Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Biomarker testing”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1999

Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma.

BACKGROUND: Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study. METHODS: In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19-34 years, forced expiratory volume in one second (FEV1) >75% predicted, concentration of histamine provoking a fall in FEV1 of 20% or more (PC20) <4 mg/ml) inhaled fluticasone propionate (500 microg twice daily) for four weeks. PC20 to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence. RESULTS: In the steroid treated group there was a significant increase in PC20, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time. CONCLUSIONS: Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.

Administration, Inhalation↗
PubMed1999

Increased exhaled nitric oxide in patients with stable chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. Since chronic obstructive pulmonary disease (COPD) is characterised by airway inflammation, a study was undertaken to determine NO levels in the exhaled air of patients with COPD. METHODS: Two groups of patients with clinically stable COPD were studied, 10 current smokers and 10 ex-smokers. Two control groups of healthy subjects consisting of 10 current smokers and 20 non-smokers were also studied. Exhaled NO levels were measured by the collection bag technique and NO chemiluminescence analyser. RESULTS: Mean (SE) levels of exhaled NO in ex-smokers and current smokers with COPD (25.7 (3.0) ppb and 10.2 (1.4) ppb, respectively) were significantly higher than in non-smoker and current smoker control subjects (9.4 (0.8) ppb and 4.6 (0.4) ppb, respectively). In current smokers with COPD exhaled levels of NO were significantly lower than in ex-smokers. In this latter group of patients there was a significant negative correlation between smoking history (pack years) and levels of exhaled NO (r = -0.8, p = 0.002). A positive correlation was seen between forced expiratory volume in one second (FEV1) and levels of exhaled NO (r = 0.65, p = 0.001) in patients with COPD. CONCLUSIONS: These data show that exhaled NO is increased in patients with stable COPD, both current and ex-smokers, compared with healthy control subjects.

Adult↗
PubMed1999

Markers of nitric oxide metabolism in sputum and exhaled air are not increased in chronic obstructive pulmonary disease.

BACKGROUND: Nitric oxide (NO) is involved in inflammation and host defence of the lung. It has been found in increased concentrations in the airways in asthmatic subjects but its levels in patients with chronic obstructive pulmonary disease (COPD) have not been investigated. A study was undertaken to determine whether markers of NO metabolism (NO in exhaled air, iNOS expression in sputum cells, and nitrite + nitrate (NO2-/NO3-) in sputum supernatant) are increased in subjects with COPD, and whether they correlate with inflammatory indices in induced sputum. The associations of these markers with smoking were also assessed. METHODS: Sixteen subjects with COPD (median age 66 years, median forced expiratory volume in one second (FEV1) 63% predicted, eight current smokers) and 16 healthy subjects (median age 63 years, median FEV1 113% predicted, eight current smokers) participated in the study. NO was measured during tidal breathing and sputum was induced by inhalation of hypertonic saline. RESULTS: No differences were observed between subjects with COPD and healthy controls in exhaled NO excretion rate (median 5.15 and 6.25 nmol/min), sputum macrophage iNOS expression (14% and 12%), and sputum supernatant NO2-/NO3- (46 and 73 microM). NO in exhaled air correlated with the percentage of sputum eosinophils in patients with COPD (rho = 0.65, p = 0.009) but not in healthy individuals. Exhaled NO and supernatant NO2-/NO3- levels were lower in healthy smokers than in healthy non/ex-smokers. CONCLUSIONS: Our findings indicate that NO metabolism is not increased in patients with stable COPD. The close association between exhaled NO levels and sputum eosinophils suggests a role for NO in airway inflammation in COPD. Studies performed during exacerbations may clarify this role.

Aged↗
PubMed1996

Breath isoprene: temporal changes in respiratory output after exposure to ozone.

