chronic obstructive pulmonary disease ( copd ) , as a common problem in the elderly , is a major cause of chronic morbidity and mortality throughout the world.1 it is characterized by chronic obstruction of expiratory flow affecting peripheral airways , and is often associated with chronic bronchitis and emphysema , thereby accelerating the decline in lung function.2,3 previous studies have found that nutritional status is the prognostic factor that is associated with the mortality in copd.46 weight loss is the major characteristic of malnutrition in copd.7 in 2002 ,  nutritional risk  was defined by the european society for parenteral and enteral nutrition ( espen).8 recently , nutritional risk was found to be associated with the exacerbation of copd in the patients who were hospitalized because of copd.9 meanwhile , it has been reported that nutritional risk is related to the development of copd in male smokers.10 in addition , the exercise capacity is also another factor related to mortality in copd.11 limitation of the exercise capacity seriously affects the quality of life in copd patients.12 therefore , many studies have aimed at strategies for improving the exercise capacity of copd patients.13,14 however , this effective and feasible strategy still needs further exploration .
it has been reported that nutritional status could affect the exercise capacity in copd patients.15,16 moreover , nutritional supply seems to contribute to improving the exercise capacity.15,17 in view of these findings , we speculated that there might be some relationship between nutritional risk and exercise capacity .
therefore , we explored this relationship in severe copd male patients in this study , which could provide evidence for the effect of nutritional supply on exercise capacity .
between january 2012 and december 2013 , a total of 58 severe copd male patients ( age range : 4778 years ) who were hospitalized in the department of respiratory medicine , shanghai pulmonary hospital , affiliated to tongji university , were enrolled in the present study .
all the patients were diagnosed with severe copd ( forced expiratory volume in 1 second as percentage of predicted , fev1%pred < 50 ) according to the new global initiative for chronic obstructive lung disease ( gold ) classification criteria of 2012.18 the patients were excluded if they had diseases in other organs ( such as the cardiovascular , renal , endocrine , digestive , and nervous systems ) .
patients provided written informed consent before inclusion . before nutritional risk assessment , the height ( m ) and weight ( kg ) of patients were measured .
body mass index ( bmi ) was calculated according to formula bmi = weight / height squared ( kg / m ) .
nutritional risk assessment was conducted using the continuous sampling method according to the nutritional risk screening ( nrs , 2002 ) criteria developed by espen.19 the nrs score ( 07 ) was the sum of the scores in disease severity , nutritional status , and age .
the nutritional status of each patient was scored based on the changes in body weight and bmi in the recent 13 months and food intake in the recent 1 week . besides
, one score was assigned to the patients who were more than 70 years old . according to the nrs score
, the patients were divided into two groups : nutritional risk group ( nrs score 3 ) and no nutritional risk group ( nrs score < 3 ) .
blood samples were collected from the right forearm radial artery before conventional pulmonary function testing ( pft ) and cardiopulmonary exercise testing ( cpet ) were performed .
blood gas analysis was performed to confirm whether partial pressure of oxygen in the artery ( pao2 ) and partial pressure of carbon dioxide in the artery ( paco2 ) were in the normal range ( pao2 : 80100 mmhg ; paco2 : 3545 mmhg ) using an abl 800 flex blood gas analyzer ( radiometer medical a / s , copenhagen , denmark ) .
a master screen diffusion system ( jaeger corp . , hoechberg , germany ) was used for pft .
prediction equations for normal lung function , which were developed in 1988 , were used in this assessment.20 the following parameters were detected in this testing : forced vital capacity ( fvc ) , forced expiratory volume in 1 second ( fev1 ) , fev1%pred , fev1/fvc ratio , residual volume ( rv ) , total lung capacity ( tlc ) , rv / tlc , and pulmonary diffusing capacity for carbon monoxide ( dlco ) .
pft was performed three times for each patient and the best result was chosen for analysis .
cpet was performed using a cardiopulmonary exercise testing system ( mastercreen - cpx ; jaeger corp . ) . before cpet was performed ,
the flow sensors and gas analyzers were strictly calibrated . in this testing , a symptom - limited incremental exercise test was performed with different loads ( 1025 w / min ) based on the conditions of the patients.21 during testing , the indicators , consisting of 12-lead electrocardiogram ( ecg ) , blood pressure , pulse oximetry , pulmonary ventilation , gas exchange of oxygen and carbon dioxide ( real - time breath - by - breath analysis ) , and anaerobic threshold ( at , v - slope analysis ) , were monitored .
