This study suggests that for older patients hospitalized with pneumonia, use prior to hospitalization of statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers may be potentially beneficial. In addition, continuing these medications during hospitalization may also be potentially beneficial for patients with pneumonia.
Background. Studies suggest that statins and angiotensin-converting enzyme (ACE) inhibitors might be beneficial for the treatment of infections. Our purpose was to examine the association of statin, ACE inhibitor, and angiotensin II receptor blocker (ARB) use with pneumonia-related outcomes.
Methods. We conducted a retrospective cohort study using Department of Veterans Affairs data of patients aged ≥65 years hospitalized with pneumonia. We performed propensity-score matching for 3 medication classes simultaneously.
Results. Of 50 119 potentially eligible patients, we matched 11 498 cases with 11 498 controls. Mortality at 30 days was 13%; 34% used statins, 30% ACE inhibitors, and 4% ARBs. In adjusted models, prior statin use was associated with decreased mortality (odds ratio [OR], 0.74; 95% confidence interval [CI], .68–.82) and mechanical ventilation (OR, 0.81; 95% CI, .70–.94), and inpatient use with decreased mortality (OR, 0.68; 95% CI, .59–.78) and mechanical ventilation (OR, 0.68; 95% CI, .60–.90). Prior (OR, 0.88; 95% CI, .80–.97) and inpatient (OR, 0.58; 95% CI, .48–.69) ACE inhibitor use was associated with decreased mortality. Prior (OR, 0.73; 95% CI, .58–.92) and inpatient ARB use (OR, 0.47; 95% CI, .30–.72) was only associated with decreased mortality. Use of all 3 medications was associated with reduced length of stay.
Conclusions. Statins, and to a lesser extent ACE inhibitors and ARBs, are associated with improved pneumonia-related outcomes. Prospective cohort and randomized controlled trials are needed to examine potential mechanisms of action and whether acute initiation at the time of presentation with these infections is beneficial.
To test the reliability, validity and responsiveness of the 13-item Shortness of Breath with Daily Activities (SOBDA) questionnaire, and determine the threshold for response and minimal important difference (MID).
6 week, randomised, double-blind, placebo-controlled study.
40 centres in the USA between 29 October 2009 and 1 July 2010.
Primary and secondary outcome measures
547 patients with chronic obstructive pulmonary disease (COPD) were enrolled and 418 entered the 2-week run-in period. Data from the run-in period were collected to test internal consistency, test–retest reliability, convergent validity and known-groups validity of the SOBDA. Three hundred and sixty six patients were randomised 2:2:1 to fluticasone propionate/salmeterol 250/50 µg, salmeterol 50 µg or placebo, twice daily. Results from the SOBDA questionnaire, Patient Global Assessment of Change Question, modified Medical Research Council Dyspnoea Scale (mMRC), Clinician Global Impression of Dysponea Severity (CGI-S), Clinician Global Impression of Change Question and Chronic Respiratory Disease Questionnaire self-administered standardised version (CRQ-SAS) were evaluated; spirometry and safety parameters were measured. Study endpoints were selected to investigate the cross-sectional and longitudinal validity of the SOBDA questionnaire in relation to the clinical criteria.
Internal consistency of the SOBDA questionnaire (Cronbach α) was 0.89. Test–retest reliability (intraclass correlation) was 0.94. The SOBDA weekly scores correlated with the patient-reported and clinician-reported mMRC, CGI-S and CRQ-SAS dyspnoea domain scores (0.29, 0.24, 0.24 and –0.68, respectively). The SOBDA weekly scores differentiated between the responders and the non-responders as rated by the patients and the clinicians. Anchor-based and supportive distribution-based analyses produced a range of the potential values for the threshold for the responders and MID.
The 13-item SOBDA questionnaire is reliable, valid and responsive to change in patients with COPD. On using anchor-based methods, the proposed responder threshold shows a −0.1 to −0.2 score change. A specific threshold value will be identified as more data are generated from future clinical trials.
NCT00984659; GlaxoSmithKline study number: ASQ112989.
THORACIC MEDICINE; RESPIRATORY MEDICINE (see Thoracic Medicine)
Patients with chronic obstructive pulmonary disease (COPD) can be categorized as having frequent (FE) or infrequent (IE) exacerbations depending on whether they respectively experience two or more, or one or zero exacerbations per year. Although most patients do not change category from year to year, some will, and the factors associated with this behaviour have not been examined.
