In 2018 and 2019, a total of 4,261 patients received prehospital inhaled bronchodilator treatment during 6,318 ambulance transports in the Central Denmark Region. The final study cohort was reached after the exclusion of 330 cases lacking primary outcome data, 15 due to hospital admissions outside the region, 62 from home treatment without hospitalization, and 253 having unaccountable missing data (Figure 1). Within the study cohort, there were 6,147 adults (18 years and older) and 171 patients under 18. Among adults, 3,686 cases were diagnosed with acute COPD exacerbation, 234 with CAP, 320 with heart disease, and 233 adults with asthma. Additionally, 1,674 cases fell under other primary ICD-10 categories (other ≥18 years). Moreover, 889 cases had established COPD without acute exacerbation, including 165 in the heart disease group, 718 in the “other ≥18 years” group, and 6 in the under-18 age category.
Among the 6,318 ambulance transports analyzed, 2,057 cases involved readmissions within the study period, resulting in a readmission rate of 32.6% (95% CI 31.4-33.7). The readmission rate showed no significant difference between sexes (data not shown). During the two-year study period, the distribution of readmissions was as follows: 588 patients were readmitted once, 228 patients twice, 166 patients between three and five times, 34 patients more than five times, and 11 patients more than ten times.
In all patient groups, except for the under-18 years category, there was a slight to moderate predominance of female participants, ranging from 52.3% to 69.5%. In the under-18 years category, the proportion of females was only 42.7% (Table 1). In terms of age, the AECOPD, CAP, HD, and “other ICD-10 ≥18 years” groups displayed a comparable median age, ranging from 73 to 78 years. Participants in the asthma group had a notably lower median age of 45 years, while for patients under 18 years of age, the median age was 4.
The prevalence and distribution of comorbidities showed significant similarities between the AECOPD and the “other ICD-10 ≥18 years” group, possibly influenced by a relatively large proportion of known COPD patients in the latter. Similarly, comorbidity patterns between the asthma and under-18 groups were comparably infrequent, with a consistently higher prevalence of comorbidities in the asthma group, likely due to its higher median age. The HD group displayed a distinct comorbidity profile with a notably high prevalence of prior myocardial infarction and congestive heart disease, along with the highest rates of hypertension, diabetes mellitus, renal disease, and atherosclerosis-related comorbidities such as peripheral vascular disease, cerebrovascular disease, and dementia (Table 2). These findings were further correlated with the Charlson Comorbidity Score, revealing that the asthma and under-18 groups exhibited the lowest scores, while the remaining groups demonstrated relatively similar scores, with the highest scores observed in the HD group (Table 2).
In assessing vital signs, comparable values were observed across the groups in terms of respiratory rate, heart rate, systolic, and diastolic blood pressures, except for individuals under the age of 18. This subgroup displayed lower blood pressure and a higher pulse rate, aligning with expected physiological variances in this age category. Notably, oxygen saturation levels exhibited variations among the groups. The asthma group and individuals under 18 demonstrated the highest oxygen saturation levels, whereas the AECOPD, CAP, and HD categories manifested the lowest levels within the study cohort (Table 1).
Exclusively considering unique patient IDs did not alter baseline characteristics, comorbidity, and physiological parameters (supplemental Table S1 and S2).
The length of hospital stay varied little among all groups (0.6-1.5 days). The HD group had the highest proportion of cases admitted to the ICU (Table 1).
