Rational use of mucoactive medications to treat pediatric airway disease.

Many airway diseases in children, notably bronchiolitis, cystic fibrosis (CF), non-CF bronchiectasis including primary ciliary dyskinesia, pneumonia, and severe asthma are associated with retention of airway secretions. Medications to improve secretions clearance, the mucoactive medications, are employed to treat these diseases with varying degrees of success. This manuscript reviews evidence for the use of these medications and future directions of study.

Human respiratory syncytial virus infection in the pre-clinical calf model.

Human respiratory syncytial virus (hRSV) is the most important respiratory pathogen in young children worldwide. Experimental modelling of hRSV disease by bovine RSV (bRSV) infection in calves provides an important tool for developing new strategies for prevention and treatment. Depending on the scientific hypothesis under investigation, this cognate host-virus model might have the disadvantage of using a highly related but not genetically identical virus. In this study, we aim to describe viral kinetics and (clinical) disease characteristics in calves inoculated with hRSV. Our results show that hRSV infects the upper and, to a lesser extent, the lower respiratory tract of calves. Infection causes upper airway clinical disease symptoms and neutrophilic infiltration of the lower airways. We conclude that a hRSV model in calves may aid future research involving distinct scientific questions related to hRSV disease in children.

Neutrophil Extracellular Traps in Respiratory Disease: guided anti-microbial traps or toxic webs?

Neutrophil recruitment to the airways and lungs is a major hallmark of many respiratory diseases. One of the more recently discovered unique innate immune effector mechanisms of neutrophils is the formation of neutrophil extracellular traps (NETs), consisting of an extracellular network of DNA fibers studded with nuclear and granule proteins. Although in the respiratory system NETs contribute to capture and inactivation of bacteria, fungi and viruses, there is a delicate 'balance' between aid and damage to the host. Accumulating evidence now suggests that NETs can have direct cytotoxic effects to lung epithelial and endothelial cells and can contribute to airway obstruction. As such, NETs may play an important role in the pathogenesis of respiratory diseases. The purpose of this review is to give an up-to-date overview of the current status of NETs in respiratory diseases. We examine both experimental and clinical data concerning the role of NETs in host defence as well as immunopathology, with special attention paid to the literature relevant for the paediatric pulmonology community. Finally, we discuss future treatment strategies that may target the formation of NETs in the airways and lungs.

Depletion of resident alveolar macrophages does not prevent Fas-mediated lung injury in mice.

Activation of the Fas/Fas ligand (FasL) system in the lungs results in a form of injury characterized by alveolar epithelial apoptosis and neutrophilic inflammation. Studies in vitro show that Fas activation induces apoptosis in alveolar epithelial cells and cytokine production in alveolar macrophages. The main goal of this study was to determine the contribution of alveolar macrophages to Fas-induced lung inflammation in mice, by depleting alveolar macrophages using clodronate-containing liposomes. Liposomes containing clodronate or PBS were instilled by intratracheal instillation. After 24 h, the mice received intratracheal instillations of the Fas-activating monoclonal antibody Jo2 or an isotype control antibody and were studied 18 h later. The Jo2 MAb induced increases in bronchoalveolar lavage fluid (BALF) total neutrophils, lung caspase-3 activity, and BALF total protein and worsened histological lung injury in the macrophage-depleted mice. Studies in vitro showed that Fas activation induced the release of the cytokine KC in a mouse lung epithelial cell line, MLE-12. These results suggest that the lung inflammatory response to Fas activation is not primarily dependent on resident alveolar macrophages and may instead depend on cytokine release by alveolar epithelial cells.