Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia

Predicting Mortality in Patients with Ventilator-Associated Pneumonia: The APACHE II Score versus the New IBMP-10 Score

Background. Ventilator-associated pneumonia (VAP) is the leading cause of mortality associated with nosocomial infection. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score at the time of diagnosis of VAP is considered the best scoring system to predict mortality in patients with VAP. The objective of this study was to develop a simple score to predict mortality in patients with VAP and to compare its results with those for the APACHE II scoring system. Methods. The new score was developed by performing a univariate analysis of data collected from 178 patients with VAP. The mortality prediction ability of the new score was compared with the APACHE II score on the basis of receiver operating characteristic curve analysis. Results. The IBMP-10 score assigned 1 point to each of the following variables: (1) the presence of i mmunodeficiency; (2) b lood pressure 10 days. The area under the curve was 0.743 for the APACHE II score and 0.824 for the IBMP-10 score (P <.001). Conclusions. This preliminary work indicates that a 5-point score, the IBMP-10, is comparable to the APACHE II score in its ability to predict mortality in patients with VAP. If future studies validate the IBMP-10 score, physicians may be have a simple tool to evaluate the disease severity and to predict outcomes in patients with VAP

Ruling Out Legionella in Community-acquired Pneumonia

BACKGROUND: Assessing the likelihood for Legionella sp. in community-acquired pneumonia is important because of differences in treatment regimens. Currently used antigen tests and culture have limited sensitivity with important time delays, making empirical broad-spectrum coverage necessary. Therefore, a score with 6 variables recently has been proposed. We sought to validate these parameters in an independent cohort. METHODS: We analyzed adult patients with community-acquired pneumonia from a large multinational database (Community Acquired Pneumonia Organization) who were treated between 2001 and 2012 with more than 4 of the 6 prespecified clinical variables available. Association and discrimination were assessed using logistic regression analysis and area under the curve (AUC). RESULTS: Of 1939 included patients, the infectious cause was known in 594 (28.9%), including Streptococcus pneumoniae in 264 (13.6%) and Legionella sp. in 37 (1.9%). The proposed clinical predictors fever, cough, hyponatremia, lactate dehydrogenase, C-reactive protein, and platelet count were all associated or tended to be associated with Legionella cause. A logistic regression analysis including all these predictors showed excellent discrimination with an AUC of 0.91 (95% confidence interval, 0.87-0.94). The original dichotomized score showed good discrimination (AUC, 0.73; 95% confidence interval, 0.65-0.81) and a high negative predictive value of 99% for patients with less than 2 parameters present. CONCLUSIONS: With the use of a large independent patient sample from an international database, this analysis validates previously proposed clinical variables to accurately rule out Legionella sp., which may help to optimize initial empiric therapy

CD4+ cell counts and HIV-RNA levels do not predict outcomes of community-acquired pneumonia in hospitalized HIV-infected patients

Outcomes of community-acquired pneumonia (CAP) in relation to CD4+ cell counts have not been established. We examined the correlation of CD4+ cell count and HIV-RNA level with the clinical outcomes of CAP in hospitalized HIV-infected patients. METHODS: This was a retrospective study of 127 adult hospitalized patients with HIV infection enrolled with the CAP Organization (CAPO), examining the time to clinical stability (TCS), length of hospital stay (LOS), and all-cause mortality. RESULTS: Mortality data were available for 117 HIV-infected patients with CAP. Death within 28 days was reported in 28 patients. The risk of mortality at 28 days was not significant when adjusted for CD4+ cell count (p=0.123), HIV-RNA <400-1000 copies/ml (p=0.093), HIV-RNA ≥ 1000-10,000 copies/ml (p=0.543), and HIV-RNA ≥ 10,000-100,000 copies/ml (p=0.383). The propensity-adjusted Cox proportional hazards regression models did not show any statistically significant differences in LOS or TCS for CD4+ cell counts (p=0.590 and p=0.420, respectively) or HIV-RNA levels (p=0.470 and p=0.080, respectively). Multivariable Cox proportional hazards models did not reveal any statistically significant relationships between CD4+ cell counts or HIV-RNA levels with LOS or TCS. CONCLUSIONS: Our study shows that clinical outcomes of HIV-infected patients with CAP are not predicted by CD4+ cell counts or HIV-RNA levels after adjusting for confounders. The management of CAP in patients with HIV infection should not be based on CD4+ cell counts or HIV-RNA levels of the HIV infection

Contrasting Inflammatory Responses in Severe and Non-severe Community-acquired Pneumonia

