http://orcid.org/0000-0001-5551-5181
Figures
Abstract
Purpose
The objectives of this study were to analyze the characteristics of male and female patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) during 2006–2014 according to the presence or absence of bronchiectasis and to study the factors associated with in-hospital mortality (IHM) in patients hospitalized with AE-COPD and concomitant bronchiectasis.
Methods
We used the Spanish National Hospital Database to analyze patients admitted with AE-COPD as their primary diagnosis. Patients included in the study were stratified according to the presence or absence of bronchiectasis as their secondary diagnosis.
Results
We identified 386,646 admissions for AE-COPD, of which 19,679 (5.09%) involved patients with concomitant bronchiectasis. When patients with and without bronchiectasis were compared, we observed that the incidence of infection by Pseudomonas aeruginosa was substantially higher in the former, as were the mean stay, cost, and percentage of readmissions, although IHM and comorbidity were lower. The course of patients with AE-COPD and bronchiectasis was characterized by a gradual increase in prevalence and mean age among men and no differences in prevalence or lower mean age in women. Mortality was 4.24% and 5.02% in patients with and without bronchiectasis, respectively, although significance was lost after a multivariate adjustment (OR 0.94; 95% CI, 0.88–1.01). The factors associated with IHM were older age, higher comorbidity, isolation of P. aeruginosa, mechanical ventilation and readmission.
Conclusions
The prevalence of admission with AE-COPD and bronchiectasis increased in men but not in women during the study period. In patients hospitalized with AE-COPD, we did not find differences in mortality when comparing the presence and absence of bronchiectasis. The analysis of temporal trends revealed a significant reduction in mortality from 2006 to 2014 in male patients with COPD and concomitant bronchiectasis, but not among women. It is important to consider the factors associated with IHM such as age, comorbidity, isolation of P. aeruginosa, mechanical ventilation and readmission to better identify those patients who are at greater risk of dying during hospitalization.
Citation: Sánchez-Muñoz G, Lopez-de-Andrés A, Hernández-Barrera V, Jiménez-García R, Pedraza-Serrano F, Puente-Maestu L, et al. (2019) Bronchiectasis in patients hospitalized with acute exacerbation of COPD in Spain: Influence on mortality, hospital stay, and hospital costs (2006-2014) according to gender. PLoS ONE 14(1): e0211222. https://doi.org/10.1371/journal.pone.0211222
Editor: Shane Patman, University of Notre Dame Australia, AUSTRALIA
Received: July 19, 2018; Accepted: January 9, 2019; Published: January 25, 2019
Copyright: © 2019 Sánchez-Muñoz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: We used third party data (data not owned nor collected by the author). These data belongs to the Spanish Ministry of Health and Social Services. Any other investigator can access these data sets and would be able to access these data in the same manner as we did. We confirm we did not have any special access privileges that others would not have. Any investigator can apply for the databases filling the questionnaire available at: http://www.mscbs.gob.es/estadEstudios/estadisticas/estadisticas/estMinisterio/SolicitudCMBDdocs/2018_Formulario_Peticion_Datos_RAE_CMBD.pdf. Once completed, researchers may submit this questionnaire to: icmbd@mscbs.es. According to the contract signed with the Spanish Ministry of Health and Social Services that provided us the databases of the Spanish National Hospital Database, (Conjunto Minimo Basico de Datos; CMBD) we cannot provide the databases to any other investigator and we have to destroy the databases once the investigation has been concluded. As a consequence of the previous we cannot upload the databases in any public repository. All other relevant data are in the paper.
Funding: This study forms part of research funded by the FIS (Fondo de Investigaciones Sanitarias—Health Research Fund, Instituto de Salud Carlos III) co-financed by the European Union through the Fondo Europeo de Desarrollo Regional (FEDER, “Una manera de hacer Europa”): grant no. PI16/00564. The authors would like to thank NEUMOMADRID (XVIII Awards Edition, 2018) for grant support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AE-COPD, exacerbation of chronic obstructive pulmonary disease; CCI, Charlson comorbidity index; CMBD, Spanish National Hospital Database (“Conjunto Minimo Basico de Datos”); CT, computed tomography; ICD-9-CM, International Classification of Disease, 9th Revision; IHM, in-hospital mortality
Introduction
Chronic obstructive pulmonary disease (COPD) and bronchiectasis are two of the most common diseases of the airway [1,2]. The prevalence of COPD in the general population is approximately 10%, although many cases go undiagnosed [1]. The disease has high rates of morbidity and mortality and is a major public health problem [2]. The prevalence of bronchiectasis varies significantly between countries [3–5], with values ranging from 52.3 cases per 100,000 adults in the USA [3] to 2.7 per 100,000 persons in Finland [4] to 3.7 per 100,000 persons in the pediatric population of New Zealand [5]. COPD represents a major health problem [6].
