Factors and mechanisms contributing to the development of preschool wheezing disorders

Abstract

Introduction: Half of all children will experience an episode of wheezing by their sixth birthday and acute episodes of wheezing in preschool children account for the majority of all childhood hospital admissions for wheeze. Recurrent preschool wheezing associates with early loss of lung function and a life-long impact on lung health. Areas covered: We reviewed the literature on PubMed from August 2010-2020 focussing on factors associated with wheeze inception and persistence, paying specific attention to mechanistic studies that have investigated the impact of early life exposures in shaping immune responses in children with underlying susceptibility to wheezing. In particular, the role of early allergen sensitization, respiratory infections, and the impact of the environment on shaping the airway microbiome and resulting immune responses are discussed. Expert opinion: There is an abundance of associative data showing the role of in utero and postnatal factors influencing wheeze onset and persistence. However, mechanistic and stratified, biomarkerbased interventional studies that confirm these associations are now needed if we are to impact the significant healthcare burden resulting from preschool wheezing disorders.

Prenatal influenza vaccination and allergic and autoimmune diseases in childhood: A longitudinal, population-based linked cohort study

“…While we cannot entirely rule out the possible influence of bias in the results from this observational study, several aspects of our study suggest a plausible protective relationship between maternal immunization and the development of allergic conditions in childhood. First, early exposure to respiratory infections, in particular viral infections, are strongly linked to the development of childhood wheezing disorders and subsequent asthma in susceptible children [ 35 , 36 ], and a history of asthma is a known risk factor of anaphylaxis and severe anaphylactic episodes, not surprisingly, as there is interaction between atopic asthma and other allergic states [ 37 ]. Maternal influenza immunization reduces the risk of all-cause respiratory infection in infants <6 months by 25% [ 38 , 39 ].…”

Current strategies for phenotyping and managing asthma in preschool children

“…Currently, there is no established prevention strategy for asthma. Investigations are ongoing regarding the identification of at-risk preschool-aged children by phenotyping them according to asthma predictive indices, exposures, triggers (allergen, exercise, virus), types of inflammation (eosinophilic, neutrophilic), structural changes (tracheomalacia, laryngeal pockets), biomarkers (periostin, contactin), and microbiology [13,14]. Recent studies have submitted enough data to stratify preschool wheezers into a few distinct clinically relevant phenotypes, and phenotype-directed therapy may become possible soon [11 ▪▪ ,12 ▪▪ ].…”

Network analyses of upper and lower airway transcriptomes identify shared mechanisms among children with recurrent wheezing and school-age asthma

“…Despite recent evidence showing that loss of airway epithelial barrier integrity and impaired wound repair capacity following insults are tightly associated with RW, the biological mechanisms underlying RW remain poorly understood (9,10). Previous studies have identified multiple environmental (e.g., atopic sensitization, tobacco exposure, and respiratory tract infections early in life) and genetic risk factors (e.g., chr17q21 locus) shared by RW and SA (8,(11)(12)(13). The intrinsic associations during disease trajectory and similarities in environmental exposures and genetic determinants suggest potential overlap in the mechanisms and pathogenic pathways of RW and SA.…”