data sources were the truven health marketscan commercial claims and encounters and the marketscan medicare supplemental databases from january 1 , 2009 , to september 30 , 2012 .
records of patients with a copd diagnosis at any diagnosis position within the intake period from july 1 , 2009 , through september 30 , 2011 , were included . claims for laboratory , pathology , or
radiology services were not used to identify individuals with a specific condition , because their use could incorrectly identify individuals as having that condition based on the reason for testing ( eg , screening ) rather than the test results ; therefore , those claims were ignored during patient selection , and diagnoses were termed non - rule - out copd .
the first occurrence of non - rule - out copd diagnosis ( international classification of diseases , ninth revision , clinical modification codes 490.xx , 491.xx , 492.xx , 494.xx , or 496.xx ) ( e - table
1 ) was defined as the index event , and the date of the index event was defined as the index date .
the study proposal was presented to and accepted by the novartis outcomes research review forum .
eligible patients were aged 40 to 90 years ( inclusive ) , had copd , and used at least one long - acting muscarinic antagonist ( lama ) , long - acting 2-adrenergic agonist ( laba ) , inhaled corticosteroid ( ics)/laba , or lama + ics + laba from 180 days before the index date through 180 days after the index date .
patients were enrolled continuously in the medical , pharmacy benefit , and fee - for - service plan from 180 days before the index date to 360 days after the index date .
comorbidities were defined as any occurrence of a specific diagnosis code from 180 days before the index date through 180 days after the index date .
this time period , which does not fall completely within the baseline period or the 360-day follow - up period , was chosen to establish and solidify the baseline patient comorbidities being evaluated .
comorbidities of interest were identified prospectively and consisted of chronic kidney disease ( ckd ) ; cardiovascular disease ( cvd ) , including heart failure , stroke , acute myocardial infarction ( mi ) , and peripheral vascular disease ; asthma ; depression ; diabetes ; osteoporosis ; and anemia .
resource consumption was measured from 180 days prior to the index date to the index date ( for baseline assessments ) and from the index date through 360 days after the index date ( for outcomes assessments ) .
resource use assessments included all - cause and disease - specific ed visits , hospitalizations , office visits ( defined as any office visit to any doctor ) , outpatient visits , and total length of hospital stay ; in this instance , disease - specific means copd- or asthma - related .
the health - care costs assessed included all - cause and disease - specific costs for ed visits , hospitalizations , office visits , and other outpatient visits , as well as medical , prescription drug , and total health - care costs .
other covariate variables included age , sex , region , employment status , and index medication ( the first drug class used during the period ) .
patient characteristics , comorbidities of interest , health - care use , and costs were summarized descriptively .
a generalized linear model ( glm ) was used to evaluate which comorbidities drive total costs after accounting for patient characteristics in the total population . after examining the data
, we selected glms with a log - link and  distribution to evaluate the incremental all - cause costs , adjusting for baseline demographics , resource use , and comorbidities . to better understand total costs that are potentially attributable to comorbidities , the average treatment effect ( change in the response by a change in a covariate ) of each comorbidity was calculated by using the recycled prediction method .
the predicted costs for patients with cvd were calculated based on the estimated glm ( with costs as the dependent variable ) by assuming all patients had cvd ( regardless of whether they had cvd ) while keeping other covariates as they were .
the predicted costs , for which every observation is treated as if it represents patients without cvd , were obtained in the same manner .
the average treatment effect was the mean difference in the predicted costs for the two groups .
thus , we compared two hypothetical populations ( one with cvd and one without cvd ) that had the exact same values for the other independent variables in the model .
cis were generated with the percentile method ( the 95% lower bound ci is the 2.5th percentile of the bootstrap distribution , and the 95% upper bound ci is the 97.5th percentile of the bootstrap distribution ) .
data sources were the truven health marketscan commercial claims and encounters and the marketscan medicare supplemental databases from january 1 , 2009 , to september 30 , 2012 .
records of patients with a copd diagnosis at any diagnosis position within the intake period from july 1 , 2009 , through september 30 , 2011 , were included . claims for laboratory , pathology , or
radiology services were not used to identify individuals with a specific condition , because their use could incorrectly identify individuals as having that condition based on the reason for testing ( eg , screening ) rather than the test results ; therefore , those claims were ignored during patient selection , and diagnoses were termed non - rule - out copd .
