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ORIGINAL ARTICLE
Comparison of in-hospital mortality in patients with COPD, asthma and asthma–COPD overlap exacerbations YASUHIRO YAMAUCHI,1,2 HIDEO YASUNAGA,3 HIROKI MATSUI,3 WAKAE HASEGAWA,1 TAISUKE JO,1,2 KAZUTAKA TAKAMI,1 KIYOHIDE FUSHIMI4 AND TAKAHIDE NAGASE1 1
Department of Respiratory Medicine, Graduate School of Medicine, and 2Division for Health Service Promotion, and 3 Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, and 4 Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan
ABSTRACT Background and objective: Obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), have airflow limitation associated with chronic inflammation. Using a national inpatient database in Japan, we aimed to evaluate factors affecting in-hospital mortality in patients with asthma, COPD or asthma–COPD overlap (ACO). Methods: We retrospectively collected data for inpatients (age >40 years) with exacerbation of COPD and/or asthma in 1073 hospitals across Japan between July 2010 and May 2013. We performed multivariable logistic regression analysis to examine the association of various factors with all-cause in-hospital mortality, including diagnosis of ACO, asthma alone and COPD alone. Results: Of 30 405 eligible patients, in-hospital mortality in patients with ACO, asthma alone and COPD alone was 2.3%, 1.2% and 9.7%, respectively. COPD patients had a significantly higher mortality than ACO patients (odds ratio 1.96; 95% confidence interval: 1.38–2.79); patients with asthma alone showed lower mortality (0.70; 0.50–0.97). Higher mortality was also significantly associated with older age, male gender, lower body mass index, more severe dyspnoea, lower level of consciousness, worse activities of daily life and higher daily dose of corticosteroids. Conclusion: Asthma alone was associated with lower mortality, but COPD alone was associated with higher mortality than ACO. Key words: asthma, asthma–chronic obstructive pulmonary disease overlap syndrome, chronic obstructive pulmonary disease, in-hospital mortality, obstructive airway disease. Abbreviations: ACO, asthma–COPD overlap; COPD, chronic obstructive pulmonary disease Correspondence: Yasuhiro Yamauchi, Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: [email protected] Received 6 January 2015; invited to revise 12 February 2015; revised 26 February 2015; accepted 10 March 2015 (Associate Editor: Melissa Benton).
Article first published online: 21 May 2015 © 2015 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE We evaluated all-cause in-hospital mortality in patients with asthma, COPD and asthma–COPD overlap (ACO), who were admitted for exacerbation. The in-hospital mortality in patients with ACO was lower than that in patients with COPD alone, but worse than that in patients with asthma alone.
INTRODUCTION Obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), cause airflow limitation, which is associated with chronic airway inflammation and may lead to respiratory failure.1–3 These two diseases have a distinct pathogenesis and clinical features, and each demands an individual treatment strategy. Asthma is characterized by reversible airway obstruction and is associated with airway hyperresponsiveness and airway inflammation; the prognosis is generally favourable, and the response to corticosteroids is good.1 Conversely, COPD is characterized by persistent airflow limitation, which is progressive and is associated with a chronic inflammatory response to noxious particles and parenchymal emphysema; COPD has a worse prognosis related to chronic respiratory failure, and generally the response to corticosteroids is poor.2 These two different diseases have individual diagnostic criteria; however, in clinical practice, the diseases often coexist, and this coexistence can affect clinical course and lead to exacerbation, which is related to high mortality. Recently, therefore, there has been increased emphasis on the comorbid condition of asthma and COPD, which is termed asthma–COPD overlap (ACO) syndrome.3 Several studies have demonstrated that compared with patients with asthma alone or COPD alone, ACO patients have a lower health-related quality of life, Respirology (2015) 20, 940–946 doi: 10.1111/resp.12556
In-hospital mortality in ACOS
frequent and severe exacerbations and require more hospitalization.4–10 Thus, it has been suggested that ACO patients have greater disease severity and poorer prognosis than patients with asthma or COPD alone; it has been recommended that ACO patients be treated more intensively using treatment for both asthma and COPD according to international guidelines.1–3 However, there is a lack of information about the clinical features of patients with ACO who are admitted to hospital because of exacerbation, particularly with respect to in-hospital mortality. Using a national inpatient database in Japan, we therefore aimed to evaluate all-cause in-hospital mortality of ACO patients and compare that to those with asthma or COPD alone. We also aimed to identify the clinical features in ACO patients and verify the factors that affect mortality in patients with obstructive airway diseases. Since the use of systemic corticosteroids is recommended in the treatment of both diseases and affects the clinical course and outcomes, we also evaluated the impact of daily administration of corticosteroids on in-hospital mortality.