Isoprene is a major hydrocarbon found in human breath. This study was conducted to evaluate whether respiratory isoprene output could serve as a monitor for ozone exposure. Healthy young adult subjects (n = 10) underwent chamber exposure on separate days to filtered air and to a variable concentration of ozone. Exposures had durations of 130 min that included alternate periods of rest and light treadmill exercise; breath was sampled pre- and postexposure. For six subjects, breath was resampled 19 +/- 1 h postexposure. Breath samples were concentrated cryogenically and analyzed by capillary gas chromatography. Isoprene output immediately postexposure was significantly reduced by ozone or filtered air (17 and 19%, respectively). These results suggest that exercise alone reduces isoprene levels in breath without an additive ozone effect. However, in the six subjects restudied 19 +/- 1 h postexposure to ozone, breath isoprene concentrations were now increased above the preexposure output by 99% (P < 0.01) and exceeded the 51% increase in output of isoprene at this time point after filtered-air exposure (P < 0.01). Therefore, breath isoprene is proposed as a noninvasive marker of a physiological response to oxidant-induced injury to epithelial membranes and fluid linings of the lower respiratory tract by ozone.

Adult↗
PubMed2002

Low levels of nitric oxide and carbon monoxide in alpha 1-antitrypsin deficiency.

Quantitations of exhaled nitric oxide (NO) and carbon monoxide (CO) have been proposed as noninvasive markers of airway inflammation. We hypothesized that exhaled CO is increased in individuals with alpha(1)-antitrypsin (AT) deficiency, who have lung inflammation and injury related to oxidative and proteolytic processes. Nineteen individuals with alpha(1)-AT deficiency, 22 healthy controls, and 12 patients with non-alpha(1)-AT-deficient chronic obstructive pulmonary disease (COPD) had NO, CO, CO(2), and O(2) measured in exhaled breath. Individuals with alpha(1)-AT deficiency had lower levels of NO and CO than control or COPD individuals. Alpha(1)-AT-deficient and COPD patients had lower exhaled CO(2) than controls, although only alpha(1)-AT-deficient patients had higher exhaled O(2) than healthy controls. NO was correlated inversely with exhaled O(2) and directly with exhaled CO(2), supporting a role for NO in regulation of gas exchange. Exhaled gases were not significantly related to corticosteroid use or lung function. Demonstration of lower than normal CO and NO levels may be useful as an additional noninvasive method to evaluate alpha(1)-AT deficiency in individuals with a severe, early onset of obstructive lung disease.

Administration, Inhalation↗
PubMed2004

Decreased exhaled nitric oxide as a marker of postinsult immune paralysis.

Nitric oxide (NO) regulates neutrophil migration and alveolar macrophage functions such as cytokine synthesis and bacterial killing, both of which are impaired in immune paralysis associated with critical illness. The aim of this study was to determine whether NO is involved in immune paralysis and whether exhaled NO measurement could help to monitor pulmonary defenses. NO production (protein expression, enzyme activity, end products, and exhaled NO measurements) was assessed in rats after cecal ligation and puncture to induce a mild peritonitis (leading to approximately 20% mortality rate). An early and sustained decrease in exhaled NO was found after peritonitis (from 1 to 72 h) compared with healthy rats [median (25th-75th percentile), 1.5 parts per billion (ppb) (1.2-1.7) vs. 4.0 ppb (3.6-4.3), P < 0.05], despite increased NO synthase-2 and unchanged NO synthase-3 protein expression in lung tissue. NO synthase-2 activity was decreased in lung tissue. Nitrites and nitrates in supernatants of isolated alveolar macrophages decreased after peritonitis compared with healthy rats, and an inhibitory experiment suggested arginase overactivity in alveolar macrophages bypassing the NO substrate. Administration of the NO synthase-2 inhibitor aminoguanidine to healthy animals reproduced the decreased neutrophil migration toward alveolar spaces that was observed after peritonitis, but L-arginine administration after peritonitis failed to correct the defect of neutrophil emigration despite increasing exhaled NO compared with D-arginine administration [4.8 (3.9-5.7) vs. 1.6 (1.3-1.7) ppb, respectively, P < 0.05]. In conclusion, the decrease in exhaled NO observed after mild peritonitis could serve as a marker for lung immunodepression.

Animals↗
PubMed2002

Time course of performance changes and fatigue markers during intensified training in trained cyclists.

