Impact of COPD diagnosis timing on clinical and economic outcomes: the ARCTIC observational cohort study

Figures & data

Table 1 Patient demographics of the early versus late diagnosis populations

Variable^a	Early diagnosis (n=3,870)	Late diagnosis (n=8,827)	p-value
Mean age (years)	68.72	69.47	0.0005
Gender, n (%)			<0.0001
Female	1,821 (47.05)	5,074 (57.48)
Male	2,049 (52.95)	3,753 (42.52)
Comorbidities
Number of Charlson Comorbidity groups (95% CI)	1.48 (1.46–1.52)	1.81 (1.79–1.83)	<0.0001
Charlson Comorbidity Index value (95% CI)	1.58 (1.54–1.62)	1.94 (1.91–1.97)	<0.0001
Comorbidities by ICD-10 code % (95% CI)
Asthma, J45	3.93 (2.76–5.04)	22.01 (21.3–22.8)	<0.0001
Rhinitis, J30/J31	0.54 (0.14–0.92)	2.02 (1.76–2.28)	<0.0001
Cardiovascular diseases, I00–I99	40.31 (39.4–42.4)	46.6 (45.4–47.4)	<0.0001
Ischemic heart diseases, I20–I25	10.78 (9.99–12.0)	12.41 (11.6–13.0)	0.009
Hypertensive diseases, I10	24.13 (23.1–25.8)	29.68 (28.6–30.5)	<0.0001
Cerebrovascular diseases, I60–I69	4.88 (4.31–5.70)	5.29 (4.78–5.70)	0.3404
Diabetes type I, E10	1.86 (1.38–2.33)	2.56 (2.24–2.88)	0.0165
Diabetes type II, E11/E13	6.77 (5.94–7.75)	10.13 (9.50–10.7)	<0.0001
Hyperlipidemia, E78.5	2.40 (1.88–2.93)	3.07 (2.72–3.42)	0.0381
Depression, F32/F33	4.81 (3.95–5.50)	7.28 (6.81–7.84)	<0.0001
Anxiety, F40/F41	3.90 (3.10–4.46)	5.39 (5.00–5.89)	<0.0001
Mild cognitive impairment, F06.7	0.34 (0.13–0.58)	0.60 (0.44–0.74)	0.0564
Osteoporosis, M80/M81	1.91 (1.48–2.51)	3.22 (2.84–3.53)	<0.0001
Fractures, S2	6.82 (6.04–7.70)	7.76 (7.19–8.29)	0.0641
Lung cancer, C34	0.93 (0.59–1.28)	1.35 (1.12–1.57)	0.0484
Medication use by ATC code,% (95% CI)
Treatment of cardiac disease, C01	13.13 (12.3–14.27)	18.55 (17.6–19.2)	<0.0001
Antihypertensives, C02	0.83 (0.52–1.17)	1.19 (0.97–1.40)	0.0687
Beta-blocking agents, C07	25.99 (24.9–27.8)	33.70 (32.6–34.5)	<0.0001
Calcium channel blockers, C08	15.87 (14.9–17.4)	22.51 (21.6–23.2)	<0.0001
Agents acting on the renin-angiotensin system, C09	24.86 (23.8–26.7)	36.04 (34.9–36.8)	<0.0001
Lipid modifying agents, C10	18.94 (17.8–20.4)	26.46 (25.5–27.2)	<0.0001
Diabetes medication, A10	7.62 (6.68–8.68)	13.15 (12.5–13.8)	<0.0001
Antidepressants, N06A	16.77 (15.3–18.0)	27.88 (27.0–28.8)	<0.0001
Central pain killers, N02BE/N02A/M01AE	28.32 (26.9–30.0)	50.38 (49.3–51.3)	<0.0001
Bisphosphonates, M05BA	2.12 (1.55–2.86)	5.66 (5.19–6.06)	<0.0001
Proton pump inhibitors, A02	16.5 (15.1–17.9)	34.6 (33.7–35.5)	<0.0001
Oral steroids, H02AB	5.45 (4.15–6.67)	29.43 (28.6–30.3)	<0.0001
Antibiotic for airways, J01AA/J01CA	14.19 (12.6–15.5)	46.55 (45.7–47.6)	<0.0001
Health care utilization
Hospital visits per year for any reason, n	0.41 (0.37–0.45)	0.56 (0.54–0.59)	<0.0001
Outpatient^b visits per year, n	1.36 (1.21–1.47)	2.24 (2.16–2.33)	<0.0001
Primary care contacts per year, n	7.76 (7.22–8.41)	13.3 (12.9–13.4)	<0.0001
Patients with primary care contacts,%	78.4 (77.1–79.7)	77.9 (77.0–78.7)	0.4739
Patients with outpatient hospital visits,%	57.2 (55.7–58.6)	72.1 (71.1–73.1)	<0.0001
Patients with overnight stays,%	33.0 (31.7–34.7)	39.7 (38.6–40.6)	<0.0001

