- Email: [email protected]
Trends in hospital admissions for obstructive lung disease from 2000 to 2010 in Portugal
Respiratory Medicine 116 (2016) 63e69
Contents lists available at ScienceDirect
Respiratory Medicine journal homepage: www.elsevier.com/locate/rmed
Trends in hospital admissions for obstructive lung disease from 2000 to 2010 in Portugal ~o Almeida Fonseca a, b, Fernando Lopes a, b, Alberto Freitas a, b Rafael Vieira a, *, Joa cido da Costa, 4200-450 Porto, Department of Health Information and Decision Sciences (CIDES), Faculty of Medicine, University of Porto, Rua Dr. Pla Portugal b cido da Costa, 4200-450 Porto, Portugal Center for Health Technology and Services Research (CINTESIS), University of Porto, Rua Dr. Pla a
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 December 2015 Received in revised form 13 May 2016 Accepted 17 May 2016 Available online 18 May 2016
The burden of hospitalisations for obstructive lung diseases (OLD) has not been sufficiently studied. We aimed to characterise the hospitalisations for OLD from 2000 to 2010 in all Portuguese public hospitals. We analysed hospital discharges with a diagnosis of OLD regarding the patients’ gender, age, residence and comorbidities. Of the 120 399 hospital admissions with a principal diagnosis of OLD, COPD (ICD-9CM 491.x, 492.x, 496) was responsible for 81%. The change in patients discharged with OLD as a principal diagnosis was only 1% from 2000 to 2010 and did not change for COPD. Hospital admissions and deaths for COPD and other OLD increased with age and were more common in men than women. In-hospital mortality for COPD decreased 34.1% from 2000 to 2010, while the median length of stay was fairly constant at 8 days. Respiratory failure, insufficiency and/or arrest, and pneumonia, are the principal diagnoses often associated with COPD. When both pneumonia and COPD were diagnosed there was an increasing trend to classify pneumonia as the principal diagnosis (64.4%e72.9%), a sign that may lead to underestimation of COPD hospitalisations. In summary, a considerable decrease in in-hospital COPD mortality was observed while hospital admissions and the length of stay did not change substantially. These results suggest that better healthcare or other factors may be counteracting the expected increase of the burden of COPD. © 2016 Elsevier Ltd. All rights reserved.
Keywords: Obstructive lung disease Chronic obstructive pulmonary disease Asthma Hospitalisations Mortality Length of stay
1. Introduction Obstructive lung diseases (OLD) include Chronic Obstructive Pulmonary disease (COPD), asthma and bronchiectasis [1,2]. COPD is a group of diseases characterised by persistent and progressive limitation of airflow, and classically includes emphysema and chronic bronchitis [3]. COPD will be the third major cause of death by 2030 [4]. COPD prevalence seems to be higher in men and increases with age [5,6]. Although COPD is often associated with other diseases, thus increasing its mortality rate, COPD as a secondary diagnosis is often underdiagnosed [7]. Hospitalisation of COPD cases already represent a major burden [8,9]. Khakban et al. showed that hospitalisations were the main driver of the high direct costs of COPD [10]. Studies on hospitalisations and the socio-economic burden of COPD in Portuguese healthcare are not available in the literature. Summarised
* Corresponding author. E-mail address: [email protected] (R. Vieira). http://dx.doi.org/10.1016/j.rmed.2016.05.018 0954-6111/© 2016 Elsevier Ltd. All rights reserved.
information on COPD hospitalisations in Portugal is available in the reports issued by the Portuguese Observatory for Respiratory Diseases [11], but, since this covers all pulmonary diseases, COPD hospitalisations are mentioned only briefly. In light of the socio-economic burden of OLD and the lack of information on OLD hospitalisations in Portugal, our study set out to analyse the evolution of in-hospital admissions, length of stay and mortality of patients admitted in Portuguese hospitals with a diagnosis of OLD, from 2000 to 2010. 2. Methods 2.1. Study design and data source We conducted a retrospective observational study using data from the national hospitalisations database, provided by the Central Administration of the Health System of the Portuguese Ministry of Health (ACSS). This database compiles administrative and clinical data on hospitalisation episodes in the Portuguese National Health Service, but it does not include data from private hospitals [12].
64
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
Diagnoses and procedures performed have been coded in Portugal, since 1989, using the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM). The relative weight of each Diagnosis Related Group (DRG) has been set by the Portuguese Health Ministry [13]. The relative weight reflects the average cost of treating a patient with that DRG [14]. 2.2. Study population We included all inpatient episodes of patients aged 18 years and older with a principal or secondary diagnosis of obstructive lung disease e ICD-9-CM codes 491.x for chronic bronchitis, 492.x for emphysema, 493.x for asthma, 494.x for bronchiectasis and 496 for chronic airway obstruction, not elsewhere classified e with a discharge date between 2000 and 2010 in mainland Portuguese hospitals. 2.3. Data collection and estimation of variables For each hospitalisation with a diagnosis of OLD, we collected data on age, gender, place of residence, length of stay and discharge status. We organised the episodes coded by ICD-9-CM into two groups: - OLD, which includes 491.x (chronic bronchitis), 492.x (emphysema), 493.x (asthma), 494.x (bronchiectasis) and 496 (chronic airway obstruction, not elsewhere classified); - COPD, which includes 491.x (chronic bronchitis), 492.x (emphysema) and 496 (chronic airway obstruction, not elsewhere classified). We recoded age into the following age groups: 18e29 years old, 30e39 years old, 40e49 years old, 50e59 years old, 60e69 years old, 70e79 years old, and 80 years and older. We classified the place of residence by level of urbanisation, into urban (high level of urbanisation), moderate and rural (low level of urbanisation) [15]. The necessary information on the population (size and variation) was collected from the National Institute of Statistics (INE), which obtained these data by conducting population censuses. 2.4. Analysis For each hospital discharge with a principal or secondary diagnosis corresponding to an obstructive lung disease, we analysed the evolution of hospital admissions and calculated the yearly ratio between each disease and the total number of hospitalisations. We calculated the mean secondary diagnoses in hospitalisations with a principal diagnoses of OLD divided by mean secondary diagnoses in all hospitalisations to adjust all OLD hospitalisations to the mean number of secondary diagnoses coded each year. We made this adjustment, as we studied hospitalisations over a long time span and the mean number of secondary diagnoses that were registered increased during this period due to a better and more complete coding of secondary diagnoses (from 1.66 per hospitalisation to 3.20 per hospitalisation, accounting for an increase of 0.15 secondary diagnoses/hospitalisation per year [16]). We also collected data on hospitalisations and mortality, and calculated the hospitalisation and mortality ratio by age group, gender and residence. We further calculated age-adjusted OLD and COPD hospitalisations and mortality (principal diagnosis) over the study period using the European (Scandinavian 1960) Standard Population. We calculated median length of stay from 2000 to 2010, as length of stay did not follow a normal distribution. Regarding mortality, we calculated the mortality ratio in hospitalisations with
a principal diagnosis of OLD/COPD, and the proportion of deaths in a hospitalisation with a principal diagnosis of OLD/COPD compared with all in-hospital deaths. We calculated Elixhauser comorbities [17] for COPD, OLD and for all diagnoses between 2000 and 2010. The Elixhauser comorbidities index was developed to identify comorbidities associated with an increase in the risk of in-hospital mortality, length of stay and its costs. We analysed the principal diagnoses most frequently associated with COPD as a secondary diagnosis. We grouped diagnoses according to the Clinical Classifications Software (CCS) for ICD-9-CM [18], and adjusted for the frequency of the diagnoses when COPD was not a secondary diagnosis. We selected all episodes with a diagnosis of COPD or pneumonia (whether as principal or secondary), and calculated the proportion of principal diagnoses of each of these clinical entities, as well as its DRG relative weights. We performed the same analysis for respiratory insufficiency, failure and/or arrest, and COPD. Finally, for time trends, we calculated the linear regression and tested the null hypothesis that the slope, B, was different from 0. Descriptive statistical analysis was performed using IBM SPSS Statistics for Windows v23 (Armonk, NY: IBM Corp.). 