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Risk factors associated with chronic obstructive pulmonary disease early readmission a
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Jian Lin , Youzu Xu , Xiaomai Wu , Meifang Chen , Ling Lin , Liuyang Gong & Jiaxi Feng
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Department of Respiratory Medicine, Taizhou Hospital of Wenzhou Medical University Linhai, ZhejiangP.R. China Published online: 26 May 2015.
Click for updates To cite this article: Jian Lin, Youzu Xu, Xiaomai Wu, Meifang Chen, Ling Lin, Liuyang Gong & Jiaxi Feng (2014) Risk factors associated with chronic obstructive pulmonary disease early readmission, Current Medical Research and Opinion, 30:2, 315-320 To link to this article: http://dx.doi.org/10.1185/03007995.2013.858623
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Current Medical Research & Opinion 0300-7995 doi:10.1185/03007995.2013.858623
Vol. 30, No. 2, 2014, 315–320
Article ST-0292/858623 All rights reserved: reproduction in whole or part not permitted
py Un t rig au fo t ht di hor r S sp ize a la d le © y, u s 20 vi e o ew p r 14 r C o an h d p ibi om In rin ted m fo rm t a . Au e si th rc aU ng or i le is al K co ed D py us is Lim fo ers tr ite rp c i b a er n d so d ut na ow io l u nl n se oa d,
Jian Lin* Youzu Xu* Xiaomai Wu Meifang Chen Ling Lin Liuyang Gong Jiaxi Feng
Department of Respiratory Medicine, Taizhou Hospital of Wenzhou Medical University, Linhai, Zhejiang, P.R. China
Address for correspondence: Jiaxi Feng, Department of Respiratory Medicine, Taizhou Hospital, Linhai 317000, P.R. China. Tel.: +86 576-85199238; Fax: +86 576-85199542; [email protected] Keywords: COPD – Exacerbation – Readmission – Risk factors Accepted: 11 October 2013; published online: 7 November 2013 Citation: Curr Med Res Opin 2014; 30:315–20
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Original article Risk factors associated with chronic obstructive pulmonary disease early readmission
*These authors contributed equally to the work
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Abstract
Background: The 31 day readmission rate is deemed to be an important indicator of the quality of medical care in China. The objectives of this study were to identify the readmission rate of acute exacerbation for chronic obstructive pulmonary disease (COPD) and to evaluate associated risk factors. Methods: We retrospectively reviewed charts for patients with acute exacerbation of COPD (AECOPD) admitted to our hospital between January 2011 and November 2012. The early-readmission group and non-earlyreadmission group were determined by whether patients were readmitted within 31 days after discharge. Logistic regression analysis was performed to identify risk factors for early readmission following an AECOPD. Results: There were 692 patients with 925 admissions during the 23 month period; 63 (6.8%) admissions met our criteria for early readmission. Multivariate analysis showed that chronic cor pulmonale (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.26–3.64, p ¼ 0.005), hypoproteinemia (OR 2.02, 95% CI 1.03–3.95, p ¼ 0.040) and an elevated PaCO2 (OR 1.03, 95% CI 1.00–1.06, p ¼ 0.027) were identified as risk factors for early readmission of AECOPD. Conclusion: The readmission rate for AECOPD was 6.8%. AECOPD patients with chronic cor pulmonale, hypoproteinemia, and a high PaCO2 are at higher risk for readmission with 31 days of hospital discharge, and medical care of these patients warrants greater attention.
Introduction
Chronic obstructive pulmonary disease (COPD) is a common chronic airway disease, and is characterized by persistent airflow limitation that is usually progressive. COPD is a leading cause of morbidity, mortality and utilization of health care resources worldwide1,2, which results in a heavy economic burden to the patient, family and society. In China, the incidence of COPD is 8.2% in the population over the age of 403, so on this basis the number of COPD patients in China is estimated to be close to 43 million. An acute exacerbation of COPD (AECOPD) is defined as an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication4. Acute exacerbation accelerates the progression of the disease, reduces quality of life, decreases activity tolerance and increases mortality5–9. On average, AECOPD rates are approximately one to two per patient-year; with hospitalization averaging approximately 0.1 to 0.2 per patient-year10. COPD readmission and risk factors Lin et al.
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Medical expenses of COPD are associated with the severity of disease, the frequency of acute exacerbations and the number of hospitalizations. Expenditures due to acute exacerbation accounted for 40% to 57% of the total costs of COPD, even up to 63%, and hospitalization accounted for 58% of the total costs11–13. Avoiding or reducing the readmission rate for COPD patients may have a great impact on improving outcomes and reducing health care resource consumption. Our literature review about risk factors influencing COPD readmission rates were discrepant because of different outcome measures, methods, and readmission periods14–17. Some COPD patients truly need early rehospitalization after discharge. We proposed to study the reasons for early rehospitalization of COPD patients in exacerbation believing that this may be important for avoiding or reducing readmissions, and for decreasing medical costs. The unplanned readmission rate within 31 days for the same or related disease is one of the medical quality index evaluation criteria in the China Healthcare Quality Indicators System (CHQIS). The aims of our study were to identify the readmission rate of AECOPD patients who were discharged from our hospital within 31 days and to comprehensively evaluate the associated risk factors.
