Accp Copd and Nutrition

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DOI 10.1378/chest.117.5_suppl_1.274S2000;117;274S-280SChest

Emiel F.M. Wouters

*Nutrition and Metabolism in COPD

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or association of this B2AR polymorphism to COPD-relatedphenotypes. Additional investigation in early-onset COPDfamilies is warranted to determine if shared genetic determi-nants for asthma and COPD can be identified.

Nutrition and Metabolism in

COPD*Emiel F.M. Wouters, MD, PhD, FCCP

(CHEST 2000; 117:274S280S)

Abbreviations: ADP adenosine diphosphate; ATP adeno-sine triphosphate; BMC bone mineral content; BMI bodymass index; COX cytochrome oxidase; FFM fat free mass;GLU glutamate; IMP inosine monophosphate; MHC myosin heavy chain; MLC myosin light chain; NAD nico-tinamide adenine dinucleotide; NADH reduced NAD; PCr creatine phosphate; Pi inorganic phosphate; REE restingenergy expenditure; sTNF-R soluble TNF-receptor; TNF tumor necrosis factor

Body Composition in COPD

The occurrence of weight loss in COPD was alreadyrecognized as a clinical finding at the end of the

nineteenth century. In the past, anthropometric charac-teristics were even used to differentiate emphysema pa-tients from chronic bronchitis patients. The pink puffer(emphysematous type) was characterized as being thin inappearance, with frequent major weight loss, whereas the

blue bloater (chronic bronchitic type) was frequentlyobese, with no marked weight loss, except occasionally interminal stages.1 Because only body weight was assessed inprevious studies, no data were available regarding bodycomposition in COPD. From a functional point of view,attention was focused on the activity-metabolizing tissue,as can be indirectly assessed by the fat free mass (FFM).In previous studies, it has been clearly demonstrated thatdepletion of FFM is a significant problem in hospitalizedpatients with severe COPD,2 as well as in outpatients withmoderate airflow obstruction.3 Body weight in these stud-ies poorly reflected FFM. Depletion of FFM was poorlyrelated to the degree of airflow obstruction, but a strongerrelationship was found with diffusing capacity.3,4

The importance of measuring FFM is emphasized bythe fact that depletion of FFM, indicating loss of musclemass, contributes significantly to peripheral muscle weak-

ness and impaired exercise capacity in COPD,58 as well asto health-related quality of life.9,10

Intrigued by the historically reported differences inanthropometry between the bronchitic and emphysema-tous patients, researchers performed studies to assess bodycomposition in both COPD subtypes. Body compositioncan now easily be assessed by different noninvasive meth-

ods, and stratification of COPD patients into an emphy-sematous group and a group with chronic bronchitis

without parenchymal involvement can be approached byhigh-resolution CT procedures.12, 13

Engelen et al11 studied body composition in a largegroup of COPD patients who had been classified, onhigh-resolution CT criteria, as suffering from either em-physema or chronic bronchitis. Whole body FFM, consist-ing of lean mass and bone mineral content (BMC), was

determined by scanning all patients and healthy volunteerson a DPX-L Bone Densitometer (Lunar Radation; Madi-son, WI). Lean mass depletion was found in 37% of theemphysema patients, in 12% of the chronic bronchitispatients, and in 4% of the healthy controls. Lean massdepletion was found in 16% of the emphysema patientsand in 8% of the chronic bronchitis patients, despitenormal body weights in both groups. Body weight andbody mass index (BMI) were lower in the emphysemagroup than in the healthy controls. The lower body

weights were the result of a lower lean mass index and alower BMC index. No significant differences were foundin the fat mass index between the two groups. Body

weight, BMI, lean mass index, and FFM indexes were notdifferent between the chronic bronchitis patients and thecontrol group. The chronic bronchitis patients had lower

values for BMC index and higher values for fat mass indexand percentage of body fat.

