Liquid chromatography/mass spectrometry analysis of exhaled leukotriene B(4 )in asthmatic children

BACKGROUND: The role of leukotriene (LT) B(4), a potent inflammatory mediator, in atopic asthmatic and atopic nonasthmatic children is largely unknown. The lack of a gold standard technique for measuring LTB(4 )in exhaled breath condensate (EBC) has hampered its quantitative assessment in this biological fluid. We sought to measure LTB(4 )in EBC in atopic asthmatic children and atopic nonasthmatic children. Exhaled nitric oxide (NO) was measured as an independent marker of airway inflammation. METHODS: Fifteen healthy children, 20 atopic nonasthmatic children, 25 steroid-naïve atopic asthmatic children, and 22 atopic asthmatic children receiving inhaled corticosteroids were studied. The study design was of cross-sectional type. Exhaled LTB(4 )concentrations were measured using liquid chromatography/mass spectrometry-mass spectrometry (LC/MS/MS) with a triple quadrupole mass spectrometer. Exhaled NO was measured by chemiluminescence with a single breath on-line method. LTB(4 )values were expressed as the total amount (in pg) of eicosanoid expired in the 15-minute breath test. Kruskal-Wallis test was used to compare groups. RESULTS: Compared with healthy children [87.5 (82.5–102.5) pg, median and interquartile range], exhaled LTB(4 )was increased in steroid-naïve atopic asthmatic [255.1 (175.0–314.7) pg, p < 0.001], but not in atopic nonasthmatic children [96.5 (87.3–102.5) pg, p = 0.59)]. Asthmatic children who were receiving inhaled corticosteroids had lower concentrations of exhaled LTB(4 )than steroid-naïve asthmatics [125.0 (25.0–245.0) pg vs 255.1 (175.0–314.7) pg, p < 0.01, respectively]. Exhaled NO was higher in atopic nonasthmatic children [16.2 (13.5–22.4) ppb, p < 0.05] and, to a greater extent, in atopic steroid-naïve asthmatic children [37.0 (31.7–57.6) ppb, p < 0.001] than in healthy children [8.3 (6.1–9.9) ppb]. Compared with steroid-naïve asthmatic children, exhaled NO levels were reduced in asthmatic children who were receiving inhaled corticosteroids [15.9 (11.5–31.7) ppb, p < 0.01]. CONCLUSION: In contrast to exhaled NO concentrations, exhaled LTB(4 )values are selectively elevated in steroid-naïve atopic asthmatic children, but not in atopic nonasthmatic children. Although placebo control studies are warranted, inhaled corticosteroids seem to reduce exhaled LTB(4 )in asthmatic children. LC/MS/MS analysis of exhaled LTB(4 )might provide a non-invasive, sensitive, and quantitative method for airway inflammation assessment in asthmatic children

Vilanterol trifenatate for the treatment of COPD

Introduction: Currently the treatment of chronic obstructive pulmonary disease (COPD) has limited effectiveness and there is a need to develop new drugs. International guidelines recommend the use of long-acting bronchodilators (β2 agonists and anti-cholinergics/muscarinics), inhaled steroids and associations between these drugs in the maintenance treatment of moderate-to-severe COPD. Area covered: Vilanterol trifenate is a new once-daily highly selective β2-agonist available in USA and Europe in association with umeclidinium bromide (a long-acting anti-muscarnic agent) and fluticasone furoate (an inhaled corticosteroid) for the once-daily maintenance treatment of COPD. Vilanterol combined in fixed-dose treatments has been tested in numerous clinical trials involving thousands of patients. Expert commentary: These new once-daily formulations have the potential to improve compliance to long-term inhaled therapy. This paper will review the clinical and experimental data regarding vilanterol use in the regular treatment of COPD as well as provide a critical discussion of possible future treatment settings

