Disease Severity at the First Hospitalization as a Predictor for Mechanical Ventilation Dependency in Elderly Patients with Chronic Obstructive Pulmonary Disease
Kuang-Ming Liao,1,2 Wei-Chieh Lin,3 Tzu-Chieh Lin,2 Chung-Yi Li4,5 and Yea-Huei Kao Yang2
1 Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan 2 Institute of Clinical Pharmacy and Pharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan
3 Medical Intensive Care Unit, Department of Internal Medicine, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan
4 Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
5 Department of Public Health, College of Public Health, China Medical University
Corresponding author: Yea-Huei KAO YANG
Address: No.138, Shengli Rd., North Dist., Tainan City 704, Taiwan (R.O.C.) Fax number:+ 886-6-2373149
Patients with chronic obstructive pulmonary disease (COPD) are predisposed to respiratory failure with ventilator dependency. This study aims to determine the risk of prolonged mechanical ventilation (PMV), defined as 22 days or more of mechanical ventilation dependency after the first day of hospital admission (index date) in patients diagnosed with COPD. A retrospective cohort was conducted using medical claim data of Taiwan’s National Health Insurance Research Database. Eligible study subjects were those who had a diagnosis of COPD made between January 1, 2005 and
December 31, 2009. Patients were then followed until being registered as a PMV case, death, or the end of the study. The comorbidities were measured from January 1, 1997 to the index date by the ICD-9 code. The study sample consisted of 6,341 patients with COPD with a mean age of 73.89 (± 12.01) years. Over a maximum of 6 years of follow-up, 654 patients developed PMV dependency, with an incidence density of 41.56 per 1,000 person-years. Patients aged 70 years and older were at significantly increased risk for PMV dependency, compared to those aged 40-49 years after
adjusting for confounders. Expenses per visit and hospital visits per year, representing the severity of the COPD, were also associated with an elevated risk of PMV. Most patients developed PMV dependency within the first two years after the index date. Physicians should be aware that elderly patients with COPD have a high risk of PMV after first hospitalization, and these patients need to be closely monitored.
Introduction:
Chronic obstructive pulmonary disease (COPD) is a not fully reversible and progressive disease which is characterized by airflow limitation. 1 As the disease
progress, patients may frequently suffer from acute exacerbation (AE) requiring hospitalization and some of them lead to respiratory failure with ventilator dependent. COPD has been shown to be the major cause of death in Taiwan adult population. The hospitalization rate was 53.9 per 10,000 people. Its mortality has increased 2.5% per year for men and has little change for women in Taiwan before 1995, but the trend has declined beyond 1995. Another study reported that the mortality rate was 4.6 per 10,000 population during the period 1991-2004.2 In addition, it has been shown that the
number of patients requiring prolonged mechanical ventilation (PMV) has increased in Taiwan. There are approximately 11,000 catastrophic illness patients with chronic respiratory failure requiring PMV support in Taiwan. The expenditure of these patients is second only to cancer, accounting for about 20 % of all cost of catastrophic illness hospitalization.3
The growing burden of COPD in Taiwan raises the needs for the research of the epidemiology of COPD to increase the understanding of the disease and its course, aid the development of effective national health policies and facilitate equitable
deployment of finite health-care resources in the prevention and management of COPD. We thereby aim to clarify the disease course of the patients requiring PMV following the first hospital admission due to COPDAE using the National Health Insurance (NHI) database in Taiwan. The NHI program has provided universal health insurance in Taiwan since 1995. More than 99% citizens are enrolled in the program.4
All medical institutions contracted with the NHI program must submit standard computerized claim documents for medical expenses.
Material and method:
Taiwan launched a single-payer National Health Insurance (NHI) program in March 1995. The NHI Research Database (NHIRD), a medical claims database, was established and used for research purposes. The NHIRD contains all claims data from the NHI Program in Taiwan, including patients’ demographic characteristics, disease diagnoses, prescription records, and medical expenditures. Approximately 99% of the total population in Taiwan was enrolled in the NHI Program. In this study, we
retrieved our study sample from 1-million beneficiaries were randomly sampled from all beneficiaries registered in 2005. All medical claims from January 1, 1997 to December 31, 2010 for those 1-million beneficiaries are available. For data protection purposes, the confidential information on individuals was scrambled and encrypted
before the NHIRD was released to the researchers and the informed consent forms were waived by the Institutional Review Board.