Patients and methods Patients Charts for patients with AECOPD who were discharged from Taizhou Hospital of Wenzhou Medical University (Zhejiang, P.R. China) over a 23 month period between January 1, 2011 and November 30, 2012 were retrospectively reviewed. The diagnosis of COPD was based on patients with long-term smoking and other risk factors, history of chronic cough, expectoration and dyspnea. Physical examination showed signs of emphysema, chest X-ray or computer tomography (CT) showed the signs of chronic bronchitis and emphysema, and blood gas analysis was associated with varying degrees of hypoxemia and/or increased carbon dioxide pressure. Some patients completed spirometric tests before admission or during hospitalization which met the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria4 for COPD. Exclusion criteria were (1) other lung disorder such as asthma, lung cancer, bronchiectasis, active tuberculosis, pneumothorax, or pleural effusion, and (2) death during hospitalization or abandonment of treatment because of disease progression.
Methods We selected patients with a primary diagnosis of COPD using international classification of diseases (ICD) coding 316
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(ICD-9: 490–492, 494–496) from the information and electronic medical record system of Taizhou Hospital. We collected the hospital number of each patient, and the name, sex, age, primary diagnosis, secondary diagnosis, date of admission, date of discharge, days of hospitalization, discharge outcome (improved, death or deterioration), classification of pulmonary function test (based on GOLD 2013 criteria, mild: forced expiratory volume in one second [FEV1] 80% predicted, moderate: 50% FEV1580% predicted, severe: 30% FEV1550% predicted, very severe: FEV1530% predicted)4, whether chest X-ray showed infiltrates or not, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), presence of anemia (hemoglobin: female5110 g/L, Male 5120 g/L), presence of polycythemia (hemoglobin: female 4150 g/L, male 4160 g/L), and presence of hypoproteinemia (serum albumin 535 g/L), all according to the last blood test results during hospitalization. Concomitant diseases (hypertension, type 2 diabetes, ischemic heart disease, chronic cor pulmonale) were recorded according to discharge diagnosis, the interval between discharge and readmission were recorded for the readmitted patients, and we confirmed patient identity by hospital number and name. The early-readmission group and non-earlyreadmission group were determined by whether patients were readmitted within 31 days after discharge.
Statistical analysis All data were analyzed by SPSS 12.0. Univariate analysis was performed using t-test or chi-squared test to determine the possible risk factors which affected readmission within 31 days after discharge. Multivariate logistic regression analysis was performed to determine the independent risk factors from the statistically significant factors with the univariate analysis. A p of50.05 was accepted as indicating a statistically significant difference.
Results Patient characteristics Between January 1, 2011 and November 30, 2012, 692 patients who were admitted to our hospital with AECOPD met the inclusion criteria for the study. The total number of admissions was 925, the total readmission rate was 39%. There were 63 admissions in 49 individuals (6.8%) that met our criteria for early readmission (Table 1). The interval between discharge and early readmission was 2–31 days, with an average of 16.92 8.76 days, and 10 cases were readmitted within 7 days after discharge (10/63, 15.9%). Baseline characteristics of patients are shown in Table 2. The age of the www.cmrojournal.com ! 2014 Informa UK Ltd
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Table 1. Number of admissions and readmissions during the study period (January 2011 to November 2012). Patients, n
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Readmissions, n (%) 0 1 2 3 4 5 7 8 12 Total admissions, n Early readmissions, n (%) Non-early readmissions, n (%)
564 (81.5) 75 (10.8) 29 (4.2) 12 (1.7) 8 (1.2) 1 (0.15) 1 (0.15) 1 (0.15) 1 (0.15) 925 63 (6.8) 862 (93.2)
Table 2. Baseline characteristics of 692 patients admitted with COPD acute exacerbations. Baseline characteristics
Mean age (years) Male sex Ischemic heart disease Type 2 diabetes Hypertension Chronic cor pulmonale Pulmonary function test performed Mild (FEV1 80% predicted) Moderate (50% FEV1580% predicted) Severe (30% FEV1550% predicted) Very severe (FEV1530% predicted)
All patients, n ¼ 692 (%) 72.95 8.399 544 (78.6) 33 (4.8) 59 (8.5) 203 (29.3) 228 (33.0) 122 (17.6) 0 (0.0) 17 (13.9) 33 (27.1) 72 (59.0)
patients ranged from 47 to 93 years, with an average of 72.95 8.40 years, 544 patients were male (78.6%). Thirty-three patients (4.8%) had a history of ischemic heart disease, 59 (8.5%) had diabetes, 203 (29.3%) had hypertension, and 228 (33.0%) had chronic cor pulmonale. A total of 122 (17.6%) patients finished completed pulmonary function testing during the admission, and based on GOLD 2013 criteria no patients (0.0%) had mild COPD, 17 (13.9%) patients had moderate, 33 (27.1%) patients had severe, and 72 (59.0%) patients had very severe COPD. Out of 925 admissions, 117 had anemia, 82 had polycythemia, and 99 had hypoproteinemia when discharged (Table 3).
Univariate analysis of early readmissions The chi-square test was used for enumeration data such as gender, presence of comorbidities (ischemic heart disease, chronic cor pulmonale, hypertension, type 2 diabetes), hypoproteinemia, anemia, and classification based on pulmonary function testing during hospitalization. The t-test was used for measurement data such as age, length of stay, ! 2014 Informa UK Ltd www.cmrojournal.com
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PaO2, and PaCO2. On the ¼ 0.05 level, the factors that had statistically significant differences included PaCO2, ischemic heart disease, chronic cor pulmonale, type 2 diabetes, hypertension, hypoproteinemia, and anemia. There were no statistically significant differences in gender, age, length of stay, PaO2, pulmonary infiltrates, polycythemia, and pulmonary function classification between the early and late readmission groups (Table 3).
