DOI 10.1378/chest.10-2439 2011;139;1354-1360; Prepublished online March 10, 2011;Chest

 and Jordi RelloGómez, Oriol Roca, Sandra Trefler, Joaquim Gea, Joan R. Masclans Alejandro Rodríguez, Thiago Lisboa, Jorge Solé-Violán, Federico Mortality in Critically Ill PatientsImpact of Nonexacerbated COPD on

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1354

CHEST Original ResearchCRITICAL CARE

Original Research

COPD is a leading cause of death in the United States, but risk stratifi cation on patients with

COPD is challenging. For the past 3 decades, clini-cians have largely relied on age and FEV 1 to assess prognosis in COPD. Although age and FEV 1 have

been well studied, considerable variability in outcome has been observed when these are used alone in assessing an individual patient-level prognosis. In addition, the contribution of nonexacerbated COPD to mortality has not been studied. We hypothesized that patients with nonexacerbated COPD requiring endotracheal intubation (ETI) have a high risk of ventilator-associated pneumonia (VAP) and higher mortality than patients without COPD. The aim of

Background: The real contribution of nonexacerbated COPD to mortality has not been studied. The aim of our study was to evaluate the impact of nonexacerbated COPD on mortality in patients requiring mechanical ventilation (MV). Methods: This prospective, observational study included critically ill, ventilated patients without evidence of respiratory infection. Patients with COPD comprised the study group. Clinical and demographics variables were recorded. The main end point was ICU mortality. Results: Of the 235 patients included, 60 (25.5%) intubated patients had COPD. The remaining 175 (74.5%) comprised the control group. Those with COPD were more often medical patients who were older and had a higher number of comorbidities and a higher APACHE (Acute Physiol-ogy and Chronic Health Evaluation) II score than intubated patients without COPD ( P , .05). The overall ICU mortality was 26.3% (62/235) and signifi cantly higher in patients with nonexac-erbated COPD (36.7% vs 22.9%, P , .05), with an attributable mortality to COPD of 13.8%. Incidence of ventilator-associated pneumonia was not signifi cantly different between patients with nonexacerbated COPD (11.9/1,000 MV days) and without COPD (16.0/1,000 MV days; P 5 .40). In the multivariate analysis, only COPD (hazard ratio [HR], 2.1; 95% CI, 1.10-3.94), shock at ICU admission (HR, 2.0; 95% CI, 1.01-4.01), and medical condition (HR, 1.7; 95% CI, 1.01-3.18) were independently associated with mortality. Conclusions: Intubated patients with nonexacerbated COPD were not exposed to a higher risk of ventilator-associated pneumonia but had a higher rate of mortality. CHEST 2011; 139(6):1354–1360

Abbreviations: ETI 5 endotracheal intubation; HR 5 hazard ratio; IQR 5 interquartile range; LRTI 5 lower respiratory tract infection; MV 5 mechanical ventilation; SOFA 5 Sequential Organ Failure Assessment; VAP 5 ventilator-associated pneumonia

Impact of Nonexacerbated COPD on Mortality in Critically Ill Patients Alejandro Rodríguez , MD , PhD ; Thiago Lisboa , MD ; Jorge Solé-Violán , MD , PhD ; Federico Gómez , MD ; Oriol Roca , MD , PhD ; Sandra Trefl er , BSc ; Joaquim Gea , MD , PhD ; Joan R. Masclans , MD , PhD ; and Jordi Rello , MD , PhD

Manuscript received September 21, 2010; revision accepted February 14, 2011. Affi liations: From the Critical Care Department (Drs Rodríguez and Lisboa and Ms Trefl er) and Microbiologic Department (Dr Gómez), Joan XXIII University Hospital, CibeRes Enfermedades Respiratorias, Universidad Rovira i Virgili-IISPV, Tarragona; Critical Care Department (Dr Solé-Violán), Dr Negrín University Hospital, Las Palmas de Gran, Canaria; Critical Care Department (Drs Roca, Masclans, and Rello), Vall d’Hebron Uni-versity Hospital, VHIR-Universitat Autonoma Barcelona, CibeRes, Barcelona; and Respiratory Department (Dr Gea), Hospital del Mar, IMIM-UPF, CibeRes, Barcelona, Spain. Funding/Support: This work was supported in part by Marató TV3, CibeRes, and AGAUR (2009/SGR/920].

