function during exercise. In the absence of evidence of airway obstruction or restrictive interstitial lung disease, the shallow breathing pattern suggests ventilatory muscle weakness as one possible explanation for increased dyspnea intensity at a given ventilation in CD patients.

The purposes of this cross-sectional study of 75 outpatients of a general oncology clinic were to assess the subjective and objective factors associated with dyspnea in cancer patients and to characterize factors that might contribute to respiratory muscle weakness demonstrated in a previous study. Patients with moderate to severe shortness of breath completed visual analogue scales (VAS) of shortness of breath (SOB) and anxiety; other data were acquired from pulmonary function tests, including maximum inspiratory pressure (MIP) and expiratory pressures; chest radiography; arterial blood gases; measurement of hemoglobin, serum potassium, phosphate, calcium, albumin, and magnesium; and ultrasound study of the diaphragm for thickness and excursion. The correlation coefficient between SOB VAS and anxiety VAS was 0.26 (P = 0.03). In stepwise multiple regression analyses, only the regression coefficient for anxiety remained significant at P < 0.05 in the multivariate model with SOB VAS as the dependent variable. The multivariate model using MIP (a measure of respiratory muscle strength) as the dependent variable, found significance for total diaphragmatic excursion, hemoglobin, phosphate, residual volume over total lung volume, vital capacity, percent predicted total lung capacity, oxygen saturation, and forced vital capacity. The regression coefficients for these variables were significant at P < 0.05 and the model accounted for 58% of the variance of MIP.

The objectives of this study were to determine the prevalence of dyspnea in the general cancer population, the intensity of the symptom as perceived by the patient, and the patient characteristics associated with the presence of dyspnea. Nine hundred and twenty-three cancer outpatients completed visual analogue scales (VAS) and verbal rating scales (VRS-D) to assess the intensity of their dyspnea. Baseline data included variables that were known covariates of dyspnea. Forty-six percent of the patients had some shortness of breath. Only 4% had a diagnosis of lung cancer and 5.4% lung metastases. Risk factors found to be significantly related to the presence of dyspnea were history of smoking; asthma or chronic obstructive pulmonary disease (COPD); lung irradiation; or a history of exposure to asbestos, coal dust, cotton dust or grain dust (P values from 0.001 to 0.038). The prevalence of dyspnea was strongly related to the number of risk factors a patient had (P < 0.0001). The VAS and VRS-D were significantly correlated, establishing concurrent validity for the VRS-D.

To ensure quality of care, palliative care programs need to document the effectiveness of their relief of physical and psychological distress. The Edmonton Symptom Assessment Scale (ESAS) is a validated, reliable instrument developed to measure 9 different symptoms in palliative care patients. To see if symptom management could be compared across institutions, we first reviewed the charts of 188 successive admissions to the palliative care unit at St. Boniface General Hospital, Winnipeg, Manitoba. Our study showed that the ESAS is a useful audit tool for assessing patterns of palliative symptom control that allows for institutional comparisons. Procedures that ensure completeness of data collection remain to be developed.

Optimal management of dyspnea in terminal cancer patients requires an understanding of the responsible pathophysiological mechanisms. This prospective study assessed visual analogue scales (VAS) of shortness of breath (SOB) and anxiety, bedside spirometry, maximum inspiratory pressure (MIP), chest radiography, arterial blood gases, hemoglobin, and electrocardiogram, if indicated, in 100 terminally ill cancer patients. Forty-nine percent of the patients had lung cancer. The median VAS scores for SOB and anxiety were 53 mm and 29 mm, respectively. Spirometry was abnormal in 93% of patients, with 5% having obstructive, 41% restrictive, and 47% mixed patterns. The median MIP was 16 cm H2O. Sixty-five percent of the patients had parenchymal or pleural involvement on chest radiograph. Twenty-nine percent had evidence of cardiac ischemia, recent or current myocardial infarction or atrial fibrillation. Patients had a median of five different abnormalities that could have contributed to their shortness of breath. Only anxiety (p = 0.001), a history of smoking (p = 0.02), and pCO2 levels were statistically significantly correlated with SOB VAS scores. The potentially correctable causes of dyspnea included hypoxia (40%), anemia (20%), and bronchospasm (52%). The finding of very low MIPs suggests severe respiratory muscle weakness may contribute significantly to dyspnea in this patient population. Further studies are needed to confirm this finding and characterize the underlying pathophysiology.

The understanding and treatment of dyspnea in the cancer patient are where the science of pain management was 15 or 20 years ago. Very few studies have examined the pathophysiologic mechanisms that cause dyspnea in cancer patients, and few investigators have evaluated therapeutic strategies to control dyspnea in this patient group. The optimal therapy for dyspnea is treatment of the underlying cause. When this is not possible, opioids and phenothiazines provide effective symptomatic relief in most cases, but many unanswered questions remain. Are these the optimal drugs, and what are their optimal doses? What are the effects of chronic dosing? Which is the best route of administration? How serious are the risks of respiratory depression? A clear consensus supports the aggressive treatment of pain in terminally ill cancer patients, even if death is hastened as an unintended consequence. No such position has yet been reached in the management of dyspnea in the same population. As a result, dyspnea is addressed only very late in the course of the disease, perhaps reducing the patient's quality of life and function at earlier stages and resulting in a very small "therapeutic window" in the terminal phase. Clearly, a need exists for more research to determine the most effective management of this common and very distressing symptom.