Patients with COPD and bronchiectasis have specific clinical characteristics, such as greater sputum production, a greater degree of dyspnea, and a higher number of exacerbations. Notably, Spanish guidelines on COPD (Ges-EPOC) propose computed tomography (CT) in patients with the “exacerbated with chronic bronchitis” phenotype to rule out bronchiectasis because this condition has specific implications for therapy [7]. In turn, prognosis is worse for patients with both diseases. Thus, the presence of bronchiectasis is associated with greater mortality in patients with COPD independently of the degree of lung function involvement, the BODE index, and the number of exacerbations [8].
Between 5% and 10% of patients with bronchiectasis also have COPD [9–11]. Furthermore, the prevalence of bronchiectasis in patients with moderate or severe COPD ranges from 4% to 72% depending on the series. In any case, this prevalence is greater than that recorded for the general population and increases with the severity of COPD. The above data support an association between both processes that is more than merely random. More in-depth analysis is necessary to clarify this association [12].
Data collection on patients hospitalized with COPD and bronchiectasis at the national level is important when evaluating the incidence, clinical characteristics, morbidity, mean stay, cost, and mortality of this association. In Spain, current national registries of patients with respiratory diseases such as bronchiectasis could provide more data on the association [13]. However, the number of patients with COPD and concomitant bronchiectasis remains very low [14].
The objectives of this study were as follows: a) To analyze the characteristics of men and women hospitalized with acute exacerbation of COPD (AE-COPD) during 2006–2014 according to the presence or absence of bronchiectasis and b) To study the factors associated with in-hospital mortality (IHM) between patients hospitalized with AE-COPD and concomitant bronchiectasis.
Material and methods
On discharging a hospitalized patient in the Spanish Health System, physicians must declare all diagnoses made and procedures performed using the codes of the International Classification of Disease, 9th Revision (ICD-9-CM). This information is collected in the Spanish National Hospital Database (“Conjunto Minimo Basico de Datos” [CMBD]), which compiles data from all hospitals in the Spanish National Health System [15]. The CMBD includes personal data (sex and date of birth), date of admission, date of discharge, discharge destination (home, deceased, or other health care/social care institution), and details of up to 14 discharge diagnoses and up to 20 procedures performed during admission.
We selected all admissions of patients with exacerbation of COPD (ICD-9-CM code 491.21) as their primary diagnosis during 3 periods of 3 years each between 2006 and 2014. We stratified the database according to the presence of bronchiectasis (ICD-9-CM code 494) as a secondary diagnosis.
We analyzed the prevalence, clinical characteristics, diagnostic procedures, and outcomes of men and women discharged after an exacerbation of COPD according to whether they also had bronchiectasis. Clinical characteristics included information on overall comorbidity at the time of hospitalization, which was graded using the Charlson comorbidity index (CCI) [16]. The CCI comprises 17 disease categories whose scores are totaled to obtain an overall score for each patient. The proportion of patients who died during admission (IHM), the length of hospital stay, and the costs were also estimated for each study period. The costs were calculated using diagnosis-related groups for the disease. These groups represent a medical cost entity applicable to a set of diseases requiring analogous management resources [17]. All costs were adjusted for inflation in Spain during the study period.
We also analyzed the variable “Readmission”. According to the Spanish National Hospital Database methodology, a “readmission” is defined as a patient that was discharged from a hospital and then readmitted to that hospital within the last month. The variable is considered positive for any patient discharged in the last month beside which was the primary diagnosis from the previous admission.
Finally, we studied predictors of IHM in men and women discharged after an exacerbation of COPD with concomitant bronchiectasis.