1832 patients completing two year follow-up in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study were examined at baseline and then yearly. Exacerbations were defined by health care utilisation. Patient characteristics compared between those patients who did or did not change exacerbation category from year 1 to year 2.
Between years 1 and 2, 221 patients (17%) changed from IE to FE and 210 patients (39%) from FE to IE. More severe disease was associated with changing from IE to FE and less severe disease from FE to IE. Over the preceding year, small falls in FEV1 and 6-minute walking distance were associated with changing from IE to FE, and small falls in platelet count associated with changing from FE to IE.
No parameter clearly predicts an imminent change in exacerbation frequency category.
SCO104960, clinicaltrials.gov identifier NCT00292552
COPD; Exacerbations; Exacerbation frequency; Exacerbation phenotype
Tiotropium bromide is an effective therapy for COPD patients. Comparing across programs tiotropium Respimat® Soft Mist™ inhaler was at least as efficacious as tiotropium HandiHaler®, however, concerns have been raised about tiotropium’s safety when given via Respimat®.
The TIOSPIR® trial (NCT01126437) compares the safety and efficacy of tiotropium Respimat® 5 μg once daily (marketed) and 2.5 μg once daily (investigational) with tiotropium HandiHaler® 18 μ once daily (marketed). The hypotheses to be tested are 1). that tiotropium Respimat® 5 μg once daily and Respimat® 2.5 μg once daily are non-inferior to HandiHaler® in terms of all-cause mortality, and 2). that tiotropium Respimat® 5 μg once daily is superior to HandiHaler® in terms of time to first exacerbation. A spirometry substudy evaluates the bronchodilator efficacy. The trial is a randomized, double-blind, double dummy, event-driven, parallel group study. Participants can use any background treatment for COPD except inhaled anticholinergic agents. The study encompasses a wide range of COPD patients, e.g. patients with stable cardiac diseases including arrhythmia can be included. Clinical sites are international and include both primary care as well as specialists.
To date, over 17,000 participants have been randomized from over 1200 sites in 50 countries with an anticipated treatment duration of 2–3 years.
TIOSPIR® will provide precise estimates of the relative safety and efficacy of the Respimat® and HandiHaler® formulations of tiotropium, assess potential dose-dependence of important outcomes and provide information on the clinical epidemiology of COPD in a large international patient cohort.
Tiotropium; COPD; Respimat® Soft Mist™ Inhaler; HandiHaler®
It has been suggested that fluid accumulation may delay recognition of acute kidney injury (AKI). We sought to determine the impact of fluid balance on the incidence of non-dialysis requiring AKI in patients with acute lung injury and to describe associated outcomes, including mortality.
Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative versus liberal fluid management and of management guided by a central venous versus pulmonary artery catheter.
Setting and Patients
1000 patients at ARDS Network hospitals.
Measurements and Main Results
The incidence of AKI, defined as an absolute rise in creatinine of ≥ 0.3 mg/dL or a relative change of > 50% over 48 hours, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of AKI before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57 versus 51%, p = 0.04). After adjustment for fluid balance, the incidence of AKI was greater in those managed with the liberal fluid protocol (66 versus 58%, p = 0.007). Patients who met AKI criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet AKI criteria both before and after adjustment for fluid balance (31 versus 12%, p < 0.001) and those who had AKI before but not after adjustment for fluid balance (31 versus 11%, p = 0.005). The mortality of those patients meeting AKI criteria after but not before adjustment for fluid balance was similar to patients with AKI both before and after adjustment for fluid balance (31% versus 38%, p = 0.18).
Fluid management influences serum creatinine and therefore the diagnosis of AKI using creatinine-based definitions. Patients with “unrecognized” AKI that is identified after adjusting for positive fluid balance have high mortality rates, and patients who have AKI before but not after adjusting for fluid balance have low mortality rates. Future studies of AKI should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.
Acute kidney injury; acute lung injury; acute respiratory distress syndrome; fluid balance; creatinine; mortality
Rationale: Treatment with inhaled corticosteroids (ICS) for those with chronic obstructive pulmonary disease (COPD) has been shown to be associated with an increased incidence of pneumonia. However, it is unclear if this is associated with increased mortality.
Objectives: The aim of this study was to examine the effects of prior use of ICS on clinical outcomes for patients with COPD hospitalized with pneumonia.
