694

CHEST Original Research

COPD
Original Research
T
he fundamental role played by GOLD (Global
Initiative for Chronic Obstructive Lung Disease)
from 2001 to date to inuence all aspects of COPD
cannot be underestimated.
1
It has helped to system-
atize diagnosis and treatment of this condition, both
in developed and in developing countries, all aimed
to reduce the individual and population burden of
COPD. COPD is considered now a common, prevent-
able, and treatable disease, characterized by airow
limitation that is usually progressive and associated
with an enhanced chronic inammatory response in
the airways and the lung to noxious particles or gases.
Exacerbations and comorbidities contribute to the
overall severity in individual patients.
2
COPD results
from inammation and/or alterations in repair mech-
anisms. The spillover of inammatory mediators from
the respiratory system into the circulation or systemic
inammation may also initiate or worsen comorbid
diseases, such as ischemic heart disease, heart failure,
osteoporosis, normocytic anemia, lung cancer, depres-
sion, and diabetes.
3

Spirometry is recognized by international clinical
guidelines as the essential test to diagnose COPD
and stage severity, based on different transformations
of the FEV
1
and other lung function variables. Indeed,
the GOLD report of 2001 and its update in 2006 rec-
ommended the staging of COPD severity according
to spirometry only.
4
However, the new GOLD update
(as of December 30, 2011) includes airow limitation,
history of COPD exacerbations, and symptoms to
classify and grade COPD severity.
2
Given recent evi-
dence on the progression and natural history of air-
ow limitation in COPD, staging was substituted for
grading to assess COPD severity in four mutually
Background: The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) update
includes airow limitation, history of COPD exacerbations, and symptoms to classify and grade
COPD severity. We aimed to determine their distribution in 11 well-dened COPD cohorts and
their prognostic validity up to 10 years to predict time to death.
Methods: Spirometry in all 11 cohorts was postbronchodilator. Survival analysis and C statistics
were used to compare the two GOLD systems by varying time points.
Results: Of 3,633 patients, 1,064 (33.6%) were in new GOLD patient group A (low risk, less symp-
toms), 515 (16.3%) were B (low risk, more symptoms), 561 (17.7%) were C (high risk, less symp-
toms), and 1,023 (32.3%) were D (high risk, more symptoms). There was great heterogeneity of
this distribution within the cohorts ( x
2
, P , .01). No differences were seen in the C statistics of old
vs new GOLD grading to predict mortality at 1 year (0.635 vs 0.639, P 5 .53), at 3 years (0.637
vs 0.645, P 5 .21), or at 10 years (0.639 vs 0.642, P 5 .76).
Conclusions: The new GOLD grading produces an uneven split of the COPD population, one-
third each in A and D patient groups, and its prognostic validity to predict time to death is no
different than the old GOLD staging based in spirometry only. CHEST 2013; 143(3):694702
Abbreviations: COCOMICS 5 Collaborative Cohorts to Assess Multicomponent Indices of COPD in Spain; GOLD 5
Global Initiative for Chronic Obstructive Lung Disease; mMRC 5 modied Medical Research Council.
Distribution and Prognostic Validity of
the New Global Initiative for Chronic
Obstructive Lung Disease Grading
Classication
Joan B. Soriano , MD ; Inmaculada Alfageme , MD ; Pere Almagro , MD ; Ciro Casanova , MD ;
Cristobal Esteban , MD ; Juan J. Soler-Catalua , MD ; Juan P. de Torres , MD ;
Pablo Martinez-Camblor , PhD ; Marc Miravitlles , MD ; Bartolome R. Celli , MD , FCCP ;
and Jose M. Marin , MD
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journal.publications.chestnet.org CHEST / 143 / 3 / MARCH 2013 695
We focused all analyses on time to death for all causes, as other
outcomes (ie, exacerbations of different types) were considered
less reliably recorded. Given the substantial patient-year exposure
within the database, survival at 1, 3, and up to 10 years was tested
to predict time to death. Standard Cox semiparametric propor-
tional hazards models were used to model the time-to-death
data.
