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forward [77-79] . Using serum samples from the CAMP cohort of 160 individuals, as well as fetal lung cells, Kho
[79]
et al. explored correlations between serum miRNA expression and a variety of parameters including: lung
function, sex and association with lung development. Furthermore, they compared their findings to other
studies performed in human subjects or cell lines to determine their potential as asthma biomarkers. Twenty-
two miRNAs were shown to associate with lung function parameters and of those 22, nine (miR-139-5p, -15b-
5p, 186-5p, 342-3p, 374a-5p, 409-3p, 454-3p, 660-5p, and -942-5p) were shown to associate with males alone and
three (miR-1290, -142-3p, and 191-5p) with females alone. Additionally, seven (miR-126-3p, -203a-3p, -26a-5p,
-30b-5p, -342-3p, -409-3p and -942-5p) of those 22 miRNAs associated with lung function were also associated
with gestational age. They then performed ontology analysis to examine pathways and potential genes in
which these miRNAs play a role. Pathways important in asthma pathogenesis including PPAR signaling and
respiratory system development were enriched suggesting potential circulating biomarkers associated with
lung function. Another study using the CAMP cohort examined the association between circulating miRNAs
[77]
in serum and airways hyper-responsiveness . They found a significant association of miR-296-5p, -548b-5p,
-138-5p, -16-5p, -1227-3p, -30d-5p, -203a-3p, and -128-3p with decreasing airway hyper-responsiveness. They
went on to confirm the results using two of the miRNAs known to be highly expressed in airway smooth
muscle cells, miR-16-5p and -30d-5p. When they used mimics of miR-16-5p and -30d-5p in vitro, they found
altered cell growth and diameter of the cells compared to the scrambled controls. Lastly, they found through
in silico interaction and pathway analysis that miR-16-5p appeared to be a hub connecting many of the other
identified miRNAs and targets. Furthermore, many of the miRNAs found in this study have been previously
[78]
identified as asthma related, which strengthened their findings. Recently, Kho et al. performed the first
study to investigate the prediction of asthma exacerbations by circulating miRNAs. A combination of three
miRNAs: miR-146b-5p, -206 and -720 were sufficient to provide predictive power to the clinical model of
asthma exacerbation and the combination of miRNA and clinical score of asthma exacerbations was superior
than either measurement on its own. Thus, the combination of a well-defined cohort, various screening
techniques, and bioinformatics analysis has yielded a wealth of new information about miRNA associations
with childhood asthma and opened the door for a cascade of future studies.

Although this collection of work has paved the way for miRNAs as potential biomarkers for asthma, all of
the above mentioned studies were performed on relatively small cohorts for the miRNAs to be considered
“true” biomarkers. Additionally, mechanistic studies of asthma on children appears to be relatively rare,
likely due to the lack of more invasive methods of sampling (e.g., biopsies). Endotyping in childhood
asthma cohorts is also relatively rare, so few detailed studies have been performed on non-allergic asthmatic
[80]
pediatric cohorts . Furthermore, the age range of the aforementioned studies was between 0 and 18
years old. Due to the heterogenic nature of asthma and the bodily-hormonal and physical-changes that
occur throughout childhood, which most likely affect the development of the disease, detailed patient
characteristics would be greatly needed to determine whether study groups are comparable to one another.

MIRNA IN ADULT ASTHMA
Evidence for miRNA involvement in asthma comes largely from murine models, but recently a number
of studies have been performed investigating human samples obtained from asthmatics. However, as
[81]
adult asthma is now considered a heterogeneous disease entailing a number of different phenotypes , we
attempted to sort these studies based on their asthma characteristics if that information could be retrieved
from the study. Is it possible for miRNAs to be used to aide in this characterization and further contribute to
the understanding of the underlying pathogenesis?

Allergic asthma
Most asthmatics belong to the allergic asthma phenotype and often atopic and allergic asthma originates
in early childhood, but it can also occur in adulthood. However, based on the information given in the