Table 1. Basal characteristics, hospital admission and physiological parameters
Factor
|
AECOPD
|
CAP
|
Heart disease
|
Asthma
|
Other ≥18 years
|
< 18 years
|
N
|
3,686
|
234
|
320
|
233
|
1,674
|
171
|
Sex (female)
|
1,944 (52.7%)
|
144 (61.5%)
|
171 (53.4%)
|
162 (69.5%)
|
875 (52.3%)
|
73 (42.7%)
|
Age, median (IQR)
|
74 (66-80)
|
74 (60-82)
|
78 (72-84)
|
45 (26-62)
|
73 (61-81)
|
4 (1-11)
|
Length of hospital stay, mean (SD)
|
1.0 (2.3)
|
1.1 (2.3)
|
1.5 (3.1)
|
0.6 (1.2)
|
0.7 (2.1)
|
0.6 (1.1)
|
ICU admission, n (%)
|
40 (1.1%)
|
3 (1.3%)
|
13 (4.1%)
|
1 (0.4%)
|
13 (0.8%)
|
2 (1.2%)
|
Physiological (vital) parameters (initial assessment in the ambulance)
|
Respiratory rate,
median (IQR)
|
30 (24-33)
|
28 (24-32)
|
30 (24-34)
|
28 (22-30)
|
28 (24-32)
|
32 (25-42)
|
Systolic blood pressure, median (IQR)
|
152 (135-174)
|
150 (133-170)
|
155 (131-178.5)
|
148.5 (131-162.5)
|
150 (131-172)
|
123 (112-134)
|
Diastolic blood pressure, median (IQR)
|
86 (74-100)
|
85 (74-98)
|
91.5 (75-109)
|
88.5 (76-98)
|
87 (74-100)
|
77 (65-84)
|
Heart rate, median (IQR)
|
104 (89-117)
|
105 (88-119)
|
103 (82-121)
|
104 (91-118.5)
|
100 (84-116)
|
125 (102-143)
|
GCS, median (IQR)
|
15 (15-15)
|
15 (15-15)
|
15 (15-15)
|
15 (15-15)
|
15 (15-15)
|
15 (15-15)
|
SpO2 <88, n (%)
|
1,337 (36.7%)
|
83 (35.8%)
|
131 (41.5%)
|
27 (11.9%)
|
501 (30.3%)
|
15 ( 9.3%)
|
SpO2 88-92%, n (%)
|
808 (22.2%)
|
54 (23.3%)
|
58 (18.4%)
|
32 (14.1%)
|
343 (20.8%)
|
25 (15.4%)
|
SpO2 93-96%, n (%)
|
894 (24.6%)
|
57 (24.6%)
|
79 (25.0%)
|
75 (33.0%)
|
396 (24.0%)
|
38 (23.5%)
|
SpO2 97-100%, n (%)
|
602 (16.5%)
|
38 (16.4%)
|
48 (15.2%)
|
93 (41.0%)
|
411 (24.9%)
|
84 (51.9%)
|
Table 1: Basal characteristics, hospital admission and physiological parameters AECOPD = acute exacerbation of chronic obstructive pulmonary disease, CAP = Community-acquired pneumonia, HD = heart disease, Other ≥18 years = other primary ICD-10 categories, ICU = intensive care unit, GCS = Glasgow Coma Scale; SpO2 = Peripheral Capillary Oxygen Saturation measured by pulse oximeter.
Table 2 10-year comorbidity
Factor
|
AECOPD
|
CAP
|
Heart Disease
|
Asthma
|
Other ≥18 years
|
<18 years
|
N
|
3,686
|
234
|
320
|
233
|
1,674
|
171
|
Myocardial infarction
|
290 (7.9%)
|
14 ( 6.0%)
|
56 (17.5%)
|
4 (1.7%)
|
117 (7.0%)
|
0 ( 0.0%)
|
Congestive heart failure
|
596 (16.2%)
|
19 (8.1%)
|
131 (40.9%)
|
4 (1.7%)
|
268 (16.0%)
|
0 (0.0%)
|
Peripheral vascular disease
|
432 (11.7%)
|
16 (6.8%)
|
49 (15.3%)
|
6 (2.6%)
|
175 (10.5%)
|
0 (0.0%)
|
Cerebrovascular disease
|
469 (12.7%)
|
31 (13.2%)
|
47 (14.7%)
|
5 (2.1%)
|
232 (13.9%)
|
1 (0.6%)
|
Hemiplegia
|
17 (0.5%)
|
2 (0.9%)
|
1 (0.3%)
|
0 (0.0%)
|
8 (0.5%)
|
2 (1.2%)
|
Dementia
|
83 (2.3%)
|
8 (3.4%)
|
15 (4.7%)
|
3 (1.3%)
|
49 (2.9%)
|
0 (0.0%)
|
Chronic pulmonary disease *
|
3,458 (93.8%)
|
34 (14.5%)
|
176 (55.0%)
|
146 (62.7%)
|
