Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes. METHODS: All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio. RESULTS: In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008). CONCLUSIONS: Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.

Fibroblast viability and phenotypic changes within glycated stiffened three-dimensional collagen matrices.

BACKGROUND: There is growing interest in the development of cell culture assays that enable the rigidity of the extracellular matrix to be increased. A promising approach is based on three-dimensional collagen type I matrices that are stiffened by cross-linking through non-enzymatic glycation with reducing sugars. METHODS: The present study evaluated the biomechanical changes in the non-enzymatically glycated type I collagen matrices, including collagen organization, the advanced glycation end products formation and stiffness achievement. Gels were glycated with ribose at different concentrations (0, 5, 15, 30 and 240 mM). The viability and the phenotypic changes of primary human lung fibroblasts cultured within the non-enzymatically glycated gels were also evaluated along three consecutive weeks. Statistical tests used for data analyze were Mann-Whitney U, Kruskal Wallis, Student's t-test, two-way ANOVA, multivariate ANOVA, linear regression test and mixed linear model. RESULTS: Our findings indicated that the process of collagen glycation increases the stiffness of the matrices and generates advanced glycation end products in a ribose concentration-dependent manner. Furthermore, we identified optimal ribose concentrations and media conditions for cell viability and growth within the glycated matrices. The microenvironment of this collagen based three-dimensional culture induces α-smooth muscle actin and tenascin-C fibroblast protein expression. Finally, a progressive contractile phenotype cell differentiation was associated with the contraction of these gels. CONCLUSIONS: The use of non-enzymatic glycation with a low ribose concentration may provide a suitable model with a mechanic and oxidative modified environment with cells embedded in it, which allowed cell proliferation and induced fibroblast phenotypic changes. Such culture model could be appropriate for investigations of the behavior and phenotypic changes in cells that occur during lung fibrosis as well as for testing different antifibrotic therapies in vitro.

Gene and Protein Expression of Fibronectin and Tenascin-C in Lung Samples from COPD Patients.

PURPOSE: Fibronectin (Fn) and tenascin-C (TnC) are two extracellular matrix proteins associated with remodeling changes. Fn and TnC gene and protein expression in lung tissue, including their predominant location in bronchial and pulmonary artery structures, have not yet been fully evaluated. The aim of the present study was to assess: (1) gene expression of Fn and TnC in lung samples from chronic obstructive pulmonary disease (COPD) and non-COPD subjects; and (2) protein content and location of Fn and TnC in both groups. METHODS: Consecutive subjects requiring lung resection due to lung cancer surgery were included. Lung specimens were examined for gene expression by quantitative real-time PCR (values expressed as fold change ratio). The analysis of their protein content and location was performed by western blot and immunohistochemical studies, respectively. Patients were divided into two cohorts according to COPD status. RESULTS: A total of 41 patients (20 with COPD and 21 without COPD) were included. An enhanced Fn gene expression was observed in the COPD group compared to the non-COPD group (4.73 ± 0.54 vs. 2.65 ± 0.57; P = 0.012), whereas no differences in gene TnC expression were observed (2.91 ± 0.44 vs. 2.60 ± 0.48; P = 0.633). No differences in lung protein content and location were found between groups. Immunohistochemical evaluation showed a predominantly vascular and bronchial location of Fn and TnC in both groups. CONCLUSIONS: An enhanced lung gene expression of Fn was observed in COPD subjects compared to non-COPD subjects. No differences were found in Fn protein expression or in TnC gene or protein expression among groups.

Roflumilast added to triple therapy in patients with severe COPD: a real life study.

BACKGROUND: Roflumilast is used in severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. However, limited information is available on its impact in a "real-life" population that may be receiving triple therapy. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of roflumilast in COPD patients already receiving triple therapy (long-acting ß-agonist/inhaled corticosteroids and long-acting muscarinic antagonist). METHODS: Prospective registry that included COPD patients who were prescribed roflumilast added to triple therapy. The yearly rate of all COPD exacerbations before and after roflumilast and side effects related to the drug were registered. RESULTS: Among 55 patients prescribed 500 mg of roflumilast. Only 50.9% (n = 28) completed 1 year of therapy (roflumilast group). A reduction of all exacerbations with roflumilast was observed (2.75 ± 0.29 vs. 3.57 ± 0.26; P = 0.022), with a particular benefit in patients with ≥4 exacerbations prior to initiating therapy (3.55 ± 0.51 vs. 5.00 ± 0.30; P = 0.034). Side effects (mainly gastrointestinal) and treatment discontinuation occurred in 69.1% and 49.1% of the overall population, respectively. CONCLUSIONS: Roflumilast, when added to triple therapy, reduces exacerbations in a "real-life" population of severe COPD patients with frequent exacerbations. However, side effects are more common and lead more frequently to discontinuation of therapy than has been reported in trials.

Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFß1.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs. METHODS: ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis. RESULTS: A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-ß1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA. CONCLUSIONS: The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.

Prognostic value of serum albumin levels in hospitalized adults with community-acquired pneumonia.

OBJECTIVE: To investigate whether serum albumin levels within 24 h of admission correlate with outcomes in community-acquired pneumonia (CAP). METHODS: Observational analysis of a prospective cohort of adults with CAP requiring hospitalization from 1995 through 2011. Serum albumin level was the independent variable. The primary end point was 30-day mortality. RESULTS: During the study period, 3463 patients with CAP required hospitalization. The median value of albumin was 31 g/L (IQR 28-35). As levels of serum albumin decrease, the risk of complications significantly increases (P < .001). Decreased albumin levels were also associated with prolonged time to reach clinical stability (P < .001), prolonged hospital stay (P < .001), ICU admission (P < .001), the need for mechanical ventilation (P < .001), and 30-day mortality (P < .001). After adjusting for potential confounders in a multivariate logistic regression analysis, serum albumin levels at admission (-5 g/L decrease) were independently associated with a higher risk of 30-day mortality (OR 2.11, 95% CI 1.73-2.56). For predicting primary end point, hypoalbuminemia (<30 g/L) significantly increased the area under ROC curves of PSI and CURB-65 scores (P ≤ .02), and identified those patients with higher risk of complications classified into low- and high-risk groups by these scores. CONCLUSIONS: Serum albumin level within 24 h of admission is a good prognostic marker in CAP. Physicians should consider albumin level when evaluating the severity of illness in patients with CAP.

Risk stratification and prognosis of acute cardiac events in hospitalized adults with community-acquired pneumonia.

OBJECTIVE: To determine the risk factors and the prognosis of acute cardiac events in patients with community-acquired pneumonia (CAP). METHODS: Observational analysis of a prospective cohort of hospitalized adults with CAP (1995-2010). A logistic regression analysis was performed to identify predictors for acute cardiac events and mortality. RESULTS: Of 3921 patients with CAP, 315 (8%) had one or more acute cardiac events during hospitalization (199 new-onset or worsening cardiac arrhythmias, 118 new-onset or worsening congestive heart failure and/or 30 myocardial infarction). In the multivariate analysis, factors associated with these events were age >65 years, chronic heart disease, chronic kidney disease, tachycardia, septic shock, multilobar pneumonia, hypoalbuminemia, and pneumococcal pneumonia. A rule based on these variables had an area under ROC curve of 0.73 (95% CI 0.70-0.76) to predict acute cardiac events. These complications occurred in 2.8% of patients classified in the low-risk (≤3 points), 9.7% in the intermediate-risk (4-5 points) and 21.2% in the high-risk (≥6 points) groups (P < .001). The overall case fatality rate was higher in patients who had acute cardiac events (19.4% vs. 6.4%; P < .001). CONCLUSION: Acute cardiac events occur frequently during hospitalization for CAP and are associated with poor prognosis. A simple rule based on demographic and clinical features may help identify patients at higher risk of these complications.

Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years.

Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995-2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively). The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV-V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001). Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01-8.62), macrolide use (OR, 2.40; 95% CI, 1.03-5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01-8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52-23.4). In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

Effect of a 3-step critical pathway to reduce duration of intravenous antibiotic therapy and length of stay in community-acquired pneumonia: a randomized controlled trial.