Body weight and composition were significantly differ-ent between the group with chronic bronchitis and thegroup with emphysema. The emphysema patients hadlower values for BMI, FFM index, and fat mass index thanthe group with chronic bronchitis. The lower FFM index

was the result of a lower lean mass index and a lower BMCindex. Based on these data, we can conclude that substan-tial differences in body composition can be found between

COPD patients and healthy volunteers, as well as betweenchronic bronchitis patients and emphysema patients.In a further study, the presence and contribution of

FFM depletion in the extremities was studied with respectto the problem of muscle weakness in COPD. Engelen etal14 reported that whole body and extremity FFM werelower in emphysematous and chronic bronchitis patientsthan in controls, but that trunk FFM was lower only inemphysematous patients. Extremity FFM was comparablebetween the COPD subtype patients. In both COPDgroups, absolute skeletal muscle function and musclefunction per kilogram of whole body FFM were lowerthan in healthy persons. Muscle function was comparable

in subjects with chronic bronchitis and in those withemphysema. Muscle function per kilogram of extremityFFM was not different between the studied groups and

was not related to FEV1.Therefore, it can be concluded that extremity FFM

wasting is associated with skeletal muscle weakness inde-pendent of the COPD subtype, but that marked differ-ences in body composition can be demonstrated betweenthe emphysematous patient and the patient suffering fromchronic bronchitis.

Although from a functional point of view, most attentionin body composition assessment is focused on FFM or onmuscle mass, recent data emphasize the intriguing role of

*From the Department of Pulmonology, University Maastricht,Maastricht, The Netherlands.Correspondence to: Emiel F.M. Wouters, MD, PhD, FCCP, De-

partment of Pulmonology, University Maastricht, PO Box 5800,6202 AZ Maastricht, The Netherlands; e-mail: [email protected]

274S Thomas L. Petty 42nd Annual Aspen Lung Conference: Mechanisms of COPD

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fat mass in energy homeostasis. Fat mass is not just anenergy reservoir; it plays an important role in energyhomeostasis by producing leptin. This adipocyte-derivedhormone represents the afferent hormonal signal to thebrain in a feedback mechanism that regulates fat mass.Leptin also has a regulating role in lipid metabolism andglucose homeostasis, and it increases thermogenesis.15,16

Additionally, it has effects on T-cell mediated immunity.17

Few data are reported on leptin metabolism in COPD

patients. Takabatake et al18 recently reported that serumleptin levels were significantly lower in COPD patientsthan in healthy controls. COPD patients in his study had asignificantly lower BMI and percentage of body fat thanthe healthy control subjects. Circulating leptin correlated

well with BMI and percentage of fat, as expected. Basedon the observations that administration of endotoxin orcytokines produced a prompt increase in serum leptin inanimals and in humans, the authors also related circulatingleptin to inflammatory markers. No relationship was found

with tumor necrosis factor (TNF) or with soluble TNF-receptor (sTNF-R) levels.17

Schols et al19 recently reported on leptin levels in bothsubtypes of COPD, emphysema and chronic bronchitis. Asexpected, emphysema patients had a lower BMI and alower fat mass than patients with chronic bronchitis.Leptin levels were significantly lower in the emphysema-tous group. Nondetectable levels of leptin were found in 8of 27 patients with emphysema (30%), relative to 2 of 18patients with chronic bronchitis (11%). Leptin was mod-erately related to fat mass in emphysema and in chronicbronchitis. In absolute terms, as well as adjusted for fatmass, leptin was significantly related to sTNF-R55 inemphysema patients but not in patients with chronicbronchitis. Remarkably, no differences in TNF-receptorscould be demonstrated between the two groups.

Both studies suggest a physiologic regulation of leptin,independent of TNF (at least in chronic bronchitis pa-tients), as well as a cytokine-leptin link in emphysematouspatients. The exact regulation of leptin needs furtherexploration in the near future.

Pathogenesis of Differences in Body

Composition in COPD Phenotypes

Disturbances in Energy Balance

Weight loss is generally approached on the concept of a

disturbed balance between energy expenditure and energyintake. Total energy expenditure can be considered as thescore of resting energy expenditure (REE), diet inducedthermogenesis, and energy spent during daily activities.REE comprises the sleeping metabolic rate and theenergy cost of arousal, and it amounts to about 70% oftotal energy expenditure in sedentary persons.