To study the cumulative effects of exercise stress and subsequent recovery on performance changes and fatigue indicators, the training of eight endurance cyclists was systematically controlled and monitored for a 6-wk period. Subjects completed 2 wk of normal (N), intensified (ITP), and recovery training. A significant decline in maximal power output (N = 338 +/- 17 W, ITP = 319 +/- 17 W) and a significant increase in time to complete a simulated time trial (N = 59.4 +/- 1.9 min, ITP = 65.3 +/- 2.6 min) occurred after ITP in conjunction with a 29% increase in global mood disturbance. The decline in performance was associated with a 9.3% reduction in maximal heart rate, a 5% reduction in maximal oxygen uptake, and an 8.6% increase in perception of effort. Despite the large reductions in performance, no changes were observed in substrate utilization, cycling efficiency, and lactate, plasma urea, ammonia, and catecholamine concentrations. These findings indicate that a state of overreaching can already be induced after 7 days of intensified training with limited recovery.

Adult↗
PubMed2006

[Role of oxidative stress in respiratory diseases and its monitoring].

Together with inflammation and subsequent remodeling of airways, an imbalance between oxidative and anti-oxidative agents is generated during the development of numerous pulmonary diseases. This process seems to be involved in both the pathogenesis and chronification of asthma, chronic obstructive pulmonary disease (COPD), SOAS, interstitial lung diseases and cystic fibrosis. Reactive oxygen species including superoxide anion, hidroxyl radicals and hydrogen peroxide (H2O2) are synthetised as a response of inflammatory cells and are responsible of the oxidation of nucleic acids, proteins and membrane lipids, leading to cell damage and enhanced inflammation. Until recently, it was difficult to quantify the airway production of reactive oxidative species (ROS). In fact, it has been only in the last few years when it has been possible to determine indirectly the levels of ROS in expired air and in tissue of asthmatic patients. The analysis of exhaled air is a single, reproducible and non-invasive technique which is useful in the study of volatile and non-volatile gases generated in different conditions. The determination of exhaled nitric oxide and carbon monoxide (CO) has a great usefulness in the assessment of asthma. Nitric oxide seems to be closely related to the physiopathology of asthma and COPD. In fact, it is correlated with the levels of sputum eosinophils and with the response to the treatment with steroids. Yet a correlation with the degree of airflow obstruction and the seriousness of the process has not been found. Exhaled CO is another indirect marker of inflammation and it is increased in asthma, COPD, cystic fibrosis and bronchectases. Even though numerous studies have shown its usefulness as a marker of inflammation and in the response to corticosteroids, its clinical application has limitations. In particular, it is not a specific and exclusive marker of oxidative stress and its levels are highly influenced by tobacco smoke. On the other hand, the association between exhaled CO and FEV1 is not clear and no relationship has been proved so far with the improvement of pulmonary function after steroid therapy and with the decrease of maximum expiratory flow at relapses. In this Review, we describe the advances in the knowledge of oxidative stress as a decisive factor in the pathogenesis of prevalent pulmonary diseases, as well as the methods allowing its analysis and monitoring.

Biomarkers↗
PubMed2006

CYP2A6 genotype, phenotype, and the use of nicotine metabolites as biomarkers during ad libitum smoking.

CYP2A6 inactivates nicotine to cotinine and cotinine to 3-hydroxycotinine. We investigated which of plasma nicotine and metabolites were most related to CYP2A6 genotype and smoking levels. We assessed demographic and smoking histories in 152 Caucasian ad libitum smokers, measured breath carbon monoxide (CO) levels, and determined plasma nicotine, cotinine, and 3-hydroxycotinine by high-performance liquid chromatography and CYP2A6 genotypes by PCR. Cigarettes per day was most closely related to CO (r = 0.60, P < 0.001) followed by plasma cotinine (r = 0.53, P < 0.001), whereas plasma cotinine was most strongly correlated with CO levels (r = 0.74, P < 0.001), confirming that cotinine is a good indicator of smoking levels; this was not limited by CYP2A6 variants. 3-Hydroxycotinine/cotinine is reported to be a good marker of CYP2A6 activity, and we found that the 3-hydroxycotinine/(cotinine + nicotine) ratio was most correlated with CYP2A6 genotype (r = 0.38, P < 0.001). Inclusion of the CYP2A6*12A allele strengthened the correlation (r = 0.46, P < 0.001), suggesting that the identification of novel alleles will continue to improve this relationship. Nicotine metabolism is slower in smokers, and we have shown that CYP2A6 is reduced by nicotine treatment in monkeys. Here, we found that plasma nicotine levels were inversely correlated with CYP2A6 activity (3-hydroxycotinine/cotinine, r = -0.41, P < 0.001) among those without CYP2A6 variants, suggesting a reduction in metabolism with higher nicotine levels. Together, these findings (a) confirm the use of plasma cotinine and CO as indicators of Caucasians' smoking levels, and that this is not limited by CYP2A6 genetic variation; (b) indicate that 3-hydroxycotinine/cotinine and 3-hydroxycotinine/(cotinine + nicotine) are moderately good indicators of the CYP2A6 genotype; and (c) support that nicotine exposure may reduce its own metabolism.

