Design and development of metal-organic framework-based nanocomposite hydrogels for quantification of deferiprone in exhaled breath condensate.

In this study, a novel fluorescence nanoprobe based on Materials of Institute Lavoisier (MIL-101) metal-organic frameworks embedding into the agarose hydrogel is fabricated using a hydrothermal technique. It uses for sensitive quantification of deferiprone in exhaled breath condensate (EBC) samples. The morphology and characterization of MIL-101/agarose nanocomposite hydrogel is studied by transmission electron microscopy, dynamic light scattering instrument, powder X-ray diffraction analysis, and Fourier transform infrared spectroscopy. The probe shows a reasonable fluorescence intensity quenching in the presence of deferiprone due to the interactions between iron centers in MIL-101 (Fe) and deferiprone, which likely form non-fluorescent complexes. The proposed nanoprobe demonstrates a linear calibration curve from 0.005 to 1.5 µg mL- 1 with a detection limit of 0.003 µg mL- 1. The intra- and inter-day precision of the reported method are 0.3% and 0.4% (n = 5, deferiprone concentration = 1.0 µg mL- 1), respectively. This method demonstrates high sensitivity and specificity towards deferiprone in the EBC samples and also presents a sensing platform with simplicity, convenience, fast implementation, and cost-effective in medical monitoring.

Utilizing nitrogen, sulfur, phosphorus, and chlorine co-doped carbon dots as a fluorescent probe for determination of vancomycin in exhaled breath condensate.

Vancomycin is employed to treat infections caused by gram-positive bacteria. Ensuring precise vancomycin dosages is essential to avoid the emergence of bacterial resistance. In the current study, a fluorescent nanoprobe was designed for vancomycin determination in exhaled breath condensate samples. The nanoprobe was based on carbon dots (CDs) doped with nitrogen, sulfur, phosphorus, and chlorine (NSPCl-doped CDs). Vancomycin significantly reduced the fluorescence of NSPCl-doped CDs and presented a quenching process in the analytical response of the probe within a concentration range of 0.01-2.0 µg mL-1 due to forming a non-fluorescent complex. The nanoprobe's intra-day and inter-day relative standard deviations were 1.4 % and 3.2 %, respectively. This nanoprobe was successfully used to determine vancomycin in the patients receiving this drug collected from the expiratory circuit of the mechanical ventilator.

Exhaled breath condensate (EBC) in respiratory diseases: recent advances and future perspectives in the age of omic sciences.

Exhaled breath condensate (EBC) is used as a promising noninvasive diagnostic tool in the field of respiratory medicine. EBC is achieved by cooling exhaled air, which contains aerosolized particles and volatile compounds present in the breath. This method provides useful information on the biochemical and inflammatory state of the airways. In respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, EBC analysis can reveal elevated levels of biomarkers such as hydrogen peroxide, nitric oxide and various cytokines, which correlate with oxidative stress and inflammation. Furthermore, the presence of certain volatile organic compounds in EBC has been linked to specific respiratory conditions, potentially serving as disease-specific fingerprints. The noninvasive nature of EBC sampling makes it particularly useful for repeated measures and for use in vulnerable populations, including children and the elderly. Despite its potential, the standardization of collection methods, analytical techniques and interpretation of results currently limits its use in clinical practice. Nonetheless, EBC holds significant promise for improving the diagnosis, monitoring and therapy of respiratory diseases. In this tutorial we will present the latest advances in EBC research in airway diseases and future prospects for clinical applications of EBC analysis, including the application of the Omic sciences for its analysis.

Comparative analysis of feature annotation methods for SESI-HRMS in exhaled breath analysis.

Secondary electrospray ionization coupled to high-resolution mass spectrometry (SESI-HRMS) is a powerful method for the analysis of exhaled breath in real time. However, feature annotation is challenging due to the flow-injection nature of the technique. To evaluate alternative methods for enhancing feature annotation, a study was conducted where the exhaled breath of sixteen subjects was condensed and analyzed using dynamic headspace vacuum in-trap extraction gas chromatography-mass spectrometry (DHS-V-ITEX-GC-MS) and liquid chromatography coupled to mass spectrometry (LC-MS) using polar and reverse-phase conditions along with a data-independent MS2-acquisition method based on multiple injections. The annotation results obtained from these methods were compared to those from SESI-HRMS. The use of these techniques on breath condensate is unprecedented. The GC-MS method primarily detected compounds of exogenous origin, particularly additives in oral hygiene products like menthol. On the other hand, LC-MS detected a vast number of features, especially with the utilized data-independent acquisition method. Chemical classes to these features were assigned in-silico. In positive ion mode, mostly amino acids and amines were detected, while the largest group in negative ion mode consisted of carboxylic acids. Approximately 25% and 5% of SESI features had a corresponding match with LC-MS and GC-MS. While both GC-MS and LC-MS methods partially overlapped with the SESI features, there was limited overlap of both in the mass-to-charge range from 150 to 200. In conclusion, both GC-MS and LC-MS analysis of breath condensate can serve as supplementary tools for annotating features obtained from SESI-MS. However, to increase confidence in the annotation results, combining these methods with additional on-line fragmentation techniques is recommended.