Eligible cases analyzed in the present study were patients who had discharge diagnoses of COPD (ICD-9-CM codes: 490-492, 496) (with AE?) and prescriptions of bronchodilating drugs, including β2-agonists (short- and long-acting), anticholinergics, and theophylline during hospitalization between January 1, 2005 and December 31, 2009. Patients younger than 40 years and with a prior history of cancer were excluded. Patients ever hospitalized between January 1, 1997 and the first-time hospitalization between January 1, 2005 and December 31, 2009 were further excluded. All patients with COPD were then considered as the cases with first-ever admission during January 1, 2005 and December 31, 2009. Patients were then followed until the onset of
respiratory failure and prolong mechanical ventilation (PMV) dependency (>21 days). Information on PMV dependence was retrieved from the catastrophic illness document.
We first described the demographic characteristics and co-morbidity of the study patients. The incidence density of PMV dependency was estimated under Poisson assumption, and a life-table method (Culter S, Ederer F. Maximum utilization of the life
table method in analyzing survival. J Chronic Dis 1958;53:457–81.) was employed to
estimate the cumulative incidence rate of PMV dependency over the study period. We used Cox’s proportional hazard regression model with adjustment for potential
confounders to assess the potential predictors for the onset of PMV dependency. The index date for each parent was the day the hospital discharge. Subjects who were not deceased before the end of the follow-up period (i.e. December 31, 2010) were
considered censored on the last day of follow-up. Subjects who died were censored on the date of death. We also performed a log (-log) test and confirmed that
proportionality between hazards is assumed for the Cox model. All statistical analyses were performed using the Statistical Analysis Software (SAS) System, version 9.3 (SAS Institute Inc., Cary, NC, USA).
Result:
There are18,042 COPD patients had hospitalization records from 1997 to 2009. Among the 18042 patients, we excluded patient younger than 40 years old or have malignancy disease or have respiratory failure catastrophic illness document and COPD coding from 1997 to 2004.
The mean age and corresponding standard deviation (SD) of the study population was 73.89±12.01 years, with a male gender predominant distribution (68.05% male). More than 69% patients ’age were older than 70 years old. Table 1 presents the distributions of demographic characteristics and selected comorbid medical disorders and their geographic area distribution between the 6341 COPD cases.
In this group, patients had a higher prevalence of coronary heart disease and
depression with 58.02% and 84.01%, respectively. The mean of hospital visit per year is 8.64 and their average of hospital length of stay is 19.42 days. The average of medical expenditure is 35589 NTD per visit. The PMV events in this cohort population were 438 in male and 216 in female, and their incidence density were 41.09 and 42.54 per 1000 patient-years. There was no significant difference between gender groups with respect to PMV in COPD patients after first time hospitalization.
Table 2 showed the overall and specific incidence densities of respiratory failure in the study cohort. The incidence density is increased in 60-69 years old and rapidly increased in more than 70 years old group with 21.44 and 56.8 per 1000 patient-years, respectively. There were no significant difference in incidence density in gender, geographic area and urbanization status. During the followed up period, most PMV cases occurred in the first 2 years (77.52%). The cumulative respiratory failure rate in 6 years is 18.55% and cumulative survival rate is 81%. A further subgroup analysis of the effects of age in PMV revealed that cumulative respiratory failure rate is increased with age. In contrast, cumulative survival rate is decreased with age. In subgroup analysis, most people who experienced PMV in the first two years after hospitalization.
Table 4 shows the sex, age, geographic area, and urbanization status-specific adjusted HRs for PMV. Adjustment of potential confounders was made for age, sex,
geographic area, urbanization status, hospital visit per year, and hospital length of stay per visit, expenses per visit and pneumonia, arrhythmia, coronary heart disease, hypertension, stroke, diabetes. During prolong mechanical ventilation, a significantly increased HR was observed for old age (≧70 years old) (AHR = 3.12, 95% CI 1.90, 5.14).
Discussion:
To our knowledge, this is the first study to analyse a nationally representative PMV after COPDAE to estimate the cumulative incidence rate and stratified by age and observed years. The study shows that age to be a risk factor for PMV following the first hospital admission due to COPD with acute exacerbation. The incidence rate of PMV increased with age in COPD patients after adjusting confounders and cumulative incidence rate of PMV most occurred in the first two years.
Previous study6 has reviewed the published retrospective and prospective studies in
COPDAE to identify the risk factors in predicting in-hospital and post-discharge mortality, and readmission of patients hospitalized for COPDAE but there is no mention about PMV after first hospitalization for COPDAE. The growing burden of COPD supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its course, ensure the development of effective national health policies and facilitate equitable deployment of finite
health-care resources in the prevention and management of COPD. From this study, patients and their family, physicians can predictable PMV in COPD patients especially in older age group after hospitalization. Hung et al.7 have examined the median survival, life
expectancies, and cumulative incidence rate of patients undergoing PMV stratified by different underlying diseases and showed life expectancies generally decreased with older age. In particular, patients with a combination diagnosis of septicaemia and shock usually survived <4 months. End of life care may be an important issue in old age COPD patient hospitalization with septic shock.