Statistical analysis
A descriptive statistical analysis was performed. Quantitative variables were expressed as the mean (SD). Qualitative variables were expressed as frequencies and percentages. Comparisons were performed using the chi-squared test, Fisher’s exact test, t test, or ANOVA, as appropriate. Multivariate analysis to investigate time trends for study variables were conducted using exact logistic regression analysis for small outcomes and logistic regression for variables with sufficient outcome. Logistic regression models were used to assess factors associated with in-hospital mortality.
To build the multivariable regression models, we performed the following process:
- We conducted bivariate analysis for each study variable to assess its association with the dependent variable.
- Selection of variables for the multivariable analysis. We included those variables with a significant association in the bivariate tests and other study variables that were found to be important by other authors in the references reviewed, even if their values were not significant.
- To decide which independent variables remained in the final model, we used the Wald statistic after including them one by one. Consecutive models were created as new variables were included. These consecutive models were compared with the previous models using the likelihood ratio test.
- Once the final model was found, we checked for the presence of collinearity and interactions between variables in the model. We limited interactions to first order (two by two) interactions. None of the collinearity or interaction analyses showed a significant association.
Estimates were made using STATA version 10.1 (StataCorp LP, College Station, Texas, USA). Statistical significance was set at a 2-tailed alpha of 0.05.
Ethical aspects
Full data confidentiality was observed according to Spanish legislation. Patient identifiers were removed before the database was provided to the authors to maintain strict patient confidentiality. It was not possible to identify individual patients in this study or in the database. Given the anonymous and mandatory nature of the dataset, it was not necessary to obtain informed consent. The Spanish Ministry of Health evaluated our study protocol, concluded that it fulfilled the ethical requirements of Spanish legislation, and provided us with the anonymous database. Ethical approval was not necessary for the above reasons.
Results
We identified a total of 386,646 admissions with AE-COPD as the main diagnosis in Spain between 2006 and 2014. Of these, 19,679 patients (5.09%) had bronchiectasis as a secondary diagnosis. Patients with COPD and bronchiectasis included 16,903 men (85.89%) and 2,776 women (14.11%).
Characteristics of the study population
Table 1 shows the characteristics of patients admitted with AE-COPD according to the presence or absence of associated bronchiectasis. Men were predominant in both groups. The mean age was higher in the patients with concomitant bronchiectasis than in those without (75.31 ± 9.15 vs. 74.72 ± 10.48 years, respectively, p<0.001). In contrast, the percentage of smokers was lower in the first group of patients (43.37% vs. 46.95% respectively, p<0.001). Comorbidity was also significantly lower in the patients with COPD and bronchiectasis (for ≥ 2 points, 21.92% vs. 27.83% respectively, p<0.001). The same occurred with obesity (5.63% vs. 10.61%, respectively, p<0.001).
As for microorganisms isolated (Table 1), the proportion of patients infected by Pseudomonas aeruginosa was significantly greater among those who had associated bronchiectasis than those who did not (11.74% vs. 2.51%, respectively, p<0.001). The results were similar for Aspergillus species (0.79% vs. 0.26%, respectively, p<0.001).
As for the procedures, CT and bronchoscopy were performed in more patients with bronchiectasis than in those without (14% and 1.73% vs. 6.81% and 0.97%, respectively, p<0.001). Furthermore, the percentage of patients who required invasive mechanical ventilation was significantly lower among those with bronchiectasis than those without (0.49% vs. 0.94%, respectively, p<0.001). The use of noninvasive mechanical ventilation was also significantly lower among patients with bronchiectasis (p = 0.024). However, oxygen therapy was more frequent in patients with concomitant bronchiectasis than in those who did not have the disease (29.47% vs. 28.49%, p = 0.003). In contrast, nebulizers were less frequent in the first group (19.77% vs. 21.32%, respectively, p<0.001).
The mean length of hospital stay was greater in patients with bronchiectasis (9.57 vs. 8.27 days, respectively, p<0.001). The same was found for the cost and proportion of readmissions (€3,971.67 vs. €3,664.75 and 22.38% vs. 17.23%, respectively, p<0.001 in both cases). In contrast, in-hospital mortality was lower in patients with COPD and bronchiectasis than in those without bronchiectasis (4.24% vs. 5.02%, respectively, p<0.001).
