Resting Energy Expenditure in Interstitial Lung Disease 1, 2
JEAN-WILLIAM FITTING, PHILIPPE FRASCAROLO, ERIC JEQUIER, and PHILIPPE LEUENBERGER
Introduction
Resent knowledge of the nutritional aspects of chronic lung disease mainly relates to chronic obstructive pulmonary disease (COPD) (1). Thus it has been shown that malnutrition is frequently associated with COPD, particularly with the most severe cases (2-6). Weight loss appears to be caused, at least in part, by a hypermetabolic state that was recently demonstrated by several groups using standard methods of calorimetry (7-10). This extra energy expenditure is currently deemed to be caused by the increased work of breathing accomplished by the respiratory muscles in COPD (1, 8, 9). In contrast, little is known about nutrition and energy requirements in interstitiallung disease. Since these disorders are also characterized by an increased work of breathing, we hypothesized that they lead to a hypermetabolic state as well. Therefore, the aim of this study was to determine the resting energy expenditure in patients with interstitial lung disease. Methods
Subjects 1\velvepatients presenting roentgenographic patterns of diffuse interstitial lung disease were studied. Their age, sex, and diagnosis are presented in table 1. In the absence of histologicexamination, four patients were considered as suffering from pulmonary fibrosis of unknown origin. Sarcoidosis was diagnosed in three patients, on the grounds of lung biopsies in two and sequence of radiologic abnormalities in one. Hypersensitivity pneumonitis was diagnosed in two patients, histiocytosis X in one, and lymphocytic interstitial pneumonitis in one, all based on lung biopsies. Silicosis was diagnosed in one patient on the grounds of nodular opacities and professional exposure. No patient presented skeletal deformity, neuromuscular disorders, or congestive heart failure. All patients were apyretic and in stable clinical condition at the time of the study. Of the 12patients, six were receiving corticosteroid therapy.
Pulmonary Function 'Tests Lung volumes were measured by body plethysmographyand forced expiratory flow rates by a heated pneumotachograph (Erich Jaeger, Wiirzburg, FRO). Carbon monoxide
SUMMARY Because Interstitial lung disease Increases the work of breathing, the aim of this study was to determine If this condition Is associated with Increased energy requirements. A group of 12 Clinically stable patients with Interstitial lung disease was studied. Patients with a history of weight loss had significantly more severe lung volume restriction. Regression analysis showed that 42% of body weight variation was explained by vital capacity (p < 0.025). Resting energy expenditure was measured by standard methods of Indirect calorimetry. The measurements were performed with a vantllated hood during prolonged steady-state periods after an overnight fast. We found that resting energy expenditure was Increased to 117.3 and 118.7%ofthe predicted basal metabolic rate, according to Fleisch and to Harris and Benedict reference values, respectively (p < 0.001). Furthermore, resting energy expenditure was Increased to 120.8% of the predicted value according to body fat-free mass (p < 0.001). This extra energy expenditure In patients with Interstitial lung disease Is similar to that recently reported In patlenta with chronic obstructive pUlmonary disease. AM REV RESPIR DIS 1990; 142:631-635
transfer was measured by the single-breath method in nine subjects and by the steadystate method in two (P. K. Morgan, Chatham, UK). One subject was unable to accomplish the maneuver. Reference values were those of the Commission of the European Communities (11)for volumes and flows and of Cotes (12) and Billiet (13) for the CO transfer factor. Arterialized ear lobe blood gases were measured by a blood gas analyzer (Radiometer, Copenhagen, Denmark) and the alveolar-arterial Po. difference [P(A - a)o.] was calculated. Respiratory muscle strength was assessed by two methods in seven subjects. The maximal inspiratory pressure sustained for 1 s during a Mueller maneuver from FRC (PImax) was measured at the mouth by an aneroid strain gauge (Haenni, Switzerland) or by a conventional balloon catheter system placed in the midesophagus and connected to a pressure transducer (Hewlett-Packard 1280,USA). Transdiaphragmatic pressure (Pdi) wasmeasured by a differential pressure transducer (Microswitch 126PC, Honeywell, USA) connected to the esophageal balloon and to a second balloon placed in the stomach. The highest Pdi generated during a maximal sniff from FRC was recorded (14).
fat-free mass (FFM) was calculated by subtracting the fat content from the body weight.