Correspondence to: Jordi Rello, MD, PhD, Critical Care Depart-ment, Vall D’Hebron University Hospital, P Vall D’Hebron 119, 129, 08035 Barcelona, Spain; e-mail: jrello.hj23.ics@gencat.cat © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians ( http://www.chestpubs.org/site/misc/reprints.xhtml ). DOI: 10.1378/chest.10-2439

www.chestpubs.org CHEST / 139 / 6 / JUNE, 2011 1355

response (WBC count . 10,000/mm 3 , rise in WBC count . 20%, or fever). Bacteriologic confi rmation was not required for diag-nosis of VAP.

In addition, we registered previous antibiotic use before ICU admission, which was defi ned as any antibiotic treatment ( . 48 h) during the 2 weeks preceding ICU admission. Prior antibiotic use before VAP onset was defi ned as any antibiotic treatment starting within the ICU for causes different from LRTI.

Patients with HIV infections or malignancy and those taking cytotoxic drugs were considered to be immunocompromised. Steroid use was defi ned as long-term oral steroid therapy, such as daily doses . 10 mg of prednisolone or the equivalent for 2 weeks. Active tobacco use was considered if the patient had smoked more than one packet per day within the past 10 years. 1

Shock was defi ned as the need for vasopressor for . 4 h after fl uid replacement at time of ICU admission. 6 Development of multiple organ failure by Sequential Organ Failure Assessment (SOFA) score 7 also was recorded. The SOFA score was computed daily, starting at ICU admission until day 7 according to stan-dard modalities. The worst value for each organ system in each 24-h period was considered. Organ failure was defined as a SOFA score � 3. 7

Attributable mortality was estimated as the difference in mor-tality rate between patients with and without COPD. Details of other defi nitions have been reported elsewhere. 8

Statistical Analysis

Continuous variables were expressed as mean � SD or median and interquartile range (IQR) if their distribution was skewed. The x 2 test and Fisher exact test were performed for categori-cal variables and the Student t test and nonparametric Mann-Whitney U test for continuous variables.

Kaplan-Meier survival curves were used to determine the probability of survival for patients with nonexacerbated COPD and those without COPD at 30 days. Survival curves were com-pared using the log-rank test.

To identify which variables at admission were associated with mortality and VAP development, multivariate Cox proportional hazard regression models were used. Signifi cant variables associ-ated with VAP and mortality in univariate analysis were included in multivariate model. Colinearity was assessed by correlation matrix. Adjusted hazard ratio (HRs) and 95% CIs were calculated for each variable. Statistical signifi cance was accepted for P , .05. Analysis was performed using SPSS version 13.0 (SPSS Inc; Chicago, Illinois) statistical software.

Results

During the study period, a total of 235 consecutive patients on MV without evidence of LRTI were included in the study. Of these, 60 (25.5%) intubated patients had COPD (study group). The remaining 175 (74.5%) patients comprised the control group. Differences in baseline characteristics between patients with and without COPD are summarized in Table 1 . Causes of ICU admission for patients with COPD were head trauma (n 5 1), multiple trauma (n 5 2), abdominal surgery (n 5 8), major vascular surgery (n 5 3), thoracic surgery (n 5 2), heart failure (n 5 13), stroke (n 5 11), cardiorespiratory arrest (n 5 3), urinary sepsis (n 5 3), pulmonary embolism (n 5 3), chronic renal failure (n 5 2), liver failure (n 5 2), and

our study was to evaluate the impact of nonexacer-bated COPD on mortality in patients requiring mechanical ventilation (MV). Our objectives were the following: (1) to assess the attributable mortality in patients with nonexacerbated COPD requiring ETI with respect to patients without COPD, (2) to determine the incidence of VAP in patients with nonexacerbated COPD, and (3) to identify risk fac-tors associated with mortality.

Materials and Methods

This prospective, observational, case-control study was per-formed in two multidisciplinary ICUs in 2007. The study was approved by the Joan XXIII Ethics Committee (042110), and written informed consent was obtained from each patient or from his or her legal representative.

