Abstract
Background: Although substantial advances have been made in the treatment of chronic obstructive pulmonary disease (COPD), little is known regarding the impact of these advancements on inpatient outcomes over time. We sought to examine temporal trends in in-hospital outcomes among adults hospitalized with COPD exacerbation.
Methods: The Healthcare Cost and Utilization Project's Nationwide Inpatient Sample was utilized to identify a cohort of adults hospitalized with COPD exacerbation, identified through International Classification of Diseases-9 codes. Baseline demographics, medical history, and clinical outcomes were assessed in 3,060,565 hospitalizations in patients with COPD exacerbation from 2006–2009.
Results: In-hospital all-cause mortality significantly decreased over the 4-year study period (5.1%, 4.7%, 4.5%, and 4.2% from 2006-2009; p < 0.001). The decline in mechanical ventilation (5.8% 5.7%, 5.3%, and 5.4% from 2006–2009; p < 0.001) was accompanied by a nearly 50% rise in noninvasive positive pressure ventilation utilization (NIPPV) (2.3%, 2.9%, 3.3%, and 3.5% from 2006–2009; p < 0.001). Average hospital length of stay (LOS) decreased over the study period (6.3, 6.1, 5.8, and 5.7 days from 2006-2009; p < 0.001). These relationships remained significant in fully-adjusted multivariate analyses (referent year 2006: p < 0.001 for years 2007–2009 for mortality, mechanical ventilation, and hospital LOS; p < 0.001 for years 2008–2009). Multivariate analysis of predictors of mortality remained similar for Years 2006–2009 with mechanical ventilation, age greater than 75 years, and NIPPV use serving as the strongest predictors of mortality.
Conclusion: During 2006–2009, a significant decline in mortality was accompanied by less frequent mechanical ventilation, more frequent NIPPV use, and shorter LOS in adults hospitalized with COPD exacerbation.
Introduction
Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death and the 12th-leading cause of morbidity in the United States. (Citation1–Citation3). Affecting more than 5% of the U.S. adult population, COPD has been associated with significant healthcare expenditures with total economic costs estimating $49.9 billion in 2010 and total direct costs of medical care estimating $29.5 billion annually (Citation4). Direct costs associated with hospitalizations for COPD exceed $20 billion annually (Citation5,Citation6). Numerous advances in COPD management have been made over the past decade (Citation7–Citation12), ranging from the introduction of long-term anti-cholinergic therapy and combined long-term beta agonist and inhaled corticosteroid therapy in stable outpatients, to the use of non-invasive positive pressure ventilation (NIPPV) use in hypercarbic respiratory acidosis (Citation10–Citation12). The impact of these measures on in-hospital outcomes over time in patients with COPD exacerbation remains unclear. Accordingly, we sought to examine temporal trends in outcomes among adults hospitalized with COPD exacerbation.
Methods
We utilized data from the 2006–2009 Nationwide Inpatient Sample (NIS), collected by the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP), which is the largest all-payer inpatient publicly available database in the United States (Citation9). International Classification of Diseases, Ninth Revision (ICD-9) codes were utilized to identify a cohort of adults hospitalized with COPD exacerbation, defined as any discharge record with a diagnosis of COPD (ICD-9 codes 491.21, 491.22, 493.22, and 496). We identified a cohort of 3,060,565 hospitalizations for COPD exacerbation, who were classified based upon year of hospital discharge. Demographic and medical history data extracted included age group, gender, race, socioeconomic status, hypertension, diabetes mellitus, renal failure, congestive heart failure, valvular heart disease, arrhythmia, myocardial infarction (prior and current) (ICD-9 codes 410.0-411.89), and cerebrovascular disease (ICD-9 codes 431, 433–436). Outcomes of interest included in-hospital all-cause mortality, mechanical ventilation (ICD-9 code 96.70-96.72), non-invasive positive pressure ventilation (ICD-9 code 93.90), and hospital length of stay (days).
Statistical analysis
The study cohort of 3,060,565 hospitalizations was classified based upon year of hospital discharge. Univariate analyses were used to compare demographics, medical history, and clinical outcomes of patients in each year. Categorical variables are presented as percentages and were compared with the chi-squared test. Continuous variables are presented as means ± standard deviation and are compared using one-way ANOVA. Multivariable logistic regression and stepwise multivariate linear regression analysis was performed to determine the association of discharge year with in-hospital mortality, mechanical ventilation, non-invasive positive pressure ventilation, and hospital length of stay respectively while adjusting for demographics and medical history. Multivariable logistic regression was also performed to determine the predictors of mortality for each discharge year. STATA 12 (StataCorp LP, College Station, TX) was used for data analysis and a two-tailed p-value of less than or equal to 0.05 was regarded as statistically significant.