19
C statistics, a measure of discrimination for survival analysis,
were employed to assess the performance of the time-to-death
models.
20
Heterogeneity and potential study effects were han-
dled by running models with the individual study as an addi-
tional stratication variable, and inferences were by the bootstrap
method.
21
In all analyses, a P value , .05 was considered for statis-
tical signicance.
Results
We obtained data of 3,633 patients with COPD
from 11 cohorts in Spain. They had an age (mean SD)
of 66.4 9.7 years, 93.3% were men, and 6.7% women.
Women were younger (59.8 11.0 years vs 66.9
9.5 years) and more frequently current smokers (43.3%
vs 26.8%) than men (both P , .05), but the size of the
female group (n 5 244) makes us reluctant to report
results by sex. At study entry, smoking exposure was
substantial (53.4 26.5 pack-years), and 71.0% were
former smokers while 27.9% were still current smok-
ers. Most participants were of moderate or higher
spirometrical severity with a % predicted FEV
1
of
53.8 19.4, and a Charlson index of 0.9 1.8 ( Table 1 ).
exclusive groups ( Fig 1 ). By conducting a patient-
based pooled analysis of 11 COPD cohorts, we aimed
to determine the distribution of the new GOLD groups
and their prognostic validity to predict time to death
in comparison with the old GOLD staging.
Materials and Methods
Our study design is of a pooled-analysis of individual patient
data,
5
from a number of COPD patient cohorts, all in Spain:
Galdakao,
6
Pamplona,
7
Requena,
8,9
Sevilla,
10
Tenerife,
11
Terrassa,
12-14

and Zaragoza.
15
Comprehensive details of the Collaborative
Cohorts to Assess Multicomponent Indices of COPD in Spain
(COCOMICS) study are available elsewhere (J. M. Marin, MD;
I. Alfageme, MD; P. Almagro, MD, et al, unpublished data). Briey ,
a minimum data set with age, sex, spirometry, and follow-up data
in all patients was required. Data were provided by the primary
investigator of each of the participating cohorts, spanning for a
period of approximately 20 years. Further details on methods
applied in each study can be found elsewhere.
6-15
Postbronchodiator-
forced spirometry was performed according to the guidelines
of the American Thoracic Society/European Respiratory Society
consensus.
16
Functional dyspnea was assessed using the modied
Medical Research Council (mMRC) dyspnea scale.
17
Comorbidi-
ties were quantied by means of the Charlson index,
18
excluding
COPD. All participants gave their informed written consent to
participate, and each study was approved by its respective ethics
committee.
Statistics
All data were quality controlled centrally, and a homogeneous
template to translate all coding was applied. Variables were then
double-checked by each principal investigator, and values that
were considered as potential errors or outliers were individually
discussed and conrmed, or removed. Comprehensive tabulations
with ranges, mean, and SD of all quantitative variables, and per-
centages of all qualitative variables, were available for each study.
Figure 1. New GOLD grading to stage COPD severity. Note
that Collaborative Cohorts to Assess Multicomponent Indices of
COPD in Spain (COCOMICS) had no CAT and we used COPD
hospitalizations as exacerbations. Patient group Alow risk, less
symptoms: typically, GOLD 1 or GOLD 2 (mild or moderate air-
ow limitation) and/or 1 exacerbation per year and mMRC , 2
or CAT score , 10. Patient group Blow risk, more symptoms: typi-
cally, GOLD 1 or GOLD 2 (mild or moderate airow limitation)
and/or 1 exacerbation per year and mMRC 2 or CAT score 10.
Patient group Chigh risk, less symptoms: typically, GOLD 3 or
GOLD 4 (severe or very severe airow limitation) and/or 2 exac-
erbations per year and mMRC , 2 or CAT score , 10. Patient
group Dhigh risk, more symptoms: typically, GOLD 3 or GOLD 4
(severe or very severe airow limitation) and/or 2 exacerba-
tions per year and mMRC . 2 or CAT score . 10. CAT 5 COPD
Assessment Test; GOLD 5 Global Initiative for Chronic Obstruc-
tive Lung Disease; mMRC 5 modied Medical Research Council.