3. Results A total of 120 399 cases of hospital admissions with a principal diagnosis of OLD were recorded in the period studied. These amount to 1.41% of all hospitalisations between 2000 and 2010, of which 97 325 (81%) were due to COPD (Table 1). Although the absolute number of hospital discharges for OLD/COPD increased from 2000 to 2010, there was no relative increase in comparison with all hospital admissions. The variation in hospital discharges of patients with OLD as a principal diagnosis was only 1% (Table 1) (95% CI for B: 0.16e0.23). In total, we identified 441 088 hospitalisations of patients with a principal or secondary diagnosis of OLD (5.15% of the total hospitalisations) from 2000 to 2010. Of these, 338 590 (77%) were classified as COPD. In this time period, there was an increase of 42% in the proportion of hospital discharges with a diagnosis of COPD (either principal or secondary) (Table 1) (95% CI for B: 0.10e0.15). However, after adjusting these data for the mean number of secondary diagnoses coded each year, we found a significant increase only in hospitalisations with a principal or secondary diagnosis of Chronic Airway Obstruction, not elsewhere classified, from 2000 to 2010. After this adjustment, hospitalisations with a diagnosis of COPD fell significantly owing to the 34.1% decrease in chronic bronchitis hospitalisations. Furthermore, hospitalisations with a diagnosis of emphysema, asthma and bronchiectasis did not show any significant trend. Seventeen per cent of the hospitalisations with a principal diagnosis of bronchiectasis had COPD as a secondary diagnosis. Of all the admissions with a principal diagnosis of OLD, 38% were patients 70e79 years old and 29% were more than 80 years old. OLD represents a larger burden for patients aged 80 years and older as it accounts for 2.3% of all hospital admissions of patients in that age group. Hospital admissions and mortality for OLD increase with age, with an age peak in the 80þ years old age group (Fig. 1). Sixty per cent of patients admitted with a principal diagnosis of OLD were male. While 1.8% of all hospital admissions of men were due to OLD, in women OLD accounts for 0.7% of hospital admissions. Mortality is higher in male patients in all age groups (Fig. 1). We studied the evolution in hospital admissions by place of residence, but we did not find any relevant differences between regions (data not shown). The inpatient median length of stay for OLD was 8 days from 2000 to 2010 (interquartile range of 4.0e11.0 days, except in 2000 and 2001e3.0 to 11.0 days e and 2010e5.0 to 11.0 days). Median length of stay for admissions for COPD fell from 9.0 days in 2000
Chronic bronchitis
Total COPD
5624 (0.07) 26 017 (0.30)
17 450 (0.20) 88 928 (1.04)
0.026 <0.001 0.753 0.002 <0.001 0.186
<0.001 269 883 (3.15) <0.001 0.001 2221 (0.03) < 0.001 19 264 (0.23) 0.798 <0.001 2411 (0.03) <0.001 54 361 (0.64) <0.001
20 715 (2.79) 22 611 (2.98) 23 921 (3.10) 24 430 (3.08) 24 511 (3.09) 25 615 (3.17) 24 042 (3.04) 26 501 (3.35) 26 158 (3.29) 25 740 (3.37) 25 639 (3.39) þ21.3% 34.1% Emphysema 250 (0.03) 245 (0.03) 220 (0.03) 241 (0.03) 218 (0.03) 217 (0.03) 156 (0.02) 175 (0.02) 157 (0.02) 155 (0.02) 187 (0.02) 26.7% 1196 (0.16) 1367 (0.18) 1510 (0.20) 1490 (0.19) 1547 (0.20) 1659 (0.21) 1694 (0.21) 1920 (0.24) 1980 (0.25) 2179 (0.29) 2722 (0.36) þ123.1% þ15.89% 273 (0.04) 299 (0.04) 310 (0.04) 296 (0.04) 291 (0.04) 242 (0.03) 145 (0.02) 113 (0.01) 158 (0.02) 127 (0.02) 157 (0.02) 43.6% Chronic 2897 (0.39) 3276 (0.43) 3723 (0.48) 4139 (0.52) 4198 (0.53) 4902 (0.61) 5051 (0.64) 5216 (0.66) 6254 (0.79) 6902 (0.90) 7803 (1.03) þ164.1% airway þ38.8% obstruction, not elsewhere classified Asthma 1682 (0.23) 1598 (0.21) 1663 (0.22) 1568 (0.20) 1534 (0.19) 1625 (0.20) 1569 (0.20) 1647 (0.21) 1580 (0.20) 1463 (0.19) 1521 (0.20) 11.3% 5621 (0.76) 5978 (0.79) 6786 (0.88) 7392 (0.93) 7282 (0.92) 7792 (0.97) 8147 (1.03) 9130 (1.15) 9388 (1.18) 10 351 (1.36) 11 061 (1.46) þ93.0% þ7.09% Bronchiectasis 438 (0.06) 394 (0.05) 403 (0.05) 398 (0.05) 381 (0.05) 381 (0.05) 485 (0.06) 676 (0.09) 677 (0.09) 645 (0.08) 746 (0.10) þ67.0% 1785 (0.24) 1843 (0.24) 2102 (0.27) 2043 (0.26) 2229 (0.28) 2138 (0.26) 2378 (0.30) 2778 (0.35) 2821 (0.35) 2776 (0.36) 3124 (0.41) þ71.6% 1.01%
0.921 120 399 (1.41) <0.001 441 088 (5.15) <0.001 0.535 97 325 (1.14) <0.001 338 590 (3.96) <0.001 0.842 92 693 (1.08)
p-value Total
D% 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000
10 285 (1.39) 10 802 (1.42) 11 156 (1.44) 11 265 (1.42) 10 712 (1.35) 11 744 (1.46) 10 264 (1.30) 11 620 (1.47) 11 187 (1.41) 10 765 (1.41) 10 599 (1.40) þ1.0% 31 211 (4.21) 33 834 (4.46) 36 670 (4.75) 38 229 (4.83) 38 382 (4.84) 40 626 (5.04) 39 675 (5.02) 43 648 (5.52) 44 655 (5.62) 45 969 (6.02) 48 189 (6.37) þ51.4% 17.2% 8165 (1.10) 8810 (1.16) 9090 (1.18) 9299 (1.17) 8797 (1.11) 9738 (1.21) 8210 (1.04) 9297 (1.18) 8930 (1.12) 8657 (1.13) 8332 (1.10) 0.0% 24 536 (3.31) 26 878 (3.54) 28 752 (3.72) 29 724 (3.75) 29 907 (3.77) 31 729 (3.93) 30 277 (3.83) 33 124 (4.19) 33 855 (4.26) 34 256 (4.49) 35 552 (4.70) þ42.1% 23.1% 7642 (1.03) 8266 (1.09) 8560 (1.11) 8762 (1.11) 8288 (1.05) 9279 (1.15) 7909 (1.00) 9009 (1.14) 8615 (1.08) 8375 (1.10) 7988 (1.06) þ2.5% OLD
Table 1 Hospital admissions of patients with OLD/COPD (raw data, except italics). First row includes principal diagnoses only. Second row includes principal and secondary diagnoses. D% refers to the percentage variation, as calculated by: (%2010e%2000)/%2000. Data shown as n (% of total hospital admissions). p-value tests H0: B s 0. Values in italics concern the variation and p-value for trends in hospitalisations with a principal or secondary diagnosis of one of the diagnoses studied, adjusted for the mean number of secondary diagnoses coded each year.
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
65
(interquartile range: 5.0e13.0) to 8 days in 2001, and remained constant from 2001 to 2010. The interquartile range was 5.0e12.0 days, except in 2001 and 2002 (5.0e13.0 days). In-hospital mortality from 2000 to 2010 decreased both in COPD (9.3%e7.5%, which is a 20.0% decrease [95% CI for B: 0.25 to 0.11]) and in OLD (7.7%e6.4%, which is a decrease of 16.4% [95% CI for B: 0.20 to 0.07]) (Table 2). The proportion of deaths from COPD and OLD, compared with all in-hospital deaths, declined from 2.0% to 1.4% (decrease of 34.1% [95% CI for B: 0.09 to 0.06]) in COPD and from 2.1% to 1.5% in OLD (decrease of 30.5% [95% CI for B: 0.09 to 0.05]) (Table 2). When analysing mortality by age group for COPD, we noticed a significant fall (p < 0.05) in older age groups. In the 18e29 and 30e39 age groups there was a non-significant decline (p > 0.05) and 40e49 years old there was a nonsignificant increase in mortality (p > 0.05) (data not shown). Age-adjusted values show that in the period studied there was a mean of 79.4 hospitalisations/100 000 inhabitants aged 18 and older/year for COPD and 103.2 hospitalisations/100 000 inhabitants aged 18 and older/year for OLD. Mortality for COPD was 5.9/ 100 000 inhabitants aged 18 and older/year, while for OLD it was 6.2/100 000 inhabitants aged 18 years and older/year (Table 3). COPD and OLD hospitalisations had more comorbidities than hospitalisations for all causes in all age groups, and comorbidities increase with age (Table 4). The principal group of diagnoses most frequently associated with COPD is respiratory failure, insufficiency and/or arrest (adult), in which COPD is a secondary diagnosis in 13.5% percent of hospitalisations. COPD is also often associated with pneumonia and is a secondary diagnosis in 10.1% of hospitalisations. According to the ICD-9-CM classification, 6 of the 10 most associated group of diseases are respiratory system disorders (Table 5). Regarding episodes with a diagnosis of COPD or pneumonia (either principal or secondary), pneumonia as the principal diagnosis rose from 64.4% to 72.9% from 2000 to 2010, while COPD decreased from 18.4% to 8.1% (Fig. 2, Panel A). We calculated the mean for DRG relative weights, which were: 1.29 for hospitalisations with a principal diagnosis of pneumonia and a secondary diagnosis of COPD; 1.47 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis of pneumonia; 1.08 for hospitalisations with a principal diagnosis of pneumonia and a secondary diagnosis that did not include COPD; 1.05 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis that did not include pneumonia. We also compared the classification of asthma and pneumonia as principal diagnosis and found similar trends (data not shown). We performed the same analysis for respiratory failure, insufficiency and/or arrest, and COPD, taking into account the results from Table 5. Our data (Fig. 2, Panel B) shows that COPD is the most common principal diagnosis. In 2000, respiratory failure, insufficiency and/or arrest was the principal diagnosis in 18.5% of the cases, but in 2001 it was the principal diagnosis in only 9.3% and in 2010 in 5.4% of hospitalisations. We further calculated the mean for DRG relative weights, and found: 2.15 for hospitalisations with a principal diagnosis of respiratory failure, insufficiency and/or arrest, and a secondary diagnosis of COPD; 1.64 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis of respiratory failure, insufficiency and/or arrest; 1.91 for hospitalisations with a principal diagnosis of respiratory failure, insufficiency and/or arrest, and a secondary diagnosis that did not include COPD; 0.84 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis that did not include respiratory failure, insufficiency and/or arrest.