Characteristics of the population suffering from COPD exacerbation and bronchiectasis according to gender
Fig 1 and Table 2 show the prevalence, clinical features, diagnosis procedures and outcomes on men and women discharged after a COPD exacerbation and who suffered from concomitant bronchiectasis in Spain from 2006 to 2014.
Footnote: * Significant time trend (p<0.05). Exact logistic regression analysis has been used to estimate the time trend for variables with small outcome. Logistic regression for variables with sufficient outcome. In both cases the models were adjusted by for age, sex, and other covariates as appropriate.
In men, the prevalence of bronchiectasis increased over time from 4.88% in 2006–2008 to 5.37% in 2012–2014 (p<0.001). No statistically significant temporal variations were found for women.
The percentage of smokers increased gradually in both sexes, from 41.7% in men and 14.21% in women during 2006–2008 to 51.15% and 29.62%, respectively, in 2012–2014 (p<0.001 in both cases). Comorbidity also increased significantly over time in both sexes (percentage of patients with ≥ 2 comorbid conditions: 18.95% in men and 15.51% in women during the first period; 26.38% in men and 22.09% in women during the second period; p<0.001 in both cases).
As for isolation of the microorganism, the frequency of infection by P. aeruginosa increased significantly in men (from 10.38% in 2006–2008 to 13.59% in 2012–2014, p<0.001). In contrast, the frequency of isolation of pneumococcus decreased over time in men (from 0.41% in 2006–2008 to 0.14% in 2012–2014, p = 0.011).
As for diagnostic procedures, the percentage of chest CT scans increased over time in men (from 12.13% in the first time period to 14.4% in the third, p<0.001). The need for invasive mechanical ventilation decreased gradually in men (from 0.73% in 2006–2008 to 0.41% in 2012–2014, p = 0.048), whereas the use of noninvasive mechanical ventilation increased (from 3.4% to 6.68%, p<0.001). The frequency of oxygen therapy and aerosol therapy increased significantly for both sexes over time.
IHM and readmissions remained stable in both sexes during the study period. The mean length of hospital stay decreased significantly in both men and women (from 10.29 and 10.21 days, respectively, in 2006–2008 to 9.07 and 8.77 days, respectively, in 2012–2014, p<0.001). The mean hospital cost decreased significantly over time from €3,931.3 to €3,813.4 in men and from €4,013.1 to €3,769.2 in women.
Predictors of IHM in patients with COPD and concomitant bronchiectasis
Fig 2 shows the factors associated with IHM in patients with COPD and concomitant bronchiectasis. After multivariable adjustment, the IHM is not different between women and men (OR 1.08 [95% CI 0.87–1.39]). Predictors of higher IHM include age >65 years, comorbidity, infection by P. aeruginosa (OR, 1.35 [95% CI 1.11–1.64]), and readmission (OR, 2.16 [95% CI, 1.86–2.50]).Another strong predictor of IHM was mechanical ventilation, both invasive (OR, 7.82 [95% CI, 4.75–12.85]) and noninvasive (OR 2.94 [95% CI, 2.33–3.70]). Oxygen therapy and current tobacco use were protective factors.
Footnote: The variables shown are those that remained in the final multivariable model.
The multivariable analysis of temporal trends revealed a significant reduction in mortality over time in patients with COPD and concomitant bronchiectasis (OR, 0.97 [95% CI, 0.94–0.99]).
The results of the factors associated with IHM in patients with COPD and concomitant bronchiectasis by gender are shown in S1 Table. For men, all variables that yielded significant results in the entire population showed significant OR. For women, only invasive and noninvasive ventilation increased the IHM, and current tobacco use was a protective factor.
Finally, using the entire database including patients with and without bronchiectasis, we found that the presence of bronchiectasis was not associated with IHM after adjusting for age, sex and CCI as possible confounders (OR 0.94 [95% CI, 0.88–1.01]).
Discussion
We found that 5.09% of patients admitted with AE-COPD had concomitant bronchiectasis. This frequency was higher in men and older persons. Previous studies report very different frequencies [18,19]. Such wide variability can be explained, at least in part, by differences in study methodology, patient characteristics, and diagnostic criteria. In the meta-analysis of Yingmeng et al [20], in which the prevalence of bronchiectasis in individuals with COPD was 54.3%, the patients had to have been diagnosed with COPD according to the GOLD criteria [21], and the diagnosis of bronchiectasis had to be confirmed using CT. As in our study, persons with COPD and bronchiectasis were older and more often men. We also recorded lower comorbidity in patients with concomitant bronchiectasis, in contrast to reports from other studies, where an association was found between the presence of bronchiectasis in patients with COPD and a greater number of comorbid conditions [22].