Multivariate analysis of early readmissions Based on the results of univariate analysis, PaCO2, ischemic heart disease, chronic cor pulmonale, type 2 diabetes, hypertension, hypoproteinemia, and anemia were included in the multivariate analysis. The logistic regression analysis showed that chronic cor pulmonale (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.26– 3.64), hypoproteinemia (OR 2.02, 95% CI 1.03–3.95) and the level of PaCO2 (OR 1.03, 95% CI 1.00–1.06) significantly increased the odds of early readmission (Table 4).
Discussion Hospitalization remains an important marker of COPD disease severity and a high cost event. Previous studies from the United States reported that 50% of health care spending was used for hospitalizations, and 13% of readmitted patients occupied more than 50% of health care resources18. Unplanned readmission is when patients are readmitted because of the same or related diseases within a short time after their discharge. There is no uniform definition for ‘early’ readmission; generally one week to one month after discharge due to the same illness or surgery are commonly used19. Internationally, unplanned readmission is an important indicator to evaluate medical quality and efficiency20,21, and 9% to 48% of unplanned readmissions can be avoided22. As mentioned above, the unplanned readmission rate of the same or related diseases within 31 days of patient discharge is part of the medical quality evaluation index in the China Healthcare Quality Indicators System (CHQIS). Our study used 31 day readmission as an index to evaluate medical quality and to explore the risk factors of COPD early readmission. In the literature, the early readmission rate of COPD varied with the different research objectives and different definitions of an early readmission. Chan and colleagues reported that the 30 day early readmission rate of 65,479 hospitalized COPD patients in Hong Kong was 24.2%23, which was similar to Jencks and colleagues who reported a readmission rate of 22.6%24, but higher than Nantsupawat and colleagues, who reported a 13.6% readmission rate14. In our study, the early readmission rate for acute exacerbation of COPD was 6.8% – lower than the above three COPD readmission and risk factors Lin et al.
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Table 3. Comparison of patients with COPD exacerbations according to early readmission status. Characteristics
All admissions (n ¼ 925)
Early readmissions (n ¼ 63)
Non-early readmissions (n ¼ 862)
p Value
Male gender Age (years) Length of stay (days) Ischemic heart disease Type 2 diabetes Hypertension Chronic cor pulmonale Pulmonary infiltrates Pulmonary function test Mild (FEV1 80% predicted) Moderate (50% FEV1580% predicted) Severe (30% FEV1550% predicted) Very severe (FEV1530% predicted) Anemia (%) Polycythemia (%) Hypoproteinemia (%) PaO2 (mmHg) PaCO2 (mmHg)
738 73.40 8.304 10.44 5.698 58 94 286 348 207 242 0 21 67 154 117 (12.6%) 82 (8.9%) 99 (10.7%) 63.46 8.885 58.51 10.236
56 72.98 þ 8.479 10.34 5.554 9 13 24 36 15 18 0 1 6 11 13 (20.6%) 7 (11.1%) 13 (20.6%) 62.22 8.618 62.41 10.185
682 73.43 8.295 11.89 7.296 49 81 262 312 192 224 0 20 61 143 104 (12.1%) 75 (8.7%) 86 (10.0%) 63.55 8.903 58.55 10.196
0.062 0.627 0.102 0.014 0.004 0.001 0.001 0.778 0.794
0.048 0.516 0.008 0.253 0.004
Data are presented as mean standard deviation. FEV1, forced expiratory volume in one second.
Table 4. Odds ratio by binary logistic regression of early readmissions. Variables Chronic cor pulmonale Ischemic heart disease Type 2 diabetes Hypertension Hypoproteinemia Anemia PaCO2
OR (95% CI)
p Value
2.142 (1.260–3.643) 1.684 (0.703–4.035) 1.628 (0.766–3.459) 1.085 (0.605–1.944) 2.018 (1.031–3.947) 1.847 (0.952–3.585) 1.029 (1.003–1.056)
0.005 0.242 0.205 0.784 0.040 0.070 0.027
CI, confidence interval; OR, odds ratio.