Our study has several limitations that are confined by the database itself. First, the database did not contain any information regarding the disease severity, including the pulmonary function test and clinical data of the PMV patients. We were therefore unable to further stratify COPD patients’ severity. We believe that this nationwide study with a large case number demonstrates the scope and power of the NHIRD database of Taiwan for population based. There is a study application the NHIRD database to validate the results using clinical data and revealed concordance between clinical observation and retrospective conclusions. 7 Second, in order to more easily
reimbursed, it is possible that some diagnoses are over-represented to fulfil all of the reimbursement regulations of the NHI. However, the NHI of Taiwan has offered a list of major categories of catastrophic illnesses that are exempt from partial co-payments,
including PMV, and each has its specific diagnostic criteria to prevent any abuse. 3 The
ICD-9 codes used for COPD exacerbations have been extensively employed in other studies,8 and the internal findings also support the coding validity. 9Third, the study
design is retrospective; therefore, prospective studies are needed to further validate the conclusions. Each patient had a different enrollment time but the same end of PMV. Our data, therefore, should be interpreted as the description of PMV after COPDAE episodes in a given period of time. We believe that due to the number of enrolled participants, and the comprehensive enrollment of hospitalization in Taiwan, the database is of normal distribution and the results are of statistical significance.
Reference:
1. Vestbo, Jorgen (2013). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Global Initiative for Chronic Obstructive Lung Disease. P2. Chapter 1.
2. Tan WC, Seale P, Ip M, Shim YS, Chiang CH, . Trends in COPD mortality and hospitalizations in countries and regions of Asia-Pacific. Respirology. 2009; 14: 90-7. 3. Mei-Chuan Hung, Hsin-Ming Lu, Likwang Chen, Fu-Chang Hu, Soa-Yu Chan, Yuan-Horng Yan, Po-Sheng Fan, Ming-Shian Lin, Cheng-Ren Chen, Lu-Cheng Kuo,
Chong-Jen Yu, Jung-Der Wang. Life expectancies and incidence rates of patients under PMV: a population-based study during 1998 to 2007 in Taiwan. Critical Care 2011, 15:R107.
4. Bureau of National Health Insurance: Insurance Coverage. [http://www. nhi.gov.tw/English/webdata/webdata.aspx?
menu=11&menu_id=296&webdata_id=1942&WD_ID=296].
5. Prevalence and Risks of Chronic Airway Obstruction A Population Cohort Study in Taiwan. CHEST. 2007; 131:705–10.
6 J. STEER, G.J. GIBSON, S.C. BOURKE. Predicting outcomes following hospitalization for acute exacerbations of COPD. Q J Med 2010; 103:817–29. 7. Cheng CL, Kao YH, Lin SJ, Lee CH, Lai ML. Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan.
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8. M.T. Wang, C.L. Tsai, Y.W. Lo et al. Risk of stroke associated with inhaled ipratropium bromide in chronic obstructive pulmonary disease: a population-based nested case-control study. Int J Cardiol.2012; 158: 279–84.
9. Meng-Ting Wang, Yu-Wen Lo, Cheng-Liang Tsai, Li-Chien Chang, Daniel C. Malone, Che-Li Chu, Jun-Ting Liou. Statin Use and Risk of COPD Exacerbation Requiring Hospitalization. Am J Med.2013; 126: 598-606.
antigens in patients treated with procainamide or acetylprocainamide. N. Engl. J. Med. 1979; 301: 1382–5. Table 1. Study cohort n % Baseline characteristics Sex Male 4315 68.05 Female 2026 31.95 Age(years) 40-49 316 4.98 50-59 622 9.81 60-69 1027 16.20 70>= 4376 69.01 Mean (±SD) 73.89 (12.01) Geographic area Northern 2298 36.24 Central 1755 27.68 Southern 2005 31.62 Eastern 279 4.40 Urbanization status Urban area 2015 31.78 Suburban area 1709 26.95 Rural area 2608 41.13
Hospital visit per year
Mean (±SD) 8.64 (28.41)
Hospital length of stay per visit (days)
Expenses per visit Mean (±SD) 35588.55 (42237.89) Comorbidity Arrhythmia Yes 2281 35.97 No 4060 64.03
Coronary heart disease
Yes 3679 58.02 No 2662 41.98 Hypertension Yes 1352 21.32 No 4989 78.68 Stroke Yes 2119 33.42 No 4222 66.58 Diabetes Yes 2330 36.74 No 4011 63.26 Depression Yes 5327 84.01 No 1014 15.99 Osteoporosis Yes 1567 24.71 No 4774 75.29 Cataract Yes 3177 50.10 No 3164 49.90 Pneumonia Yes 3509 55.34 No 2832 44.66 Total 6341 100.00
Table 2.
