Exhaled Condensate Research Articles

Roles of Inflammatory Biomarkers in Exhaled Breath Condensates in Respiratory Clinical Fields.

Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.

CORONAVIRUS DISEASECOVID-19: NEW POSSIBILITIES OF DIAGNOSIS

The аim of research – to determinine the diagnostic expediency of using lung condensateas a bioenvironment for the detection of SARS-CoV-2 virus in children with coronavirusdisease COVID-19.Materials and methods. The study was conducted on the basis of infectious diseasesdepartments of the Chernivtsi Children’s Regional Clinical Hospital during December2021 to January 2022. Verifi cation of coronavirus disease COVID-19 was performed bypolymerase chain reaction with reverse transcriptase (set COVID-19 Multiplex RT-PCRin real time regime from Labsystems Diagnostics Oy) with simultaneous detection of threemajor genes ORF1ab, nucleus (E) and envelope (E). The material for the study werenasopharyngeal swabs and pulmonary expiratory. Results. We examined 32 hospitalized children diagnosed with COVID-19 with a meanage of 10,43 ± 0,72 (min = 3, max = 17). The share of boys was 34,4%, girls – 64,6%(p = 0,05), which indicates the practical absence of diff erences in gender. Biomaterialcollection – nasopharyngeal swabs and pulmonary expiration were performed on 6,71± 0,58 (min = 2, max = 16) day of the disease. SARS-CoV-2 virus RNA was detected in46,8% of patients, which almost coincided with the PCR results of 40,62% (p> 0,05).Estimating viral load, the mean value of cycles for PCR of nasopharyngeal smear was30,86 ± 1,39, and for pulmonary expiration – 32,39 ± 1,26. Taking into account theaverage values, depending on the detected gene, it was found that the number of cyclesfor the smear gene E constituted 30,06 ± 1,37 (min = 19, max = 38), the N gene – 30,93 ±1,33 (min = 20, max = 38) for the ORF1ab gene 31,6 ± 1,48 (min = 20, max = 40). Thenumber of cycles for the condensate gene E is 32,6 ± 1,24 (min = 25, max = 38); geneN – 33,36 ± 1,09 (min = 28, max = 39), for ORF1ab – 34,08 ± 1,06 (min = 28, max = 39).The results of the correlation analysis of paraclinical examination of children hospitalizedfor coronavirus disease COVID-19 showed that the use of PCR smear test, comparedwith Ig M, increased the risk of infection with a chance ratio (OR) of 2,27 (95% CI1,26-4,08), relative risk (RR) 1,47 (95% CI 1,01-2,15), absolute risk (R) 0,20. Whenreceiving a positive test result, the post-test probability of a positive result increased12,8%, with a negative one – the result decreased 7,5%. Estimating viral load for geneE, OR = 2,8 (95% CI 1,58-4,98), RR = 1,66 (95% CI 1,22-2,28), R = 0,25, for genes N,ORF1ab OR = 3,2 (95% CI 1,79-5,71), RR = 1,77 (95% CI 1,29-2,44), R = 0,28.Conclusions. At comparative analysis of PCR, performed in diff erentbioenvironmentsof children, the obtainedresults are evidence of better specifi city in the detection of thepathogen when using a traditional smear of the nasopharyngeal mucosa compared withthe use of pulmonary expiratory. However, the study of exhaled condensate can be usedto reduce the isolation time of patients.

Approaches to studying the pathogenesis of asthma

A phenotype describes a group of patients who present with similar clinically observable characteristics. An endotype is a subgroup of patients who share the same pathophysiologic processes that lead to disease presentation. Asthma is a complex chronic disorder that consists of many identifiable phenotypes and two generally accepted endotypes. Understanding the characteristics of the underlying inflammation requires lung biopsies or bronchoalveolar lavage studies, which are invasive and potentially dangerous. There are ongoing investigations that study biomarkers to define asthma phenotypes and endotypes. This article reviews the potential utility of pharmacogenomics, exhaled breath condensates, and serum biomarkers in defining asthma phenotypes and endotypes.
 
