Reviews and feature article
Breathomics in the setting of asthma and chronic obstructive pulmonary disease

https://doi.org/10.1016/j.jaci.2016.08.004Get rights and content

Exhaled breath contains thousands of volatile organic compounds that reflect the metabolic process occurring in the host both locally in the airways and systemically. They also arise from the environment and airway microbiome. Comprehensive analysis of breath volatile organic compounds (breathomics) provides opportunities for noninvasive biomarker discovery and novel mechanistic insights. Applications in patients with obstructive lung diseases, such as asthma and chronic obstructive pulmonary disease, include not only diagnostics (especially in children and other challenging diagnostic areas) but also identification of clinical treatable traits, such as airway eosinophilia and risk of infection/exacerbation, that are not specific to diagnostic labels. Although many aspects of breath sampling and analysis are challenging, proof-of-concept studies with mass spectrometry and electronic nose technologies have provided independent studies with moderate-to-good diagnostic and phenotypic accuracies. The present review evaluates the data obtained by using breathomics in (1) predicting the inception of asthma or chronic obstructive pulmonary disease, (2) inflammatory phenotyping, (3) exacerbation prediction, and (4) treatment stratification. The current findings merit the current efforts of large multicenter studies using standardized sampling, shared analytic methods, and databases, including external validation cohorts. This will position this noninvasive technology in the clinical assessment and monitoring of chronic airways diseases.

Section snippets

Definitions

Metabolomics is the study of the metabolic content of a given system, whether that be a cell, organ system, or organism. In exhaled breath gas analysis we detect volatile organic compounds (VOCs) that can arise from or be affected by metabolism, and the term breathomics is currently used to describe this.20 However, it must be emphasized that exhaled breath VOCs do not exclusively represent lung metabolism. Here we describe the sources of breath VOCs and the implications for sampling.

Origins of exhaled breath VOCs

The VOC

Diagnosis: Classifying patients with asthma/COPD versus control subjects

All work to date has been performed in patients with an established diagnosis of asthma or COPD and in control subjects to generate proof of concept that breath VOCs are different in health and disease. In general, there are often potentially relevant clinical parameters that can differ between the case and control groups that could confound the results, such as medication use, comorbidities, and smoking. If breath signals are to prove useful as (composite) biomarkers for diagnosis, they must

Conclusions

Most studies on breathomics in patients with obstructive airways diseases have focused on the diagnosis of asthma or COPD. The major limitation of all except one46 of these studies is that most were not intended to provide a new diagnosis. Furthermore, the disease label might not be as important as the identification of treatable traits.19 There is a clear need for noninvasive biomarkers in patient stratification. Exhaled breath analysis as a substitute for sputum eosinophils can lead to

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    Disclosure of potential conflict of interest: P. Sterk has received a grant from Innovative Medicines Initiative. The rest of the authors declare that they have no relevant conflicts of interest.

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