Adolescent↗
PubMed2000

Exhaled nitric oxide--is it really a good marker of airway inflammation in bronchial asthma?

BACKGROUND: The concentration of exhaled nitric oxide ([NO]) has been reported to reflect the inflammatory process of airways in patients with bronchial asthma, particularly when they are steroid naive. However, it is not fully understood whether it equally reflects the degree of airway inflammation in patients receiving inhaled corticosteroids, but whose symptoms are not necessarily well controlled. OBJECTIVE: To examine whether the exhaled [NO] really reflects airway inflammation in patients with bronchial asthma, regardless of treatment with inhaled steroids. METHODS: Exhaled [NO] was measured in patients with bronchial asthma (43 steroid treated and 32 steroid naive), chronic obstructive pulmonary disease (COPD) (n = 36), bronchiectasis (n = 10) and in control subjects (n = 26). We examined in each asthmatic group whether the exhaled [NO] correlated with parameters reflecting airway inflammation. RESULTS: Exhaled [NO] was significantly correlated with symptom score, clinical severity, circulating eosinophil count, and the percentage of eosinophils in induced sputum in the steroid-naive asthmatics, but not in the steroid-treated asthmatics, although airway inflammation in this group was not well controlled, as evidenced by clinical symptoms and the higher percentage of eosinophils in induced sputum. Exhaled [NO] from the patients with COPD (6.2 +/- 0. 7 ppb) or bronchiectasis (5.4 +/- 1.3 ppb) was not significantly increased compared with the controls (6.0 +/- 1.0 ppb), and was significantly lower than in the asthmatic patients as a whole (19.0 +/- 2.0 ppb). CONCLUSIONS: Although exhaled [NO] is a useful marker of airway inflammation for differential diagnosis and evaluation of severity in steroid-naive patients with bronchial asthma, it may not be as useful in steroid-treated patients.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Increased vitronectin and endothelin-1 in the breath condensate of patients with fibrosing lung disease.

BACKGROUND: Non-specific interstitial pneumonia (NSIP) and fibrosing alveolitis associated with systemic sclerosis (FASSc) are diseases of unknown aetiology that are characterised by the accumulation of mononuclear cells, followed by the progressive deposition of collagen within the interstitium and subsequent destruction of lung airspace. Better understanding of mediators involved in fibrosis may be useful for early diagnosis and in clinical monitoring of disease progression. OBJECTIVE: The aim of this study was to investigate the presence of two profibrotic markers, the vitronectin and the endothelin-1 (ET-1) in the airways of NSIP and FASSc patients. METHODS: Ten NSIP (6 males, age 57 +/- 2 years) and 15 FASSc (8 males, age 55 +/- 4 years) patients were recruited along with 10 normal subjects (4 male, age 52 +/- 2 years). Vitronectin and ET-1 concentrations were measured in their breath condensate, using a specific enzyme immunoassay. RESULTS: Higher levels of vitronectin and ET-1 were observed in NSIP and FASSc patients [median 92.8 (91.7-93.9) microg/ml; median 8.3 (7.9-9.3) pg/ml] than in control subjects [median 80.3 (89.3-91.4) microg/ml; p < 0.01; median 5.3 (4.9-5.9) pg/ml, p < 0.0001]. We also found increased concentrations of vitronectin in patients with clinical deterioration compared to those remaining stable and in ex-smokers compared to non-smokers and, increased vitronectin and ET-1 in patients treated with steroids compared to untreated patients. CONCLUSION: These findings justify further studies of vitronectin and ET-1 levels in exhaled breath condensate, as a means of monitoring activity and predicting progression of pulmonary fibrosis.

Biomarkers↗
PubMed2003

Acute effect of air pollution on respiratory complaints, exhaled NO and biomarkers in nasal lavages of allergic children during the pollen season.