 Key words: asthma, pathogenesis, pharmacogenetics, exhaled condensates, biomarkers

Value of soluble triggering receptor expression on myeloid cells-1 level of alveolar fluid in early diagnosis of ventilator-associated pneumonia: a Meta-analysis

Serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a useful biomarker of bacterial infection. However, the diagnostic value of sTREM-1 of alveolar fluid in pulmonary infection is still unclear. This article aimed to explore the value of sTREM-1 of alveolar fluid in the early diagnosis of ventilator-associated pneumonia (VAP) by systematic review of relevant literatures. CNKI, Wanfang, VIP, PubMed/Medline and Embase databases were retrieved. Articles on diagnosis of VAP by sTREM-1 before June 30, 2019 were collected. QUADAS-2 scale provided by Cochrane Collaboration Network was used to evaluate the quality of diagnostic experiments. RevMan 5.3 and Stata 13.0 software were used to complete Meta-analysis. The levels of sTREM-1 between VAP and non-VAP patients were analyzed by Meta-analysis, and then diagnostic test Meta-analysis was conducted. Heterogeneity, sensitivity and publication bias were analyzed. A total of 24 articles were enrolled. QUADAS-2 scale indicated that the selected literature had low bias and high clinical adaptability. (1) In Meta-analysis of sTREM-1 level in alveolar fluid, 20 articles were selected and found to have high heterogeneity (I2 = 94.4%, P = 0.000). The random effects models were used for Meta-analysis. It was indicated that the sTREM-1 level in alveolar fluid of VAP group was significantly higher than that of non-VAP group with significant difference [standardized mean difference (SMD) was 1.47, 95% confidence interval (95%CI) was 1.00-1.95, Z = 6.14, P = 0.000]. By subgroup analysis and Meta-regression analysis, no source of heterogeneity was found. Sensitivity analysis suggested that the results of this Meta-analysis were robust and credible, and Begg funnel plot analysis showed that there was no significant publication bias (Z = 1.46, P = 0.143). (2) A total of 18 articles were included in the Meta-analysis of diagnostic experiments. Deek funnel plot showed publication bias (P = 0.012). The combined sensitivity was 0.87 (95%CI was 0.81-0.91), specificity was 0.80 (95%CI was 0.73-0.86), and diagnostic odds ratio (DOR) was 26 (95%CI was 13-50). Subgroup analysis of three different sources of alveolar fluid (bronchoalveolar lavage fluid, endotracheal aspiration fluid and exhaled ventilator condensate) showed that STREM-1 had a certain value in early diagnosis of VAP. The I2 of combined DOR was 35.4%, and I2 of sensitivity was 79.46%, I2 of specificity was 77.61%, suggesting heterogeneity in the selected literature. Subgroup analysis found that nationality, subject design, sample source, sample size and diagnostic "gold criteria" were related to heterogeneity, but not age. The area under synthetic receiver operating characteristic (SROC) curve (AUC) was 0.90 (95%CI was 0.87-0.92). The detection of sTREM-1 level in alveolar fluid can be used for the early diagnosis of VAP with high sensitivity and specificity. If combined with other biomarkers, it may have more diagnostic value.

Toilets dominate environmental detection of severe acute respiratory syndrome coronavirus 2 in a hospital

Respiratory and fecal aerosols play confirmed and suspected roles, respectively, in transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An extensive environmental sampling campaign of both toilet and non-toilet environments was performed in a dedicated hospital building for patients with coronavirus disease 2019 (COVID-19), and the associated environmental factors were analyzed. In total, 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected within and beyond four three-bed isolation rooms. The data of the COVID-19 patients were collected. The building environmental design and the cleaning routines were reviewed. Field measurements of airflow and CO2 concentrations were conducted. The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms, and 36 from other surfaces outside the isolation rooms in the hospital. Four of these samples were positive, namely two ward door handles, one bathroom toilet seat cover, and one bathroom door handle. Three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever, and one bathroom ceiling exhaust louver. Of the 46 air samples, one collected from a corridor was weakly positive. The two exhaled condensate samples and the two expired air samples were negative. The fecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 in the hospital, highlighting the importance of surface and hand hygiene for intervention.

Application of a Piezoelectric Nose to Assessing the Respiratory System in Calves by Volatile Compounds

The selection and application of an array of piezoelectric sensors for assessing the state of respiratory organs in calves by the composition of the headspace of the exhaled condensate are discussed. We considered the relationship between the output recorded data, calculated data of the sensor array, and the state of the respiratory system of an animal, determined by the results of clinical and laboratory studies. The features of chemical composition of the headspace of samples of the exhaled breath condensate in the norm and with inflammation are described. The results enable recommendations on an array of piezoelectric sensors with selected modifiers and the recorded and calculated parameters of the “electronic nose” to develop a method for the rapid diagnosis of inflammatory diseases of the respiratory system in calves by the composition of the volatile fraction of the exhaled breath condensate.

