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Effects of particulate air pollution on BPDE-DNA adducts, telomere length, and mitochondrial DNA copy number in human exhaled breath condensate and BEAS-2B cells.

Traffic-related particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) have been linked to respiratory diseases and cancer risk in humans. Genomic damage, including benzo[a]pyrene diolepoxide (BPDE)-DNA adducts as well as alterations in telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) are associated with respiratory diseases. This study aimed to investigate the association between exposure to traffic-related particulate pollutants and genomic damage in exhaled breath condensate (EBC) in human subjects and a bronchial epithelial cell line (BEAS-2B). Among the 60 healthy recruited subjects, residents living in high-traffic-congested areas were exposed to higher concentrations of PM2.5 (1.66-fold, p&#xa0;<&#xa0;0.01), UFPs (1.79-fold, p&#xa0;<&#xa0;0.01), PM2.5-PAHs (1.50-fold, p&#xa0;<&#xa0;0.01), and UFPs-PAHs (1.35-fold, p&#xa0;<&#xa0;0.05), than those in low-traffic-congested areas. In line with increased exposure to particulate air pollution, the high-traffic-exposed group had significantly increased BPDE-DNA adducts (1.40-fold, p&#xa0;<&#xa0;0.05), TL shortening (1.24-fold, p&#xa0;<&#xa0;0.05), and lower mtDNA-CN (1.38-fold, p&#xa0;<&#xa0;0.05) in EBC. The observations in the human study linking exposure to PM2.5, UFPs, PM2.5-PAHs, and UFPs-PAHs with the aforementioned biological effects were confirmed by an in vitro cell-based study, in which BEAS-2B cells were treated with diesel exhaust particulate matter (DEP) containing fine and ultrafine PM and PAHs. Increased BPDE-DNA adducts levels, shortened TL, and decreased mtDNA-CN were also found in treated BEAS-2B cells. The shortened TL and decreased mtDNA-CN were in part mediated by decreased transcript levels of hTERT, and SIRT1, which are involved in telomerase activity and mitochondrial biogenesis, respectively. These results suggest that exposure to traffic-related particulate pollutants can cause genomic instability in respiratory cells, which may increase the health risk of respiratory diseases and the development of cancer.

Humans

Molecular profiling of exhaled breath condensate in respiratory diseases.

BACKGROUND: Respiratory disorders, , continue to pose a major global health burden. Their complexity and heterogeneity challenge accurate diagnosis, effective monitoring, and therapeutic decision-making. Exhaled breath condensate (EBC) provides a reliable, non-invasive means of sampling the molecular environment of the airways. AIM: This review presents the state-of-the-art in EBC-based omics approaches-particularly metabolomics and proteomics-to characterize molecular signatures associated with chronic respiratory (e.g. asthma, chronic obstructive pulmonary disease, and rhinitis) and infectious diseases (e.g. COVID-19). RESULTS: We critically examine findings from studies applying nuclear magnetic resonance (NMR), mass spectrometry (MS), and sensor-based technologies to analyze EBC across various respiratory conditions. NMR, valued for its reproducibility and minimal sample preparation, consistently discriminates among disease phenotypes, identifies distinct metabotypes, and monitors treatment response over time. MS-based approaches afford enhanced sensitivity and specificity, enabling detailed profiling of inflammatory mediators, such as lipid-derived eicosanoids and amino acid derivatives. Proteomic studies reveal protein-level alterations associated with inflammation and tissue remodeling. In COVID-19 and long COVID, metabolomic and volatile compound profiling distinguishes affected individuals from healthy controls suggesting clinical potential. However, inconsistent sample processing and lack of analytical standardization remain limiting factors. CONCLUSIONS: EBC profiling shows clear promise for improving diagnosis, monitoring, and stratification in respiratory medicine. Yet, translation into clinical practice is hindered by limited standardization and validation. Broader, longitudinal studies will be essential to establish robust molecular signatures across disease states. This review underscores the timely need to implement breathomics investigations to gain mechanistic insight into the underlying biology of respiratory diseases.