The objective of this study was to compare systemic and local cytokine profiles and neutrophil responses in patients with severe versus non-severe community-acquired pneumonia (CAP). Hospitalized patients with CAP were grouped according to the pneumonia severity index (PSI), as non-severe (PSI < 91 points) or severe (PSI 65 91 points). Blood and sputum samples were collected upon admission. Compared to non-severe CAP patients, the severe CAP group showed higher plasma levels of pro- and anti-inflammatory cytokines but in contrast, lower sputum concentrations of pro-inflammatory cytokines. Blood neutrophil functional responses were elevated in CAP patients compared to healthy controls. However, neutrophils from severe CAP patients showed reduced respiratory burst activity compared to the non-severe group. Results indicate that patients with severe CAP fail to mount a robust local pro-inflammatory response but exhibit instead a more substantial systemic inflammatory response, suggesting that a key driver of CAP severity may be the ability of the patient to generate an optimal local inflammatory response. \ua9 2014 Springer Science+Business Media New York

A Worldwide Perspective of Atypical Pathogens in Community-Acquired Pneumonia

Rationale: Controversy still exists in the international literature regarding the need to use antimicrobials covering atypical pathogens when initially treating hospitalized patients with community-acquired pneumonia (CAP). In different regions of the world, monotherapy with a \u3b2-lactam antimicrobial is common. Objectives: We sought to correlate the incidence of CAP due to atypical pathogens in different regions of the world with the proportion of patients treated with an atypical regimen in those same regions. In addition, we sought to compare clinical outcomes of patients with CAP treated with and without atypical coverage. Methods: A secondary analysis was performed using two comprehensive international databases. World regions were defined as North America (I), Europe (II), Latin America (III), and Asia and Africa (IV). Time to reach clinical stability, length of hospital stay, and mortality were compared between patients treated with and without atypical coverage. Measurements and Main Results: The incidence of CAP due to atypical pathogens from 4,337 patients was 22, 28, 21, and 20% in regions I-IV, respectively. The proportion of patients treated with atypical coverage from 2,208 patients was 91, 74, 53, and 10% in regions I-IV, respectively. Patients treated with atypical coverage had decreased time to clinical stability (3.7 vs. 3.2 d, p < 0.001), decreased length of stay (7.1 vs. 6.1 d, p < 0.01), decreased total mortality (11.1 vs. 7%, p < 0.01), and decreased CAP-related mortality (6.4 vs. 3.8%, p = 0.05). Conclusions: The significant global presence of atypical pathogens and the better outcomes associated with antimicrobial regimens with atypical coverage support empiric therapy for all hospitalized patients with CAP with a regimen that covers atypical pathogens

A worldwide perspective of nursing home-acquired pneumonia compared with community-acquired pneumonia

© 2014 by Daedalus Enterprises.BACKGROUND: Nursing home-acquired pneumonia (NHAP) is the leading cause of death among long-term care patients and the second most common cause of transfers to acute care facilities. The aim of this study was to characterize the incidence, microbiology, and outcomes for hospitalized patients with community-acquired pneumonia (CAP) and NHAP. METHODS: A secondary analysis of 5,160 patients from the Community-Acquired Pneumonia Organization database was performed. World regions were defined as the United States and Canada (I), Latin America (II), and Europe (III). RESULTS: From a total of 5,160 hospitalized patients with CAP, NHAP was identified in 287 (5.6%) patients. Mean age was 80 y. NHAP distribution by region was 6% in region I, 3% in region II, and 7% in region III. Subjects with NHAP had higher frequencies of neurological disease, diabetes mellitus, congestive heart failure, and renal failure than did subjects with CAP (P &lt; .001). ICU admission was

Chemokine levels in mice infected with KY/136 or KY/180.

<p>The levels of notable chemokine responses are shown for 1, 3 and 5 DPI in six to eight week old DBA/2 mice that were infected intranasally with 10⁵ TCID₅₀ of KY/180E or KY/136E (<i>n</i> = 10 mice per virus group per time point). Statistical significance was determined by day using Kruskal-Wallis test followed by pairwise Wilcoxon Rank Sum <i>post hoc</i> test with Holm’s adjustment for multiple comparisons. <i>P</i>-values <0.05 are indicated by the following method: “a” = KY/180 is significantly different from mock; “b” = KY/136 is significantly different from mock; “c” = KY/180 is significantly different from KY/136.</p

Chemokine levels in mice infected with pandemic and seasonal H1N1 influenza viruses.

<p>Six to eight week old DBA/2 mice were infected intranasally with 10⁵ TCID₅₀ with a seasonal virus isolate (BN/59), Kentucky (KY/80, KY/136, KY/96, KY/99, KY/104, KY/108, KY/108, KY/110, KY/180, KY/190) or other H1N1 pandemic isolates (CA/07, NY/18) from 2009. Chemokine levels were measured at 3 and 6 DPI as described in the materials and methods and presented as mean +/− SEM (n = 6 per group when possible).</p