BACKGROUND: The length of hospital stay (LOS) for community-acquired pneumonia (CAP) varies considerably, even though this factor has a major impact on the cost of care. We aimed to determine whether the use of a 3-step critical pathway is safe and effective in reducing duration of intravenous antibiotic therapy and length of stay in hospitalized patients with CAP. METHODS: We randomly assigned 401 adults who required hospitalization for CAP to follow a 3-step critical pathway including early mobilization and use of objective criteria for switching to oral antibiotic therapy and for deciding on hospital discharge or usual care. The primary end point was LOS. Secondary end points were the duration of intravenous antibiotic therapy, adverse drug reactions, need for readmission, overall case-fatality rate, and patients' satisfaction. RESULTS: Median LOS was 3.9 days in the 3-step group and 6.0 days in the usual care group (difference, -2.1 days; 95% CI, -2.7 to -1.7; P < .001). Median duration of intravenous antibiotic therapy was 2.0 days in the 3-step group and 4.0 days in the usual care group (difference, -2.0 days; 95% CI, -2.0 to -1.0; P < .001). More patients assigned to usual care experienced adverse drug reactions (4.5% vs 15.9% [difference, -11.4 percentage points; 95% CI, -17.2 to -5.6 percentage points; P < .001]). No significant differences were observed regarding subsequent readmissions, case fatality rate, and patients' satisfaction with care. CONCLUSIONS: The use of a 3-step critical pathway was safe and effective in reducing the duration of intravenous antibiotic therapy and LOS for CAP and did not adversely affect patient outcomes. Such a strategy will help optimize the process of care of hospitalized patients with CAP, and hospital costs would be reduced. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN17875607.

Community-acquired pneumonia in patients with liver cirrhosis: clinical features, outcomes, and usefulness of severity scores.

We performed an observational analysis of a prospective cohort of nonimmunocompromised hospitalized adults with community-acquired pneumonia (CAP) to determine the epidemiology, clinical features, and outcomes of patients with liver cirrhosis. We also analyzed the prognostic value of several severity scores. Of 3420 CAP episodes, 90 occurred in patients with liver cirrhosis. The median value of the Model for End-Stage Liver Disease (MELD) was 14 (range, 6-36). On the Child-Pugh (CP) score, 56% of patients were defined as grade B and 22% as grade C. Patients with liver cirrhosis were younger (61.8 vs. 66.8 yr; p = 0.001) than patients without cirrhosis, more frequently presented impaired consciousness at admission (33% vs. 14%; p < 0.001) and septic shock (13% vs. 6%; p = 0.011), and were more commonly classified in high-risk Pneumonia Severity Index (PSI) classes (classes IV-V) (74% vs. 58%; p = 0.002). Streptococcus pneumoniae (47% vs. 33%; p = 0.009) and Pseudomonas aeruginosa (4.4% vs. 0.9%; p = 0.001) were more frequently documented in patients with cirrhosis. Bacteremia was also more common in these patients (22% vs. 13%; p = 0.023). Areas under the curve (AUCs) from disease-specific scores (MELD, CP, PSI, and CURB-65 [confusion, urea, respiratory rate, blood pressure, and age ≥65 yr]) were comparable in predicting severe disease (30-d mortality and intensive care unit [ICU] admission). A new score based on MELD, multilobar pneumonia, and septic shock at admission (MELD-CAP) had an AUC of 0.945 (95% confidence interval [CI], 0.872-0.983) for predicting severe disease and was significantly different from other scores. Early (5.6% vs. 2.1%; p = 0.048) and overall (14.4% vs. 7.4%; p < 0.024) mortality rates were higher in cirrhotic patients than in patients without cirrhosis. Factors associated with mortality were impaired consciousness, multilobar pneumonia, ascites, acute renal failure, bacteremia, ICU admission, and MELD score. Among the severity scores, MELD-CAP was the only score associated with severe disease (odds ratio [OR], 1.33; 95% CI, 1.09-1.52) and mortality (OR, 1.21; 95% CI, 1.03-1.42). In conclusion, CAP in patients with liver cirrhosis presents a distinctive clinical picture and is associated with higher mortality than is found in patients without cirrhosis. The severity of hepatic dysfunction plays an important role in the development of adverse events. Cirrhosis-specific scores may be useful for predicting and stratifying cirrhotic patients with CAP who have a high risk of severe disease.

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial.