66
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
Fig. 1. Panels A & B: Hospitalisations with a principal diagnosis of COPD or OLD, by age and gender. Data is shown as the proportion of hospitalisations with a principal diagnosis of COPD or OLD standardised for age and gender total hospitalisations. Panels C & D: In-hospital mortality of discharges with a principal diagnosis of COPD or OLD, by age and gender. Data is shown as the mortality ratio among hospitalisations with a principal diagnosis of COPD or OLD.
Table 2 In-hospital mortality of patients with a principal diagnosis of OLD/COPD. % of deaths in OLD/COPD episodes refers to the proportion of deaths that among discharges with a principal diagnosis of OLD/COPD relative to the number of hospitalisations in that year (e.g. in the year 2000, for 100 hospitalisations with a principal diagnosis of OLD, 7.7 of patients died in hospital). % of all deaths refers to the proportion of deaths among discharges with a principal diagnosis of OLD/COPD relative to the total deaths in that year (e.g. in the year 2000, OLD accounted for 2.1 deaths in every 100 deaths that occurred in 2000). D refers to variation and was calculated by: (2010e2000)/2000. p-value tests H0: B s 0.
OLD
COPD
N % of % of N % of % of
deaths in OLD episodes all deaths deaths in COPD episodes all deaths
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
D
p-value
Total
790 7.7 2.1 763 9.3 2.0
827 7.7 2.1 797 9.0 2.0
815 7.3 2.0 792 8.7 1.9
834 7.4 2.0 797 8.6 1.9
748 7.0 1.8 708 8.0 1.7
876 7.5 1.9 835 8.6 1.9
683 6.7 1.6 648 7.9 1.5
717 6.2 1.6 686 7.4 1.5
716 6.4 1.5 662 7.4 1.4
743 6.9 1.6 700 8.1 1.5
681 6.4 1.5 623 7.5 1.4
13.8% 16.4% 30.5% 18.3% 20.0% 34.1%
0.022 0.001 <0.001 0.009 <0.001 <0.001
8430 7.0 1.8 8011 8.2 1.7
4. Discussion In this study, we found that there was no increase in hospitalisations for COPD as the principal diagnosis, except for chronic bronchitis. One explanation may be that COPD exacerbations leading to hospitalisations are not coded as COPD, with other
diagnoses such as pneumonia being preferred. We also noted that in-hospital mortality decreased 30% for COPD from 2000 to 2010, which may indicate better healthcare. However, the median length of stay was fairly constant at 8 days. The prevalence of COPD increases with age [19e21]. However, the relation between COPD and age in hospital admissions has been
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69 Table 3 Age-adjusted data for hospitalisations and mortality in OLD and COPD (principal diagnosis only). We used the European (Scandinavian 1960) Standard Population for age-adjustment. Data
Age-adjusted value (per 100 000 inhabitants aged 18 years and older, per year)
OLD hospitalisations COPD hospitalisations OLD mortality COPD mortality
103.2 79.4 6.2 5.9
67
Obstructive Lung Disease, although it is not yet known if age is a risk factor, or if age simply reflects the exposure to risk factors throughout life [3]. Many studies have shown a higher prevalence of COPD in men [3,5,6], although, according to the World Health Organisation, COPD now affects both genders almost equally [22]. Aryal et al. suggest that gender affects COPD in a complex way through a combination of behavioural, environmental and genetic factors [23]. The increase of smoking among women may partly explain this increase in the prevalence of COPD among women [3,23e25].
Table 4 Elixhauser Comorbidities for OLD and COPD (principal diagnosis), and for all hospitalisations. Elixhauser comorbidities (mean number) Age groups
OLD
95%CI
COPD
95% CI
All hospital admissions
95%CI
18e29 30e39 40e49 50e59 60e69 70e79 80þ Total
0.31 0.56 1.01 1.37 1.56 1.75 1.80 1.58
0.28e0.33 0.53e0.59 0.98e1.05 1.35e1.40 1.54e1.58 1.73e1.76 1.78e1.82 1.58e1.59
0.43 0.90 1.28 1.54 1.62 1.78 1.81 1.71
0.35e0.51 0.81e0.98 1.23e1.33 1.51e1.57 1.60e1.64 1.78e1.80 1.80e1.83 1.70e1.72
0.12 0.23 0.54 0.81 1.08 1.32 1.48 0.84
0.115e0.117 0.227e0.230 0.539e0.543 0.809e0.813 1.077e1.081 1.317e1.321 1.474e1.479 0.839e0.840
Table 5 Principal diagnoses when COPD is reported as secondary diagnosis. Values were adjusted for frequency of diagnoses. Diagnosis (as classified by CCS)
%
Respiratory failure; insufficiency; arrest (adult) Pneumonia (except that caused by tuberculosis or sexually transmitted disease) Cancer of bronchus; lung Pleurisy; pneumothorax; pulmonary collapse Congestive heart failure; nonhypertensive Acute bronchitis Pulmonary heart disease Other lower respiratory disease Lung disease due to external agents Hypertension with complications and secondary hypertension
13.5 10.1 9.9 9.4 9.2 7.8 7.8 7.1 7.0 6.1
Fig. 2. Panel A. Classification of COPD and pneumonia as principal diagnoses, when both are present in the hospitalisation. Values shown are % of principal diagnosis. Panel B. Classification of COPD and respiratory failure, insufficiency and/or arrest as principal diagnosis, when both are present in the hospitalisation. Values shown are % of principal diagnosis.
much less studied. We observed a marked increase in hospital admissions for COPD in age groups up to 70e79 years old and stabilisation in patients over 70. This association between COPD and age is also recognised by the Global Initiative for Chronic
Regarding hospitalisations, we found more admissions of men with COPD. This might be because female smoking in Portugal is still increasing, being placed at stage II of the tobacco epidemic, while men can be placed at stages III or IV [26].
68
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
Harries and co-workers showed that the mean length of stay in London’s hospitals fell from 8.2 days in 2006 to 7.0 days in 2010 [27]. In Portugal, the length of stay for COPD remained 8 days since 2001, in spite of the overall effort to cut the length of hospitalisation to reduce national health system costs [27]. The World Health Organisation expects COPD to become the 3rd leading cause of death (it was 4th in 2004) [4], even though some studies show a decrease in mortality due to COPD both globally [28] and in the European Union [29]. In-hospital mortality has been less studied [7]. Importantly, there was a decrease of 19% in in-hospital mortality from 2000 to 2010. The burden of COPD in global inhospital mortality has also fallen as the COPD in-hospital mortality, in comparison with all causes of in-hospital mortality, declined by 30% from 2000 to 2010. Nonetheless, COPD still accounts for 1.7% of all deaths occurring during hospital admissions in Portugal. The burden of COPD is often underestimated, and COPD as a secondary diagnosis is often underreported [7]. We have found that COPD, as a comorbidity, is mostly associated with diseases of the respiratory system, in particular respiratory insufficiency/arrest/ failure and pneumonia. It is also associated with lung or bronchial cancer and circulatory/heart diseases, such as heart failure, heart disease and hypertension. These results agree with those reported by Holguin et al. that showed an association between COPD and diseases such as pneumonia, congestive heart failure and respiratory failure [7]. It is known that the classification of diseases in hospital admissions has inaccuracies, and this is also true for the classification of COPD [30]. Being aware of the relationship between COPD and pneumonia [3], we studied the evolution of the classification of patients admitted with both pneumonia and COPD. Our results suggest that over this 10-year period pneumonia has been the principal diagnosis in most cases, and the gap between pneumonia and COPD is widening. We performed the same analysis for pneumonia and asthma, which showed the same trend. This indicates that COPD diagnoses seem to be passed over in favour of pneumonia, which can indicate the under-coding of COPD in Portuguese hospitals. We speculated that a possible reason for coding a hospitalisation with pneumonia as principal diagnosis and COPD as secondary diagnosis could be that this would place the hospitalisation in a DRG with a higher relative weight, which would be favourable in terms of funding. However, in Portugal, hospitalisations with COPD as principal diagnosis and pneumonia as secondary diagnosis have a higher DRG relative weight. It is possible that pneumonia is more often chosen as principal diagnosis as it is the factor that leads to the exacerbation of COPD and subsequent hospital admission. Still, whenever the critical reason for hospital admission is having COPD, it would be preferable to code such hospital discharges as exacerbated COPD. Regarding hospitalisations with a diagnosis of COPD and respiratory failure, insufficiency and/or arrest, our results show that COPD is more often coded as principal diagnosis than respiratory failure, insufficiency and/or arrest. The association between respiratory failure, insufficiency and/or arrest and COPD is well described in the peer-reviewed literature [7], and patients with COPD and respiratory insufficiency have higher mortality rates [31]. Our data also shows that COPD as a secondary diagnosis is often associated with respiratory failure, insufficiency and/or arrest. However, COPD is usually the principal diagnosis. This is not affected by its DRG, as our data regarding the DRG relative weights shows that hospitalisations with a principal diagnosis of respiratory failure, insufficiency and/or arrest are placed in a higher DRG than COPD hospitalisations. It is important to acknowledge the strengths and limitations of this study. We gathered and analysed nationwide data on the frequency and mortality of hospital admissions over a 10-year period,
