Background-Few studies have investigated the disease burden and genetic diversity of human rhinoviruses (HRV) in developing countries.

Background Prospective data on viral etiology and clinical characteristics of bronchiolitis and upper respiratory illness in infants is limited. Methods This prospective cohort enrolled previously healthy term infants during inpatient or outpatient visits for acute upper respiratory illness (URI) or bronchiolitis during September - May 2004–2008. Illness severity was determined using an ordinal bronchiolitis severity score. Common respiratory viruses were identified by real-time RT-PCR. Results Of 648 infants, 67% were enrolled during inpatient visits and 33% during outpatient visits. Seventy percent had bronchiolitis, 3% croup, and 27% URI. Among infants with bronchiolitis, 76% had RSV, 18% HRV, 10% influenza, 2% coronavirus, 3% HMPV, and 1% PIV. Among infants with croup, 39% had HRV, 28% PIV, 28% RSV, 11% influenza, 6% coronavirus, and none HMPV. Among infants with URI, 46% had HRV, 14% RSV, 12% influenza, 7% coronavirus, 6% PIV, and 4% HMPV. Individual viruses exhibited distinct seasonal, demographic, and clinical expression. Conclusions The most common infections among infants seeking care in unscheduled medical visits for URI or bronchiolitis were RSV and HRV. Demographic differences were observed between patients with different viruses, suggesting that host and viral factors play a role in phenotypic expression of viral illness.

Rationale: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear. Objectives: To determine the role of HRV in pediatric asthma exacerbations and the mechanisms mediating wheezing. Methods: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma. Measurements and Main Results: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21-2.99; P ¼ 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-l 1 levels were higher in wheezing children infected with HRV compared with nonwheezing (P , 0.001) and increased with worsening symptoms (P , 0.001). Moreover, after adjusting for IFN-l 1 , children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57-2.46; P ¼ 0.66). Conclusions: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-l 1 responses mediate exacerbations caused by HRV. Modulation of IFN-l 1 should be studied as a therapeutic target for exacerbations caused by HRV.Keywords: asthma; interferon-l; rhinovirus; children; asthma exacerbation Asthma exacerbations are the main cause of hospitalization in children, and occur in association with respiratory viral infections (1, 2). Human rhinoviruses (HRV) are frequently isolated in the upper airways of children during respiratory infections and during asthma attacks, and have been postulated to trigger these crises (3, 4). However, whether HRV are detected during asthma crises because they are the most frequent cause of upper respiratory infections (URI; which accompany asthma attacks), or because they can specifically elicit asthma exacerbations is unclear. To our knowledge, no pediatric study has compared the viral etiology of URI in patients with asthma with and without wheezing to investigate the specific association between HRV URI and asthma attacks.Several hypotheses have been advanced to explain the mechanisms that trigger asthma crises during respiratory infections (4-7). Focused mainly on HRV-associated episodes, two nonexclusive theories attribute asthma attacks to direct viral injury and immune-mediated exacerbations ...

The effectiveness of attenuated Salmonella in inhibiting tumor growth has been demonstrated in many therapeutic models, but the precise mechanisms remain incompletely understood. In this study, we show that the anti-tumor capacity of Salmonella depends on a functional MyD88-TLR pathway and is independent of adaptive immune responses. Since myeloid suppressor cells play a critical role in tumor growth, we investigated the consequences of Salmonella treatment on myeloid cell recruitment, phenotypic characteristics, and functional activation in spleen and tumor tissue of B16.F1 melanoma-bearing mice. Salmonella treatment led to increased accumulation of splenic and intratumoral CD11b(+)Gr-1(+) myeloid cells, exhibiting significantly increased expression of various activation markers such as MHC class II, costimulatory molecules, and Sca-1/Ly6A proteins. Gene expression analysis showed that Salmonella treatment induced expression of iNOS, arginase-1 (ARG1), and IFN-γ in the spleen, but down-regulated IL-4 and TGF-β. Within the tumor, expression of iNOS, IFN-γ, and S100A9 was markedly increased, but ARG1, IL-4, TGF-β, and VEGF were inhibited. Functionally, splenic CD11b(+) cells maintained their suppressive capacity following Salmonella treatment, but intratumoral myeloid cells had significantly reduced suppressive capacity. Our findings demonstrate that administration of attenuated Salmonella leads to phenotypic and functional maturation of intratumoral myeloid cells making them less suppressive and hence enhancing the host's anti-tumor immune response. Modalities that inhibit myeloid suppressor cells may be useful adjuncts in cancer immunotherapy.

Background Human rhinoviruses (HRVs) cause common colds, and the recently discovered HRV-C is increasingly associated with lower respiratory illness among populations such as children and asthmatic patients. Objective To determine how HRV-C is associated with respiratory illness and to evaluate changes in prevalence and species over 2 decades. Methods A prospective study of children younger than 5 years was performed at the Vanderbilt Vaccine Clinic over a 21-year period. Nasal-wash specimens from children presenting with upper or lower respiratory illness at acute care visits were tested for HRV and HRV-positives genotyped. Demographic and clinical features were compared between children with or without HRV, and with different HRV species. Results HRV was detected in 190 of 527 (36%) specimens from a population of 2009 children from 1982 through 2003. Of these, 36% were HRV-C. Age (P = .039) and month of illness (P <.001) were associated with HRV infection and HRV species. HRV-C was significantly associated with lower respiratory illness, compared with HRV-A (P = .014). HRV-A and HRV-C prevalence fluctuated throughout the 21-year period; HRV-C was more prevalent during winter (P = .058). Conclusions HRV-C is not a new virus but has been significantly associated with childhood lower respiratory illness in this population for several decades. Temporal changes in virus prevalence occur, and season may predict virus species. Our findings have implications for diagnostic, preventive, and treatment strategies due to the variation in disease season and severity based on species of HRV infection.