***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Previous studies have shown that opiates increase the maximal external work performed at exhaustion in patients with chronic obstructive pulmonary disease ( COPD ) . The mechanism responsible for this improvement in exercise tolerance is unknown . The purpose of this study was to determine the effects of an oral morphine solution ( 0.8 mg/kg ) on the exercise tolerance , perception of dyspnea , and arterial blood gases of patients with COPD . Thirteen eucapnic patients with stable COPD ( FEV1 = 0.99 + /- 0.48 ) underwent duplicate incremental cycle ergometer tests to exhaustion ( Emax ) after the ingestion of placebo and after the ingestion of morphine . After the ingestion of morphine , the maximal workload increased by 18 % ( p less than 0.001 ) and the VO2 increased by 19.3 % ( p less than 0.001 ) . Ten of the 13 patients had a higher ventilation at Emax after morphine ingestion . Despite the higher ventilation at Emax after morphine , the mean Borg score was not significantly higher . At Emax after morphine ingestion , the PaO2 ( 65.8 + /- 11.6 mm Hg ) was significantly lower and the PaCO2 ( 43.5 + /- 8.3 mm Hg ) was significantly higher than at Emax after placebo ( 71.9 + /- 15.5 and 38.3 + /- 8.5 , respectively ) . When data at the highest equivalent workload were analyzed , the ventilation and the Borg scores were significantly lower , whereas the VO2 and VCO2 were comparable . From this study , we conclude that the administration of opiates can substantially increase the exercise capacity of patients with COPD . The improved exercise tolerance appears to be related to both a higher PaCO2 result ing in lowered ventilation requirements for a given workload and also to a reduced perception of breathlessness for a given level of ventilation We have shown previously that the administration of morphine ( 0.8 mg/kg ) to patients with COPD increases the VO2max by 19.3 percent . A recent study demonstrated that the administration of low-dose nebulized morphine ( approximately 2 mg ) increased the endurance time of patients with severe lung disease by 1 min ( 35 percent ) with few systemic side effects . This double-blind crossover study evaluated the effects of various doses of nebulized morphine ( 0 , 1 , 4 , and 10 mg ) on the exercise tolerance and the psychologic status of COPD patients . In the present study , eight COPD patients ( FEV1 = 0.90 + /- 0.26 L , workload max = 76 + /- 29 W , VO2max = 950 + /- 264 ml , VEmax = 34 + /- 7 L ) , who were ventilatory limited were tested on four separate days . On each testing day , the patients underwent incremental exercise testing and psychologic testing before and 45 min after receiving the nebulized solution . The mean changes ( + /- SD ) in the exercise test results after each of the four different regimens were as follows : [ table : see text ] Although there tended to be larger increases in the workload , VO2max , and VEmax after the largest dose of morphine , none of the changes was statistically significant . Likewise , there were no significant differences in spirometry , resting metabolic measurements , or psychologic test scores after the four different regimens . We conclude that aerosolized morphine in the doses used in this study has no significant beneficial effect on the exercise tolerance of patients with COPD OBJECTIVES We sought to test the hypothesis that suppression of chemosensitivity ( respiratory response to arterial blood gases ) with dihydrocodeine may improve dyspnea and exercise tolerance in patients with chronic heart failure . BACKGROUND Exertional dyspnea is a common limiting symptom in patients with chronic heart failure . The mechanisms underlying this symptom are not fully understood but may be related to increased ventilation caused , in part , by the augmentation of chemosensitivity . Suppression of chemosensitivity with mild opiates may thus improve this symptom as well as exercise tolerance . METHODS Twelve men with chronic heart failure ( mean [ + /-SE ] age 65.5 + /- 1.5 years , range 58 to 75 ; left ventricular ejection fraction 21.3 + /- 3.0 % , range 8 to 39 ) received placebo or dihydrocodeine ( 1 mg/kg body weight ) on two separate days in a r and omized , double-blind design . One hour