the first occurrence of non - rule - out copd diagnosis ( international classification of diseases , ninth revision , clinical modification codes 490.xx , 491.xx , 492.xx , 494.xx , or 496.xx ) ( e - table
1 ) was defined as the index event , and the date of the index event was defined as the index date .
the study proposal was presented to and accepted by the novartis outcomes research review forum .
eligible patients were aged 40 to 90 years ( inclusive ) , had copd , and used at least one long - acting muscarinic antagonist ( lama ) , long - acting 2-adrenergic agonist ( laba ) , inhaled corticosteroid ( ics)/laba , or lama + ics + laba from 180 days before the index date through 180 days after the index date .
patients were enrolled continuously in the medical , pharmacy benefit , and fee - for - service plan from 180 days before the index date to 360 days after the index date .
comorbidities were defined as any occurrence of a specific diagnosis code from 180 days before the index date through 180 days after the index date .
this time period , which does not fall completely within the baseline period or the 360-day follow - up period , was chosen to establish and solidify the baseline patient comorbidities being evaluated .
comorbidities of interest were identified prospectively and consisted of chronic kidney disease ( ckd ) ; cardiovascular disease ( cvd ) , including heart failure , stroke , acute myocardial infarction ( mi ) , and peripheral vascular disease ; asthma ; depression ; diabetes ; osteoporosis ; and anemia .
resource consumption was measured from 180 days prior to the index date to the index date ( for baseline assessments ) and from the index date through 360 days after the index date ( for outcomes assessments ) .
resource use assessments included all - cause and disease - specific ed visits , hospitalizations , office visits ( defined as any office visit to any doctor ) , outpatient visits , and total length of hospital stay ; in this instance , disease - specific means copd- or asthma - related . the health - care costs assessed included all - cause and disease - specific costs for ed visits , hospitalizations , office visits , and other outpatient visits , as well as medical , prescription drug , and total health - care costs .
other covariate variables included age , sex , region , employment status , and index medication ( the first drug class used during the period ) .
patient characteristics , comorbidities of interest , health - care use , and costs were summarized descriptively .
a generalized linear model ( glm ) was used to evaluate which comorbidities drive total costs after accounting for patient characteristics in the total population . after examining the data
, we selected glms with a log - link and  distribution to evaluate the incremental all - cause costs , adjusting for baseline demographics , resource use , and comorbidities . to better understand total costs that are potentially attributable to comorbidities , the average treatment effect ( change in the response by a change in a covariate ) of each comorbidity was calculated by using the recycled prediction method .
the predicted costs for patients with cvd were calculated based on the estimated glm ( with costs as the dependent variable ) by assuming all patients had cvd ( regardless of whether they had cvd ) while keeping other covariates as they were .
the predicted costs , for which every observation is treated as if it represents patients without cvd , were obtained in the same manner .
the average treatment effect was the mean difference in the predicted costs for the two groups .
thus , we compared two hypothetical populations ( one with cvd and one without cvd ) that had the exact same values for the other independent variables in the model .
cis were generated with the percentile method ( the 95% lower bound ci is the 2.5th percentile of the bootstrap distribution , and the 95% upper bound ci is the 97.5th percentile of the bootstrap distribution ) .
patient characteristics on the index date are summarized in table 1 , and health - care use and costs from the 180 days preceding the index date through the index date are summarized in table 2 .
the most common comorbidity was cvd ( 34.8% ) , followed by diabetes ( 22.8% ) , asthma ( 14.7% ) , anemia ( 14.2% ) , ckd ( 9.9% ) , depression ( 9.9% ) , and osteoporosis ( 6.9% ) .
most patients ( 52.8% ) had one or two comorbidities of interest . patients with ckd and anemia experienced the highest incidence of all - cause ed visits leading to hospitalizations ( 23.2% and 20.4% , respectively ) and all - cause hospitalizations ( 38.0% and 33.8% , respectively ) .
the percentages of all - cause office visits and of all - cause other outpatient visits were generally similar across the various comorbidity groups ( all - cause office visits , 93.8%-95.4% ; all - cause other outpatient visits , 95.1%-97.7% ) and were higher than those for patients with no baseline comorbidities of interest ( 83.9% and 84.6% , respectively ) .
ics = inhaled corticosteroid ; laba = long - acting 2-adrenergic agonist ; lama = long - acting muscarinic antagonist .
ckd = chronic kidney disease ; cvd = cardiovascular disease ; ics = inhaled corticosteroid ; laba = long - acting 2-adrenergic agonist ; lama = long - acting muscarinic agonist ; mi = myocardial infarction .