864 (51.6%)
|
85 (49.7%)
|
Diabetes mellitus (without complications)
|
215 (5.8%)
|
12 (5.1%)
|
25 (7.8%)
|
4 (1.7%)
|
100 (6.0%)
|
1 (0.6%)
|
Diabetes mellitus (with chronic complications)
|
158 (4.3%)
|
17 (7.3%)
|
28 (8.8%)
|
2 (0.9%)
|
101 (6.0%)
|
0 (0.0%)
|
Mild liver disease
|
63 (1.7%)
|
3 (1.3%)
|
2 (0.6%)
|
0 (0.0%)
|
40 (2.4%)
|
0 (0.0%)
|
Moderate/severe liver disease
|
14 (0.4%)
|
3 (1.3%)
|
0 (0.0%)
|
0 (0.0%)
|
14 (0.8%)
|
0 (0.0%)
|
Connective tissue disease
|
148 (4.0%)
|
13 (5.6%)
|
18 (5.6%)
|
12 (5.2%)
|
77 (4.6%)
|
1 (0.6%)
|
Ulcer disease
|
142 (3.9%)
|
11 (4.7%)
|
14 (4.4%)
|
0 (0.0%)
|
68 (4.1%)
|
0 (0.0%)
|
Moderate/severe renal disease
|
338 (9.2%)
|
17 (7.3%)
|
53 (16.6%)
|
10 (4.3%)
|
171 (10.2%)
|
0 (0.0%)
|
Any tumor
|
496 (13.5%)
|
37 (15.8%)
|
49 (15.3%)
|
5 (2.1%)
|
242 (14.5%)
|
0 (0.0%)
|
Leukemia
|
11 (0.3%)
|
4 (1.7%)
|
2 (0.6%)
|
0 (0.0%)
|
7 (0.4%)
|
0 (0.0%)
|
Lymphoma
|
44 (1.2%)
|
1 (0.4%)
|
2 (0.6%)
|
1 (0.4%)
|
17 (1.0%)
|
0 (0.0%)
|
Metastatic solid tumor
|
52 (1.4%)
|
8 (3.4%)
|
7 (2.2%)
|
2 (0.9%)
|
41 (2.4%)
|
0 (0.0%)
|
AIDS
|
1 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
3 (0.2%)
|
0 (0.0%)
|
Charlson Comorbidities Score
|
Score 0
|
3 (0.1%)
|
18 (7.7%)
|
0 (0.0%)
|
46 (19.7%)
|
126 (7.5%)
|
84 (49.1%)
|
Score 1
|
93 (2.5%)
|
22 (9.4%)
|
6 (1.9%)
|
89 (38.2%)
|
114 (6.8%)
|
84 (49.1%)
|
Score 2
|
214 (5.8%)
|
22 (9.4%)
|
12 (3.8%)
|
24 (10.3%)
|
147 (8.8%)
|
1 (0.6%)
|
Score 3
|
543 (14.7%)
|
30 (12.8%)
|
30 ( 9.4%)
|
24 (10.3%)
|
201 (12.0%)
|
2 (1.2%)
|
Score 4
|
796 (21.6%)
|
53 (22.6%)
|
54 (16.9%)
|
29 (12.4%)
|
288 (17.2%)
|
0 (0.0%)
|
Score 5
|
714 (19.4%)
|
34 (14.5%)
|
60 (18.8%)
|
14 (6.0%)
|
286 (17.1%)
|
0 (0.0%)
|
Score 6
|
618 (16.8%)
|
18 (7.7%)
|
42 (13.1%)
|
5 (2.1%)
|
195 (11.6%)
|
0 (0.0%)
|
Score 7
|
343 (9.3%)
|
10 (4.3%)
|
47 (14.7%)
|
0 (0.0%)
|
120 (7.2%)
|
0 (0.0%)
|
Score 8
|
170 (4.6%)
|
11 (4.7%)
|
29 (9.1%)
|
0 (0.0%)
|
89 (5.3%)
|
0 (0.0%)
|
Score 9
|
88 (2.4%)
|
10 (4.3%)
|
20 (6.2%)
|
1 (0.4%)
|
51 (3.0%)
|
0 (0.0%)
|
Score 10
|
48 (1.3%)
|
4 (1.7%)
|
7 (2.2%)
|
1 (0.4%)
|
28 (1.7%)
|
0 (0.0%)
|
Score 11
|
30 (0.8%)
|
1 (0.4%)
|
10 (3.1%)
|
0 (0.0%)
|
17 (1.0%)
|
0 (0.0%)
|
Score 12
|
18 (0.5%)
|
1 (0.4%)
|
3 (0.9%)
|
0 (0.0%)
|
7 (0.4%)
|
0 (0.0%)
|
Score 13
|
8 (0.2%)
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
4 (0.2%)
|
0 (0.0%)
|
Score 16
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
0 (0.0%)
|
1 (0.1%)
|
0 (0.0%)
|
Table 2: 10-year Charlson comorbidities based on ICD-10 codes. *AECOPD patients excluded from this category received their first diagnosis of COPD during the current admission.
AECOPD = acute exacerbation of chronic obstructive pulmonary disease, CAP = Community-acquired pneumonia, HD = heart disease, Other ≥18 years = other primary ICD-10 categories. AIDS = Acquired Immunodeficiency Syndrome.