Methods: We conducted a retrospective cohort study using the national administrative databases of the Department of Veterans Affairs. Eligible patients had a preexisting diagnosis of COPD, had a discharge diagnosis of pneumonia, and received treatment with one or more appropriate pulmonary medications before hospitalization. Outcomes included mortality, use of invasive mechanical ventilation, and vasopressor use.
Measurements and Main Results: There were 15,768 patients (8,271 with use of ICS and 7,497 with no use of ICS) with COPD who were hospitalized for pneumonia. There was also a significant difference for 90-day mortality (ICS 17.3% vs. no ICS 22.8%; P < 0.001). Multilevel regression analyses demonstrated that prior receipt of ICS was associated with decreased mortality at 30 days (odds ratio [OR] 0.80; 95% confidence interval [CI], 0.72–0.89) and 90 days (OR 0.78; 95% CI, 0.72–0.85), and decreased use of mechanical ventilation (OR 0.83; 95% CI, 0.72–0.94). There was no significant association between receipt of ICS and vasopressor use (OR 0.88; 95% CI, 0.74–1.04).
Conclusions: For patients with COPD, prior use of ICS is independently associated with decreased risk of short-term mortality and use of mechanical ventilation after hospitalization for pneumonia.
inhaled corticosteroids; pneumonia; chronic obstructive pulmonary disease; mortality
Community-acquired pneumonia (CAP) is a serious condition associated with significant morbidity and potential long-term mortality. Although the majority of patients with CAP are treated as outpatients, the greatest proportion of pneumonia-related mortality and healthcare expenditure occurs among the patients who are hospitalized. There has been considerable interest in determining risk factors and severity criteria assessments to assist with site-of-care decisions. For both inpatients and outpatients, the most common pathogens associated with CAP include Streptococcus pneumoniae, Haemophilus influenzae, group A streptococci and Moraxella catarrhalis. Atypical pathogens, Gram-negative bacilli, methicillin-resistant Staphylococcus aureus (MRSA) and viruses are also recognized aetiological agents of CAP. Despite the availability of antimicrobial therapies, the recent emergence of drug-resistant pneumococcal and staphylococcal isolates has limited the effectiveness of currently available agents. Because early and rapid initiation of empirical antimicrobial treatment is critical for achieving a favourable outcome in CAP, newer agents with activity against drug-resistant strains of S. pneumoniae and MRSA are needed for the management of patients with CAP.
antimicrobial therapy; PSI/CURB-65 score; clinical outcomes
Several studies have suggested an increased risk of cardiovascular events, primarily acute myocardial infarction, around the time of hospital admission for pneumonia. Therefore we examined cardiovascular events, including myocardial infarction, congestive heart failure, unstable angina, stroke, and serious cardiac arrhythmias, within 90 days after hospitalization for pneumonia.
Using data from the administrative databases of the Department of Veterans Affairs, we examined a cohort of subjects hospitalized with pneumonia between October 2001 and September 2007. Subjects were at least 65 years of age. We examined the incidence of myocardial infarction, congestive heart failure, cardiac arrhythmias, unstable angina, and stroke by ICD-9 codes excluding those with a diagnosis prior to the admission for pneumonia.
The cohort comprised 50,119 subjects with a mean age of 77.5 years (SD 6.7 years), and 98% of the cohort was male. The 90-day incidence of cardiovascular events was 1.5% for myocardial infarction, 10.2% for congestive heart failure, 9.5% for arrhythmia, 0.8% for unstable angina, and 0.2% for stroke. The majority of events occurred during the hospitalization for pneumonia.
A clinically important number of subjects in this cohort suffered a cardiovascular event within 90 days of hospital admission, suggesting that such events may have an important role in post-pneumonia mortality. Additional research is needed to determine whether interventions may reduce the number of cardiovascular events after pneumonia.
pneumonia; cardiovascular disease; congestive heart failure; cardiac arrhythmia; myocardial infarction
Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP.