REE can now be adequately and easily assessed byindirect calorimetry. Initially, a lot of attention was fo-cused on assessment of resting or basal energy expendi-ture in COPD patients, assuming that the contribution ofactivity-related expenditure would be limited in this groupof impaired patients. An increased REE has been reported

in different studies.20 In the past, the increase in REE wasexplained by increases in the work of breathing21; how-ever, growing evidence exists that REE reflects the workof breathing22 rather than the level of inflammation inCOPD patients.23,24 The limited role of REE on thedevelopment of FFM depletion was demonstrated by thedata of Creutzberg et al.25 These authors demonstrated asimilar distribution of FFM depletion in normometabolicand hypermetabolic COPD patients. This observation was

supported by Baarends et al,26

who showed that there wasno significant difference in free-living total daily energyexpenditure between clinically stable patients with COPD

with an elevated REE and those with a normal REE.Variations in total daily energy expenditure reflect differ-ences in expenditure for activities but not for REE. Even inCOPD patients with severe airflow limitation, total dailyenergy expenditure was significantly higher than in healthysubjects.26 These differences can be attributed to a decreasedmechanical efficiency in COPD patients.27

Systematic analyses of dietary intake in COPD patientsare scarce. Schols et al2 reported an inadequate dietaryintake for energy expenditure, especially in the more disabled

COPD population. In a recent study, these authors foundthat sTNF-R55, a marker for inflammation, and leptin weresignificantly related to dietary intake in absolute terms as wellas adjusted for REE.19 The role of systemic inflammation wasconfirmed by the data of Creutzberg et al,28 demonstrating asignificant relationship between baseline dietary intakeand soluble intercellular adhesion molecule-1 (Fig 1).

A disturbed energy balance, at least in a subgroup ofCOPD patients, is further supported by the outcome ofnutritional intervention studies in COPD patients.29 De-spite the positive outcomes of nutritional intervention inthe majority of COPD patients, Creutzberg et al28 dem-onstrated that aging, relative anorexia and elevated sys-

temic inflammatory responses, as assessed by circulatinglevels of sTNF-R55, are associated with nonresponses tonutritional therapy.

Muscle Protein Degradation in COPD

Depletion of FFM is a prominent finding in COPDpatients. Accelerated muscle proteolysis is considered theprimary cause of the loss of lean body mass, not only inCOPD, but also in many other chronic diseases. Althoughmultiple proteolytic systems that serve distinct functionsare described in mammalian cells, the ubiquitin-protea-some pathway is the most important in the normal turn-

over of most cellular proteins and in the acceleratedbreakdown of muscle proteins in catabolic states. Theubiquitin-proteasome pathway is a multi-enzymatic pro-cess of degradation that requires adenosine 5-triphos-phate (ATP).

Activation of the ubiquitin-proteasome pathway hasbeen reported in a variety of models and clinical condi-tions.30 The regulating role of glucocorticoids on muscleproteolysis is very important. It has been clearly demon-strated, from rats in the fasting state, that glucocorticoids,together with other signals, are required to increasemessenger RNAs encoding ubiquitin and proteasomesubunits and for ubiquitin-protein conjugates in mus-

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cles.31,32 Glucocorticoids not only stimulate proteolysis,but inhibit protein synthesis and the transport of aminoacids into the muscle to promote the mobilization ofamino acids for gluconeogenesis.

Data of direct effects of inflammatory mediators ondifferentiated skeletal muscle cells are limited. Li et al33

studied underlying mechanisms of TNF-induced effects indifferentiated skeletal muscles. They demonstrated thatTNF stimulated time- and concentration-dependent re-ductions in total protein content and loss of myosin heavychain content. These changes were evident at low TNFconcentrations that did not alter muscle DNA content and

were not associated with a decrease in myosin heavy chainsynthesis. This TNF signal is transduced in part byactivation of nuclear factor-kB, a process that involvesubiquitin conjugation and proteasomal degradation ofinhibitory protein-kB. There is an urgent need for abetter understanding of the mechanisms and regulation of

protein breakdown in COPD patients to improve treat-ment prospects.

Differences in Muscular Adaptation in

COPD Subtypes

Besides these differences in body composition in pa-tients with COPD, as well as differences between emphy-sematous and chronic bronchitic patients, recent dataindicate marked modifications in the metabolic machineryand energetic system of skeletal and respiratory muscles inCOPD.