METHODS Data source We used the Diagnosis Procedure Combination database, which is a nationwide inpatient database in Japan, in this study. The database comprises administrative claims data and discharge abstract data. It includes the main diagnosis, primary diagnosis on admission, comorbidities present on admission and complications occurring during hospitalization, which are coded using the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes accompanied by text data in Japanese. The database also contains the following details: the patient’s age, gender, body height and weight; smoking index (defined as the number of cigarettes smoked per day multiplied by the number of years smoked); severity of dyspnoea based on the Hugh-Jones dyspnoea scale11 (details of the dyspnoea scale appear in Supplementary Appendix S1); level of consciousness based on the Japan Coma Scale on admission;12,13 grade of activities of daily life on admission converted to the Barthel index;14 intensive care unit (ICU) admission during hospitalization; mechanical ventilation; total dose and duration of administration of corticosteroids; outcome; and discharge status. This study was approved by the Institutional Review Board of The University of Tokyo. The board waived the requirement for patient informed consent because of the anonymous nature of the data. Patient selection We retrospectively collected data for patients aged over 40 years who were admitted to hospital because of COPD exacerbation (ICD-10 codes J44.0 and J44.1) and/or asthma exacerbation (J46) as the main diagnosis or primary diagnosis and were discharged © 2015 Asian Pacific Society of Respirology
941 between 1 July 2010 and 31 March 2013. The COPD and asthma status were based on physician-based diagnoses. We divided the patients into three groups—those with ACO, asthma alone and COPD alone—according to the following criteria. The ACO group included patients who were admitted because of asthma exacerbation and had COPD (J41–J44) as a comorbidity on admission, or those who were admitted because of COPD exacerbation and had asthma (J45 and J46) as a comorbidity on admission. The asthma-alone group included patients who were admitted because of asthma exacerbation as the main diagnosis but did not have COPD as a comorbidity on admission. The COPD-alone group included patients who were admitted because of COPD exacerbation but did not have asthma as a comorbidity on admission.
Comorbidities on admission and complications during hospitalization Comorbidities on admission and complications that occurred during hospitalization were identified using ICD-10 codes (the detailed ICD-10 codes appear in Supplementary Appendix S1): pneumonia caused by pathogenic microbes; aspiration pneumonia; interstitial pneumonia; lung cancer; heart failure; ischaemic heart disease; cardiac arrhythmia; pulmonary embolism; cor pulmonale; cerebral vascular diseases; chronic liver disease; chronic renal failure; anxiety; depression; and bone fracture. Calculation of daily corticosteroid dose To evaluate the association between mortality and daily corticosteroid dose, the daily dose of systemic corticosteroids was calculated: we divided the total amount of corticosteroids administered during hospitalization (converted to an equivalent dose of prednisolone) by the total number of days of corticosteroid administration. The details of the conversion of corticosteroids to an equivalent dose of prednisolone are presented in Supplementary Appendix S1. The daily dose of corticosteroids was classified into four groups: low-dose group (equivalent to ≤30 mg/day prednisolone); medium-dose group (30–60 mg/day); medium-dose to high-dose group (60–100 mg/day); and high-dose group (>100 mg/day). Outcome The primary outcome was all-cause in-hospital mortality. The secondary outcomes were length of hospital stay (days), length of ICU stay (days) and duration of mechanical ventilation (days). Statistical analysis We used the chi-square test to compare the proportions among the groups, analysis of variance to examine the average values among the groups, a post hoc Tukey’s test to compare the average values between individual pairs of groups and the Kruskal– Wallis test to compare the median values among the Respirology (2015) 20, 940–946
942
Y Yamauchi et al.
