Incidence and outcomes of patients hospitalized with COPD exacerbation with and without pneumonia

Figures & data

Figure 1 Proportion of pneumonic and nonpneumonic COPD exacerbations according to number of exacerbations, Denmark, 2006–2012.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Figure 2 Incidence rates of pneumonic and nonpneumonic COPD exacerbations in individuals aged 40 years and older in Denmark, 2006–2012.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 1 Baseline characteristics of patients with a first-time hospitalization for a COPD exacerbation in Denmark, 2006–2012

Characteristic	Exacerbation type
	Nonpneumonic exacerbation		Pneumonic exacerbation
	No	%	No	%
Overall	33,552	100	18,968	100
Respiratory medications in the year prior to first hospitalization
No respiratory medication use	7,897	23.5	5,309	28.0
Use of respiratory medications other than inhaled corticosteroids	11,030	32.9	6,592	34.8
Use of inhaled corticosteroids	3,388	10.1	1,788	9.4
Use of oral corticosteroids	8,979	26.8	3,917	20.7
Continuous use of oral corticosteroids	2,258	6.7	1,362	7.2
Sex
Female	18,400	54.8	9,411	49.6
Male	15,152	45.2	9,557	50.4
Age, years
40–49	1,538	4.6	552	2.9
50–59	4,036	12.0	1,792	9.4
60–69	7,954	23.7	4,125	21.7
70–79	11,247	33.5	6,421	33.9
80–89	7,789	23.2	5,291	27.9
90 and older	988	2.9	787	4.1
Marital status
Married	13,281	42.3	7,336	42.6
Widowed	9,841	29.3	5,765	30.4
Divorced	6,472	19.3	3,338	17.6
Unmarried	1,779	5.3	857	4.5
Unknown	1,143	3.4	794	4.2
CCI score
0	16,527	49.3	8,083	42.6
1	6,811	20.3	4,077	21.5
2	5,067	15.1	3,146	16.6
≥3	5,147	15.3	3,662	19.3

Abbreviations: CCI, Charlson Comorbidity Index; COPD, chronic obstructive pulmonary disease.

Figure 3 Proportion of comorbidities in patients with pneumonic and nonpneumonic COPD exacerbations, Denmark, 2006–2012.

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 2 Health resource utilization among patients with a first-time nonpneumonic or pneumonic COPD exacerbation, Denmark 2006–2012

Health resource utilization	Exacerbation type		Prevalence proportion ratio pneumonic vs nonpneumonic (95% CI)
	Nonpneumonic	Pneumonic
Median LOS (IQR), days	4 (2–8)	7 (4–11)	–
ICU stay
N (%)	2,585 (7.7)	2,373 (12.5)	1.63 (1.54–1.71)
Mechanical ventilation
N (%)	1,106 (3.3)	1,315 (6.9)	2.10 (1.95–2.27)
Noninvasive mechanical ventilation
N (%)	2,240 (6.7)	1,841 (9.7)	1.45 (1.37–1.54)
Inotropic use
N (%)	756 (2.3)	920 (4.9)	2.15 (1.94–2.37)
Dialysis
N (%)	157 (0.5)	154 (0.8)	1.74 (1.39–2.17)
30-day acute readmission of any cause
N (%)	5,886 (17.5)	3,453 (18.2)	1.04 (1.00–1.08)

Abbreviations: CI, confidence interval; COPD, chronic obstructive pulmonary disease; ICU, intensive care unit; IQR, interquartile range; LOS, length of stay.

Table 3 Crude and adjusted risk of 30-day mortality according to number of exacerbationa

Exacerbation number	Exacerbation type	Patients, N	30-day mortality (%)	Crude HR (95% CI)	Adjusted HRb (95% CI)
First	Nonpneumonic	33,552	8.3	1 (reference)	1 (reference)
	Pneumonic	18,968	12.1	1.35 (1.31–1.39)	1.20 (1.17–1.24)
Second	Nonpneumonic	18,774	10.2	1 (reference)	1 (reference)
	Pneumonic	11,878	15.0	1.33 (1.29–1.38)	1.14 (1.11–1.18)
Third	Nonpneumonic	13,173	10.4	1 (reference)	1 (reference)
	Pneumonic	7,356	15.2	1.27 (1.22–1.32)	1.12 (1.08–1.17)
Fourth	Nonpneumonic	9,727	10.5	1 (reference)	1 (reference)
	Pneumonic	4,907	13.5	1.20 (1.15–1.26)	1.08 (1.03–1.14)
Fifth	Nonpneumonic	7,524	10.4	1 (reference)	1 (reference)
	Pneumonic	3,450	14.1	1.22 (1.16–1.29)	1.10 (1.04–1.16)
Sixth	Nonpneumonic	5,873	10.1	1 (reference)	1 (reference)
	Pneumonic	2,553	13.3	1.19 (1.12–1.27)	1.12 (1.06–1.19)
Seventh or greater	Nonpneumonic	31,254	8.9	1 (reference)	1 (reference)
	Pneumonic	10,770	11.3	1.17 (1.13–1.20)	1.10 (1.07–1.13)

Notes:

a Risk of death is assessed from the admission date with first exacerbation among all patients with a first exacerbation, from the admission date with second exacerbation among all patients who have a second exacerbation, and so forth.

b Adjusted for age, sex, CCI score, and respiratory medications as a marker of COPD severity.