During 2 months of the pollen season, the acute and putative adjuvant effect of traffic-related air pollution on respiratory health was investigated in children sensitised to grass pollen or house dust mite (HDM). Respiratory complaints were objectified via measurement of exhaled NO and inflammatory mediators in nasal lavage (NAL). During the study children, skin prick negative (n = 31) or positive to grass pollen (n = 22), HDM (n = 34) or grass pollen + HDM (n = 32), kept a daily diary on respiratory symptoms, and NAL and exhaled air was sampled twice a week. The level of air pollutants and pollen was monitored continuously. Like children sensitised to HDM, those sensitised to pollen reported respiratory complaints (shortness of breath, itchy eyes or blocked nose) more frequently than non-sensitised children during (but not before) the pollen season; the respiratory complaints of sensitised children were independent of the pollen level. In addition, exposure to increased levels of PM(10) induces 'shortness of breath' in pollen- and HDM-sensitised children, whereas ozone induces a blocked nose in HDM-sensitised children. Combined exposure to PM(10) + pollen and O(3) + pollen induces a blocked nose in both HDM-sensitised children and children sensitised to pollen + HDM. Significant positive associations were found between eNO and the levels of NO(2), CO, PM(2.5) and pollen in both sensitised and non-sensitised children. At the start of the pollen season, the NAL concentration of eosinophils and ECP in pollen-sensitised children was increased compared to winter, but their levels were not further affected by increased exposure to pollen or air pollution. In conclusion, during the pollen season, sensitised children continuously report a high prevalence of respiratory complaints which coincides with increased levels of upper and lower airway inflammatory markers. No additional pro-inflammatory effect of air pollution was observed, which indicates that air pollution does not facilitate allergen-induced inflammatory responses.

Air Pollution↗
PubMed1999

Infection with Helicobacter pylori is not a major independent risk factor for stable coronary heart disease: lack of a role of cytotoxin-associated protein A-positive strains and absence of a systemic inflammatory response.

BACKGROUND: There is controversy about the association between Helicobacter pylori infection and manifestations of coronary heart disease (CHD), the potential role of the more virulent H pylori strains, and whether or not a positive serostatus is related to increased levels of markers of systemic inflammation. METHODS AND RESULTS: We assessed the prevalence of an infection with H pylori and in particular the anti-cytotoxin-associated protein A (CagA) antibody response of the more virulent strains expressing CagA in 312 patients with stable CHD and in 479 control subjects. Serological prevalence of H pylori infection (IgG titer) was significantly higher in patients than in control subjects after adjustment for age and sex (44.2% versus 31.3%, P<0.001). After adjustment for various covariates in multiple logistic regression, the odds ratio (OR) for CHD was 1.3 (95% CI, 0.9 to 1.9) given a positive IgG serostatus. The prevalence of CagA-positive strains was 27.9% in patients and 21.7% in control subjects (P=0.076 adjusted for age and sex). The OR for CHD in the fully adjusted model was 1.1 (95% CI, 0.7 to 1.7). None of the inflammatory markers (C-reactive protein, fibrinogen, plasma viscosity, or leukocytes) was significantly different according to serostatus. CONCLUSIONS: In this large case-control study, the association of H pylori infection with stable CHD was strongly reduced and was no longer statistically significant after controlling for potential confounders. We also found no independent association between the more virulent strains and CHD. In addition, a positive serostatus was not associated with a systemic inflammatory response. Thus, these data do not support the hypothesis that infection with H pylori might be a major risk factor for stable CHD.

Aged↗
PubMed2004

Oxidative stress and preeclampsia: rationale for antioxidant clinical trials.

Preeclampsia remains a frequent and potentially dangerous complication of pregnancy. The cause remains largely unknown, but oxidative stress and a generalized inflammatory state are features of the maternal syndrome. The placenta appears to be the principal source of free radical synthesis but maternal leukocytes and the maternal endothelium are also likely contributors. Recent reports have suggested an important role for placental trophoblast NAD(P)H oxidase in free radical generation in preeclampsia. The antioxidant vitamin E is now known to have multiple actions in addition to prevention of lipid peroxidation (ie, inhibition of NAD(P)H oxidase activation and the inflammatory response). In view of the abnormally low plasma vitamin C concentrations in preeclampsia, a combination of vitamins C and E is a promising prophylactic strategy for prevention of preeclampsia. Several multicenter randomized clinical trials are now underway. The potential use of antioxidants and the recognized, albeit modest, benefit of low-dose aspirin prophylaxis have heightened the need for a reliable predictive test for preeclampsia. A combination test involving several relevant biomarkers is likely to provide the best predictive potential.

