Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Jartti, Tuomas; Smits, Hermelijn H.; Bønnelykke, Klaus; Bircan, Ozlem; Elenius, Varpu; Konradsen, Jon R.; Maggina, Paraskevi; Makrinioti, Heidi; Stokholm, Jakob; Hedlin, Gunilla; Papadopoulos, Nikolaos; Ruszczynski, Marek; Ryczaj, Klaudia; Schaub, Bianca; Schwarze, Jürgen; Skevaki, Chrysanthi; Stenberg-Hammar, Katarina; Feleszko, Wojciech

The airway mucosa of asthmatics, who have allergic airway inflammation, has been shown to be associated with reduced type I and type III interferon responses. 62, 63 To understand the particularly high pathogenic potential of RV-C, it is important to note that CDHR3 has recently been identified as a unique receptor for RV-C. 18 Interestingly, a polymorphism in the CDHR3 gene (resulting in a higher expression of CDHR3 on the epithelial surface) was associated with the increased risk of childhood asthma. 27 RV-C has also evolved specific molecular tools to reduce IFN-β expression and downstream signaling in airway epithelial cells, 64 which may possibly explain the more severe course of respiratory RV-C infections. In addition, RV infections of airway epithelial cells are strong inducers of type 2 innate cytokines, such as IL-25 and IL-33, which subsequently initiate or boost type 2 immunity in the lungs via IL-5-and IL-13-producing innate lymphoid cells (ILC) 2 and Th 2 cells ( Figure 4B) . Surprisingly, the induction of innate cytokines by RV infections was stronger in airway epithelial cells from asthmatics compared to healthy controls. 65 Also, the induction of type 2 innate cytokines may be more pronounced during early childhood, as compared to adult mice, human rhinovirus infections in neonatal mice showed more pronounced IL-13 and IL-25 expression, mucus secretion, and airway hyperresponsiveness. 66 This process may be further boosted or coinciding by an early spontaneous wave of IL-33-dependent type 2 cytokines and cells in developing lungs of neonatal mice. 55, 56 Overall, although RV infections are linked to the induction of milder epithelial inflammation than RSV infections, they tend to reduce type I IFN expression and cause inflammation with Th 2 cell characteristics, disrupted tight junction expression, and high cytokine levels that promote bronchospasm, edema, and mucus production and lead to airway obstruction and wheeze. 1 supportive treatment, that is, oxygen, nasal suctioning, mechanical ventilation, and hydration. 67 High flow oxygen therapy using nasal cannula has shown promising results. 68 There is conflicting information across clinical guidelines about the role of nebulized hypertonic saline in acute management of bronchiolitis. Only a few current guidelines recommend bronchodilators. 2 Overall, corticosteroids (see details below), nebulized epinephrine, or antibiotics are not recommended. 2 Because of the current frustration with the existing treatment modalities (high use of bronchodilators, antibiotics, and corticosteroids) and as the majority of the previous trials have not been based on virus-specific data, is further research required in order to direct focus to more personalized management plans in the treatment of acute bronchiolitis. 69