later , hypoxic and hypercapnic chemosensitivities were assessed using the transient inhalations of pure nitrogen and the rebreathing of 7 % carbon dioxide in 93 % oxygen , followed by treadmill cardiopulmonary exercise testing . The symptoms of dyspnea and fatigue during the exercise test were assessed using a modified Borg scale from 0 to 10 . RESULTS There was a significant fall in hypoxic and hypercapnic chemosensitivities with dihydrocodeine administration compared with placebo ( 0.447 + /- 0.096 vs. 0.746 + /- 0.104 liter/min per percent arterial oxygen saturation , p = 0.005 ; 2,480 + /- 0.234 vs. 2.966 + /- 0.283 liter/min per mm Hg , p = 0.01 , respectively ) . Exercise duration was prolonged from 455 + /- 27 s on placebo to 512 + /- 27 s ( p = 0.001 ) with dihydrocodeine , and peak oxygen consumption increased from 18.0 + /- 0.6 to 19.7 + /- 0.6 ml/kg per min ( p = 0.002 ) . The ventilatory response to exercise , characterized by the regression slope relating minute ventilation to carbon dioxide output , decreased from 34.19 + /- 2.35 to 30.85 + /- 1.91 ( p = 0.01 ) . With dihydrocodeine administration , the change in the modified Borg score for dyspnea was -0.80 ( p = 0.003 ) at 6 min and -0.33 ( p = 0.52 ) at peak exercise , whereas that for fatigue did not change significantly . Arterial oxygen saturation was maintained during exercise despite dihydrocodeine administration ( 99.3 % at rest vs. 98.9 % at peak exercise , p = 0.21 ) . CONCLUSIONS Augmented chemosensitivity is important in the pathophysiology of chronic heart failure . Its suppression with dihydrocodeine was associated with a reduction of exercise ventilation , an improvement in exercise tolerance and a decrease in breathlessness . Pharmacologic modulation of chemosensitivity may benefit patients with chronic heart failure and merits further investigation OBJECTIVE We have shown that the administration of 0.8 mg/kg of morphine ( M ) to patients with COPD result ed in a 20 % increase in the maximum oxygen consumption ( Vo2max ) , but was associated with significant drowsiness and euphoria . The objective of the present study was to ascertain whether lower doses of M alone or in combination with prochlorperazine ( PC ) or promethazine ( P ) could elicit significant increases in exercise tolerance . DESIGN The exercise capacity , psychological status , and reaction times were assessed before and 60 min after the patients received placebo ( PLAC ) , 30 mg M orally , 30 mg M plus 10 mg PC ( M-PC ) , or 30 mg M plus 25 mg P ( M-P ) in a r and omized double-blind crossover study . In a secondary study , nine patients were tested on three separate days before and after receiving PLAC , 25 mg P , or 30 mg M plus 25 mg P. PATIENTS Seven COPD patients ( FEV1=0.99 + /- 0.30 L , Vo2max=990 + /- 315 mL/min ) who were ventilatory-limited . SETTING Veterans Affairs medical center . RESULTS After the patients ingested M-P , the increase in the Vo2max ( 129.0 + /- 104 mL/min ) , the workload ( 10.0 + /- 6.5 W ) and the maximum minute ventilation ( 4.0 + /- 3.9 L/min ) were significantly greater ( p<0.05 ) than after PLAC ingestion ( -4.8 + /- 79 mL/min , 1.4 + /- 6.9 W , and -1.6 + /- 2.4 L/min , respectively ) . Changes after the ingestion of M , P , o r M-PC were intermediate . The M-PC combination adversely affected the patient 's reported mental status ( Bond visual analog scale ) more than the M-P or M regimens . No regimen significantly affected the reaction time . CONCLUSIONS We conclude that the administration of 30 mg of M plus 25 mg of P significantly improves the exercise tolerance of patients with COPD , without significantly impairing the mental capabilities of the subjects . The utility of this regimen over longer time periods needs to be evaluated This study compared the effects of nebulized versus subcutaneous morphine on the intensity of dyspnea in cancer patients . Patients with a resting dyspnea intensity > or =3 on a 0 - 10 scale ( 0=no dyspnea , 10=worst possible dyspnea ) who received regular oral or parenteral opioids were included . On day 1 , patients received either subcutaneous ( SC ) morphine plus nebulized placebo or nebulized morphine plus SC placebo . On day 2 , a crossover was made . Dyspnea intensity , side effects , and blinded preference of treatment were assessed . Eleven patients completed the study .  