from 2000 to 2010. We had access to data from Portuguese public hospitals, which account for 85% of all hospitalisation episodes in Portugal. Nonetheless, we recognise that this study has some limitations, mostly related to its design and sources of data. First of all, we rely on the quality of diagnoses and coding of diseases. For this reason, the validity of using hospital discharge data is limited, and the combination of this with other data sources has provided better results [30]. We were not able to check the validity of the diagnoses, as this was not the objective of this descriptive analysis. We have followed similar designs of other descriptive studies on COPD hospitalisations. A prospective or retrospective analysis of individual patient records is needed to establish the validity of COPD diagnoses in hospital databases, as previously done in other clinical fields [32]. It is also important to note that admissions classified as chronic airway obstruction, not elsewhere classified (496) are probably misclassifications and might even overestimate our results for COPD. In conclusion, our study shows that OLD hospitalisations are a significant burden in Portugal, with COPD accounting for most of it. We found a considerable decrease in in-hospital COPD mortality, while hospital admissions and the length of stay did not substantially change over the period. Results obtained from hospitalisations databases should be viewed as hypothesis generation studies, to be tested with other study designs using detailed clinical data. Nevertheless, these results do suggest that better healthcare or other factors may be counteracting the expected increase of the burden of COPD. Acknowledgements The authors thank the Central Health System Administration (ACSS) for providing access to the dataset. The authors also thank the Center for Health Technology and Services Research (CINTESIS) for providing the conditions to perform this study. The authors further thank Mr Tim Stoffel for proofreading the manuscript and providing valuable feedback. References [1] A. Maitra, V. Kumar, The lung, in: V. Kumar, A.K. Abbas, N. Fausto, R. Mitchell (Eds.), Robbins Basic Pathol, eighth ed., Elsevier Health Sciences, Philadelphia, PA, 2007, pp. 479e540. [2] S.R. Kim, Y.K. Rhee, Overlap between asthma and COPD: where the two diseases converge, Allergy. Asthma Immunol. Res. 2 (2010) 209e214, http:// dx.doi.org/10.4168/aair.2010.2.4.209. [3] Global Initiative for Obstructive Lung Disease, Global Strategy for Diagnosis, Management, and Prevention of COPD, 2014. www.goldcopd.org/uploads/ users/files/GOLD_Report_2014_Jan23.pdf (accessed 23.10.14). [4] World Health Organization, World Health Statistics, 2008, p. 112. http://www. who.int/whosis/whostat/EN_WHS08_TOCintro.pdf. [5] M. Cazzola, E. Puxeddu, G. Bettoncelli, L. Novelli, A. Segreti, C. Cricelli, et al., The prevalence of asthma and COPD in Italy: a practice-based study, Respir. Med. 105 (2011) 386e391, http://dx.doi.org/10.1016/j.rmed.2010.09.022. [6] F.W.K. Chan, F.Y.Y. Wong, C.H.K. Yam, W. Cheung, E.L.Y. Wong, M.C.M. Leung, et al., Risk factors of hospitalization and readmission of patients with COPD in Hong Kong population: analysis of hospital admission records, BMC Health Serv. Res. 11 (2011) 186, http://dx.doi.org/10.1186/1472-6963-11-186. [7] F. Holguin, E. Folch, S.C. Redd, D.M. Mannino, Comorbidity and mortality in COPD- related hospitalizations in the United States, 1979 to 2001, Chest J. 128 (2005) 2005e2011. [8] F.T. Shaya, D. Dongyi, M.O. Akazawa, C.M. Blanchette, J. Wang, D.W. Mapel, et al., Burden of concomitant asthma and COPD in a Medicaid population, Chest 134 (2008) 14e19, http://dx.doi.org/10.1378/chest.07-2317. [9] R.J. Milne, R. Beasley, Hospital admissions for chronic obstructive pulmonary disease in New Zealand, N. Z. Med. J. 128 (2015) 23e35. [10] A. Khakban, D.D. Sin, J.M. FitzGerald, R. Ng, Z. Zafari, B. McManus, et al., 10year trends in direct costs of COPD: a population based study, Chest (2015), http://dx.doi.org/10.1378/chest.15-0721. rio Nacional das Doenças Respirato rias, 10.o Relato rio Panorama das [11] Observato rias em Portugal Caminhos para o Futuro, 2015. Doenças Respirato [12] A. Freitas, T. Silva-Costa, F. Lopes, I. Garcia-Lema, A. Teixeira-Pinto, P. Brazdil,
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
[13]
[14] [15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
et al., Factors influencing hospital high length of stay outliers, BMC Health Serv. Res. 12 (2012) 265, http://dx.doi.org/10.1186/1472-6963-12-265. rio da Saúde, Portaria n.o 839-A/2009 de 31 de Julho, (2009). http:// Ministe www.acss.min-saude.pt/Portals/0/Portaria839_A_2009.pdf (accessed 23.03.16). C.M. Borges, F. Lopes, Peso Relativo Dum GDH, 2009. http://portalcodgdh.minsaude.pt/index.php/Peso_relativo_dum_GDH (accessed 23.03.16). D. Ayres-Sampaio, A.C. Teodoro, N. Sillero, C. Santos, J. Fonseca, A. Freitas, An investigation of the environmental determinants of asthma hospitalizations: an applied spatial approach, Appl. Geogr. 47 (2014) 10e19, http://dx.doi.org/ 10.1016/j.apgeog.2013.11.011. A. Freitas, I. Lema, A. da Costa-Pereira, Comorbidity coding trends in hospital administrative databases, in: New Adv. Inf. Syst. Technol, Springer, 2016, pp. 609e617. H. Quan, V. Sundararajan, P. Halfon, A. Fong, B. Burnand, J.-C. Luthi, et al., Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data, Med. Care 43 (2005) 1130e1139, http://dx.doi.org/ 10.1097/01.mlr.0000182534.19832.83. Agency for Healthcare Policy and Research, Clinical Classifications Software (CCS) Summary and Download Information and Downloading Information, 1999. www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp (accessed 18.03.16). M. Cazzola, C. Donner, N.A. Hanania, One hundred years of respiratory medicine chronic obstructive pulmonary disease (COPD)dRepublished article, Respir. Med. COPD Updat. 4 (2008) 8e25, http://dx.doi.org/10.1016/ j.rmedu.2007.11.019. J. Cardoso, J.R. Ferreira, J. Almeida, J.M. Santos, F. Rodrigues, M.J. Matos, et al., Chronic obstructive pulmonary disease in Portugal: pneumobil (1995) and 2002 prevalence studies revisited, Rev. Port. Pneumol. 19 (2013) 88e95, http://dx.doi.org/10.1016/j.rppneu.2012.11.005. ^ncia da doença pulmonar obstrutiva cro nica em Lisboa, Portugal: Prevale estudo burden of obstructive lung disease, Rev. Port. Pneumol. 19 (2013) 96e105. http://www.sciencedirect.com/science/article/pii/ S0873215913000202 (accessed 24.09.14). World Health Organisation, Chronic Obstructive Pulmonary Disease (COPD), 2015. http://www.who.int/mediacentre/factsheets/fs315/en/ (accessed
69
31.07.15). [23] S. Aryal, E. Diaz-guzman, D.M. Mannino, Influence of Sex on Chronic Obstructive Pulmonary Disease Risk and Treatment Outcomes, 2014, pp. 1145e1154. [24] S.C. Hitchman, G.T. Fong, Gender empowerment and female-to-male smoking prevalence ratios, Bull. World Health Organ 89 (2011) 195e202, http:// dx.doi.org/10.2471/BLT.10.079905. [25] World Health Organisation, WHO Report on the Global Tobacco Epidemic, 2013, p. 2013. [26] H. Carreira, M. Pereira, A. Azevedo, N. Lunet, Trends in the prevalence of smoking in Portugal: a systematic review, BMC Public Health 12 (2012) 958, http://dx.doi.org/10.1186/1471-2458-12-958. [27] T.H. Harries, H.V. Thornton, S. Crichton, P. Schofield, A. Gilkes, P.T. White, Length of stay of COPD hospital admissions between 2006 and 2010: a retrospective longitudinal study, Int. J. Chron. Obstruct. Pulmon. Dis. 10 (2015) 603. [28] P.G.J. Burney, J. Patel, R. Newson, C. Minelli, M. Naghavi, Global and regional trends in COPD mortality, 1990-2010, Eur. Respir. J. (2015) 1e9, http:// dx.doi.org/10.1183/09031936.00142414. pez-Campos, M. Ruiz-Ramos, J.B. Soriano, Mortality trends in chronic [29] J.L. Lo obstructive pulmonary disease in Europe, 1994-2010: a joinpoint regression analysis, Lancet Respir. Med. 2 (2014) 54e62, http://dx.doi.org/10.1016/ S2213-2600(13)70232-7. [30] C.R. Cooke, M.J. Joo, S.M. Anderson, T. a Lee, E.M. Udris, E. Johnson, et al., The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease, BMC Health Serv. Res. 11 (2011) 37, http://dx.doi.org/10.1186/1472-6963-11-37. €rres, M. Pfeifer, Treatment of respiratory failure in COPD, [31] S. Budweiser, R.A. Jo Int. J. Chron. Obstruct. Pulmon. Dis. 3 (2008) 605e618. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC2650592/. [32] A. Miguel, L.F. Azevedo, F. Lopes, A. Freitas, A.C. Pereira, Methodologies for the detection of adverse drug reactions: comparison of hospital databases, chart review and spontaneous reporting, Pharmacoepidemiol Drug Saf. 22 (1) (2013) 98e102, http://dx.doi.org/10.1002/pds.3348.