Abbreviations: CCI, Charlson Comorbidity Index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio.

Table 4 Crude and adjusted risk of a subsequent exacerbation according to number of exacerbationa

Exacerbation number	Exacerbation type	Patients with exacerbation, N	Proportion with a subsequent exacerbation (%)	Median time to subsequent exacerbation (days)	Crude HR (95% CI)	Adjusted HRb (95% CI)
First	Pneumonic	14,560	43.4	213	1 (reference)	1 (reference)
	Nonpneumonic	7,073	37.3	206	0.94 (0.92–0.97)	0.93 (0.91–0.96)
Second	Pneumonic	10,949	58.3	142	1 (reference)	1 (reference)
	Nonpneumonic	5,786	48.7	146	0.87 (0.85–0.90)	0.88 (0.85–0.91)
Third	Pneumonic	8,581	65.1	106	1 (reference)	1 (reference)
	Nonpneumonic	4,131	56.2	120	0.90 (0.86–0.93)	0.92 (0.88–0.95)
Fourth	Pneumonic	6,838	70.3	83	1 (reference)	1 (reference)
	Nonpneumonic	3,016	61.5	97	0.86 (0.82–0.90)	0.87 (0.84–0.91)
Fifth	Pneumonic	5,433	72.2	75	1 (reference)	1 (reference)
	Nonpneumonic	2,223	64.4	86	0.90 (0.85–0.94)	0.91 (0.86–0.95)
Sixth	Pneumonic	4,405	75.0	66	1 (reference)	1 (reference)
	Nonpneumonic	1,739	68.1	74	0.93 (0.88–0.98)	0.94 (0.89–1.00)
Seventh or greater	Pneumonic	25,839	82.7	38	1 (reference)	1 (reference)
	Nonpneumonic	8,151	75.7	48	0.86 (0.84–0.89)	0.88 (0.86–0.90)

Notes:

a Risk of new exacerbation is assessed from the admission date with first exacerbation among all patients with a first exacerbation, from the admission date with second exacerbation among all patients who have a second exacerbation, and so forth.

b Adjusted for age, sex, CCI score, and respiratory medications as a marker of COPD severity.

Abbreviations: CCI, Charlson Comorbidity Index; CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio.

Table S1 ICD and ATC classification system codes used in the study

Codes used for identifying COPD exacerbation
Simple and mucopurulent chronic bronchitis	ICD-10: J41
Chronic bronchitis	ICD-10: J42
Emphysema	ICD-10: J43
COPD	ICD-10: J44
Respiratory failure	ICD-10: J96
Acute respiratory infection	ICD-10: J00–J06, J09–J11, J13, J14–J18, J20–J22
Chronic lower respiratory disease	ICD-10: J40–J47
Acute respiratory distress	ICD-10: J80
Abscess of lung or pyothorax/empyema	ICD-10: J85–J86
Codes used for identifying pneumonia	ICD-10: J12–J18
Charlson Comorbidity Index
Score 1
Myocardial infarction	ICD-10: I21, I22, I23
Congestive heart failure	ICD-10: I50, I11.0, I13.0, I13.2
Peripheral vascular disease	ICD-10: I70, I71, I72, I73, I74, I77
Cerebrovascular disease	ICD-10: I60–I69, G45, G46
Dementia	ICD-10: F00–F03, F05.1, G30
Chronic pulmonary disease*	ICD-10: J40, J45–J47, J60–J67, J68.4, J70.1, J70.3, J84.1, J92.0, J96.1, J98.2, J98.3
Connective tissue disease	ICD-10: M05, M06, M08, M09, M30, M31, M32, M33, M34, M35, M36, D86
Ulcer disease	ICD-10: K22.1, K25–K28
Mild liver disease	ICD-10: B18, K70.0–K70.3, K70.9, K71, K73, K74, K76.0
Diabetes types 1 and 2	ICD-10: E10.0, E10.1, E10.9, E11.0, E11.1, E11.9
Score 2
Hemiplegia	ICD-10: G81, G82
Moderate-to-severe renal disease	ICD-10: 12, I13, N00–N05, N07, N11, N14, N17–N19, Q61
Diabetes with end-organ damage	ICD-10: E10.2–E10.8, E11.2–E11.8
Any tumor	ICD-10: C00–C75
Leukemia	ICD-10: C91–C95
Lymphoma	ICD-10: C81–C85, C88, C90, C96
Score 3
Moderate-to-severe liver disease	ICD-10: B15.0, B16.0, B16.2, B19.0, K70.4, K72, K76.6, I85
Score 6
Metastatic solid tumor	ICD-10: C76–C80
AIDS	ICD-10: B21–B24
Additional comorbidities
Alcoholism-related diseases	ICD-10: F10.7–F10.9, G31.2, G62.1, G72.1, I42.6, K.29.2, K70, K86.0
Atrial fibrillation/flutter	ICD-10: I48
Asthma	ICD-10: J45
Hypertension	ICD-10: I10–I13
Osteoporosis	ICD-10: M80, M81
Venous thromboembolism	ICD-10: I80.1–3; I26.0; I26.9
Additional codes
Mechanical ventilation	Treatment code: BGDA0
Noninvasive mechanical ventilation	Treatment code: BGDA1
Dialysis	ICD-10: BJFD0
Treatment with inotropic agents	Treatment code: BFHC92; BFHC93; BFHC95
Respiratory medications
1) COPD with continuous oral glucocorticoid treatment	≥1 prescription for medications with ATC code H02AB group (except injections) 365 days before index date, with medication possession ratio >0.7, ie, total number of pills in package(s) covering more than 70% of the 365 days
2) COPD with oral glucocorticoid treatment	≥1 prescription for medications with ATC code H02AB group (except injections) 365 days before index date
3) COPD with inhaled corticosteroid treatment	≥1 prescription 365 days before index date of inhaled corticosteroids: beclomethasone, mometasone, fluticasone, budesonide (ATC codes R03BA01, R03BA02, R03BA03, R03BA05, R03BA07), or combinations of inhaled corticosteroids and long acting β-agonists: salmeterol + fluticasone and formoterol + budesonide (ATC codes R03AK06 and R03AK07, respectively)
4) COPD treated with other therapies than corticosteroids	≥1 prescriptions for medications with ATC code R03 group other than those in group 3 within 365 days before index date

