CLINICAL RESEARCH STUDY
Depression and Health-Related Quality of Life in Chronic
Obstructive Pulmonary Disease
Theodore A Omachi, MD, MBA,aPatricia P Katz, PhD,bEdward H Yelin, PhD,b,cSteven E Gregorich, PhD,d
Carlos Iribarren, MD, MPH, PhD,ePaul D Blanc, MD, MSPH,a,fMark D Eisner, MD, MPHa,f
aDivision of Pulmonary and Critical Care Medicine, Department of Medicine,bInstitute for Health Policy Studies,cDivision of
Rheumatology, Department of Medicine,dDivision of General Internal Medicine, Department of Medicine, University of California, San
Francisco;eDivision of Research, Kaiser Permanente, Oakland, Calif;fDivision of Occupational and Environmental Medicine,
Department of Medicine, University of California, San Francisco.
BACKGROUND: Prior research on the risk of depression in chronic obstructive pulmonary disease (COPD)
has yielded conflicting results. Furthermore, we have an incomplete understanding of how much depres-
sion versus respiratory factors contributes to poor health-related quality of life.
METHODS: Among 1202 adults with COPD and 302 demographically matched referents without COPD,
depressive symptoms were assessed using the 15-item Geriatric Depression Score. We measured COPD
severity using a multifaceted approach, including spirometry, dyspnea, and exercise capacity. We used the
Airway Questionnaire 20 and the Physical Component Summary Score to assess respiratory-specific and
overall physical quality of life, respectively.
RESULTS: In multivariate analysis adjusting for potential confounders including sociodemographics and all
examined comorbidities, COPD subjects were at higher risk for depressive symptoms (Geriatric Depres-
sion Score ?6) than referents (odds ratio [OR] 3.6; 95% confidence interval [CI], 2.1-6.1; P ?.001).
Stratifying COPD subjects by degree of obstruction on spirometry, all subgroups were at increased risk of
depressive symptoms relative to referents (P ?.001 for all). In multivariate analysis controlling for COPD
severity as well as sociodemographics and comorbidities, depressive symptoms were strongly associated
with worse respiratory-specific quality of life (OR 3.6; 95% CI, 2.7-4.8; P ?.001) and worse overall
physical quality of life (OR 2.4; 95% CI, 1.8-3.2; P ?.001).
CONCLUSIONS: Patients with COPD are at significantly higher risk of having depressive symptoms than
referents. Such symptoms are strongly associated with worse respiratory-specific and overall physical health-
related quality of life, even after taking COPD severity into account.
© 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, 778.e9-778.e15
KEYWORDS: Chronic obstructive; Depression; Health status; Pulmonary disease; Quality of life
A primary objective of treatment for patients with chronic
disease is to improve health-related quality of life.1For
patients with chronic obstructive pulmonary disease (COPD),
pulmonary rehabilitation is known to improve health-related
quality of life, but this benefit is not fully explained by im-
provement in cardiorespiratory function.2-4For example, a
recent Cochrane meta-analysis concluded that pulmonary re-
habilitation programs significantly improved health-related
quality of life, even though the improvement in exercise ca-
pacity was below the threshold of clinical significance.4This
finding raises the intriguing possibility that psychosocial fac-
tors, such as depression, are critical determinants of health
status in COPD.
Funding: Dr. Omachi was supported by the Agency for Healthcare
Research and Quality, Grant number F32 HS017664. Dr. Eisner was
supported by R01HL077618 from the National Heart, Lung, and Blood
Institute, National Institutes of Health, and UCSF Bland Lane FAMRI
Center of Excellence on Secondhand Smoke CoE2007.
Conflict of Interest: None.
Authorship: All authors had access to the data and a role in writing the
Requests for reprints should be addressed to Theodore A. Omachi, MD,
MBA, Department of Medicine, University of California, San Francisco,
Box 0111, 505 Parnassus Avenue, San Francisco, CA 94143-0111.
E-mail address: firstname.lastname@example.org
0002-9343/$ -see front matter © 2009 Elsevier Inc. All rights reserved.
