Risk Factors Affecting Development and Persistence of Preschool Wheezing: Consensus Document of the Emilia-Romagna Asthma (ERA) Study Group

Abstract

Wheezing at preschool age (i.e., before the age of six) is common, occurring in about 30% of children before the age of three. In terms of health care burden, preschool children with wheeze show double the rate of access to the emergency department and five times the rate of hospital admissions compared with school-age asthmatics. The consensus document aims to analyse the underlying mechanisms involved in the pathogenesis of preschool wheezing and define the risk factors (i.e., allergy, atopy, infection, bronchiolitis, genetics, indoor and outdoor pollution, tobacco smoke exposure, obesity, prematurity) and the protective factors (i.e., probiotics, breastfeeding, vitamin D, influenza vaccination, non-specific immunomodulators) associated with the development of the disease in the young child. A multidisciplinary panel of experts from the Emilia-Romagna Region, Italy, addressed twelve key questions regarding managing preschool wheezing. Clinical questions have been formulated by the expert panel using the PICO format (Patients, Intervention, Comparison, Outcomes). Systematic reviews have been conducted on PubMed to answer these specific questions and formulate recommendations. The GRADE approach has been used for each selected paper to assess the quality of the evidence and the degree of recommendations. Based on a panel of experts and extensive updated literature, this consensus document provides insight into the pathogenesis, risk and protective factors associated with the development and persistence of preschool wheezing. Undoubtedly, more research is needed to improve our understanding of the disease and confirm the associations between certain factors and the risk of wheezing in early life. In addition, preventive strategies must be promoted to avoid children’s exposure to risk factors that may permanently affect respiratory health.

Human bocavirus respiratory infection: Tracing the path from viral replication and virus‐cell interactions to diagnostic methods

“…Viral infections that induce a predominant Th2 response (like rhinovirus and RSV) are considered a risk factor for recurrent wheezing. 74,75 At COLAZO SALBETTI ET AL.…”

“…76,77 On the other hand, transient low levels of IgG subclass 4 are associated with recurrent wheezing requiring multiple hospitalisations in childhood and IgA deficiency may predispose to recurrent respiratory infections and wheezing. 75,78 One report found HBoV1 at high frequency in infants with wheezing and low IgA and IgG4 levels, suggesting a possible involvement in recurrent wheezing during childhood. 79 However, the cytokine response in respiratory secretions and peripheral blood has been poorly approached, which encourages further research.…”

“…Biochemical analyses of respiratory secretions show that Th1 cytokine levels correlate with clearance of viral infection, whereas Th2 cytokines have been associated with wheezing episodes during acute illness. Viral infections that induce a predominant Th2 response (like rhinovirus and RSV) are considered a risk factor for recurrent wheezing 74,75 . At present there is insufficient data on Th1/Th2 profiles in HBoV1 infection; until now it has not been associated with a Th2‐polarised response 76,77 .…”

“…At present there is insufficient data on Th1/Th2 profiles in HBoV1 infection; until now it has not been associated with a Th2‐polarised response 76,77 . On the other hand, transient low levels of IgG subclass 4 are associated with recurrent wheezing requiring multiple hospitalisations in childhood and IgA deficiency may predispose to recurrent respiratory infections and wheezing 75,78 . One report found HBoV1 at high frequency in infants with wheezing and low IgA and IgG4 levels, suggesting a possible involvement in recurrent wheezing during childhood 79 .…”

Impact of SARS-CoV-2 Infection in Children with Asthma and Impact of COVID-19 Vaccination: Current Evidence and Review of the Literature

“…Asthma is the most common chronic disease of childhood in the world, and asthma exacerbation is frequently caused by viral infections [ 11 , 12 ]. Initially, asthma patients were classified as an at-risk group for COVID-19 severe forms, but whether asthma has worse COVID-19 consequences is not yet clear [ 13 ].…”