Measurement of Energy Expenditure Resting energy expenditure (REE) was determined by computerized open-circuit, indirect calorimetry, as previously described (17). A transparent plastic, ventilated hood was placed over the subject's head and made airtight around the neck. To avoid air loss, negative pressure was maintained in the hood. Ventilation was measured by a pneumotachograph (Hewlett-Packard 47303 A, USA). A sample of the air flowing in and out of the hood was continuously collected for analysis. The oxygen content was measured by a paramagnetic analyzer (Magnos 40, Hartmann & Braun, Frankfurt, FRO) and carbon dioxide content by an infrared analyzer (Uras 30, Hartmann & Braun) whose accuracy was tested with calibration gases before each measurement. The system was characterized by a short response time (90070 of the response after 3 min). The stability of the overall system was tested over periods of 4 to 5 h and showed less than 1% variability. The oxygen consumption, the carbon dioxide production, and the respiratory quotient (RQ) were calculated. Thking into account Haldane's correction and the calor-
Nutritional Assessment History of weight changes over the past year were obtained from subjects' recollection or from medical charts when available. Weight was expressed as a percentage of ideal body weight (IBW). For each subject, the body fat content was estimated by measuring skin fold thickness at four sites - bicipital, tricipital, subscapular, and suprailiac-with a caliper (Lange caliper, Cambridge Scientific Industries Inc., Cambridge, MD) (15, 16).The body
(Received in original form June 5, 1989 and in revised form December 11, 1989) 1 From the Division de Pneumologie, Departement de Medecine Interne, Centre Hospitalier Universitaire Vaudois, and the Institut de Physiologie,Universitede Lausanne, Lausanne, Switzerland. 2 Correspondence and requests for reprints should be addressed to Dr, J. W. Fitting, Division de Pneumologie-CHUV, 1011 Lausanne, Switzerland.
631
632
FITTING, FRASCAROLO, JEQUIER. AND LEUENBERGER
cle weakness was not found, as either Pl max was at least 65 cm H 20 or sniff Pdi was at least 100 em H 20.
TABLE 1 PATIENTS WITH INTERSTITIAL LUNG DISEASE Subject
1
2 3 4 5 6 7
8 9
Age
Sex
Diagnosis
65 64 24 46 71 39 48 61 59
M M M
Unknown origin Silicosis Histiocytosis X Sarcoidosis Unknown origin Sarcoidosis Hypersensitivity pneumonitis Unknown origin Lymphocytic interstitial pneumonitis Unknown origin Sarcoidosis Hypersensitivity pneumonitis
10
77
11
30 41
12
F M
F M M F M M M
ic equivalent of oxygen as determined by the RQ, the energy expenditure was calculated. In all subjects, calorimetry was performed at 8 A.M. after an overnight fast. The subjects were lying supine with the head elevated at 30° and placed in the hood. They were asked to remain completely quiet, and they did not watch television or listen to radio. The experimenters ensured that the subjects did not move or sleep. After initiating the measurements, time was allowed for energy expenditure to stabilize. The REE was then determined over a 20-min period of steady state. The REE was expressed in kcal/min and compared to three different sets of normal values. First, it wascompared to predicted basal metabolic rate (BMR) according to Fleisch (18)and to Harris and Benedict (19). Second, the REE was compared to the predicted value based on body FFM as established in 46 normal subjects in our laboratory: REE = 0.016 FFM + 0.198 kcal/min.
Thyroid Function Free thyroxine index (FTI), total T] and T4 , T 3 uptake, and thyroid stimulating hormone (TSH) were measured in 11 ofthe 12patients.