studies, but similar to the 31 day readmission rate of 2.67% to 6.3% in five large general hospitals in Beijing, China25. To some extent, the different readmission rates may be related to the different payment policies of medical fees in different countries and regions. For example, in Hong Kong, more than 92% of the medical fees of public hospitals were paid by government budget allocation, not by private payment. The core of COPD is inflammation. Extrapulmonary complications of COPD may be associated with the systemic inflammatory response. In addition, the degree of airflow limitation is related to the severity of COPD, and exacerbations and comorbidities contribute to the overall severity in individual patients4. Previous studies have found that the risk of readmission for AECOPD is related to factors including the frequency of acute exacerbations in the previous year, FEV1%, low body mass index, PaCO2, chronic cor pulmonale, short duration of hospitalization, and hyperglycemia14–17,26–30. Cardiovascular disease is the most important comorbidity in COPD, and is also an important cause of death in 318
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patients with COPD. Cardiovascular disease has no effect on the risk of acute exacerbation of COPD, but increases the risk of life-threatening acute exacerbation attack, and is a risk factor for COPD readmission17. There were discrepancies in the impact of ischemic heart disease on early readmission in the medical literature. Nantsupawat and coworkers suggested that 29.6% of hospitalized COPD patients had ischemic heart disease, and comorbid ischemic heart disease was associated with an increased risk for readmission (OR 6.4)14. Chen et al. reported that ischemic heart disease was frequent in COPD inpatients (26.3%) and was associated with an increased risk for COPD readmissions in female patients31. In our research data, only 4.8% of hospitalized COPD patients had coexisting ischemic heart disease, and we did not find a correlation with early readmission. The different incidence may be due to absence of a diagnosis related groups-prospective payment system (DRGs-PPS) which may have caused insufficient diagnosis. FEV1, PaCO2, PaO2, pulmonary hypertension or coexisting cor pulmonale are important indicators for COPD disease severity. Gonzalez and colleagues prospectively studied 90 cases of moderate to severe hospitalized COPD patients, and they suggested that coexisting chronic cor pulmonale was a risk factor for readmission within 3 months27. Liu and coworkers found that the decline of FEV1 increased risk of readmission within 14 days15. Our study showed that increased PaCO2 and coexisting cor pulmonale increased the risk of COPD early readmission, suggesting that the severity of disease itself has to do with the risk of early readmission. Only 17.6% of patients in our study completed pulmonary function test, thus attention should be paid in application of lung www.cmrojournal.com ! 2014 Informa UK Ltd
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function for diagnosis, severity assessment and monitoring disease progression of COPD23. We also found that PaO2 as another indicator reflecting severity of COPD was unrelated to early readmission. COPD combined with anemia was more common than polycythemia in our study. The incidence of anemia in COPD was between 10% and 15%, and anemia increases the severity of dyspnea, reduces exercise tolerance, and increases risk of death32,33. Barba et al. studied 289,077 hospitalized AECOPD patients and found 9.8% of cases coexisted with anemia, and anemia increased the risk of readmission by 25% in the two-year study period34. Despite the results of this study showing that anemia and polycythemia were common in COPD, anemia and polycythemia were unrelated to the occurrence of early readmission in our patients. COPD is often accompanied by malnutrition; 38% of AECOPD inpatients were malnourished, and 18% had hypoproteinemia in one study35. Body mass index (BMI), body weight as a percentage of standard weight, fat-free mass (FFM), and serum albumin level are the common indicators used in evaluating nutritional status. Serum albumin reflects storage levels of visceral protein, and depletion may be an indicator of serious malnutrition. Many studies have suggested that malnutrition increases the risk of acute exacerbation and readmission of COPD11,35,36. Our study also found that hypoproteinemia was an important risk factor for COPD early readmission, and hypoproteinemia more than doubled the risk of early readmission (OR 2.018, 95% CI 1.031–3.947, p ¼ 0.04). COPD combined with malnutrition leads to weakness of respiratory muscles, decline of ventilatory function, and impaired immune function, which may be the causes of early readmission. Consequently, attention should be paid to correcting malnutrition in the treatment of acute exacerbation of COPD. Acute exacerbation of COPD is associated with bacterial and viral infections and air pollution. COPD exacerbations with a chest X-ray consistent with pneumonia are associated with worse outcomes, including inpatient mortality, 90 day mortality, and frequent readmissions14,16,37,38. Nantsupawat and coworkers demonstrated that a chest X-ray with pulmonary infiltrates was a risk factor for COPD early readmission14. However, our study did not find similar results. In a retrospective analysis of related factors associated with COPD readmission, Bahadori and colleagues found the length of stay in patients admitted several times were shorter than in patients admitted one time during the study period (21 months); multiple logistic regression analysis showed that short length of hospitalization was a risk factor for readmission16. In our study, the length of stay was unrelated to early readmission. Compared to Nantsupawat and colleagues’ study which showed an average of length of stay of 4.9 days, the length of hospital stay was longer in our ! 2014 Informa UK Ltd www.cmrojournal.com
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study (an average of 10.44 days). Acute exacerbation of COPD is often attributed to pulmonary infection in the hospitalized AECOPD cases accompanied with pulmonary infiltrates. Further studies are needed to demonstrate whether a course of anti-infective therapy for AECOPD patients with pulmonary infiltrates on chest X-ray will reduce early readmission. There are limitations to this study. Reliance on clinical diagnosis rather than international guideline diagnosis for COPD (GOLD 2013) is a weakness and may have led to a mixed patient population that included patients with other chronic pulmonary diseases and skewed the results. Few women were identified in the review, which may reflect under-diagnosis or a lower prevalence of COPD in women in China. This was also a retrospective study, and confirmation of the findings should be sought in prospective studies.
Conclusion In summary, increased PaCO2, coexisting chronic cor pulmonale and hypoproteinemia were the risk factors for AECOPD early readmission we found in our population. Increased PaCO2 and coexisting chronic cor pulmonale were related to the severity of lung disease itself, and correction of hypoproteinemia may reduce COPD early readmission.
Transparency Declaration of funding This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Declaration of financial/other relationships J.L., Y.X., X.W., M.C., L.L., L.G., and J.F. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships. Acknowledgements We are grateful to David Larrabee MD, Brian Robinson MD and Liegan Chia MD for revision of this manuscript.
