Mechanisms of exertional dyspnea in patients with cancer.

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.

Physiological changes and clinical correlations of dyspnea in cancer outpatients.

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.

Dyspnea in cancer patients: prevalence and associated factors.

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.

The Edmonton Symptom Assessment Scale (ESAS) as an audit tool.

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.

Dyspnea in the advanced cancer patient.

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.

Management of dyspnea and cough in patients with cancer.

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.

Home versus hospital death: assessment of preferences and clinical challenges.

In Canada hospital beds have been reduced in number, and there is increased fiscal pressure for patients with advanced terminal illness to be cared for in their own homes until death. In this issue (see pages 361 to 367) Drs. Ian R. McWhinney and Martin J. Bass and Ms. Vanessa Orr report that people who die at home rather than in hospital are more likely to be cared for by family members other than a spouse and to have the services of a private duty nurse. The literature has shown that health problems of elderly spouses, occupational and other responsibilities of family members, and the physical, psychologic and financial strain of providing home care can make it difficult to honour a terminally ill person's wish to die at home. The findings of McWhinney and colleagues point to the existence of a two-tiered health care system in which those who have access to private duty nursing are able to stay at home to die. Their study also raises three key questions that must be addressed in the assessment of patient preferences as to place of death: Should family members be included in the assessment? How should preferences be measured? and What is an appropriate time frame for such an assessment? Although McWhinney and colleagues identify characteristics of care associated with place of death and underline the need for careful assessment of patient preferences regarding place of death, further research is needed to build on these findings. In the current context of health care reform, we need to examine more closely the type and intensity of services needed to support patients and their families in the final stages of a terminal illness.

When does palliative care begin? A needs assessment of cancer patients with recurrent disease.

This cross-sectional study compared the prevalence and intensity of needs expressed by cancer patients at the time of first recurrence (n = 75) with those of patients at the time of disease progression (n = 75). On a 72-item Likert-type scale participants rated from "none" to "very much" the severity of physical symptoms; emotional, psychological, and social problems; and difficulties with activities of daily living. The progressive disease group reported more problems than the first recurrence group in 11 of 24 (47%, p < 0.05) symptom-related questions. The progressive disease group also expressed greater needs in 19% of the function-related questions. There were no differences in reported psychological problems, responses to recurrence, or greatest concern between the two groups. These results support the need for palliative care throughout the entire course of illness.

Physician/nursing roles and perspectives in relationship to delivery of palliative care.

Palliative or hospice care developed as a new discipline because the needs of the dying patient and family were not adequately met by the established health care system. The focus on the technological aspects of medicine for diagnosis and treatment has resulted in the neglect of the social, emotional and spiritual problems experienced by patients suffering from a terminal disease. Care of the dying is an active process that requires frequent assessments and the aggressive pursuit of appropriate therapies to control both physical and emotional symptoms. Models of practice used by medicine and nursing are compared and related to the delivery of effective and compassionate care to the dying.

Primary chemotherapy for obstructive jaundice caused by intermediate-grade non-Hodgkin lymphoma.

BACKGROUND: Advanced non-Hodgkin lymphoma (NHL) usually is treated with doxorubicin-based combination chemotherapy. Because doxorubicin is excreted by the biliary route, many authorities recommend alternative initial interventions in patients with NHL causing obstructive jaundice. METHODS: The authors retrospectively reviewed the records of patients at Rochester General Hospital with NHL between 1983 and 1989 with obstructive jaundice at initial diagnosis. RESULTS: Five patients with obstructive jaundice due to intermediate-grade NHL were treated with combination chemotherapy without prior surgical or endoscopic biliary decompression, or radiation therapy. Three received higher doses of doxorubicin than called for in standard dose modification tables. Jaundice was relieved rapidly in all five patients without unexpected toxic effects, and all five patients entered remission (three had partial remission and two complete remission). CONCLUSIONS: Because biliary obstruction resolves rapidly after administration of chemotherapy for this disease, it is possible that standard dose reductions for doxorubicin and vincristine that are appropriate for patients with hepatocellular disease may be excessive for patients with obstructive jaundice resulting from lymphoma. The results of this study indicate that combination chemotherapy is appropriate initial therapy for patients with newly diagnosed NHL with obstructive jaundice.

Advances in data assessment. Application to the etiology of nausea reported during chemotherapy, concerns about significance testing, and opportunities in clinical trials.

Typical inferential statistical procedures, such as the t-test and analysis of variance, compare differences in mean values of variables. This approach can sometimes obscure rather than illuminate research data. Here we present and discuss alternative data analytic techniques. Potential advantages of box plots over conventional t-tests for understanding data are shown by comparing the area under high and low frequencies from spectral curves of autonomic changes following chemotherapy treatment. Typical t-tests provide information regarding statistical significance in terms of the differences in group means; box plots and related exploratory techniques provide information regarding the characteristics of the distributions within the groups as well as examination of potential outliers. Multivariate analysis of variance (MANOVA) and other multivariate techniques are commonly used to deal with potentially complex data sets with multiple outcome measures. The potential advantages of visual clustering techniques such as star plots, Chernoff faces, and Andrew's Function Plots are demonstrated by examining changes in facial pallor caused by chemotherapy-induced nausea and vomiting. Typical MANOVA approaches can identify potential differences in mean values between groups; visual clustering approaches do this by graphically presenting complex interrelationships for individual cases. This approach enhances the visual interpretation of potential interactions that would be obscured by simply focusing on overall mean values. Preliminary data from a meta-analysis on the effect of metoclopramide on chemotherapy-induced vomiting demonstrates the potential uses and advantages of this summary technique over simple tabular summaries. We found significant relationships between the effect size of the drug and variables such as the year of study publication and whether the publication was an article or an abstract. While none of these techniques are meant to replace traditional inferential statistics, they offer advantages in terms of data exploration and understanding relationships within data sets that are not clearly addressed by other methods. They are potentially valuable alternatives worthy of exploration. Finally, we discuss issues of interim analyses and multiple endpoint assessment for clinical trials.