s. pneumoniae; s. aureus; cephalosporins; pneumonia; ceftaroline; community acquired pneumonia
Antibiotics, along with oral corticosteroids, are standard treatments for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The ultimate aims of treatment are to minimize the impact of the current exacerbation, and by ensuring complete resolution, reduce the risk of relapse. In the absence of superiority studies of antibiotics in AECOPD, evidence of the relative efficacy of different drugs is lacking, and so it is difficult for physicians to select the most effective antibiotic. This paper describes the protocol and rationale for MAESTRAL (moxifloxacin in AECBs [acute exacerbation of chronic bronchitis] trial; www.clinicaltrials.gov: NCT00656747), one of the first antibiotic comparator trials designed to show superiority of one antibiotic over another in AECOPD. It is a prospective, multinational, multicenter, randomized, double-blind controlled study of moxifloxacin (400 mg PO [ per os] once daily for 5 days) vs amoxicillin/clavulanic acid (875/125 mg PO twice daily for 7 days) in outpatients with COPD and chronic bronchitis suffering from an exacerbation. MAESTRAL uses an innovative primary endpoint of clinical failure: the requirement for additional or alternate treatment for the exacerbation at 8 weeks after the end of antibiotic therapy, powered for superiority. Patients enrolled are those at high-risk of treatment failure, and all are experiencing an Anthonisen type I exacerbation. Patients are stratified according to oral corticosteroid use to control their effect across antibiotic treatment arms. Secondary endpoints include quality of life, symptom assessments and health care resource use.
AECOPD; moxifloxacin; amoxicillin/clavulanic acid; clinical trial design; exacerbation; antibiotic
Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids. Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.
A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months’ duration was performed. Trials had similar inclusion and exclusion criteria. Exacerbation definition was standardized. Patients were divided into two groups, ie, D (anticholinergics discontinued at randomization, previously prescribed) and ND (anticholinergics not discontinued, not previously prescribed).
Demographics were balanced between the D (n = 5846) and ND (n = 6317) groups, except for higher cumulative smoking (56 pack-years versus 48 pack-years), lower forced expiratory volume in one second (FEV1)/forced vital capacity (43% versus 48%), and lower baseline FEV1 (35.8% predicted versus 42.4% predicted) in the D group. In both groups, tiotropium reduced the risk for an exacerbation (hazard ratio [HR] = 0.83, P < 0.0001 [D] versus 0.79, P < 0.0001 [ND]) and a hospitalized exacerbation (HR = 0.85, P = 0.0467 versus 0.79, P = 0.0094). Tiotropium reduced the number of exacerbations per patient-year (rate ratio [RR] = 0.82, P < 0.0001 [D] versus RR = 0.80, P < 0.0001 [ND]) and associated hospitalizations per patient-year (RR = 0.88, P = 0.015 [D] versus RR = 0.74, P < 0.0001 [ND]).
Tiotropium reduced exacerbations in patients who did and did not have anticholinergics discontinued upon randomization in clinical trials.
chronic obstructive pulmonary disease; clinical trials; exacerbations; inhaled anticholinergics; tiotropium
Chronic obstructive pulmonary disease (COPD) is a leading cause of disability and mortality. Caring for patients with COPD, particularly those with advanced disease who experience frequent exacerbations, places a significant burden on health care budgets, and there is a global need to reduce the financial and personal burden of COPD. Evolving scientific evidence on the natural history and clinical course of COPD has fuelled a fundamental shift in our approach to the disease. The emergence of data highlighting the heterogeneity in rate of lung function decline has altered our perception of disease progression in COPD and our understanding of appropriate strategies for the management of stable disease. These data have demonstrated that early, effective, and prolonged bronchodilation has the potential to slow the rate of decline in lung function and to reduce the frequency of exacerbations that contribute to functional decline. The goals of therapy for COPD are no longer confined to controlling symptoms, reducing exacerbations, and maintaining quality of life, and slowing disease progression is now becoming an achievable aim. A challenge for the future will be to capitalize on these observations by improving the identification and diagnosis of patients with COPD early in the course of their disease, so that effective interventions can be introduced before the more advanced, disabling, and costly stages of the disease. Here we critically review emerging data that underpin the advances in our understanding of the clinical course and management of COPD, and evaluate both current and emerging pharmacologic options for effective maintenance treatment.
COPD; chronic obstructive pulmonary disease; long-acting bronchodilator; early treatment
Many physicians recommend that patients receive follow-up chest imaging after the diagnosis of pneumonia to ensure that a pulmonary malignancy is not missed. However there is little research evidence to support this practice. Our aims were to assess the frequency of the diagnosis of pulmonary malignancy, and to identify risk factors for pulmonary malignancy following hospitalization for pneumonia.
