Preschool wheeze (PSW), occurring between the ages of one and five years, most commonly reflects acute obstruction of the distal airways. It affects 1 in 2 children by 6 years, and acute attacks in this age-group are the leading cause of hospital admission during childhood. PSW is predictive of asthma at school age, low lung function persisting into adulthood, and chronic obstructive pulmonary disease in later life. Current treatments to prevent attacks are limited in their effectiveness, and modification of disease progression is not possible with current treatment strategies. Abnormalities in early life pulmonary immune development, associated with adverse environmental exposures are implicated as critical in the development of PSW. However, very little is known about how the pathophysiological features and mechanisms underlying impaired lung function and airway remodelling in PSW.
I hypothesised that children with PSW have a dysregulated lower airway immune environment associated with microbial dysbiosis and airway remodelling. Using bronchoalveolar lavage and bronchial biopsy samples, I compared leukocyte populations, inflammatory mediators, microbiome, airway macrophage (AM) transcriptome, and measures of airway remodelling, between severe PSW and non-wheezing control children.
I found no evidence of a type 2 inflammatory responses in this cohort of children with PSW. I observed the lower airway immune environment to be neutrophilic, with an abundance of inflammatory cytokines. The neutrophilia was associated with the presence of pathogens but was not a PSW specific finding. Specific features of the PSW airway were an over-abundance of Moraxella species, a proinflammatory AM transcriptome associated with the presence of Moraxella, and increased reticular basement membrane thickness, indicative of airway remodelling.
Collectively these data suggest that the lower airway immune environment is indeed dysregulated in PSW, and implicate PSW specific features such as Moraxella abundance and AM phenotypic differences as potential drivers of remodelling.