spouse / child / dependent relation . within the period from 180 d before the index date through 180 d after the index date ( inclusive ) .
includes heart failure , stroke , acute mi , and peripheral vascular disease . baseline resource use and
resource use from the index date ( exclusive ) through 180 d before the index date ( inclusive ) .
the prevalence of copd- or asthma - related hospitalizations was highest among patients with asthma at baseline ( 8.3% ) ; for the other baseline comorbidities , the frequencies of copd- or asthma - related hospitalizations were similar , ranging from 3.4% ( osteoporosis ) to 3.9% ( depression ) .
mean all - cause total health - care costs from the 180 days before the index date through the index date were highest among patients with ckd ( $ 19,405 ) and anemia ( $ 18,011 ) and lowest among those with asthma ( $ 10,583 ) and osteoporosis ( $ 11,438 ) .
mean copd- or asthma - related total health - care costs were highest among patients with asthma ( $ 1,845 ) and osteoporosis ( $ 1,566 ) .
in addition to those shown in table 2 , analyses were conducted based on the number of comorbidities present .
patients with four or more comorbidities experienced the highest incidence of ed visits leading to hospitalizations ( 33.1% ) , compared with 22.2% in those with three comorbidities , 13.8% in those with two comorbidities , 7.4% in those with one comorbidity , and 2.5% in those with no comorbidities .
similarly , the rate of all - cause hospitalizations was highest in patients with four or more comorbidities ( 50.4% ) and lowest in those with no comorbidities ( 5.0% ) .
all - cause total health - care costs increased as the number of comorbidities increased ( zero comorbidities of interest , $ 4,790 ; four or more comorbidities of interest , $ 27,895 ) , as did copd- or asthma - related total health - care costs ( zero comorbidity of interest , $ 871 ; four or more comorbidities of interest , $ 2,216 ) . during the time period from the index date through 360 days after the index date ,
38.6% of patients with copd and ckd and 34.3% of patients with copd and anemia had all - cause ed visits leading to hospitalizations ( fig 2a ) .
the percentage of patients experiencing all - cause hospitalizations was highest among those with ckd ( 57.0% ) and anemia ( 52.6% ) ( fig 2a ) .
the percentage of patients with copd- or asthma - related hospitalizations was highest among those with asthma ( 17.4% ) and cvd ( 12.0% ) ( fig 2a ) .
all - cause total health - care costs during the time period from the index date through 360 days following the index date were highest among patients with copd and ckd ( $ 41,288 ) and patients with copd and anemia ( $ 38,870 ) ( table 3 ) .
copd- or asthma - related total health - care costs were highest among patients with copd and asthma ( $ 5,389 ) and those with copd and ckd ( $ 5,117 ) .
a , b , resource use from index date through 360 d after the index date for each outcome .
ckd = chronic kidney disease ; cvd = cardiovascular disease ; er = emergency room .
total medical costs by comorbidity and number of comorbidities data are presented as mean ( sd ) .
costs are from index date through 360 d after the index date and are in 2012 us dollars . see table 1 legend for expansion of abbreviations .
patients with four or more comorbidities of interest experienced the highest incidence of ed visits leading to hospitalizations ( 50.1% vs 9.5% with no comorbidities ) and all - cause hospitalizations ( 68.7% vs 16.7% with no comorbidities ) ( fig 2b ) .
all - cause total health - care costs and copd- or asthma - related total health - care costs both increased as the number of comorbidities increased ( table 3 ) .
the reference group selected for the glm was female patients with copd aged 40 to 64 years , living in the south , employed , having an index medication of ics / laba fixed or loose - dose combination with no ed visits or hospitalizations regardless of relationship to asthma or copd , and who did not have ckd , cvd , asthma , depression , diabetes , osteoporosis , or anemia . in this group ,
a ratio , based on the impact on total health - care costs , was estimated for each variable in the model ( table 4 ) and represents multiplicative effects .
ratios for variables included in the generalized linear model arithmetic mean cost for the reference group was $ 12,408 .
characteristics with the greatest impact on costs included depression ( ratio , 1.35 ) , ckd ( ratio , 1.43 ) , anemia ( ratio , 1.54 ) , and cvd ( ratio , 1.55 ) comorbidities ( table 4 ) . the average treatment effect for each comorbidity after adjusting for age , sex , geographic location , baseline health - care use , employment status , and index copd medication is shown in figure 3 .