Manuscript received May 7, 2012; revision accepted August 20,
2012.
Afliations: From the Fundacin Caubet-Cimera Centro Inter-
nacional de Medicina Respiratoria Avanzada (Dr Soriano), Bunyola,
Spain; rea Hospitalaria de Valme (Dr Alfageme), Sevilla, Spain;
Internal Medicine (Dr Almagro), Mtua Terrassa, Universitat
de Barcelona, Barcelona, Spain; Hospital Universitario Nuestra
Seora de Candelaria (Dr Casanova), Tenerife, Spain; Hospital
Galdakao-Usansolo (Dr Esteban), Galdakao, Bizkaia, Spain; Unidad
de Neumologa (Dr Soler-Catalua), Servicio de Medicina Interna,
Hospital General de Requena, Valencia, Spain; Clnica Universidad
de Navarra (Dr de Torres), Pamplona, Spain; Ocina de Investigacin
Biosanitaria de Asturies and Oviedo University (Dr Martinez-
Camblor), Oviedo, Spain; Hospital Clnic (Dr Miravitlles), Institut
DInvestigacions Biomdiques August Pi i Sunyer (IDIBAPS),
Barcelona, Spain; Pulmonary and Critical Care Medicine (Dr Celli),
Harvard University, Brigham and Womens Hospital , Boston, MA;
and Hospital Universitario Miguel Servet (Dr Marin), Zaragoza ,
Spain .
Funding/Support: The authors have reported to CHEST that no
funding was received for this study.
Correspondence to: Joan B. Soriano, MD, Program of Epidemi-
ology and Clinical Research, CIMERA, Recinte Hospital Joan
March, Carretera Soller Km 12. 07110-Bunyola, Illes Balears,
Spain; e-mail: jbsoriano@caubet-cimera.es
2013 American College of Chest Physicians. Reproduction
of this article is prohibited without written permission from the
American College of Chest Physicians. See online for more details.
DOI: 10.1378/chest.12-1053
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696 Original Research
There were no differences in the C statistics of old
vs new GOLD staging to predict survival at 1 year
(0.635 vs 0.639, P 5 .53), at 3 years (0.637 vs 0.645,
P 5 .21), or at 10 years (0.639 vs 0.642, P 5 .76). Actu-
ally, visually displaying the survival curves accord-
ing to the new GOLD grading shows that it takes
longer than 3 years to separate the survival curves of
group B (low risk, more symptoms) vs group C (high
risk, less symptoms) ( Fig 3 ). Quantitatively, the hazard
ratios relative to the new GOLD A staging were no
different in B vs C, namely group B 1.70 95% CI
(1.38-2.10), group C 1.69 95% CI (1.39-2.08), and
group D 2.79 95% CI (2.35-3.32). There was again
great heterogeneity on the time to death according to
the new GOLD grading within the cohorts ( x
2
, P , .01)
(e-Fig 1).
Table 2 summarizes the construction of the new
GOLD grading system from old GOLD, showing the
contribution of collapsing the spirometry criteria from
four to two strata, and then sequentially adding exac-
erbations and symptoms. The change in C statistics at
10 years is not remarkable, from 0.639 in old GOLD,
to an actual signicant decrease in GOLD I-II and
III-IV (at 0.617, P 5 .003), then a signicant increase
by adding exacerbations (C statistic 0.618, P 5 .008),
and a nal nonsignicant C statistic for the new GOLD
grading of 0.642 ( P 5 .76), as mentioned previously.
Finally, the impact in mortality if the entry dening
criteria by GOLD 2011 is either spirometry, exacer-
bations, or both is presented in Figure 4 . It can be
seen that the COPD hospitalizations-only criteria had
the mildest effect on survival, followed by spirometry-
only, but without statistical signicance with a hazard
ratio of 0.98 and a 95% CI (0.68-1.41). However, both
together had an additive, deleterious effect: 1.56,
95% CI (1.27-1.91).
