Background Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in older adults. Comparison of RSV and influenza infection in hospitalized older adults may increase awareness of adult RSV disease burden. Methods Hospitalized adults aged ≥60 years who tested positive for RSV or influenza between 1 January 2011 and 30 June 2015 were identified from Kaiser Permanente Southern California electronic medical records. Baseline characteristics, comorbidities, utilization, and outcomes were compared. Results The study included 645 RSV- and 1878 influenza-infected hospitalized adults. Patients with RSV were older than those with influenza (mean, 78.5 vs 77.4 years; P = .035) and more likely to have congestive heart failure (35.3% vs 24.5%; P < .001) and chronic obstructive pulmonary disease (COPD) (29.8% vs 24.3%; P = .006) at baseline. In adjusted analyses, RSV infection was associated with greater odds of length of stay ≥7 days (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.2–1.8; P < .001); pneumonia (OR = 2.7; 95% CI, 2.2–3.2; P < .001); intensive care unit admission (OR = 1.3; 95% CI, 1.0–1.7; P = .023); exacerbation of COPD (OR = 1.7; 95% CI, 1.3–2.4; P = .001); and greater mortality within 1 year of admission (OR = 1.3; 95% CI, 1.0–1.6; P = .019). Conclusions RSV infection may result in greater morbidity and mortality among older hospitalized adults than influenza. Increased recognition of adult RSV disease burden will be important in the evaluation and use of new RSV vaccines and antivirals.

Eosinophilic esophagitis (EE) is an emerging disease associated with both food and respiratory allergy characterized by extensive esophageal tissue remodeling and abnormal esophageal gene expression including increased IL-13. We investigated the ability of increased airway IL-13 to induce EE-like changes. Mice that overexpress an IL-13 transgene in the lung (but not esophagus) accumulated esophageal IL-13 and developed prominent esophageal remodeling with epithelial hyperplasia, angiogenesis, collagen deposition and increased circumference. IL-13-induced marked changes in esophageal transcripts overlapped with the human EE esophageal transcriptome. IL-13-induced esophageal eosinophilia was eotaxin-1 (but not eotaxin-2) dependent but remodeling occurred independent of eosinophils, as demonstrated by studying eosinophil lineage-deficient IL-13 transgenic mice. IL-13-induced remodeling was significantly enhanced by IL-13Rα2 gene deletion, indicating an inhibitory effect of IL-13Rα2. In the murine system, there was partial overlap between IL-13-induced genes in the lung and esophagus, yet the transcriptomes were also divergent at the tissue level. In human esophagus, IL-13 levels correlated with the magnitude of the EE transcriptome. In conclusion, inducible airway expression of IL-13 results in an esophageal gene expression and extensive tissue remodeling pattern that resembles human EE. Notably, we have identified a pathway for inducing EE-like changes that is IL-13-driven, eosinophil-independent and suppressed by IL-13Rα2.

To clarify the role and regulation of eosinophils, we subjected several key eosinophil-related genetically engineered mice to a chronic model of allergic airway inflammation aiming to identify results that were independent of the genetic targeting strategy. In particular, mice with defects in eosinophil development (⌬dbl-GATA) and eosinophil recruitment [mice deficient in CCR3 (CCR3 knockout) and mice deficient in both eotaxin-1 and eotaxin-2 (eotaxin-1͞2 double knockout)] were subjected to Aspergillus fumigatus-induced allergic airway inflammation. Allergen-induced eosinophil recruitment into the airway was abolished by 98%, 94%, and 99% in eotaxin-1͞2 double knockout, CCR3 knockout, and ⌬dbl-GATA mice, respectively. Importantly, allergen-induced type II T helper lymphocyte cytokine production was impaired in the lungs of eosinophil-and CCR3-deficient mice. The absence of eosinophils correlated with reduction in allergen-induced mucus production. Notably, by using global transcript expression profile analysis, a large subset (29%) of allergen-induced genes was eosinophil-and CCR3-dependent; pathways downstream from eosinophils were identified, including in situ activation of coagulation in the lung. In summary, we present multiple lines of independent evidence that eosinophils via CCR3 have a central role in chronic allergic airway disease.allergy ͉ asthma ͉ chemokine ͉ cytokine