for the time period from the index date through 360 days following the index date , a patient with copd and anemia had , on average , $ 10,762 more in total health - care costs than a patient with copd but without anemia .
cvd and ckd increased total health - care costs by $ 9,882 and $ 8,912 , respectively .
difference in average total health - care cost by comorbidity from index date through 360 d after the index date in 2012 us dollars .
patient characteristics on the index date are summarized in table 1 , and health - care use and costs from the 180 days preceding the index date through the index date are summarized in table 2 .
the most common comorbidity was cvd ( 34.8% ) , followed by diabetes ( 22.8% ) , asthma ( 14.7% ) , anemia ( 14.2% ) , ckd ( 9.9% ) , depression ( 9.9% ) , and osteoporosis ( 6.9% ) .
most patients ( 52.8% ) had one or two comorbidities of interest . patients with ckd and anemia experienced the highest incidence of all - cause ed visits leading to hospitalizations ( 23.2% and 20.4% , respectively ) and all - cause hospitalizations ( 38.0% and 33.8% , respectively ) .
the percentages of all - cause office visits and of all - cause other outpatient visits were generally similar across the various comorbidity groups ( all - cause office visits , 93.8%-95.4% ; all - cause other outpatient visits , 95.1%-97.7% ) and were higher than those for patients with no baseline comorbidities of interest ( 83.9% and 84.6% , respectively ) .
ics = inhaled corticosteroid ; laba = long - acting 2-adrenergic agonist ; lama = long - acting muscarinic antagonist .
ckd = chronic kidney disease ; cvd = cardiovascular disease ; ics = inhaled corticosteroid ; laba = long - acting 2-adrenergic agonist ; lama = long - acting muscarinic agonist ; mi = myocardial infarction .
spouse / child / dependent relation . within the period from 180 d before the index date through 180 d after the index date ( inclusive ) .
includes heart failure , stroke , acute mi , and peripheral vascular disease . baseline resource use and
resource use from the index date ( exclusive ) through 180 d before the index date ( inclusive ) .
the prevalence of copd- or asthma - related hospitalizations was highest among patients with asthma at baseline ( 8.3% ) ; for the other baseline comorbidities , the frequencies of copd- or asthma - related hospitalizations were similar , ranging from 3.4% ( osteoporosis ) to 3.9% ( depression ) .
mean all - cause total health - care costs from the 180 days before the index date through the index date were highest among patients with ckd ( $ 19,405 ) and anemia ( $ 18,011 ) and lowest among those with asthma ( $ 10,583 ) and osteoporosis ( $ 11,438 ) .
mean copd- or asthma - related total health - care costs were highest among patients with asthma ( $ 1,845 ) and osteoporosis ( $ 1,566 ) .
in addition to those shown in table 2 , analyses were conducted based on the number of comorbidities present .
patients with four or more comorbidities experienced the highest incidence of ed visits leading to hospitalizations ( 33.1% ) , compared with 22.2% in those with three comorbidities , 13.8% in those with two comorbidities , 7.4% in those with one comorbidity , and 2.5% in those with no comorbidities .
similarly , the rate of all - cause hospitalizations was highest in patients with four or more comorbidities ( 50.4% ) and lowest in those with no comorbidities ( 5.0% ) .
all - cause total health - care costs increased as the number of comorbidities increased ( zero comorbidities of interest , $ 4,790 ; four or more comorbidities of interest , $ 27,895 ) , as did copd- or asthma - related total health - care costs ( zero comorbidity of interest , $ 871 ; four or more comorbidities of interest , $ 2,216 ) .
during the time period from the index date through 360 days after the index date , 38.6% of patients with copd and ckd and 34.3% of patients with copd and anemia had all - cause ed visits leading to hospitalizations ( fig 2a ) .
the percentage of patients experiencing all - cause hospitalizations was highest among those with ckd ( 57.0% ) and anemia ( 52.6% ) ( fig 2a ) .
the percentage of patients with copd- or asthma - related hospitalizations was highest among those with asthma ( 17.4% ) and cvd ( 12.0% ) ( fig 2a ) .
all - cause total health - care costs during the time period from the index date through 360 days following the index date were highest among patients with copd and ckd ( $ 41,288 ) and patients with copd and anemia ( $ 38,870 ) ( table 3 ) .
copd- or asthma - related total health - care costs were highest among patients with copd and asthma ( $ 5,389 ) and those with copd and ckd ( $ 5,117 ) . a , b , resource use from index date through 360 d after the index date for each outcome .