Notes: ^aVariables quoted for 2 years prior to COPD diagnosis (index) date unless otherwise stated; all variables except age itself are calculated with age as a covariate. ^bOutpatient visit: a visit where the patient does not stay overnight at the hospital.

Abbreviations: ATC, anatomical therapeutic chemical; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ICD-10, international classification of disease code.

Figure 1 Study cohorts and criteria for early versus late COPD diagnosis. ^aIndicator diagnosis codes; Pneumonia J10–J18; respiratory diseases J00–J99, excluding pneumonia; oral steroids H02AB; antibiotics for respiratory disease J01AA, J01CA; prescription for respiratory disease R01–R03, R05–R07; lung function measurements from spirometry database and laboratory module in EMR. Disposition of patients by COPD and concomitant asthma versus COPD only is based on diagnosis at any time during the patient’s disease history.

Abbreviation: EMR, electronic medical records.

Figure 2 Risk of exacerbations and mortality by stage of diagnosis (early vs late). Risk of exacerbations (A) and mortality (B) in the total population and risk of exacerbations (C) and mortality (D) in patients excluding those with concomitant asthma, in the year following diagnosis.

Table 2 Influence of asthma on time to first exacerbation and mortality, early versus late COPD diagnosis

Outcome	All patients late diagnosis (n=8,827)	Late diagnosis concomitant asthma (n=3,868)	COPD-only
			Early diagnosis (n=3,222)	Late diagnosis (n=4,959)
Column heading versus early diagnosis with concomitant asthma (n=648)
Exacerbation	1.42 (1.31–1.55)^a	1.43 (1.31–1.56)^a	0.89 (0.81–0.97)^b	1.41 (1.30–1.54)^a
Mortality	1.41 (1.11–1.80)^b	1.42 (1.12–1.81)^b	1.71 (1.34–2.17)^a	1.82 (1.44–2.31)^a

Notes: ^aP<0.0001; ^bP<0.05. Data are for the 2 years following COPD diagnosis, presented as HR (95% confidence interval), patients with early versus late diagnosis. Concomitant asthma includes patients with a comorbid asthma diagnosis.

Abbreviations: COPD, chronic obstructive pulmonary disease; HR, hazard ratio.

Table 3 Direct health care costs and utilization in patients with early versus late COPD diagnosis