By excluding patients with a prior diagnosis of pulmonary malignancy, we examined the incidence of a new pulmonary malignancy diagnosis in inpatients ≥65 years with a discharge diagnosis of pneumonia in fiscal years 2002–2007, and at least one year of Department of Veterans Affairs outpatient care prior to the index admission.
Of 40,744 patients hospitalized with pneumonia, 3,760 (9.2%) patients were diagnosed with pulmonary malignancy after their index pneumonia admission. Median time to diagnosis was 297 days with only 27% diagnosed within 90-days of admission. Factors significantly associated with a new diagnosis of pulmonary malignancy included history of chronic pulmonary disease, any prior malignancy, white race, being married, and tobacco use. Increasing age, Hispanic ethnicity, need for intensive care unit admission, and a history of congestive heart failure, stroke, dementia, or diabetes with complications were associated with a lower incidence of pulmonary malignancy.
A small, but clinically important, proportion of patients are diagnosed with pulmonary malignancy post-hospitalization for pneumonia. Additional research is needed to examine whether previously undiagnosed pulmonary malignancies may be detected at admission, or soon after, for those hospitalized with pneumonia.
pneumonia; cancer; incidence
Prior research has shown that hypoglycemia is associated with worse outcomes for the elderly, in sepsis, and in children with pneumonia. The purpose of this study was to examine whether hypoglycemia (< 70 mg/dL) is associated with increased 30-day mortality, after adjusting for potential confounders, for adults hospitalized with pneumonia.
A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, and had a chest x-ray consistent with, community-acquired pneumonia. Our primary analysis was a multivariable logistic regression with the dependent variable of 30-day mortality with independent variable of hypoglycemia, diabetes, severity of illness utilizing the Pneumonia Severity Index, and pneumonia-related processes of care.
Data were abstracted on 787 subjects at the two hospitals. Mortality was 8.1% at 30-days. At presentation, 55% of subjects were low risk, 33% were moderate risk, and 12% were high risk. In our cohort 2.8% (n=22) had hypoglycemia at presentation. Unadjusted mortality for those who were hypoglycemic was 27.3% vs. 8.6% for those who were not (p=0.0003). In the multivariable analysis, hypoglycemia (odds ratio 4.1, 95% confidence interval 1.4–11.7) was significantly associated with 30-day mortality.
After adjusting for severity of illness and other potential confounders hypoglycemia is significantly associated with 30-day mortality for patients hospitalized with pneumonia. Patients with hypoglycemia should be placed in closely monitored settings even when by pneumonia specific risk systems they would normally be discharged.
pneumonia; hypoglycemia; mortality
Community-acquired pneumonia continues to have a significant impact on elderly individuals, who are affected more frequently and with more severe consequences than younger populations. As the population ages it is expected that the medical and economic impact of this disease will increase. Despite these concerns, little progress has been made in research specifically focusing on community-acquired pneumonia in the elderly. Data continue to show that a high index of suspicion, early antimicrobial therapy and appropriate medications to cover typical pathogens are extremely important in treating community-acquired pneumonia in older individuals. This review is designed to serve as an update to our previous work published in Aging Health in 2006, with specific emphasis on the most recent evidence published since that time.
aged; microbiology; pneumonia; severity of illness index; therapeutics
African-Americans admitted to U.S. hospitals with community-acquired pneumonia (CAP) are more likely than Caucasians to experience prolonged hospital length of stay (LOS), possibly due to either differential treatment decisions or patient characteristics.
We assessed associations between race and outcomes (Intensive Care Unit [ICU] variables, LOS, 30-day mortality) for African-American or Caucasian patients over 65 years hospitalized in the Veterans Health Administration (VHA) with CAP (2002-2007). Patients admitted to the ICU were analyzed separately from those not admitted to the ICU. VHA patients who died within 30 days of discharge were excluded from all LOS analyses. We used chi-square and Fisher's exact statistics to compare dichotomous variables, the Wilcoxon Rank Sum test to compare age by race, and Cox Proportional Hazards Regression to analyze hospital LOS. We used separate generalized linear mixed-effect models, with admitting hospital as a random effect, to examine associations between patient race and the receipt of guideline-concordant antibiotics, ICU admission, use of mechanical ventilation, use of vasopressors, LOS, and 30-day mortality. We defined statistical significance as a two-tailed p ≤ 0.0001.