Progress and prospects of biomarkers of bronchopulmonary dysplasia in premature infants

Bronchopulmonary dysplasia(BPD)is one of the most serious lung diseases in premature infants and an important cause of death in preterm infants.The pathophysiological mechanism of BPD is still unclear.The preventive and targeted treatment strategies for this disease are also very limited.However, various biomarkers have been found in blood, alveolar lavage fluid, exhaled gas condensate, and urine.It is used to identify high-risk children with BPD early and to predict the severity and prognosis of the disease. Key words: Biomarker; Bronchopulmonary dysplasia; Premature

How do cancer-sniffing dogs sort biological samples? Exploring case-control samples with non-targeted LC-Orbitrap, GC-MS, and immunochemistry methods

Early identification of disease onset is regarded as an important factor for successful medical intervention. However, cancer and other long-term latency diseases are rare and may take years to manifest clinically. As such, there are no gold standards with which to immediately validate proposed preclinical screening methodologies. There is evidence that dogs can sort samples reproducibly into yes/no categories based on case-control training, but the basis of their decisions is unknown. Because dogs are sniffing air, the distinguishing chemicals must be either in the gas-phase or attached to aerosols and/or airborne particles. Recent biomonitoring research has shown how to extract and analyze semi- and non-volatile compounds from human breath in exhaled condensates and aerosols. Further research has shown that exhaled aerosols can be directly collected on standard hospital-style olefin polypropylene masks and that these masks can be used as a simple sampling scheme for canine screening. In this article, detailed liquid chromatography-high resolution mass spectrometry (LC-HR-MS) with Orbitrap instrumentation and gas chromatography-mass spectrometry (GC-MS) analyses were performed on two sets of masks sorted by consensus of a four-dog cohort as either cancer or control. Specifically, after sorting by the dogs, sample masks were cut into multiple sections and extracted for LC-MS and GC-MS non-targeted analyses. Extracts were also analyzed for human cytokines, confirming the presence of human aerosol content above levels in blank masks. In preliminary evaluations, 345 and 44 high quality chemical features were detected by LC-MS and GC-MS analyses, respectively. These features were used to develop provisional orthogonal projection to latent structures-discriminant analysis (OPLS-DA) models to determine if the samples classified as cancer (case) or non-cancer (control) by the dogs could be separated into the same groups using analytical instrumentation. While the OPLS-DA model for the LC-HR-MS data was able to separate the two groups with statistical significance, although weak explanatory power, the GC-MS model was not found to be significant. These results suggest that the dogs may rely on the less volatile compounds from breath aerosol that were analyzed by LC-HR-MS than the more volatile compounds observed by GC-MS to sort mask samples into groups. These results provide justification for more expansive studies in the future that aim to characterize specific chemical features, and the role(s) of these features in maintaining homeostatic biological processes.

Soluble triggering receptor expressed on myeloid cells-1 as a useful biomarker for diagnosing ventilator-associated pneumonia after congenital cardiac surgery in children.

The present study aimed to assess the usefulness of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in the diagnosis of ventilator-associated pneumonia (VAP) in paediatric patients with congenital heart disease (CHD) following cardiac surgery. The current prospective study enrolled 48 patients with congenital heart diseases who were suspected of having VAP; these patients were undergoing cardiac surgery between August 2016 and October 2017 in the Cardiac Intensive Care Unit of Shanghai Children's Medical Center (Shanghai, China). A total of 31 patients were diagnosed with VAP using a polymerase chain reaction (PCR) assay, while 17 patients without VAP were designated as the Non-VAP group. A bronchoscopy was performed and samples were collected for measurement on the day that VAP was diagnosed. The sTREM-1 levels were measured in bronchoalveolar lavage fluid (BALF) and exhaled ventilator condensate (EVC). BALF specimens were also sent to the microbiology laboratory for PCR assays and quantitative culturing. The positive detection rate of bacteria using the PCR assay and traditional culture was 64.6% (31/48) and 39.6% (19/48). sTREM-1 was significantly higher in the BALF (146.21 pg/ml vs. 118.06 pg/ml) and EVC (125.29 pg/ml vs. 120.48 pg/ml) of patients with VAP demonstrated compared with the patients without VAP. The findings suggest that the detection of sTREM-1 in BALF and EVC samples may be useful for the diagnosis of VAP following heart surgery in children.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial

Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. People with IPF have increased concentrations of autotaxin in lung tissue and lysophosphatidic acid (LPA) in bronchoalveolar lavage fluid and exhaled condensate. GLPG1690 (Galapagos, Mechelen, Belgium) is a novel, potent, selective autotaxin inhibitor with good oral exposure. We explored the effects of GLPG1690 in patients with IPF. This was a randomised, double-blind, placebo-controlled phase 2a study done in 17 centres in Italy, Ukraine and the UK. Eligible patients were aged 40 years or older, non-smokers, not taking pirfenidone or nintedanib, and had a centrally confirmed diagnosis of IPF. We used a computer-generated randomisation schedule to assign patients 1:3 to receive placebo or 600 mg oral GLPG1690 once daily for 12 weeks. The primary outcomes were safety (adverse events), tolerability, pharmacokinetics, and pharmacodynamics. Spirometry was assessed as a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02738801. Between March 24, 2016, and May 2, 2017, 72 patients were screened., of whom 49 were ineligible and 23 were enrolled in eight centres (six in Ukraine and two in the UK). Six patients were assigned to receive placebo and 17 to receive GLPG1690. 20 patients completed the study after one in each group discontinued because of adverse events and one in the GLPG1690 group withdrew consent. Four (67%) patients in the placebo group and 11 (65%) in the GLPG1690 group had treatment-emergent adverse events, most of which were mild to moderate. The most frequent events in the GLPG1690 group were infections and infestations (ten events) and respiratory, thoracic, and mediastinal disorders (eight events) with no apparent differences from the placebo group. Two (12%) patients in the GLPG1690 group had events that were judged to be related to treatment. Serious adverse events were seen in two patients in the placebo group (one had a urinary tract infection, acute kidney injury, and lower respiratory tract infection and the other had atrioventricular block, second degree) and one in the GLPG1690 group (cholangiocarcinoma that resulted in discontinuation of treatment). No patients died. The pharmacokinetic and pharmacodynamic profiles of GLPG1690 were similar to those previously shown in healthy controls. LPA C18:2 concentrations in plasma were consistently decreased. Mean change from baseline in forced vital capacity at week 12 was 25 mL (95% CI -75 to 124) for GLPG1690 and -70 mL (-208 to 68 mL) for placebo. Our findings support further development of GLPG1690 as a novel treatment for IPF. Galapagos.

Exhaled breath condensate as an alternative sample for drug monitoring.

Exhaled breath condensate as an alternative sample for drug monitoring.

Exhaled breath condensate methods adapted from human studies using longitudinal metabolomics for predicting early health alterations in dolphins.

Monitoring health conditions is essential to detect early asymptomatic stages of a disease. To achieve this, blood, urine and breath samples are commonly used as a routine clinical diagnostic. These samples offer the opportunity to detect specific metabolites related to diseases and provide a better understanding of their development. Although blood samples are commonly used routinely to monitor health, the implementation of a relatively noninvasive technique, such as exhaled breath condensate (EBC) analysis, may further benefit the well-being of both humans and other animals. EBC analysis can be used to track possible physical or biochemical alterations caused by common diseases of the bottlenose dolphin (Tursiops truncatus), such as infections or inflammatory-mediated processes. We have used an untargeted metabolomic method with liquid chromatography-mass spectrometry analysis of EBC samples to determine biomarkers related to disease development. In this study, five dolphins under human care were followed up for 1 year. We collected paired blood, physical examination information, and EBC samples. We then statistically correlated this information to predict specific health alterations. Three dolphins provided promising case study information about biomarkers related to cutaneous infections, respiratory infections, dental disease, or hormonal changes (pregnancy). The use of complementary liquid chromatography platforms, with hydrophilic interaction chromatography and reverse-phased columns, allowed us to detect a wide spectrum of EBC biomarker compounds that could be related to these health alterations. Moreover, these two analytical techniques not only provided complementary metabolite information but in both cases they also provided promising diagnostic information for these health conditions. Graphical abstract Collection of the exhaled condensed breath from a bottlenose dolphin from U.S. Navy Marine Mammal Program (MMP).