Patients with COPD admitted to the ICU with ETI and with-out evidence of lower respiratory tract infection (LRTI) who were expected to need MV for . 48 h were eligible for inclusion (study population). Patients without COPD with ETI and without evi-dence of LRTI and expected to need MV for . 48 h comprised the control group. The exclusion criteria were tracheotomy at ICU admission, nasal intubation, documented massive gastric aspira-tion, and COPD exacerbation.

COPD was defi ned as a disease state characterized by the pres-ence of airfl ow limitation due to chronic bronchitis or emphysema. The airfl ow obstruction may be accompanied by airway hyperre-activity and may be partially reversible. 1 The diagnosis of COPD was confi rmed with premorbid pulmonary function testing when available. In the absence of documented airfl ow obstruction, we used clinical criteria, medical records with compatible physical fi ndings, and evidence of hyperinfl ation on chest radiograph. 2

Exacerbated COPD was defi ned as an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and sputum that is beyond normal day-to-day variations, is acute in onset, and may warrant a change in medication in a patient with underlying COPD according to Dewan et al 3 and GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria. 4 Patients with nonexacerbated COPD were defi ned as those with COPD but not fulfi lling criteria for exacerbation.

Patients were intubated according to clinical status and phy-sician indication. The oropharyngeal cavity was cleaned with 0.12% chlorhexidine solution according to local protocol. Contin-uous subglottic drainage or selective digestive decontamination was not used. The ventilator circuit was not changed routinely. A head and moisture exchanger was positioned between the Y piece and the patient. These devices were changed every 48 h or more frequently if necessary. Patients were kept in a semirecumbent position during most of the MV period. All patients received stress ulcer prophylaxis.

Clinical and demographic profi les at the time of admission to the ICU, including age, sex, and comorbidities, were recorded. Comorbidities were defi ned as the presence of one or more dis-tinct disorders in addition to COPD, regardless of whether the comorbid condition was directly related to COPD. 5

Microbiologic analyses were prospectively performed on all included patients. Samples consisted of quantitative culture of endotracheal aspirates that were obtained on the day of VAP sus-picion in all patients (VAP culture). VAP was diagnosed when new, persistent pulmonary infi ltrates not otherwise explained appeared on chest radiograph plus the presence of local (puru-lent respiratory secretions) and systemic signs of infl ammatory

1356 Original Research

utable mortality to COPD was estimated to be 13.8%. A Kaplan-Meier survival curve ( Fig 1 ) shows a signifi -cant difference (log-rank, 9.05; P 5 .003) in 30-day ICU mortality for patients with and without COPD. Age, SOFA score at ICU admission, medical condi-tion, shock at admission, and COPD were the vari-ables associated with ICU mortality in the univariate analysis. One patient with COPD died within 48 h, fi ve between 3 and 7 days, and 18 . 1 week after ICU admission.

Seventy-four (31.5%) patients developed VAP. Ten (16.6%) patients with COPD and 63 (36.0%) without COPD developed VAP ( P , .05). However, when the episodes of VAP were calculated per 1,000 MV days, VAP incidence was not signifi cantly different between patients with nonexacerbated COPD (11.9/1000 MV days) and those without COPD (16.0/1,000 MV days, P 5 .40). VAP was documented after a median of 7.5 days (IQR, 2-10 days) in patients with COPD and 4 days (IQR, 3-6 days) in those without COPD ( P 5 .41). Among patients with nonexacerbated COPD, VAP incidence was not different between survivors (13.2%) and nonsurvivors (22.7%) ( P 5 .34) ( Table 3 ). In addition, the mortality rate was not signifi cantly different between patients with non-exacerbated COPD with VAP (50%) and without VAP (34.0%) ( P 5 .33). The mean total SOFA score was higher in nonsurvivors than survivors on day 1

other (n 5 7). Severity of illness at admission, assessed by APACHE (Acute Physiology and Chronic Health Evaluation) II score, was higher in patients with COPD ( P , .05). Those with COPD were more often medical patients and older than intubated patients without COPD. Spirometric fi ndings prior to ICU admission were available in only 11 (18.3%) patients. According to the GOLD stages of COPD severity, fi ve patients were stage II, fi ve stage III, and one stage IV. Only 21 (35%) patients with COPD received inhaled steroids.