Of 40,878 patients, African-Americans (n = 4,936) were less likely to be married and more likely to have a substance use disorder, neoplastic disease, renal disease, or diabetes compared to Caucasians. African-Americans and Caucasians were equally likely to receive guideline-concordant antibiotics (92% versus 93%, adjusted OR = 0.99; 95% CI = 0.81 to 1.20) and experienced similar 30-day mortality when treated in medical wards (adjusted OR = 0.98; 95% CI = 0.87 to 1.10). African-Americans had a shorter adjusted hospital LOS (adjusted HR = 0.95; 95% CI = 0.92 to 0.98). When admitted to the ICU, African Americans were as likely as Caucasians to receive guideline-concordant antibiotics (76% versus 78%, adjusted OR = 0.99; 95% CI = 0.81 to 1.20), but experienced lower 30-day mortality (adjusted OR = 0.82; 95% CI = 0.68 to 0.99) and shorter hospital LOS (adjusted HR = 0.84; 95% CI = 0.76 to 0.93).
Elderly African-American CAP patients experienced a survival advantage (i.e., lower 30-day mortality) in the ICU compared to Caucasians and shorter hospital LOS in both medical wards and ICUs, after adjusting for numerous baseline differences in patient characteristics. There were no racial differences in receipt of guideline-concordant antibiotic therapies.
The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.
We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.
We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.
Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.
Influencing the progression of COPD has long been an elusive goal of drug therapy. Directly or indirectly, this has again been investigated in two of the largest, long-term drug trials in COPD: Towards a Revolution in COPD Health (TORCH) and Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT®). Neither trial achieved statistical significance in their respective primary outcomes; however, both make considerable contributions to understanding of how the progression of COPD may be influenced. The objective of this article is to review the data from these different trials with a view to what can be learnt about the management of COPD. The long-term improvements in lung function, health-related quality of life, and possibly survival from the use of long-acting bronchodilators in these trials suggest an influence on progression of the disease. With the more optimistic view of benefits from drug treatment of COPD that these trials provide, a review of prescribing practices is warranted.
bronchodilators; FEV1; fluticasone; inhaled corticosteroids; mortality; salmeterol; tiotropium
Data on differences in clinical characteristics and management of COPD in different countries and settings are limited. We aimed to characterize the profile of patients with COPD in a number of countries and their treatment in order to evaluate adherence to recommendations of international guidelines.
This was an observational, international, cross-sectional study on patients with physician-diagnosed COPD. Demographic and clinical characteristics, risk factors, and treatment were collected by their physician via an internet web-based questionnaire developed for the study.
A total of 77 investigators from 17 countries provided data on 833 patients. The countries with the highest number of patients included were: Argentina (128), Ecuador (134), Spain (162), and Hong Kong (153). Overall, 79.3% were men and 81% former smokers, with a mean FEV1 = 42.7%, ranging from 34.3% in Hong Kong to 58.8% in Ecuador. Patients reported a mean of 1.6 exacerbations the previous year, with this frequency being significantly and negatively correlated with FEV1(%) (r = −0.256; p < 0.0001). Treatment with short-acting bronchodilators and theophyllines was more frequent in Ecuador and Hong Kong compared with Spain and Argentina, and in patients belonging to lower socioeconomic levels (p < 0.0001 for all comparisons). Inadequacy of treatment with inhaled corticosteroids and theophyllines was high, with significant differences among countries.
Differences in the clinical characteristics and management of COPD were significant across countries. Adherence to international guidelines appears to be low. Efforts should be made to disseminate and adapt guidelines to the socioeconomic reality of different settings.
COPD; epidemiology; EPOCA; socioeconomics
The purpose of this study was to examine whether prior outpatient antibiotic use is associated with increased 30-day mortality, after adjusting for potential confounders, for those subsequently hospitalized with pneumonia.
A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, and had a chest x-ray consistent with, community-acquired pneumonia. Our primary analysis was a multivariable logistic regression with the dependent variable of 30-day mortality.
Data was abstracted on 733 subjects at the two hospitals. Mortality was 8.1% at 30-days. At presentation, 55% of subjects were low risk, 33% were moderate risk, and 12% were high risk. In our cohort 17% (n = 128) of subjects received antibiotics within 30-days of presentation. Unadjusted mortality for those who had received prior antibiotics was 7.0% vs. 8.3% for those who had not (p = 0.6). In the multivariable analysis prior use of antibiotics (odds ratio 0.98, 95% confidence interval 0.5–2.1) was not significantly associated with 30-day mortality.