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Risk factors associated with chronic obstructive pulmonary disease early readmission a
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Jian Lin , Youzu Xu , Xiaomai Wu , Meifang Chen , Ling Lin , Liuyang Gong & Jiaxi Feng
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Department of Respiratory Medicine, Taizhou Hospital of Wenzhou Medical University Linhai, ZhejiangP.R. China Published online: 26 May 2015.
Click for updates To cite this article: Jian Lin, Youzu Xu, Xiaomai Wu, Meifang Chen, Ling Lin, Liuyang Gong & Jiaxi Feng (2014) Risk factors associated with chronic obstructive pulmonary disease early readmission, Current Medical Research and Opinion, 30:2, 315-320 To link to this article: http://dx.doi.org/10.1185/03007995.2013.858623
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Current Medical Research & Opinion 0300-7995 doi:10.1185/03007995.2013.858623
Vol. 30, No. 2, 2014, 315–320
Article ST-0292/858623 All rights reserved: reproduction in whole or part not permitted
py Un t rig au fo t ht di hor r S sp ize a la d le © y, u s 20 vi e o ew p r 14 r C o an h d p ibi om In rin ted m fo rm t a . Au e si th rc aU ng or i le is al K co ed D py us is Lim fo ers tr ite rp c i b a er n d so d ut na ow io l u nl n se oa d,
Jian Lin* Youzu Xu* Xiaomai Wu Meifang Chen Ling Lin Liuyang Gong Jiaxi Feng
Department of Respiratory Medicine, Taizhou Hospital of Wenzhou Medical University, Linhai, Zhejiang, P.R. China
Address for correspondence: Jiaxi Feng, Department of Respiratory Medicine, Taizhou Hospital, Linhai 317000, P.R. China. Tel.: +86 576-85199238; Fax: +86 576-85199542; [email protected] Keywords: COPD – Exacerbation – Readmission – Risk factors Accepted: 11 October 2013; published online: 7 November 2013 Citation: Curr Med Res Opin 2014; 30:315–20
No
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Original article Risk factors associated with chronic obstructive pulmonary disease early readmission
*These authors contributed equally to the work
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Abstract
Background: The 31 day readmission rate is deemed to be an important indicator of the quality of medical care in China. The objectives of this study were to identify the readmission rate of acute exacerbation for chronic obstructive pulmonary disease (COPD) and to evaluate associated risk factors. Methods: We retrospectively reviewed charts for patients with acute exacerbation of COPD (AECOPD) admitted to our hospital between January 2011 and November 2012. The early-readmission group and non-earlyreadmission group were determined by whether patients were readmitted within 31 days after discharge. Logistic regression analysis was performed to identify risk factors for early readmission following an AECOPD. Results: There were 692 patients with 925 admissions during the 23 month period; 63 (6.8%) admissions met our criteria for early readmission. Multivariate analysis showed that chronic cor pulmonale (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.26–3.64, p ¼ 0.005), hypoproteinemia (OR 2.02, 95% CI 1.03–3.95, p ¼ 0.040) and an elevated PaCO2 (OR 1.03, 95% CI 1.00–1.06, p ¼ 0.027) were identified as risk factors for early readmission of AECOPD. Conclusion: The readmission rate for AECOPD was 6.8%. AECOPD patients with chronic cor pulmonale, hypoproteinemia, and a high PaCO2 are at higher risk for readmission with 31 days of hospital discharge, and medical care of these patients warrants greater attention.
Introduction
Chronic obstructive pulmonary disease (COPD) is a common chronic airway disease, and is characterized by persistent airflow limitation that is usually progressive. COPD is a leading cause of morbidity, mortality and utilization of health care resources worldwide1,2, which results in a heavy economic burden to the patient, family and society. In China, the incidence of COPD is 8.2% in the population over the age of 403, so on this basis the number of COPD patients in China is estimated to be close to 43 million. An acute exacerbation of COPD (AECOPD) is defined as an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication4. Acute exacerbation accelerates the progression of the disease, reduces quality of life, decreases activity tolerance and increases mortality5–9. On average, AECOPD rates are approximately one to two per patient-year; with hospitalization averaging approximately 0.1 to 0.2 per patient-year10. COPD readmission and risk factors Lin et al.
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Medical expenses of COPD are associated with the severity of disease, the frequency of acute exacerbations and the number of hospitalizations. Expenditures due to acute exacerbation accounted for 40% to 57% of the total costs of COPD, even up to 63%, and hospitalization accounted for 58% of the total costs11–13. Avoiding or reducing the readmission rate for COPD patients may have a great impact on improving outcomes and reducing health care resource consumption. Our literature review about risk factors influencing COPD readmission rates were discrepant because of different outcome measures, methods, and readmission periods14–17. Some COPD patients truly need early rehospitalization after discharge. We proposed to study the reasons for early rehospitalization of COPD patients in exacerbation believing that this may be important for avoiding or reducing readmissions, and for decreasing medical costs. The unplanned readmission rate within 31 days for the same or related disease is one of the medical quality index evaluation criteria in the China Healthcare Quality Indicators System (CHQIS). The aims of our study were to identify the readmission rate of AECOPD patients who were discharged from our hospital within 31 days and to comprehensively evaluate the associated risk factors.
