Doi:10.1016/j.pcrj.2005.09.00

Primary Care Respiratory Journal (2006) 15, 84—91
COPD as a multicomponent disease: Inventory
of dyspnoea, underweight, obesity and fat free
mass depletion in primary care

Lotte M.G. Steuten , Eva C. Creutzberg ,
Hubertus J.M. Vrijhoef
, Emiel F. Wouters
a Department of Health Care Studies, Faculty of Health Sciences, Maastricht University,P.O. Box 616, 6200 MD Maastricht, The Netherlandsb Centre for Integrated Rehabilitation and Organ Failure (CIRO), Horn; Clinical Research Unit,Horn, The Netherlandsc Department of Respiratory Medicine, University Hospital Maastricht, Maastricht,The Netherlandsd Department of Integrated Care, University Hospital Maastricht, Maastricht, The Netherlands Received 27 April 2005; accepted 15 September 2005 KEYWORDS
Aims: To describe the distribution of COPD disease severity in primary care based on airway obstruction, and to assess the extent to which dyspnoea scores, body mass index (BMI) and fat free mass (FFM) index contribute to the distribution of COPD severity in primary care.
Design: Cross sectional population-based study.
Methods: 317 patients with COPD were recruited from an outpatient diseasemanagement programme. Prevalence of moderate to severe dyspnoea, underweight,obesity and FFM depletion by GOLD stage were measured.
Results: According to GOLD guidelines, 29% of patients had mild COPD, 48%moderate, 17% severe and 5% very severe. A substantial number of patients classifiedas GOLD stage 2 reported severe dyspnoea (28.1%) and/or suffered from FFMdepletion (16.3%). Prevalence of low body weight strongly increased in GOLD stage4. Prevalence of obesity is highest in GOLD stages 1 and 2.
Conclusion: The use of a multidimensional grading system, taking into accountdyspnoea as well as the nutritional status of COPD patients, is likely to influencethe distribution of disease severity in a primary care population. This might have ∗ Corresponding author. Tel.: +31 43 3881557; fax: +31 43 3884162.
E-mail address: L.Steuten@zw.unimaas.nl (L.M.G. Steuten).
1471-4418/$30.00 2005 General Practice Airways Group. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.pcrj.2005.09.001 implications for prevention, non-medical treatment, and estimates of health careutilisation in primary care.
2005 General Practice Airways Group. Published by Elsevier Ltd. All rights reserved.
Introduction
hand, is strongly associated with an increase indyspnoea, both in the general population as well Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation Dyspnoea represents the most disabling symptom that is not fully reversible. The airflow limitation of COPD and is a better predictor of the risk of death is usually both progressive and associated with an than is the FEV1 Both the GOLD guidelines abnormal inflammatory response of the lungs to noxious particles or gases. The most important recommend that a patient’s perception of dyspnoea cause of COPD is a long-term smoking history should be included in any new staging system for COPD. The degree of dyspnoea can be measured morbidity worldwide and is predicted to become with the MRC dyspnoea scale which correlates the third most frequent cause of death and the fifth with other dyspnoea scales and scores of health leading cause of disability by the year 2020 status Moreover, it is simple to administer Moreover, the condition is often under-diagnosed and therefore feasible to apply in a primary care The Global Initiative for Chronic Obstructive Given the above, and in accordance with the Lung Disease (GOLD) guidelines established a BODE-study it is desirable to pay attention definition as well as a classification system of to respiratory, perceptive and systemic aspects in airway obstruction The diagnosis of COPD is order to produce a composite picture of disease confirmed by a reduced forced expiratory volume severity of COPD. The BODE-study, however, was performed in a secondary care setting with a of COPD, varying from stage 0 with patients group of elderly patients, most of them suffering being ‘at risk’, to stage 4 for patients with ‘very severe COPD’. Although spirometric classification representative of a primary care population.
has proved to be useful in predicting health Moreover, despite data describing the prevalence status utilization of healthcare resources of COPD, the distribution of disease severity in the development of exacerbations and mortality primary care population is mainly unknown in COPD, it is generally accepted that a single Therefore, the aims of this study were: (1) to describe the distribution of COPD disease severity represents the complex clinical consequences of in primary care based on airway obstruction; COPD. Other risk factors such as the presence and (2) to assess the extent to which dyspnoea of hypoxemia or hypercapnia, a short distance scores, BMI and FFM index contribute to the walked in a fixed time, a high degree of functional distribution of COPD severity in primary care.