groups. We performed a multivariable logistic regression to analyse patient-level factors associated with in-hospital mortality after adjustment for withinhospital clustering by means of a generalized estimating equation.15 The threshold for significance was a value of P < 0.05. We performed all statistical analyses using SPSS version 22.0 (IBM SPSS Inc., Armonk, NY, USA).
RESULTS Patient characteristics We identified 30 405 patients who were admitted for exacerbation of asthma and/or COPD including ACO (n = 6279), asthma alone (n = 19 865) and COPD alone (n = 4261) from 1073 hospitals during the study period. The patients’ characteristics appear in Table 1. The comorbidities on admission are presented in Table 2. The proportions of most comorbidities in the
Table 1
ACO group were lower than those in the COPD-alone group. Table 2 also shows the usage of systemic corticosteroid. The proportion of corticosteroids administered in the ACO group was identical to that in asthma group. The average daily dose of corticosteroids in the COPD group was significantly lower than that in the ACO and asthma-alone groups.
Outcomes The outcomes of the patients are presented in Table 3. All-cause in-hospital mortality was 2.3% in the ACO group and 9.7% in the COPD group. The proportions of ICU admission and mechanical ventilation were highest in the COPD group. The length of hospital stay, length of ICU stay and duration of mechanical ventilation were greatest in the COPD group. Multivariable logistic regression analysis for all-cause in-hospital mortality The results of the multivariable logistic regression analysis for all-cause in-hospital mortality are
Patient characteristics
Age (years) 40–64 65–74 75–84 ≥85 Gender Male Female Body mass index (kg/m2)
ORIGINAL ARTICLE
Comparison of in-hospital mortality in patients with COPD, asthma and asthma–COPD overlap exacerbations YASUHIRO YAMAUCHI,1,2 HIDEO YASUNAGA,3 HIROKI MATSUI,3 WAKAE HASEGAWA,1 TAISUKE JO,1,2 KAZUTAKA TAKAMI,1 KIYOHIDE FUSHIMI4 AND TAKAHIDE NAGASE1 1
Department of Respiratory Medicine, Graduate School of Medicine, and 2Division for Health Service Promotion, and 3 Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo, and 4 Department of Health Policy and Informatics, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan
ABSTRACT Background and objective: Obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), have airflow limitation associated with chronic inflammation. Using a national inpatient database in Japan, we aimed to evaluate factors affecting in-hospital mortality in patients with asthma, COPD or asthma–COPD overlap (ACO). Methods: We retrospectively collected data for inpatients (age >40 years) with exacerbation of COPD and/or asthma in 1073 hospitals across Japan between July 2010 and May 2013. We performed multivariable logistic regression analysis to examine the association of various factors with all-cause in-hospital mortality, including diagnosis of ACO, asthma alone and COPD alone. Results: Of 30 405 eligible patients, in-hospital mortality in patients with ACO, asthma alone and COPD alone was 2.3%, 1.2% and 9.7%, respectively. COPD patients had a significantly higher mortality than ACO patients (odds ratio 1.96; 95% confidence interval: 1.38–2.79); patients with asthma alone showed lower mortality (0.70; 0.50–0.97). Higher mortality was also significantly associated with older age, male gender, lower body mass index, more severe dyspnoea, lower level of consciousness, worse activities of daily life and higher daily dose of corticosteroids. Conclusion: Asthma alone was associated with lower mortality, but COPD alone was associated with higher mortality than ACO. Key words: asthma, asthma–chronic obstructive pulmonary disease overlap syndrome, chronic obstructive pulmonary disease, in-hospital mortality, obstructive airway disease. Abbreviations: ACO, asthma–COPD overlap; COPD, chronic obstructive pulmonary disease Correspondence: Yasuhiro Yamauchi, Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Email: [email protected] Received 6 January 2015; invited to revise 12 February 2015; revised 26 February 2015; accepted 10 March 2015 (Associate Editor: Melissa Benton).
