Clinical profile for future bronchiectasis on LCA
We identified one (100.0%) distinct clinical profile for Indigenous
infants at-risk for future bronchiectasis (Table-4) and one without any
risk (0.0%) (Profile-B). Infants in Profile-C who all had
bronchiectasis also had the highest frequency of markers of severity for
bronchiolitis i.e. supplemental oxygen requirement (100.0%), moderate
accessory muscle use (84.7%), any co-morbidity (75.4%) and any
bacteria (93.1%). Profile-A was the second most severe group with
bronchiectasis in 35.4%, preterm birth in 90.7%, low birth weight in
89.2% and previous respiratory hospitalisation in 39.6%. However, many
infants in this profile lacked known markers of severity (e.g. prolonged
LOS, supplemental oxygen requirement etc).
\soutDISCUSSION
In this first study using LCA in a cohort at-risk of bronchiectasis
rather than asthma, we identified 5 distinct clinical profiles among the
164 Indigenous infants hospitalised with bronchiolitis. The most
striking characteristics were Profile-A phenotype was being preterm
(90.7%), low birth-weight (89.2%) and weight-for-length z-score
<-1 (82.7%). Profile-B phenotype were characterised by all
(100.0%) requiring oxygen supplementation (100%) yet absence of future
chronic symptoms necessitating chest CT scan (0.0%) whilst all in
Profile-C had future bronchiectasis (100.0%) and at the point of
hospitalisation, most (93.0%) had NP bacteria. Profile-D was
characterised by the absence of low birth-weight (100.0%) yet low
weight for length z-score of <-2 (36.0%) and hRV infection
(49.4%) and infants in Profile-E had low concurrent co-morbidity
(33.9%).
Use of clinical phenotypes for various diseases have been appreciated
increasingly over the last decade in a range of conditions. LCA has been
generally used for this and to the best of our knowledge, there are only
two such published studies3,4 involving infants with
bronchiolitis. Both these novel studies3,4 were based
in high-income settings where asthma is the outcome of interest. In the
absence of any such studies in a setting where infants are at high risk
of chronic suppurative lung disease30, we undertook
this study to determine of LCA can identify phenotypes that may inform
future interventions relevant to children at high-risk of
bronchiectasis.
Uniquely, we identified two main clinical profiles with future
bronchiectasis i.e. all in Profile-C had bronchiectasis and the second
most common group with bronchiectasis was Profile-A (35.0%). Over a
third of infants were included in these profiles which included many
known risk factors for severe disease. It was not surprising that these
profiles included the greatest number of infants with bacterial carriage
and current co-morbidities. In Australia, Indigenous children
particularly from remote communities often live in overcrowded
homes30, are exposed to early and dense acquisition of
respiratory bacteria (Streptococcus pneumoniae, Haemophilus
influenzae and Moraxella catarrhalis )31 which are
associated with poorer clinical outcomes (chronic wet
cough18 and bronchiectasis30) in our
setting. Whilst the above finding need confirmation in a large cohort
from multi-centres, our novel findings highlight that LCA could be used
for phenotyping children at-risk of future bronchiectasis and
subsequently inform targeted interventions for these infants that could
possibly prevent future bronchiectasis.
Unsurprising, our phenotypes are very different from that of Dumas and
colleagues’3 for many reasons, of which the most
important is the different target population. Further our study was
substantially smaller, we excluded infants admitted to the intensive
care unit, and did not include all the variables examined by Dumas and
colleagues3. Nevertheless, we identified 5 distinct
clinical profiles by use of LCA. Profile-B was the third largest group
with markers of severity (e.g. marked accessory muscle use, oxygen
requirement and prolonged LOS). This group is common to that of the USA
cohort,3 whereby Dumas and
colleagues3 reported a severe profile among infants
with RSV, moderate to severe accessory muscle use and prolonged LOS
(>3-days). The same result however was not replicated in
the Finish study3 where these markers of severity
(e.g. retractions and LOS) were distributed across two profiles.
However, our Profile-B included oxygen requirement, a factor that was
not included in Dumas and colleagues’3 LCA profile.
The limitations of the original studies whereby this cohort was obtained
from, were previously published19-21. However, this
study has further other important limitations. Firstly, we did not use
BIC because our relatively small sample size restricted the use of BIC
as cohorts of <400 that BIC underestimate
classes32. We thus used aBIC, suitable for smaller
cohort26,32. As aBIC still suggested that the sample
is sufficiently large (n≥200)32, we thus included
entropy as a second information criterion33 in
class-models. Secondly, our data was cross-sectional and weakened by the
lack of longer follow-up. Thirdly, our data were limited to Indigenous
hospitalised for bronchiolitis with the lack of community-based children
and the absence of recurrent wheezing and asthma, important factors in
studies from high-income settings34.
In conclusion, our study is unique as, for the first time, we identified
5 clinical phenotypes in an at-risk population by using LCA. Two
profiles were important for future bronchiectasis. Importantly, our data
further highlights the heterogeneity of bronchiolitis phenotypes among
infants. We now need confirmation of our novel findings in a large
multi-centre cohort to determine such phenotypes in children at-risk of
future bronchiectasis. Such work could subsequently inform targeted
interventions for these infants that could possibly prevent future
bronchiectasis, an increasingly recognised condition worldwide of which
a significant proportion commences in childhood13.