Development and validation of a predictive model to identify patients at risk of severe COPD exacerbations using administrative claims data

Figures & data

Figure 1 Patient-selection timeline.

Note: Patients were required to be enrolled continuously for 6 months prediagnosis and 12 months postdiagnosis.

Table 1 COPD-exacerbation definitions

Exacerbation type	Definition
Nonsevere exacerbations (ambulatory)	A medical claim for an ER or outpatient visit with the following: 1. COPD diagnosis code (ICD-9-CM code 491.xx, 492.xx, or 496.xx) in the primary position OR 2. Respiratory failure diagnosis code (ICD-9-CM code 518.81, 518.83, or 518.84) in the primary position accompanied by a COPD diagnosis code in the secondary position OR 3. Any diagnosis code indicative of an acute exacerbation (ICD-9-CM codes 466–466.19, 480–486, 487.0, 490, 493.12, 493.22, 493.92, 494.1, 506.0–506.3, 511.0–511.1, or 518.82) in the primary position and a COPD diagnosis code in the secondary position AND 1. A prescription claim for any of the antibiotics commonly used for respiratory infections within 7 days of the visit OR 2. A prescription claim for an oral corticosteroid within 7 days of the visit
Severe exacerbation (requiring hospitalization)	A medical claim for a hospitalization with the following: 1. COPD diagnosis code in the primary position OR 2. Any diagnosis code indicative of an acute exacerbation in the primary position and a COPD diagnosis code in the secondary position OR 3. Respiratory failure diagnosis code in the primary position accompanied by a COPD diagnosis code in the secondary position

Abbreviations: ER, emergency room; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification.

Table 2 Baseline demographic characteristics of study population

Characteristics	Severe COPD exacerbations in prediction period		No severe COPD exacerbations in prediction period		P-value
	(n=5,317)		(n=40,405)
Age (years), mean, SDa	71.4	8.0	71.4	7.9	0.8411
Age (years), median, IQRb	71.0	11.0	71.0	11.0	0.9316
Age bracket, n, %c
55–59 years	412	7.7	3,189	7.9	0.3008
60–69 years	1,867	35.1	14,136	35.0
70–79 years	2,068	38.9	16,095	39.8
80–89 years	970	18.2	6,985	17.3
Sex, n, %c
Female	3,096	58.2	24,475	60.6	0.0042
Male	2,221	41.8	15,929	39.4
Unknown	<10	0	<10	0
Race/ethnicity, n, %c
White	3,610	67.9	27,764	68.7	<0.0001
Black	307	5.8	3,235	8.0
Hispanic	42	0.8	460	1.1
Others	49	0.9	512	1.3
Unknown	1,309	24.6	8,434	20.9
Geographic region, n, %c
Northeast	118	2.2	708	1.8	<0.0001
Midwest	1,421	26.7	9,662	23.9
South	3,559	66.9	27,611	68.3
West	219	4.1	2,424	6.0
Dual-eligibility, n, %c,d	129	2.5	1,531	3.9	<0.0001
Low-income-subsidy recipient, n, %c,d	278	5.3	2,779	7.0	<0.0001
Line of business, n, %c
Commercial	83	1.6	970	2.4	0.0001
Medicare	5,234	98.4	39,435	97.6

Note:

a Student’s t-test;

b Wilcoxon rank sum;

c χ²;

d denominators Medicare patients only.

Abbreviation: IQR, interquartile range.

Figure 2 Patient attrition.

Abbreviation: ICD-9, International Classification of Diseases, Ninth Revision.