Contents lists available at ScienceDirect
Respiratory Medicine journal homepage: www.elsevier.com/locate/rmed
Trends in hospital admissions for obstructive lung disease from 2000 to 2010 in Portugal ~o Almeida Fonseca a, b, Fernando Lopes a, b, Alberto Freitas a, b Rafael Vieira a, *, Joa cido da Costa, 4200-450 Porto, Department of Health Information and Decision Sciences (CIDES), Faculty of Medicine, University of Porto, Rua Dr. Pla Portugal b cido da Costa, 4200-450 Porto, Portugal Center for Health Technology and Services Research (CINTESIS), University of Porto, Rua Dr. Pla a
a r t i c l e i n f o
a b s t r a c t
Article history: Received 22 December 2015 Received in revised form 13 May 2016 Accepted 17 May 2016 Available online 18 May 2016
The burden of hospitalisations for obstructive lung diseases (OLD) has not been sufficiently studied. We aimed to characterise the hospitalisations for OLD from 2000 to 2010 in all Portuguese public hospitals. We analysed hospital discharges with a diagnosis of OLD regarding the patients’ gender, age, residence and comorbidities. Of the 120 399 hospital admissions with a principal diagnosis of OLD, COPD (ICD-9CM 491.x, 492.x, 496) was responsible for 81%. The change in patients discharged with OLD as a principal diagnosis was only 1% from 2000 to 2010 and did not change for COPD. Hospital admissions and deaths for COPD and other OLD increased with age and were more common in men than women. In-hospital mortality for COPD decreased 34.1% from 2000 to 2010, while the median length of stay was fairly constant at 8 days. Respiratory failure, insufficiency and/or arrest, and pneumonia, are the principal diagnoses often associated with COPD. When both pneumonia and COPD were diagnosed there was an increasing trend to classify pneumonia as the principal diagnosis (64.4%e72.9%), a sign that may lead to underestimation of COPD hospitalisations. In summary, a considerable decrease in in-hospital COPD mortality was observed while hospital admissions and the length of stay did not change substantially. These results suggest that better healthcare or other factors may be counteracting the expected increase of the burden of COPD. © 2016 Elsevier Ltd. All rights reserved.
Keywords: Obstructive lung disease Chronic obstructive pulmonary disease Asthma Hospitalisations Mortality Length of stay
1. Introduction Obstructive lung diseases (OLD) include Chronic Obstructive Pulmonary disease (COPD), asthma and bronchiectasis [1,2]. COPD is a group of diseases characterised by persistent and progressive limitation of airflow, and classically includes emphysema and chronic bronchitis [3]. COPD will be the third major cause of death by 2030 [4]. COPD prevalence seems to be higher in men and increases with age [5,6]. Although COPD is often associated with other diseases, thus increasing its mortality rate, COPD as a secondary diagnosis is often underdiagnosed [7]. Hospitalisation of COPD cases already represent a major burden [8,9]. Khakban et al. showed that hospitalisations were the main driver of the high direct costs of COPD [10]. Studies on hospitalisations and the socio-economic burden of COPD in Portuguese healthcare are not available in the literature. Summarised
* Corresponding author. E-mail address: [email protected] (R. Vieira). http://dx.doi.org/10.1016/j.rmed.2016.05.018 0954-6111/© 2016 Elsevier Ltd. All rights reserved.
information on COPD hospitalisations in Portugal is available in the reports issued by the Portuguese Observatory for Respiratory Diseases [11], but, since this covers all pulmonary diseases, COPD hospitalisations are mentioned only briefly. In light of the socio-economic burden of OLD and the lack of information on OLD hospitalisations in Portugal, our study set out to analyse the evolution of in-hospital admissions, length of stay and mortality of patients admitted in Portuguese hospitals with a diagnosis of OLD, from 2000 to 2010. 2. Methods 2.1. Study design and data source We conducted a retrospective observational study using data from the national hospitalisations database, provided by the Central Administration of the Health System of the Portuguese Ministry of Health (ACSS). This database compiles administrative and clinical data on hospitalisation episodes in the Portuguese National Health Service, but it does not include data from private hospitals [12].
64
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
Diagnoses and procedures performed have been coded in Portugal, since 1989, using the International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM). The relative weight of each Diagnosis Related Group (DRG) has been set by the Portuguese Health Ministry [13]. The relative weight reflects the average cost of treating a patient with that DRG [14]. 2.2. Study population We included all inpatient episodes of patients aged 18 years and older with a principal or secondary diagnosis of obstructive lung disease e ICD-9-CM codes 491.x for chronic bronchitis, 492.x for emphysema, 493.x for asthma, 494.x for bronchiectasis and 496 for chronic airway obstruction, not elsewhere classified e with a discharge date between 2000 and 2010 in mainland Portuguese hospitals. 2.3. Data collection and estimation of variables For each hospitalisation with a diagnosis of OLD, we collected data on age, gender, place of residence, length of stay and discharge status. We organised the episodes coded by ICD-9-CM into two groups: - OLD, which includes 491.x (chronic bronchitis), 492.x (emphysema), 493.x (asthma), 494.x (bronchiectasis) and 496 (chronic airway obstruction, not elsewhere classified); - COPD, which includes 491.x (chronic bronchitis), 492.x (emphysema) and 496 (chronic airway obstruction, not elsewhere classified). We recoded age into the following age groups: 18e29 years old, 30e39 years old, 40e49 years old, 50e59 years old, 60e69 years old, 70e79 years old, and 80 years and older. We classified the place of residence by level of urbanisation, into urban (high level of urbanisation), moderate and rural (low level of urbanisation) [15]. The necessary information on the population (size and variation) was collected from the National Institute of Statistics (INE), which obtained these data by conducting population censuses. 2.4. Analysis For each hospital discharge with a principal or secondary diagnosis corresponding to an obstructive lung disease, we analysed the evolution of hospital admissions and calculated the yearly ratio between each disease and the total number of hospitalisations. We calculated the mean secondary diagnoses in hospitalisations with a principal diagnoses of OLD divided by mean secondary diagnoses in all hospitalisations to adjust all OLD hospitalisations to the mean number of secondary diagnoses coded each year. We made this adjustment, as we studied hospitalisations over a long time span and the mean number of secondary diagnoses that were registered increased during this period due to a better and more complete coding of secondary diagnoses (from 1.66 per hospitalisation to 3.20 per hospitalisation, accounting for an increase of 0.15 secondary diagnoses/hospitalisation per year [16]). We also collected data on hospitalisations and mortality, and calculated the hospitalisation and mortality ratio by age group, gender and residence. We further calculated age-adjusted OLD and COPD hospitalisations and mortality (principal diagnosis) over the study period using the European (Scandinavian 1960) Standard Population. We calculated median length of stay from 2000 to 2010, as length of stay did not follow a normal distribution. Regarding mortality, we calculated the mortality ratio in hospitalisations with
a principal diagnosis of OLD/COPD, and the proportion of deaths in a hospitalisation with a principal diagnosis of OLD/COPD compared with all in-hospital deaths. We calculated Elixhauser comorbities [17] for COPD, OLD and for all diagnoses between 2000 and 2010. The Elixhauser comorbidities index was developed to identify comorbidities associated with an increase in the risk of in-hospital mortality, length of stay and its costs. We analysed the principal diagnoses most frequently associated with COPD as a secondary diagnosis. We grouped diagnoses according to the Clinical Classifications Software (CCS) for ICD-9-CM [18], and adjusted for the frequency of the diagnoses when COPD was not a secondary diagnosis. We selected all episodes with a diagnosis of COPD or pneumonia (whether as principal or secondary), and calculated the proportion of principal diagnoses of each of these clinical entities, as well as its DRG relative weights. We performed the same analysis for respiratory insufficiency, failure and/or arrest, and COPD. Finally, for time trends, we calculated the linear regression and tested the null hypothesis that the slope, B, was different from 0. Descriptive statistical analysis was performed using IBM SPSS Statistics for Windows v23 (Armonk, NY: IBM Corp.). 