A cross-sectional study on metoprolol concentrations in various biological samples and their inter-correlations.

BACKGROUND: Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples. METHODS: Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations. RESULTS: Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6-500, 0.4-500, and 0.7-10,000 µg·L- 1 regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L- 1) and (0.60, 0.40, and 0.70 µg·L- 1) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3-4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L- 1. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations. CONCLUSION: Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments.

Extraction and characterization of exosomes from the exhaled breath condensate and sputum of lung cancer patients and vulnerable tobacco consumers-potential noninvasive diagnostic biomarker source.

Noninvasive sample sources of exosomes, such as exhaled breath and sputum, which are in close proximity to the tumor microenvironment and may contain biomarkers indicative of lung cancer, are far more permissive than invasive sample sources for biomarker screening. Standardized exosome extraction and characterization approaches for low-volume noninvasive samples are critically needed. We isolated and characterized exhaled breath condensate (EBC) and sputum exosomes from healthy nonsmokers (n= 30), tobacco smokers (n= 30), and lung cancer patients (n= 40) and correlated the findings with invasive sample sources. EBC samples were collected by using commercially available R-Tubes. To collect sputum samples the participants were directed to take deep breaths, hold their breath, and cough in a collection container. Dynamic light scattering, nanoparticle tracking analysis, and transmission electron microscopy were used to evaluate the exosome morphology. Protein isolation, western blotting, exosome quantification via EXOCET, and Fourier transform infrared spectroscopy were performed for molecular characterization. Exosomes were successfully isolated from EBC and sputum samples, and their yields were adequate and sufficiently pure for subsequent downstream processing and characterization. The exosomes were confirmed based on their size, shape, and surface marker expression. Remarkably, cancer exosomes were the largest in size not only in the plasma subgroups, but also in the EBC (p < 0.05) and sputum (p= 0.0036) subgroups, according to our findings. A significant difference in exosome concentrations were observed between the control sub-groups (p < 0.05). Our research confirmed that exosomes can be extracted from noninvasive sources, such as EBC and sputum, to investigate lung cancer diagnostic biomarkers for research, clinical, and early detection in smokers.

The Role of Exhaled Breath Condensate in Chronic Inflammatory and Neoplastic Diseases of the Respiratory Tract.

Asthma and chronic obstructive pulmonary disease (COPD) are among the most common chronic respiratory diseases. Chronic inflammation of the airways leads to an increased production of inflammatory markers by the effector cells of the respiratory tract and lung tissue. These biomarkers allow the assessment of physiological and pathological processes and responses to therapeutic interventions. Lung cancer, which is characterized by high mortality, is one of the most frequently diagnosed cancers worldwide. Current screening methods and tissue biopsies have limitations that highlight the need for rapid diagnosis, patient differentiation, and effective management and monitoring. One promising non-invasive diagnostic method for respiratory diseases is the assessment of exhaled breath condensate (EBC). EBC contains a mixture of volatile and non-volatile biomarkers such as cytokines, leukotrienes, oxidative stress markers, and molecular biomarkers, providing significant information about inflammatory and neoplastic states in the lungs. This article summarizes the research on the application and development of EBC assessment in diagnosing and monitoring respiratory diseases, focusing on asthma, COPD, and lung cancer. The process of collecting condensate, potential issues, and selected groups of markers for detailed disease assessment in the future are discussed. Further research may contribute to the development of more precise and personalized diagnostic and treatment methods.

Non-invasive detection of Aspergillosis in ventilated patients: Galactomannan analysis in exhaled breath.