IL-13 overexpression in the lung induces inflammatory and remodeling responses that are prominent features of asthma. Whereas most studies have concentrated on the development of IL-13-induced disease, far fewer studies have focused on the reversibility of IL-13-induced pathologies. This is particularly important because current asthma therapy appears to be poor at reversing lung remodeling. In this manuscript, we used an externally regulatable transgenic system that targets expression of IL-13 to the lung with the aim of characterizing the reversibility process. After 4 wk of doxycycline (dox) exposure, IL-13 expression resulted in mixed inflammatory cell infiltration, mucus cell metaplasia, lung fibrosis, and airspace enlargement (emphysema). After withdrawal of dox, IL-13 protein levels were profoundly reduced by 7 d and below baseline by 14 d. During this time frame, the level of lung eosinophils returned to near normal, whereas macrophages, lymphocytes, and neutrophils remained markedly elevated. IL-13-induced mucus cell metaplasia significantly decreased (91%) 3 wk after withdrawal of dox, showing strong correlation with reduced eosinophil levels. In contrast, IL-13-induced lung fibrosis did not significantly decline 4 wk after dox withdrawal. Importantly, IL-13-induced emphysema persisted, but modestly declined 4 wk after dox. Examination of transcript expression profiles identified a subset of genes that remained increased weeks after transgene expression was no longer detected. Notably, numerous IL-13-induced cytokines and enzymes were reversible (IL-6 and cathepsins), whereas others were sustained (CCL6 and chitinases) after IL-13 withdrawal, respectively. Thus, several hallmark features of IL-13-induced lung pathology persist and are dissociated from eosinophilia after IL-13 overexpression ceases.Keywords: asthma; cytokines; eosinophils; inflammation; lung Allergic asthma is characterized by chronic inflammation of the airways, airway wall remodeling, and a decline in respiratory function. In asthma, structural changes in the airway include mucus cell metaplasia, increased deposition of extracellular matrix proteins (e.g., collagen and proteoglycans), and hyperplasia of myofibroblasts and smooth muscle cells (1, 2). Airway remodeling and persistent inflammation contribute to disease pathogenesis of asthma. Animal studies have defined a critical effector role for IL-13 in many pathologic features of experimental asthma, including airway inflammation, tissue fibrosis, and mucus hypersecretion by goblet cells (3-5).The effector functions mediated by IL-13 include a diverse array of biological activities (6). IL-13-deficient animals, novel IL-13 antagonists, and transgenic overexpression modeling sys- tems have successfully defined a central role for IL-13 in some inflammatory diseases of the lung (6). In animal models, pulmonary overexpression of IL-13 results in inflammation, airway fibrosis, mucus metaplasia, airway hyperresponsiveness, and enhanced lung volumes and compliance (5, 7). The inflammatory ...

Interleukin (IL)-13 transgene overexpression in the lung induces features of chronic inflammatory lung disorders, including an eosinophil-rich inflammatory cell infiltration, airway hyper-reactivity, and remodeling of the airway (eg, subepithelial fibrosis, goblet cell metaplasia, and smooth muscle hypertrophy and hyperplasia). Here, we aimed to define the role of eosinophils and eosinophil signaling molecules [eg, eotaxins and CC chemokine receptor (CCR) 3] in IL-13-mediated airway disease. To accomplish this, we mated IL-13-inducible lung transgenic mice with mice deficient in eosinophil chemoattractant molecules (eotaxin-1, eotaxin-2, and their receptor CCR3) and with mice genetically deficient in eosinophils (⌬dbl-GATA). We report that in the absence of eotaxin-2 or CCR3, there was a profound reduction in IL-13-induced eosinophil recruitment into the lung lumen. In contrast, in the absence of eotaxin-1, there was a fourfold increase in IL-13-mediated eosinophil recruitment into the airway. IL-13 transgenic mice deficient in CCR3 had a 98% reduction in lung eosinophils. Furthermore, the reduction in pulmonary eosinophils correlated with attenuation in IL-13-induced mucus cell metaplasia and collagen deposition. Mechanistic analysis identified alterations in pulmonary protease and transforming growth factor-␤ 1 expression in eosinophil-deficient mice. Taken together , these data definitively identify a functional contribution by eosinophils on the effects of chronic IL-13 expression in the lung. Asthma, one of the most common serious chronic diseases of childhood, is an inflammatory lung disease characterized by airway wall remodeling and reduced respiratory function. The chronic inflammatory process, with an airway infiltrate composed primarily of CD4 ϩ lymphocytes and eosinophils, contributes to airway remodeling, defined as altered lung structural changes.1 These structural changes in the airway include mucus cell metaplasia and increased deposition of collagen, proteoglycans, and other matrix proteins in the subepithelial layer.2 Importantly, these structural changes are implicated, at least partially, in the clinical manifestations of asthma.

Background We describe the clinical epidemiology and outcomes among a large cohort of older adults hospitalized with respiratory syncytial virus (RSV) infection in the US. Methods Hospitalized adults aged ≥60 years who tested positive for RSV between 01/01/2011-6/30/2015 were identified from Kaiser Permanente Southern California. Patient-level demographics, comorbidities, clinical presentation, utilization, complications, and mortality were evaluated. Results There were 664 participants hospitalized with RSV (61% female, 64% aged ≥75 years). Baseline chronic diseases were prevalent (all &gt;30%). Nearly two-thirds (66%) developed pneumonia, 80% of which were radiographically confirmed. Very severe tachypnea (≥26 breaths per minute) was common (56%). Approximately 21% required ventilator support and 18% were admitted to the intensive care unit. Mortality during hospitalization was 5.6% overall (4.6% in 60-74 year-olds and 6.1% in ≥75 year-olds). Cumulative mortality within 30 days, 3 months, 6 months, and 12 months of admission was 8.6%, 12.3%, 17.2%, and 25.8%, respectively. Conclusion RSV infection in hospitalized older adults often manifested as severe, life-threatening lower respiratory tract illness with high rates of pneumonia, requirement for ventilatory support, and short- and long-term mortality. Increased recognition of the substantial RSV disease burden in adults will be important in the evaluation and use of urgently needed interventions.

BACKGROUND: Meningococcal conjugate vaccination is recommended in the United States. This study evaluates the safety of quadrivalent meningococcal conjugate vaccine in a cohort aged 11 to 21 years.

One incident EOI of asthma late in the 1-year observation period and sporadic distribution of SMAEs were observed. These data do not suggest safety concerns associated with MenACWY-CRM vaccination in children 2-10 years old.