afterward , exercise without load was performed for 3 minutes , and then the load was gradually increased until some symptoms ( such as leg pain , exhaustion , or difficulty in breathing ) occurred . in addition , the testing would be stopped when one of the following conditions occurred : 1 ) 2 mm of st - segment depression with chest pain or 3 mm of st segment without chest pain ; 2 ) frequent ventricular premature beat ; 3 ) second- or third - degree atrioventricular block ; 4 ) systolic blood pressure 250 mmhg or / and diastolic blood pressure 120 mmhg ; 5 ) decreased blood pressure 30 mmhg compared to the baseline level ; or 6 ) pulse oxygen saturation 80% .
the prediction value for cept was calculated according to the american thoracic society / american college of chest physicians statement on cpet in 2003.22,23 after testing , the following data were recorded : peak load , peak vo2 ( peak oxygen uptake ) , peak vo2%pred ( peak oxygen uptake as percentage of predicted ) , peak vo2/kg ( peak oxygen uptake per kilogram of body mass ) , peak o2 pulse ( peak oxygen pulse ) .
the correlations between nrs score and peak vo2 , peak o2 pulse , or peak load were determined using pearson correlation analysis .
between january 2012 and december 2013 , a total of 58 severe copd male patients ( age range : 4778 years ) who were hospitalized in the department of respiratory medicine , shanghai pulmonary hospital , affiliated to tongji university , were enrolled in the present study .
all the patients were diagnosed with severe copd ( forced expiratory volume in 1 second as percentage of predicted , fev1%pred < 50 ) according to the new global initiative for chronic obstructive lung disease ( gold ) classification criteria of 2012.18 the patients were excluded if they had diseases in other organs ( such as the cardiovascular , renal , endocrine , digestive , and nervous systems ) .
before nutritional risk assessment , the height ( m ) and weight ( kg ) of patients were measured .
body mass index ( bmi ) was calculated according to formula bmi = weight / height squared ( kg / m ) .
nutritional risk assessment was conducted using the continuous sampling method according to the nutritional risk screening ( nrs , 2002 ) criteria developed by espen.19 the nrs score ( 07 ) was the sum of the scores in disease severity , nutritional status , and age .
the nutritional status of each patient was scored based on the changes in body weight and bmi in the recent 13 months and food intake in the recent 1 week . besides
, one score was assigned to the patients who were more than 70 years old . according to the nrs score
, the patients were divided into two groups : nutritional risk group ( nrs score 3 ) and no nutritional risk group ( nrs score < 3 ) .
blood samples were collected from the right forearm radial artery before conventional pulmonary function testing ( pft ) and cardiopulmonary exercise testing ( cpet ) were performed .
blood gas analysis was performed to confirm whether partial pressure of oxygen in the artery ( pao2 ) and partial pressure of carbon dioxide in the artery ( paco2 ) were in the normal range ( pao2 : 80100 mmhg ; paco2 : 3545 mmhg ) using an abl 800 flex blood gas analyzer ( radiometer medical a / s , copenhagen , denmark ) .
prediction equations for normal lung function , which were developed in 1988 , were used in this assessment.20 the following parameters were detected in this testing : forced vital capacity ( fvc ) , forced expiratory volume in 1 second ( fev1 ) , fev1%pred , fev1/fvc ratio , residual volume ( rv ) , total lung capacity ( tlc ) , rv / tlc , and pulmonary diffusing capacity for carbon monoxide ( dlco ) .
pft was performed three times for each patient and the best result was chosen for analysis .
cpet was performed using a cardiopulmonary exercise testing system ( mastercreen - cpx ; jaeger corp . ) . before cpet was performed ,
the flow sensors and gas analyzers were strictly calibrated . in this testing , a symptom - limited incremental exercise test was performed with different loads ( 1025 w / min ) based on the conditions of the patients.21 during testing , the indicators , consisting of 12-lead electrocardiogram ( ecg ) , blood pressure , pulse oximetry , pulmonary ventilation , gas exchange of oxygen and carbon dioxide ( real - time breath - by - breath analysis ) , and anaerobic threshold ( at , v - slope analysis ) , were monitored .