Depression is thought to be associated with worse health
status in patients with COPD, but studies on this subject
generally have been hampered by either small sample sizes
or incomplete information to adjust for COPD severity.5-7
Moreover, although depression appears to be more common
in COPD patients than in the gen-
eral population, there have been
few studies addressing this ques-
tion.5,8One systemic review con-
cluded that the evidence for a
significant risk of depression in
COPD patients remained inconclu-
sive.9Indeed, some studies have
found an increased level of depres-
sion in patients with COPD,10,11
while others have not.12,13
Our study uses a large observa-
tional cohort to study depressive
symptoms in COPD. We hypoth-
esized that individuals with COPD
would be more likely to have de-
pressive symptoms than demo-
graphically matched referent sub-
jects without COPD, that more
severe COPD would be associated
with a higher likelihood of having depressive symptoms,
and that depressive symptoms would be strongly associated
with health-related quality of life even after controlling for
The Function, Living, Outcomes, and Work study is an
ongoing cohort study of patients with COPD and matched
referents without COPD.14The cohort was derived from
members of Kaiser Permanente (KP). Previously, patient
recruitment has been described in detail.14Briefly, we iden-
tified all adult KP members living within a 30-mile radius of
our research clinic who were treated recently for COPD.14
The age range was restricted to 40-65 years because an
important focus of the Function, Living, Outcomes, and
Work study is examining the long-term prevention of
COPD-associated morbidities. Using KP databases, we iden-
tified all patients who met each of 2 criteria: one based on
health-care utilization and the second based on medication
prescription. The health care utilization criterion was ?1 out-
patient visits or hospitalizations for COPD over the prior 12
months. The medication criterion was ?2 prescriptions for a
COPD-related medication during a 12-month window sur-
rounding the COPD utilization date. We previously compared
this algorithm with medical record review and demonstrated
that it accurately identifies adults with COPD.15
We recruited 1212 COPD patients who completed both
structured telephone interviews and research clinic visits.
Ten subjects were excluded because they did not meet the
Global Initiative for Chronic Obstructive Lung Disease cri-
teria for COPD based on interviews and spirometry,16yield-
ing a COPD cohort of 1202 subjects.
We aimed to recruit 300 control subjects without COPD.
We initially identified 373 referent subjects, without histor-
ical utilization for COPD, who were matched to COPD
subjects by age, sex, and race. By
design, we excluded 71 subjects
who had spirometric evidence of
airway obstruction at the time of
research clinic evaluation, leaving
302 referent subjects.
The study was approved by both
the University of California, San
Francisco Committee on Human
Research Institute’s institutional re-
view board, and all participants pro-
vided written informed consent.
even after adjusting for respiratory symp-
toms and impairment, clinicians should
consider depression in COPD to be an
important clinical problem in its own
As previously described, subjects
underwent structured telephone
interviews followed by a research
clinic visit.14Interviews obtained
medical comorbidities, tobacco his-
tory, sociodemographic characteristics, and the 15-item short-
form Geriatric Depression Scale (GDS). We chose the GDS
because it was developed to counter the problem of overlap
among symptoms of a physical illness such as COPD and the
somatic symptoms considered indicative of depression.9The
GDS has been validated both in nongeriatric populations gen-
erally as well as specifically in younger adults with obstructive
GDS has a sensitivity of 88% and a specificity of 62% com-
pared with structured clinical interview for diagnosing major
depression.20Following precedent, we therefore defined de-
pressive symptoms as present if subjects reported ?6 of 15
possible symptoms on the GDS.21
For COPD patients, respiratory-specific quality of life
was assessed using the validated revised Airways Question-
naire 20 (AQ20-R).22-24Lower scores reflect more favor-
able health status. Physical quality of life as reflective of
generic health status was measured using the Short-Form
(SF)-12 Physical Component Summary (PCS) score. The
SF-12 PCS is derived from the Medical Outcomes Study
SF-36 instrument, which has been extensively validated in
the general population and among adults with COPD.25,26
Higher scores reflect more favorable health status. Although
both the PCS and AQ20-R scores are continuous variables,
they can be grouped for clinical interpretability. On an a
priori basis, we divided these scores into 4 strata based on
the quartiles observed in the COPD cohort.
COPD Severity Assessment
For subjects with COPD, COPD severity was assessed in
several ways. We conducted spirometry according to Amer-
● Chronic obstructive pulmonary disease
(COPD) is associated with an increased
risk of depressive symptoms. Clinicians
should be alert to the possibility of de-
pression in their COPD patients.