Humans

Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children.

BACKGROUND: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. METHODS: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children's school and home addresses. RESULTS: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR&#x2009;=&#x2009;1.595), exercise-induced wheezing (OR&#x2009;=&#x2009;1.726), itchy eyes (OR&#x2009;=&#x2009;1.417), and current nasal problems (OR&#x2009;=&#x2009;1.334) (P&#x2009;<&#x2009;0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P&#x2009;<&#x2009;0.05). An increase of 1 &#x3bc;g/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. CONCLUSIONS: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. IMPACT: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables. This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants. An increase of 1 &#x3bc;g/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children.

Humans

Metabolism of nitrosamines in vivo. V Investigation on 14CO2 exhalation, liver RNA labelling and isolation of two metabolites from urine after administration of [2, 5-14C-]dinitrosopiperazine to rats.

The synthesis of N, N'-dinitrosopiperazine and N-nitrosopiperazine, both 14C-labelled in the 2-and 5-position is described. After i.p. application of 10 mg/69.5 muCi/kg[2, 5-14C]-N, N'-dinitrosopiperazine to rats no labelled 7-methylguanine was detected in the liver RNA; 1% of the radioactivity was exhaled as 14CO2, 1% excreted via the bile and about 40% excreted in the urine. Two of the urine metabolites were identified as 3-hydroxynitrosopyrrolidine and 1-nitrosopiperazinone-(3).

Animals

Nature and fate of insecticide residues inhaled by rats in cigarette smoke.

Radioactive carbaryl, carbofuran, parathion, leptophos, and DDT were added to cigarettes and the mainstream smoke was directed to the lungs of rats via the trachea. Total radiocarbon transfer to the lungs ranged from 9 to 15% of that in the tobacco burned during a smoking process involving eight 5-ml puffs. Exhalation of 14C residues during this time was 24 to 30% of that inhaled with all insecticides except carbofuran, of which 42% of the residues was exhaled. After 5 hr, total exhalation of the consumed radiocarbon was 35% for parathion, 65% for carbofuran, and approximately 50% for the other products. The nature of the 14C residues inhaled, their urinary and fecal excretion, and their deposition in and dissipation from various organs and tissues are presented.

Animals

Effects of diethyldithiocarbamate on the catabolism of tyrosine in the rat brain.

500 mg/kg sodium diethyldithiocarbamate (DDC) and trace quantities of uniformly labelled 14C-tyrosine were administered simultaneously to male albino rats of Porton-Wistar strain of approximately 210 g body weight. Thirty minutes later total radioactivity, the concentration and the specific activity of free tyrosine were increased both in plasma and in the brain by 40% compared with rats untreated with DDC. The incorporation of 14C from 14C-tyrosine into the fraction corresponding to the elution of glutamine-glutamate from the amberlite resin column was 80% less in the brain 30 min after DDC. The exhalation of 14CO2 was depressed by 80% in the first hour after DDC. When 14C-tyrosine was given 3.5 h after DDC the only differences between experimental and control rats were the increased incorporation of 14C into the glutamine-glutamate and aspartate fractions and the increased exhalation of 14CO2 which became significiant in the third and fourth half hour periods after the injection of 14C-tyrosine. From the experiments it is concluded that DDC, an inhibitor of dopamine-beta-hydroxylase, also interferes with the major catabolic pathway of tyrosine.

Animals

Using the OPTIMAL Theory to Optimize Aerodynamics in Respiratory Training for Healthy Adults and Individuals With Parkinson's Disease.