3. Results A total of 120 399 cases of hospital admissions with a principal diagnosis of OLD were recorded in the period studied. These amount to 1.41% of all hospitalisations between 2000 and 2010, of which 97 325 (81%) were due to COPD (Table 1). Although the absolute number of hospital discharges for OLD/COPD increased from 2000 to 2010, there was no relative increase in comparison with all hospital admissions. The variation in hospital discharges of patients with OLD as a principal diagnosis was only 1% (Table 1) (95% CI for B: 0.16e0.23). In total, we identified 441 088 hospitalisations of patients with a principal or secondary diagnosis of OLD (5.15% of the total hospitalisations) from 2000 to 2010. Of these, 338 590 (77%) were classified as COPD. In this time period, there was an increase of 42% in the proportion of hospital discharges with a diagnosis of COPD (either principal or secondary) (Table 1) (95% CI for B: 0.10e0.15). However, after adjusting these data for the mean number of secondary diagnoses coded each year, we found a significant increase only in hospitalisations with a principal or secondary diagnosis of Chronic Airway Obstruction, not elsewhere classified, from 2000 to 2010. After this adjustment, hospitalisations with a diagnosis of COPD fell significantly owing to the 34.1% decrease in chronic bronchitis hospitalisations. Furthermore, hospitalisations with a diagnosis of emphysema, asthma and bronchiectasis did not show any significant trend. Seventeen per cent of the hospitalisations with a principal diagnosis of bronchiectasis had COPD as a secondary diagnosis. Of all the admissions with a principal diagnosis of OLD, 38% were patients 70e79 years old and 29% were more than 80 years old. OLD represents a larger burden for patients aged 80 years and older as it accounts for 2.3% of all hospital admissions of patients in that age group. Hospital admissions and mortality for OLD increase with age, with an age peak in the 80þ years old age group (Fig. 1). Sixty per cent of patients admitted with a principal diagnosis of OLD were male. While 1.8% of all hospital admissions of men were due to OLD, in women OLD accounts for 0.7% of hospital admissions. Mortality is higher in male patients in all age groups (Fig. 1). We studied the evolution in hospital admissions by place of residence, but we did not find any relevant differences between regions (data not shown). The inpatient median length of stay for OLD was 8 days from 2000 to 2010 (interquartile range of 4.0e11.0 days, except in 2000 and 2001e3.0 to 11.0 days e and 2010e5.0 to 11.0 days). Median length of stay for admissions for COPD fell from 9.0 days in 2000
Chronic bronchitis
Total COPD
5624 (0.07) 26 017 (0.30)
17 450 (0.20) 88 928 (1.04)
0.026 <0.001 0.753 0.002 <0.001 0.186
<0.001 269 883 (3.15) <0.001 0.001 2221 (0.03) < 0.001 19 264 (0.23) 0.798 <0.001 2411 (0.03) <0.001 54 361 (0.64) <0.001
20 715 (2.79) 22 611 (2.98) 23 921 (3.10) 24 430 (3.08) 24 511 (3.09) 25 615 (3.17) 24 042 (3.04) 26 501 (3.35) 26 158 (3.29) 25 740 (3.37) 25 639 (3.39) þ21.3% 34.1% Emphysema 250 (0.03) 245 (0.03) 220 (0.03) 241 (0.03) 218 (0.03) 217 (0.03) 156 (0.02) 175 (0.02) 157 (0.02) 155 (0.02) 187 (0.02) 26.7% 1196 (0.16) 1367 (0.18) 1510 (0.20) 1490 (0.19) 1547 (0.20) 1659 (0.21) 1694 (0.21) 1920 (0.24) 1980 (0.25) 2179 (0.29) 2722 (0.36) þ123.1% þ15.89% 273 (0.04) 299 (0.04) 310 (0.04) 296 (0.04) 291 (0.04) 242 (0.03) 145 (0.02) 113 (0.01) 158 (0.02) 127 (0.02) 157 (0.02) 43.6% Chronic 2897 (0.39) 3276 (0.43) 3723 (0.48) 4139 (0.52) 4198 (0.53) 4902 (0.61) 5051 (0.64) 5216 (0.66) 6254 (0.79) 6902 (0.90) 7803 (1.03) þ164.1% airway þ38.8% obstruction, not elsewhere classified Asthma 1682 (0.23) 1598 (0.21) 1663 (0.22) 1568 (0.20) 1534 (0.19) 1625 (0.20) 1569 (0.20) 1647 (0.21) 1580 (0.20) 1463 (0.19) 1521 (0.20) 11.3% 5621 (0.76) 5978 (0.79) 6786 (0.88) 7392 (0.93) 7282 (0.92) 7792 (0.97) 8147 (1.03) 9130 (1.15) 9388 (1.18) 10 351 (1.36) 11 061 (1.46) þ93.0% þ7.09% Bronchiectasis 438 (0.06) 394 (0.05) 403 (0.05) 398 (0.05) 381 (0.05) 381 (0.05) 485 (0.06) 676 (0.09) 677 (0.09) 645 (0.08) 746 (0.10) þ67.0% 1785 (0.24) 1843 (0.24) 2102 (0.27) 2043 (0.26) 2229 (0.28) 2138 (0.26) 2378 (0.30) 2778 (0.35) 2821 (0.35) 2776 (0.36) 3124 (0.41) þ71.6% 1.01%
0.921 120 399 (1.41) <0.001 441 088 (5.15) <0.001 0.535 97 325 (1.14) <0.001 338 590 (3.96) <0.001 0.842 92 693 (1.08)
p-value Total
D% 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000
10 285 (1.39) 10 802 (1.42) 11 156 (1.44) 11 265 (1.42) 10 712 (1.35) 11 744 (1.46) 10 264 (1.30) 11 620 (1.47) 11 187 (1.41) 10 765 (1.41) 10 599 (1.40) þ1.0% 31 211 (4.21) 33 834 (4.46) 36 670 (4.75) 38 229 (4.83) 38 382 (4.84) 40 626 (5.04) 39 675 (5.02) 43 648 (5.52) 44 655 (5.62) 45 969 (6.02) 48 189 (6.37) þ51.4% 17.2% 8165 (1.10) 8810 (1.16) 9090 (1.18) 9299 (1.17) 8797 (1.11) 9738 (1.21) 8210 (1.04) 9297 (1.18) 8930 (1.12) 8657 (1.13) 8332 (1.10) 0.0% 24 536 (3.31) 26 878 (3.54) 28 752 (3.72) 29 724 (3.75) 29 907 (3.77) 31 729 (3.93) 30 277 (3.83) 33 124 (4.19) 33 855 (4.26) 34 256 (4.49) 35 552 (4.70) þ42.1% 23.1% 7642 (1.03) 8266 (1.09) 8560 (1.11) 8762 (1.11) 8288 (1.05) 9279 (1.15) 7909 (1.00) 9009 (1.14) 8615 (1.08) 8375 (1.10) 7988 (1.06) þ2.5% OLD
Table 1 Hospital admissions of patients with OLD/COPD (raw data, except italics). First row includes principal diagnoses only. Second row includes principal and secondary diagnoses. D% refers to the percentage variation, as calculated by: (%2010e%2000)/%2000. Data shown as n (% of total hospital admissions). p-value tests H0: B s 0. Values in italics concern the variation and p-value for trends in hospitalisations with a principal or secondary diagnosis of one of the diagnoses studied, adjusted for the mean number of secondary diagnoses coded each year.
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
65
(interquartile range: 5.0e13.0) to 8 days in 2001, and remained constant from 2001 to 2010. The interquartile range was 5.0e12.0 days, except in 2001 and 2002 (5.0e13.0 days). In-hospital mortality from 2000 to 2010 decreased both in COPD (9.3%e7.5%, which is a 20.0% decrease [95% CI for B: 0.25 to 0.11]) and in OLD (7.7%e6.4%, which is a decrease of 16.4% [95% CI for B: 0.20 to 0.07]) (Table 2). The proportion of deaths from COPD and OLD, compared with all in-hospital deaths, declined from 2.0% to 1.4% (decrease of 34.1% [95% CI for B: 0.09 to 0.06]) in COPD and from 2.1% to 1.5% in OLD (decrease of 30.5% [95% CI for B: 0.09 to 0.05]) (Table 2). When analysing mortality by age group for COPD, we noticed a significant fall (p < 0.05) in older age groups. In the 18e29 and 30e39 age groups there was a non-significant decline (p > 0.05) and 40e49 years old there was a nonsignificant increase in mortality (p > 0.05) (data not shown). Age-adjusted values show that in the period studied there was a mean of 79.4 hospitalisations/100 000 inhabitants aged 18 and older/year for COPD and 103.2 hospitalisations/100 000 inhabitants aged 18 and older/year for OLD. Mortality for COPD was 5.9/ 100 000 inhabitants aged 18 and older/year, while for OLD it was 6.2/100 000 inhabitants aged 18 years and older/year (Table 3). COPD and OLD hospitalisations had more comorbidities than hospitalisations for all causes in all age groups, and comorbidities increase with age (Table 4). The principal group of diagnoses most frequently associated with COPD is respiratory failure, insufficiency and/or arrest (adult), in which COPD is a secondary diagnosis in 13.5% percent of hospitalisations. COPD is also often associated with pneumonia and is a secondary diagnosis in 10.1% of hospitalisations. According to the ICD-9-CM classification, 6 of the 10 most associated group of diseases are respiratory system disorders (Table 5). Regarding episodes with a diagnosis of COPD or pneumonia (either principal or secondary), pneumonia as the principal diagnosis rose from 64.4% to 72.9% from 2000 to 2010, while COPD decreased from 18.4% to 8.1% (Fig. 2, Panel A). We calculated the mean for DRG relative weights, which were: 1.29 for hospitalisations with a principal diagnosis of pneumonia and a secondary diagnosis of COPD; 1.47 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis of pneumonia; 1.08 for hospitalisations with a principal diagnosis of pneumonia and a secondary diagnosis that did not include COPD; 1.05 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis that did not include pneumonia. We also compared the classification of asthma and pneumonia as principal diagnosis and found similar trends (data not shown). We performed the same analysis for respiratory failure, insufficiency and/or arrest, and COPD, taking into account the results from Table 5. Our data (Fig. 2, Panel B) shows that COPD is the most common principal diagnosis. In 2000, respiratory failure, insufficiency and/or arrest was the principal diagnosis in 18.5% of the cases, but in 2001 it was the principal diagnosis in only 9.3% and in 2010 in 5.4% of hospitalisations. We further calculated the mean for DRG relative weights, and found: 2.15 for hospitalisations with a principal diagnosis of respiratory failure, insufficiency and/or arrest, and a secondary diagnosis of COPD; 1.64 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis of respiratory failure, insufficiency and/or arrest; 1.91 for hospitalisations with a principal diagnosis of respiratory failure, insufficiency and/or arrest, and a secondary diagnosis that did not include COPD; 0.84 for hospitalisations with a principal diagnosis of COPD and a secondary diagnosis that did not include respiratory failure, insufficiency and/or arrest.