In the general population, the mean number of comorbidities was 1.3 � 1.0. Compared with patients without COPD, patients with nonexacerbated COPD had a higher number of comorbidities (mean, 1.0 � 0.9 vs 2.0 � 1.1; P 5 .01). Active tobacco use, diabetes mellitus, and cardiomyopathy were more frequently observed in patients with COPD ( Table 1 ). However, only COPD was associated with ICU mortality ( Table 2 ) in the univariate analysis. Among patients with COPD, no comorbidity was associated with ICU mortality ( Table 3 ).

The overall ICU mortality was 26.3% (62/235) and signifi cantly higher in patients with nonexacerbated COPD (36.7% vs 22.9%, P , .05) ( Table 1 ). The attrib-

Table 1— Characteristics of Patients

VariablePatients With

COPD Patients Without

COPD

Subjects, No. 60 175Age, y 68.5 � 11.3 a 53.4 � 19.1Male sex 51 (85.0) 128 (73.1)Admission type Medical 44 (73.3) a 71 (40.6) Surgical 13 (21.7) 39 (22.3) Trauma 3 (5.0) 65 (37.1) a APACHE II at ICU admission 21.5 � 6.3 a 19.5 � 6.5Comorbidities Active tobacco use 40 (66.6) a 69 (39.4) Diabetes mellitus 21 (35) a 32 (18.3) Steroids use 23 (38.3) a 6 (3.4) Immunocompromise 4 (6.7) 19 (10.9) Cardiomyopathy 27 (45) a 44 (25.1)SOFA score at ICU admission 7.3 � 2.8 6.9 � 2.6CRP at ICU admission, mg/dL 11.5 � 10.5 11.9 � 11.2Shock at ICU admission 32 (53.3) 104 (59.4)Pa o 2 /F io 2 , mm Hg 267.2 � 131.4 264.2 � 125.8Previous antibiotic use before VAP

48 (80.0) 154 (88.0)

ICU mortality 22 (36.7) a 40 (22.9)Hospital mortality 23 (38.3) 49 (29.2)Length of MV for survivors 14.0 � 11.6 13.4 � 5.6ICU LOS for survivors 23.7 � 23.5 29.8 � 24.3Hospital LOS for survivors 42.1 � 30.4 47.4 � 32.4

Data are presented as mean � SD or No. (%), unless otherwise indi-cated. APACHE 5 Acute Physiology and Chronic Health Evaluation; CRP 5 C-reactive protein; LOS 5 length of stay; MV 5 mechanical ven-tilation; SOFA 5 Sequential Organ Failure Assessment; VAP 5 ventilator-associated pneumonia. a P , .05. Table 2— Characteristics of Patients According

to the ICU Outcome

VariableSurvivors (n 5 173)

Nonsurvivors (n 5 62) P Value

Age, y 55.9 � 18.9 61.3 � 17.0 .03Male sex 135 (78.0) 44 (71.0) .26APACHE II score 19.2 � 6.6 22.4 � 5.8 .91First SOFA score 6.5 � 2.4 8.3 � 2.7 .01CRP at ICU admission, mg/dL

11.1 � 10.1 13.9 � 13.2 .20

Admission type Medical 74 (42.8) 41 (66.1) .02 Surgical 41 (23.7) 11 (17.4) .33 Trauma 58 (33.5) 10 (16.1) .01Comorbidity or risk factor COPD 38 (22.0) 22 (35.5) .03 Diabetes mellitus 37 (21.4) 16 (25.8) .47 Active tobacco use 77 (44.5) 32 (51.6) .33 Steroids use 20 (11.6) 9 (14.5) .54 Immunocompromise 17 (9.8) 6 (9.7) .97 Cardiomyopathy 47 (27.2) 24 (38.7) .09Shock at admission 88 (50.9) 48 (77.4) .01Pa o 2 /F io 2 , mm Hg 266.6 � 122.4 260.3 � 140.4 .76VAP 58 (33.5) 17 (27.2) .37Previous antibiotic use before ICU admission

35 (20.2) 16 (25.8) .37

Previous antibiotic use before VAP

145 (83.8) 57 (91.9) .11

Data are presented as mean � SD or No. (%), unless otherwise indi-cated. See Table 1 legend for expansion of abbreviations.