BACKGROUND: The OPTIMAL (Optimizing Performance Through Intrinsic Motivation and Attention for Learning) theory is a motor learning framework proposing that optimizing intrinsic motivation enhances motor performance and learning. The theory identifies three key components-Enhanced Expectancies (EE), Autonomy Support (AS) and External Focus of Attention (EF)-which facilitate more efficient, goal-directed movement. These components have been shown to improve motor outcomes in limb-based tasks; however, their application to respiratory training, particularly in clinical contexts such as voice and swallowing therapy in patients with Parkinson's disease (pwPD), has not yet been systematically explored. AIMS: This study aimed to investigate whether implementing OPTIMAL theory strategies during a respiratory muscle strength training (RMST) task improves immediate respiratory motor performance in healthy adults and pwPD. Additionally, we aimed to examine the effects of these strategies on motivation and cognitive engagement. METHODS: This quasi-randomized, single-session trial included 47 participants: Healthy CONTROL (n = 17), Healthy OPTIMAL (n = 16) and PD OPTIMAL (n = 14). Healthy participants were quasi-randomly assigned to either intervention or control conditions, whereas pwPD completed the intervention only. All participants completed a single respiratory session that included baseline, practice and retention phases. Outcome measures included peak expiratory flow, cough peak expiratory flow, cognitive engagement (EEG-based Cognitive Engagement Index) and self-administered motivation questionnaire. OUTCOMES AND RESULTS: Exhalation force improved from baseline to retention in the Healthy OPTIMAL group (baseline: M = 296 L/min; retention: M = 338 L/min; p < 0.001) and the PD OPTIMAL group (baseline: M = 315 L/min; retention: M = 370 L/min; p < 0.0001), but not in the Healthy CONTROL group (p > 0.05). No significant changes in cough strength were observed in any group. No correlations were found between cognitive engagement and exhalation force or motivation scores. However, motivation increased more in the Healthy OPTIMAL group (Questionnaire 1: M = 57.2; Questionnaire 2: M = 60.7) and the PD OPTIMAL group (Questionnaire 1: M = 60.1; Questionnaire 2: M = 62.8) than in the Healthy CONTROL group (Questionnaire 1: M = 61.1; Questionnaire 2: M = 62.5). CONCLUSIONS AND IMPLICATIONS: Implementing the OPTIMAL theory enhances immediate respiratory motor performance in both healthy participants and pwPD. OPTIMAL theory has clinical value in voice and swallowing therapy, although further research is needed to establish long-term efficacy and clinical impact. WHAT THIS PAPER ADDS: What is already known on the subject Motivation is a critical factor in rehabilitation. The OPTIMAL theory has been shown to improve both motivation and motor performance in limb-based tasks. Its impact on respiratory training, however, has not been previously examined. What this paper adds to the existing knowledge This study shows that applying OPTIMAL strategies during a respiratory muscle strength training task significantly improved peak expiratory flow in both healthy adults and people with Parkinson's disease. What are the potential or clinical implications of this work? Integrating the OPTIMAL theory principles into respiratory therapy may enhance motor outcomes, supporting voice, swallowing and cough rehabilitation.

Humans

Infectivity titers of adenovirus type 5 suspensions after exposure to cigarette smoke.

Suspension of adenovirus type 5 in 2.0 ml of cell culture fluid at 37 degrees C were subjected to smoke from four cigarettes over a 4-h period. The cigarettes were smoked in a normal manner, and the inhaled smoke was exhaled through glass tubing into the virus-containing fluid. The virus suspensions were then titrated, using monolayer cultures of HEp-2 cells. Smoke from filter-tipped or regular cigarettes caused a 2- to 3-log drop in titer of tissue culture infectious doses of adenovirus type 5 per 0.1 ml of virus suspension. No reductions in titers were observed with parallel suspensions of the virus subjected to normal inhaled and exhaled air.

Adenoviruses, Human

The Human Breath Volatilome Responds to Exercise and Recovery: An Untargeted Profiling Study.

