skip to main content

Title: Preliminary method for profiling volatile organic compounds in breath that correlate with pulmonary function and other clinical traits of subjects diagnosed with cystic fibrosis: a pilot study

Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx), which in turn accelerate pulmonary function decline and decrease survival rate. An overarching challenge is that there is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant research priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other CF clinical factors, exhaled breath samples were collected from 18 subjects with CF, with some experiencing PEx and others serving as a baseline. Exhaled breath was collected in Tedlar bags during tidal breathing and cryotransferred to headspace vials for VOC analysis by solid phase microextraction coupled to gas chromatography–mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator treatment (HEMT), and more » the need for inhaled tobramycin) were also explored. Two volatile aldehydes (octanal and nonanal) were upregulated in patients not taking the HEMT. VOCs correlating to potential confounding variables were removed and then analyzed by regression for significant correlations with FEV1pp measurements. Interestingly, the VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowestp-value when comparing subjects at baseline and during PEx. Other VOCs that were differentially expressed due to PEx that were identified in this study include durene, 2,4,4-trimethyl-1,3-pentanediol 1-isobutyrate and 5-methyltridecane. Receiver operator characteristic curves were developed and showed 3,7-dimethyldecane had higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that VOCs in exhaled breath may be a rich source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.

« less
; ; ; ; ; ;
Publication Date:
Journal Name:
Journal of Breath Research
Page Range or eLocation-ID:
Article No. 027103
IOP Publishing
Sponsoring Org:
National Science Foundation
More Like this
  1. Fast diagnostic results using breath analysis are an anticipated possibility for disease diagnosis or general health screenings. Tests that do not require sending specimens to medical laboratories possess capabilities to speed patient diagnosis and protect both patient and healthcare staff from unnecessary prolonged exposure. The objective of this work was to develop testing procedures on an initial healthy subject cohort in Hawaii to act as a range-finding pilot study for characterizing the baseline of exhaled breath prior to further research. Using comprehensive two-dimensional gas chromatography (GC×GC), this study analyzed exhaled breath from a healthy adult population in Hawaii to profile the range of different volatile organic compounds (VOCs) and survey Hawaii-specific differences. The most consistently reported compounds in the breath profile of individuals were acetic acid, dimethoxymethane, benzoic acid methyl ester, and n-hexane. In comparison to other breathprinting studies, the list of compounds discovered was representative of control cohorts. This must be considered when implementing proposed breath diagnostics in new locations with increased interpersonal variation due to diversity. Further studies on larger numbers of subjects over longer periods of time will provide additional foundational data on baseline breath VOC profiles of control populations for comparison to disease-positive cohorts.
  2. Building insulation materials can affect indoor air by (i) releasing primary volatile organic compounds (VOCs) from building enclosure cavities to the interior space, (ii) mitigating exposure to outdoor pollutants through reactive deposition (of oxidants, e.g. , ozone) or filtration (of particles) in infiltration air, and (iii) generating secondary VOCs and other gas-phase byproducts resulting from oxidant reactions. This study reports primary VOC emission fluxes, ozone (O 3 ) reaction probabilities ( γ ), and O 3 reaction byproduct yields for eight common, commercially available insulation materials. Fluxes of primary VOCs from the materials, measured in a continuous flow reactor using proton transfer reaction-time of flight-mass spectrometry, ranged from 3 (polystyrene with thermal backing) to 61 (cellulose) μmol m −2 h −1 (with total VOC mass emission rates estimated to be between ∼0.3 and ∼3.3 mg m −2 h −1 ). Major primary VOC fluxes from cellulose were tentatively identified as compounds likely associated with cellulose chemical and thermal decomposition products. Ozone-material γ ranged from ∼1 × 10 −6 to ∼30 × 10 −6 . Polystyrene with thermal backing and polyisocyanurate had the lowest γ , while cellulose and fiberglass had the highest. In the presence of O 3 , totalmore »observed volatile byproduct yields ranged from 0.25 (polystyrene) to 0.85 (recycled denim) moles of VOCs produced per mole of O 3 consumed, or equivalent to secondary fluxes that range from 0.71 (polystyrene) to 10 (recycled denim) μmol m −2 h −1 . Major emitted products in the presence of O 3 were generally different from primary emissions and were characterized by yields of aldehydes and acetone. This work provides new data that can be used to evaluate and eventually model the impact of “hidden” materials ( i.e. , those present inside wall cavities) on indoor air quality. The data may also guide building enclosure material selection, especially for buildings in areas of high outdoor O 3 .« less
  3. Abstract