This study evaluates the non-invasive diagnosis of Invasive Aspergillosis Pneumonia (IPA) in mechanically ventilated patients by measuring galactomannan (GM) in exhaled breath condensate (EBC). Utilizing a rat model and a novel EBC collection device, we compared GM levels in bronchoalveolar lavage fluid (BALF) and EBC, supplemented by cytokine profiling. Analysis of 75 patients confirmed the device's efficacy, with EBC-GM and BALF-GM showing high diagnostic accuracy (AUC = 0.88). The threshold of 0.235 ng/ml for EBC-GM achieved 92.8 % sensitivity and 66.7 % specificity, with a strong correlation (r = 0.707, P < 0.001) with BALF-GM. This approach offers a safe, effective alternative to invasive diagnostics, enhancing precision with IL-6 and TNF-α measurements. The number registered on clinicaltrails.gov is NCT06333379.

Worse pulmonary function in association with cumulative exposure to nanomaterials. Hints of a mediation effect via pulmonary inflammation.

BACKGROUND: Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project. RESULTS: Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV1 and FEF25 - 75%, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1ß and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV1/FVC ratio. This pattern was not observed for other pulmonary function parameters. CONCLUSIONS: Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.

Clinical Application of Exhaled Breath Condensate in Diagnosis of Diseases.

Respiratory diseases are highly prevalent in the general population, and the morbidity, mortality, and healthcare burden on society at large have been on the rise worldwide. For example, lung cancer is a major contributor to cancer-related mortality around the globe, and identifying clinically relevant biomarkers for lung cancer detection at both early and metastatic stages has been a pressing need. Human metabolism is complicated and may vary with different individuals. Despite advances in the treatment and the early screening of respiratory diseases, most diagnoses are established at a late stage, i.e., when genetic and epigenetic changes have developed. A promising source of biomarkers indicative of the pathogenesis of respiratory diseases is exhaled breath condensate (EBC), a biological fluid and a natural matrix of the respiratory tract. Molecules, such as DNAs, RNAs, proteins, metabolites, and others, are found in EBC, and their presence/absence or changes in concentrations can serve as biomarkers. This review discusses the exhaled breath composition, candidate EBC biomarkers, and the potential to use EBC for diagnosing diseases, therapeutic monitoring, and screening high-risk individuals.

Development and validation of a method for analysis of 25 cannabinoids in oral fluid and exhaled breath condensate.

Currently, there is a significant demand in forensic toxicology for biomarkers of cannabis exposure that, unlike ∆9-tetrahydrocannabinol, can reliably indicate time and frequency of use, be sampled with relative ease, and correlate with impairment. Oral fluid (OF) and exhaled breath condensate (EBC) are alternative, non-invasive sample matrices that hold promise for identifying cannabis exposure biomarkers. OF, produced by salivary glands, is increasingly utilized in drug screening due to its non-invasive collection and is being explored as an alternative matrix for cannabinoid analysis. EBC is an aqueous specimen consisting of condensed water vapor containing water-soluble volatile and non-volatile components present in exhaled breath. Despite potential advantages, there are no reports on the use of EBC for cannabinoid detection. This study developed a supported liquid extraction approach and LC-QqQ-MS dMRM analytical method for quantification of 25 major and minor cannabinoids and metabolites in OF and EBC. The method was validated according to the ANSI/ASB 036 standard and other published guidelines. LOQ ranged from 0.5 to 6.0 ng/mL for all cannabinoids in both matrices. Recoveries for most analytes were 60-90%, with generally higher values for EBC compared to OF. Matrix effects were observed with some cannabinoids, with effects mitigated by use of matrix-matched calibration. Bias and precision were within ± 25%. Method applicability was demonstrated by analyzing ten authentic OF and EBC samples, with positive detections of multiple analytes in both matrices. The method will facilitate comprehensive analysis of cannabinoids in non-invasive sample matrices for the development of reliable cannabis exposure biomarkers.

The Non-Invasive Detection of Pulmonary Exacerbations in Disorders of Mucociliary Clearance with Breath Analysis: A Systematic Review.

Background: Disorders of mucociliary clearance, such as cystic fibrosis (CF), primary ciliary dyskinesia (PCD) and bronchiectasis of unknown origin, are characterised by periods with increased respiratory symptoms, referred to as pulmonary exacerbations. These exacerbations are hard to predict and associated with lung function decline and the loss of quality of life. To optimise treatment and preserve lung function, there is a need for non-invasive and reliable methods of detection. Breath analysis might be such a method. Methods: We systematically reviewed the existing literature on breath analysis to detect pulmonary exacerbations in mucociliary clearance disorders. Extracted data included the study design, technique of measurement, definition of an exacerbation, identified compounds and diagnostic accuracy. Results: Out of 244 identified articles, 18 were included in the review. All studies included patients with CF and two also with PCD. Age and the definition of exacerbation differed between the studies. There were five that measured volatile organic compounds (VOCs) in exhaled breath using gas chromatography with mass spectrometry, two using an electronic nose and eleven measured organic compounds in exhaled breath condensate. Most studies showed a significant correlation between pulmonary exacerbations and one or multiple compounds, mainly hydrocarbons and cytokines, but the validation of these results in other studies was lacking. Conclusions: The detection of pulmonary exacerbations by the analysis of compounds in exhaled breath seems possible but is not near clinical application due to major differences in results, study design and the definition of an exacerbation. There is a need for larger studies, with a longitudinal design, international accepted definition of an exacerbation and validation of the results in independent cohorts.