Statistical Analysis Stepwise regression analysis was used to establish relationships betweenweightand REE (dependent variables) and vital capacity, P(A - a)02' and DLCO (independent variables). Vital capacity was compared in the groups with and without weight loss by the MannWhitney V-test. The REE in kilocalories per minute was compared to predicted value by a paired t test. All reported values are mean ± SEM. Results
Pulmonary Function Tests Vital capacity was 57.9 ± 6.5010 of predicted, total lung capacity 70.0 ± 5.9% of predicted, DLeo 69.0 ± 8.6% of predicted, Pao2 67.1 ± 4.4 mm Hg, Paco2 36.0 ± 1.4 mm Hg, and calculated P(A - a)o2 28.4 ± 4.7 mm Hg. Individual values are presented in table 2. The seven patients (Patients 1,2,3,6, 7, 9, and 10)whose respiratory muscle strength was assessed included the four most underweight « 85% IBW). Significant mus-
TABLE
Nutritional Status Since severalpatients' recollectionslacked precision, only qualitative analysis of weight fluctuations wasconsidered. Eight subjects lost weight over the year preceding the study, whereas four either remained stable or increased weight. Five patients weighed less than 90% of ideal body weight, all of them with weight loss over the past year. The individual anthropometric and nutritional parameters are presented in table 3. As illustrated in figure I, the patients with important lung volume restriction tended to weigh less. Stepwise regression analysis showed that 42% of the variation in weight (010 IBW) was explained by vital capacity (% of predicted) (P < 0.025) and 55 % by vital capacity and P(A - a)o2 together (p < 0.05). Vital capacity also differed according to history of weight change: vital capacity was less than 70% of predicted (46.8 ± 6.1% of predicted) in the eight subjects with weightloss, whereas it was above that limit (80.3 ± 5.7% of predicted) in the four subjects without weight loss (p < 0.01). Energy Expenditure REE was 1.16 ± 0.05 kcal/min, corresponding to 117.3 ± 3.2% of predicted BMR (p < 0.001) according to Fleisch (18), to 118.7 ± 3.8% of predicted BMR (p < 0.001) according to Harris and Benedict (19), and to 120.8 ± 2.7% of predicted value according to body FFM (p < 0.001, table 4). The relationship be-
2
PULMONARY FUNCTION TESTS
Subject
1 2 3 4 5 6 7 8 9 10 11 12 Mean SEM
VC (% predicted)
43 63 23 31 78 59 66 29 97 72 74 60 57.9 6.5
TLC (% predicted)
64 84
45 37 66 71 60 47 96 83 98 89 70.0 5.9
VRITLC
FEV,/FVC
DLco
Kco
Pac.
P(A-a)o.
(%)
(% predicted)
(% predicted)
(% predicted)
(mmHg)
(mmHg)
58 55 58 41 19 44
26 61 42 50 43
52 45.8 3.7
115 87 111 109 110 106 120 94 100 104 79 101 103.0 3.4
8588 25 11238 42 54 86 76 103 50 69.0 8.6
113 75 64 40 72 94 107 115 57 81.9 8.9
44 79 84 54 56 96 75 63 61 61 79 53 67.1 4.4
55 11 15 38 33 4 20 21 31 48 17 48
28.4 4.7
Definitionof abbreviations:VC = vitalcapacity; TLC = tota/lung capacity;VR = residual volume;FVC - forcedvitalcapacity; Oleo = carbonmonoxide diffusingcapacity; Pao, - arterial oxygen pressure; P(A - a)o, • alveolar-arterial Po, difference. • Oleo was measured by the steady-state method in Patients 1 and 4.
METABOLISM IN INTERSTITIALLUNG DISEASE
633 1.6
TABLE 3 ANTHROPOMETRIC AND NUTRITIONAL PARAMETERS
• •
1.5 Subject
Height (cm)
Weight (kg)
Weight (% IBW)
BMI (kglm")
Fat (%)
FFM (kg)
Weight Loss
1 2 3 4 5 6 7 8 9 10 11 12 Mean SEM
176.5 169.0 167.0 162.0 162.0 153.0 168.5 178.5 159.0 167.0 167.0 176.0 167.1 2.2
55.5 51.5 51.0 59.0 67.0 42.0 60.2 62.0 72.9 89.3 69.0 67.5 62.2 3.5
78.9 79.7 80.8 106.3 111.7 83.2 93.6 86.4 135.8 141.5 109.4 96.6 100.3 6.2
17.8 18.0 18.3 22.5 25.5 17.9 21.2 19.5 28.8 32.0 24.7 21.8 22.3 1.3
13.3 13.3 8.5 29.9 27.5 20.6 14.9 17.5 42.0 35.4 26.5 15.8 22.1 2.9
48.1 44.7 46.7 41.4 48.6 33.3 51.2 51.2 42.3 57.5 50.7 56.8 47.7 1.9
Yes Yes Yes Yes No Yes Yes Yes No No No Yes
lA
:sE
JEAN-WILLIAM FITTING, PHILIPPE FRASCAROLO, ERIC JEQUIER, and PHILIPPE LEUENBERGER
Introduction