● Because depressive symptoms appear to
strongly impact quality of life in COPD,
778.e10 Omachi et alDepression and Quality of Life in COPD
ican Thoracic Society guidelines.27Although we did not
administer bronchodilators before spirometry, 90% of sub-
jects had taken their own short-acting bronchodilator within
4 hours of spirometry or had taken a long-acting broncho-
dilator earlier in the same day.
Submaximal exercise performance was assessed using
the 6-Minute Walk Test (6MWT).28,29Subjects who rou-
tinely used home oxygen or who had a resting oxygen
saturation ?90% were supplied with supplemental oxygen
during the test. The primary outcome was meters walked in
Oxygen saturation was assessed at rest using pulse oxim-
etry. For subjects with prescribed supplemental oxygen
(n?61), oxygen saturation was assessed on their prescribed
We also used a previously validated survey-based COPD
severity score, which is based on responses to survey items
that comprise 5 domains of COPD severity: degree of re-
spiratory symptoms, prior systemic corticosteroid use, other
COPD medication use, previous hospitalization or intuba-
tion for respiratory disease, and home oxygen use.30Poten-
tial scores range from 0 to 35.
We furthermore determined the BODE Index, which is a
multidimensional score, predictive of death in COPD, that
incorporates many of the above measures.31Specifically, it
includes body mass index (BMI) [B], airflow obstruction as
measured by FEV1(forced expiratory volume in 1 second)
[O], dyspnea [D], and exercise capacity [E], measured by
Differences in characteristics between COPD subjects and
referents were compared using the t test for continuous
normally distributed variables and chi-squared tests for cat-
egorical variables. We used chi-squared tests for linear trend
for ordinal variables.
Risk of Depressive Symptoms Relative to Referents. We
used multivariate logistic regression to determine the ad-
justed odds ratio (OR) of having depressive symptoms in
COPD subjects relative to referents, taking into account
sociodemographics and comorbidities. We analyzed the
COPD group as a whole relative to referents and also
stratified by degree of airway obstruction as measured by
FEV1%-predicted categorizations specified by Global Ini-
tiative for Chronic Obstructive Lung Disease.16We used
likelihood ratio testing to determine whether different ORs
within a given multivariate logistic regression were differ-
ent from each other.
COPD Severity and Risk of Depression. To further eval-
uate whether COPD is associated with depression, we ex-
amined whether higher COPD severity was associated with
a greater likelihood of having depressive symptoms. To do
so, we developed several multivariate logistic regression
models. Each model used depressive symptoms as the out-
come variable and included the same potential confounders
(sociodemographics, comorbidities, tobacco history, and
BMI) but included a different measure of COPD severity as
a predictor variable.
Impact of Depression on Quality of Life among COPD
Patients. We also evaluated the association between depres-
sive symptoms and health-related quality of life, controlling
for COPD severity. Here we developed 2 multivariate lo-
gistic regression models, each with a different quality of life
outcome variable. Each model incorporated the same po-
tential confounders, listed above, as well as both the BODE
Index and COPD Severity Score to adjust for COPD sever-
ity. We chose the BODE index because, as a single measure,
it incorporates multiple measures of COPD severity, includ-
ing FEV1and 6MWT. We also incorporated the COPD
Severity Score because, as a survey-based measure of such
factors as COPD-specific utilization, it has the potential to
capture a dimension of COPD severity not assessed by the
BODE Index. Because our objective here was to determine
the extent to which depressive symptoms are associated
with quality of life after maximally adjusting for COPD
severity, it was most conservative to simultaneously include
both the BODE Index and COPD Severity Score. For our
categorizations of overall physical and respiratory-specific
quality of life, we used ordinal logistic regression.32The
ordinal logistic model invokes the proportional odds as-
sumption and estimates a single OR for the association
between a predictor and a multi-level categorical outcome
(in this case, the 4 strata of the PCS and AQ20-R).