ckd = chronic kidney disease ; cvd = cardiovascular disease ; er = emergency room .
total medical costs by comorbidity and number of comorbidities data are presented as mean ( sd ) .
costs are from index date through 360 d after the index date and are in 2012 us dollars . see table 1 legend for expansion of abbreviations .
patients with four or more comorbidities of interest experienced the highest incidence of ed visits leading to hospitalizations ( 50.1% vs 9.5% with no comorbidities ) and all - cause hospitalizations ( 68.7% vs 16.7% with no comorbidities ) ( fig 2b ) .
all - cause total health - care costs and copd- or asthma - related total health - care costs both increased as the number of comorbidities increased ( table 3 ) .
the reference group selected for the glm was female patients with copd aged 40 to 64 years , living in the south , employed , having an index medication of ics / laba fixed or loose - dose combination with no ed visits or hospitalizations regardless of relationship to asthma or copd , and who did not have ckd , cvd , asthma , depression , diabetes , osteoporosis , or anemia . in this group ,
a ratio , based on the impact on total health - care costs , was estimated for each variable in the model ( table 4 ) and represents multiplicative effects .
ratios for variables included in the generalized linear model arithmetic mean cost for the reference group was $ 12,408 .
characteristics with the greatest impact on costs included depression ( ratio , 1.35 ) , ckd ( ratio , 1.43 ) , anemia ( ratio , 1.54 ) , and cvd ( ratio , 1.55 ) comorbidities ( table 4 ) . the average treatment effect for each comorbidity after adjusting for age , sex , geographic location , baseline health - care use , employment status , and index copd medication is shown in figure 3 .
for the time period from the index date through 360 days following the index date , a patient with copd and anemia had , on average , $ 10,762 more in total health - care costs than a patient with copd but without anemia .
cvd and ckd increased total health - care costs by $ 9,882 and $ 8,912 , respectively .
difference in average total health - care cost by comorbidity from index date through 360 d after the index date in 2012 us dollars .
our results were consistent with those of previously published work , in that a significant burden of comorbidity was associated with copd , and comorbid conditions were associated with incremental increases in resource use and health - care costs .
total health - care costs during the period from the index date through 360 days following the index date were greatest among patients with copd and ckd or anemia ; copd- or asthma - related total health - care costs were greatest among patients with copd and asthma and ckd .
these results were driven , in part , by high incidences of all - cause ed visits leading to hospitalizations among patients with copd and ckd or anemia , and a high incidence of copd- or asthma - related hospitalization among patients with copd and asthma .
multivariable analyses adjusted for age , sex , geographic location , baseline health - care use , employment status , and index copd medication showed that the effect of comorbidities on total health - care costs was greatest for anemia .
this finding is consistent with the high incidences of all - cause ed visits leading to hospitalizations and all - cause hospitalizations among patients with copd and anemia .
substantial treatment effects of cvd and ckd ( about $ 9,000 ) are likely attributable , in part , to the high incidence ( about 50% ) of all - cause hospitalization in both groups .
cavailles et al reviewed the pathophysiologic and epidemiologic links between copd and the comorbidities studied here , and concluded that shared risk factors and the influence of chronic systemic inflammation are likely contributors to these relationships .
smoking is a major risk factor for both copd and cvd , and cvd was the most common comorbidity in the copd population ; thus , the frequent coexistence of these two conditions is unsurprising .
however , the literature also suggests that the systemic inflammation associated with copd produces a  procoagulant state  and endothelial dysfunction that may contribute to thromboembolic events .
in fact , at least one study has shown that the link between cardiovascular events ( including death ) and copd is independent of smoking status and other confounding coronary risk factors .
there is no evidence of a direct role for copd - related inflammation in anemia , which was identified as the most costly of the comorbidities in this study .
however , older age , malnutrition , and cvd frequently accompany copd and are believed to play a role in the development of anemia in patients with copd .
consistent with our findings , ornek et al determined that anemia significantly increased the cost of copd treatment in patients hospitalized for acute exacerbation of copd . furthermore , anemia was independently prognostic for premature mortality , hospital admissions , and cumulative duration of hospitalization in patients with severe copd receiving long - term oxygen therapy .
our results support ckd as a key driver of total health - care costs as well as copd- and asthma - related health - care costs in patients with copd , although it was not as prevalent as other comorbidities studied .