Patients and methods Patients Charts for patients with AECOPD who were discharged from Taizhou Hospital of Wenzhou Medical University (Zhejiang, P.R. China) over a 23 month period between January 1, 2011 and November 30, 2012 were retrospectively reviewed. The diagnosis of COPD was based on patients with long-term smoking and other risk factors, history of chronic cough, expectoration and dyspnea. Physical examination showed signs of emphysema, chest X-ray or computer tomography (CT) showed the signs of chronic bronchitis and emphysema, and blood gas analysis was associated with varying degrees of hypoxemia and/or increased carbon dioxide pressure. Some patients completed spirometric tests before admission or during hospitalization which met the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria4 for COPD. Exclusion criteria were (1) other lung disorder such as asthma, lung cancer, bronchiectasis, active tuberculosis, pneumothorax, or pleural effusion, and (2) death during hospitalization or abandonment of treatment because of disease progression.
Methods We selected patients with a primary diagnosis of COPD using international classification of diseases (ICD) coding 316
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(ICD-9: 490–492, 494–496) from the information and electronic medical record system of Taizhou Hospital. We collected the hospital number of each patient, and the name, sex, age, primary diagnosis, secondary diagnosis, date of admission, date of discharge, days of hospitalization, discharge outcome (improved, death or deterioration), classification of pulmonary function test (based on GOLD 2013 criteria, mild: forced expiratory volume in one second [FEV1] 80% predicted, moderate: 50% FEV1580% predicted, severe: 30% FEV1550% predicted, very severe: FEV1530% predicted)4, whether chest X-ray showed infiltrates or not, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), presence of anemia (hemoglobin: female5110 g/L, Male 5120 g/L), presence of polycythemia (hemoglobin: female 4150 g/L, male 4160 g/L), and presence of hypoproteinemia (serum albumin 535 g/L), all according to the last blood test results during hospitalization. Concomitant diseases (hypertension, type 2 diabetes, ischemic heart disease, chronic cor pulmonale) were recorded according to discharge diagnosis, the interval between discharge and readmission were recorded for the readmitted patients, and we confirmed patient identity by hospital number and name. The early-readmission group and non-earlyreadmission group were determined by whether patients were readmitted within 31 days after discharge.
Statistical analysis All data were analyzed by SPSS 12.0. Univariate analysis was performed using t-test or chi-squared test to determine the possible risk factors which affected readmission within 31 days after discharge. Multivariate logistic regression analysis was performed to determine the independent risk factors from the statistically significant factors with the univariate analysis. A p of50.05 was accepted as indicating a statistically significant difference.
Results Patient characteristics Between January 1, 2011 and November 30, 2012, 692 patients who were admitted to our hospital with AECOPD met the inclusion criteria for the study. The total number of admissions was 925, the total readmission rate was 39%. There were 63 admissions in 49 individuals (6.8%) that met our criteria for early readmission (Table 1). The interval between discharge and early readmission was 2–31 days, with an average of 16.92 8.76 days, and 10 cases were readmitted within 7 days after discharge (10/63, 15.9%). Baseline characteristics of patients are shown in Table 2. The age of the www.cmrojournal.com ! 2014 Informa UK Ltd
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Table 1. Number of admissions and readmissions during the study period (January 2011 to November 2012). Patients, n
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Readmissions, n (%) 0 1 2 3 4 5 7 8 12 Total admissions, n Early readmissions, n (%) Non-early readmissions, n (%)
564 (81.5) 75 (10.8) 29 (4.2) 12 (1.7) 8 (1.2) 1 (0.15) 1 (0.15) 1 (0.15) 1 (0.15) 925 63 (6.8) 862 (93.2)
Table 2. Baseline characteristics of 692 patients admitted with COPD acute exacerbations. Baseline characteristics
Mean age (years) Male sex Ischemic heart disease Type 2 diabetes Hypertension Chronic cor pulmonale Pulmonary function test performed Mild (FEV1 80% predicted) Moderate (50% FEV1580% predicted) Severe (30% FEV1550% predicted) Very severe (FEV1530% predicted)
All patients, n ¼ 692 (%) 72.95 8.399 544 (78.6) 33 (4.8) 59 (8.5) 203 (29.3) 228 (33.0) 122 (17.6) 0 (0.0) 17 (13.9) 33 (27.1) 72 (59.0)
patients ranged from 47 to 93 years, with an average of 72.95 8.40 years, 544 patients were male (78.6%). Thirty-three patients (4.8%) had a history of ischemic heart disease, 59 (8.5%) had diabetes, 203 (29.3%) had hypertension, and 228 (33.0%) had chronic cor pulmonale. A total of 122 (17.6%) patients finished completed pulmonary function testing during the admission, and based on GOLD 2013 criteria no patients (0.0%) had mild COPD, 17 (13.9%) patients had moderate, 33 (27.1%) patients had severe, and 72 (59.0%) patients had very severe COPD. Out of 925 admissions, 117 had anemia, 82 had polycythemia, and 99 had hypoproteinemia when discharged (Table 3).
Univariate analysis of early readmissions The chi-square test was used for enumeration data such as gender, presence of comorbidities (ischemic heart disease, chronic cor pulmonale, hypertension, type 2 diabetes), hypoproteinemia, anemia, and classification based on pulmonary function testing during hospitalization. The t-test was used for measurement data such as age, length of stay, ! 2014 Informa UK Ltd www.cmrojournal.com
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PaO2, and PaCO2. On the ¼ 0.05 level, the factors that had statistically significant differences included PaCO2, ischemic heart disease, chronic cor pulmonale, type 2 diabetes, hypertension, hypoproteinemia, and anemia. There were no statistically significant differences in gender, age, length of stay, PaO2, pulmonary infiltrates, polycythemia, and pulmonary function classification between the early and late readmission groups (Table 3).