Within 30 days of hospital admission, 593 patients in the study population died, resulting in a total mortality rate (IR) of 10.7% (95% CI 9.8-11.6). The 30-day mortality rate in the AECOPD group was 10.2% (95% CI 9.1-11.3), lower than the rates in the CAP, HD, and "other ≥18 years" groups, which had 30-day mortality rates of 12.1% (95% CI 7.4-16.8), 15.3% (95% CI 10.6-19.9), and 13.5% (95% CI 11.5-15.4), respectively (Table 3). Notably, in both the asthma and “patients under 18 years” groups, no deaths occurred within 30 days after admission (Table 3).
When conducting a relative comparison of 30-day mortality using AECOPD as the reference, the CAP group exhibited an insignificant 18.7% increase in the mortality rate (IRR 1.187 (95% CI 0.792-1.781)), while the HD and "Other ≥18 years" groups demonstrated significant increased rates of 49.5% (IRR 1.495, 95% CI 1.079-2.072) and 32.0% (IRR 1.320, 95% CI 1.103-1.579), respectively (Table 3).
Within 1 year of hospital admission, 1255 patients died, resulting in a total 1-year mortality rate (IR) of 32.1% (95% CI 30.2-34.0). Interestingly, when considering the 1-year mortality rates, the differences between groups diminished to insignificant increased mortality rates ranging from 1.2% to 15.2% (IRR 1.012 (95% CI 0.763-1.343) - IRR 1.152 (95% CI 0.905-1.466)) in the CAP, HD, and "Other ≥18 years" groups. The 1-year mortality rates remained very low in both the asthma and “patients under 18 years” groups at 2.5% (95% CI 0.3-4.8) and 0.6% (95% CI 0.0-1.9).
The 30-day mortality rates observed among males and females showed differences within the CAP, 'Other ≥18 years', and HD groups. In the CAP group, the 30-day mortality rate (IR) for females was 8.9% (95% CI 3.8-14.0), compared with 17.5% (95% CI 8.1-26.9) for males; in the 'Other ≥18 years' group, the rate was 12.3% (95% CI 9.8-14.8) for females versus 14.7% (95% CI 11.9-17.6) for males. Conversely, in the HD group, females exhibited a higher 30-day mortality rate of 16.8% (95% CI 10.0-23.5) compared to 13.6% (95% CI 7.1-20.0) for males (Table 4).
These sex-based disparities also extended to the 1-year mortality rate. In the CAP group, females had a lower mortality rate of 29.8% (95% CI 19.0-40.6) compared to 42.0% (95% CI 24.8-59.3) for males. Similarly, in the 'Other ≥18 years' group, the mortality rate for females was 33.3% (95% CI 28.2-38.3) versus 40.7% (95% CI 34.8-46.6) for males. Meanwhile, in the HD group, females still exhibited the highest 1-year mortality rate at 42.3% (95% CI 29.6-55.0), compared to 35.4% (95% CI 23.0-47.7) for males.
Table 3. Absolute and relative 30-day and 1-year mortality
Absolute 30-day mortality
|
Groups
|
IR (95% CI)
|
AECOPD
|
0.102 (0.091-0.113)
|
Community-acquired pneumonia (CAP)
|
0.121 (0.074-0.168)
|
Heart Disease (HD)
|
0.153 (0.106-0.199)
|
Astma
|
0.000 (0.000-0.000)
|
Other ≥18 years
|
0.135 (0.115-0.154)
|
Patients < 18y
|
0.000 (0.000-0.000)
|
Total
|
0.107 (0.098-0.116)
|
Relative 30-day mortality with the AECOPD group as reference
|
Groups
|
IRR (95% CI)
|
AECOPD
|
1 (ref)
|
Community-acquired pneumonia (CAP)
|
1.187 (0.792-1.781)
|
Heart Disease (HD)
|
1.495 (1.079-2.072)
|
Astma
|
n/a
|
Other ≥18 years
|
1.320 (1.103-1.579)
|
Patients < 18y
|
n/a
|
Absolute 1-year mortality
|
Groups
|
IR (95% CI)
|
AECOPD
|
0.339 (0.312-0.366)
|
Community-acquired pneumonia (CAP)
|
0.343 (0.250-0.436)
|
Heart Disease
|
0.390 (0.302-0.479)
|
Astma
|
0.025 (0.003-0.048)
|
Other ≥18 years
|
0.368 (0.329-0.406)
|
Patients < 18y
|
0.006 (0.000-0.019)
|
Total
|
0.321 (0.302-0.340)
|
Relative 1-year mortality with the AECOPD group as reference
|
Groups
|
IRR (95% CI)
|
AECOPD
|
1 (ref)
|
Community-acquired pneumonia (CAP)
|
1.012 (0.763,1.343)
|
Heart Disease
|
1.152 (0.905,1.466)
|
Astma
|
0.075 (0.031,0.180)
|
Other ≥18 years
|
1.085 (0.951,1.238)
|
Patients < 18y
|
0.019 (0.003,0.133)
|
Table 3: Absolute and relative 30-day and 1-year mortality presented as incidence rates (IR) and incidence rate ratios (IRR) with 95% confidence intervals (CI). AECOPD = acute exacerbation of chronic obstructive pulmonary disease, Other ≥18 years = other primary ICD-10 categories.
