Bronchoalveolar Lavage in Children: Still the Gold Standard
Shivanthan Shanthikumar1,2,3 and Sarath C Ranganathan1,2,3
- Respiratory and Sleep Medicine, Royal Children’s Hospital, Melbourne,
Australia
- Respiratory Diseases, Murdoch Children’s Research Institute,
Melbourne, Australia
- Department of Paediatrics, University of Melbourne, Melbourne,
Australia
Corresponding Author; Dr Shivanthan Shanthikumar; Respiratory
Medicine, Royal Children’s Hospital, 50 Flemington Road, Parkville, VIC,
3052, Australia;
shivanthan.shanthikumar@rch.org.au
Acknowledgements; The authors have no conflicts of interest to
declare
Dear Editor,
We read with great interest the recent article by Craven et al ,
entitled “High levels of inherent variability in microbiological
assessment of bronchoalveolar lavage samples from children with
persistent bacterial bronchitis and healthy
controls .”1 In a small study of 18 children, funded
by GlaxoSmithKline, the authors demonstrate variability in the results
of bronchoalveolar lavage (BAL) collected from controls and children
with protracted bacterial bronchitis (PBB). Specifically, they show that
when the BAL was divided and sent to two laboratories the results were
discordant in terms of both the organisms isolated and their relative
abundance. From these data the authors draw conclusions which include
questioning “assumptions about this procedure being the gold
standard .” Whilst these data are of interest, there are significant
limitations to their value especially when considering existing
literature.
One of the key findings of the study is the discordant results between
laboratories. A lack of detail regarding the methods used at each site
is a major limitation. It is recognised that laboratory processes can
affect the yield of samples collected from patients with chronic airway
infection, and the need for a consistent approach has led to disease
specific consensus guidelines on this topic.2 The
discordant results seen in the study could result from different
laboratory handling of specimens, and hence the findings of this study
could purely be explained by a difference in practice between two
centres, not least of which was the transport of samples to the second
laboratory in STGG. Molecular studies have identified that even media
considered sterile can contain numerous organisms albeit in low
densities.3 We note that it was laboratory 2 where
additional bacteria were cultured from the BAL.
Hare et al analysed BAL samples from 655 children collected and
analysed at two different sites compared with 18 samples in the study of
Craven et al .4 They compared bacterial pathogen
load (control, negative, 102 colony forming units per
ml (CFU/ml), 103 CFU/ml, 104 CFU/ml,
105 CFU/ml) and inflammatory markers to determine an
appropriate definition for infection. They found that a bacterial
pathogen load of ≥104 CFU/ml was associated with
increased markers of inflammation and hence an appropriate threshold for
defining infection. This was in keeping with previous
studies.4 Whilst the authors contend the current paper
does not support the use of ≥104 CFU/ml, given it only
includes 13 children with PBB an explanation of the findings of Hareet al in their considerably larger study and other studies needs
explanation.
Another key finding of the study was the limited correlation between
semiquantitative and quantitative methods of measuring bacterial
pathogen load. Whilst there has not been direct comparison of different
methods of determining bacterial pathogen load in PBB and other
paediatric suppurative disorders, a large amount of data speaks to the
validity of using a semiquantitative or qualitative approach. For
instance, the previously discussed Hare et al study utilised a
semiquantitative approach, and was able to clearly identify a threshold
for lower airway infection that was associated with inflammation. In
addition, the qualitative approach used by AREST CF (the long running
study of CF patients cited in the article) to define infection is
supported by the fact that this definition is associated with important
clinical outcomes. For example, in a recent AREST-CF study analysing
1161 BAL from 265 children with CF, the presence of early life infection
using the AREST-CF definition, was associated with future risk of
structural lung disease severity.5
Further, we have used molecular studies to assess the microbiome in CF
and shown considerable agreement between pathogen-dominated microbiota
and routine laboratory bacterial culture even though these samples were
assessed by two different techniques, in two laboratories in different
continents and analysed two decades apart in time.6
Despite the data that contradicts the findings of their study, and while
not discussed by the authors themselves, we do contend that use of both
quantitative and semi-quantitative microbiologic cultures are likely
problematic given that bacterial density is influenced by the dilution
from the 0.9% saline used to lavage the target lobe. Dilution further
depends on the volume of return retrieved on suctioning. The consensus
has been that standardising for this dilution is not required but data
supporting this are few.
In summary, there are significant issues that limit the value of the key
findings of the study by Craven et al . A large amount of
published data in PBB and cystic fibrosis support the use of BAL as a
biological specimen associated with important clinical outcomes. These
studies have been conducted in multiple centres, over many years, and
included many children. While the findings of Craven et alhighlight there can be inconsistencies in results, this potentially
speaks to the methods used by the laboratories involved in handing the
small number of samples. When these findings are compared to the large
amount of evidence already generated, they should prompt evaluation of
local practices and not just a reconsideration of whether BAL is the
gold standard method of sampling the lower airway of children with
suppurative lung disease. While we believe that BAL remains the gold
standard for the detection of lower respiratory infection we do not
believe it is a perfect test and its use and many limitations need to be
considered and minimised.
Therefore, we agree with the authors that interpretation of microbial
culture results utilizing BAL samples can be challenging. However, we
disagree that assumptions about this procedure being the “gold
standard” fail to take into account its many limitations as despite
these BAL remains the best test to detect endobronchial infection that
is associated with lower respiratory inflammation especially in CF.