Resent knowledge of the nutritional aspects of chronic lung disease mainly relates to chronic obstructive pulmonary disease (COPD) (1). Thus it has been shown that malnutrition is frequently associated with COPD, particularly with the most severe cases (2-6). Weight loss appears to be caused, at least in part, by a hypermetabolic state that was recently demonstrated by several groups using standard methods of calorimetry (7-10). This extra energy expenditure is currently deemed to be caused by the increased work of breathing accomplished by the respiratory muscles in COPD (1, 8, 9). In contrast, little is known about nutrition and energy requirements in interstitiallung disease. Since these disorders are also characterized by an increased work of breathing, we hypothesized that they lead to a hypermetabolic state as well. Therefore, the aim of this study was to determine the resting energy expenditure in patients with interstitial lung disease. Methods
Subjects 1\velvepatients presenting roentgenographic patterns of diffuse interstitial lung disease were studied. Their age, sex, and diagnosis are presented in table 1. In the absence of histologicexamination, four patients were considered as suffering from pulmonary fibrosis of unknown origin. Sarcoidosis was diagnosed in three patients, on the grounds of lung biopsies in two and sequence of radiologic abnormalities in one. Hypersensitivity pneumonitis was diagnosed in two patients, histiocytosis X in one, and lymphocytic interstitial pneumonitis in one, all based on lung biopsies. Silicosis was diagnosed in one patient on the grounds of nodular opacities and professional exposure. No patient presented skeletal deformity, neuromuscular disorders, or congestive heart failure. All patients were apyretic and in stable clinical condition at the time of the study. Of the 12patients, six were receiving corticosteroid therapy.
Pulmonary Function 'Tests Lung volumes were measured by body plethysmographyand forced expiratory flow rates by a heated pneumotachograph (Erich Jaeger, Wiirzburg, FRO). Carbon monoxide
SUMMARY Because Interstitial lung disease Increases the work of breathing, the aim of this study was to determine If this condition Is associated with Increased energy requirements. A group of 12 Clinically stable patients with Interstitial lung disease was studied. Patients with a history of weight loss had significantly more severe lung volume restriction. Regression analysis showed that 42% of body weight variation was explained by vital capacity (p < 0.025). Resting energy expenditure was measured by standard methods of Indirect calorimetry. The measurements were performed with a vantllated hood during prolonged steady-state periods after an overnight fast. We found that resting energy expenditure was Increased to 117.3 and 118.7%ofthe predicted basal metabolic rate, according to Fleisch and to Harris and Benedict reference values, respectively (p < 0.001). Furthermore, resting energy expenditure was Increased to 120.8% of the predicted value according to body fat-free mass (p < 0.001). This extra energy expenditure In patients with Interstitial lung disease Is similar to that recently reported In patlenta with chronic obstructive pUlmonary disease. AM REV RESPIR DIS 1990; 142:631-635
transfer was measured by the single-breath method in nine subjects and by the steadystate method in two (P. K. Morgan, Chatham, UK). One subject was unable to accomplish the maneuver. Reference values were those of the Commission of the European Communities (11)for volumes and flows and of Cotes (12) and Billiet (13) for the CO transfer factor. Arterialized ear lobe blood gases were measured by a blood gas analyzer (Radiometer, Copenhagen, Denmark) and the alveolar-arterial Po. difference [P(A - a)o.] was calculated. Respiratory muscle strength was assessed by two methods in seven subjects. The maximal inspiratory pressure sustained for 1 s during a Mueller maneuver from FRC (PImax) was measured at the mouth by an aneroid strain gauge (Haenni, Switzerland) or by a conventional balloon catheter system placed in the midesophagus and connected to a pressure transducer (Hewlett-Packard 1280,USA). Transdiaphragmatic pressure (Pdi) wasmeasured by a differential pressure transducer (Microswitch 126PC, Honeywell, USA) connected to the esophageal balloon and to a second balloon placed in the stomach. The highest Pdi generated during a maximal sniff from FRC was recorded (14).
fat-free mass (FFM) was calculated by subtracting the fat content from the body weight.