For all analyses, we used Stata/SE software (version 9.2,
StataCorp LP, College Station, Tex). For all logistic regres-
sion models, the Hosmer-Lemeshow test demonstrated ad-
equate goodness-of-fit (P ?.20 for all models).32The pro-
portional odds assumption was verified for both ordinal
logistic regression analyses (P ?.20 for both models).32
By design, patients with and without COPD were similar in
age, sex, and race (Table 1). Compared with referents,
patients with COPD had a higher prevalence of all exam-
ined comorbidities, higher average BMI, and greater prev-
alence of depressive symptoms (P ?.001 for all).
COPD and the Risk of Depressive Symptoms
In multivariate analysis adjusting for sociodemographics
and comorbidities, depressive symptoms were much more
common in patients with COPD than in referents (OR 3.6;
95% CI 2.1-6.1; P ?.001). In addition, when COPD sub-
jects were stratified by FEV1categorization, all subgroups
were more likely to have depressive symptoms relative to
referents, with the OR highest among those with the lowest
FEV1(Table 2). A chi-squared test for trend revealed that
greater COPD severity, based on greater categorical impair-
ment in FEV1, was associated with increasing risk of de-
pressive symptoms (P ?.001).
778.e11The American Journal of Medicine, Vol 122, No 8, August 2009
To examine whether COPD severity unmeasured by lung
function might explain why patients with higher FEV1man-
ifest greater odds of depressive symptoms than referents, we
dichotomized subjects based on the median value of the
COPD Severity Score within each FEV1%-predicted stra-
tum (Table 3). Thus, for example, the median value of the
COPD Severity Score in the subgroup of patients with FEV1
?80% predicted was 7. Patients in this subgroup whose
COPD Severity Score was above the median (ie, ?7) were
at greater risk of having depressive symptoms relative to the
referent population (OR 4.3, 95% CI, 2.3-8.0) than patients
in this subgroup whose COPD Severity Score was below the
median (ie, ?7) (OR 1.8; 95% CI, 0.9-3.8); likelihood ratio
testing revealed that the OR of 4.3 was statistically signif-
icantly different from the OR of 1.8 (P?.009). This result
suggests that variability in COPD severity is related to
variability in depressive symptoms even in subjects with
Among the subgroup with COPD, greater COPD severity
was associated with increased likelihood of depressive
symptoms after controlling for covariates. This was ob-
served for each method used to assess COPD severity
Depressive Symptoms and Quality of Life in
When examining the relationship between depressive symp-
toms and health-related quality of life, after adjusting for
both potential confounders and COPD severity measures,
we found that depressive symptoms were associated
strongly with worse respiratory-specific quality of life (OR
3.6; 95% CI, 2.7-4.8; P ?.001) and worse overall physical
quality of life (OR 2.4; 95% CI, 1.8-3.2; P ?.001) (Table 5).
In a population-based sample, COPD was associated with a
greater risk of depressive symptoms compared with a
matched referent group. The fact that increasing COPD
severity is associated with an increasing likelihood of de-
pressive symptoms provides further evidence for an associ-
ation between COPD and depression. Depressive symptoms
also appeared to negatively impact quality of life, highlight-
ing the importance of depression in these patients. Targeting
depression in COPD could therefore be an attractive strat-
egy to improve health status.
Previous research on the risk of depression faced by
patients with COPD has yielded conflicting results.5-13The
study by van Manen and colleagues,11with 162 COPD
subjects, is the largest prior study on this subject that also
included both a referent population and pulmonary function
measurement. Interestingly, this study showed an increase
COPD Compared with Referents
Prevalence and Odds of Depression in Patients with
Symptoms* OR† (95% CI)
549 142 (25.9%) 2.9 (1.7-5.1)
25874 (28.7%) 4.6 (2.5-8.4)
11239 (34.8%) 8.0 (4.1-15.7)
302 17 (5.6%)
75 (26.5%) 3.1 (1.7-5.6)
COPD ? chronic obstructive pulmonary disease; OR ? odds ratio;
CI ? confidence interval; FEV1? forced expiratory volume in 1 second.
*Geriatric depression score ?6.
†Odds ratio for COPD vs referents for each subgroup of COPD. Results
are from multivariate logistic regression adjusted for age, sex, marital
status, race, education, annual household income, body mass index, and
all comorbidities listed in Table 1. Other factors associated with depres-
sive symptoms in multivariate analysis were younger age, sex, education,
annual household income, body mass index, and history of stroke, sleep
apnea, and lower back pain (P ?.05 for all). In chi-squared test for
trend, decreasing FEV1categorizations were associated with increasing
odds of depressive symptoms (P ?.001).