breathlessness, as well as a low body mass and/or In addition, we investigated any differences fat free mass (FFM) index, are associated with an between the proportion of males and females within each GOLD stage suffering from severe As in other chronic inflammatory conditions, dyspnoea, underweight, obesity or depleted FFM.
weight loss and tissue depletion are commonly The potential impact of exercise capacity on disease severity in a primary care population was tissue depletion varies from 20% in clinically not studied, since it is not feasible to perform stable outpatients up to 35% in patients who are routinely the six-minute walking test in this setting, eligible for pulmonary rehabilitation. In addition, given the number of patients, the lack of machinery the selective wasting of FFM despite relative in the GPs’ offices, and the limited time for preservation of fat mass, has been reported in COPD patients. Loss of FFM adversely affects respiratoryand peripheral muscle function, exercise capacityand health status and several studies using different COPD populations have convincinglyshown that a low body mass index (BMI), low FFM, and weight loss are associated with an increased and March 2003 from an outpatient disease management program that was implemented in the Maastricht region of the Netherlands (NL).
affects their mobility. Disability was defined Twenty general practitioners (GPs) from 16 general according to the WHO definition of disability, practices participated in the programme. Inclusion being ‘any restriction or lack of ability to perform criteria were: diagnosis of COPD, based on an activity in the manner or within the range spirometry; and age ≥18 years. Exclusion criteria considered normal for a human being’ The were: serious co-morbidity such as lung cancer or MRC dyspnoea scale consists of five statements congestive heart failure. Following a well-defined being: 1 = ‘I only get breathless with strenuous procedure, respiratory nurse specialists evaluated exercise’; 2 = ‘I get short of breath when hurrying respiratory symptoms and lung function of patients on the level or up a slight hill’; 3 = ‘I walk slower submitted by the GPs. This procedure took place in than people of the same age on the level because the primary care setting. Diagnosis and definition of of breathlessness or have to stop for breath COPD severity was established in accordance with when walking at my own pace on the level’; the GOLD guidelines by the core team consisting 4 = ‘I stop for breath after walking 100 meters or of a pulmonologist, a GP and a nurse specialist.
after a few minutes on the level’; 5 = ‘I am too GOLD stage 0 (at risk) is diagnosed when patients breathless to leave the house’. Patients select report chronic cough and sputum production whilst the grade that applies to them. Patients are their lung function is still normal. GOLD stage 1 considered moderately or seriously disabled due to (mild COPD) is defined as a ratio of FEV1/forced breathlessness if their MRC score is ≥3 since this vital capacity (FVC) <70% but with the FEV1 ≥ 80% is associated with worsening of exercise tolerance, predicted. GOLD stage 2 (moderate COPD) is diagnosed if the FEV1 is between 50% and 80%predicted. Gold stage 3 (severe COPD) is defined Anthropometrical measurements
as an FEV1 between 30% and 50% predicted, andGOLD stage 4 (very severe COPD) is diagnosed if Measurement of height was made by clinical FEV1 is less than 30% predicted. Patients with a stadiometer in bare or stocking feet. Body weight confirmed diagnosis of COPD were included in the was measured with a calibrated precision scale with study. Written informed consent was obtained from subjects wearing their normal clothes but without shoes. To correct for this, 1 kg of the measuredbody weight was subtracted for each person. BMI, Lung function measurements
defined as weight (kilograms) divided by the squareof height (meters), was calculated. Patients were Post-bronchodilator FEV1 was measured according considered underweight if their BMI was ≤21 kg/m2, to the ATS criteria before and after administration of a bronchodilator (salbutamol, 400 ␮g) using ahand held spirometer (Vitalograph; Vitalograph Measuring fat free mass
Ltd, Buckingham, United Kingdom). Patients wereinstructed not to use bronchodilators on the day of pulmonary function assessment or at least bioelectrical impedance analysis with the Bodystat not within six hours before measurement. Nurse 1500 (Bodystat Ltd; Isle of Man, British Isles).