Experiencing indoor navigation on mobile devices

Recently, indoor navigation on mobile devices has received attention from both startups and large vendors, since it has many relevant practical and commercial applications. User positioning and navigation using GPS signals is becoming more and more popular, mainly due to the increasing availability of acceptable quality sensors into low-cost consumer devices as smartphones. However, indoor GPS-navigation is highly unreliable because of the poor communication with satellites and the lack of detailed maps. In this paper we discuss the technologies allowing the indoor computation of accurate location and orientation data, as well as other issues and challenges that indoor navigation apps should cope with. In particular, we present and make explicit reference to a system for indoor navigation (running on a smartphone), which has been designed by the Authors, including the main problems that have been tackled during its implementation

Cochlear Implant Results in Older Adults with Post-Lingual Deafness: The Role of “Top-Down” Neurocognitive Mechanisms

To date, no clear specific cognitive predictors of speech perception outcome in older adult cochlear implant (CI) users have yet emerged. The aim of this prospective study was to increase knowledge on cognitive and clinical predictors of the audiological outcome in adult cochlear implant users. A total of 21 patients with post-lingual deafness, who were candidates for cochlear implantation, were recruited at the Department of Ear, Nose and Throat, University of Torino (Italy) and subjected to a pre-operatory neuropsychological assessment (T0) and an audiological examination after 12 months of implantation (T12). Patients who, at T12, had a 60 dB verbal recognition above 80%, were younger (z = −2.131, p = 0.033) and performed better in the Verbal Semantic Fluency Test at T0 (z = −1.941, p = 0.052) than subjects who had a 60 dB verbal recognition at T12 below 80%. The most significant predictors of the CI audiological outcome at T12 were age (β = −0.492, p = 0.024) and patients’ TMT-A performance at baseline (β = −0.486, p = 0.035). We conclude that cognitive processing speed might be a good predictor of the level of speech understanding in older adult patients with CI after one year of implantation

Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation

<p>Abstract</p> <p>Background</p> <p>Little is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation.</p> <p>Methods</p> <p>Induced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits.</p> <p>Results</p> <p>Sputum SLPI and CC-16 levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.005 and p = 0.08 respectively). SLPI and CC16 levels did not differ before and 6 months after smoking cessation (p = 0.118 and p = 0.543 respectively), neither before and 1 year after smoking cessation (p = 0.363 and p = 0.470 respectively). Nasal lavage SLPI was decreased 12 months after smoking cessation (p = 0.033). Nasal lavage elafin levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.007), but there were no changes 6 months and 1 year after smoking cessation.</p> <p>Conclusions</p> <p>Only nasal lavage SLPI decrease after 1 year after smoking cessation. We may speculate that there is an ongoing inflammatory process stimulating the production of counter-regulating proteins in the airways of healthy ex-smokers.</p

Cognitive correlates in amyotrophic lateral sclerosis: a population-based study in Italy.

BACKGROUND:There is less data available regarding the characteristics of cognitive impairment in patients with amyotrophic lateral sclerosis (ALS) in a population-based series. METHODOLOGY:Patients with ALS incident in Piemonte, Italy, between 2009 and 2011 underwent an extensive neuropsychological battery. Cognitive status was classified as follows: normal cognition, frontotemporal dementia (ALS-FTD), executive cognitive impairment (ALS-ECI), non-executive cognitive impairment (ALS-NECI), behavioural impairment (ALS-Bi), non-classifiable cognitive impairment. We also assessed 127 age-matched and gender-matched controls identified through patients' general practitioners. RESULTS:Out of the 281 incident patients, 207 (71.9%) underwent the neuropsychological testing; of these, 19 were excluded from the analysis due previous conditions affecting cognition. Ninety-one (49.7%) patients were cognitively normal, 23 (12.6%) had ALS-FTD, 36 (19.7%) ALS-ECI, 10 (5.5%) ALS-NECI, 11 (6.0%) ALS-Bi and 11 (6.0%) non-classifiable cognitive impairment, 1 had comorbid Alzheimer's disease. Patients with ALS-FTD were older, had a lower education level, and had a shorter survival than any other cognitive group. Of the nine cases with C9ORF72 mutation, six had ALS-FTD, two ALS-ECI and one was cognitively normal; one of the five patients with SOD1 mutations and one of the five patients with TARBDP mutations had ALS-Bi. CONCLUSIONS:About 50% of Italian patients with ALS had some degree of cognitive impairment, in keeping with a previous Irish study, despite the largely different genetic background of the two populations. The lower educational attainment in patients with ALS-FTD indicated a possible role of cognitive reserve in ALS-related cognitive impairment. ALS-ECI and ALS-NECI may represent discrete cognitive syndromes in the continuum of ALS and FTD