‡Comparing the whole COPD group to referents in multivariate anal-
ysis adjusted for the same covariates yields an odds ratio for depressive
symptoms of 3.6 (95% CI, 2.1-6.1).
Characteristics of 1202 Patients with COPD and 302
(n ? 302)
(n ? 1202) P Value
Age, mean (SD) years
Married or cohabitating
Annual household income
Coronary artery disease
Congestive heart failure
Lower back pain
index (mean) (SD),
17 (6)330 (27)
COPD ? chronic obstructive pulmonary disease.
*Data are presented as number (column percentage) except where
indicated otherwise. Tobacco history percentages among COPD subjects
do not add up to 100% because of rounding.
†Geriatric depression score ?6.
778.e12Omachi et al Depression and Quality of Life in COPD
in depressive symptoms among subjects with severe COPD
(FEV1?50% of predicted) but not in their cohort as a
whole or in the less severe subgroups.11We cannot be sure
of the reason for our differing conclusions, but this may
have to do with higher rates of mood disorders generally in
the United States relative to The Netherlands, where that
study was performed.33Prior research has suggested that
cultural differences among nations may affect the expres-
sion of depressive symptoms and be responsible for differ-
ing risk factors for major depression in various countries.34
Our finding that higher COPD severity is associated with
a higher likelihood of depressive symptoms provides further
validity to the concept that COPD is associated with depres-
sion. However, our cross-sectional analysis cannot deter-
mine completely the causal pathway between COPD and
depressive symptoms. It is possible that COPD causes de-
pression or that depression causes COPD via its association
with cigarette smoking.35Both pathways also may be op-
erative. Alternatively, shared genetic and environmental
factors may predispose independently to both smoking and
depression.36,37Thus, because COPD might not be causing
depression directly, targeting improved respiratory physiol-
ogy in COPD might not alleviate depressive symptoms.
We found that depressive symptoms were associated
strongly with health-related quality of life. Even though the
risk of depressive symptoms increased with increasing
COPD severity, the relationship between depressive symp-
toms and health-related quality of life was present taking
into account such severity. These results are particularly
important because depression complicating COPD is often
overlooked in clinical practice.37Our results suggest that
attempts to improve the quality of life of COPD patients
should not underestimate the importance of depression as a
potentially mediating factor. Moreover, there is evidence
that treating depression in COPD improves quality of
life.38,39Although this might include antidepressive phar-
macotherapy,39interventions such as pulmonary rehabilita-
tion, which often includes psychosocial support, might also
improve mood and reduce depressive symptoms.4,40-42Al-
ternatively, psychological counseling within the context of a
physician visit may be important.43Because of the strong
association between depressive symptoms and quality of
life, further study about effective methods of treating de-
pression in COPD appear clearly warranted.
Several study limitations must be considered. Although
the inclusion criteria required health care utilization for
COPD Severity with Depressive Symptoms within Each Strata of FEV1
Dichotomization of FEV1%-Predicted Subgroups into High and Low COPD Severity Scores: Examining the Association of
COPD Severity Score‡
OR* (95% CI) for Depressive Symptoms†
Low COPD Severity Score
High COPD Severity Score
P Value for OR Difference
FEV1? forced expiratory volume in 1 second; COPD ? chronic obstructive pulmonary disease; OR ? odds ratio; CI ? confidence interval.
*Odds ratio of depressive symptoms is relative to referent group without COPD. Each FEV1stratum was dichotomized based on the median COPD Severity
Score within that stratum. Results are from multivariate logistic regression adjusted for age, sex, marital status, race, education, annual household income,
body mass index, and all comorbidities listed in Table 1.
†Depressive symptoms defined as geriatric depression score ?6.
‡The COPD Severity Score is a survey-based measure of COPD severity that takes into account respiratory symptoms, COPD medication usage, prior
hospitalizations and intubations for COPD, and home oxygen usage. See Methods.
