Journal of breath research最新文献

Millions of people worldwide are exposed to environmental arsenic in drinking water, resulting in both malignant and nonmalignant diseases. Interestingly, early life exposure by itself is sufficient to produce higher incidences of these diseases later in life. Based on the delayed onset of disease, we hypothesized that early life arsenic exposure would also induce long-term alterations in the metabolic profile. The objective of this study was to examine metabolomic biomarkers in exhaled breath condensate (EBC) of individuals exposed to arsenic in drinking water early in life, but not later. One hundred and fifty subjects (75 males and 75 females) were initially recruited from Antofagasta, Chile, some of whom were exposed to high water arsenic levels (⩾870µg l^-1; HighAE group), and others, low water arsenic levels (⩽110µg l^-1; LowAE group) early in life (1958-1970). EBC samples were collected for targeted and untargeted metabolomic biomarker analysis. The results showed significantly shorter individuals and reduced pulmonary functions (forced vital capacity, FVC and forced expiratory volume in 1 s, FEV₁) in both males and females in the high-arsenic groups. Males exposed to high arsenic levels also had reduced red blood cell concentrations, as well as higher concentrations of the oxidative stress metabolites 8-OH-2dG and 8-iso-PGF2α. Females in the high-arsenic group showed reductions in 8-OH-2dG. Untargeted analysis revealed metabolomic markers that differentiated the HighAE group from the LowAE group, with a subgroup of markers whose concentrations were proportional to the level of arsenic exposure. Targeted and untargeted analyses of EBC using liquid chromatography-mass spectrometry indicated that adults exposed to high arsenic levels in drinking water in utero and during early childhood retained a modified metabolic profile 47 years after the end of exposure.

Adenoid hypertrophy (AH) is a common condition among pediatric and adolescent populations. The clinical diagnosis primarily relies on rhinoscopy, with a notable absence of noninvasive early diagnostic methods. This study sought to identify potential biomarkers to facilitate the early diagnosis of AH. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was employed to analyze and compare urine samples from 40 patients with AH and 30 healthy controls. To validate and enhance the findings from untargeted metabolomics, targeted metabolomics was conducted using UHPLC-QqQ-MS/MS, aiming to elucidate the relationship between AH and metabolic pathways. The untargeted metabolomics analysis, utilizing multivariate techniques, identified significant differences in the levels of 20 endogenous metabolites in urine samples between the AH and healthy groups. Further investigation of metabolic pathways indicated that sphingolipid and riboflavin metabolism are implicated in the pathogenesis of AH. Riboflavin and phytosphingosine were identified as potential biomarkers using targeted metabolomics. In this study, a comprehensive approach involving both untargeted and targeted metabolomics was employed to investigate diagnostic biomarkers of AH. The abnormal expression levels of riboflavin and phytosphingosine may be related to inflammation, oxidative damage, and immunomodulatory dysfunction in the pathogenesis of AH. The results showed that the identified biomarkers may serve as a novel tool for early diagnosis and tracking of disease progression.

Currently, there are no standardized procedures for sampling exhaled volatile organic compounds (VOCs) from dairy cows. Therefore, this study aimed to compare exhaled VOCs captured on solid-phase extraction (SPE) cartridges using five variants of three breath collection devices (face mask and GreenFeed system [C-Lock, South Dakota, US] collecting unfiltered [GreenFeed_U] and filtered [GreenFeed_F] air). The variants were: a tight-fitting face mask (Mask_N), the Mask_Nwith the openings sealed using activated carbon filters (Mask_F), the Mask_Ncovered with an over-mask ventilated with synthetic air for cow breathing (Mask_V), the GreenFeed_U, and the GreenFeed_F. The variants were compared in two experiments (trial registration number (2023-30-FR) regarding possible VOC carryover over the samples (experiment 1) and their suitability for sampling exhaled VOC from cows (experiment 2). In both experiments, the SPE cartridges were connected to capture VOCs from collected air before GC-MS-based analysis. In experiment 1, our data showed evidence for VOC deposits and potential VOC carryover, particularly for GreenFeed_U(16.3%). In exhaled breath samples from experiment 2, we detected 1217 ± 197 peaks. After subtracting the background air peaks, the exhaled VOCs consisted mostly of esters (20.9%), ketones (13.2%), and alkanes (13.0%). Mask_Vdetected the highest number of aldehydes, ketones, alcohols, alkanes, and alkenes, and GreenFeed_Uthe highest number of esters. The highest relative concentrations of most individual exhaled VOC were detected using Mask_V. The tested variants, except Mask_Fdue to low acceptance of the animals, seemed suitable for exhaled VOC sampling, with Mask_Vseemed to be most suitable due to the detection of the highest VOC number and the lowest VOC carryover.