Exercise induces metabolic and physiological changes across multiple organs. These changes have been studied via several human biofluids, including urine and blood; however, they remain mainly underexplored in exhaled breath. In this exploratory pilot study, we performed untargeted profiling of breath volatile compounds (VCs) to investigate how exercise and recovery influence breath chemical composition. Breath samples were collected from 71 university athletes from three sporting disciplines. Across 143 breath samples, a total of 1,204 unique breath VCs were detected. There were distinct volatilomic responses to physical activity and recovery, regardless of the athlete's sport. Comparison of paired samples using volcano analysis collected before and during exercise identified 80 breath VCs that significantly increased and 182 that significantly decreased. Similarly, a comparison of samples collected before and after exercise identified 11 compounds that decreased significantly. These findings demonstrate that exercise induces measurable changes in the breath volatilome. However, due to the lack of standardized exercise intensity measures and physiological monitoring, the results should be considered exploratory and interpreted cautiously within the field of exercise science.

Exhaled breath analysis

Histamine metabolism in cluster headache and migraine. Catabolism of 14C histamine.

Various parameters of histamine metabolism were studied in patients with migraine, cluster headache and chronic paroxysmal hemicrania. These included urinary excretion of radioactivity and of 14C histamine and its metabolites, exhaled 14CO2 and fecal radioactivity after oral as well as subcutaneous administration of radioactive histamine. No marked deviation from the normal was found except in one patient with the cluster headache variant, chronic paroxysmal hemicrania, in whom an aberration in 14C histamine degradation seemed to be present. Only minute quantities of the 14C histamine metabolite C14 imidazoleacetic acid riboside seemed to be formed during a period with severe paroxysms. During a symptom-free period no deviation from normal was observed. The most likely explanation for this finding seems to be a defect in the conversion of imidazoleacetic acid to its riboside. This defect may possibly explain the increased urinary excretion of histamine in this particular patient. The relationship of this metabolic aberration to the production of headache still remains dubious for various reasons.

Biotransformation

Rate of drug metabolism in man measured by 14CO2-breath analysis.

Exhalation of 14CO2 in breath has been used to assess the rate of hepatic demethylation of (14C-dimethyl)aminopyrine, but due to the complexity of aminopyrine metabolism the pharmacokinetics of the procedure are insufficiently understood. Therefore, studies were performed in five individuals after oral administration of (14C-methoxy)glycodiazine, a model substance with relatively simple kinetic properties. Plasma concentrations of the drug and urinary output of its metabolites measured by high pressure liquid chromatography were analysed by a two-compartment open model. The terminal disappearance of 14CO2 from breath was practically identical with the terminal disappearance of glycodiazine from plasma, which could be correlated with the plasma clearance of free glycodiazine. The mean transit time of 14C-atoms from plasma to breath was 3 h. These results contribute to the pharmacokinetic basis for use of 14C-demethylation breath tests. In particular, they are consistent with the hypothesis that 14CO2-breath analysis may be used to assess certain pharmacokinetic parameters of appropriately labelled test compounds. These parameters may not necessarily be a direct reflection of the rate of demethylation.

Adult

[Increased demethylation of aminopyrine under long-term treatment with anticonvulsive drugs (author's transl)].

Demethylation of aminopyrine was measured in 25 healthy controls and 19 epileptics on long-term treatment with anticonvulsants by the 14C-aminopyrine breath test. Compared to controls epileptics exhibited increased cumulative 14CO2-exhalation rates (88.7% at 30 min, 62.6% at 2 h and 24.8% at 8h) following ingestion of 2 mu Ci 14C-aminopyrine. The results suggest that long-term treatment with antiepileptic drugs results in increased demethylating function of the liver which can be easily detected by a simple breath analysis technique like decreased demethylation in chronic liver disease.

Aminopyrine

Modeling airborne transmission of viral genome using computational fluid dynamics simulation: A case study for SARS-CoV-2 virus.