Note:

* Excluding COPD ICD-10: J41–J44.

Abbreviations: ATC, Anatomical Therapeutic Chemical; COPD, chronic obstructive pulmonary disease; ICD, International classification of diseases.

Table S2 Sensitivity analysis categorizing patients with a discharge diagnosis of “chronic obstructive pulmonary disease with acute lower respiratory infection” (ICD-10: J44.0) as having a pneumonic COPD exacerbation

Exacerbation number	Exacerbation type	Risk of 30-day mortality			Risk of a subsequent hospitalization for a COPD exacerbation
		No of patients (%)	30-day mortality (%)	Adjusted HRa (95% CI)	Median time to subsequent exacerbation (days)	Proportion with a subsequent exacerbation (%)	Adjusted HRa (95% CI)
First	Nonpneumonic	28,582 (54.4)	8.4	1 (reference)	209	42.8	1 (reference)
	Pneumonic	23,938 (45.6)	11.3	1.15 (1.11–1.18)	214	39.2	0.97 (0.94–1.00)
Second	Nonpneumonic	15,928 (52.0)	10.5	1 (reference)	141	57.9	1 (reference)
	Pneumonic	14,724 (48.0)	13.7	1.10 (1.07–1.14)	146	51.0	0.91 (0.88–0.94)
Third	Nonpneumonic	11,046 (53.8)	10.6	1 (reference)	105	65.0	1 (reference)
	Pneumonic	9,483 (46.2)	14.0	1.12 (1.08–1.16)	117	58.4	0.94 (0.91–0.97)
Fourth	Nonpneumonic	8,164 (55.8)	10.8	1 (reference)	82	70.0	1 (reference)
	Pneumonic	6,470 (44.2)	12.3	1.07 (1.02–1.11)	94	64.0	0.90 (0.87–0.94)
Fifth	Nonpneumonic	6,308 (57.5)	10.7	1 (reference)	74	72.1	1 (reference)
	Pneumonic	4,666 (42.5)	12.8	1.10 (1.04–1.15)	84	66.7	0.92 (0.88–0.97)
Sixth	Nonpneumonic	4,923 (58.4)	10.2	1 (reference)	63	75.2	1 (reference)
	Pneumonic	3,503 (41.6)	12.4	1.11 (1.05–1.18)	74	69.7	0.92 (0.88–0.97)
Seventh or greater	Nonpneumonic	26,414 (62.9)	8.7	1 (reference)	38	82.8	1 (reference)
	Pneumonic	15,610 (31.7)	10.8	1.09 (0.07–1.12)	45	77.6	0.91 (0.89–0.93)

Note:

a Adjusted for age, sex, CCI score, and respiratory medications as a marker of COPD severity.

Abbreviations: CI, confidence interval; CCI, Charlson Comorbidity Index; COPD, chronic obstructive pulmonary disease; HR, hazard ratio.