epidemiologic studies have confirmed copd as a risk factor for ckd , and the literature suggests that renal function is sensitive to hypoxemia and hypercarbia . additionally , arterial stiffness associated with copd may damage glomeruli , and some copd medications may have nephrotoxic effects .
the presence of chronic renal failure significantly increased the cost of care in patients hospitalized for acute exacerbation of copd .
finally , copd- or asthma - related total health - care costs were higher among patients with copd and asthma than among those with any other comorbidity .
 overlap syndrome  refers to patients who have components of both conditions , and it is often used to describe elderly individuals in whom the distinction between asthma and copd is difficult to make . in a study of nearly 25,000 insured adults with copd , those with asthma had 1.6 times greater odds of having respiratory - related ed visits , hospitalizations , or both than did those with copd alone and demonstrated an approximately 50% increase in respiratory - related health - care costs .
hospital cost use for copd or bronchiectasis was also evaluated in a recent analysis of the nationwide inpatient sample and the nationwide emergency department sample database of the healthcare cost and utilization project .
although significant trends were not found in age - adjusted rates of hospital discharges from 2001 to 2012 , ed visits from 2006 to 2011 , or 30-day readmissions from 2009 to 2012 , the mean charges and costs of all discharges increased considerably from 2001 to 2012 , with aggregate charges for inpatient stays increasing from $ 8,023,983,422 in 2001 to $ 18,112,392,566 in 2012 .
this study was subject to several limitations . because it was restricted to patients who were on long - acting therapies , patients with the mildest form of copd and patients with more advanced disease who were not appropriately prescribed long - acting therapies
inherent to claims data research , the clinical accuracy of the coding could not be assessed .
in addition , patients with health maintenance organizations or full or partial capitated point - of - service insurance coverage were excluded from this study because the financial information for this population was incomplete .
further , this analysis did not include patients on medicaid and it contained < 8% of patients with managed medicare .
no information was available regarding the severity of disease and the level of treatment adherence .
an analysis in the younger , working - age copd population ( 45 - 64 years of age ) showed that these costs ( which include the costs of impaired productivity at work , lost productivity because of early retirement , disability pensions paid , and tax revenue lost ) are considerably higher than the direct medical cost of copd .
in conclusion , these results show that a high prevalence of patients with copd and multiple comorbidities have associated high resource use and costs , especially within the all - cause use category .
further research on comorbid conditions affecting the treatment adherence of patients with copd , copd pathogenic pathways , and worsening overall prognosis is necessary to elucidate the role of comorbidities in copd .
 background : the morbidity and mortality associated with copd exacts a considerable economic burden . comorbidities in copd are associated with poor health outcomes and increased costs . 
 our objective was to assess the impact of comorbidities on copd - associated costs in a large administrative claims dataset.methods:this was a retrospective observational study of data from the truven health marketscan commercial claims and encounters and the marketscan medicare supplemental databases from january 1 , 2009 , to september 30 , 2012 . 
 resource consumption was measured from the index date ( date of first occurrence of non - rule - out copd diagnosis ) to 360 days after the index date . 
 resource use ( all - cause and disease - specific [ ie , copd- or asthma - related ] ed visits , hospitalizations , office visits , other outpatient visits , and total length of hospital stay ) and health - care costs ( all - cause and disease - specific costs for ed visits , hospitalizations , office visits , and other outpatient visits and medical , prescription , and total health - care costs ) were assessed . 
 generalized linear models were used to evaluate the impact of comorbidities on total health - care costs , adjusting for age , sex , geographic location , baseline health - care use , employment status , and index copd medication.results:among 183,681 patients with copd , the most common comorbidities were cardiovascular disease ( 34.8% ) , diabetes ( 22.8% ) , asthma ( 14.7% ) , and anemia ( 14.2% ) . 
 most patients ( 52.8% ) had one or two comorbidities of interest . 
 the average all - cause total health - care costs from the index date to 360 days after the index date were highest for patients with chronic kidney disease ( $ 41,288 ) and anemia ( $ 38,870 ) . 
 the impact on total health - care costs was greatest for anemia ( $ 10,762 more , on average , than a patient with copd without anemia).conclusions : our analysis demonstrated that high resource use and costs were associated with copd and multiple comorbidities . 
Materials and Methods
Study Design
Patients
Variables
Data Analysis
Results
Patients
Postindex Resource Use and Costs by Comorbidities
Model Results
Discussion
Conclusions
Supplementary Material