afterward , exercise without load was performed for 3 minutes , and then the load was gradually increased until some symptoms ( such as leg pain , exhaustion , or difficulty in breathing ) occurred . in addition , the testing would be stopped when one of the following conditions occurred : 1 ) 2 mm of st - segment depression with chest pain or 3 mm of st segment without chest pain ; 2 ) frequent ventricular premature beat ; 3 ) second- or third - degree atrioventricular block ; 4 ) systolic blood pressure 250 mmhg or / and diastolic blood pressure 120 mmhg ; 5 ) decreased blood pressure 30 mmhg compared to the baseline level ; or 6 ) pulse oxygen saturation 80% . the prediction value for cept
was calculated according to the american thoracic society / american college of chest physicians statement on cpet in 2003.22,23 after testing , the following data were recorded : peak load , peak vo2 ( peak oxygen uptake ) , peak vo2%pred ( peak oxygen uptake as percentage of predicted ) , peak vo2/kg ( peak oxygen uptake per kilogram of body mass ) , peak o2 pulse ( peak oxygen pulse ) .
the correlations between nrs score and peak vo2 , peak o2 pulse , or peak load were determined using pearson correlation analysis .
among the total 58 severe copd male patients , 25 were assessed as having nutritional risk and assigned to the nutritional risk group .
the other 33 patients without nutritional risk were enrolled into the no nutritional risk group . the age ( no nutritional risk group , 63.739.03 years ; nutritional risk group , 61.527.13 years ; p=0.319 ) and the height ( no nutritional risk group , 166.526.10 cm ; nutritional risk group , 167.125.83 cm ; p=0.707 ) of the patients in the nutritional risk group were similar to those in the no nutritional risk group . however , the weight ( no nutritional risk group , 64.586.31 kg ; nutritional risk group , 51.244.68 kg ; p<0.0001 ) and bmi ( no nutritional risk group , 23.302.02 m / kg ; nutritional risk group , 18.341.33 m / kg ; p<0.0001 ) of the patients in the nutritional risk group were significantly lower than those in the no nutritional risk group ( table 1 ) . before exercise
, there was no statistically significant difference in pao2 ( no nutritional risk group , 73.3010.71 ; nutritional risk group , 73.6813.00 ; p=0.903 ) and paco2 ( no nutritional risk group , 42.856.82 ; no nutritional risk group , 41.957.84 ; p=0.643 ) between severe copd male patients with and without nutritional risk ( table 2 ) .
there was no significant difference between severe copd male patients with and without nutritional risk in fvc ( no nutritional risk group , 2.260.53 ; nutritional risk group , 2.290.67 ; p=0.850 ) , fev1 ( no nutritional risk group , 0.860.25 ; nutritional risk group , 0.800.23 ; p=0.353 ) , fev1%pred ( no nutritional risk group , 32.408.47 ; nutritional risk group , 29.008.97 ; p=0.146 ) , fev1/fvc ( no nutritional risk group , 37.925.34 ; nutritional risk group , 36.398.47 ; p=0.433 ) , tlc ( no nutritional risk group , 7.891.39 ; nutritional risk group , 7.801.93 ; p=0.844 ) , rv ( no nutritional risk group , 5.661.31 ; nutritional risk group , 5.662.12 ; p=1.000 ) , and rv / tlc ( no nutritional risk group , 71.286.53 ; nutritional risk group , 71.4011.01 ; p=0.962 ) . nevertheless , the dlco ( no nutritional risk group , 11.984.02 ; nutritional risk group , 8.974.37 ; p=0.009 ) of the patients in the no nutritional risk group was significantly higher than that of the patients in the nutritional risk group . as shown in table 4 ,
the severe copd male patients in the no nutritional risk group had significantly higher peak vo2 ( no nutritional risk group , 1,068.33327.38 ; nutritional risk group , 871.24219.37 ; p=0.008 ) , peak vo2%pred ( no nutritional risk group , 60.2717.13 ; nutritional risk group , 52.0412.64 ; p=0.048 ) , and peak o2 pulse ( no nutritional risk group , 8.802.37 ; nutritional risk group , 7.321.47 ; p=0.008 ) than those in the nutritional risk group .
but there was no significant difference between the groups in peak load ( no nutritional risk group , 61.2130.04 ; nutritional risk group , 49.4820.82 ; p=0.100 ) and peak vo2/kg ( no nutritional risk group , 16.574.61 ; nutritional risk group , 16.923.50 ; p=0.753 ) .
figure 1 shows the correlation between the nrs score and peak vo2 , peak o2 pulse , or peak load .
the results show that there are significant negative correlations between the nrs score and peak vo2 ( r=0.353 , p<0.01 ) , peak o2 pulse ( r=0.322 , p<0.05 ) , or peak load ( r=0.272 , p<0.05 ) in severe copd male patients .