Table 3 Baseline clinical characteristics of study population

Characteristics	Severe COPD exacerbations in prediction period		No severe COPD exacerbations in prediction period		P-value
	n=5,317		n=40,405
Any prior COPD exacerbation, n, %c	3,078	57.9	12,956	32.1	<0.0001
Mean, SD	1.02	1.17	0.45	0.77	<0.0001
One	1,659	31.2	9,392	23.2	<0.0001
Two	807	15.2	2,502	6.2	<0.0001
Three or more	612	11.5	1,062	2.6	<0.0001
Any prior severe COPD exacerbation, n, %c	1,928	36.3	5,679	14.1	<0.0001
Mean, SDa	0.50	0.78	0.16	0.41	<0.0001
One	1,382	26.0	5,103	12.6	<0.0001
Two	408	7.7	508	1.3	<0.0001
Three or more	39	1.6	32	0.1	<0.0001
Deyo–Charlson Comorbidity Index, mean, SDa	4.2	2.5	3.1	2.2	<0.0001
Median, IQRb	4.0	4.0	2.0	3.0	<0.0001
Comorbidities of interest, n, %c
Anxiety disorders	1,307	24.6	7,768	19.2	<0.0001
Cerebrovascular disease	1,317	24.8	8,174	20.2	<0.0001
Chronic kidney disease	1,405	26.4	9,250	22.9	<0.0001
Congestive heart failure	2,167	40.8	10,990	27.2	<0.0001
Coronary artery disease	2,640	49.7	17,056	42.2	<0.0001
Depressive disorders	723	30.4	6,268	23.9	<0.0001
Obesity	1,024	19.3	8,323	20.6	0.0228
Osteoarthritis	1,954	36.8	14,592	36.1	0.3645
Osteoporosis	549	23.1	6,333	24.1	0.2558
Sleep apnea	268	11.3	2,544	9.7	0.0133
Type 2 diabetes mellitus	2,293	43.1	16,149	40.0	<0.0001
Arteriosclerosis	1,036	19.5	6,764	16.7	<0.0001
Lower respiratory tract infections	2,789	52.5	14,478	35.8	<0.0001
Upper respiratory tract infections	1,273	23.9	9,939	24.6	0.2957
COPD-medication use
Long-acting bronchodilators, n, %c	2,784	52.4	15,622	38.7	<0.0001
30-day supply, mean, SDa	4.03	5.90	2.62	4.78	<0.0001
Long-acting muscarinic antagonists (LAMAs), n, %c	1,539	28.9	6,932	17.2	<0.0001
30-day supply, mean, SDa	1.69	3.40	0.98	2.72	<0.0001
Long-acting β2-agonists (LABAs), n, %c	159	3.0	593	1.5	<0.0001
30-day supply, mean, SDa	0.15	1.10	0.07	0.77	<0.0001
LABA + LAMA, n, %c	0	0.0	0	0.0
30-day supply, mean, SDa	0.00	0.00	0.00	0.00
LABA + inhaled corticosteroid (ICS), n, %c	2,196	41.3	12,363	30.6	<0.0001
30-day supply, mean, SDa	2.20	3.55	1.57	3.11	<0.0001
Short-acting bronchodilators, n, %c	3,643	68.5	21,414	53.0	<0.0001
30-day supply, mean, SDa	4.25	5.88	2.36	4.23	<0.0001
Short-acting β2-agonists (SABAs), n, %c	2,973	55.9	17,821	44.1	<0.0001
30-day supply, mean, SDa	2.59	4.12	1.59	3.12	<0.0001
Short-acting muscarinic antagonists (SAMAs), n, %c	639	12.0	2,715	6.7	<0.0001
30-day supply, mean, SDa	0.45	1.74	0.21	1.16	<0.0001
SABA + SAMA, n, %c	1,437	27.0	6,107	15.1	<0.0001
30-day supply, mean, SDa	1.21	3.01	0.56	2.02	<0.0001
ICSs, n, %c	2,582	48.6	14,719	36.4	<0.0001
30-day supply, mean, SDa	2.60	3.76	1.87	3.34	<0.0001
Systemic corticosteroids, n, %c	3,037	57.1	16,339	40.4	<0.0001
30-day supply, mean, SDa	1.40	2.98	0.65	2.04	<0.0001
Phosphodiesterase 4 inhibitors, n, %c	28	0.5	113	0.3	0.0023
30-day supply, mean, SDa	0.02	0.34	0.01	0.23	0.0425
Methylxanthines, n, %c	414	7.8	1,432	3.5	<0.0001
30-day supply, mean, SDa	0.53	2.30	0.25	1.60	<0.0001
Respiratory antibiotics, n, %c	3,261	61.3	21,373	52.9	<0.0001
30-day supply, mean, SDa	0.69	1.92	0.49	1.71	<0.0001
Others, n, %c
Oxygen-therapy use	2,773	52.2	11,038	27.3	<0.0001
Influenza vaccination	3,036	57.1	23,134	57.3	0.8295
Pneumococcal vaccination	563	10.6	4,072	10.1	0.2461
Smoking-cessation medications	168	3.2	764	1.9	<0.0001
Smoking-cessation counseling	2,248	42.3	11,796	29.2	<0.0001
Month of exacerbation, n, %c
January	511	9.6	1,842	4.6	<0.0001
February	459	8.6	1,536	3.8	<0.0001
March	489	9.2	1,681	4.2	<0.0001
April	441	8.3	1,464	3.6	<0.0001
May	427	8.0	1,372	3.4	<0.0001
June	378	7.1	1,190	2.9	<0.0001
July	471	8.9	1,332	3.3	<0.0001
August	421	7.9	1,340	3.3	<0.0001
September	427	8.0	1,458	3.6	<0.0001
October	422	7.9	1,524	3.8	<0.0001
November	437	8.2	1,512	3.7	<0.0001
December	494	9.3	1,642	4.1	<0.0001
Month of severe exacerbation, n, %c
January	119	5.0	501	1.9	<0.0001
February	93	3.9	379	1.4	<0.0001
March	87	3.7	393	1.5	<0.0001
April	96	4.0	325	1.2	<0.0001
May	84	3.5	321	1.2	<0.0001
June	61	2.6	287	1.1	<0.0001
July	60	2.5	271	1.0	<0.0001
August	93	3.9	280	1.1	<0.0001
September	84	3.5	303	1.2	<0.0001
October	79	3.3	313	1.2	<0.0001
November	94	4.0	317	1.2	<0.0001
December	116	4.9	407	1.6	<0.0001

Note:

a Student’s t-test;

b Wilcoxon rank sum;

c χ².

