To the Editor:
We thank Peel et al for their comments. We acknowledge that breathomics was underrepresented in our review1 and that we failed to appropriately distinguish exhaled breath (EB) and exhaled breath condensate (EBC). We agree that breath metabolomics represents an exciting facet of asthma research that may have substantial for potential for clinical translation. We also wish to make the following points.
Breathomics has been defined as the “metabolomics of breath”; however, it is interchangeably used to include eNOSE studies,2 which are not, in our opinion, inherently “metabolomic” in nature. Fewer than one-half the breath-based studies included in our review used the term “breathomics,” and the lack of consistency even of terminology in metabolomics complicates the synthesis and interpretation of the literature. Further, although, as Peel et al note, some published standards for breath-based studies exist, they have not been universally adopted.3 EBC and EB are still plagued by issues inherent to all metabolomics studies, including incomplete coverage, measures of relative abundance, highly dimensional noisy data sets and confounding, as well as breath-specific challenges such as the absence of a valid dilution factor for EBC.4 Regardless, both EBC and EB have notable advantages over other biosamples, primarily their noninvasive collection and their proximal relationship to the lung and respiratory tract. Accordingly, impressive results have been reported from breath-based studies.2, 4 Replication of significant findings is a key issue for metabolomics. The relevant studies noted by Peel et al that were not included in our original review1 strengthen our conclusions and demonstrate replication for additional metabolites noted in our review, including decane, 4-isopropenyl-1-methylcyclohexene, 1-isopropyl-3-methylbenzene, pentane, and methylated alkanes,2 providing further evidence for their role in asthma.
We welcome the news that international collaborations are working to provide guidelines for standardized methodology to maximize across-study comparability.3 We also second the call by van der Schee et al5 for the development of a “breath cloud” to aid the development of translatable biomarkers. Such initiatives are vital to move the field forward, and we hope that with the collaboration of the whole asthma metabolomics community, including those with expertise in breath, we will soon see the first metabolic biomarkers of asthma in the clinic.
Footnotes
FINANCIAL/NONFINANCIAL DISCLOSURES: See earlier cited article for author conflicts of interest.
References
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