Multivariate analysis of early readmissions Based on the results of univariate analysis, PaCO2, ischemic heart disease, chronic cor pulmonale, type 2 diabetes, hypertension, hypoproteinemia, and anemia were included in the multivariate analysis. The logistic regression analysis showed that chronic cor pulmonale (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.26– 3.64), hypoproteinemia (OR 2.02, 95% CI 1.03–3.95) and the level of PaCO2 (OR 1.03, 95% CI 1.00–1.06) significantly increased the odds of early readmission (Table 4).
Discussion Hospitalization remains an important marker of COPD disease severity and a high cost event. Previous studies from the United States reported that 50% of health care spending was used for hospitalizations, and 13% of readmitted patients occupied more than 50% of health care resources18. Unplanned readmission is when patients are readmitted because of the same or related diseases within a short time after their discharge. There is no uniform definition for ‘early’ readmission; generally one week to one month after discharge due to the same illness or surgery are commonly used19. Internationally, unplanned readmission is an important indicator to evaluate medical quality and efficiency20,21, and 9% to 48% of unplanned readmissions can be avoided22. As mentioned above, the unplanned readmission rate of the same or related diseases within 31 days of patient discharge is part of the medical quality evaluation index in the China Healthcare Quality Indicators System (CHQIS). Our study used 31 day readmission as an index to evaluate medical quality and to explore the risk factors of COPD early readmission. In the literature, the early readmission rate of COPD varied with the different research objectives and different definitions of an early readmission. Chan and colleagues reported that the 30 day early readmission rate of 65,479 hospitalized COPD patients in Hong Kong was 24.2%23, which was similar to Jencks and colleagues who reported a readmission rate of 22.6%24, but higher than Nantsupawat and colleagues, who reported a 13.6% readmission rate14. In our study, the early readmission rate for acute exacerbation of COPD was 6.8% – lower than the above three COPD readmission and risk factors Lin et al.
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Table 3. Comparison of patients with COPD exacerbations according to early readmission status. Characteristics
All admissions (n ¼ 925)
Early readmissions (n ¼ 63)
Non-early readmissions (n ¼ 862)
p Value
Male gender Age (years) Length of stay (days) Ischemic heart disease Type 2 diabetes Hypertension Chronic cor pulmonale Pulmonary infiltrates Pulmonary function test Mild (FEV1 80% predicted) Moderate (50% FEV1580% predicted) Severe (30% FEV1550% predicted) Very severe (FEV1530% predicted) Anemia (%) Polycythemia (%) Hypoproteinemia (%) PaO2 (mmHg) PaCO2 (mmHg)
738 73.40 8.304 10.44 5.698 58 94 286 348 207 242 0 21 67 154 117 (12.6%) 82 (8.9%) 99 (10.7%) 63.46 8.885 58.51 10.236
56 72.98 þ 8.479 10.34 5.554 9 13 24 36 15 18 0 1 6 11 13 (20.6%) 7 (11.1%) 13 (20.6%) 62.22 8.618 62.41 10.185
682 73.43 8.295 11.89 7.296 49 81 262 312 192 224 0 20 61 143 104 (12.1%) 75 (8.7%) 86 (10.0%) 63.55 8.903 58.55 10.196
0.062 0.627 0.102 0.014 0.004 0.001 0.001 0.778 0.794
0.048 0.516 0.008 0.253 0.004
Data are presented as mean standard deviation. FEV1, forced expiratory volume in one second.
Table 4. Odds ratio by binary logistic regression of early readmissions. Variables Chronic cor pulmonale Ischemic heart disease Type 2 diabetes Hypertension Hypoproteinemia Anemia PaCO2
OR (95% CI)
p Value
2.142 (1.260–3.643) 1.684 (0.703–4.035) 1.628 (0.766–3.459) 1.085 (0.605–1.944) 2.018 (1.031–3.947) 1.847 (0.952–3.585) 1.029 (1.003–1.056)
0.005 0.242 0.205 0.784 0.040 0.070 0.027
CI, confidence interval; OR, odds ratio.