Discussion
We report that the new GOLD grading produces
an uneven split of the COPD population, one-third
each in A and D patient groups, while one in six patients
with COPD are B and C, respectively, which to our
knowledge is a novel nding. Of interest, its prognos-
tic validity to predict time to death is no different than
the old GOLD staging based in spirometry only. We
believe the new GOLD grading makes more clinical
sense, as decisions on treatment should not only be
based (they never were) on airow limitation, but also
on other clinically relevant assessments, like past exac-
erbations and current symptoms. However, it could
be misleading to consider that the newly proposed
grading system indicates growing severity and predicts
death consistently, and we actually demonstrate this
is not the case.
Based on spirometry only, they were classied accord-
ing to old GOLD as 368 (10.2%) mild, 1,612 (44.8%)
moderate, 1,255 (34.9%) severe, and 366 (10.2%) very
severe.
To construct the new GOLD grading criteria, the
following sequence was performed. Of the 3,633 total
patients, we had data on COPD hospitalizations in
2,846 participants, spirometry in 3,601, and mMRC
dyspnea in 3,163. The at-risk criteria (spirometry
and/or COPD hospitalization) included 3.632 patients,
of which 1,773 were of high risk and therefore are
completely well classied (either C or D). Then, of
the 1,859 within low risk, there were 1,283 with both
criteria (again completely well classied, either as A
or B). However, the remainder, 576 (15.9%) could have
their severity underrated, as the unknown variable
could have classied them into the high-risk group.
According to the new GOLD grading, 1,064 (33.6%)
were graded new GOLD patient group A (low risk,
less symptoms), 515 (16.3%) were B (low risk, more
symptoms), 561 (17.7%) were C (high risk, less symp-
toms), and 1,023 (32.3%) were D (high risk, more
symptoms) (e-Table 1). There was great heterogeneity
of both staging distributions within the cohorts ( Fig 2 )
( x
2
, P , .01).
Table 1 Demographic and Clinical Characteristics
of Patients at Baseline/Enrollment of Old GOLD
and New GOLD
Characteristics Total
No. 3,633
Person-y 15,878.17
Age, y 66.39 9.73
Male sex 3,389 (93.3)
Pack-y 53.65 36.03
Smoking status
Former 2,532 (71.0)
Current 996 (27.9)
Never 38 (1.1)
BMI 27.86 4.98
pFEV
1
, % 53.77 19.43
mMRC 2.59 1.14
6MWT 397 130
Past COPD exacerbationss 0.89 1.81
Old GOLD groups
Mild 368 (10.2)
Moderate 1,612 (44.8)
Severe 1,255 (34.9)
Very severe 366 (10.2)
New GOLD groups
A 1,064 (33.6)
B 515 (16.3)
C 561 (17.7)
D 1,023 (32.3)
Data are given as mean SD or No. (%). Spirometry in all 11 cohorts
was postbronchodilator. 6MWT 5 6-min walking test; GOLD 5 Global
Initiative for Chronic Obstructive Lung Disease; mMRC 5 modied
Medical Research Council; pFEV
1
5 predicted FEV
1
.
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journal.publications.chestnet.org CHEST / 143 / 3 / MARCH 2013 697
Figure 2. Distribution of COCOMICS participants by old GOLD and new GOLD, by cohort. A, Old
GOLD. B, New GOLD 2011. See Figure 1 legend for expansion of abbreviations.
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698 Original Research
Figure 3. Ten-year survival (Kaplan-Meier curves) of COCOMICS participants by old GOLD and
new GOLD. A, Old GOLD. Cox model adjusted by cohort. HR (95% CI). COPD old GOLD II, 1.78
(1.29-2.46). COPD old GOLD III, 2.84 (2.06-3.92). COPD old GOLD IV, 4.05 (2.87-5.72). B, New
GOLD 2011. Cox model adjusted by cohort (differences between stages B and C disappears). HR (95% CI).