§Based on likelihood ratio testing. For example, within the subgroup of patients with FEV1? 80% predicted, those with a high COPD Severity Score
had a significantly higher risk of depressive symptoms relative to referents without COPD (OR ? 4.3) than those whose COPD Severity Score was
low (OR ? 1.8) (P ? .009 for difference between these 2 ORs).
P ? .009
P ? .84
to Depressive Symptoms (GDS Score?6) Among Patients with
COPD (n ? 1202)
Relationship of Various Measures of COPD Severity
OR (95% CI)
6-minute walk test*
COPD Severity Score*
COPD ? chronic obstructive pulmonary disease; GDS ? Geriatric De-
pression Score; OR ? odds ratio; CI ? confidence interval; FEV1? forced
expiratory volume in 1 second.
Each row represents a separate multivariate logistic regression analy-
sis that includes the following covariates: younger age, sex, race, marital
status, education, annual household income, tobacco history, body mass
index, and all comorbidities listed in Table 1.
*Per 1 standard deviation in each of the measures: FEV1% predicted
(unit decrement ? 23%); 6-minute walk test (unit decrement ? 120 m);
oxygen saturation (unit decrement 2.5%); COPD Severity Score (unit
increment [higher score reflects 1severity] ? 6.1 points); BODE Index
(unit increment [higher score reflects 1severity] ? 2.4 points).
778.e13The American Journal of Medicine, Vol 122, No 8, August 2009
COPD and COPD medication usage, it is possible that some
subjects had asthma rather than COPD. However, all pa-
tients also had a physician diagnosis of COPD and reported
having the condition. The observed lifetime smoking prev-
alence was similar to that in other population-based epide-
miologic studies of COPD, supporting the diagnosis of
COPD rather than asthma.44,45Nonetheless, we cannot ex-
clude the possibility that some subjects, especially those
with less obstruction on spirometry, might have conditions
other than COPD. However, we note that reduced FEV1was
associated with a higher likelihood of depressive symptoms;
thus, eliminating subjects with higher FEV1from our cohort
would only have strengthened our finding that subjects with
COPD are at higher risk of depressive symptoms than
Because an important focus in the prospective follow-up
of our cohort will be studying the long-term prevention of
COPD-associated morbidities, we intentionally sampled
younger adults with COPD (ages 40-65 years). Although we
adjusted for age within our multivariate models, we cannot
be sure of the applicability of our results to older adults with
COPD. In addition, KP members, because they have health
care access, may also be different from the general popula-
tion of adults with COPD. Mitigating this limitation, the
sociodemographic characteristics of Northern California KP
members are similar to those of the regional population.46,47
Moreover, selection bias could have been introduced by
nonparticipation in the study and could in turn affect the
generalizability of our results. However, our participation
rates were comparable or better than many other studies on
Our measure of depression, the GDS, is not intended to
diagnose major depression but rather depressive symptoms.
Nonetheless, patients with depressive symptoms warrant
further evaluation in clinical practice, and treatment for
depression is often recommended even in the absence of a
diagnosis of major depression.48One advantage of the GDS
over other measures of depressive symptoms is that it is less
contaminated with somatic symptoms such as poor appetite
and poor sleep that can be symptoms of either depression or
of COPD itself.9,11This reduces the likelihood that we are
overestimating depression in this setting.
In conclusion, we found that patients with COPD, at all
levels of airway obstruction, were at higher risk of depres-
sive symptoms than referents. Furthermore, increasing COPD
severity was associated with an increasing likelihood of
depressive symptoms. Even so, after taking COPD severity
into account, depressive symptoms were strongly associated
with worse quality of life.
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Quality of Life
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OR* (95% CI)
P ValueOR* (95% CI)
COPD Severity Score§
COPD ? chronic obstructive pulmonary disease; OR ? odds ratio; CI ? confidence interval.
The 2 columns of health-related quality of life measures represent 2 different multivariate models that simultaneously included the independent
variables shown above as well as the following covariates: age, sex, race, marital status, education, annual household income, tobacco history, body mass
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a dyspnea scale, and exercise capacity (see Methods). Higher BODE Index scores reflect greater COPD severity.
§Odds ratios presented per 1 standard deviation increment in COPD Severity Score. Higher COPD Severity Scores reflect greater severity.
778.e14 Omachi et alDepression and Quality of Life in COPD
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