Variable^a	Early diagnosis (N=3,870)	Late diagnosis (N=8,827)	p-value
Cost per patient, Euro (95% CI)
Total for respiratory drugs (R03)	386.5 (353.7–419.4)	900.1 (878.3–921.8)	<0.0001
Public cost	314.0 (283.9–344.1)	782.1 (762.1–802)	<0.0001
Individual patient cost	72.6 (68.4–76.8)	118.0 (115.3–120.8)	<0.0001
Total drug cost per patient	460.8 (396.6–524.9)	716.6 (674.2–759.1)	<0.0001
Public cost	373.2 (310.4–436.0)	595.3 (553.7–636.8)	<0.0001
Individual patient cost	87.6 (80.0–95.3)	121.4 (116.4–126.5)	<0.0001
Utilization per patient per year, n (95% CI)
Nights at hospital (COPD-related; J45)	0.16 (0.03–0.38)	1.17 (1.02–1.30)	<0.0001
Nights at hospital (non-COPD)	11.65 (11.04–12.55)	11.58 (11.01–12.02)	0.5487
Hospitalization events (COPD-related; J44)	0.03 (0.01–0.05)	0.17 (0.16–0.18)	<0.0001
Hospitalization events (non-COPD)	1.68 (1.59–1.78)	1.79 (1.72–1.85)	0.0933
Out hospital visits^b (COPD-related; J45)	0.04 (0.02–0.06)	0.15 (0.14–0.16)	<0.0001
Out hospital visits^b (non-COPD)	3.76 (3.44–4.02)	4.74 (4.56–4.94)	<0.0001
Primary care contact with physician	13.06 (12.41–13.73)	15.77 (15.33–16.21)	<0.0001
Primary care contact with persons other than physician	9.20 (8.42–9.98)	12.48 (11.96–13.00)	<0.0001
Number of referrals	0.99 (0.91–1.06)	1.22 (1.17–1.28)	<0.0001

Notes: ^aAll variables are calculated with age as a covariate. Data are for the 2 years following COPD diagnosis. ^bOut hospital visit: a visit where the patient does not stay overnight at the hospital. R03 indicates the ATC prescription code for respiratory disease. Exchange rates in 2013, 8 Swedish Krona= 1 Euro.

Figure 3 Time trend in direct costs (Euro/year) according to the stage of diagnosis (early vs late). In the year 2007, 2010, 2012 and 2013, total yearly costs were significantly higher for late diagnosis versus early diagnosis.

Figure 4 Direct costs during the 2 years after COPD diagnosis by early vs late diagnosis. Costs were calculated from Swedish Krona based on exchange rates in 2013.

Abbreviations: hospital nights, number of nights where the patient has been at the hospital; hospital visit, outpatient care where the patient did not stay overnight at the hospital.

Table 4 Health care resource utilization stratified by a concomitant diagnosis of asthma, early versus late diagnosis

Variable^a	Early diagnosis			Late diagnosis
	Concomitant asthma (N=648)	COPD only (N=3,222)	p-value^b	Concomitant asthma (N=3,868)	COPD only (N=4,959)	p-value^b
Mean age, years	66.27	69.21	<0.0001	68.51	70.22	<0.001
Number of hospital visits per year for any reason	0.35	0.42	0.0912	0.60	0.53	0.0225
Number of out hospital visits per year^c	1.11	1.41	0.0168	2.20	2.27	0.4461
Number of primary care contacts per year	7.44	7.82	0.4790	15.97	11.16	<0.0001
Patients with overnight stays,%	28.70	33.80	0.0118	41.11	38.66	0.0196
Patients with primary care contact,%	79.48	78.21	0.4758	82.01	74.61	<0.0001

Notes: ^aAll variables except age itself are calculated with age as a covariate. Data are for the 2 years prior to COPD diagnosis. ^bp-values indicate comparisons between patients with a concomitant diagnosis of asthma and those with COPD-only. ^cOut hospital visit: a visit where the patient does not stay overnight at the hospital.