Fiber Type Composition

Fiber types can be classified based on differences inimmunoreactivity for antibodies specific to different my-osin heavy chain (MHC) isoforms. In human muscles,

three different MHC isoforms are expressed: MHC-1,MHC-2A, and MHC-2B. In the same way, myosin lightchain (MLC) isoforms can be determined. The followingMLC isoforms can be discerned: the fast and slow iso-forms of regulatory MLC (MLC-2s and MLC-2f) andthree isoforms of alkaline MLC (MLC-1s, MLC-1f, andMLC-3f). Satta et al34 studied the fiber type compositionof the musculus vastus lateralis in COPD patients. Theyreported that the proportion of the fast MHC-2B isoform

was increased in patients with COPD. While diffusingcapacity, vital capacity, and FEV1 were positively corre-lated with slow MHC isoform content, only diffusingcapacity was negatively correlated with fast MHC isoform

content. The co-ordinated expression between MHC andMLC isoforms was also altered in COPD patients, sug-gesting that the co-ordinated protein expression was lost inthe skeletal muscles of COPD patients. The authorssuggest that these changes can partially be explained byreduced availability of oxygen. An impaired diffusingcapacity is generally considered a feature of emphysema ina COPD population,13 and arterial oxygen desaturation isa frequently reported finding in patients with impaireddiffusing capacity.35 Further data on muscle compositionare needed in these COPD subtypes. The hypotheticalrole of tissue hypoxia also needs to be explored.

These adaptations of the skeletal muscle toward a

Figure 1. Energy dysbalance and inflammation. Inflammation influences energy expenditure by anincrease of REE. Inflammation negatively influences energy uptake by increasing levels of leptin, afat-derived hormone. Leptin represents the afferent hormonal signal to the brain regulating food intakeby the hypothalamic transmitter neuropeptide Y. DIT dietary intake.




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predominance of anaerobic glycolytic type 2 muscle fibersaffect the aerobic capacity of the muscle and may causethe type 2 predominant muscle to be more prone tofatigue, because anaerobic fibers synthesize ATP lessefficiently than aerobic metabolism, and because produc-tion of lactic acid is marked higher. 3638

Interestingly, opposite changes seem to occur in thediaphragms of patients with COPD. Levine et al39 reportedincreases of slow MHC-1 and lower percentages of MHC-2A

and MHC-2B in diaphragms of COPD patients, suggestingan adaptation that increases resistance to fatigue.

Biochemical Adaptations of Muscle Metabolism inCOPD Subtypes

Early lactic acidosis during exercise is reported in asignificant number of COPD patients.40 Maltais et al41

compared the arterial lactic acid kinetics during exercise tothe oxidative capacity of the skeletal muscles in COPDpatients. Muscle biopsies were taken from the musculus

vastus lateralis. These authors reported significantly lower

activity of the oxidative enzymes in COPD patients.Furthermore, the relationship of lactic acid to oxygenconsumption during exercise was significantly related tothe reduced oxidative capacity. Oxidative capacity in thisstudy was assessed by citrate synthase, catalyzing the firststep of the Krebs cycle, and by 3-hydroxyacyl CoA dehy-drogenase, involved in the fatty acid oxidation. Afterendurance training, the same authors reported a signifi-cant inverse relationship between the percentage changesin the activity of citrate synthase and 3-hydroxyacyl CoAdehydrogenase and the percentage changes in arteriallactic acid during exercise.42 It remains unclear if thedecrease in oxidative capacity can be attributed to changesin muscle structure or to intrinsic adaptations of musclemetabolism.

Besides changes in enzyme concentrations, differencesin intermediary metabolites can explain differences inlactate kinetics. Engelen et al43 investigated the exercise-induced lactate response in COPD patients, stratified inpatients with emphysema and chronic bronchitis, based onhigh-resolution CT findings. Lactate response in COPDpatients was compared with groups of control subjects,physically active and physically inactive. Lactate responseto exercise was steeper in the emphysema group than inthe chronic bronchitis group or in the physically inactive

group. Lactate steepness during exercise was higher in thechronic bronchitis group than in the physically inactivegroup. A significant linear relationship was found betweenmuscle glutamate (GLU) and lactate steepness duringexercise. It can be hypothesized that decreases in muscleGLU can have different effects on lactate metabolism.The decreased GLU concentration can induce a shift inthe alanine aminotransferase reaction, resulting in anincrease of pyruvate concentration and, secondarily, inlactate concentration. A decrease in alanine aminotrans-ferase activity can also result in a decreased influx of Krebscycle metabolites, resulting in an impaired Krebs cycleactivity. Decreased muscle GLU concentrations in the

presence of marked elevated glutamine concentrations inmuscle biopsies were reported by Pouw et al.23

Little information is yet available on lactate metabolismin COPD. In general, an increase in lactate productionleads to an enhanced liver lactate uptake and an increasein liver gluconeogenesis. However, hypoxia causes a clearinhibition in GLU at the phosphoenolpyruvatekinase level:the transcription of phosphoenolpyruvatekinase is de-pressed under hypoxic conditions.44 In vivo studies in

COPD patients are needed to investigate lactate metabo-lism.