Antioxidants↗
PubMed2026

Plasma von Willebrand Factor and ADAMTS13 Interact With APOE-&#x3b5;4 in Predicting Longitudinal Brain Atrophy and Cognitive Decline Over a 9-Year Follow-Up.

BACKGROUND: Von Willebrand factor (VWF) and ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, 13) are linked to dementia risk, and limited evidence suggests apolipoprotein E (APOE)-&#x3b5;4 alters VWF release. This study assessed whether baseline VWF and ADAMTS13 levels predict neurodegeneration and cognitive decline and evaluated effect modification by APOE-&#x3b5;4 carriership. METHODS: Vanderbilt Memory and Aging Project cohort participants (n=332, 73&#xb1;7&#x2009;years, 59% male) completed serial blood draw, neuropsychological assessment, and brain magnetic resonance imaging over 6.4&#x2009;years (range 1.4-9.7&#x2009;years). Baseline plasma VWF and ADAMTS13 levels were quantified using mass spectrometry and Olink. Fully adjusted linear mixed-effects models related protein&#xd7;time and protein&#xd7;APOE-&#x3b5;4&#xd7;time interaction terms to longitudinal brain magnetic resonance imaging and neuropsychological outcomes. RESULTS: Lower baseline ADAMTS13 predicted faster declines in language (&#x3b2;=0.11, P=0.01), information processing speed (&#x3b2;=0.27, P=0.001), executive function (&#x3b2;=0.01, P=0.03), episodic memory (&#x3b2;=0.01, P=0.03), and visuospatial ability (&#x3b2;=0.11, P=0.001) and faster increases in global (&#x3b2;=-0.29, P=0.01) and frontal (&#x3b2;=-0.17, P=0.01) white matter hyperintensity volumes. Associations between ADAMTS13 and faster rates of cognitive decline and white matter injury were driven by APOE-&#x3b5;4 carriers. Models relating VWF to longitudinal outcomes were null. APOE-&#x3b5;4 interacted with VWF on longitudinal gray matter volumetric outcomes, such that faster rates of global gray matter atrophy were observed with higher baseline VWF levels among APOE-&#x3b5;4 noncarriers only (&#x3b2;=-1530.5, P<0.001). CONCLUSIONS: ADAMTS13 shows promise as a potential plasma biomarker for brain aging outcomes, but additional research is warranted to understand the performance of VWF in the presence versus absence of an APOE-&#x3b5;4 allele.

Humans↗
PubMed1998

Exhaled nitric oxide in human lung transplantation. A noninvasive marker of acute rejection.

Acute allograft rejection in animals and humans has been associated with increased nitric oxide production in the graft. Exhaled nitric oxide (ENO) measurement is a noninvasive method of assessing inflammation in airway diseases, e.g., asthma, which might be applicable to lung transplant recipients. Over 12 months, ENO of lower respiratory origin was measured in 108 lung transplant recipients with a mean time after transplant of 1,083 d. ENO (mean +/- SEM; ppb) in stable patients (19.5 +/- 1.1; p < 0.001) was not different from that of healthy controls (23.8 +/- 3.2). ENO was significantly higher in episodes of clinical acute rejection (51.1 +/- 6.3) compared with stable patients but not elevated in bronchiolitis obliterans syndrome (18.6 +/- 1.5) or pulmonary infection (25.9 +/- 4.0). A retrospective analysis of bronchoscopy findings and concurrent ENO (n = 99) showed that ENO did not vary according to histological findings (normal, acute rejection grade I, nonspecific inflammatory change) or with a positive BAL culture. ENO was not correlated with differential lymphocyte and neutrophil counts. ENO appears to be a valid marker of clinical acute rejection in human lung transplantation as distinct from infection or bronchiolitis obliterans. Furthermore, bronchoscopic findings in the absence of a clinical illness were not associated with a rise in ENO.

Adult↗