Measurement of Energy Expenditure Resting energy expenditure (REE) was determined by computerized open-circuit, indirect calorimetry, as previously described (17). A transparent plastic, ventilated hood was placed over the subject's head and made airtight around the neck. To avoid air loss, negative pressure was maintained in the hood. Ventilation was measured by a pneumotachograph (Hewlett-Packard 47303 A, USA). A sample of the air flowing in and out of the hood was continuously collected for analysis. The oxygen content was measured by a paramagnetic analyzer (Magnos 40, Hartmann & Braun, Frankfurt, FRO) and carbon dioxide content by an infrared analyzer (Uras 30, Hartmann & Braun) whose accuracy was tested with calibration gases before each measurement. The system was characterized by a short response time (90070 of the response after 3 min). The stability of the overall system was tested over periods of 4 to 5 h and showed less than 1% variability. The oxygen consumption, the carbon dioxide production, and the respiratory quotient (RQ) were calculated. Thking into account Haldane's correction and the calor-
Nutritional Assessment History of weight changes over the past year were obtained from subjects' recollection or from medical charts when available. Weight was expressed as a percentage of ideal body weight (IBW). For each subject, the body fat content was estimated by measuring skin fold thickness at four sites - bicipital, tricipital, subscapular, and suprailiac-with a caliper (Lange caliper, Cambridge Scientific Industries Inc., Cambridge, MD) (15, 16).The body
(Received in original form June 5, 1989 and in revised form December 11, 1989) 1 From the Division de Pneumologie, Departement de Medecine Interne, Centre Hospitalier Universitaire Vaudois, and the Institut de Physiologie,Universitede Lausanne, Lausanne, Switzerland. 2 Correspondence and requests for reprints should be addressed to Dr, J. W. Fitting, Division de Pneumologie-CHUV, 1011 Lausanne, Switzerland.
631
632
FITTING, FRASCAROLO, JEQUIER. AND LEUENBERGER
cle weakness was not found, as either Pl max was at least 65 cm H 20 or sniff Pdi was at least 100 em H 20.
TABLE 1 PATIENTS WITH INTERSTITIAL LUNG DISEASE Subject
1
2 3 4 5 6 7
8 9
Age
Sex
Diagnosis
65 64 24 46 71 39 48 61 59
M M M
Unknown origin Silicosis Histiocytosis X Sarcoidosis Unknown origin Sarcoidosis Hypersensitivity pneumonitis Unknown origin Lymphocytic interstitial pneumonitis Unknown origin Sarcoidosis Hypersensitivity pneumonitis
10
77
11
30 41
12
F M
F M M F M M M
ic equivalent of oxygen as determined by the RQ, the energy expenditure was calculated. In all subjects, calorimetry was performed at 8 A.M. after an overnight fast. The subjects were lying supine with the head elevated at 30° and placed in the hood. They were asked to remain completely quiet, and they did not watch television or listen to radio. The experimenters ensured that the subjects did not move or sleep. After initiating the measurements, time was allowed for energy expenditure to stabilize. The REE was then determined over a 20-min period of steady state. The REE was expressed in kcal/min and compared to three different sets of normal values. First, it wascompared to predicted basal metabolic rate (BMR) according to Fleisch (18)and to Harris and Benedict (19). Second, the REE was compared to the predicted value based on body FFM as established in 46 normal subjects in our laboratory: REE = 0.016 FFM + 0.198 kcal/min.
Thyroid Function Free thyroxine index (FTI), total T] and T4 , T 3 uptake, and thyroid stimulating hormone (TSH) were measured in 11 ofthe 12patients.