Results
Demographics and medical history
Over the 4-year study period, there were a total of 3,060,565 hospitalizations of adults with COPD exacerbation and the annual cohort size of this population ranged from 756,823 to 774,497. Demographic characteristics and medical history of the COPD cohorts by selected calendar year are reported in Table . The percentage of patients under the age of 65 years increased from 30.1% in 2006 to 32.6% in 2009 while the percentage over the age of 75 years decreased from 40.0% in 2006 to 37.3% in 2009 (p < 0.001). Hospitalization rates for women also increased over the study period from 50.2% in 2006 to 51.0% and 50.9% in 2008 and 2009 respectively (p < 0.001). The year 2009 also noted the lowest proportion of individuals from areas with an annual income of greater than $45,000 (15.1% in 2009 vs 16.4% in 2006, p < 0.001). Diabetes mellitus became increasingly prevalent (26.6% in 2006 vs 29.6% in 2009, p < 0.001) over the 4-year period while myocardial infarction at presentation decreased in prevalence (6.7% in 2006 vs 5.8% in 2009, p < 0.001). Rates of cerebrovascular disease were similar in each year.
Table 1. Demographics
Unadjusted clinical outcomes
In-hospital all-cause mortality significantly decreased over the 4-year study period (5.1%, 4.7%, 4.5%, and 4.2% from 2006–2009; p < 0.001) (Figure ). The decline in mechanical ventilation (5.8% 5.7%, 5.3%, and 5.4% from 2006–2009; p < 0.001) (Figure A) was accompanied by a nearly 50% rise in noninvasive positive pressure ventilation utilization (2.3%, 2.9%, 3.3%, and 3.5% from 2006–2009; p < 0.001) (Figure B). Average hospital length of stay decreased over the study period (6.3, 6.1, 5.8, and 5.7 days from 2006–2009; p < 0.001) (Figure ).
Figure 1. All-cause in-hospital mortality rates in patients hospitalized with COPD exacerbation.
Figure 2. Rates of (A) mechanical ventilation and (B) noninvasive positive pressure ventilation in patients hospitalized with COPD exacerbation.
Figure 3. Average hospital length of stay in days in patients hospitalized with COPD exacerbation.
Multivariate analyses
In multivariate logistic regression analysis, a decrease in all-cause in-hospital mortality was noted from 2006 to 2009 {Referent year 2006: Odds Ratio (OR) 0.95 [95% Confidence Interval (CI) 0.94–0.97] in Year 2007; OR 0.92 (95% CI 0.90–0.93) in Year 2008; and OR 0.84 (95% CI 0.83–0.86) in Year 2009} (Table ). Reduced mechanical ventilation was also noted over the study period [Referent year 2006: OR 0.95 (95% CI 0.94–0.96) in Year 2008; and OR 0.95 (95% CI 0.94–0.97) in Year 2009] accompanied by an increase in NIPPV utilization [Referent year 2006: OR 1.30 (95% CI 1.27–1.32) in Year 2007; OR 1.48 (95% CI 1.45–1.51) in Year 2008; and OR 1.57 (95% CI 1.55–1.60) in Year 2009]. Multivariate linear regression demonstrated a reduction in hospital length of stay [Referent year 2006: beta-coefficient -0.07 in Year 2007, beta-coefficient -0.31 in Year 2008, and beta-coefficient -0.45 in Year 2009 (p < 0.001 for all)] (Table ).
Table 2. Multivariate logistic regression models
Table 3. Multivariate linear regression of hospital length of stay
Multivariate logistic regression analyses of in-hospital mortality performed for each discharge year identified the following independent predictors of mortality: age group, gender, race, socioeconomic status (in 2008 and 2009 only), hypertension, diabetes mellitus, renal failure, congestive heart failure, valvular heart disease, arrhythmia, myocardial infarction at presentation (2006, 2007, and 2009 only), prior myocardial infarction, cerebrovascular disease, mechanical ventilation, and NIPPV use (Table ). The strongest predictors of mortality in each discharge year included: mechanical ventilation use [OR 11.03 (95% CI 10.75–11.31) in Year 2006; OR 11.43 (95% CI 11.13–11.74) in Year 2007; OR 12.76 (95% CI 12.41–13.11) in Year 2008; and OR 13.44 (95% CI 13.06–13.82) in Year 2009], age greater than 75 years old [OR 2.66 (95% CI 2.57–2.74) in Year 2006; OR 2.80 (95% CI 2.71–2.89) in Year 2007; OR 3.07 (95% CI 2.97–3.18) in Year 2008; and OR 3.20 (95% CI 3.09–3.32) in Year 2009], and NIPPV utilization [OR 2.43 (95% CI 2.31–2.55) in Year 2006; OR 2.55 (95% CI 2.44–2.67) in Year 2007; OR 2.58 (95% CI 2.47–2.70) in Year 2008; and OR 2.88 (95% CI 2.76–3.01) in Year 2009].