specialists were specially trained to perform the Injector electrodes are placed on the dorsal pulmonary function measurements. Spirometers surfaces of the foot and wrist, and detector were calibrated daily. All patients were studied electrodes are placed between the radius and in a sitting position. Data from the flow-volume ulna (styloid process) and at the ankle (between curve with the highest sum of FVC and FEV1 were the medial and lateral malleoli). The FFM-index used for calculations. FEV1 was expressed as FEV1% (FFMI) was calculated from height2/resistance and predicted, based on gender, height, and age, using body weight using a regression formula corrected the reference values of the European Respiratory for COPD. Patients were considered as having a depleted FFM if FFMI ≤15 kg/m2(women) or Dyspnoea measurement
Statistical considerations
The Medical Research Council (MRC) scale wasused for grading the effect of breathlessness on Patients were classified by means of lung function daily activities. The scale measures perceived (GOLD stage), MRC score, BMI and FFMI. Descriptive respiratory disability by allowing patients to statistics were applied in order to identify the indicate the extent to which their breathlessness prevalence of GOLD stages in a primary care population. Also, the numbers of patients classified in GOLD stages 0, 1 or 2, whilst having an an MRC score ≥3, a BMI ≤21 kg/m2 or >30 kg/m2, MRC score ≥3, or a BMI either ≤21 kg/m2 or or a FFMI ≤15 kg/m2 (women) or ≤16 kg/m2 >30 kg/m2, or a FFMI ≤15 kg/m2 (women) or (men), by GOLD stage. A substantial proportion of ≤16 kg/m2 (men), were computed. Differences GOLD 2 patients reported severe dyspnoea (28.1%) in baseline characteristics between GOLD stages and/or suffered from FFM depletion (16.3%). The were assessed for statistical significance at ˛ = 0.05 prevalence of low body weight increased by 10% using independent-samples t-tests for normally over GOLD stages 1 to 3, but strongly increased distributed data and Mann-Whitney-U-tests for the in GOLD stage 4. The prevalence of obesity was variables sex and smoking. Potential differences between the proportion of males and females Significant sex differences were found with suffering from severe dyspnoea, underweight, regard to FFM-depletion in GOLD stage 2 (p = 0.002) obesity or depleted FFM within each GOLD stage and severe dyspnoea in GOLD stage 3 (p = 0.021).
were analysed with Chi-square tests at a 5%uncertainty level. All analyses were performedusing the Statistical Package for Social Sciences Discussion
(SPSS Inc., Chicago, IL, U.S.A.). All data arepresented as means (±sd) unless stated otherwise.
In this study the distribution of COPD severityin an outpatient population has been assessedaccording Moreover, the proportion of patients withmild to moderate COPD (GOLD stage 1 and 2) suffering from severe dyspnoea, underweight, obesity or FFM-depletion was investigated. Also, 317 subjects with a diagnosis of COPD are shown gender prevalence differences with regard to these patients were classified as having mild COPD, 48% In terms of our first research question on the as moderate, 17% as severe and 5% as very severe.
distribution of COPD disease severity, 77.8% of The relative number of females decreased with patients had mild or moderate COPD, and 22.2% increasing severity of the disease. The percentage had severe or very severe disease as defined by of smokers was highest in the GOLD 2 group (48.3%), GOLD criteria. The distribution of disease severity while the average number of pack years smoked in primary care in this study compares well with was highest in GOLD 3 (40.2 ± 25.1 yrs). The other studies performed in The Netherlands and average number of pack years differed between the UK. The relatively small number of females in men (32.6 ± 21.8) and women (27.3 ± 15.2), this GOLD stages 2, 3 and 4 might be explained by lower difference being statistically significant (p = .034) prevalence rates of COPD for women as previously (Students t-test, two-sided with ˛ = .05).
reported by Feenstra et al. Also, it may be Baseline characteristics categorized by GOLD stage.
* Indicates statistical significant difference between this GOLD stage and the preceding one, tested with an independent- samples t-test or a Mann-Whitney-U test when appropriate (˛ = 0.05).
influenced by the lower number of smoking pack years in women, as found in this study, or genderdifferences in occupational exposures With respect to our second objective, we found that a substantial proportion of primary care patients with mild to moderate COPD reported moderate to severe dyspnoea (mild 9.7%; moderate 28.1%) and/or serious muscle wasting (mild 11.8%;moderate 16.3%). Prevalence of low body weight only strongly increased in patients with very severe COPD while prevalence of obesity was highest among patients with mild to moderate COPD.
Gender differences were found with regard to depleted FFM in GOLD stage 2 and severe dyspnoeain stage 3. It needs to be stressed that the prevalence of FFM depletion within an outpatient population is normally found to be around 25%,independently from disease severity, as compared to the prevalence of 11.8% to 16.3% that we found in this study. Consequently, our data seem tobe underestimating the potential impact of FFM- depletion on distribution of disease severity in primary care, rather than overestimating.