Article first published online: 21 May 2015 © 2015 Asian Pacific Society of Respirology
SUMMARY AT A GLANCE We evaluated all-cause in-hospital mortality in patients with asthma, COPD and asthma–COPD overlap (ACO), who were admitted for exacerbation. The in-hospital mortality in patients with ACO was lower than that in patients with COPD alone, but worse than that in patients with asthma alone.
INTRODUCTION Obstructive airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), cause airflow limitation, which is associated with chronic airway inflammation and may lead to respiratory failure.1–3 These two diseases have a distinct pathogenesis and clinical features, and each demands an individual treatment strategy. Asthma is characterized by reversible airway obstruction and is associated with airway hyperresponsiveness and airway inflammation; the prognosis is generally favourable, and the response to corticosteroids is good.1 Conversely, COPD is characterized by persistent airflow limitation, which is progressive and is associated with a chronic inflammatory response to noxious particles and parenchymal emphysema; COPD has a worse prognosis related to chronic respiratory failure, and generally the response to corticosteroids is poor.2 These two different diseases have individual diagnostic criteria; however, in clinical practice, the diseases often coexist, and this coexistence can affect clinical course and lead to exacerbation, which is related to high mortality. Recently, therefore, there has been increased emphasis on the comorbid condition of asthma and COPD, which is termed asthma–COPD overlap (ACO) syndrome.3 Several studies have demonstrated that compared with patients with asthma alone or COPD alone, ACO patients have a lower health-related quality of life, Respirology (2015) 20, 940–946 doi: 10.1111/resp.12556
In-hospital mortality in ACOS
frequent and severe exacerbations and require more hospitalization.4–10 Thus, it has been suggested that ACO patients have greater disease severity and poorer prognosis than patients with asthma or COPD alone; it has been recommended that ACO patients be treated more intensively using treatment for both asthma and COPD according to international guidelines.1–3 However, there is a lack of information about the clinical features of patients with ACO who are admitted to hospital because of exacerbation, particularly with respect to in-hospital mortality. Using a national inpatient database in Japan, we therefore aimed to evaluate all-cause in-hospital mortality of ACO patients and compare that to those with asthma or COPD alone. We also aimed to identify the clinical features in ACO patients and verify the factors that affect mortality in patients with obstructive airway diseases. Since the use of systemic corticosteroids is recommended in the treatment of both diseases and affects the clinical course and outcomes, we also evaluated the impact of daily administration of corticosteroids on in-hospital mortality.
METHODS Data source We used the Diagnosis Procedure Combination database, which is a nationwide inpatient database in Japan, in this study. The database comprises administrative claims data and discharge abstract data. It includes the main diagnosis, primary diagnosis on admission, comorbidities present on admission and complications occurring during hospitalization, which are coded using the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes accompanied by text data in Japanese. The database also contains the following details: the patient’s age, gender, body height and weight; smoking index (defined as the number of cigarettes smoked per day multiplied by the number of years smoked); severity of dyspnoea based on the Hugh-Jones dyspnoea scale11 (details of the dyspnoea scale appear in Supplementary Appendix S1); level of consciousness based on the Japan Coma Scale on admission;12,13 grade of activities of daily life on admission converted to the Barthel index;14 intensive care unit (ICU) admission during hospitalization; mechanical ventilation; total dose and duration of administration of corticosteroids; outcome; and discharge status. This study was approved by the Institutional Review Board of The University of Tokyo. The board waived the requirement for patient informed consent because of the anonymous nature of the data. Patient selection We retrospectively collected data for patients aged over 40 years who were admitted to hospital because of COPD exacerbation (ICD-10 codes J44.0 and J44.1) and/or asthma exacerbation (J46) as the main diagnosis or primary diagnosis and were discharged © 2015 Asian Pacific Society of Respirology
941 between 1 July 2010 and 31 March 2013. The COPD and asthma status were based on physician-based diagnoses. We divided the patients into three groups—those with ACO, asthma alone and COPD alone—according to the following criteria. The ACO group included patients who were admitted because of asthma exacerbation and had COPD (J41–J44) as a comorbidity on admission, or those who were admitted because of COPD exacerbation and had asthma (J45 and J46) as a comorbidity on admission. The asthma-alone group included patients who were admitted because of asthma exacerbation as the main diagnosis but did not have COPD as a comorbidity on admission. The COPD-alone group included patients who were admitted because of COPD exacerbation but did not have asthma as a comorbidity on admission.