Non-invasive detection of orthotopic human lung tumors by microRNA expression profiling of mouse exhaled breath condensates and exhaled extracellular vesicles.

Aim: The lung is the second most frequent site of metastatic dissemination. Early detection is key to improving survival. Given that the lung interfaces with the external environment, the collection of exhaled breath condensate (EBC) provides the opportunity to obtain biological material including exhaled miRNAs that originate from the lung. Methods: In this proof-of-principal study, we used the highly metastatic MDA-MB-231 subline 3475 breast cancer cell line (LM-3475) to establish an orthotopic lung tumor-bearing mouse model and investigate non-invasive detection of lung tumors by analysis of exhaled miRNAs. We initially conducted miRNA NGS and qPCR validation analyses on condensates collected from unrestrained animals and identified significant miRNA expression differences between the condensates of lung tumor-bearing and control mice. To focus our purification of EBC and evaluate the origin of these differentially expressed miRNAs, we developed a system to collect EBC directly from the nose and mouth of our mice. Results: Using nanoparticle distribution analyses, TEM, and ONi super-resolution nanoimaging, we determined that human tumor EVs could be increasingly detected in mouse EBC during the progression of secondary lung tumors. Using our customizable EV-CATCHER assay, we purified human tumor EVs from mouse EBC and demonstrated that the bulk of differentially expressed exhaled miRNAs originate from lung tumors, which could be detected by qPCR within 1 to 2 weeks after tail vein injection of the metastatic cells. Conclusion: This study is the first of its kind and demonstrates that lung tumor EVs are exhaled in mice and provide non-invasive biomarkers for detection of lung tumors.

Assessing the inhaled dose of nanomaterials by nanoparticle tracking analysis (NTA) of exhaled breath condensate (EBC) and its relationship with lung inflammatory biomarkers.

The widespread and increasing use of nanomaterials has resulted in a higher likelihood of exposure by inhalation for nanotechnology workers. However, tracking the internal dose of nanoparticles deposited at the airways level, is still challenging. To assess the suitability of particle number concentration determination as biomarker of internal dose, we carried out a cross sectional investigation involving 80 workers handling nanomaterials. External exposure was characterized by portable counters of particles DISCminiTM (Testo, DE), allowing to categorize 51 workers as exposed and 29 as non-exposed (NE) to nanoparticles. Each subject filled in a questionnaire reporting working practices and health status. Exhaled breath condensate was collected and analysed for the number of particles/ml as well as for inflammatory biomarkers. A clear-cut relationship between the number of airborne particles in the nano-size range determined by the particle counters and the particle concentration in exhaled breath condensate (EBC) was apparent. Moreover, inflammatory cytokines (IL-1ß, IL-10, and TNF-α) measured in EBC, were significantly higher in the exposed subjects as compared to not exposed. Finally, significant correlations were found between external exposure, the number concentration of particles measured by the nanoparticle tracking analysis (NTA) and inflammatory cytokines. As a whole, the present study, suggests that NTA can be regarded as a reliable tool to assess the inhaled dose of particles and that this dose can effectively elicit inflammatory effects.

Exhaled breath condensate contains extracellular vesicles (EVs) that carry miRNA cargos of lung tissue origin that can be selectively purified and analyzed.

Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh-EVs). Using our customizable antibody-purification assay, EV-CATCHER, we initially determined that exh-EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh-EVs harbour lung-specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh-EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV-CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti-CCSP/SFTPC EV-CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh-EV subpopulations from EBC allows non-invasive sampling of EVs produced by lung tissues.

