The potential role of exhaled breath analysis in the diagnostic process of pneumonia—a systematic review

Abstract

Diagnostic strategies currently used for pneumonia are time-consuming, lack accuracy and suffer from large inter-observer variability. Exhaled breath contains thousands of volatile organic compounds (VOCs), which include products of host and pathogen metabolism. In this systematic review we investigated the use of so-called 'breathomics' for diagnosing pneumonia. A Medline search yielded 18 manuscripts reporting on animal and human studies using organic and inorganic molecules in exhaled breath, that all could be used to answer whether analysis of VOC profiles could potentially improve the diagnostic process of pneumonia. Papers were categorised based on their specific aims; the exclusion of pneumonia; the detection of specific respiratory pathogens; and whether targeted or untargeted VOC analysis was used. Ten studies reported on the association between VOCs and presence of pneumonia. Eight studies demonstrated a difference in exhaled VOCs between pneumonia and controls; in the individual studies this discrimination was based on unique sets of VOCs. Eight studies reported on the accuracy of a breath test for a specific respiratory pathogen: five of these concerned pre-clinical studies in animals. All studies were valued as having a high risk of bias, except for one study that used an external validation cohort. The findings in the identified studies are promising. However, as yet no breath test has been shown to have sufficient diagnostic accuracy for pneumonia. We are in need of studies that further translate the knowledge from discovery studies to clinical practice.

Applications of Electronic-Nose Technologies for Noninvasive Early Detection of Plant, Animal and Human Diseases

“…Studies of animal and human pulmonary diseases have identified potential biomarkers from analyses of VOC profiles in exhaled breath which may be used to determine the cause of specific diseases and improve the accuracy of disease diagnostic processes for pneumonia and other respiratory diseases [48]. A summary of metabolomic data collected from several studies on pneumonia showed the same consistent VOCs with changes in concentrations of healthy vs. diseased patients based on VOC profiles based on breathomics.…”

Molecular Diagnostics in Pulmonary Infections

“…Another use of mass spectrometry is in the characterization of volatile organic compounds (VOCs)so-called "breathomics," which has been hailed as a promising noninvasive method of sampling the respiratory tract [35]. Exhaled air contains numerous VOCs, including metabolites related to both host and pathogen.…”

Contrary to popular belief, ventilator-associated lower respiratory tract infections are less common in immunocompromised patients

“…Longitudinal analysis of patients developing VA-LRTIs might shed more light on this in the near future, as it has done for the development of exacerbations in cystic fibrosis [22] and COPD [23]. A combination of analysis of the microbiome [24,25], the metabolic environment [26][27][28] and inflammatory markers [29] might provide insight into the host-pathogen interactions that are required for the development of VA-LRTIs and will provide more details on the exact immunological mechanisms that do play a role [30].…”