PT  - JOURNAL ARTICLE
AU  - Shu Mei Teo
AU  - Howard HF Tang
AU  - Danny Mok
AU  - Louise M Judd
AU  - Stephen C Watts
AU  - Kym Pham
AU  - Barbara J. Holt
AU  - Merci Kusel
AU  - Michael Serralha
AU  - Niamh Troy
AU  - Yury A Bochkov
AU  - Kristine Grindle
AU  - Robert F Lemanske, Jr
AU  - Sebastian L Johnston
AU  - James E Gern
AU  - Peter D Sly
AU  - Patrick G Holt
AU  - Kathryn E Holt
AU  - Michael Inouye
TI  - Dynamics of the upper airway microbiome in the pathogenesis of asthma-associated persistent wheeze in preschool children
AID  - 10.1101/222190
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 222190
4099  - http://biorxiv.org/content/early/2017/11/20/222190.short
4100  - http://biorxiv.org/content/early/2017/11/20/222190.full
AB  - Repeated cycles of infection-associated lower airway inflammation drives the pathogenesis of persistent wheezing disease in children. Tracking these events across a birth cohort during their first five years, we demonstrate that >80% of infectious events indeed involve viral pathogens, but are accompanied by a shift in the nasopharyngeal microbiome (NPM) towards dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change in NPM frequently precedes the appearance of viral pathogens and acute symptoms. In non-sensitized children these events are associated only with “transient wheeze” that resolves after age three. In contrast, in children developing early allergic sensitization, they are associated with ensuing development of persistent wheeze, which is the hallmark of the asthma phenotype. This suggests underlying pathogenic interactions between allergic sensitization and antibacterial mechanisms.