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
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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
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