Relationship between Oxidative Stress, Physical Activity, and Vitamin Intake in Patients with Asthma

Oxidative stress plays an important role in the pathogenesis of bronchial asthma. Antioxidant nutrition and supplementation have been used to reduce oxidative stress. However, a clinical trial with antioxidant supplementation showed no beneficial effects in patients with asthma. On the other hand, physical activity is related to the prognosis of chronic obstructive pulmonary disease (COPD) and is also related to oxidant status. We investigated the relationships between oxidative stress, serum levels of vitamins, dietary vitamin intake, daily activities, and pulmonary functions in patients with asthma. Eighteen patients with bronchial asthma were enrolled in this study. Reactive oxidative stress was assessed by measuring organic hydroperoxides (diacron reactive oxygen metabolites: dROM) in sera and by measuring H2O2 levels in exhaled breath condensates. The biological antioxidant capacity in serum was evaluated by measuring antioxidant potential capacity against ferric ion. We also assessed pulmonary functions, fraction of exhaled nitric oxide, serum levels of vitamins, dietary vitamin intake, and physical activities. There were no relationships between the index of oxidative stress (dROM and H2O2 in exhaled breathe condensates) and pulmonary functions, serum levels of vitamins, daily vitamin intakes, and activity levels in patients with asthma. The status of transient oxidative stress may not be related to daily activities, vitamin levels, and pulmonary functions in patients with asthma in a real-life setting. However, our results were obtained in the short-term period from a small number of subjects, so a large longitudinal study is required to ascertain the relationships between oxidative stress, physical activity and vitamin intake in patients with asthma.

Increased IL-6 and IL-4 in exhaled breath condensate of patients with nasal polyposis

Nasal polyposis (NP) occurs in about 1-4% of the worldwide population. Increased plasma concentrations of different pro-inflammatory cytokines have been observed in NP, and might be related to the pathogenesis of this syndrome. The present study was designed to investigate IL-6 and IL-4 concentrations in nasal and oral exhaled breath condensate of patients with early and advanced NP, and following polypectomy. Ten individuals with polyposis in early status, twenty-three patients affected by advanced status of NP and ten healthy controls were enrolled into the study. Exhaled breath condensate was collected by all individuals, according to a previous standardised method. An immunoassay kit was used to measure IL-6 and IL-4 levels. Concentrations of oral and nasal exhaled IL-6 and IL-4 were significantly higher in patients with early nasal polyposis and advanced nasal polyposis, compared to healthy controls. A statistically significant decrease of nasally but not of orally exhaled IL-6 (p < 0.001) and IL-4 (p < 0.05) was observed after polypectomy. We consider oral and nasal exhaled condensate of IL-6 and IL-4 as valid inflammatory and oxidative stress marker in patients with nasal polyposis.

The systemic inflammome of severe obesity before and after bariatric surgery.

IntroductionObesity is associated with low-grade systemic inflammation. The “inflammome” is a network layout of the inflammatory pattern. The systemic inflammome of obesity has not been described as yet. We hypothesized that it can be significantly worsened by smoking and other comorbidities frequently associated with obesity, and ameliorated by bariatric surgery (BS). Besides, whether or not these changes are mirrored in the lungs is unknown, but obesity is often associated with pulmonary inflammation and bronchial hyperresponsiveness.ObjectivesWe sought to: (1) describe the systemic inflammome of morbid obesity; (2) investigate the effects of sex, smoking, sleep apnea syndrome, metabolic syndrome and BS upon this systemic inflammome; and, (3) determine their interplay with pulmonary inflammation.MethodsWe studied 129 morbidly obese patients (96 females; age 46±12 years; body mass index [BMI], 46±6 kg/m2) before and one year after BS, and 20 healthy, never-smokers, (43±7 years), with normal BMI and spirometry.ResultsBefore BS, compared with controls, all obese subjects displayed a strong and coordinated (inflammome) systemic inflammatory response (adiponectin, C-reactive protein, interleukin (IL)-8, IL-10, leptin, soluble tumor necrosis factor-receptor 1(sTNF-R1), and 8-isoprostane). This inflammome was not modified by sex, smoking, or coexistence of obstructive sleep apnea and/or metabolic syndrome. By contrast, it was significantly ameliorated, albeit not completely abolished, after BS. Finally, obese subjects had evidence of pulmonary inflammation (exhaled condensate) that also decreased after BS.ConclusionsThe systemic inflammome of morbid obesity is independent of sex, smoking status and/or comorbidities, it is significantly reduced by BS and mirrored in the lungs.

Role of soluble triggering receptor expressed on myeloid cells-1 for diagnosing ventilator-associated pneumonia after cardiac surgery: an observational study

BackgroundThe diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery.MethodsThis was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1.ResultsThirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29).ConclusionMeasurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.