Bacterial volatile organic compounds (VOCs) have been investigated as a non-invasive approach to diagnosis of infectious diseases. Here, we aimed to explore potential diagnostic markers by profiling VOCs in cultures of unique clinicalClostridioides difficileisolates and stool samples from pediatric patients withC. difficileinfection (CDI) using headspace solid-phase microextraction coupled with gas chromatography combined with mass spectrometry (HS-SPME-GC-MS). A total of 106 individual compounds were detected in 39C. difficileisolate cultures, of which 1-hexanol, ethanol and 4-methylvaleric acid were detected in all bacterial cultures, and 2-methyl-butanoic acid, 1-pentanol, 2-methyl-1-propanol,p-xylene and 6-methyl-2-heptanone were found in 38 (97.4%), 37 (94.9%), 34 (87.2%), 34 (87.2%) and 32 (82.1%) isolate cultures, respectively. The most abundant compound was 4-methylvaleric acid (relative abundance 14.71%, interquartile range 11.73%, 16.38%). A direct comparison of six paired isolates and stools revealed the transfer ofC. difficileisolate VOCs to feces: ethanol was detected in all six pairs, 4-methylvaleric acid was in five pairs and 1-hexanol in four pairs. Fecal VOC patterns between the CDI children and healthy children were significantly different. Receiver operating characteristic analysis showed that 1-propanol, 6-methyl-2-heptanone, phenylethyl alcohol and ethanol presented the highest discrimination value for differentiating feces of CDI children from healthy children. Our data indicate that fecal 1-propanol, 6-methyl-2-heptanone, phenylethyl alcohol and ethanol may be used as potential screening biomarkers for diagnosing CDI.

Some cases of halitosis associated with small intestinal bacterial overgrowth (SIBO) are refractory to antibiotic therapy. The low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) diet (LFD) has emerged as an alternative therapeutic option for SIBO. This retrospective study is the first to investigate the efficacy of LFD in refractory SIBO-associated halitosis. We consecutively reviewed data from 141 patients with refractory SIBO-associated halitosis who underwent a four-week LFD intervention. Halitosis was diagnosed using organoleptic test. Volatile sulfur compounds-including hydrogen sulfide, methyl mercaptan (MM) and dimethyl sulfide (DMS)-were quantified in nasal breath using the OralChroma device. SIBO was confirmed via hydrogen/methane breath test. Serum nutritional parameters were measured to assess nutritional status. Dietary adherence was evaluated using the FODMAP Adherence Report Scale. All patients demonstrated good adherence to the LFD, with no significant changes in nutritional parameters post-treatment. Overall, 80.85% and 78.72% of the patients exhibited SIBO resolution and halitosis improvement, respectively. DMS levels significantly decreased after treatment [41.84 ± 10.73 parts per billion (ppb)vs.19.22 ± 7.91 ppb,P< 0.001]. In contrast, baseline hydrogen sulfide (17.08 ± 12.30 ppb) and MM (13.50 ± 5.65 ppb) levels were low and remained unchanged post-treatment (P> 0.05). Moreover, post-treatment comparison between SIBO-negative and SIBO-positive groups revealed a higher rate of halitosis improvement in the SIBO-negative group (90.35%vs.29.63%, P< 0.001), accompanied by significantly lower DMS levels (17.15 ± 5.81 ppbvs.23.63 ± 9.99 ppb,P= 0.006). Therefore, we conclude that a four-week LFD intervention appears effective for refractory SIBO-associated halitosis, with great adherence and no risk of malnutrition. Its mechanism likely involves SIBO alleviation, thereby reducing intestinal production and breath excretion of volatile malodorous compounds, particularly DMS.