COPD new GOLD B, 1.70 (1.38-2.10). COPD new GOLD C, 1.69 (1.39-2.08). COPD new GOLD
D, 2.79 (2.35-3.32). See Figure 1 legend for expansion of abbreviations.
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Strengths and Limitations of the Current Study
The COCOMICS strengths include a large sample
size of nearly 16,000 person-years, allowing for statis-
tical power in most subanalyses; very few participants
were lost to follow-up, as cohorts were built from cli n-
ical practice in large hospital centers managing these
patients. Homogeneity (as all patients with COPD
are Spanish, granted by law with guaranteed univer-
sal, free-of charge health coverage up to now) gave
robustness in the interpretation/assessment of health
outcomes. There was internal consistency, as all inves-
tigators followed the same COPD clinical guidelines
for pharmacologic and nonpharmacologic treatments.
Finally, by including cohorts of patients with different
origins and severity, we covered a diverse population.
However, our study does have limitations. The COPD
Assessment Test (CAT) questionnaire
26
for assessing
other symptoms beyond dyspnea was not available at
the onset of all our cohorts, so we may have underes-
timated symptom severity by using the mMRC only.
There was no full information on COPD hospitaliza-
tion history in two cohorts (Pamplona and Zaragoza I),
so the experience from 795 and 717 persons-years,
respectively (which corresponds to 9.5% of all follow-up
data), was lost. Not all participants had data in all var-
iables, and key variables like milder exacerbations or
cause of death were not collected consistently or in
all participants. Note that Zaragoza II contributed
one-third of study participants (1,150 of 3,633) and
over one-third of the patient-years (6,520 of 15,878),
adding valuable statistical power, but weighing up
substantially to one single cohort. Regrettably, data
regarding history of past COPD exacerbations and/or
prospective use of health resources (ED visits and
hospitalizations) were not collected in all cohorts, and
in the few who collected them consistently, the meth-
ods were considered too diverse to be pooled together.
In particular, perhaps the most important limitation
of our study was using hospitalizations-only to deter-
mine COPD exacerbations, rather than also including
outpatient episodes. We performed an a posteriori
analysis in two of the 11 cohorts in which all types of
COPD exacerbations were systematically collected,
and that we considered had the greatest validity and
similar denitions of ambulatory COPD exacerbations
(e-Appendix 1). For this reanalysis, ambulatory COPD
exacerbations were dened as those COPD exacer-
bations that did not require a hospitalization; that
is, they only required an ED visit, or a GP or other
doctor attention. From the 766 individuals assessed,
114 (14.9%) would actually change group: that is,
76 (9.9%) from A to C, and 38 (5.0%) from B to D.
Importantly, our conclusions did not change; the new
GOLD 2011 severity grading became even less pre-
dictive of death if ambulatory COPD exacerbations
The new GOLD grading was constructed by extrap-
olating information of prospectively collected data
from one clinical study and two large medium-term
clinical trials
22-24
(page 14 of 74).
2
All three have been
landmark studies, but their representativity to real-
life clinical patients can be debated, and not all had
other relevant variables like exercise measured.
25
We
used a relatively new tool, pooled analysis, which col-
lects individual patient-level data and analyzes studies
as a single, new study. This has advantages over classic
meta-analyses as it avoids many of the methodologic
pitfalls related to classic meta-analytic techniques that
rely exclusively on published data.
5

Table 2 Constructing the New GOLD Grading System
From the Old GOLD Staging
GOLD C Statistics P Values vs Old GOLD
Old GOLD 0.639 1.00
GOLD I-II vs III-IV 0.617 .003
Risk (New GOLD)
a
0.618 .008
New GOLD
b
0.642 .76
Change in C statistics at 10 years. See Table 1 for expansion of
abbreviations.

a
Spirometry and exacerbations contribute to the variable risk in the
new GOLD staging system (two groups).

b
The new GOLD staging system is created by adding mMRC dyspnea
to the previous one, creating four groups.