Dyspnea decreased from a median of 5 ( range , 3 - 8 ) to 3 ( range , 0 - 7 ) after SC morphine ( P=0.025 ) and from 4 ( range , 3 - 9 ) to 2 ( range , 0 - 9 ) after nebulized morphine ( P=0.007 ) . There was no significant difference in dyspnea intensity between nebulized and subcutaneous morphine at 60 minutes . Unfortunately , due to limited sample size , there was insufficient power to rule out a significant difference between both routes of administration . Nebulized morphine offered dyspnea relief similar to that of SC morphine . Larger r and omized controlled trials in patients with both  continuous dyspnea and earlier  stages of dyspnea  are justified The aim of this study was to assess the effects of diamorphine on breathlessness and exercise tolerance in patients with severe chronic airflow obstruction and normal arterial carbon dioxide tension ( PCO2 ) levels ( " pink puffer " syndrome ) . In this double-blind , cross-over , r and omized study we examined both acute and chronic effects of single and multiple doses of oral diamorphine in 14 " pink puffer " patients . Their mean resting forced expiratory volume in one second ( FEV1 ) was 36 % predicted normal , mean arterial oxygen tension ( PaO2 ) was 9.2 kPa and mean PaCO2 was 5.2 kPa . Ten patients took either diamorphine 2.5 or 5 mg or placebo elixir 6 hourly for 2 weeks , recording on a diary card dyspnoea , sleepiness and well-being on a visual analogue scale ( VAS ) . The final treatment was given 30 min before measuring spirometry , arterial blood gases , plasma morphine levels , 6 min walking distances , time walked on treadmill and self- assessment of dyspnoea on a VAS scale after exercise . On two further days , eight patients took two doses , 4 h apart , of either diamorphine 7.5 mg or placebo elixir . Spirometry , 6 min walking distance with a VAS score for dyspnoea were measured before and at 1 h after each dose . Morphine levels and blood gases were also measured . Whether given in single or repeated doses , oral diamorphine had no significant effect on exercise tolerance and breathlessness when compared with placebo . Diamorphine 2.5 - 7.5 mg produced neither sleepiness nor a deterioration in blood gases . However , plasma levels associated with analgesic efficacy were not achieved with these doses . Thus , as given in this study , oral diamorphine is unlikely to have therapeutic potential in the treatment of dyspnoea in the " pink puffer " syndrome Systemic opiates may relieve dyspnoea and improve exercise tolerance in patients with chronic obstructive pulmonary disease ( COPD ) . Small doses of inhaled opiates may have similar effects ; however , recent studies have shown no benefit . We studied higher doses of inhaled morphine and measured systemic absorption to determine whether any beneficial actions are local or systemic . Twenty and 40 mg doses and 0.9 % saline were nebulized in a r and omized , double-blind study of 16 patients with stable COPD . Patients performed 6 min walk tests immediately after the nebulized test solution ( Walk 1 ) and again 60 min later ( Walk 2 ) . Arterial oxygen saturation ( Sa , O2 ) , modified Borg dyspnoea score and cardiac frequency were recorded during each walk . There was no difference between placebo and either dose of nebulized morphine on these measurements . The higher dose of nebulized morphine achieved a higher plasma concentration . The highest plasma concentration was measured immediately after nebulization , and this decreased steadily in the hour thereafter ( p<0.002 ) . There was no correlation between the change in walk distance and the change in plasma morphine concentration after either dose of nebulized morphine . We conclude that higher doses of nebulized morphine do not improve exercise endurance or 
    Output:
    
Most examined the effect of opioids , generally morphine , on dyspnea .
No controlled trials examined  systemic corticosteroids  in the treatment of cancer patients , and of the other non-opioid drugs examined , only oral promethazine , a phenothiazine , showed some benefit in the relief of dyspnea .
Conclusions Systemic opioids , administered orally or parenterally , can be used to manage dyspnea in cancer patients .