The study results suggest that the use of a multidimensional grading system which takes the nutritional status of COPD patients into account as well as dyspnoea, is likely to influence the distribution of COPD severity in a primary care population. However, the exact impact of using such a multidimensional system instead of the GOLD criteria is hard to assess because not all necessary data are available in primary care. For example, the multidimensional grading system as proposed by Celli et al. seems difficult to apply in primary care since data on exercise capacity are generally not available here. Data on FFM, however, are more commonly available and they have been shown to be strongly related to exercise capacity Measures of BMI on the other hand were found to be of relatively less importance in determining disease severity, as has also been reflected in the BODE-index where relatively little weight was attached to changes in BMI Therefore, more emphasis might be placed on assessing body composition in primary care, and it seems worthwhile to include this measure in a multidimensional grading system.
A shift in severity distribution might have treatment, and estimates of health care utilisation.
Firstly, since the majority of patients in primary care suffer from mild to moderate COPD, they are at risk of deterioration in their disease with increasing age. Also, many of these patients are still current smokers, with smoking prevalence rates of 43.5% in mild COPD and 48.3% in moderate disease.
Since smoking cessation reduces the subsequent rate of lung function decline in patients with mild advice is also worthwhile since obesity is associated to moderate airflow limitation the chief benefits of smoking cessation are to be expected Overall, the results of this study imply that in these patient groups. A combined strategy of awareness of dyspnoea and of the nutritional nicotine-replacement therapy with counselling or aspects of COPD is necessary in order to avoid antidepressants (bupropion or nortryptiline) with underscoring COPD disease severity in primary care.
counselling, in which the physiological as well as This should be accomplished by integrating simple the psychological aspects of smoking cessation are measurements of dyspnoea and nutritional status within classification systems for disease severity.
Secondly, a substantial proportion of patients classified in GOLD stage 1 or 2 already show smoking cessation, exercise training and nutritional symptoms of moderate to severe disability due to interventions can be used as a means of secondary dyspnoea and/or serious muscle wasting. Previous prevention Furthermore, these findings have studies have suggested that any given FEV1 may be implications for the estimation of the future burden associated with a wide range of disability of COPD in terms of health care utilisation therefore that direct measurements of disability Since health care utilisation is commonly matched are clearly complimentary in assessing the severity to stages of disease severity (commonly the GOLD of disease. Moreover, dyspnoea is a better predictor stages), the estimated amount of health care utilisation within a specific disease stage and Thirdly, both retrospective and prospective within a specific time lag needs to be recalculated studies within several COPD populations provide when the distribution of patients over these evidence for a relationship between low BMI and disease severity stages changes. Not only patient higher mortality rates with relative risks numbers per severity stage will change, but from ranging from 1.42 in women to 1.64 in men previous studies it is also known that low BMI as well as depleted FFM are related to higher underweight patients are more dyspnoeic than utilisation of, for example, in-patient services normal weight patients, partly as a consequence The relationship between MRC score and health of decreased respiratory muscle strength The care utilisation needs to be investigated more functional consequences of being underweight but extensively for this purpose. In addition, mortality also of having FFM depletion have been reflected rates per severity stage need to be adjusted in a decreased health status as measured by the because of the impact that dyspnoea, BMI and FFM St. George’s Respiratory Questionnaire (SGRQ) and decreased physical functioning. Depletion ofFFM caused greater impairment in the activityand impact scores of the SGRQ than weight loss Conflict of interest
The specific relationship between FFM andmortality was first reported by Marquis et al.
demonstrating that a small midthigh musclecross-sectional area and FEV1 were found to bethe only significant predictors of mortality in References
patients with stable COPD (mean FEV1 42 ± 16%predicted). Recently, Schols et al. have shown [1] Pauwels RA, Buist S, Calverly PMA, Jenkins CR, Hurd that FFM (relative risk: 0.90; 95% CI: 0.48, 0.96; SS. Global Strategy for the Diagnosis, Management andPrevention of Chronic Obstructive Pulmonary Disease.
p = 0.003) is an independent predictor of mortality NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) Workshop Summary. Am J Respir Crit Care Several studies have shown that restoration of the distorted energy balance by nutritional support, [2] Murray CJ, Lopez AD. Alternative projections of mortality in combination with training or revalidation, results and disability by cause 1990—2020: Global Burden ofDisease Study. The Lancet 1997;349:1436—42.
in a significant increase in body weight, fat-free [3] Wouters EF. Economic analysis of the Confronting COPD mass, respiratory muscle function and even in survey: an overview of results. Respir Med 2003;97:S3—14.