Predicting indoor air quality during infectious disease conditions relies on models simulating particle materials (PM)/bioaerosols distribution. Understanding the thermo-fluid properties of exhaled air is crucial for comprehending disease transmission dynamics. This study employs a computational fluid dynamics (CFD) model to simulate cough-induced particle dispersion in a closed space. Furthermore, the number of released particles and the presence of SARS-CoV-2 viral genomes by a cough were assessed (in eight COVID-19 patients). According to the CFD model, in the first 30&#xa0;s of cough, the vertical height and lateral breadth of the particles' dispersion were up to 138cm and 92cm, respectively. As the distance from the patient's respiratory zone increased, the lateral distribution width of particles expanded, reaching 1.3&#xa0;m at 2.4&#xa0;m away. Larger droplets (>&#x2009;62.5&#xb5;) were deposited at shorter distances, while smaller particles remained airborne longer. The comparison of experimental and simulated results focused on particle dispersion at specific distances from the patient, particularly in the 2.5&#xb5; range. The distribution pattern of PM2.5 and PM10 at a distance of 1 and 2&#xa0;m for women, not men, is similar to the distribution pattern of PM in CFD modeling. Viral genome detection was more prevalent in particles near the left side of the body, especially within the first 20&#xa0;min post-cough, exhibiting a correlation with CFD predictions.

Airborne transmission

Nasal secretion from normal subjects.

A new method of collection of nasal secretion, by dilution with condensed mositure of the exhaled air, is described. This method may be defined as a sefl-administered nasal lavage. The method permits quantitative determination of pH, relative viscosity, and electrolyte and protein composition. Concentrations of sodium, potassium, calcium, total protein, IgA, IgG, IgM, secretory compoenent and polysaccharide are reported for normal subjects. Significant correlations were noted between the relative viscosity and variables: dry weight, total protein and calcium.

Calcium

Clinical insights into catathrenia: A real-world analysis from a tertiary sleep center.

INTRODUCTION: Catathrenia is a rare sleep-related breathing disorder marked by groaning during prolonged expiration, often underrecognized or misdiagnosed as obstructive or central sleep apnoea (OSA or CSA) or parasomnia. Understanding its clinical and polysomnographic features is essential for accurate diagnosis and management. MATERIALS AND METHODS: We performed a retrospective observational study of adult patients diagnosed with catathrenia at Servi&#xe7;o de Medicina do Sono de Coimbra. Diagnosis was established by attended overnight polysomnography (PSG) with synchronised audio-video recording. Demographic data, symptoms, comorbidities, PSG variables, treatment modalities, and outcomes were reviewed. Catathrenia events were defined as deep inhalation followed by prolonged exhalation with monotonous groaning. RESULTS: Ten patients were included. Median age was 46&#x2009;years (range 27-78), mostly female (70%). Common comorbidities included obesity (n&#x2009;=&#x2009;4), depression (n&#x2009;=&#x2009;2), Parkinson's disease (n&#x2009;=&#x2009;1), and restless legs syndrome (n&#x2009;=&#x2009;1). Six patients (60%) had concomitant obstructive sleep apnoea (OSA). Seven patients had excessive daytime sleepiness (Epworth Sleepiness Scale&#x2009;>&#x2009;10). All catathrenia episodes occurred exclusively during REM sleep. Continuous positive airway pressure (CPAP) therapy was the most frequently used treatment and was associated with objective or subjective improvement in most patients. Two patients experienced spontaneous remission. CONCLUSION: Catathrenia remains underdiagnosed and can mimic other sleep disorders. Recognition of its REM-sleep predominance and PSG pattern is essential. Individualised treatment, often involving PAP therapy, may improve symptoms and patient outcomes.

Humans

A simple method of monitoring carbon dioxide output in anaesthetized patients.

The mean CO2 output during anaesthesia in paralyzed patients can be monitored by continuous capnographic analysis of the total exhaled gases, the latter being mechanically integrated by pumice canisters. The gas is evacuated from the Hafnia A circuit via an ejector flowmeter. The results are not influenced by the flow rates employed.

Anesthesia