As for the microorganisms isolated, we found a greater proportion of infections by P. aeruginosa and Aspergillus species in patients with AE-COPD and bronchiectasis. The association between the presence of potentially pathogenic microorganisms such as P. aeruginosa and bronchiectasis in patients with COPD has been confirmed in previous studies [20, 23–26]. Furthermore, while P. aeruginosa isolation increased, pneumococcal isolation decreased in men discharged after an AE-COPD who suffered from concomitant bronchiectasis. Among the causes that could justify these results are a more frequent search for P. aeruginosa or more frequent use of pneumococcal vaccination over time in this group of patients.
Diagnostic test results showed that more CT scans and bronchoscopies were performed in patients with bronchiectasis. The potential explanations for this finding are as follows: first, CT is the method of choice for diagnosing this disease; and, second, hemoptysis or infectious processes that require collection of respiratory samples are more likely in these patients than in those with no concomitant bronchiectasis.
We found no differences in the use of noninvasive mechanical ventilation in the 2 groups of patients evaluated; however, invasive ventilation was more frequently used in AE-COPD patients without bronchiectasis. Greater age and poorer lung function in patients with AE-COPD and bronchiectasis may explain the fact that noninvasive ventilation is established as the ceiling of therapy in some cases, thus ruling out more aggressive management. Nevertheless, although admission to the intensive care unit is unusual in patients with bronchiectasis, it is becoming increasingly frequent, as shown by Navaratnam et al [27].
Cost, length of hospital stay, and number of readmissions were higher in COPD patients with bronchiectasis than in those who did not have bronchiectasis. De la Rosa et al also found higher costs in patients with COPD and associated bronchiectasis [28]. In any case, few studies have analyzed the financial cost of bronchiectasis, although available data appear to indicate that it is a major health care expense [29,30].
We found that crude in-hospital mortality was significantly lower in patients with AE-COPD and bronchiectasis, although the differences disappeared after the multivariate adjustment. Previous studies showed that the risk of death in COPD increased significantly in the presence of bronchiectasis [8,24,25]. Given the greater risk involved, patients with COPD and bronchiectasis may seek medical care earlier, may be admitted to the hospital with less severe disease, and may receive more care from physicians, thus accounting for our findings. However, consistent with our findings, no association was recorded between the presence of bronchiectasis and mortality in a study of 406 patients who had COPD and severe exacerbations [22] or a study with 338 patients who had no previous exacerbations [31].
Our study showed that the vast majority (>85%) of exacerbations occurred among men, although other studies have reported that women can be more susceptible to exacerbations than men [32]. This gender discrepancy has also been described by other authors [19]. Furthermore, we observed various differences according to gender. For men, there was a gradual increase over time in the prevalence of bronchiectasis, mean age, comorbidity, number of chest CT scans performed, and percentage of isolations of P. aeruginosa. Comorbidity also increased over time in women. In contrast, the mean age tended to decrease in women, and no significant differences were observed for the prevalence of admissions, the use of CT scans and bronchoscopy, or the percentage of isolations of P. aeruginosa. These findings could be explained by the lower number of women evaluated; therefore, it seems reasonable to perform additional studies with larger numbers of women to draw conclusions on this point. Furthermore, we observed an increase in the use of noninvasive mechanical ventilation, oxygen therapy, and aerosol therapy over time.
The mean length of hospital stay and cost decreased during the study period in both men and women with AE-COPD and concomitant bronchiectasis, as recorded in other studies on patients with bronchiectasis [33]. We also found a decrease in in-hospital mortality and the number of readmissions, as reported elsewhere in patients with COPD [34].
The factors associated with greater in-hospital mortality in patients with AE-COPD and concomitant bronchiectasis were age, comorbidity, isolation of P. aeruginosa, readmission, and use of mechanical ventilation (both invasive and noninvasive). Other authors have also found that the use of this therapeutic modality during hospitalization is associated with an increased risk of mortality in patients with acute exacerbations of bronchiectasis [35]. In contrast, smoking was a protective factor, likely because the more severely ill patients or those with more advanced disease are more likely to quit smoking or because the diagnostic coding was skewed. Few studies have evaluated general mortality rates in patients with bronchiectasis [36,37]. Roberts et al [37] reported a 3% annual gradual increase in mortality due to bronchiectasis in England and Wales during 2001–2007. In contrast, our study between 2006 and 2014 recorded a reduction in mortality over time, thus potentially indicating that the management of these patients has been improving over time.