among the total 58 severe copd male patients , 25 were assessed as having nutritional risk and assigned to the nutritional risk group .
the other 33 patients without nutritional risk were enrolled into the no nutritional risk group .
the age ( no nutritional risk group , 63.739.03 years ; nutritional risk group , 61.527.13 years ; p=0.319 ) and the height ( no nutritional risk group , 166.526.10 cm ; nutritional risk group , 167.125.83 cm ; p=0.707 ) of the patients in the nutritional risk group were similar to those in the no nutritional risk group . however , the weight ( no nutritional risk group , 64.586.31 kg ; nutritional risk group , 51.244.68 kg ; p<0.0001 ) and bmi ( no nutritional risk group , 23.302.02 m / kg ; nutritional risk group , 18.341.33 m / kg ; p<0.0001 ) of the patients in the nutritional risk group were significantly lower than those in the no nutritional risk group ( table 1 ) .
before exercise , there was no statistically significant difference in pao2 ( no nutritional risk group , 73.3010.71 ; nutritional risk group , 73.6813.00 ; p=0.903 ) and paco2 ( no nutritional risk group , 42.856.82 ; no nutritional risk group , 41.957.84 ; p=0.643 ) between severe copd male patients with and without nutritional risk ( table 2 ) .
there was no significant difference between severe copd male patients with and without nutritional risk in fvc ( no nutritional risk group , 2.260.53 ; nutritional risk group , 2.290.67 ; p=0.850 ) , fev1 ( no nutritional risk group , 0.860.25 ; nutritional risk group , 0.800.23 ; p=0.353 ) , fev1%pred ( no nutritional risk group , 32.408.47 ; nutritional risk group , 29.008.97 ; p=0.146 ) , fev1/fvc ( no nutritional risk group , 37.925.34 ; nutritional risk group , 36.398.47 ; p=0.433 ) , tlc ( no nutritional risk group , 7.891.39 ; nutritional risk group , 7.801.93 ; p=0.844 ) , rv ( no nutritional risk group , 5.661.31 ; nutritional risk group , 5.662.12 ; p=1.000 ) , and rv / tlc ( no nutritional risk group , 71.286.53 ; nutritional risk group , 71.4011.01 ; p=0.962 ) .
nevertheless , the dlco ( no nutritional risk group , 11.984.02 ; nutritional risk group , 8.974.37 ; p=0.009 ) of the patients in the no nutritional risk group was significantly higher than that of the patients in the nutritional risk group .
as shown in table 4 , the severe copd male patients in the no nutritional risk group had significantly higher peak vo2 ( no nutritional risk group , 1,068.33327.38 ; nutritional risk group , 871.24219.37 ; p=0.008 ) , peak vo2%pred ( no nutritional risk group , 60.2717.13 ; nutritional risk group , 52.0412.64 ; p=0.048 ) , and peak o2 pulse ( no nutritional risk group , 8.802.37 ; nutritional risk group , 7.321.47 ; p=0.008 ) than those in the nutritional risk group .
but there was no significant difference between the groups in peak load ( no nutritional risk group , 61.2130.04 ; nutritional risk group , 49.4820.82 ; p=0.100 ) and peak vo2/kg ( no nutritional risk group , 16.574.61 ; nutritional risk group , 16.923.50 ; p=0.753 ) .
figure 1 shows the correlation between the nrs score and peak vo2 , peak o2 pulse , or peak load .
the results show that there are significant negative correlations between the nrs score and peak vo2 ( r=0.353 , p<0.01 ) , peak o2 pulse ( r=0.322 , p<0.05 ) , or peak load ( r=0.272 , p<0.05 ) in severe copd male patients .
lack of exercise capacity limits the quality of life of copd patients.12 some previous studies have found that there was an association between the nutritional status and exercise capacity in copd patients.15,16 however , it is still unclear whether a correlation exists between nutritional risk and exercise capacity in copd patients .
therefore , we investigated the relationship between nutritional risk and exercise capacity in severe copd male patients . in this study
, we found significantly lower weight and bmi in severe copd male patients with nutritional risk compared to those of severe copd male patients without nutritional risk , which are the characteristics of copd patients with nutritional risk.2426 besides , pft showed that dlco in severe copd male patients without nutritional risk was significantly higher than that in severe copd male patients with nutritional risk .