Figure 4. Impact in mortality if the entry dening criteria by
GOLD 2011, is either spirometry, or exacerbations, or both. Cox
model adjusted by cohort. Only spirometry, 1. Only exacerbations,
0.98 (0.68-1.41). Both, 1.56 (1.27-1.91). Exac. 5 exacerbations.
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700 Original Research
will remain controversial until more evidence is built
to move from earlier expert opinion.
Conclusions
We conclude that the new GOLD grading produces
an uneven split of the COPD population, one-third
each in A and D patient groups. Its prognostic valid-
ity to predict time to death is no different from the
old GOLD staging based in spirometry only.
Acknowledgments
Author contributions: Dr Soriano is the guarantor of the manu-
script and takes responsibility for its data.
Dr Soriano: contributed to and approved the manuscript, con-
ceived the original idea for the manuscript, developed the plan of
analysis, and drafted the report.
Dr Alfageme: contributed to and approved the manuscript and
collected clinical data.
Dr Almagro: contributed to and approved the manuscript and col-
lected clinical data.
Dr Casanova: contributed to and approved the manuscript and
collected clinical data.
Dr Esteban: contributed to and approved the manuscript and col-
lected clinical data.
Dr Soler-Catalua: contributed to and approved the manuscript
and collected clinical data.
Dr de Torres: contributed to and approved the manuscript and
collected clinical data.
Dr Martinez-Camblor: contributed to and approved the manu-
script and developed the plan of analysis.
Dr Miravitlles: contributed to and approved the manuscript and
developed the plan of analysis.
Dr Celli: contributed to and approved the manuscript and col-
lected clinical data.
Dr Marin: contributed to and approved the manuscript and col-
lected clinical data.
Financial/nonnancial disclosures: Dr Soriano received phar-
maceutical company grants from GlaxoSmithKline plc in 2011
and Chiesi Farmaceutici in 2012 via his home institution, and also
participated in speaking activities, industry advisory committee,
or other related activities sponsored by Almirall S.A.; Boehringer
Ingelheim GmbH; Pzer, Inc; Chiesi Farmaceutici; GlaxoSmithKline
plc; and Novartis AG during the period 2010-2012. Dr Alfageme
has received speaker fees from Boehringer Ingelheim GmbH and
Pzer, Inc during the period 2010-2012. Dr Almagro participated
in speaking activities, industry advisory committee, or other related
activities sponsored by Takeda Pharmaceuticals International GmbH;
Almirall S.A.; Boehringer Ingelheim GmbH; Pzer, Inc; Chiesi
Farmaceutici; GlaxoSmithKline plc; ESTEVE; Merck, Sharp &
Dohme Corp; and Novartis AG during the period 2010-2012.
Dr Casanova declares to participating in speaking activities dur-
ing the period 2010-2012 related to the following industry sources:
Almirall S.A.; Takeda Pharmaceuticals International GmbH; Chiesi
Farmaceutici; GlaxoSmithKline plc; and Novartis AG; and declares
not to have any other potential conicts of interest to report regard-
ing the contents of this manuscript. Dr Soler-Catalua participated
in speaking activities, industry advisory committee, or other related
activities sponsored by Almirall S.A.; AstraZeneca; Boehringer
Ingelheim GmbH; Pzer, Inc; Ferrer; GlaxoSmithKline plc; Takeda
Pharmaceuticals International GmbH; Merck, Sharp & Dohme
Corp; Novartis AG; and Grupo Uriach during the period 2010-
2012. Dr de Torres received fees for speaking activities for
GlaxoSmithKline plc; AstraZeneca; Novartis AG; Merck, Sharp &
Dohme Corp; and Takeda Pharmaceuticals International GmbH
and received consultancy fees for participating in the Takeda
Pharmaceuticals International GmbH and Novartis AG Advisory
Boards during the period 2010-2012. Dr Miravitlles has received
speaker fees from Boehringer Ingelheim GmbH; Pzer, Inc; Bayer
were factored in. Other limitations include the scanty
numbers of women with COPD (7%), reecting the
reality of cli nical COPD in our populations. For anal-
ysis on treatments or of time-dependent variables, it
was not possible to assess changes in medication,
smoking habits, and other factors. Even in the very
long-term, our analyses assumed that the patients
condition did not change from baseline, which in some
variables may not be so (changing medication, becom-
ing a frequent exacerbator, or developing a new
comorbidity). Although some COPD variables show
stability and repeatability, these analyses had no reg-
ular monitoring and restaging or regrading.