66
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
Fig. 1. Panels A & B: Hospitalisations with a principal diagnosis of COPD or OLD, by age and gender. Data is shown as the proportion of hospitalisations with a principal diagnosis of COPD or OLD standardised for age and gender total hospitalisations. Panels C & D: In-hospital mortality of discharges with a principal diagnosis of COPD or OLD, by age and gender. Data is shown as the mortality ratio among hospitalisations with a principal diagnosis of COPD or OLD.
Table 2 In-hospital mortality of patients with a principal diagnosis of OLD/COPD. % of deaths in OLD/COPD episodes refers to the proportion of deaths that among discharges with a principal diagnosis of OLD/COPD relative to the number of hospitalisations in that year (e.g. in the year 2000, for 100 hospitalisations with a principal diagnosis of OLD, 7.7 of patients died in hospital). % of all deaths refers to the proportion of deaths among discharges with a principal diagnosis of OLD/COPD relative to the total deaths in that year (e.g. in the year 2000, OLD accounted for 2.1 deaths in every 100 deaths that occurred in 2000). D refers to variation and was calculated by: (2010e2000)/2000. p-value tests H0: B s 0.
OLD
COPD
N % of % of N % of % of
deaths in OLD episodes all deaths deaths in COPD episodes all deaths
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
D
p-value
Total
790 7.7 2.1 763 9.3 2.0
827 7.7 2.1 797 9.0 2.0
815 7.3 2.0 792 8.7 1.9
834 7.4 2.0 797 8.6 1.9
748 7.0 1.8 708 8.0 1.7
876 7.5 1.9 835 8.6 1.9
683 6.7 1.6 648 7.9 1.5
717 6.2 1.6 686 7.4 1.5
716 6.4 1.5 662 7.4 1.4
743 6.9 1.6 700 8.1 1.5
681 6.4 1.5 623 7.5 1.4
13.8% 16.4% 30.5% 18.3% 20.0% 34.1%
0.022 0.001 <0.001 0.009 <0.001 <0.001
8430 7.0 1.8 8011 8.2 1.7
4. Discussion In this study, we found that there was no increase in hospitalisations for COPD as the principal diagnosis, except for chronic bronchitis. One explanation may be that COPD exacerbations leading to hospitalisations are not coded as COPD, with other
diagnoses such as pneumonia being preferred. We also noted that in-hospital mortality decreased 30% for COPD from 2000 to 2010, which may indicate better healthcare. However, the median length of stay was fairly constant at 8 days. The prevalence of COPD increases with age [19e21]. However, the relation between COPD and age in hospital admissions has been
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69 Table 3 Age-adjusted data for hospitalisations and mortality in OLD and COPD (principal diagnosis only). We used the European (Scandinavian 1960) Standard Population for age-adjustment. Data
Age-adjusted value (per 100 000 inhabitants aged 18 years and older, per year)
OLD hospitalisations COPD hospitalisations OLD mortality COPD mortality
103.2 79.4 6.2 5.9
67
Obstructive Lung Disease, although it is not yet known if age is a risk factor, or if age simply reflects the exposure to risk factors throughout life [3]. Many studies have shown a higher prevalence of COPD in men [3,5,6], although, according to the World Health Organisation, COPD now affects both genders almost equally [22]. Aryal et al. suggest that gender affects COPD in a complex way through a combination of behavioural, environmental and genetic factors [23]. The increase of smoking among women may partly explain this increase in the prevalence of COPD among women [3,23e25].
Table 4 Elixhauser Comorbidities for OLD and COPD (principal diagnosis), and for all hospitalisations. Elixhauser comorbidities (mean number) Age groups
OLD
95%CI
COPD
95% CI
All hospital admissions
95%CI
18e29 30e39 40e49 50e59 60e69 70e79 80þ Total
0.31 0.56 1.01 1.37 1.56 1.75 1.80 1.58
0.28e0.33 0.53e0.59 0.98e1.05 1.35e1.40 1.54e1.58 1.73e1.76 1.78e1.82 1.58e1.59
0.43 0.90 1.28 1.54 1.62 1.78 1.81 1.71
0.35e0.51 0.81e0.98 1.23e1.33 1.51e1.57 1.60e1.64 1.78e1.80 1.80e1.83 1.70e1.72
0.12 0.23 0.54 0.81 1.08 1.32 1.48 0.84
0.115e0.117 0.227e0.230 0.539e0.543 0.809e0.813 1.077e1.081 1.317e1.321 1.474e1.479 0.839e0.840
Table 5 Principal diagnoses when COPD is reported as secondary diagnosis. Values were adjusted for frequency of diagnoses. Diagnosis (as classified by CCS)
%
Respiratory failure; insufficiency; arrest (adult) Pneumonia (except that caused by tuberculosis or sexually transmitted disease) Cancer of bronchus; lung Pleurisy; pneumothorax; pulmonary collapse Congestive heart failure; nonhypertensive Acute bronchitis Pulmonary heart disease Other lower respiratory disease Lung disease due to external agents Hypertension with complications and secondary hypertension
13.5 10.1 9.9 9.4 9.2 7.8 7.8 7.1 7.0 6.1
Fig. 2. Panel A. Classification of COPD and pneumonia as principal diagnoses, when both are present in the hospitalisation. Values shown are % of principal diagnosis. Panel B. Classification of COPD and respiratory failure, insufficiency and/or arrest as principal diagnosis, when both are present in the hospitalisation. Values shown are % of principal diagnosis.
much less studied. We observed a marked increase in hospital admissions for COPD in age groups up to 70e79 years old and stabilisation in patients over 70. This association between COPD and age is also recognised by the Global Initiative for Chronic
Regarding hospitalisations, we found more admissions of men with COPD. This might be because female smoking in Portugal is still increasing, being placed at stage II of the tobacco epidemic, while men can be placed at stages III or IV [26].
68
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
Harries and co-workers showed that the mean length of stay in London’s hospitals fell from 8.2 days in 2006 to 7.0 days in 2010 [27]. In Portugal, the length of stay for COPD remained 8 days since 2001, in spite of the overall effort to cut the length of hospitalisation to reduce national health system costs [27]. The World Health Organisation expects COPD to become the 3rd leading cause of death (it was 4th in 2004) [4], even though some studies show a decrease in mortality due to COPD both globally [28] and in the European Union [29]. In-hospital mortality has been less studied [7]. Importantly, there was a decrease of 19% in in-hospital mortality from 2000 to 2010. The burden of COPD in global inhospital mortality has also fallen as the COPD in-hospital mortality, in comparison with all causes of in-hospital mortality, declined by 30% from 2000 to 2010. Nonetheless, COPD still accounts for 1.7% of all deaths occurring during hospital admissions in Portugal. The burden of COPD is often underestimated, and COPD as a secondary diagnosis is often underreported [7]. We have found that COPD, as a comorbidity, is mostly associated with diseases of the respiratory system, in particular respiratory insufficiency/arrest/ failure and pneumonia. It is also associated with lung or bronchial cancer and circulatory/heart diseases, such as heart failure, heart disease and hypertension. These results agree with those reported by Holguin et al. that showed an association between COPD and diseases such as pneumonia, congestive heart failure and respiratory failure [7]. It is known that the classification of diseases in hospital admissions has inaccuracies, and this is also true for the classification of COPD [30]. Being aware of the relationship between COPD and pneumonia [3], we studied the evolution of the classification of patients admitted with both pneumonia and COPD. Our results suggest that over this 10-year period pneumonia has been the principal diagnosis in most cases, and the gap between pneumonia and COPD is widening. We performed the same analysis for pneumonia and asthma, which showed the same trend. This indicates that COPD diagnoses seem to be passed over in favour of pneumonia, which can indicate the under-coding of COPD in Portuguese hospitals. We speculated that a possible reason for coding a hospitalisation with pneumonia as principal diagnosis and COPD as secondary diagnosis could be that this would place the hospitalisation in a DRG with a higher relative weight, which would be favourable in terms of funding. However, in Portugal, hospitalisations with COPD as principal diagnosis and pneumonia as secondary diagnosis have a higher DRG relative weight. It is possible that pneumonia is more often chosen as principal diagnosis as it is the factor that leads to the exacerbation of COPD and subsequent hospital admission. Still, whenever the critical reason for hospital admission is having COPD, it would be preferable to code such hospital discharges as exacerbated COPD. Regarding hospitalisations with a diagnosis of COPD and respiratory failure, insufficiency and/or arrest, our results show that COPD is more often coded as principal diagnosis than respiratory failure, insufficiency and/or arrest. The association between respiratory failure, insufficiency and/or arrest and COPD is well described in the peer-reviewed literature [7], and patients with COPD and respiratory insufficiency have higher mortality rates [31]. Our data also shows that COPD as a secondary diagnosis is often associated with respiratory failure, insufficiency and/or arrest. However, COPD is usually the principal diagnosis. This is not affected by its DRG, as our data regarding the DRG relative weights shows that hospitalisations with a principal diagnosis of respiratory failure, insufficiency and/or arrest are placed in a higher DRG than COPD hospitalisations. It is important to acknowledge the strengths and limitations of this study. We gathered and analysed nationwide data on the frequency and mortality of hospital admissions over a 10-year period,