INTRODUCTION: The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. METHODS: This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. RESULTS: Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. CONCLUSIONS: MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission. TRIAL REGISTRATION: International Standard Randomized Controlled Trials Register, ISRCTN22426306.

Outpatient treatment of Pseudomonas aeruginosa bronchial colonization with long-term inhaled colistin, tobramycin, or both in adults without cystic fibrosis.

STUDY OBJECTIVE: To compare clinical and microbiologic outcomes in adults without cystic fibrosis who had Pseudomonas aeruginosa bronchial colonization and were receiving inhaled colistin or colistin plus tobramycin with those who were receiving inhaled tobramycin as outpatient treatment. DESIGN: Prospective, observational cohort study. SETTING: Referral pneumology service at a tertiary university care hospital. PATIENTS: Eighty-one Caucasian adults without cystic fibrosis who received 97 courses of inhaled colistin alone, colistin plus tobramycin, or inhaled tobramycin alone as outpatient treatment of P. aeruginosa bronchial colonization between January 2004 and December 2008. MEASUREMENTS AND MAIN RESULTS: The frequency and duration of hospitalizations for respiratory exacerbations were the primary outcomes compared among treatment groups. Secondary outcomes were emergence of bacterial resistance, antibiotic use during admission, emergence of other opportunistic microorganisms, achievement of sustained P. aeruginosa eradication in the airways, and mortality, as well as safety and changes in respiratory function. No significant differences between colistin and tobramycin were found in the mean number of hospital admissions, duration of hospitalizations, duration of antibiotic treatment, adverse events, mortality, or emergence of other opportunistic microorganisms. Emergence of resistance to colistin was lower than resistance to tobramycin (hazard ratio 0.09, 95% confidence interval [CI] 0.03-0.32). Patients treated with both inhaled antibiotics had fewer days of hospitalization and fewer days of antibiotic use than those treated with tobramycin alone (relative risk [RR] 0.33, 95% CI 0.10-1.12, and RR 0.27, 95% CI 0.08-0.93, respectively). CONCLUSION: Results with colistin were similar to those with tobramycin for inhaled treatment of P. aeruginosa colonization in this population; however, combined use of colistin and tobramycin appeared to be associated with fewer days of hospitalization and shorter duration of antibiotic treatment. Prospective, double-blind, placebo-controlled trials of outpatient nebulized antibiotics, especially colistin plus tobramycin, should be performed to ascertain the efficacy of this therapy for treatment of P. aeruginosa colonization in patients without cystic fibrosis.

Epidemiology, clinical features and outcomes of pneumonia in patients with chronic kidney disease.

BACKGROUND: Although infection remains among the most common causes of morbidity and mortality in patients with chronic kidney disease (CKD), data on epidemiology, clinical features and outcomes of pneumonia in this population are scarce. METHODS: Observational analysis of a prospective cohort of hospitalized adults with pneumonia, between 13 February 1995 and 30 April 2010, in a tertiary teaching hospital. CKD patients, defined as patients with a baseline glomerular filtration rate <60 mL/min/1.73 m(2), were compared with non-CKD patients. RESULTS: During the study period, 3800 patients with pneumonia required hospitalization. Two-hundred and three (5.3%) patients had CKD, of whom 46 were on dialysis therapy. Patients with CKD were older (77 versus 70 years; P < 0.001), were more likely to have comorbidities (82.3 versus 63.3%; P < 0.001) and more commonly classified into high-risk pneumonia severity index classes (89.6 versus 57%; P < 0.001) than were the remaining patients. Streptococcus pneumoniae was the most frequent pathogen (28.1 versus 34.7%; P = 0.05). Mortality was higher in patients with CKD (15.8 versus 8.3%; P < 0.001). Among CKD patients, age [+1 year increase; adjusted odds ratio, 1.25; 95% confidence interval (CI) 1.07-1.46] and cardiac complications during hospitalization (adjusted odds ratio, 9.23; 95% CI 1.39-61.1) were found to be independent risk factors for mortality, whereas prior pneumococcal vaccination (adjusted odds ratio, 0.05; 95% CI 0.005-0.69) and leukocytosis at hospital admission (adjusted odds ratio, 0.10; 95% CI 0.01-0.64) were protective factors. CONCLUSIONS: Pneumonia is a serious complication in CKD patients. Independent factors for mortality are older age and cardiac complications, whereas prior pneumococcal vaccination and leucokytosis at hospital admission are protective factors. These findings should encourage physicians to increase pneumococcal vaccine coverage among CKD patients.