The main strength of our study lies in its large sample size and standardized methodology. The Spanish National Hospital Database methodology has not changed since it was implemented in 1987. Nevertheless, our study is subject to limitations. First, the use of ICD-9-CM diagnostic codes to identify patients hospitalized for COPD and bronchiectasis constitutes a potential source of bias in terms of the quality of data and extrapolation to reality. Given that we cannot verify that COPD was diagnosed based on spirometry or that all diagnoses of bronchiectasis were confirmed by CT, both diagnoses could be under- or overestimated. Notably, less than 10% of patients had a chest CT during their admission, which would have confirmed or excluded a diagnosis of bronchiectasis. Some patients may have already had bronchiectasis diagnosed on CT prior to their admission, but the low prevalence of CT orders (especially among patients “with bronchiectasis”) remains a concern regarding diagnosis accuracy. Furthermore, since the results are limited to the coded variables, relevant data may not be included, such as the severity of airflow obstruction and the treatment or diagnosis procedures received. It is logical to think that the management of hospitalized patients for AE-COPD has changed and improved over the study period as more modern diagnosis methods and treatments become available. However, Ginde et conducted a study to assess the validity of ICD 9 CM codes to identify AE-COPD in the emergency department finding that code 491.2x proved to be effective to identify most cases [38].
Despite these limitations, the CMBD has the advantage of being mandated by the Spanish National Health System and that it covers nearly 100% of admissions in Spain [39]. In addition, Spain is a large country with a public health system that provides full medical coverage free of charge to the entire population; therefore, patients come from a variety of socioeconomic categories, thus improving the external validity of our results.
Conclusions
The prevalence of admission with AE-COPD and bronchiectasis increased in men but not in women during the study period. We did not find differences in mortality in patients hospitalized with AE-COPD depending on the presence of absence of bronchiectasis. The analysis of temporal trends revealed a significant reduction in mortality from 2006 to 2014 in patients with COPD and concomitant bronchiectasis. It is important to consider the factors associated with IHM such as age, comorbidity, isolation of P. aeruginosa, mechanical ventilation and readmission to better identify those patients who are at greater risk of dying during hospitalization.
Additional studies are necessary to better explain the differences found between men and women.
Supporting information
S1 Table. Predictors of in hospital mortality among men and woman discharged after a COPD exacerbation and suffering concomitant bronchiectasis in Spain from 2006–2014.
The variables shown are those that remained in the final multivariable model. VNIFM variable not included in the final model.
https://doi.org/10.1371/journal.pone.0211222.s001
(DOCX)
References
- 1. Buist AS, McBurnie MA, Vollmer WM, Gillespie S, Burney P, Mannino DM, et al. International variation in the prevalence of COPD (the BOLD Study): a population based prevalence study. Lancet. 2007; 370:741–750. pmid:17765523
- 2. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a sistematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388:1545–602. pmid:27733282
- 3. Weycker D, Edelsberg J, Oster G, Tino G. Prevalence and economic burden of bronchiectasis. Clin Pulm Med. 2005; 12:205–209.