Hyperglycemia can shorten red blood cell (RBC) lifespan, leading to incorrectly measured glycated hemoglobin (HbA1c) values. Correcting for the impact of the RBC lifespan on HbA1c is a critical issue in clinical practice. Before establishing a generally accepted correction formula to account for the impact of RBC lifespan on HbA1c, it is necessary to investigate the duration necessary to emake the hyperglycemia-induced RBC lifespan shortening reverse to normal. This longitudinal clinical trial examined the RBC lifespan in 31 hospitalized patients with type 2 diabetes mellitus by measuring the concentration of exhaled endogenous carbon monoxide. The 31 non-smoking patients with type 2 diabetes were all admitted due to blood glucose (BG) imbalance, and their RBC lifespan was tested at admission, discharge (after ∼2 weeks of intensive glycemic control), and 3 months after discharge. During the period from admission to three months after discharge, RBC lifespan significantly increased in the patients as they underwent drug treatment to control BG (P< 0.05) effectively. HbA1c, fasting plasma glucose, and 2 h postprandial glucose decreased significantly. This study found that (i) a shortened RBC lifespan caused by hyperglycemia is reversible, and (ii) the time required for this reversal is three months of effective drug treatment to control BG.

The non-invasive biological marker exhaled nitric oxide (FE_NO) is increasingly used in asthma, but its clinical role in COPD is less established. FE_NOhas been reported to be both high and low outside the COPD exacerbation period. The study aimed to follow FE_NOvalues over two years during stable conditions in a cohort of COPD subjects participating in the TIE-study (Tools Identifying Exacerbation). The follow-up study included 353 subjects who attended three visits one year apart. The subjects that were ex-smokers (n= 265) had higher FE_NO,50values (median and IQR) compared with current smokers (n= 88), at inclusion 15 (10, 24) versus 9 (7, 15) ppb, after one year 15 (10, 24) versus 10 (7, 18) ppb, and after two years 14 (9, 22) versus 10 (7, 17) ppb, allp< 0.001. All subjects were further divided into two FE_NOgroups: <20 ppb (72%) and ⩾20 ppb (28%). After one year, 81% of the participants remained in the low group and 65% in the high FE_NOgroup. After two years, 71% remained in the low group and 52% in the high FE_NOgroup. The persistent low FE_NOgroup had statistically significantly lower FEV₁%pred and FVC%pred compared to the high FE_NOgroup for all three visits. Among the ex-smokers, the proportion of subjects reporting dyspnoea (mMRC ⩾ 2) was higher in the persistent low FE_NOgroup than in the persistent high FE_NOgroup at all three visits. In conclusion, good consistency in FE_NOover two years is promising for monitoring FE_NOduring stable disease. COPD subjects with persistent low FE_NOhad poorer lung function and reported more dyspnoea than subjects with persistent high FE_NO.