Lactate might be viewed as a key metabolic event,permitting the metabolism to modify according to hypoxicconditions, as frequently found in patients with COPD.According to this hypothesis, the increased lactate can beconsidered as a metabolic tool, permitting the oxidation ofeither lactate or glucose as aerobic substrates, according toa metabolic priority, yet sparing glucose for privilegedtissues like the heart.45

Energy and Mitochondrial Metabolism in COPD

In mammals, there is a very tight connection betweenoxygen consumption and ATP production and utilization;90% of oxygen consumption is responsible for 90% of ATPsynthesis, and 10% of ATP synthesis in our body isindependent of oxygen. Under normal conditions, the rateof oxygen delivery to the cell must be precisely adjusted toavoid excessive free radical production. The mitochondrialrespiratory chain is an essential element in the transduc-tion of energy during life. Mitochondria occupy a pivotalposition in aerobic ATP reduction through oxidative phos-phorylation of adenosine diphosphate (ADP). All energy-producing reactions generate reducing equivalents in the

form of reduced nicotinamide adenine dinucleotide(NADH) and reducing flavins, which are ultimately oxi-dized by oxygen through a chain of oxidoreduction reac-tions occurring in complexes that reside in the innermitochondrial membrane.46 This process of oxidativephosphorylation is pushed by the redox potential (NADH/NAD) and is limited by the phosphate potential (ATP/ADP.Pi).

Experimental data on muscle energy and mitochondrialmetabolism in patients with stable COPD are scarce. Arecent study reported on subcellular adaptations of thehuman diaphragm in patients with COPD.47 Patients

suffering from COPD showed a higher mitochondrialdensity than subjects without airways obstruction. Fur-thermore, an inverse correlation was found between thedegree of airways obstruction and mitochondrial density.Mitochondrial density was directly related to the level ofhyperinflation and indirectly related to respiratory musclefunction. In addition, clusters of mitochondria as well asmitochondrial paracrystalline inclusions were frequentlyfound in COPD patients. These changes in the concen-tration of energetic organelles are in accordance with apersistent mechanical overload of the respiratory muscles,

while the presence of paracrystalline inclusions probablyreflect metabolic mismatching in the mitochondria.




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Sauleda et al48 reported that COPD patients with chronicrespiratory failure showed increased cytochrome oxidase(COX) activity, and that COX activity was inversely relatedto arterial oxygen tension. However, COX messengerRNA was not different between patients and controlsubjects. These data suggest adaptations of COX muscleactivity under hypoxemic conditions, regulated at thetranslational level by increasing the number of mitochon-drial ribosomes.

The application of 31 P-nuclear magnetic resonance hasenabled a direct and noninvasive assessment of tissuelevels of high-energy phosphates and pH, even underdynamic conditions such as exercise testing. High levels ofATP, creatine phosphate (PCr) and NADH reflect a highenergy state, whereas elevated levels of ADP, adenosinemonophosphate, inorganic phosphate (Pi) and oxidizedNAD commonly reflect a low energy state. The PCr/Piratio or phosphorylation potential is an important measureof the energy status of the cell and can be used todetermine the adequacy of energy reserves for vital func-tions. The PCr/Pi ratio is thought to be closely related tothe ATP/ADP ratio, and a reduction of the ratio reflects an

impairment in the oxidative metabolism of the muscle.Energy-rich phosphagens can also be analyzed in musclesamples obtained by muscle biopsy.