Likely, the new GOLD grading has a different dis-
tribution in other clinical settings. Intuitively, in other
tertiary centers like ours, patient group D prevails, as
the most severe patients are often in the at-risk cate-
gory (either by spirometry and/or exacerbations) and
will have symptoms frequently. Counterintuitively,
patients will also be very frequently assessed into group
A as the most frequent participants in most COPD
clinical trials are those with moderate airow limita-
tion; but in this case, they are either maximally treated
or accommodated to avoid physical efforts,
27
ergo
reporting less symptoms. We can speculate that in the
primary care level, there might be a predominance of
patient group B, as patients with COPD should have
less frequently severe or very severe airow limitation
and experience less COPD exacerbations, so they would
not be in the at-risk categories. But they are having
symptoms as they are requesting medical care. Again
counterintuitively, it can be seen in Figure 3 , that our
COPD cohorts from Internal Medicine (Terrassa I,
II, and III) or from a mid-size Respiratory Regional
Unit (Requena I and II), both contributed the most
patients with COPD in patient group D. More research
by other groups reporting their group distributions
will be expected. Our time to death outcomes are less
likely to be replicated by other groups, as our experi-
ence might be difcult to match given the very long-
term data and large person-time size included here.
Our nding of no differentiation of groups B and C
before 3 years might be puzzling to obtain in time to
death, so perhaps time to rst exacerbation could be
used as an alternative. As recently reported, severe
exacerbations at any stage of COPD are associated
with a higher risk of short-term and long-term all-
cause mortality,
28
and the very short-term prognosis
(up to 3 months) is associated with comorbidities.
29

The possibility of a more personalized treatment of
patients with COPD, according to severity combining
spirometry,
30
with symptoms and exacerbations, had
been postulated previously elsewhere.
31-33
We agree
with the new GOLD recommendations that it is the
way to move forward, although denitive thresholds
need to be established.
2
Any therapeutic decisions
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journal.publications.chestnet.org CHEST / 143 / 3 / MARCH 2013 701
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AG; Novartis AG; Talecris; Takeda Pharmaceuticals Interna-
tional GmbH;Merck, Sharp & Dohme; and Novartis AG and
consulting fees from Boehringer Ingelheim GmbH; Pzer, Inc;
GlaxoSmithKline plc; Bayer AG; Novartis AG; Almirall S.A.; Merck,
Sharp & Dohme Corp; and Takeda Pharmaceuticals International
GmbH during the period 2010-2012. Dr Celli has served in the
GlaxoSmithKline plc-sponsored ECLIPSE and the SUMMIT trial;
in Advisory Boards for AstraZeneca and Novartis AG; received
pharmaceutical company grant monies from AstraZeneca to his
home institution; and is consultant to a pharmaceutical or medical
device company, and received speaker fees from GlaxoSmithKline
plc, AstraZeneca, Rox Pharmaceutical, Almirall S.A., and Boehringer
Ingelheim GmbH during the period 2010-2012. While Drs De Torres,
Miravitlles, and Celli have served on industry advisory boards for
companies that make COPD drugs, and Drs Soriano, Alfageme,
Almagro, Casanova, Soler-Catalua, de Torres, Miravitlles, and
Celli have given industry-sponsored lectures during the period
2010-2012, the industry did not pay/fund this study. In-full
individual disclosures by all authors are found in e-Appendix 1.
Drs Esteban, Martnez-Camblor, and Marin have reported that no
potential conflicts of interest exist with any companies/orga-
nizations whose products or services may be discussed in this
article.
Additional information: The e-Appendix, e-Figure, and e-Table
can be found in the Supplemental Materials area of the online
article.
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