[4] Ferrer M, Alonso J, Morera J, et al. Chronic obstructive nutritional support for severely underweight COPD pulmonary disease stage and health-related quality of life.
patients may only have limited effect on the [5] Friedman M, Serby C, Menjoge S, Wilson J, Hileman D, recovery of functional exercise abilities, because Witek T. Pharmacoeconomic evaluation of a combination compliance appears to be difficult For the of ipratropium plus albuterol compared with ipratropium obese patients in these GOLD stages, nutritional alone and albuterol alone in COPD. Chest 1999;115:635—41.
[6] Burge PS, Calverley PM, Jones PW, Spencer S, Anderson JA, [25] Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Maslen TK. Randomised, double blind, placebo controlled Wedzicha JA. Usefulness of the MRC dyspnoea scale as a study of fluticasone propionate in patients with moderate to measure of disability in patients with chronic obstructive severe chronic obstructive pulmonary disease: the ISOLDE pulmonary disease. Thorax 1999;54:581—6.
[26] Mahler DA, Einberg DH, Wells CK, Feinstein AR. The [7] Celli BR, Cote CG, Marin JM, et al. The body-mass index, airflow obstruction, dyspnoea, and exercise capacity agreement, and physiologic correlates of two new clinical index in chronic obstructive pulmonary disease. NEJM [27] Hajiro T, Nishimura K, Tsukino M, Ikeda A, Koyama [8] Nocturnal Oxygen Therapy Trial Group. Continuous or H, Izumi T. Comparison of discriminative properties nocturnal therapy in hypoxemic chronic obstructive among disease-specific questionnaires for measuring health pulmonary disease: a clinical trial. Ann Intern Med related quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157: [9] The Intermittent Positive Pressure Breathing Trial Group.
Intermittent positive pressure breathing therapy of chronic obstructive pulmonary disease: a clinical trial. Ann Intern et al. A dynamic population model of disease progression in COPD. Eur Respir J 2005;26:223—33.
[10] Gerardi DA, Lovett L, Benoit-Connors ML, Reardon JZ, [29] Quanjer PH, Tammeling GJ, Cotes JE, Pedersen OF, Peslin ZuWallack RL. Variables related to increased mortality R, Yernault JC. Lung volumes and forced ventilatory flows.
following outpatient pulmonary rehabilitation. Eur Respir Report Working party Standardization of Lung Function Tests, European Community for Steel and Coal; Official [11] Nishimura K, Izumi T, Tsukino M, Oga T. Dyspnoea is a Statement for the European Respiratory Society. Eur Respir better predictor of 5-year survival than airway obstruction in patients with COPD. Chest 2002;121:1434—40.
[12] Schols AM, Slangen J, Volovics L, Wouters EF. Weight loss is a reversible factor in the prognosis of chronic obstructive pulmonary disease. Am J Respir Crit Care Med chronic obstructive pulmonary disease. Nutrition 2003;19: [13] Landbo C, Prescott E, Lange P, Vestbo J, Almdal TP. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med aging and smoking on the future burden of chronic obstructive pulmonary disease. Am J Respir Crit Care Med [32] Varkey AB. Chronic obstructive pulmonary disease in chronic obstructive pulmonary disease. Am J Clin Nutr women: exploring gender differences. Curr Opin Pulm Med [15] Wouters EF, Creutzberg EC, Schols AM. Systemic effects in [33] Le Moual N, Kennedy SM, Kauffman F. Occupational exposures and asthma in 14,000 adults from the general [16] Baarends EM, Schols AM, Mostert R, Wouters EF. Peak population. Am J Epidemiol 2004;160:1108—16.
exercise response in relation to tissue depletion in patients [34] Franssen FME, Broekhuizen R, Janssen PP, Wouters EFM, with chronic obstructive pulmonary disease. Eur Respir J Schols AMWJ. Effects of whole-body exercise training on body composition and functional capacity in normal-weight [17] Palange P, Forte S, Felli A, Galassetti P, Serra P, Carlone patienst with COPD. Chest 2004;125:2021—8.