    Breast cancer is the most common cancer detected in women and current screening methods for the disease are not sensitive. Volatile organic compounds (VOCs) include endogenous metabolites that provide information about health and disease which might be useful to develop a better screening method for breast cancer. The goal of this study was to classify mice with and without tumors and compare tumors localized to the mammary pad and tumor cells injected into the iliac artery by differences in VOCs in urine. After 4T1.2 tumor cells were injected into BALB/c mice either in the mammary pad or into the iliac artery, urine was collected, VOCs from urine headspace were concentrated by solid phase microextraction and results were analyzed by gas chromatography-mass spectrometry quadrupole time-of-flight. Multivariate and univariate statistical analyses were employed to find potential biomarkers for breast cancer and metastatic breast cancer in mice models. A set of six VOCs classified mice with and without tumors with an area under the receiver operator characteristic (ROC AUC) of 0.98 (95% confidence interval [0.85, 1.00]) via five-fold cross validation. Classification of mice with tumors in the mammary pad and iliac artery was executed utilizing a different set of six VOCs, withmore »a ROC AUC of 0.96 (95% confidence interval [0.75, 1.00]).

    « less
  4. Molecular composition, viscosity, and liquid–liquid phase separation (LLPS) were investigated for secondary organic aerosol (SOA) derived from synthetic mixtures of volatile organic compounds (VOCs) representing emission profiles for Scots pine trees under healthy and aphid-herbivory stress conditions. Model “healthy plant SOA” and “stressed plant SOA” were generated in a 5 m 3 environmental smog chamber by photooxidation of the mixtures at 50% relative humidity (RH). SOA from photooxidation of α-pinene was also prepared for comparison. Molecular composition was determined with high resolution mass spectrometry, viscosity was determined with the poke-flow technique, and liquid–liquid phase separation was investigated with optical microscopy. The stressed plant SOA had increased abundance of higher molecular weight species, reflecting a greater fraction of sesquiterpenes in the stressed VOC mixture compared to the healthy plant VOC mixture. LLPS occurred in both the healthy and stressed plant SOA; however, stressed plant SOA exhibited phase separation over a broader humidity range than healthy plant SOA, with LLPS persisting down to 23 ± 11% RH. At RH ≤25%, both stressed and healthy plant SOA viscosity exceeded 10 8 Pa s, a value similar to that of tar pitch. At 40% and 50% RH, stressed plant SOA had the highest viscosity,more »followed by healthy plant SOA and then α-pinene SOA in descending order. The observed peak abundances in the mass spectra were also used to estimate the SOA viscosity as a function of RH and volatility. The predicted viscosity of the healthy plant SOA was lower than that of the stressed plant SOA driven by both the higher glass transition temperatures and lower hygroscopicity of the organic molecules making up stressed plant SOA. These findings suggest that plant stress influences the physicochemical properties of biogenic SOA. Furthermore, a complex mixture of VOCs resulted in a higher SOA viscosity compared to SOA generated from α-pinene alone at ≥25% RH, highlighting the importance of studying properties of SOA generated from more realistic multi-component VOC mixtures.« less
  5. COVID-19 may present with a variety of clinical syndromes, however, the upper airway and the lower respiratory tract are the principle sites of infection. Previous work on respiratory viral infections demonstrated that airway inflammation results in the release of volatile organic compounds as well as nitric oxide. The detection of these gases from patients’ exhaled breath offers a novel potential diagnostic target for COVID-19 that would offer realtime screening of patients for COVID-19