studies, but similar to the 31 day readmission rate of 2.67% to 6.3% in five large general hospitals in Beijing, China25. To some extent, the different readmission rates may be related to the different payment policies of medical fees in different countries and regions. For example, in Hong Kong, more than 92% of the medical fees of public hospitals were paid by government budget allocation, not by private payment. The core of COPD is inflammation. Extrapulmonary complications of COPD may be associated with the systemic inflammatory response. In addition, the degree of airflow limitation is related to the severity of COPD, and exacerbations and comorbidities contribute to the overall severity in individual patients4. Previous studies have found that the risk of readmission for AECOPD is related to factors including the frequency of acute exacerbations in the previous year, FEV1%, low body mass index, PaCO2, chronic cor pulmonale, short duration of hospitalization, and hyperglycemia14–17,26–30. Cardiovascular disease is the most important comorbidity in COPD, and is also an important cause of death in 318
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patients with COPD. Cardiovascular disease has no effect on the risk of acute exacerbation of COPD, but increases the risk of life-threatening acute exacerbation attack, and is a risk factor for COPD readmission17. There were discrepancies in the impact of ischemic heart disease on early readmission in the medical literature. Nantsupawat and coworkers suggested that 29.6% of hospitalized COPD patients had ischemic heart disease, and comorbid ischemic heart disease was associated with an increased risk for readmission (OR 6.4)14. Chen et al. reported that ischemic heart disease was frequent in COPD inpatients (26.3%) and was associated with an increased risk for COPD readmissions in female patients31. In our research data, only 4.8% of hospitalized COPD patients had coexisting ischemic heart disease, and we did not find a correlation with early readmission. The different incidence may be due to absence of a diagnosis related groups-prospective payment system (DRGs-PPS) which may have caused insufficient diagnosis. FEV1, PaCO2, PaO2, pulmonary hypertension or coexisting cor pulmonale are important indicators for COPD disease severity. Gonzalez and colleagues prospectively studied 90 cases of moderate to severe hospitalized COPD patients, and they suggested that coexisting chronic cor pulmonale was a risk factor for readmission within 3 months27. Liu and coworkers found that the decline of FEV1 increased risk of readmission within 14 days15. Our study showed that increased PaCO2 and coexisting cor pulmonale increased the risk of COPD early readmission, suggesting that the severity of disease itself has to do with the risk of early readmission. Only 17.6% of patients in our study completed pulmonary function test, thus attention should be paid in application of lung www.cmrojournal.com ! 2014 Informa UK Ltd
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function for diagnosis, severity assessment and monitoring disease progression of COPD23. We also found that PaO2 as another indicator reflecting severity of COPD was unrelated to early readmission. COPD combined with anemia was more common than polycythemia in our study. The incidence of anemia in COPD was between 10% and 15%, and anemia increases the severity of dyspnea, reduces exercise tolerance, and increases risk of death32,33. Barba et al. studied 289,077 hospitalized AECOPD patients and found 9.8% of cases coexisted with anemia, and anemia increased the risk of readmission by 25% in the two-year study period34. Despite the results of this study showing that anemia and polycythemia were common in COPD, anemia and polycythemia were unrelated to the occurrence of early readmission in our patients. COPD is often accompanied by malnutrition; 38% of AECOPD inpatients were malnourished, and 18% had hypoproteinemia in one study35. Body mass index (BMI), body weight as a percentage of standard weight, fat-free mass (FFM), and serum albumin level are the common indicators used in evaluating nutritional status. Serum albumin reflects storage levels of visceral protein, and depletion may be an indicator of serious malnutrition. Many studies have suggested that malnutrition increases the risk of acute exacerbation and readmission of COPD11,35,36. Our study also found that hypoproteinemia was an important risk factor for COPD early readmission, and hypoproteinemia more than doubled the risk of early readmission (OR 2.018, 95% CI 1.031–3.947, p ¼ 0.04). COPD combined with malnutrition leads to weakness of respiratory muscles, decline of ventilatory function, and impaired immune function, which may be the causes of early readmission. Consequently, attention should be paid to correcting malnutrition in the treatment of acute exacerbation of COPD. Acute exacerbation of COPD is associated with bacterial and viral infections and air pollution. COPD exacerbations with a chest X-ray consistent with pneumonia are associated with worse outcomes, including inpatient mortality, 90 day mortality, and frequent readmissions14,16,37,38. Nantsupawat and coworkers demonstrated that a chest X-ray with pulmonary infiltrates was a risk factor for COPD early readmission14. However, our study did not find similar results. In a retrospective analysis of related factors associated with COPD readmission, Bahadori and colleagues found the length of stay in patients admitted several times were shorter than in patients admitted one time during the study period (21 months); multiple logistic regression analysis showed that short length of hospitalization was a risk factor for readmission16. In our study, the length of stay was unrelated to early readmission. Compared to Nantsupawat and colleagues’ study which showed an average of length of stay of 4.9 days, the length of hospital stay was longer in our ! 2014 Informa UK Ltd www.cmrojournal.com
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study (an average of 10.44 days). Acute exacerbation of COPD is often attributed to pulmonary infection in the hospitalized AECOPD cases accompanied with pulmonary infiltrates. Further studies are needed to demonstrate whether a course of anti-infective therapy for AECOPD patients with pulmonary infiltrates on chest X-ray will reduce early readmission. There are limitations to this study. Reliance on clinical diagnosis rather than international guideline diagnosis for COPD (GOLD 2013) is a weakness and may have led to a mixed patient population that included patients with other chronic pulmonary diseases and skewed the results. Few women were identified in the review, which may reflect under-diagnosis or a lower prevalence of COPD in women in China. This was also a retrospective study, and confirmation of the findings should be sought in prospective studies.
Conclusion In summary, increased PaCO2, coexisting chronic cor pulmonale and hypoproteinemia were the risk factors for AECOPD early readmission we found in our population. Increased PaCO2 and coexisting chronic cor pulmonale were related to the severity of lung disease itself, and correction of hypoproteinemia may reduce COPD early readmission.
Transparency Declaration of funding This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Declaration of financial/other relationships J.L., Y.X., X.W., M.C., L.L., L.G., and J.F. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article. CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships. Acknowledgements We are grateful to David Larrabee MD, Brian Robinson MD and Liegan Chia MD for revision of this manuscript.
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