الفهرس 
Introduction
Acute lower respiratory infectionsOnly 14 pages are availabe for public view
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Abstract
Respiratory tract infections (RTIs) are estimated to cause 703.000 deaths annually in children below five years. The majority of RTIs in children are caused by viruses, yet the number of antivirals approved for treatment of these infections is very limited. Moreover, it is sometimes complicated to distinguish between bacterial and viral RTIs, which results in overuse of antibiotics. Lower respiratory tract infections (LRTI) are the most common cause of critical illness in infants and children. These infections commonly lead to Acute Respiratory Distress Syndrome (ARDS) which has a mortality of up to 20% and causes significant long-term morbidity. ARDS is caused by viral and bacterial infection as well as by sepsis and major trauma. The utility of non-invasive nasosorption and Bronchosorption devices have been assessed for sampling airway mucosal lining fluid in infants with respiratory syncytial virus (RSV) infection, children with atopy, and adults with various respiratory conditions. Severe disease is thought to result from uncontrolled viral replication, an excessive immune response, or both. In the present study we aimed to define the risk of PARDS in viral bronchiolitis especially those with RSV. Accurately quantify airway mucosal inflammatory response in patient with LRTI especially those with RSV. Provide biomarkers for disease sub-types, severity and prognosis for viral bronchiolitis. Compare nasal and bronchial responses in patients with viral bronchiolitis. A hundred children with a range of viral and bacterial causes of LRTI were included in the current study. We measured local immune responses (or signatures) in LRTI and ARDS due to LRTI. The study assessed airway mucosal inflammatory response through non-invasive sampling of the airway mucosa and molecular profiling of cytokines, metabolites and gene expression. Hierarchical clustering of time weighted averages (TWA) was performed to investigate cytokine and chemokine levels, and gene expression profiling was conducted. This was used for understanding of the host inflammatory response in infants with severe LRTI leading to respiratory failure; and will enable the rational assessment and development of new therapies. Retrospective study of infants with ALRTI admitted to PICU showed quarter of the infants fulfilled criteria of ARDS with RSV was the most common virus bacterial infection was identified as a risk factor for development of ARDS in infants with ALRTI. In our cohort infants with severe ALRTI were younger weighed less than moderate cases. Viral PCR were positive in 85% of the cases. Reduced cytokine/chemokine levels in infants with severe disease compared to moderate ones. The only indicator of enhanced responses in severe disease was greater MUC5AC and IL17A expression. RSV was the most common pathogen associated with AVLRI in this study. Cases of severe RSV bronchiolitis had lower nasal viral loads and reduced interferon (IFN)-γ and CCL5/RANTES levels compared to those with moderate disease. The decreased response to infection in severe cases could therefore be influenced by age; however, no correlation was evident between age and inflammatory mediator levels or RSV load. This study also confirmed the utility of nasosorption for quantifying RSV load. Relative to NPA and ETT samples, RSV load on nasosorption samples were lower but still detectable using a sensitive qPCR assay. However lower sensitivity of nasosorption samples in a multiplex clinical PCR assay for 10 viral pathogens. Identification of viral infection using nasosorption may therefore be of limited clinical utility but provides a less-invasive alternative to NPA that is well suited to clinical studies where repeatability and tolerability are needed. Our observations cast doubt on the two major theories advanced to explain the severity of disease in children with viral infections of the respiratory tract. Conclusions ARDS is quite common in cases with lower respiratory infection under two years, however associated with more benign course compared to other causes of ARDS as sepsis. NS is a new non-invasive, repeatable sampling method that can be used to study pediatric viral bronchiolitis. RSV viral load is lower in cases of respiratory failure. IFN levels are similarly lower in cases with respiratory failure. No evidence of bias towards type-2 immunity. IL-17 and mucins may contribute to severity. Severity is multifactorial driven by the reciprocal relationship between viral load and interferon breaks down in severe disease, where mucus production may mediate airway plugging and respiratory failure.