Abbreviation: IQR, interquartile range.

Table 4 Baseline health care-resource utilization of study population

Healthcare resource utilization characteristics	Severe COPD exacerbations in prediction period		No severe COPD exacerbations in prediction period		P-value
	(n=5,317)		(n=40,405)
All-cause resource use, n, %b	5,311	99.9	40,330	99.8	0.2355
Mean, SDa	25.0	17.9	22.3	17.2	<0.0001
All-cause outpatient visits, n, %b	5,296	99.6	40,266	99.7	0.5543
Mean, SDa	22.3	16.6	20.8	16.3	<0.0001
One	45	0.8	276	0.7	0.1801
Two	53	1.0	402	1.0	0.9897
Three or more	5,198	97.8	39,588	98.0	0.2956
All-cause hospitalizations, n, %b	3,056	57.5	14,340	35.5	<0.0001
Mean, SDa	1.3	1.7	0.6	1.0	<0.0001
One	1,418	26.7	9,018	22.3	<0.0001
Two	769	14.5	3,260	8.1	<0.0001
Three or more	869	16.3	2,062	5.1	<0.0001
All-cause emergency-room visits, n, %b	2,741	51.6	15,661	38.8	<0.0001
Mean, SDa	1.4	2.6	0.9	2.0	<0.0001
One	1,182	22.2	7,527	18.6	<0.0001
Two	593	11.2	3,565	8.8	<0.0001
Three	966	18.2	4,569	11.3	<0.0001
COPD-related resource use, n, %b	4,701	88.4	29,449	72.9	<0.0001
Mean, SDa	4.5	5.0	2.3	3.2	<0.0001
COPD-related outpatient visits, n, %b	3,801	71.5	23,048	57.0	<0.0001
Mean, SDa	2.7	3.9	1.6	2.7	<0.0001
One	1,032	19.4	8,972	22.2	<0.0001
Two	731	13.7	5,246	13.0	0.1199
Three or more	2,038	38.3	8,830	21.9	<0.0001
COPD-related hospitalizations, n, %b	2,746	51.6	10,288	25.5	<0.0001
Mean, SDa	1.0	1.5	0.4	0.7	<0.0001
One	1,428	26.9	7,374	18.3	<0.0001
Two	664	12.5	2,001	5.0	<0.0001
Three or more	654	12.3	913	2.3	<0.0001
COPD-related emergency-room visits, n, %b	1,858	34.9	7,925	19.6	<0.0001
Mean, SDa	0.8	1.8	0.4	1.1	<0.0001
One	955	18.0	4,605	11.4	<0.0001
Two	397	7.5	1,750	4.3	<0.0001
Three	506	9.5	1,570	3.9	<0.0001

Note:

a Student’s t-test;

b χ².

Table 5 Predictive model: stepwise logistic regression

	OR (95% CI)
Severe exacerbations in baseline period	1.50 (1.36–1.65)
Deyo–Charlson comorbidity score	1.47 (1.43–1.52)
COPD-related inpatient stays in baseline period	1.39 (1.26–1.53)
Oxygen use in baseline period	1.38 (1.31–1.44)
Geographical region – Northeast	1.31 (1.05–1.64)
Race – white	1.21 (1.04–1.40)
Geographical region – Midwest	1.16 (1.04–1.30)
COPD-related outpatient visits in baseline period	1.15 (1.09–1.22)
COPD-related emergency-room visit in baseline period	1.15 (1.08–1.22)
Methylxanthine use in baseline period	1.13 (1.03–1.24)
Albuterol–ipratropium use in baseline period	1.11 (1.05–1.170)
Smoking-cessation counseling in baseline period	1.06 (1.01–1.11)
Systemic corticosteroids in baseline period	1.04 (1.02–1.05)
All-cause emergency-room visits in baseline period	1.04 (1.01–1.06)
Short-acting β-agonists in baseline period	1.03 (1.02–1.04)
COPD-related outpatient visits in baseline period	1.03 (1.01–1.04)
Long-acting β-agonists in baseline period	1.02 (1.02–1.03)
Geographical region – South	1.00 (0.91–1.11)
All-cause outpatient visits in baseline period	0.99 (0.99–1.00)
Coronary artery disease in baseline period	0.94 (0.89–0.99)
Race – others	0.94 (0.64–1.37)
Congestive heart failure in baseline period	0.90 (0.85–0.95)
Obesity in baseline period	0.88 (0.83–0.93)
All-cause inpatient visits in baseline period	0.88 (0.81–0.95)
Cerebrovascular disease in baseline period	0.86 (0.81–0.91)
Race – black	0.86 (0.70–1.05)
Low income subsidy status on index date	0.85 (0.77–0.94)
Type 2 diabetes mellitus in baseline period	0.76 (0.72–0.80)
Race – Hispanic	0.72 (0.47–1.09)
Chronic kidney disease in baseline period	0.70 (0.65–0.74)
Commercial health plan on index date	0.68 (0.56–0.83)