The rapid transfer of volatiles from alveolar blood into the lungs and then out of the body in exhaled breath leads to the common and natural conclusion that these volatiles provide information on health and metabolic processes, with considerable potential as biomarkers for use in the screening, diagnosis and monitoring of diseases. Whilst these exhaled volatiles could well serve as biomarkers for human metabolic processes, thereby providing insights into the clinical and nutritional status of individuals, there exist various confounding factors that limit their easy application. A major confounding factor is the introduction of microbially produced oral volatiles into the exhaled breath, yet these volatiles are often ignored in discovery volatile research studies. Here, we provide a comparative cross-sectional study of selected volatiles commonly found in exhaled breath. Using gas chromatography-ion mobility spectrometry, we monitored these selected volatiles in nasal and oral end-tidal exhaled breath samples from twenty-one volunteers. The signal intensities from untargeted volatile detection were analysed for variances using principal component analysis (PCA), revealing a clear separation correlated with the sampling method. Four compounds representing sampling method-independent (acetone, isoprene, methanol, and 2-pentanone) and four corresponding to sampling method-dependent (1-propanol, 2-propanol, ethanol, and acetoin) were identified and selected based on their high PCA loadings. These compounds are further analysed and discussed to illustrate the extent to which the oral microbiome can influence volatile concentrations in exhaled breath. An additional noteworthy finding of this study is that the nasally sampled selected exhaled volatiles are little influenced by the inhalation route (oral or nasal). The outcome from this study is clear, namely that in order to reduce the influence of the oral microbiome on untargeted discovery breath research studies, end-tidal exhaled nasal breath samples should be taken for endogenous volatile analysis, otherwise oral microbial volatiles could be falsely identified as biomarkers. This is particularly important given the continuous rise in the use of machine learning algorithms and artificial intelligence to identify variations in volatilomes. The development and commercialisation of simple, user-friendly and comfortable end-tidal exhaled nasal sample collection devices are required for nasal sampling to become widely adopted.

Breath contains numerous classes of compounds and biomolecules that could potentially be used as biomarkers for infectious disease as well as a range of other respiratory conditions or states. The goal of this work was to develop a testbed for simultaneous, multi-modal breath measurements. To validate the capabilities of this testbed, a pilot human-subjects research study was conducted to gather a wide range of correlated breath measurements. Seventeen healthy subjects provided breath samples at baseline respiratory rate for particle size, lipid composition and bacterial nucleic acid composition analysis. The majority of the particles the participants exhaled at baseline were smaller than 5μm, consistent with previous literature. A deviation from baseline was detected in one participant immediately prior to COVID-19 symptom onset. This feature persisted for weeks after infection. The exhaled breath particulate contained lipids found in lung surfactant, indicating origin in the lung. Although bacterial DNA was not significantly higher in the exhaled breath particulate than in the environmental background, the metagenome of the breath was distinct from the environment, oral cavity and nasal passages of the participants. The low abundance of the breath microbiome limited analysis. No assertions of statistical significance are offered due to the limited nature of the study scope, the multi-modal breath testbed has promise for discovery of breath biomarkers and as a reference for biomarkers of different classes that are currently being used.

Obtaining multiple sample types from the same exhaled breath condensate (EBC) sample can reduce the number of samples needed for diagnostics purposes, allowing for sampling to be completed quicker and making it even easier to collect breath from patients. In this study, we performed analysis for volatile organic compounds (VOCs) and proteins from the same EBC sample. Pooled EBC samples were split into two groups: three samples that utilized immersion thin film-solid phase microextraction (TF-SPME) sampling for VOC analysis and three samples that did not undergo TF-SPME sampling (non-TF-SPME). All six EBC samples were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS) for proteomics analysis. VOCs were analyzed via two-dimensional gas chromatography-mass spectrometry (GC x GC-MS). One hundred and eighty-four VOCs were found to be more abundant in EBC samples compared to blank or controls. There was no significant difference in the number of proteins detected in the TF-SPME samples compared to the non-TF-SPME samples and 144 of the 206 total unique proteins detected were found in both sample groups. These results indicate that TF-SPME sampling does not negatively affect the number of proteins that can be detected in EBC. This work is a step towards linking VOC and protein data together to obtain multi-omics breath data from a single breath sample. EBC samples were collected as part of a vaccination clinical trial (NCT05346302).