A randomized controlled trial of supplemental oxygen versus air in cancer patients with dyspnea. A double-blind, randomised, controlled Phase II trial of Heliox28 gas mixture in lung cancer patients with dyspnoea on exertion. The efficacy of early continuous positive airway pressure therapy in patients with acute cardiogenic pulmonary edema. Does oxygen help dyspnea in patients with cancer? Ambulatory oxygen in chronic heart failure. Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial. Non-pharmacological intervention for breathlessness in lung cancer. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema. Short-term results and long-term follow-up. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group.
The symptomatic benefits of oxygen in patients with cancer who have nonhypoxic dyspnea are not well defined.
                To determine whether or not oxygen is more effective than air in decreasing dyspnea and fatigue and increasing distance walked during a 6-minute walk test.
                Patients with advanced cancer who had no severe hypoxemia (i.e., had an O2 saturation level of > or = 90%) at rest and had a dyspnea intensity of > or = 3 on a scale of 0-10 (0 = no shortness of breath, 10 = worst imaginable shortness of breath) were recruited from an outpatient thoracic clinic at a comprehensive cancer center. This was a double-blind, randomized crossover trial. Supplemental oxygen or air (5 L/min) was administered via nasal cannula during a 6-minute walk test. The outcome measures were dyspnea at 3 and 6 minutes, fatigue at 6 minutes, and distance walked. We also measured oxygen saturation levels at baseline, before second treatment phase, and at the end of study.
                In 33 evaluable patients (31 with lung cancer), no significant differences between treatment groups were observed in dyspnea, fatigue, or distance walked (dyspnea at 3 minutes: P = 0.61; dyspnea, fatigue, and distance walked at 6 minutes: P = 0.81, 0.37, and 0.23, respectively).
                Currently, the routine use of supplemental oxygen for dyspnea during exercise in this patient population cannot be recommended. Helium has a low density and the potential of reducing the work of breathing and improving alveolar ventilation when replacing nitrogen in air. A Phase II, double-blind, randomised, prospective, controlled trial was undertaken to assess whether Heliox28 (72% He/28% O(2)) compared with oxygen-enriched air (72% N(2)/28% O(2)) or medical air (78.9% N(2)/21.1% O(2)) could reduce dyspnoea and improve the exercise capability of patients with primary lung cancer and dyspnoea on exertion (Borg >3). A total of 12 patients (seven male, five female patients, age 53-78) breathed the test gases in randomised order via a facemask and inspiratory demand valve at rest and while performing 6-min walk tests. Pulse oximetry (SaO(2)) was recorded continuously. Respiratory rate and dyspnoea ratings (Borg and VAS) were taken before and immediately post-walk. Breathing Heliox28 at rest significantly increased SaO(2) compared to oxygen-enriched air (96+/-2 cf. 94+/-2, P<0.01). When compared to medical air, breathing Heliox28 but not oxygen-enriched air gave a significant improvement in the exercise capability (P<0.0001), SaO(2) (P<0.05) and dyspnoea scores (VAS, P<0.05) of lung cancer patients. Although continuous positive airway pressure (CPAP) therapy using a face mask is known to improve oxygenation, the intrapulmonary shunt reduction remains unsettled. Our study was designed to explore this issue. From 1985 to 1987 80 patients with acute cardiogenic pulmonary edema were randomly chosen to receive either serial CPAP therapy or high-flow face mask oxygen therapy without CPAP (control) for the purpose of evaluating the efficacy of CPAP therapy. After screening for exclusion, only 55 patients were included in the first 3-hour investigation period. PaO2 in the CPAP group showed a significant increase by the end of the initial study; whereas intrapulmonary shunt and alveolar-arterial oxygen tension gradient AaDO2 revealed simultaneously a significant reduction. Conversely, neither PaO2 nor intrapulmonary shunt (or AaDO2) in the control group demonstrated any significant beneficial changes. As for cardiovascular function, only the CPAP therapy achieved a significant reduction in rate pressure product in contrast to the control (face mask) therapy alone. In terms of therapeutic failure, 10 patients in the control group failed. However, in the CPAP group only 5 patients had failed at the end of the first 3-hour study period. Overall, the cumulative therapeutic failure rate was 28% in the CPAP group and 60% in the control group during a 6-hour observation study. However, there was no significant difference between the two groups in 24-hour hospital mortality.(ABSTRACT TRUNCATED AT 250 WORDS) Dyspnea in patients with advanced cancer is a common symptom that is difficult to treat. This study investigated whether oxygen helps to relieve rest dyspnea in patients with advanced cancer. In a single-blind controlled trial, oxygen and air were administered in random order to hospice patients reporting dyspnea at rest. Measurements of arterial oxygen saturation, lung function, and dyspnea (using a visual analogue scale [VAS] and Borg score) were made before and after each gas had been given for 15 min. Data from 38 patients were used: analysis of variance revealed that mean VAS levels during baseline conditions, breathing room air (59 mm), were significantly reduced after administration of either air (48 mm; p < 0.001) or oxygen (45 mm; p < 0.001); there was no significant difference for the mean VAS scores between oxygen and air administration. There was no statistically significant order of treatment effect. There was no difference in the response to oxygen or air in patients with a history of cardiopulmonary disease. The improvement in dyspnea with oxygen could not be predicted from a subject's initial level of hypoxia. Results suggested that benzodiazepines may potentiate the effect of oxygen. The overall conclusion is that oxygen and air can have a significant effect in reducing dyspnea at rest in patients with advanced cancer. Ambulatory oxygen therapy may be of benefit in bicycle exercise tests. We have assessed the effects of ambulatory oxygen during walk tests in 12 patients with chronic heart failure. In 6 min walks with the patient breathing air, mean (SD) arterial oxygen saturation (SaO2) fell from 94.4 (3.7)% at rest to 90.1 (6.1)% (p = 0.014) on exercise. 