S. Nutritional state and exercise tolerance in patients with [35] Anthonisen NR. Smoking, lung function, and mortality.
[18] Engelen MP, Schols AM, Does JD, Wouters EF. Skeletal muscle [36] Wagena EJ, Huibers MJ, Van Schaijk CP. Therapies for weakness is associated with wasting of extremity fat-free smoking cessation (antidepressants, nicotine replacement mass but not with airflow obstruction in patients with and counselling) and implications for the treatment of chronic obstructive pulmonary disease. Am J Clin Nutr patients with chronic obstructive pulmonary disease. Ned Tijdsch Geneeskd 2001;145(31):1492—6 (in Dutch).
[19] Palange P, Forte S, Onorati P, et al. Effect of reduced body [37] Sahebjami H, Sathianpitayakul E. Influence of body weight weight on muscle aerobic capacity in patients with COPD.
in emphysema. Am J Respir Crit Care Med 2000;161: [20] Mostert R, Goris A, Weling-Scheepers C, Wouters EF, Schols [38] Shoup R, Dalsky G, Warner S, et al. Body composition and AM. Tissue depletion and health related quality of life in health-related quality of life in patients with obstructive patients with chronic obstructive pulmonary disease. Respir airways disease. Eur Respir J 1997;10:1576—80.
[21] Schols AM. Nutrition in chronic obstructive pulmonary muscle cross-sectional area is a better predictor of disease. Curr Opin Pulm Med 2000;6:110—5.
mortality than body mass index in patients with chronic [22] Berner YN. The contribution of obesity to dyspnoea in obstructive pulmonary disease. Am J Respir Crit Care Med elderly people. Age Ageing 2001;30(6):530.
[23] Ho SF, O’Mahony MS, Steward JA, Breay P, Buchalter M, Burr [40] Efthimiou J, Fleming J, Gomez C, Spiro SG. The effect of ML. Dyspnoea and quality of life in older people at home.
supplementary oral nutrition in poorly nourished patients with chronic obstructive pulmonary disease. Am Rev Respir [24] Definitions, epidemiology, pathophysiology, diagnosis, and staging. Am J Resp Crit Care Med 1995;152(Suppl): [41] Whittaker JS, Ryan CF, Buckley PA, Road JD. The effects of refeeding on peripheral and respiratory muscle function in malnourished chronic obstructive pulmonary disease [44] Fuenzalida CHE, Petty TL, Jones PLM, Hambridge HM. The patients. Am Rev Respir Dis 1990;142:283—8.
immune response to short-term nutritional intervention in [42] Rogers RM, Donahoe M, Costantino J. Physiologic effects of advanced chronic obstructive pulmonary disease. Am Rev oral supplemental feeding in malnourished patients with chronic obstructive pulmonary disease. Am Rev Respir Dis [45] Ferreira IMB, Brooks D, Lacasse Y, Goldstein RS. Nutritional support for individuals with COPD: a meta-analysis. Chest [43] Schols AMWJ, Soeters PB, Mostert RM, Pluymers RJ, Frantzen PJ, Wouters EFM. Physiological effects of [46] Decramer M, Gosselink R, Troosters T, Verschueren M, Evers nutritional support and anabolic steroids in COPD patients.
G. Muscle weakness is related to utilization of health care Am J Respir Crit Care Med 1995;152:1268—74.
resources in COPD patients. Eur Respir J 1997;10:417—23.

Source: http://www.fightmalnutrition.eu/fileadmin/images/home_care/literatuur/Steuten__Prim_Care_Resp_J_2005.pdf

January 2005.pdf

Newsletter of the Pennsylvania Health Law Project Statewide Help Line: 1-800-274-3258 On the Internet: www.phlp.org TTY: 1-866-236-6310 Medical Assistance to Change in Rural PA on March 1 Access Plus to Feature Disease Management, Require Referrals in 42 Counties Last year DPW decided for the foreseeable future not to expand HealthChoices (mandatory man-aged care for MA recipients) b

Pone.0001350 1.5

External Validation of a Measurement Tool to AssessSystematic Reviews (AMSTAR)Beverley J. Shea1,2*, Lex M. Bouter3, Joan Peterson4, Maarten Boers5, Neil Andersson1,6, Zulma Ortiz7, Tim Ramsay4, Annie Bai8, Vijay K. Shukla8,Jeremy M. Grimshaw41 Community Information and Epidemiological Technologies (CIET), Ottawa, Ontario, Canada, 2 Institute for Research in Extramural Medicine (EMGOInstitute), Vr

Copyright ©2018 Drugstore Pdf Search