COPD
No. of subjects No. of events ID b (95% CI c) Sex Male 4315 438 41.09 (37.31-45.10) Female 2026 216 42.54 (37.05-48.60) Age(years) 40-49 316 16 15.32 (8.76-24.88) 50-59 622 25 12.61 (8.16-18.61) 60-69 1027 66 21.44 (16.58-27.28) 70>= 4376 547 56.8 (52.11-61.74) Geographic area Northern 2298 213 36.78 (32.01-42.07) Central 1755 207 48.27 (41.92-55.32) Southern 2005 211 43.01 (37.41-49.23) Eastern 279 23 31.14 (19.74-46.72) Urbanization status Urban area 2015 212 42.82 (37.25-48.99) Suburban area 1709 171 40.33 (34.51-46.84) Rural area 2608 271 41.53 (36.70-46.75) Total a 6341 654 41.56 (38.42-44.85)
a Inconsistency between total population and population summed for individual variable was due to missing information
b ID= incidence density (per 1,000 patient-years), CI=confidence interval c Based on Poisson assumption
Table 3. Period No. of event Rate of failure Rate of survival Cumulative survival Cumulative failure(/100) 0-2 507 0.10 0.90 0.90 9.87 2-4 103 0.04 0.96 0.86 13.57 4-6 44 0.06 0.94 0.81 18.55
Period No. ofevent Rate offailure survivalRate of Cumulativesurvival failure(/100)Cumulative Age 40-50 0-2 14 0.05 0.95 0.95 4.96 2-4 2 0.01 0.99 0.94 6.02 4-6 0 0.00 1.00 0.94 6.02 Age 50-60 0-2 20 0.04 0.96 0.96 3.70 2-4 2 0.01 0.99 0.96 4.28 4-6 3 0.03 0.97 0.93 6.85 Age 60-70 0-2 50 0.06 0.94 0.94 5.73 2-4 9 0.02 0.98 0.93 7.40 4-6 7 0.04 0.96 0.89 11.08 Age 70+ 0-2 423 0.12 0.88 0.88 12.29 2-4 90 0.06 0.94 0.82 17.60 4-6 34 0.08 0.92 0.76 24.37
Table 4.
Crude HR a (95% CI a) †AHR b (95% CI a) ‡AHR c (95% CI a) Sex Male 0.96 (0.81-1.13) 1.04 (0.88-1.22) 1.04 (0.88-1.22) Female(ref.) Age(years) 40-49(ref.) 50-59 0.82 (0.44-1.53) 0.83 (0.44-1.56) 0.83 (0.44-1.56) 60-69 1.35 (0.78-2.33) 1.32 (0.76-2.27) 1.32 (0.76-2.27) 70>= 3.28 (1.99-5.39) 3.12 (1.90-5.14) 3.12 (1.90-5.14) Geographic area Northern 1.16 (0.76-1.78) 0.91 (0.57-1.44) 0.91 (0.57-1.44) Central 1.49 (0.97-2.30) 1.37 (0.89-2.12) 1.37 (0.89-2.12) Southern 1.35 (0.88-2.08) 1.12 (0.72-1.75) 1.12 (0.72-1.75) Eastern(ref.) Urbanization status Urban area 1.03 (0.86-1.23) 1.18 (0.96-1.44) 1.18 (0.96-1.44) Suburban area 0.97 (0.80-1.17) 1.05 (0.84-1.30) 1.05 (0.84-1.30) Rural area(ref.)
Hospital visit per year 1.00 (1.00-1.00) 1.00 (1.00-1.00) 1.00 (1.00-1.00) Hospital length of stay
per visit (days) 1.02 (1.02-1.02) 1.02 (1.02-1.02) 1.02 (1.02-1.02) Expenses per visit 1.00 (1.00-1.00) 1.00 (1.00-1.00) 1.00 (1.00-1.00) a HR=hazard ratio; CI= confidence interval
b AHR=adjusted hazard ratio; based on Cox proportional hazard regression model with adjustment for age, sex, geographic area, urbanization status, Hospital visit per year, Hospital length of stay per visit, Expenses per visit.
C Based on Cox proportional hazard regression model with adjustment for age, sex, geographic area, urbanization status, Hospital visit per year, Hospital length of stay per visit, Expenses per visit and Arrhythmia, Coronary heart disease, Hypertension, Stroke, Diabetes, Depression, Osteoporosis, Cataract, Pneumonia.
Table 1. Characteristics of the patients admitted for COPD with acute exacerbation in 2005-2009.
Table 2. Overall and specific incidence densities of respiratory failure in the study cohort
Table 3. Follow-up period-specific cumulative incidence rate of respiratory failure in the study cohort.
Table 4. Hazard ratio of respiratory failure in relation to baseline characteristics of the study subjects, 2000-2010