18F-FDG-PET correlates of cognitive impairment in ALS

Objective: To identify the metabolic signature of the various levels of cognitive deficits in amyotrophic lateral sclerosis (ALS) using 18F-2-fluoro-2-deoxy-D-glucose-PET (18F-FDG-PET). Methods: A total of 170 ALS cases consecutively enrolled at the ALS Center of Turin underwent brain 18F-FDG-PET and were classified as displaying normal cognition (ALS-Cn; n 5 94), full-blown frontotemporal dementia (ALS-FTD; n 5 20), executive or nonexecutive cognitive impairment not fulfilling FTD criteria (ALS-Ci; n 5 37), prevalent behavioral changes (n 5 9), or nonclassifiable impairment (n 5 10) according to neuropsychological testing. Group comparisons of 18F-FDG-PET pattern were carried out among the cognitive subgroups. Results: We found a significantly reduced frontal and prefrontal metabolism in ALS-FTD as compared to ALS-Cn, while ALS-Ci showed an intermediate metabolic behavior in frontal cortex, being hypometabolic as compared to ALS-Cn, and relatively hypermetabolic as compared to ALS-FTD. Hypometabolism in frontal regions was associated in all comparisons to hypermetabolism in cerebellum, midbrain, and corticospinal tracts: the more severe the cognitive decline, the larger the size of the cluster and the statistical significance of 18F-FDG uptake differences. Conclusions: This study demonstrated in a large cohort of patients with ALS a continuum of frontal lobe metabolic impairment reflecting the clinical and anatomic continuum ranging from pure ALS, through ALS with intermediate cognitive deficits, to ALS-FTD, and showing that patients with intermediate cognitive impairment display a characteristic metabolic pattern. Since 18F-FDG-PET allows us to estimate the cerebral lesion load in vivo in neurodegenerative diseases, it might be helpful to investigate in ALS its association with neuropsychological testing along the disease course to disclose the early metabolic signature of possible cognitive impairment

Comparative analysis of selected exhaled breath biomarkers obtained with two different temperature-controlled devices

<p>Abstract</p> <p>Background</p> <p>The collection of exhaled breath condensate (EBC) is a suitable and non-invasive method for evaluation of airway inflammation. Several studies indicate that the composition of the condensate and the recovery of biomarkers are affected by physical characteristics of the condensing device and collecting circumstances. Additionally, there is an apparent influence of the condensing temperature, and often the level of detection of the assay is a limiting factor. The ECoScreen2 device is a new, partly single-use disposable system designed for studying different lung compartments.</p> <p>Methods</p> <p>EBC samples were collected from 16 healthy non-smokers by using the two commercially available devices ECoScreen2 and ECoScreen at a controlled temperature of -20°C. EBC volume, pH, NOx, LTB₄, PGE₂, 8-isoprostane and cys-LTs were determined.</p> <p>Results</p> <p>EBC collected with ECoScreen2 was less acidic compared to ECoScreen. ECoScreen2 was superior concerning condensate volume and detection of biomarkers, as more samples were above the detection limit (LTB₄and PGE₂) or showed higher concentrations (8-isoprostane). However, NOx was detected only in EBC sampled by ECoScreen.</p> <p>Conclusion</p> <p>ECoScreen2 in combination with mediator specific enzyme immunoassays may be suitable for measurement of different biomarkers. Using this equipment, patterns of markers can be assessed that are likely to reflect the complex pathophysiological processes in inflammatory respiratory disease.</p