Severe RSV infection in infancy is associated with increased risk of recurrent wheezing in childhood. Both acute and long-term alterations in airway functions are thought to be related to inefficient anti-viral immune response. The airway epithelium, the first target of respiratory syncytial virus (RSV), normally acts as an immunological barrier able to elicit an effective immune reaction but may also be programmed to directly promote a Th2 response, independently from Th2 lymphocyte involvement. Recognition of RSV transcripts and viral replication intermediates by bronchial epithelial cells brings about release of TSLP, IL-33, HMGB1 and IL-25, dubbed “alarmins”. These epithelial cell-derived proteins are particularly effective in stimulating innate lymphoid cells 2 (ILC2) to release IL-4, IL-5, and IL-13. ILC2, reflect the innate counterparts of Th2 cells and, when activate, are potent promoters of airway inflammation and hyperresponsiveness in RSV bronchiolitis and childhood wheezing/asthma. Long-term epithelial progenitors or persistent epigenetic modifications of the airway epithelium following RSV infection, may play a pathogenetic role in the short and long-term increased susceptibility to obstructive lung diseases in response to RSV in the young. Additionally, ILC2 function may be further regulated by RSV-induced changes in gut microbiota community composition that can be associated with disease severity in infants. A better understanding of the alarmin-ILC interactions in childhood might provide insights into the mechanisms characterizing these immune-mediated diseases and indicate new targets for prevention and therapeutic interventions.

Obstructive airway disorders are common in infancy and early childhood. The leading example of such disorder is post-viral wheezing, predominantly the well characterized disorder that follows respiratory syncytial virus (RSV) infection and leads to intermittent, long-term wheezing. The underlying mechanisms of the airway reactivity related to RSV infection have been extensively studies and are associated with dysregulation of the nonadrenergic-noncholinergic (NANC) system, via upregulation of neurotransmitters, typically Substance P. Neuroendocrine hyperplasia of infancy (NEHI), while a less common entity, is a disorder of infancy characterized by more severe and long-term obstructive airway disease. NEHI is pathophysiologically characterized by abundance of neuroendocrine cells in the airways containing the neuroimmune mediator bombesin, the release of which is presumed to be the driver of the persistent small airway obstruction and functional air-trapping. Here we review the NANC and NEC neurotransmitter systems and their studied roles in pulmonary diseases with a focus on their role in lung development, and subsequent various pediatric lung diseases. We focus on the juxtaposition of the separate neuroimmune mechanisms underlying the pathogenesis of post-RSV recurrent wheezing and NEHI persistent small airway obstruction. We finally raise the question whether substance P is indeed specific to post-RSV infection and bombesin to NEHI and then propose a unifying concept of post-viral spectrum of respiratory disorders that may encompass these two entities and possibly others.

The immunopathology of respiratory syncytial virus (RSV) infection, the most common cause of lower respiratory tract infections (LRTI) in the pediatric population, with severe disease being the exception. The variability of the clinical presentation is incompletely explained by host, viral and environmental factors but, in infants and young children, disease severity is certainly linked to the physiological immune immaturity. There is evidence that the maturation of the host immune response is, at least in part, promoted by the composition of the nasopharyngeal microbiome that, modulating excessive inflammation, can counteract the predisposition to develop viral respiratory infections and lower the risk of disease severity. However, interaction between the nasopharyngeal microbiota and respiratory viruses can be bidirectional. Microbial dysbiosis can drive disease pathogenesis but may also represents a reflection of the disease-induced alterations of the local milieu. Moreover, viruses like RSV, can also increase the virulence of potential pathogens in nasopharynx, which is a main reservoir of bacteria, and therefore promote their spread to the lower airways causing superinfection. Negative changes in microbial community composition in early life may constitute a heightened risk towards severe RSV respiratory infection and bacterial superinfection, whilst specific groups of microorganisms can be associated with protection. A better understanding into the potential negative and positive role of the different nasopharyngeal bacterial species in disease prevention as well as into the possible benefits of microbiome therapeutic manipulation, may improve patient outcomes.

Background. In secondary tracheomalacia due to mediastinal vascular anomalies one of the most prevalent symptom is recurrent lower respiratory tract (LRT) infections, related to defective airway clearance. Whether this condition could result in persistent LRT inflammation and subclinical infection is not known. Patients and methods. Children with tracheomalacia due to mediastinal vascular anomalies, recurrent (>3/y) LRT infections were evaluated while in stable condition. Computed tomography (CT) scan and bronchoscopy with bronchoalveolar lavage (BAL) were performed. Results. 31 children were included in the study: 21 with aberrant innominate artery (AIA), 4 with right aortic arch (RAA) and 1 with double aortic arch (DAA) and 5 with AIA associated with RAA. Cytological evaluation of BAL fluid showed increased neutrophil percentages and normal lymphocyte and eosinophil proportions. Microorganism growth was detected in 35.5% of BAL samples, with a bacterial load >105 colony-forming-units (CFU)/mL only in 10,2% of them. Most isolates were positive for Haemophilus influenzae, followed by Streptococcus pneumoniae, Group A β-hemolytic streptococci and Moraxella catarrhalis. Chest CT scan demonstrated the presence of bronchiectasis in 13% of the children, of which only one had a positive BAL culture for Haemophilus influenzae. Conclusions. Only in a small subgroup of children, persistent neutrophilic alveolitis was associated with a significant bacterial load and the presence of bronchiectasis. Because most pathogens detected in BAL samples cultures can produce biofilms, caution should be used in inappropriate antibiotic prescription in these patients that, chiefly in those with bronchiectasis, in which chest physiotherapy can be of great benefit.