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Several factors may play a role in increased mortal-ity for COPD. 9,10 In addition, muscle dysfunction may occur within hours of the initiation of MV. 11 Further-more, neuromuscular dysfunction has been reported frequently in patients with sepsis, multiple organ dys-function, or both. 12 This muscle dysfunction could be more frequent in patients with COPD because of several reasons. A strong association between administration of steroids and a higher incidence of ICU-acquired paresis has been described. 13 More recently, cigarette smoke-induced oxidative stress has been described as a contributor to muscle loss and dys-function in patients with COPD. 14 Indeed, the inci-dence of ICU-acquired weakness in patients with COPD may be higher because of a sedentary lifestyle related to the impairment of pulmonary function. 15

Nevertheless, higher mortality observed in patients with COPD may not be explained by a higher inci-dence of VAP. No signifi cant difference in VAP inci-dence was observed between the study and control groups. Likewise, it was comparable to the incidence reported in a large, prospective, longitudinal, multi-center study that included 147 different ICUs and ? 15,000 critically ill patients. 16 Mechanisms of VAP development and of bacterial pathogenesis in COPD should be taken into account to explain this result. First, the main route of VAP development is through microaspiration of microorganisms that have colo-nized the oropharyngeal tract. Hence, more effective VAP prevention strategies should be oriented to decreasing oropharyngeal colonization or the bacte-rial load of the oropharynx. In the present study, oral care with chlorhexidine was used equally in both groups. Likewise, all other strategies of VAP preven-tion were used uniformly in both groups.

Second, previous colonization of the airway might not be an important issue for VAP development in patients with COPD. Colonization is defi ned as the presence of the pathogen in the airways that does not cause any damage to the host or any induced host response. 17 In patients with COPD, bacterial coloni-zation has been related to infl ammation of the distal airways, suggesting that it may play a role in COPD progression. 18 However, no relation between previ-ous colonization or increase in bacterial load of a preexisting pathogen and exacerbations has been described. In fact, it seems that the acquisition of a new bacterial strain and the imbalance between the virulence of the pathogen and the host lung defenses might be the main mechanisms of bacterial patho-genesis in patients with COPD. 19 Consequently, inci-dence of VAP should be expected to be the same in both groups.

Moreover, among patients with nonexacerbated COPD, VAP did not exert any effect on mortality. The effect of VAP on mortality of critically ill patients

(8.3 � 2.7 vs 6.5 � 2.4; P , .01) ( Table 2 ). However, SOFA score was not different at ICU admission between patients with nonexacerbated COPD and those without COPD ( Table 1 ). Among patients with COPD, nonsurvivors had a mean total SOFA score signifi cantly higher than that of survivors (8.3 � 3.2 vs 6.7 � 2.3, P 5 .03) at ICU admission and for all subsequent days until day 7 ( Fig 2 ).

To determine which variables were independently associated with mortality, age, medical condition, tobacco use, steroid therapy, cardiomyopathy, COPD, SOFA score at ICU admission, VAP, and shock at admission were included in multivariate analysis (Cox proportional hazard regression). Only COPD (HR, 2.12; 95% CI, 1.08-4.13; P 5 .02), shock at ICU admission (HR, 2.20; 95% CI, 1.07-4.49; P 5 .03), and medical condition (HR, 1.79; 95% CI, 1.01-3.18; P 5 .04) were independently associated with mortality.

Discussion

The most important fi nding of this study is that intubated patients with nonexacerbated COPD were not exposed to a higher risk of VAP but had higher mortality. These patients were older and had more comorbidities and shock than the patients without COPD. However, a regression analysis adjusting for these potential confounders identifi ed that only pres-ence of COPD, medical condition, and shock at ICU admission were factors independently associated with higher mortality in intubated patients without evidence of LRTI.

