Increased frequency dependence of specific airway resistance in patients with laryngeal hemiplegia

The aim of this study was to investigate whether patients with laryngeal hemiplegia (LH) show a frequency-dependent increase in specific airway resistance (sRaw), measured by body plethysmography. In addition to the flow-volume loop, usually considered in the functional evaluation of upper airway obstructions, variations in sRaw at respiratory frequencies of 30\ub15 (=0.5 Hz), 60\ub15 (=1 Hz) and 90\ub15 breaths\ub7min-1 (=1.5 Hz) in 21 never-smoking patients (LH group, mean age\ub1SD 55\ub112.09 yrs; 17 females) whose unilateral vocalcord paralysis was documented by laryngoscopy and who had no signs or symptoms of other respiratory diseases studied. They were compared to 21 healthy control subjects (C group: 50.1\ub115.44 yrs; 10 females). The sRaw values at 30\ub15 breaths\ub7min-1 were similar in the two groups (5.54\ub11.88 versus 5.68\ub11.06 cmH2O\ub7s-1; p=NS), but at increasing frequencies (30\ub15, 60\ub15 and 90\ub15 breaths\ub7min-1), they progressively and significantly increased in the LH patients (from 5.54\ub11.88 to 6.63\ub11.96 and 8.05\ub12.6 cmH2O\ub7s-1; p<0.0005), and not significantly in controls (5.68\ub11.06, 5.85\ub10.95 and 5.9\ub11.12 cmH2O\ub7s; p=NS). Linear discriminant analysis using \u394sRaw (sRaw at 1.5 Hz-sRaw at 0.5 Hz) and forced inspiratory flow at 50% of the vital capacity made it possible to correctly classify all of the controls and 19 of the 21 patients. In conclusion, the multiple, rapid and noninvasive plethysmographical testing of frequency-dependent increase in specific airway resistance with the flow-volume loop, allows the sufficiently satisfactory discrimination of laryngeal hemiplegia patients from controls

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

Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear. Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients. Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens. Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1 beta, IL-8, and IL-1 beta. Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.Peer reviewe

Excitability of the Primary Motor Cortex Increases More Strongly with Slow- than with Normal-Speed Presentation of Actions

Introduction: The aim of the present study was to investigate how the speed of observed action affects the excitability of the primary motor cortex (M1), as assessed by the size of motor evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS). Copyright:Methods: Eighteen healthy subjects watched a video clip of a person catching a ball, played at three different speeds (normal-, half-, and quarter-speed). MEPs were induced by TMS when the model\u27s hand had opened to the widest extent just before catching the ball ("open") and when the model had just caught the ball ("catch"). These two events were locked to specific frames of the video clip ("phases"), rather than occurring at specific absolute times, so that they could easily be compared across different speeds. MEPs were recorded from the thenar (TH) and abductor digiti minimi (ADM) muscles of the right hand.Results: The MEP amplitudes were higher when the subjects watched the video clip at low speed than when they watched the clip at normal speed. A repeated-measures ANOVA, with the factor VIDEO-SPEED, showed significant main effects. Bonferroni\u27s post hoc test showed that the following MEP amplitude differences were significant: TH, normal vs. quarter; ADM, normal vs. half; and ADM, normal vs. quarter. Paired t-tests showed that the significant MEP amplitude differences between TMS phases under each speed condition were TH, "catch" higher than "open" at quarter speed; ADM, "catch" higher than "open" at half speed.Conclusions: These results indicate that the excitability of M1 was higher when the observed action was played at low speed. Our findings suggest that the action observation system became more active when the subjects observed the video clip at low speed, because the subjects could then recognize the elements of action and intention in others

Esperienza con ciprofloxacina impiegata in terapia sequenziale nella riacutizzazione della bronchite cronica nel paziente ospedalizzato

On 30 hospitalized, aged (>65 years old, mean age: 75,3) patients, both sexes, affected by acute exacerbation of chronic bronchitis (AECB), we have evaluated both clinically and microbiologically, the efficacy of ciprofloxacin "sequentially" administared (initial venous treatment followed by oral admi-nistration of the same drug). Ciprofloxacin has been given i.V., 200 mg twice-a-day for 5 days, followed by 5 more days of oral administration, 500 mg twice-a-day. Laboratory tests have been repeatedly performed, sputum bacteriology at T0, T4, T10 and T20 days. In the cultured 30 samples of sputum, 30 bacterial isolates were found which were considered responsible for the AECB: none of them was Ciprofloxacin-resistant. On the 4th day, 63,3% of the sputa resulted sterile; while Gram- pathogens were microbiologically all eradicated, the S.pneumoniae eradication was obtained only at the end of therapy. Total percentage of eradication, at the end of therapy was=86,6%, a result corresponding exactly to the clinical success/resolution of symptoms, the germs showed no resistance to Ciprofloxacin. Its "sequential" mode of use so represents a valuable indication for the treatment of AECB in the aged patients