Most striking are the reduced levels of the high energyphosphates in rest observed in COPD patients. Pouw etal49 found a lower phosphocreatine/creatine ratio and alower ATP/ADP ratio in COPD patients. Furthermore,she reported that inosine monophosphate levels (IMP)

were slightly, but statistically significantly elevated inCOPD patients. The latter may be due to increaseddegradation of accumulating adenosine monophosphateby deamination, which probably reflects reduced aerobiccapacity.50 Remarkably, IMP-positive COPD patients

were characterized by a significantly lower diffusing ca-pacity. IMP levels were negatively related to the ATP/ADP ratio, suggesting an imbalance between ATP utiliza-tion and resynthesis. The insufficient energy supply is evenmore prominent during exercisea marked drop in thePCr/Pi ratio and a fast drop in pH were found in the calfmuscles of COPD patients5153 performing exercise, andsimilar results were obtained in the forearm muscles.5457

Marked acidification of the exercising muscle demon-

strates lactate accumulation. Nuclear magnetic resonancestudies also have demonstrated a delayed recovery ofPCr/Pi ratio and of pH in COPD patients.57 Besidesintrinsic changes in muscle metabolism, contributing toimpaired aerobic capacity, an increased percentage of type2B fiber contributes to a reduced PCr/Pi during exerciseand delays recovery of PCr/Pi after exercise.52,57 Furtherdata are needed to unravel the disturbed energy supply inCOPD in view of the metabolic alterations, the shifts infiber composition, and the subcellular changes in COPD.

Conclusion

Recent research has clearly demonstrated that COPD ischaracterized by complex metabolic disturbances. Furtherstudies need to unravel the complexity of metabolicalterations related to inflammation, hypoxia, hypercapnia,and energy deprivation. It has become clear that differentfactors contribute to muscle alterations in COPD and thatthe relative contribution of each factor can differ betweenpatients as well as between muscle types. Based on theimportant role of muscle function on experienced morbid-ity and quality of life, treatment needs to be based onadequate characterizations of patients. These characteriza-tions need to include, at least, assessments of skeletal andrespiratory muscle function and muscle mass (Fig 2).

Figure 2. Characterization of COPD.




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Comparison of Bone MineralDensity in Elderly FemalePatients With COPD andBronchial Asthma*

Hideki Katsura, MD; and Kozui Kida, MD, FCCP

(CHEST 2000; 117:280S)

Abbreviations: BA bronchial asthma; BMD bone mineraldensity

It is well recognized that osteoporosis and bone fracturesare common diseases that adversely affect the activities

of daily living and quality of life of many elderly patients,especially women. Recent studies have shown that osteo-porosis is quite common in patients with end-stage pul-monary diseases, such as cystic fibrosis, and COPD pa-tients who are candidates for lung transplantation. Suchstudies also have demonstrated an association betweenchronic systemic corticosteroid use and lower bone min-eral density (BMD) in these lung diseases. However, theassertion that COPD patients who have never receivedsystemic corticosteroids have a high incidence of osteopo-rosis remains controversial. We tested the hypothesis thatosteoporosis is worse in elderly COPD compared withbronchial asthma (BA) patients. A total of 44 elderlyfemale patients with mild to moderate COPD (n 20) orBA (n 24) who had not received any systemic cortico-steroids were enrolled. Total body and lumbar BMD weremeasured by dual energy x-ray absorptiometry along withbone metabolism markers, biochemical, lifestyle, and an-

thropometric variables, and the data were compared be-tween the two groups. When lumbar BMD was expressedas z score, representing the number of standard deviationsbetween a patients BMD and the age- and body weight-matched mean BMD, z scores for patients with COPD

were significantly lower than that of patients with BA(1.08 0.34 vs 0.33 0.27; p 0.01). In COPD, bodymass index was significantly lower than in BA (22.0 0.8

vs 24.6 0.9; p 0.04), and this was positively correlatedwith BMD (lumbar spine, r 0.55, p 0.02; total body,r 0.49, p 0.03). Other biochemical and anthropomet-ric valuables showed no correlation with BMD. We con-clude that in elderly female patients, osteoporosis is worsein COPD than in BA. The reason for this difference isuncertain; however, it should be noted that the worseningof osteoporosis debases activities of daily living and in-creases the chance of acute exacerbation because ofsuppressed expectoration due to uncontrolled body pain.

*From the Pulmonary Division, Tokyo Metropolitan GeriatricHospital, Tokyo, Japan.Correspondence to: Hideki Katsura, MD, Pulmonary Division,Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-Cho, Ita-

bashi, Tokyo, 173-0015 Japan

280S Thomas L. Petty 42nd Annual Aspen Lung Conference; Mechanisms of COPD



9/9

DOI 10.1378/chest.117.5_suppl_1.274S2000;117; 274S-280SChest

Emiel F.M. Wouters

*Nutrition and Metabolism in COPD

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