Table 4. Multivariate logistic regression models for in-hospital mortality for each discharge year
Discussion
In this cross-sectional, contemporary, nationally representative study of adults hospitalized with COPD exacerbation, several findings are noteworthy. First, inpatient all-cause mortality rates declined over the 4-year study period. Second, a rise in NIPPV utilization was accompanied by a decline in mechanical ventilation. Finally, average hospital length of stay shortened from 2006 to 2009. Few studies to date have examined trends in inpatient outcomes among adults hospitalized with COPD exacerbation, specifically in the United States.
Despite significant advances in therapy and national efforts to reduce its burden, COPD continues to be a major cause of morbidity and mortality in the United States (Citation1–Citation3, Citation7–Citation14) and worldwide (Citation13, Citation15–Citation21). Total hospitalizations and emergency department visits over the past decade have significantly increased in the United States (Citation22). In 2011, the American College of Chest Physicians in conjunction with the American College of Physicians, American Thoracic Society, and European Respiratory Society issued a clinical practice guideline update promoting the use of spirometry in those with respiratory symptoms for diagnostic purposes and the use of inhaled bronchodilators in patients with stable COPD (Citation12). For patients with more severe disease (i.e., FEV1< 60% predicted), the use of long-acting inhaled beta-agonists, anticholinergics, and corticosteroids is also advocated in addition to long-term oxygen therapy and pulmonary rehabilitation (Citation12).
Previous studies have conflicted regarding the direction of trends in death rates for patients with COPD (Citation16, Citation20, Citation21, Citation23). Compared to 2006, we demonstrated a decline in risk-adjusted mortality rates with a relative risk reduction of 16% in 2009. International studies have documented mortality reductions of 12–24% during similar time periods (Citation16, Citation20). A Canadian study noted long-term mortality rates to be as high as 70% at approximately 17 years following a first hospitalization for COPD (Citation21). Thun and colleagues noted that the rate of death from male and female smokers over the age of 50 increased significantly in a 2000-2010 cohort compared to cohorts from 1959–1965 and 1982–1988 (Citation23).
Our study also noted declining rates of myocardial infarction (during the hospitalization), however even after risk-adjusted analysis, a significant decrease persisted in inpatient mortality rates. Hospital presentation with a myocardial infarction was associated with higher mortality while history of a prior myocardial infarction was independently predictive of lower mortality. Lifestyle changes, frequent physician follow-up, management of co-morbidities, and improved compliance to guideline-based medications (i.e., aspirin, statins, beta-blockers) are likely to contribute to the survival benefit in the latter group.
The increase in NIPPV utilization (accompanied by the decline in mechanical ventilation) has been previously documented (Citation20, Citation24, Citation25). Prior data has demonstrated the independent association of NIPPV use with numerical indicators (i.e., PaO2, PaCO2) of impaired gas exchange (Citation24, Citation26). Factors associated with NIPPV receipt have included older age and white race (Citation25). By resting fatigued respiratory muscles and preventing the need for endotracheal intubation and mechanical ventilation, NIPPV has been associated with decreased mortality and hospital length of stay, decreased need for mechanical ventilation, and improvement in blood pH and respiratory rate within the first hour of presentation (Citation24). Patients with a high burden of co-morbidities and concomitant pneumonia have higher rates of NIPPV failure and are more likely to require mechanical ventilation (Citation25).
Hospitalization is a significant cost promoter in overall COPD expenditures in the U.S (Citation27–Citation29). While data regarding intensive care unit (ICU) admission and ICU length of stay was not available in our study, prior data has noted that inpatient costs for encounters with ICU or intubation varied minimally from 2005 to 2008 (Citation29). Readmission rates in the United States for COPD-related conditions are also contributing to costs. Among COPD inpatients, 1-year readmission rates can vary from 13%–19% and of these readmissions, approximately 30% and 50% occur within 30 days and 60 days, respectively, following hospital discharge (Citation27). Disease management programs, including home telemonitoring systems (Citation30), aimed to reduce frequency of exacerbations and other COPD-related hospitalizations may significantly reduce the high burden of inpatient costs.
Study limitations
Several limitations to this study exist. First, it is possible that the increase in hospitalizations over the study period was attributable, at least in part, to changes in coding practices over time. The use of ICD-9 codes to identify patients with COPD exacerbation may underestimate hospitalization rates and misclassify patients with other respiratory disorders (Citation31). Second, our analyses showed that patient age decreased over the study period, which may in part be due to early detection bias. Third, the uses of guideline-directed screening and therapies (including antibiotics, steroids, bronchodilators, etc.) as noted in (Citation12), which have previously been documented to affect clinical outcomes in COPD patients, were not studied. Finally, this study was limited to inpatient outcomes; hence, long-term follow-up data was not available.
Conclusions
The study period from 2006 to 2009 was associated with a significant decline in in-hospital mortality, less-frequent mechanical ventilation, more frequent non-invasive positive pressure ventilation, and shorter hospital length of stay in adults hospitalized with COPD exacerbation. Future studies examining correlation of temporal changes in COPD management with improvements in clinical outcomes are warranted.
Declaration of Interest Statement
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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