Statistical Analysis Stepwise regression analysis was used to establish relationships betweenweightand REE (dependent variables) and vital capacity, P(A - a)02' and DLCO (independent variables). Vital capacity was compared in the groups with and without weight loss by the MannWhitney V-test. The REE in kilocalories per minute was compared to predicted value by a paired t test. All reported values are mean ± SEM. Results
Pulmonary Function Tests Vital capacity was 57.9 ± 6.5010 of predicted, total lung capacity 70.0 ± 5.9% of predicted, DLeo 69.0 ± 8.6% of predicted, Pao2 67.1 ± 4.4 mm Hg, Paco2 36.0 ± 1.4 mm Hg, and calculated P(A - a)o2 28.4 ± 4.7 mm Hg. Individual values are presented in table 2. The seven patients (Patients 1,2,3,6, 7, 9, and 10)whose respiratory muscle strength was assessed included the four most underweight « 85% IBW). Significant mus-
TABLE
Nutritional Status Since severalpatients' recollectionslacked precision, only qualitative analysis of weight fluctuations wasconsidered. Eight subjects lost weight over the year preceding the study, whereas four either remained stable or increased weight. Five patients weighed less than 90% of ideal body weight, all of them with weight loss over the past year. The individual anthropometric and nutritional parameters are presented in table 3. As illustrated in figure I, the patients with important lung volume restriction tended to weigh less. Stepwise regression analysis showed that 42% of the variation in weight (010 IBW) was explained by vital capacity (% of predicted) (P < 0.025) and 55 % by vital capacity and P(A - a)o2 together (p < 0.05). Vital capacity also differed according to history of weight change: vital capacity was less than 70% of predicted (46.8 ± 6.1% of predicted) in the eight subjects with weightloss, whereas it was above that limit (80.3 ± 5.7% of predicted) in the four subjects without weight loss (p < 0.01). Energy Expenditure REE was 1.16 ± 0.05 kcal/min, corresponding to 117.3 ± 3.2% of predicted BMR (p < 0.001) according to Fleisch (18), to 118.7 ± 3.8% of predicted BMR (p < 0.001) according to Harris and Benedict (19), and to 120.8 ± 2.7% of predicted value according to body FFM (p < 0.001, table 4). The relationship be-
2
PULMONARY FUNCTION TESTS
Subject
1 2 3 4 5 6 7 8 9 10 11 12 Mean SEM
VC (% predicted)
43 63 23 31 78 59 66 29 97 72 74 60 57.9 6.5
TLC (% predicted)
64 84
45 37 66 71 60 47 96 83 98 89 70.0 5.9
VRITLC
FEV,/FVC
DLco
Kco
Pac.
P(A-a)o.
(%)
(% predicted)
(% predicted)
(% predicted)
(mmHg)
(mmHg)
58 55 58 41 19 44
26 61 42 50 43
52 45.8 3.7
115 87 111 109 110 106 120 94 100 104 79 101 103.0 3.4
8588 25 11238 42 54 86 76 103 50 69.0 8.6
113 75 64 40 72 94 107 115 57 81.9 8.9
44 79 84 54 56 96 75 63 61 61 79 53 67.1 4.4
55 11 15 38 33 4 20 21 31 48 17 48
28.4 4.7
Definitionof abbreviations:VC = vitalcapacity; TLC = tota/lung capacity;VR = residual volume;FVC - forcedvitalcapacity; Oleo = carbonmonoxide diffusingcapacity; Pao, - arterial oxygen pressure; P(A - a)o, • alveolar-arterial Po, difference. • Oleo was measured by the steady-state method in Patients 1 and 4.
METABOLISM IN INTERSTITIALLUNG DISEASE
633 1.6
TABLE 3 ANTHROPOMETRIC AND NUTRITIONAL PARAMETERS
• •
1.5 Subject
Height (cm)
Weight (kg)
Weight (% IBW)
BMI (kglm")
Fat (%)
FFM (kg)
Weight Loss
1 2 3 4 5 6 7 8 9 10 11 12 Mean SEM
176.5 169.0 167.0 162.0 162.0 153.0 168.5 178.5 159.0 167.0 167.0 176.0 167.1 2.2
55.5 51.5 51.0 59.0 67.0 42.0 60.2 62.0 72.9 89.3 69.0 67.5 62.2 3.5
78.9 79.7 80.8 106.3 111.7 83.2 93.6 86.4 135.8 141.5 109.4 96.6 100.3 6.2
17.8 18.0 18.3 22.5 25.5 17.9 21.2 19.5 28.8 32.0 24.7 21.8 22.3 1.3
13.3 13.3 8.5 29.9 27.5 20.6 14.9 17.5 42.0 35.4 26.5 15.8 22.1 2.9
48.1 44.7 46.7 41.4 48.6 33.3 51.2 51.2 42.3 57.5 50.7 56.8 47.7 1.9
Yes Yes Yes Yes No Yes Yes Yes No No No Yes
lA
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