[Factors associated with prolonged hospital stay in community-acquired pneumonia]. / Factores relacionados con una estancia media hospitalaria prolongada en la neumonía adquirida en la comunidad.

INTRODUCTION: The length of hospital stay in patients with community-acquired pneumonia (CAP) varies considerably, even though this factor has a great impact on the cost of care for this condition. The objective of this study was to identify factors associated with prolonged hospitalization in these patients (>8 days). METHODS: Observational analysis of a prospective cohort of nonimmunosuppressed adults with CAP requiring hospitalization from 1995 through 2006. RESULTS: We documented a total of 2688 consecutive episodes of CAP. Patients who required intensive care unit admission from the emergency room (n=107), those who died during hospitalization (n=200), and patients hospitalized for more than 30 days (n=60) were excluded from the analysis. The median duration of hospital stay was 8 days (IQR, 6-11). Factors independently associated with prolonged hospital stay by stepwise multiple logistic regression analysis were advanced age (OR=1.58; 95% CI, 1.002-2.503), alcohol abuse (OR=2.07; 95% CI, 1.341-3.199), high-risk Pneumonia Severity Index class (OR=1.72; 95% CI, 1.094-2.703), aspiration pneumonia (OR=4.57; 95% CI, 1.085-19.285), pleural empyema (OR=3.73; 95% CI, 1.978-7.04), and time to clinical stability (OR=1.13; 95% CI, 1.065-1.196). CONCLUSIONS: Several factors that were independently associated with longer hospital stay in adult patients with CAP. These factors should be considered when evaluating the adequacy of the duration of hospitalization in a specific center and when designing future studies investigating new strategies to reduce the length of hospital stay.

Factores relacionados con una estancia media hospitalaria prolongada en la neumonía adquirida en la comunidad / Factors associated with prolonged hospital stay in community-acquired pneumonia

Introducción: existen diferencias considerables en la duración de la estancia media de los pacientes hospitalizados por neumonía adquirida en la comunidad (NAC). La estancia media es la variable con mayor impacto en el coste económico del manejo de la NAC. El objetivo de nuestro estudio fue identificar los factores relacionados con una estancia media hospitalaria prolongada (>8 días). Métodos: estudio observacional de una cohorte prospectiva de pacientes adultos no inmunodeprimidos con NAC que precisaron hospitalización entre 1995 y 2006. Resultados: se documentaron 2.688 episodios consecutivos de NAC. Se excluyó del análisis a los pacientes que precisaron ingreso en UCI desde el servicio de urgencias (n=107), los fallecidos durante la hospitalización (n=200) o aquellos con una estancia media mayor de 30 días (n=60). La mediana de la duración del ingreso fue 8 días (intervalo, 6¿11). Los factores relacionados con una estancia media prolongada en el análisis multivariable fueron la edad avanzada (riesgo relativo [RR]=1,58; intervalo de confianza [IC] del 95%, 1,002¿2,503), el abuso de alcohol (RR=2,07; IC del 95%, 1,341¿3,199), la gravedad de la NAC (RR=1,72; IC del 95%, 1,094¿2,703), la neumonía aspirativa (RR=4,57; IC del 95%, 1,085¿19,285), el derrame pleural complicado (RR=3,73; IC del 95%, 1,978¿7,04) y el tiempo hasta la estabilidad clínica (RR=1,13; IC del 95%, 1,065¿1,196). Conclusiones: los factores identificados deberían ser considerados al evaluar la idoneidad de la duración del ingreso hospitalario en la NAC en una institución determinada, así como en el diseño de estudios que propongan nuevas estrategias para reducir la estancia media (AU)