Discriminative potential of exhaled breath condensate biomarkers with respect to chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) affecting 334 million people in the world remains a major cause of morbidity and mortality. Proper diagnosis of COPD is still a challenge and largely solely based on spirometric criteria. We aimed to investigate the potential of nitrosative/oxidative stress and related metabolic biomarkers in exhaled breath condensate (EBC) to discriminate COPD patients. METHODS: Three hundred three participants were randomly selected from a 15,000-transit worker cohort within the Respiratory disease Occupational Biomonitoring Collaborative Project (ROBoCoP). COPD was defined using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria as post-bronchodilator ratio of Forced Expiratory Volume in 1st second to Forced Vital Capacity < 0.7 in spirometry validated by an experienced pulmonologist. Discriminative power of biomarker profiles in EBC was analyzed using linear discriminant analyses. RESULTS: Amongst 300 participants with validated spirometry, 50.3% were female, 52.3 years old in average, 36.0% were current smokers, 12.7% ex-smokers with mean tobacco exposure of 15.4 pack-years. Twenty-one participants (7.0%) were diagnosed as COPD, including 19 new diagnoses, 12 of which with a mild COPD stage (GOLD 1). Amongst 8 biomarkers measured in EBC, combination of 2 biomarkers, Lactate and Malondialdehyde (MDA) significantly discriminated COPD subjects from non-COPD, with a 71%-accuracy, area under the receiver curve of 0.78 (p-value < 0.001), and a negative predictive value of 96%. CONCLUSIONS: These findings support the potential of biomarkers in EBC, in particular lactate and MDA, to discriminate COPD patients even at a mild or moderate stage. These EBC biomarkers present a non-invasive and drugless technique, which can improve COPD diagnosis in the future.

Metal and oxidative potential exposure through particle inhalation and oxidative stress biomarkers: a 2-week pilot prospective study among Parisian subway workers.

OBJECTIVE: In this pilot study on subway workers, we explored the relationships between particle exposure and oxidative stress biomarkers in exhaled breath condensate (EBC) and urine to identify the most relevant biomarkers for a large-scale study in this field. METHODS: We constructed a comprehensive occupational exposure assessment among subway workers in three distinct jobs over 10 working days, measuring daily concentrations of particulate matter (PM), their metal content and oxidative potential (OP). Individual pre- and post-shift EBC and urine samples were collected daily. Three oxidative stress biomarkers were measured in these matrices: malondialdehyde (MDA), 8-hydroxy-2'deoxyguanosine (8-OHdG) and 8-isoprostane. The association between each effect biomarker and exposure variables was estimated by multivariable multilevel mixed-effect models with and without lag times. RESULTS: The OP was positively associated with Fe and Mn, but not associated with any effect biomarkers. Concentration changes of effect biomarkers in EBC and urine were associated with transition metals in PM (Cu and Zn) and furthermore with specific metals in EBC (Ba, Co, Cr and Mn) and in urine (Ba, Cu, Co, Mo, Ni, Ti and Zn). The direction of these associations was both metal- and time-dependent. Associations between Cu or Zn and MDAEBC generally reached statistical significance after a delayed time of 12 or 24 h after exposure. Changes in metal concentrations in EBC and urine were associated with MDA and 8-OHdG concentrations the same day. CONCLUSION: Associations between MDA in both EBC and urine gave opposite response for subway particles containing Zn versus Cu. This diverting Zn and Cu pattern was also observed for 8-OHdG and urinary concentrations of these two metals. Overall, MDA and 8-OHdG responses were sensitive for same-day metal exposures in both matrices. We recommend MDA and 8-OHdG in large field studies to account for oxidative stress originating from metals in inhaled particulate matter.

Exploring the Potential Role of Metabolomics in COPD: A Concise Review.

Chronic Obstructive Pulmonary Disease (COPD) is a pathological condition of the respiratory system characterized by chronic airflow obstruction, associated with changes in the lung parenchyma (pulmonary emphysema), bronchi (chronic bronchitis) and bronchioles (small airways disease). In the last years, the importance of phenotyping and endotyping COPD patients has strongly emerged. Metabolomics refers to the study of metabolites (both intermediate or final products) and their biological processes in biomatrices. The application of metabolomics to respiratory diseases and, particularly, to COPD started more than one decade ago and since then the number of scientific publications on the topic has constantly grown. In respiratory diseases, metabolomic studies have focused on the detection of metabolites derived from biomatrices such as exhaled breath condensate, bronchoalveolar lavage, and also plasma, serum and urine. Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy are powerful tools in the precise identification of potentially prognostic and treatment response biomarkers. The aim of this article was to comprehensively review the relevant literature regarding the applications of metabolomics in COPD, clarifying the potential clinical utility of the metabolomic profile from several biologic matrices in detecting biomarkers of disease and prognosis for COPD. Meanwhile, a complete description of the technological instruments and techniques currently adopted in the metabolomics research will be described.