Timothy Lee Wiemken

Pneumonia remains a common cause of morbidity and mortality in the US. Although, communityacquired pneumonia (CAP) has traditionally been considered an acute process, more recently, data have emerged showing that patients surviving an episode of CAP are at increased risk of death long after hospital discharged. In this descriptive review, we examine the current knowledge of long-term mortality and propose a hypothesis explaining the pathogenesis of long-term mortality in patients with CAP.

Community acquired pneumonia (CAP) due to Streptococcus pneumoniae still occurs in at risk populations, despite the availability of effective vaccines. Laboratory confirmation of S. pneumoniae remains challenging in cases of CAP despite advances in blood culture techniques and the availability of nucleic acid amplification tests such as PCR-based methods. Urine specimens are an attractive sample type because they are non-invasive compared to bronchial washes or whole blood specimens for patients with CAP. While urine specimens have been used successfully in antigen detection assays, they have not been extensively evaluated for PCR-based assays. In this preliminary study, we evaluated the potential for a real-time PCR assay targeting the S. pneumoniae autolysin gene (lytA) to detect in archived urine samples from patients with CAP. Results indicate that the real time lytA PCR assay on the Luminex ARIES® system shows promise as a screening tool for patients with CAP based on comparison to urine antigen detection assay results.

Background: Advanced age is associated with immunosenescence as well as increased risk for poor outcomes during episodes of community-acquired pneumonia (CAP). Data on neutrophil function in hospitalized elderly patients with CAP is lacking. In this study we compared neutrophil function in elderly and non-elderly hospitalized patients with CAP. Methods: Prospective study of healthy controls (HC) and patients hospitalized with CAP nonelderly (NE-CAP) and elderly (E-CAP). Blood samples were obtained on the day of hospitalization. The following neutrophil functional assays were performed: degranulation of secretory vesicles (CD35), degranulation of specific granules (CD66b), phagocytosis, and hydrogen peroxide (H2O2) production. The Mann-Whitney U-test was used to compare differences in neutrophil function. Results: A total of 12 HC, 28 NE-CAP, and 12 E-CAP were evaluated. There were no significant differences between NE-CAP and E-CAP patients in regard to CD35 expression (p=0.465), CD66b expression (p=0.601), phagocytosis (p=0.654), or H2O2 production (p=0.541) Conclusions: We failed to demonstrate any significant difference in neutrophil function in nonelderly versus elderly patients hospitalized with CAP in relation to membrane expression of CD35 and CD66b, phagocytosis, and respiratory burst. Abnormal neutrophil function is unlikely to be an important component of the immunosenescence described in elderly patients with CAP.

Purpose: Patients with severe community-acquired pneumonia (CAP) are believed to have an exaggerated inflammatory response to bacterial infection. Therapies aiming to modulate the inflammatory response have been largely unsuccessful, perhaps reflecting that CAP is a heterogeneous disorder that cannot be modulated by a single anti-inflammatory approach. We hypothesize that the host inflammatory response to pneumonia may be characterized by distinct cytokine patterns, which can be harnessed for personalized therapies. Methods: Here, we use hierarchical cluster analysis of cytokines to examine if patterns of inflammatory response in 13 hospitalized patients with CAP can be defined. This was a secondary data analysis of the Community-Acquired Pneumonia Inflammatory Study Group (CAPISG) database. The following cytokines were measured in plasma and sputum on the day of admission: interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, CXCL8 (IL-8), IL-10, IL-12p40, IL-17, interferon (IFN)γ, tumor necrosis factor (TNF)α, and CXCL10 (IP-10). Hierarchical agglomerative clustering algorithms were used to evaluate clusters of patients within plasma and sputum cytokine determinations. Results: A total of thirteen patients were included in this pilot study. Cluster analysis identified distinct inflammatory response patterns of cytokines in the plasma, sputum, and the ratio of plasma to sputum. Conclusions: Inflammatory response patterns in plasma and sputum can be identified in hospitalized patients with CAP. Characterization of the local and systemic inflammatory response may help to better discriminate patients for enrollment into clinical trials of immunomodulatory therapies.

Background: Reports from the 2009 H1N1 influenza A virus (2009 H1N1) pandemic indicate increased mortality in obese patients hospitalized with pneumonia. However, articles published prior to the pandemic have suggested that obesity may be a protective factor for mortality in these patients. The objective of this study was to compare the impact of obesity on mortality in hospitalized patients with pneumonia due to the 2009 H1N1 versus pneumonia due to other etiologies. Methods: This was a secondary analysis of the CAPO international cohort study. Study groups were defined as follows: Group One, pneumonia due to 2009 H1N1: Patients hospitalized with pneumonia after March 2009 with a positive RT-PCR for 2009 H1N1 and Group Two, pneumonia due to other etiologies: Patients hospitalized with pneumonia before March 2009. Body Mass Index (BMI) was used to predict the influence of obesity on mortality. The effect of BMI on mortality was analyzed using a propensity-adjusted logistic regression model. Results: From the total of 897 patients, 215 (24%) had pneumonia due to 2009 H1N1. After adjustment, increased BMI was associated with increased mortality in patients with pneumonia due to 2009 H1N1 and with decreased mortality in patients with pneumonia due to other etiologies. Conclusions: Obesity is associated with poor outcomes in patients with pneumonia due to 2009 H1N1 but is protective in patients with pneumonia due to other etiologies. Defining the molecular mechanisms by which obesity influences outcomes in patients with pneumonia may help to develop novel therapeutic strategies. Funding: US Department of Homeland Security.

Background: Transmissibility of several etiologies of lower respiratory tract infections (LRTI) may vary based on outdoor climate factors. The objective of this study was to evaluate the impact of outdoor temperature, relative humidity, and absolute humidity on the incidence of hospitalizations for lower respiratory tract infections due to influenza, rhinovirus, and respiratory syncytial virus (RSV). Methods: This was a secondary analysis of an ancillary study of the Community Acquired Pneumonia Organization (CAPO) database. Respiratory viruses were detected using the Luminex xTAG respiratory viral panel. Climate factors were obtained from the National Weather Service. Adjusted Poisson regression models with robust error variance were used to model the incidence of hospitalization with a LRTI due to: 1) influenza, 2) rhinovirus, and 3) RSV (A and/or B), separately. Results: A total of 467 hospitalized patients with LRTI were included in the study; 135 (29%) with influenza, 41 (9%) with rhinovirus, and 27 (6%) with RSV (20 RSV A, 7 RSV B). The average, minimum, and maximum absolute humidity and temperatur e variables were associated with hospitalization due to influenza LRTI, while the relative humidity variables were not. None of the climate variables were associated with hospitalization due to rhinovirus or RSV. Conclusions: This study suggests that outdoor absolute humidity and temperature are associated with hospitalizations due to influenza LRTIs, but not with LRTIs due to rhinovirus or RSV. Understanding factors contributing to the transmission of respiratory viruses may assist in the prediction of future outbreaks and facilitate the development of transmission prevention interventions.