Comorbidities on admission and complications during hospitalization Comorbidities on admission and complications that occurred during hospitalization were identified using ICD-10 codes (the detailed ICD-10 codes appear in Supplementary Appendix S1): pneumonia caused by pathogenic microbes; aspiration pneumonia; interstitial pneumonia; lung cancer; heart failure; ischaemic heart disease; cardiac arrhythmia; pulmonary embolism; cor pulmonale; cerebral vascular diseases; chronic liver disease; chronic renal failure; anxiety; depression; and bone fracture. Calculation of daily corticosteroid dose To evaluate the association between mortality and daily corticosteroid dose, the daily dose of systemic corticosteroids was calculated: we divided the total amount of corticosteroids administered during hospitalization (converted to an equivalent dose of prednisolone) by the total number of days of corticosteroid administration. The details of the conversion of corticosteroids to an equivalent dose of prednisolone are presented in Supplementary Appendix S1. The daily dose of corticosteroids was classified into four groups: low-dose group (equivalent to ≤30 mg/day prednisolone); medium-dose group (30–60 mg/day); medium-dose to high-dose group (60–100 mg/day); and high-dose group (>100 mg/day). Outcome The primary outcome was all-cause in-hospital mortality. The secondary outcomes were length of hospital stay (days), length of ICU stay (days) and duration of mechanical ventilation (days). Statistical analysis We used the chi-square test to compare the proportions among the groups, analysis of variance to examine the average values among the groups, a post hoc Tukey’s test to compare the average values between individual pairs of groups and the Kruskal– Wallis test to compare the median values among the Respirology (2015) 20, 940–946
942
Y Yamauchi et al.
groups. We performed a multivariable logistic regression to analyse patient-level factors associated with in-hospital mortality after adjustment for withinhospital clustering by means of a generalized estimating equation.15 The threshold for significance was a value of P < 0.05. We performed all statistical analyses using SPSS version 22.0 (IBM SPSS Inc., Armonk, NY, USA).
RESULTS Patient characteristics We identified 30 405 patients who were admitted for exacerbation of asthma and/or COPD including ACO (n = 6279), asthma alone (n = 19 865) and COPD alone (n = 4261) from 1073 hospitals during the study period. The patients’ characteristics appear in Table 1. The comorbidities on admission are presented in Table 2. The proportions of most comorbidities in the
Table 1
ACO group were lower than those in the COPD-alone group. Table 2 also shows the usage of systemic corticosteroid. The proportion of corticosteroids administered in the ACO group was identical to that in asthma group. The average daily dose of corticosteroids in the COPD group was significantly lower than that in the ACO and asthma-alone groups.
Outcomes The outcomes of the patients are presented in Table 3. All-cause in-hospital mortality was 2.3% in the ACO group and 9.7% in the COPD group. The proportions of ICU admission and mechanical ventilation were highest in the COPD group. The length of hospital stay, length of ICU stay and duration of mechanical ventilation were greatest in the COPD group. Multivariable logistic regression analysis for all-cause in-hospital mortality The results of the multivariable logistic regression analysis for all-cause in-hospital mortality are
Patient characteristics
Age (years) 40–64 65–74 75–84 ≥85 Gender Male Female Body mass index (kg/m2)