21/min oxygen increased resting SaO2 from 93.7 (4.0)% (air cylinder) to 96.5 (3.0)% (p < 0.001) with no effect on minimum SaO2, distance, or breathlessness. During endurance walks, 4 l/min oxygen increased minimum SaO2 from 90.4 (5.6)% to 93.5 (4.7)% (p = 0.011) but also had no effect on breathlessness or distance. Ambulatory oxygen in currently available cylinders cannot be recommended for patients with chronic heart failure. We report the results of a prospective controlled trial of the effect of hyperbaric oxygen as an adjuvant in radiotherapy of head and neck cancer. Patients were allocated randomly to treatment in oxygen or air. The radiotherapy in both groups was identical in planning, dose, and fractionation--i.e., 3500 rads in 10 fractions in 3 weeks. There was no difference in the survival rate between the two groups. However, significantly better local tumour control was seen in the hyperbaric-oxygen group, particularly in smaller lesions; there was significantly greater need for salvage surgery in the air group. Radiation effects on normal tissue appeared somewhat greater in the oxygen series, especially on laryngeal cartilage. To evaluate the effect of non-pharmacological intervention for breathlessness in lung cancer on breathlessness ratings and patient functioning.
                Randomised controlled pilot study.
                A nurse led clinic in a specialist cancer centre.
                20 patients with advanced small cell and non-small cell lung cancer.
                Weekly sessions with a nurse research practitioner over 3-6 weeks using counselling, breathing re-training, relaxation and teaching coping and adaptation strategies.
                Visual analogue scale ratings of breathlessness, distress caused by breathlessness, functional capacity, ability to perform activities of daily living and the Hospital Anxiety and Depression Scale.
                Improvements in median scores on all measures were observed in the intervention group with the exception of depression, compared with the control group where median scores were static or worsened. Distress from breathlessness was improved by a median of 53%, breathlessness at worst by 35% and functional capacity by 21%. In contrast, distress in the control group worsened by a median of 10%. Significant improvements compared with the control group were observed in breathlessness at best (p < 0.02), breathlessness at worst (p < 0.05), distress caused by breathlessness (p < 0.01), functional capacity (p < 0.02) and ability to perform activities of daily living (p < 0.03) but were not observed for anxiety or depression.
                Lung cancer patients suffering from breathlessness benefited from this rehabilitative approach to breathlessness management and strategies employed in this pilot study warrant further multicentre research. Macmillan nurses and palliative care teams are recommended to explore the potential of adopting similar approaches. To investigate whether serial incremental continuous positive airway pressure (CPAP) has any short-term or long-term advantages over face-mask oxygen therapy by way of intrapulmonary shunt reduction, 100 patients admitted to the coronary care unit for the treatment of acute cardiogenic pulmonary edema were studied. All patients received Swan-Ganz catheterization. Hemodynamic and pulmonary function parameters were recorded over the next 6 h, and the patients were followed until hospital discharge. All survivors received regular follow-up at 1-month intervals in the outpatient clinic. During the first-stage investigation period (3 h) PaO2 in the CPAP group showed a significant increase, whereas the intrapulmonary shunt and alveolar-arterial oxygen tension gradient (P[A-a]O2) was significantly reduced (p < 0.005). The CPAP group had significantly lower rate-pressure product and higher stroke volume index compared with the control group. The therapeutic failure rate over 6 h was 24% in the CPAP group and 50% in the control group (p < 0.01). The CPAP group had a significantly lower incidence of tracheal intubation and ventilator therapy than the control group; however, there was no significant difference in short-term mortality and hospital stay between the two groups. In conclusion, although study size was not large enough to demonstrate a difference in mortality, CPAP therapy resulted in physiologic cardiovascular and pulmonary function improvement and significantly reduced the need for intubation; however, it did not decrease mortality in patients with acute cardiogenic pulmonary edema, and a much larger study is needed to investigate this possibility. To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed.
                Prospective, multicenter, randomized, double-blind, placebo-controlled study.
                Intensive care units of 30 academic, teaching, and community hospitals in the United States.
                Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization.
                Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm.
                Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm.
                From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome.
The failure to demonstrate a beneficial effect for oxygen breathing over air breathing in cancer or cardiac failure was limited by the small volume of research studies available for inclusion, the small numbers of participants and by the methods used in the studies.