Table S1 Risk of exacerbations and mortality according to the stage of diagnosis (early versus late): total population

Years since index date	Risk of exacerbation, percentage of patients without event (95% CI)		Risk of mortality, percentage of patients without event (95% CI)
	Early diagnosis	Late diagnosis	Early diagnosis	Late diagnosis
2.5	35.0 (33.5–36.5)	18.1 (17.3–18.9)	83.7 (82.5–84.9)	82.6 (81.8–83.5)
5.0	22.7 (21.3–24.1)	10.7 (10.0–11.4)	71.5 (69.9–73.0)	69.6 (68.5–70.7)
7.5	16.2 (14.9–17.5)	7.4 (6.7–8.1)	59.4 (57.6–61.2)	58.9 (57.6–60.3)
10.0	12.8 (11.6–14.1)	5.8 (5.2–6.5)	48.8 (46.8–50.8)	48.1 (46.4–49.7)
12.5	11.4 (10.2–12.7)	5.1 (4.4–5.8)	38.7 (36.5–41.0)	39.1 (37.1–41.0)
15.0	10.5 (9.2–11.9)	4.7 (4.0–5.5)	30.8 (28.0–33.6)	30.8 (28.2–33.5)
17.5	10.0 (8.5–11.6)	4.7 (4.0–5.5)	24.4 (20.2–28.9)	24.8 (19.7–30.1)

Abbreviation: CI, confidence interval.

Table S2 Risk of exacerbations and mortality according to the stage of diagnosis (early versus late): patients excluding those with concomitant asthma (COPD-only population)

Years since index date	Risk of exacerbation, percentage of patients without event (95% CI)		Risk of mortality, percentage of patients without event (95% CI)
	Early diagnosis	Late diagnosis	Early diagnosis	Late diagnosis
2.5	35.9 (34.3–37.6)	19.0 (17.9–20.2)	81.6 (80.1–82.9)	80.2 (79.0–81.4)
5.0	24.0 (22.4–25.5)	12.0 (11.0–13.1)	68.6 (66.9–70.3)	65.3 (63.7–66.9)
7.5	17.4 (15.9–18.9)	8.3 (7.3–9.4)	56.1 (54.0–58.1)	53.9 (51.9–55.8)
10.0	14.2 (12.8– 15.6)	6.3 (5.3–7.4)	45.6 (43.3–47.8)	42.9 (40.5–45.3)
12.5	12.8 (11.4–14.3)	5.4 (4.4–6.6)	36.3 (33.7–38.9)	34.5 (31.6–37.5)
15.0	11.7 (10.1–13.3)	4.8 (3.6–6.2)	29.7 (26.4–33.1)	24.3 (20.0–28.9)
17.5	11.7 (10.1–13.3)	4.8 (3.6–6.2)	24.7 (19.6–30.1)	20.6 (13.5–28.8)

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease.

Table S3 Time trend in direct overall costs (Euro/year) according to the stage of diagnosis (early versus late)

Year	Total, €/year	Early diagnosis, €/year	Late diagnosis, €/year
2006	9,776.4	8,474.2	10,835
2007	9,450.4	7,890.3	10,656
2008	9,202.5	8,515.4	9,692.2
2009	10,715	9,346.9	11,611
2010	10,626	8,825.2	11,673
2011	11,126	9,687.3	11,871
2012	10,947	9,138.5	11,816
2013	10,859	8,994.9	11,677

Table S4 Health care resource utilization direct costs over 2 years after index date according to stage of diagnosis (late vs early)

	Early diagnosis, €	Late diagnosis, €
Drugs, respiratory (R03)	386.5	900.1
Drugs, other	460.8	716.6
Hospital nights, COPD (J45)	191.6	1,397.48
Hospital nights, not COPD	13,944.89	13,865.85
Hospital visits, COPD (J45)	15.0	56.25
Hospital visits, not COPD	1,410.0	1,777.5
Primary care contacts, physician	2,386.72	2,881.97
Primary care contacts, not physician	685.4	929.76

Notes: Costs were based on unit costs for hospital nights (9,580 SEK), hospital visits (3,000 SEK), primary care visits, physician (1,462 SEK) and primary care visits, nurse (596 SEK) and converted to Euros based on exchange rates in 2013 (8/1).

Abbreviations: COPD, chronic obstructive pulmonary disease; SEK, Swedish Krona; Hospital nights, number of nights where the patient has been at the hospital; hospital visit, outpatient care where the patient did not stay overnight at the hospital.