Table 4 Absolute and relative 30-day and 1-year mortality stratified by sex
|
Females
|
Males
|
Patients (unique ID)
|
2293
|
1968
|
Ambulance transports, n
|
3369
|
2949
|
Age all groups, median (IQR)
|
73 (63; 80)
|
73 (63; 80)
|
Absolute 30-day mortality
|
Groups
|
IR (95% CI)
Females
|
IR (95% CI)
Males
|
AECOPD
|
0.104 (0.088-0.120)
|
0.099 (0.083-0.116)
|
CAP
|
0.089 (0.038-0.140)
|
0.175 (0.081-0.269)
|
Heart Disease
|
0.168 (0.100-0.235)
|
0.136 (0.071-0.200)
|
Astma
|
0.000 (0.000-0.000)
|
0.000 (0.000-0.000)
|
Other ≥18 years
|
0.123 (0.098-0.148)
|
0.147 (0.119-0.176)
|
Patients < 18y
|
0.000 (0.000-0.000)
|
0.000 (0.000-0.000)
|
Total
|
0.104 (0.092-0.116)
|
0.110 (0.097-0.124)
|
Relative 30-day mortality with AECOPD as reference
|
Groups
|
IRR (95% CI) Females
|
IRR (95% CI) Males
|
AECOPD
|
1 (ref)
|
1 (ref)
|
CAP
|
0.853 (0.473,1.539)
|
1.763 (1.005-3.092)
|
Heart Disease
|
1.608 (1.046,2.471)
|
1.363 (0.825-2.253)
|
Astma
|
n/a
|
n/a
|
Other ≥18 years
|
1.179 (0.914,1.521)
|
1.483 (1.150-1.913)
|
Patients < 18y
|
n/a
|
n/a
|
Absolute 1-year mortality
|
Groups
|
IR (95% CI)
Females
|
IR (95% CI)
Males
|
AECOPD
|
0.334 (0.297,0.370)
|
0.345 (0.305-0.385)
|
CAP
|
0.298 (0.190,0.406)
|
0.420 (0.248-0.593)
|
Heart Disease
|
0.423 (0.296,0.550)
|
0.354 (0.230-0.477)
|
Astma
|
0.037 (0.005,0.070)
|
0.000 (0.000-0.000)
|
Other ≥18 years
|
0.333 (0.282,0.383)
|
0.407 (0.348-0.466)
|
Patients < 18y
|
0.000 (0.000,0.000)
|
0.011 (0.000-0.031)
|
Total
|
0.308 (0.283,0.333)
|
0.336 (0.308-0.365)
|
Relative 1-year mortality with AECOPD as reference
|
Groups
|
IRR (95% CI) Females
|
IRR (95% CI) Males
|
AECOPD
|
1 (ref)
|
1 (ref)
|
CAP
|
0.894 (0.612-1.305)
|
1.218 (0.796-1.866)
|
Heart Disease
|
1.267 (0.921-1.743)
|
1.025 (0.709-1.482)
|
Astma
|
0.112 (0.046-0.270)
|
0.000 (0.000-0.000)
|
Other ≥18 years
|
0.998 (0.828-1.202)
|
1.179 (0.979-1.421)
|
Patients < 18y
|
0.000 (0.000-0.000)
|
0.031 (0.004-0.217)
|
Table 4: Absolute and relative 30-day and 1-year mortality with the AECOPD group as reference presented as incidence rates (IR) and incidence rate ratios (IRR) with 95% confidence intervals (CI). AECOPD = acute exacerbation of chronic obstructive pulmonary disease, CAP = Community-acquired pneumonia, HD = heart disease, Other ≥18 years = other primary ICD-10 categories.