- 4. Säynäjäkangas O, Keistinen T, Tuuponen T, Kivelä SL. Bronchiectasis in Finland: trends in hospital treatment. Respir Med. 1997; 91: 395–398. pmid:9327038
- 5. Twiss J, Metcalfe R, Edwards E, Byrnes C. New Zealand national incidence of bronchiectasis "too high" for a developed country. Arch Dis Child. 2005; 90: 737–740. pmid:15871981
- 6. Martínez-García MA, Máiz L, Olveira C, Girón RM, de la Rosa D, Blanco M, et al. Spanish Guidelines on the Evaluation and Diagnosis of Bronchiectasis in Adults. Arch Bronconeumol. 2018; 54:79–87. pmid:29128130
- 7. Miravitlles M, Soler-Cataluña JJ, Calle M, Molina J, Almagro P, Quintano JA, et al. Spanish Guidelines for Management of Chronic Obstructive Pulmonary Disease(GesEPOC) 2017. Pharmacological Treatment of Stable Phase. Arch Bronconeumol. 2017; 53:324–335. pmid:28477954
- 8. Martínez-García MA, De la Rosa D, Soler-Cataluña JJ, Donat Y, Catalán Serra P, Agramunt M, et al. Prognostic value of bronchiectasis in patients with moderate-to-severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013; 187:823–831. pmid:23392438
- 9. Gao Y, Guan W, Liu S, Wang L Cui JJ, Chen RC, et al. Aetiologý of bronchiectais in adults: A systematic literature review. Respirology, 2016; 21:1376–1383. pmid:27321896
- 10. Lonni S, Chalmers JD, Goeminne PC, McDonnell Mj, Dimakou K, De Soyza A, et al. Etiology of non-cystic fibrosis bronchiectasis in adults and its correlation to disease severity. Ann Am Thorac Soc. 2015; 12:1764–1770. pmid:26431397
- 11. Olveira C, Padilla A, Martínez-García MA, de la Rosa D, Girón RM, Vendrell M, et al. Etiology of bronchiectasis in a cohort of 2047 patients. An analysis of the Spanish Historical Bronchiectasis Registry. Arch Bronconeumol. 2017; 53:366–374. pmid:28118936
- 12. Martínez-Garcia MA, Miravitlles M. Bronchiectasis in COPD patients: more than a comorbidity? Int J Chron Obstruct Pulmon Dis. 2017: 12:1401–1414. pmid:28546748
- 13. Lara B, Morales P, Blanco I, Vendrell M, de Gracia Roldán J, Monreal M, et al. Respiratory disease registries in Spain: fundamentals and organization Arch Bronconeumol. 2011; 47:389–396. pmid:21601971
- 14. De la Rosa D, Martínez-García MA, Girón RM, Vendrell M, Olveira C, Borderias L, et al. Clinical impact of chronic obstructive pulmonary disease on non-cystic fibrosis bronchiectasis. A study on 1790 patients from the Spanish Bronchiectasis Historical Registry. PLoS One. 2017;12:e0177931. pmid:28542286
- 15.
El Gobierno de España Ministerio de Empleo y Seguridad Social. Explotación estadística del Conjunto Mínimo Básico de Datos Hospitalarios. Nota metodológica. Norma estatal. www.msssi.gob.es/estadEstudios/estadisticas/docs/NORMAGRD2011/norma_estatal_2011_notas_metod.pdf.
- 16. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992; 45:613–619. pmid:1607900
- 17.
Instituto Nacional de la Salud. CMBD Insalud. Análisis de los GRDs. Año 2000. www.ingesa.msc.es/estadEstudios/documPublica/cmbd2000.htm.
- 18. Dou S, Zheng C, Cui L, Xie M, Wang W, Tian H, et al. High prevalence of bronchiectasis in emphysema-predominant COPD patients. Int J Chron Obstruct Pulmon Dis. 2018; 13:2041–2047. pmid:29988718
- 19. Kawamatawong T, Onnipa J, Suwatanapongched T. Relationship between the presence of bronchiectasis and acute exacerbation in Thai COPD patients. International Journal of COPD 2018:13 761–769. pmid:29535516
- 20. Ni Yingmeng, Shi Guochao, Yu Youchao, Hao Jimin, Chen Tiantian, Song Huihui. Clinical characteristics of patients with chronic obstructive pulmonary disease with comorbid bronchiectasis: a systematic review and meta-analysis. Int J Chron Obstruct Pulmon Dis. 2015: 10:1465–1475. pmid:26251586
- 21.
Global strategy for the diagnosis, management, and preventionn of chronic obstructive pulmonary disease; 2014. Available at: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2015_Apr2.pdf.