Introduction: The length of hospital stay in patients with community-acquired pneumonia (CAP) varies considerably, even though this factor has a great impact on the cost of care for this condition. The objective of this study was to identify factors associated with prolonged hospitalization in these patients (>8 days). Methods: Observational analysis of a prospective cohort of nonimmunosuppressed adults with CAP requiring hospitalization from 1995 through 2006. Results: We documented a total of 2688 consecutive episodes of CAP. Patients who required intensive care unit admission from the emergency room (n=107), those who died during hospitalization (n=200), and patients hospitalized for more than 30 days (n=60) were excluded from the analysis. The median duration of hospital stay was 8 days (IQR, 6-11). Factors independently associated with prolonged hospital stay by stepwise multiple logistic regression analysis were advanced age (OR=1.58; 95% CI, 1.002¿2.503), alcohol abuse (OR=2.07; 95% CI, 1.341¿3.199), high-risk Pneumonia Severity Index class (OR=1.72; 95% CI, 1.094¿2.703), aspiration pneumonia (OR=4.57; 95% CI, 1.085¿19.285), pleural empyema (OR=3.73; 95% CI, 1.978¿7.04), and time to clinical stability (OR=1.13; 95% CI, 1.065¿1.196). Conclusions: Several factors that were independently associated with longer hospital stay in adult patients with CAP. These factors should be considered when evaluating the adequacy of the duration of hospitalization in a specific center and when designing future studies investigating new strategies to reduce the length of hospital stay (AU)

Health care-associated pneumonia requiring hospital admission: epidemiology, antibiotic therapy, and clinical outcomes.

BACKGROUND: Health care-associated pneumonia (HCAP) has been proposed as a new category of respiratory infection. However, limited data exist to validate this entity. We aimed to ascertain the epidemiology, causative organisms, antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for HCAP requiring hospitalization. METHODS: Observational analysis of a prospective cohort of nonseverely immunosuppressed hospitalized adults with pneumonia. Patients who had recent contact with the health care system through nursing homes, home health care programs, hemodialysis clinics, or prior hospitalization were considered to have HCAP. RESULTS: Of 727 cases of pneumonia, 126 (17.3%) were HCAP and 601 (82.7%) were community acquired. Compared with patients with community-acquired pneumonia, patients with HCAP were older (mean age, 69.5 vs 63.7 years; P < .001), had greater comorbidity (95.2% vs 74.7%; P < .001), and were more commonly classified into high-risk pneumonia severity index classes (67.5% vs 48.8%; P < .001). The most common causative organism was Streptococcus pneumoniae in both groups (27.8% vs 33.9%). Drug-resistant pneumococci were more frequently encountered in cases of HCAP. Legionella pneumophila was less common in patients with HCAP (2.4% vs 8.8%; P = .01). Aspiration pneumonia (20.6% vs 3.0%; P < .001), Haemophilus influenzae (11.9% vs 6.0%; P = .02), Staphylococcus aureus (2.4% vs 0%; P = .005), and gram-negative bacilli (4.0% vs 1.0%; P = .03) were more frequent in HCAP. Patients with HCAP more frequently received an initial inappropriate empirical antibiotic therapy (5.6% vs 2.0%; P = .03). The overall case-fatality rate (< 30 days) was higher in patients with HCAP (10.3% vs 4.3%; P = .007). CONCLUSIONS: At present, a substantial number of patients initially seen with pneumonia in the emergency department have HCAP. These patients require a targeted approach when selecting empirical antibiotic therapy.

Outcome of non-invasive domiciliary ventilation in elderly patients.

STUDY OBJECTIVES: To analyze the short- and long-term effects of domiciliary non-invasive ventilation (NIV) in the elderly. METHODS: From 1990 to 2005 all patients who initiated NIV at age 75 or older were included in the study. The mean follow-up period was 36 (24) months. Data were obtained from a database record. RESULTS: Forty-three patients, mean age 77 (1.9) years and hypercapnic respiratory failure secondary to restrictive, neuromuscular or hypoventilatory disease were included. The short-term effects included a significant improvement in arterial blood gases and nocturnal desaturations during NIV compared to baseline: PaO(2) increased a mean of 19 mmHg (P<0.0001), PaCO(2) decreased a mean of 16 mmHg (P<0.0001) and nocturnal time with SaO(2)<90% decreased a mean of 72% (P<0.0001). Arterial blood gases while breathing room air also improved significantly at 6 months after NIV initiation. Five patients (11%) discontinued treatment; this group did not differ from patients who continued NIV. Mean compliance was 8.3 (3.1)h/day. In the long-term effects, we observed that the initial improvement of arterial blood gases breathing room air was maintained throughout the followup period. The number of hospital admissions and days of hospital stay decreased significantly (P<0.0001 and 0.001, respectively) after NIV initiation. The poorest survival was observed in ALS patients (median 10.9 (2.3) months) significantly lower than the survival for the other diagnostic groups (median 58.5 (4.8) months), P=0.0013. CONCLUSIONS: NIV is an effective treatment in the elderly. It improves arterial blood gases and nocturnal desaturations, decreases hospital admissions and is associated with long survival. So advanced age should not be considered as an exclusion criteria to prescribe NIV.

Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the impact of systematic respiratory assessment and bulbar involvement.

STUDY OBJECTIVES: To analyze (1) the impact of a protocol of early respiratory evaluation of the indications for home mechanical ventilation (HMV) in patients with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and of bulbar involvement on the survival of patients receiving noninvasive ventilation (NIV). DESIGN AND SETTING: Retrospective study in a tertiary care referral center. PATIENTS: HMV was indicated in 86 patients with ALS, with 22 patients (25%) presenting with intolerance to treatment associated with bulbar involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to initiating the protocol (group A) and in the remaining 49 patients after protocol initiation (group B). RESULTS: In group A, the majority of patients began treatment with HMV during an acute episode requiring ICU admission (p = 0.001) and tracheal ventilation (p = 0.025), with a lower percentage of patients beginning HMV treatment without respiratory insufficiency (p = 0.013). No significant differences in survival rates were found between groups A and B among patients treated with NIV. Greater survival was observed in group B (p = 0.03) when patients with bulbar involvement were excluded (96%). Patients without bulbar involvement at the start of therapy with NIV presented a significantly better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement to be an independent prognostic factor for survival (relative risk, 1.6; 95% confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in survival were observed between patients with bulbar involvement following treatment with NIV and those with intolerance, except for the subgroup of patients who began NIV treatment with hypercapnia (p = 0.0002). CONCLUSIONS: Early systematic respiratory evaluation in patients with ALS is necessary to improve the results of HMV. Further studies are required to confirm the benefits of NIV treatment in patients with bulbar involvement, especially in the early stages.

Clinical outcomes for hospitalized patients with Legionella pneumonia in the antigenuria era: the influence of levofloxacin therapy.

BACKGROUND: Although the reduction in case-fatality rate recently observed among patients with Legionella pneumonia has been largely attributed to the progressive utilization of urine antigen testing, other factors, such as changes in empirical antibiotic therapy, may also have contributed. We have analyzed more-recent outcomes of Legionella pneumonia in an institution where urine antigen testing was reflexly performed in cases of community-acquired pneumonia without an etiological diagnosis. METHODS: From a prospective series of 1934 consecutive cases of community-acquired pneumonia in nonimmunocompromised adults, 139 cases of Legionella pneumophila pneumonia were selected for observational review. Legionella cases were analyzed for outcome with respect to antibiotic treatment, mortality, complications, length of stay, time to defervescence, and stability. RESULTS: The early case-fatality rate was 2.9% (4 of 139 patients), and the overall case-fatality rate was 5% (7 of 139 patients). One hundred twenty patients (86.3%) received an appropriate initial therapy, which included macrolides (i.e., erythromycin or clarithromycin) in 80 patients and levofloxacin in 40. Levofloxacin progressively replaced macrolides as the initial therapy during the study period. Compared with patients who received macrolides, patients who received levofloxacin had a faster time to defervescence (2.0 vs. 4.5 days; P<.001) and to clinical stability (3 vs. 5 days; P=.002). No differences were found regarding the development of complications (25% vs. 25%; P=.906) and case-fatality rate (2.5% vs. 5%; P=.518). The median length of hospital stay was 8 days in patients treated with levofloxacin and 10 days in those who received macrolides (P=.014). CONCLUSIONS: Legionella pneumonia is still associated with significant complications in hospitalized patients, but recent mortality is substantially lower than that found in earlier series. Levofloxacin may produce a faster clinical response than older macrolides, allowing for shorter hospital stay.