Serum, urine, and breath-related biomarkers in the diagnosis of obstructive sleep apnea in children

The scarcity of pediatric sleep laboratories has thus far precluded timely diagnosis and treatment of pediatric obstructive sleep apnea (OSA), thereby increasing the risk for residual OSA-associated morbidities. Recent developments in transcriptomics, proteomics, and exhaled condensate biomarker discovery will be reviewed in the context of exploring the validity of such methods towards development of reliable and validated diagnostic approaches for pediatric OSA. Gene expression arrays have revealed significant and reproducible changes in a restricted number of genes that should enable discriminatory ability in the recognition of OSA in children. Similarly, a number of urinary proteins have been identified that display outstanding receiver-operator properties towards the diagnosis of pediatric OSA. The technological improvements in both exhaled breath online high-pressure fast chromatography and biosensor surfaces with affinity for volatile compounds should also permit noninvasive diagnosis of pediatric OSA when combined and integrated with computational methods. It is likely that the modest efforts thus far realized in the context of biomarker discovery for the diagnosis and clinical monitoring of OSA in children will experience major acceleration in the upcoming years and lead to a completely novel paradigm in the screening and diagnosis of this disease.

Diagnosing Ventilator-Associated Pneumonia in Critically Ill Patients With Sepsis

Timely diagnosis and prognostic assessment of ventilator-associated pneumonia remain major challenges in critical care. To explore the value of soluble triggering receptor expressed on myeloid cells 1, procalcitonin, and the Clinical Pulmonary Infection Score in the diagnosis and prognostic assessment of ventilator-associated pneumonia. For 92 patients, bronchoalveolar lavage fluid was cultured for detection of microorganisms, serum levels of the receptor and procalcitonin and levels of the receptor in exhaled ventilator condensate were measured, and the Clinical Pulmonary Infection Score was calculated. On the day of diagnosis, patients who had pneumonia had higher serum levels of the receptor, procalcitonin, and C-reactive protein; higher white blood cell counts; and higher pulmonary infection and Sequential Organ Failure Assessment scores than did patients without pneumonia. White blood cell count (odds ratio, 1.118; 95% CI, 1.139-1.204) and serum levels of the receptor (odds ratio, 1.002; 95% CI, 1.000-1.005) may be risk factors for VAP. Serum levels of the receptor plus the pulmonary infection score were the most reliable for diagnosis; the area under the receiver operating characteristic curve was 0.972 (95% CI, 0.945-0.999), sensitivity was 0.875, and specificity was 0.95. For 28-day survival, procalcitonin level combined with pulmonary infection score was the most reliable for prognostic assessment (area under the curve, 0.848; 95% CI, 0.672-1.025). In patients with ventilator-associated pneumonia, serum levels of the receptor plus the pulmonary infection score are useful for diagnosis, and procalcitonin levels plus the pulmonary infection score are useful for prognostic assessment.

Influence of CPAP treatment on airway and systemic inflammation in OSAS patients

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent respiratory disorders in the upper airways during sleep. Although continuous positive airway pressure (CPAP) has been accepted to be the most effective treatment for OSAS, its role on inflammation remains debatable. In this study, our aim was to examine the influence of 3 months of CPAP treatment on tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), 8-isoprostane, and peroxynitrite levels in exhaled breathing condensates (EBC) and serum. Thirty-five patients who were newly diagnosed as moderate or severe OSAS with full night polysomnography and used CPAP therapy regularly for 3 months were included in the study. Polysomnography, spirometric tests, fasting blood samples, and EBC were ascertained on entry into the study and after 3 months of treatment. All patients were assessed monthly for treatment adherence and side effects. We found that all polysomnographic parameters were normalized after CPAP therapy in the control polysomnogram. Also, all markers in EBC and nitrotyrosine and 8-isoprostane levels in serum were decreased significantly with CPAP treatment. Sedimentation rate, C-reactive protein, IL-6, and TNF-α remained unchanged in serum after treatment. We found that baseline nitrotyrosine levels were significantly correlated with apnea-hypopnea index, oxygen desaturation index, and percent time in SpO2 < 90 % (p < 0.01). CPAP therapy has primarily a relevant impact on airways, and nitrotyrosine levels correlated well with severity of OSAS. This treatment decreases both inflammation and oxidative stress levels in airways in OSAS patients. Also, this treatment helps to decrease systemic oxidative stress levels in serum.

Exhaled Breath Condensates: Analyzing the Expiratory Plume

Exhaled Breath Condensates: Analyzing the Expiratory Plume