it has been reported that reduced dlco could impair exercise capacity in patients with heart failure through increased dead space ventilation.27 meanwhile , a low dlco could impair oxygen transport by a reduction in maximum oxygen consumption.28 moreover , it has been reported that weakened exercise capacity is attributed to reduced locomotor muscle oxygen transport.29,30 normally , oxygen transport would adaptively vary with oxygen demand during exercise,31,32 and oxygen uptake would increase during exercise for biochemical adaptations.33,34 thus , the exercise capacity can decline through impaired oxygen transport , which can not adaptively regulate the oxygen uptake during exercise . as expected , the impaired oxygen transport might limit the oxygen uptake in severe copd male patients with nutritional risk , as seen in this study .
cpet showed that the peak vo2 and peak o2 pulse of the nutritional risk group were significantly lower than those of the no nutritional risk group and there were significant negative correlations between the nrs score and peak vo2 or peak o2 pulse .
these results indicate that the oxygen uptake of severe copd male patients with nutritional risk was significantly lower than that of severe copd male patients without nutritional risk , which might be due to the impaired oxygen transport in copd,33,35 thereby affecting the utilization of oxygen.36 it was reported that inadequate oxygen supply during exercise caused accumulation of oxygen deficit , which was responsible for the reduced exercise capacity in patients with copd.37,38 meanwhile , decreased muscle oxygen utilization could reduce the exercise capacity in patients with copd.39 thus , impaired oxygen transport may be the main reason for reduced exercise capacity in copd patients with nutritional risk .
in addition , it has been reported that nutritional depletion is related to the respiratory and peripheral skeletal muscle function in outpatients with copd.40,41 nutritional supplements have been found to be useful for the prevention and treatment of exercise - induced skeletal muscle injury.42 moreover , muscle function is associated with the oxygen transport.4345 thus , patients with nutritional risk may have decreased exercise capacity due to impaired oxygen transport . given these facts
, there may be a close relationship between nutritional risk and exercise capacity . furthermore , blood gas analysis indicated that the pao2 and paco2 of patients were all in normal ranges before exercise and they were similar between groups . however , the pao2 and paco2 were not measured after the exercise .
the changes induced by exercise in oxygen and co2 pressure in arterial blood could not be assessed .
further studies are required to investigate whether nutritional risk could affect the changes induced by exercise in oxygen and co2 pressures in arterial blood .
second , we assessed only the total weight but not the fat - free mass , so further studies are required .
in addition , not all of the indicators in pft and cept were found to be associated with the nutritional risk .
thus , the relationship between nutritional risk and exercise capacity should be further investigated in female patients and also studies with large sample sizes for verifying the result of this study .
the results of this study supported the association between exercise capacity and nutritional risk according to nrs 2002 in severe copd male patients
. the impairment of oxygen transport may be the main mechanism of this relationship between nutritional risk and exercise capacity .
 objectivethe nutritional status of chronic obstructive pulmonary disease ( copd ) patients is associated with their exercise capacity . in the present study , we have explored the relationship between nutritional risk and exercise capacity in severe male copd patients.methodsa total of 58 severe copd male patients were enrolled in this study . 
 the patients were assigned to no nutritional risk group ( n=33 ) and nutritional risk group ( n=25 ) according to the nutritional risk screening ( nrs , 2002 ) criteria . 
 blood gas analysis , conventional pulmonary function testing , and cardiopulmonary exercise testing were performed on all the patients.resultsresults showed that the weight and bmi of the patients in the nutritional risk group were significantly lower than in the no nutritional risk group ( p<0.05 ) . 
 the pulmonary diffusing capacity for carbon monoxide of the no nutritional risk group was significantly higher than that of the nutritional risk group ( p<0.05 ) . 
 besides , the peak vo2 ( peak oxygen uptake ) , peak o2 pulse ( peak oxygen pulse ) , and peak load of the nutritional risk group were significantly lower than those of the no nutritional risk group ( p<0.05 ) and there were significantly negative correlations between the nrs score and peak vo2 , peak o2 pulse , or peak load ( r<0 , p<0.05).conclusionthe association between exercise capacity and nutritional risk based on nrs 2002 in severe copd male patients is supported by these results of this study . 
Introduction
Materials and methods
Patients
Nutritional risk assessment
Blood gas analysis
PFT and CPET
Statistical analyses
Results
Characteristics of patients
Results for blood gas analysis
Pulmonary function comparison between groups
Results for CPET
Correlation between NRS score and peak VO
Discussion
Conclusion