from 2000 to 2010. We had access to data from Portuguese public hospitals, which account for 85% of all hospitalisation episodes in Portugal. Nonetheless, we recognise that this study has some limitations, mostly related to its design and sources of data. First of all, we rely on the quality of diagnoses and coding of diseases. For this reason, the validity of using hospital discharge data is limited, and the combination of this with other data sources has provided better results [30]. We were not able to check the validity of the diagnoses, as this was not the objective of this descriptive analysis. We have followed similar designs of other descriptive studies on COPD hospitalisations. A prospective or retrospective analysis of individual patient records is needed to establish the validity of COPD diagnoses in hospital databases, as previously done in other clinical fields [32]. It is also important to note that admissions classified as chronic airway obstruction, not elsewhere classified (496) are probably misclassifications and might even overestimate our results for COPD. In conclusion, our study shows that OLD hospitalisations are a significant burden in Portugal, with COPD accounting for most of it. We found a considerable decrease in in-hospital COPD mortality, while hospital admissions and the length of stay did not substantially change over the period. Results obtained from hospitalisations databases should be viewed as hypothesis generation studies, to be tested with other study designs using detailed clinical data. Nevertheless, these results do suggest that better healthcare or other factors may be counteracting the expected increase of the burden of COPD. Acknowledgements The authors thank the Central Health System Administration (ACSS) for providing access to the dataset. The authors also thank the Center for Health Technology and Services Research (CINTESIS) for providing the conditions to perform this study. The authors further thank Mr Tim Stoffel for proofreading the manuscript and providing valuable feedback. References [1] A. Maitra, V. Kumar, The lung, in: V. Kumar, A.K. Abbas, N. Fausto, R. Mitchell (Eds.), Robbins Basic Pathol, eighth ed., Elsevier Health Sciences, Philadelphia, PA, 2007, pp. 479e540. [2] S.R. Kim, Y.K. Rhee, Overlap between asthma and COPD: where the two diseases converge, Allergy. Asthma Immunol. Res. 2 (2010) 209e214, http:// dx.doi.org/10.4168/aair.2010.2.4.209. [3] Global Initiative for Obstructive Lung Disease, Global Strategy for Diagnosis, Management, and Prevention of COPD, 2014. www.goldcopd.org/uploads/ users/files/GOLD_Report_2014_Jan23.pdf (accessed 23.10.14). [4] World Health Organization, World Health Statistics, 2008, p. 112. http://www. who.int/whosis/whostat/EN_WHS08_TOCintro.pdf. [5] M. Cazzola, E. Puxeddu, G. Bettoncelli, L. Novelli, A. Segreti, C. Cricelli, et al., The prevalence of asthma and COPD in Italy: a practice-based study, Respir. Med. 105 (2011) 386e391, http://dx.doi.org/10.1016/j.rmed.2010.09.022. [6] F.W.K. Chan, F.Y.Y. Wong, C.H.K. Yam, W. Cheung, E.L.Y. Wong, M.C.M. Leung, et al., Risk factors of hospitalization and readmission of patients with COPD in Hong Kong population: analysis of hospital admission records, BMC Health Serv. Res. 11 (2011) 186, http://dx.doi.org/10.1186/1472-6963-11-186. [7] F. Holguin, E. Folch, S.C. Redd, D.M. Mannino, Comorbidity and mortality in COPD- related hospitalizations in the United States, 1979 to 2001, Chest J. 128 (2005) 2005e2011. [8] F.T. Shaya, D. Dongyi, M.O. Akazawa, C.M. Blanchette, J. Wang, D.W. Mapel, et al., Burden of concomitant asthma and COPD in a Medicaid population, Chest 134 (2008) 14e19, http://dx.doi.org/10.1378/chest.07-2317. [9] R.J. Milne, R. Beasley, Hospital admissions for chronic obstructive pulmonary disease in New Zealand, N. Z. Med. J. 128 (2015) 23e35. [10] A. Khakban, D.D. Sin, J.M. FitzGerald, R. Ng, Z. Zafari, B. McManus, et al., 10year trends in direct costs of COPD: a population based study, Chest (2015), http://dx.doi.org/10.1378/chest.15-0721. rio Nacional das Doenças Respirato rias, 10.o Relato rio Panorama das [11] Observato rias em Portugal Caminhos para o Futuro, 2015. Doenças Respirato [12] A. Freitas, T. Silva-Costa, F. Lopes, I. Garcia-Lema, A. Teixeira-Pinto, P. Brazdil,
R. Vieira et al. / Respiratory Medicine 116 (2016) 63e69
[13]
[14] [15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
et al., Factors influencing hospital high length of stay outliers, BMC Health Serv. Res. 12 (2012) 265, http://dx.doi.org/10.1186/1472-6963-12-265. rio da Saúde, Portaria n.o 839-A/2009 de 31 de Julho, (2009). http:// Ministe www.acss.min-saude.pt/Portals/0/Portaria839_A_2009.pdf (accessed 23.03.16). C.M. Borges, F. Lopes, Peso Relativo Dum GDH, 2009. http://portalcodgdh.minsaude.pt/index.php/Peso_relativo_dum_GDH (accessed 23.03.16). D. Ayres-Sampaio, A.C. Teodoro, N. Sillero, C. Santos, J. Fonseca, A. Freitas, An investigation of the environmental determinants of asthma hospitalizations: an applied spatial approach, Appl. Geogr. 47 (2014) 10e19, http://dx.doi.org/ 10.1016/j.apgeog.2013.11.011. A. Freitas, I. Lema, A. da Costa-Pereira, Comorbidity coding trends in hospital administrative databases, in: New Adv. Inf. Syst. Technol, Springer, 2016, pp. 609e617. H. Quan, V. Sundararajan, P. Halfon, A. Fong, B. Burnand, J.-C. Luthi, et al., Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data, Med. Care 43 (2005) 1130e1139, http://dx.doi.org/ 10.1097/01.mlr.0000182534.19832.83. Agency for Healthcare Policy and Research, Clinical Classifications Software (CCS) Summary and Download Information and Downloading Information, 1999. www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp (accessed 18.03.16). M. Cazzola, C. Donner, N.A. Hanania, One hundred years of respiratory medicine chronic obstructive pulmonary disease (COPD)dRepublished article, Respir. Med. COPD Updat. 4 (2008) 8e25, http://dx.doi.org/10.1016/ j.rmedu.2007.11.019. J. Cardoso, J.R. Ferreira, J. Almeida, J.M. Santos, F. Rodrigues, M.J. Matos, et al., Chronic obstructive pulmonary disease in Portugal: pneumobil (1995) and 2002 prevalence studies revisited, Rev. Port. Pneumol. 19 (2013) 88e95, http://dx.doi.org/10.1016/j.rppneu.2012.11.005. ^ncia da doença pulmonar obstrutiva cro nica em Lisboa, Portugal: Prevale estudo burden of obstructive lung disease, Rev. Port. Pneumol. 19 (2013) 96e105. http://www.sciencedirect.com/science/article/pii/ S0873215913000202 (accessed 24.09.14). World Health Organisation, Chronic Obstructive Pulmonary Disease (COPD), 2015. http://www.who.int/mediacentre/factsheets/fs315/en/ (accessed
69
31.07.15). [23] S. Aryal, E. Diaz-guzman, D.M. Mannino, Influence of Sex on Chronic Obstructive Pulmonary Disease Risk and Treatment Outcomes, 2014, pp. 1145e1154. [24] S.C. Hitchman, G.T. Fong, Gender empowerment and female-to-male smoking prevalence ratios, Bull. World Health Organ 89 (2011) 195e202, http:// dx.doi.org/10.2471/BLT.10.079905. [25] World Health Organisation, WHO Report on the Global Tobacco Epidemic, 2013, p. 2013. [26] H. Carreira, M. Pereira, A. Azevedo, N. Lunet, Trends in the prevalence of smoking in Portugal: a systematic review, BMC Public Health 12 (2012) 958, http://dx.doi.org/10.1186/1471-2458-12-958. [27] T.H. Harries, H.V. Thornton, S. Crichton, P. Schofield, A. Gilkes, P.T. White, Length of stay of COPD hospital admissions between 2006 and 2010: a retrospective longitudinal study, Int. J. Chron. Obstruct. Pulmon. Dis. 10 (2015) 603. [28] P.G.J. Burney, J. Patel, R. Newson, C. Minelli, M. Naghavi, Global and regional trends in COPD mortality, 1990-2010, Eur. Respir. J. (2015) 1e9, http:// dx.doi.org/10.1183/09031936.00142414. pez-Campos, M. Ruiz-Ramos, J.B. Soriano, Mortality trends in chronic [29] J.L. Lo obstructive pulmonary disease in Europe, 1994-2010: a joinpoint regression analysis, Lancet Respir. Med. 2 (2014) 54e62, http://dx.doi.org/10.1016/ S2213-2600(13)70232-7. [30] C.R. Cooke, M.J. Joo, S.M. Anderson, T. a Lee, E.M. Udris, E. Johnson, et al., The validity of using ICD-9 codes and pharmacy records to identify patients with chronic obstructive pulmonary disease, BMC Health Serv. Res. 11 (2011) 37, http://dx.doi.org/10.1186/1472-6963-11-37. €rres, M. Pfeifer, Treatment of respiratory failure in COPD, [31] S. Budweiser, R.A. Jo Int. J. Chron. Obstruct. Pulmon. Dis. 3 (2008) 605e618. http://www.ncbi.nlm. nih.gov/pmc/articles/PMC2650592/. [32] A. Miguel, L.F. Azevedo, F. Lopes, A. Freitas, A.C. Pereira, Methodologies for the detection of adverse drug reactions: comparison of hospital databases, chart review and spontaneous reporting, Pharmacoepidemiol Drug Saf. 22 (1) (2013) 98e102, http://dx.doi.org/10.1002/pds.3348.