Receipt of prior outpatient antibiotics is not significantly associated with 30-day mortality for patients hospitalized with pneumonia. Our study supports current efforts to increase the number of patients with pneumonia who are treated as outpatients.
Prediction of death and prolonged mechanical ventilation is important in terms of projecting resource utilization and in establishing protocols for clinical studies of acute lung injury (ALI). We aimed to identify risk factors for a combined end-point of death and/or prolonged ventilator dependence and developed an ALI-specific prediction model.
In this retrospective analysis of three multicenter clinical studies, we identified predictors of death or ventilator dependence from variables prospectively recorded during the first three days of mechanical ventilation. After the prediction model was derived in an international cohort of patients with ALI, it was validated in two independent samples of patients enrolled in a clinical trial involving 17 academic centers and a North American population-based cohort.
A combined end-point of death and/or ventilator dependence at 14 days or later occurred in 68% of patients in the international cohort, 60% of patients in the clinical trial, and 59% of patients in the population-based cohort. In the derivation cohort, a model based on age, oxygenation index on day 3, and cardiovascular failure on day 3 predicted death and/or ventilator dependence. The prediction model performed better in the clinical trial validation cohort (area under the receiver operating curve 0.81, 95% confidence interval 0.77 to 0.84) than in the population-based validation cohort (0.71, 95% confidence interval 0.65 to 0.76).
A model based on age and cardiopulmonary function three days after the intubation is able to predict, moderately well, a combined end-point of death and/or prolonged mechanical ventilation in patients with ALI.
National clinical practice guidelines have recommended specific empiric antimicrobial regimes for patients with severe community-acquired pneumonia. However, evidence confirming improved mortality with many of these regimes is lacking. Our aim was to determine the association between the empiric use of a β-lactam with fluoroquinolone, compared with other recommended antimicrobial therapies, and mortality in patients hospitalized with severe community-acquired pneumonia.
A retrospective observational study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of community-acquired pneumonia and had a chest X-ray and a discharge ICD-9 diagnosis consistent with this. Subjects were excluded if they received 'comfort measures only' during the admission, had been transferred from another acute care hospital, did not meet criteria for severe pneumonia, or were treated with non-guideline-concordant antibiotics. A multivariable logistic regression model was used to assess the association between 30-day mortality and the use of a β-lactam antibiotic with a fluoroquinolone compared with other guideline-concordant therapies, after adjustment for potential confounders including a propensity score.
Data were abstracted on 172 subjects at the two hospitals. The mean age was 63.5 years (SD 15.0). The population was 88% male; 91% were admitted through the emergency department and 62% were admitted to the intensive care unit within the first 24 hours after admission. Mortality was 19.8% at 30 days. After adjustment for potential confounders the use of a β-lactam with a fluoroquinolone (odds ratio 2.71, 95% confidence interval 1.2 to 6.1) was associated with increased mortality.
The use of initial empiric antimicrobial therapy with a β-lactam and a fluoroquinolone was associated with increased short-term mortality for patients with severe pneumonia in comparison with other guideline-concordant antimicrobial regimes. Further research is needed to determine the range of appropriate empiric antimicrobial therapies for patients with severe community-acquired pneumonia.
Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients at risk for some types of infections. We examined the effect of prior outpatient use of ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia.
A retrospective cohort study conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of, had a chest x-ray consistent with, and had a discharge ICD-9 diagnosis of pneumonia. Subjects were excluded if they were "comfort measures only" or transferred from another acute care hospital. Subjects were considered to be on a medication if they were taking it at the time of presentation.
Data was abstracted on 787 subjects at the two hospitals. Mortality was 9.2% at 30-days and 13.6% at 90-days. At presentation 52% of subjects were low risk, 34% were moderate risk, and 14% were high risk. In the multivariable conditional logistic regression analysis, after adjusting for potential confounders, the use of ACE inhibitors at presentation (odds ratio 0.44, 95% confidence interval 0.22–0.89) was significantly associated with 30-day mortality.
Prior outpatient use of an ACE inhibitor was associated with decreased mortality in patients hospitalized with community-acquired pneumonia despite their use being associated with comorbid illnesses likely to contribute to increased mortality. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.