- 22. Gatheral T, Kumar N, Sansom B, Lai D, Nair A, Vlahos I, Baker EH. COPD-related bronchiectasis; independent impact on disease course and outcomes. COPD. 2014; 11:605–614. pmid:24983298
- 23. Gallego M, Pomares X, Espasa M, Castañer E, Solé M, Suárez D, et al. Pseudomonas aeruginosa isolates in severe chronic obstructive pulmonary disease: characterization and risk factors. BMC Pulm Med. 2014; 14:103. pmid:24964956
- 24. Mao B, Lu HW, Li MH, Fan LC, Yang JW, Miao XY, et al. The existence of bronchiectasis predicts worse prognosis in patients with COPD. Sci Rep. 2015; 5:10961. pmid:26077673
- 25. Du Q, Jn J, Liu X, Sun Y. Bronchiectasis as a comorbidity of chronic obstructive pulmonary disease: a sistematic review and meta-analysis. PloS One. 2016; 11:e0150532. pmid:26978269
- 26. Jin Jianmin, Yu Wenling, Li Shuling, Lu Lijin, Liu Xiaofang, Sun Yongchang. Factors associated with bronchiectasis in patients with moderate-severe chronic obstructive pulmonary disease. Medicine (Baltimore). 2016; 95:e4219.
- 27. Navaratnam V, Muirhead CR, Hubbard RB, De Soyza A. Critical care admission trends and outcomes in individuals with bronchiectasis in the UK. QJM. 2016; 109:523–6. pmid:26582824
- 28. De la Rosa D, Martínez-Garcia MA, Olveira C, Girón R, Máiz L, Prados C, et al. Annual direct medical costs of bronchiectasis treatment: Impact of severity, exacerbations, chronic bronchial colonization and chronic obstructive pulmonary disease coexistence. Chron Respir Dis. 2016 Apr 12. pii: 1479972316643698.
- 29. Weycker D, Edelsberg J, Oster G, Tino g Prevalence and economic burden of bronchiectasis. Clin Pulm Med. 2005;12:205–209.
- 30. Joish VN, Spilsbury Cantalupo M, Operschall E, Luong B, Boklage S. Economic burden of non-cystyc fibrosis bronchiectasis in the first year after diagnosis from a US health plan perspective. Appl Health Econ Health Policy. 2013; 11:299–304. pmid:23580074
- 31. Jairam PM, van der Graaf Y, Lammers JW, Mali WP, de Jong PA. Incidenal findings on chest CT imaging are associated with increased COPD exacerbations and mortality. Thorax. 2015; 70:725–31. pmid:26024687
- 32. Kokturk N, Kilic H, Baha A, Lee SD, Jones PW. Sex difference in chronic obstructive lung disease. Does it matter? A concise review. COPD. 2016;13:799–806. pmid:27398767
- 33. Sanchez-Muñoz G, López de Andrés A, Jiménez-García R, Carrasco-Garrido P, Hernández-Barrera V, Pedraza-Serrano F, et al. Time trends in hospital admissions for bronchiectasis: analysis of the Spanish National Hospital Discharge Data (2004 to 2013). PLos One. 2016; 11:e0162282. pmid:27622273
- 34. De Miguel-Díez J, Jiménez-García R, Hernández-Barrera V, Carrasco Garrido P, Puente-Maestu L, Ramírez-García L, et al. Readmissions following an initial hospitalization by COPD exacerbation in Spain from 2006 to 2012. Respirology. 2016; 21:489–496. pmid:26648085
- 35. Finklea JD, Khan G, Thomas S, Song J, Myers D, Arroliga AC. Predictors of mortality in hospitalized patients with acute exacerbation of bronchiectasis. Respir Med. 2010;104:816–21. pmid:20363606
- 36. Goeminne PC, Scheers H, Decraene A, Seys S, Dupont LJ. Risk factors for morbidity and death in non-cystic fibrosis bronchiectasis: a retrospective crosssectional analysis of CT diagnosed bronchiectatic patients. Respiratory Research. 2012; 13:21. pmid:22423975
- 37. Roberts HJ, Hubbard R. Trends in bronchiectasis mortality in England and Wales. Respir Med. 2010; 104:981–985. pmid:20303725
- 38. Ginde AA, Tsai CL, Blanc PG, Camargo CA Jr. Positive predictive value of ICD-9-CM codes to detect acute exacerbation of COPD in the emergency department. Jt Comm J Qual Patient Saf. 2008;34:678–80. pmid:19025089
- 39.
Instituto Nacional de la Salud. Conjunto Mínimo Básico de Datos. Hospitales del INSALUD 2001. www.ingesa.msc.es/estadEstudios/documPublica/pdf/CMBD-2001.pdf.