Table 3— Characteristics of Patients With COPD According to the ICU Outcome

VariableSurvivors (n 5 38)

Nonsurvivors (n 5 22) P Value

Age, y 68.3 � 11.3 68.8 � 11.6 .85Male sex 32 (84.2) 19 (86.4) .82APACHE II score 20.6 � 6.3 23.1 � 6.3 .14First SOFA score 6.7 � 2.3 8.2 � 3.1 .03CRP at ICU admission, mg/dL

11.1 � 9.9 12.1 � 11.9 .20

Comorbidity or risk factor Diabetes mellitus 13 (34.2) 8 (36.4) .86 Active tobacco use 25 (65.8) 15 (68.2) .85 Steroids use 15 (39.5) 8 (36.4) .81 Immunocompromise 3 (7.9) 1 (4.5) .61 Cardiomyopathy 16 (42.1) 11 (50.0) .55Shock at admission 18 (47.0) 14 (63.6) .22Pa o 2 /F io 2 , mm Hg 266.6 � 122.4 260.3 � 140.4 .76VAP 5 (13.2) 5 (22.7) .34Previous antibiotic use before ICU admission

8 (21.1) 6 (27.3) .55

Previous antibiotic use before VAP

28 (73.7) 20 (90.9) .11

Data are presented as mean � SD or No. (%), unless otherwise indi-cated. See Table 1 legend for expansion of abbreviations.

1358 Original Research

ferent results obtained in the present study. Patients with COPD included in a study by Nseir et al 31 were mainly admitted to the ICU because of an acute exac-erbation of their lung disease. In contrast, all the patients included in the present study had no exacer-bation of their COPD.

The present study is not exempt from limitations. Indeed, it included major imbalances in comorbid-ities and admission types between the cases and control subjects, a lack of an objective defi nition of COPD in the majority of study subjects, and a lack of information about the causes of death (which could provide a rationale for the described fi ndings). The attributable mortality as described would seem appropriate for otherwise well-matched case and con-trol groups but not for the groups presented here. Previous studies 1,2,32,33 in critically ill patients that addressed the same issue did not provide information with regard to severity of COPD. Therefore, further studies should analyze the impact of lung impairment severity on the survival of patients with nonexacer-bated COPD receiving MV.

In conclusion, the present study demonstrates that COPD is a factor independently associated with mor-tality in critically ill patients without evidence of LRTI. Furthermore, no difference in incidence of VAP was observed between patients with nonexacer-bated COPD and critically ill control subjects, suggest-ing that mechanisms of VAP development may not be related to the previous existence of lung disease.

remains controversial. In some studies, VAP has been described as an independent risk factor for mortality, 20-22 whereas in others, it has not. 23,24 In a case-control strategy to assess the attributable mortality of VAP, the differences in the results reported persisted, with attributable mortality ranging from 0% to 50%. 25-30

To our knowledge, only one previous case-control study analyzed the effect of VAP on mortality of criti-cally ill patients with COPD 31 and demonstrated that VAP is associated with higher mortality rates and longer duration of MV and ICU stay in this patient population. However, an important differ-ence in the population included may explain the dif-

Figure 1. Kaplan-Meier survival curve for hospitalized patients with and without COPD.

Figure 2. Mean SOFA scores in patients with COPD on days 1 to 7 in survivors and nonsurvivors ( P , .001 between the two groups). SOFA 5 Sequential Organ Failure Assessment.

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Acknowledgments Author contributions: Dr Rodríguez had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Rodríguez: contributed to the conception and design of this study, acquisition of data, analysis and interpretation of data, and manuscript preparation. Dr Lisboa: contributed to acquisition and interpretation of data and manuscript preparation. Dr Solé-Violán: contributed to the analysis and interpretation of the data and manuscript preparation. Dr Gómez : contributed to the performance of the microbiologic analyses and manuscript preparation. Dr Roca: contributed to the analysis and interpretation of the data and manuscript preparation. Ms Trefl er: contributed to the acquisition and interpretation of the data and manuscript preparation. Dr Gea: contributed to the analysis and interpretation of the data and manuscript preparation. Dr Masclans: contributed to the analysis and interpretation of the data and manuscript preparation. Dr Rello: contributed to the conception and design of this study and manuscript preparation. Financial/nonfi nancial disclosures: The authors have reported to CHEST that no potential confl icts of interest exist with any companies/organizations whose products or services may be dis-cussed in this article. Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

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DOI 10.1378/chest.10-2439; Prepublished online March 10, 2011; 2011;139; 1354-1360Chest

Oriol Roca, Sandra Trefler, Joaquim Gea, Joan R. Masclans and Jordi RelloAlejandro Rodríguez, Thiago Lisboa, Jorge Solé-Violán, Federico Gómez,Impact of Nonexacerbated COPD on Mortality in Critically Ill Patients

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