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PubMed | University Utrecht, University of Genoa, CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy, University of Turin and 4 more.
Type: | Journal: The Journal of allergy and clinical immunology | Year: 2016

Severe asthma might be associated with neutrophil recruitment and Th17 cytokines over-expression in bronchial biopsies.To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild (MA)-to-severe (SA) asthmatics in relation to exacerbation rate.Inflammatory cells and IL-17AHigher number (p<0.05) of neutrophils, IL-17AIL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation suggesting a pathogenic role of IL-17F in frequent exacerbators.


Tosca M.,Instituto Giannina Gaslini | Sivestri M.,Instituto Giannina Gaslini | Accogli A.,Instituto Giannina Gaslini | Rossi G.A.,Instituto Giannina Gaslini | Ciprandi G.,IRCCS AOU San Martino
Immunotherapy | Year: 2014

Aim: Allergen immunotherapy (AIT) is indicated in IgE-mediated respiratory allergy. Recently, it has been reported that serum-specific IgE (sIgE) levels >10 kU/l may predict AIT efficacy in adults with allergic rhinitis. The aim of the present preliminary study was to investigate whether this cut-off could also be associated with perception of effective AIT in children with allergic asthma and/or rhinitis due to house dust mites (HDM). Methods: A total of 31 allergic children (17 males; mean age of 12.5 years) with levels of serum sIgE to HDM >10 kU/l were evaluated. Eight allergic children (five males; mean age of 13.4 years) with levels of serum sIgE to HDM <10 kU/l were considered as control. All patients were treated with sublingual immunotherapy for 3 years with HDM allergen extract. Childrens perception of AIT efficacy was assessed by visual analog scale (VAS), considering both symptom severity and drug use. Responder patients were defined with >6 VAS. Severity of nasal symptoms was assessed by nasal VAS, and asthma control was evaluated by asthma control test; both were considered before and after AIT. Results: All children (but one) with sIgE >10 kU/l perceived AIT efficacy, whereas only one child with sIgE <10 kU/l perceived AIT benefit (p < 0.001). There was a strong relationship between perception of AIT efficacy by VAS and serum sIgE levels (r = 0.615; p < 0.001). Also, nasal VAS and asthma control tests significantly improved only in children with sIgE >10 kU/l (p < 0.001 for both). Conclusion: Allergen-sIgE assessment before AIT prescription might represent a useful tool to individuate potential responders. © 2014 Future Medicine Ltd.


Valgimigli M.,Erasmus Medical Center | Gagnor A.,Cardiology Unit | Calabro P.,The Second University of Naples | Frigoli E.,Cardiology Unit | And 32 more authors.
The Lancet | Year: 2015

Summary Background It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. Methods We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. Findings We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). Interpretation In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. Funding The Medicines Company and Terumo. © 2015 Elsevier Ltd.


Giaretti W.,IRCCS AOU San Martino | Monteghirfo S.,IRCCS AOU San Martino | Pentenero M.,University of Turin | Gandolfo S.,University of Turin | And 2 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2013

Background: Chromosomal instability and aneuploidy may represent biomarkers of oral exposure to damaging agents and early signs of clinical disease according to the theory of "oral field cancerization." Methods: The hypothesis was tested that the DNA index (DI) values, obtained by high-resolution DNA flow cytometry (DNA-FCM), may potentially contribute to oral cancer risk prediction. For this purpose, the DI of oral fields of normal-appearing mucosa and oral potentially malignant disorders (OPMDs) in 165 consecutive patients was tested for association with dysplasia and/or the oral subsites of tongue and floor of the mouth taken as high-risk intermediate endpoints surrogate of cancer clinical endpoints. The association was evaluated by logistic regression using patient gender, age, tobacco, cigarette smoking habit, and alcohol abuse as confounding variables. Results: Different DI models provided evidence of statistical significant associations. Subdividing the DI values in diploid, near-diploid aneuploid, and high or multiple aneuploid from both OPMDs and oral normalappearing mucosa, ORs, respectively, of 1, 4.3 (P = 0.001), and 18.4 (P < 0.0005) were obtained. Conclusion: Routine DI analysis by high-resolution DNA-FCM seems potentially useful to complement dysplasia and subsite analysis for assessment of oral cancer risk prediction and for a better management of the patients with OPMDs. Work is in progress to validate the present findings in a prospective study with clinical endpoints. Impact: Identifying DNA abnormalities in oral premalignancy may lead to biomarkers of oral exposure and cancer risk and potentially to more effective prevention measures. © 2013 American Association for Cancer Research.


Sorbello V.,University of Turin | Ciprandi G.,IRCCS AOU San Martino | Di Stefano A.,Laboratorio Of Citoimmunopatologia Dellapparato Cardio Respiratorio | Massaglia G.M.,San Luigi Hospital | And 7 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2015

Severe asthma (SA) is associated with neutrophil recruitment and T helper (TH)17 chemokine overexpression in bronchial biopsies. We aimed to evaluate IL-17A and IL-17F expression in nasal/bronchial lamina propria of atopic mild-to-severe asthmatics and controls in relation to neutrophilia and asthma exacerbations. Cryostat sections of nasal/bronchial biopsies obtained from 14 SA and 14 mild asthma (MA) stable atopic patients with rhinitis, and seven healthy controls were analyzed by immunohistochemistry for neutrophils, IL-17A and IL-17F expression. Atopic SA showed an increase in asthma exacerbations number, IL-17F and IL-17A expression in nasal/bronchial lamina propria compared to MA and controls, and a higher expression of bronchial neutrophils in SA compared to MA and controls. In all asthmatics, significant relationships were found between bronchial IL-17F and neutrophils/FEV1, nasal IL-17F and bronchial neutrophil/IL-17 markers and between the latter and exacerbations, suggesting that nasal IL-17F might be informative on bronchial IL17-driven neutrophilia in atopic SA. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Ciprandi G.,IRCCS AOU San Martino | Sivestri M.,Instituto Giannina Gaslini
Journal of Investigational Allergology and Clinical Immunology | Year: 2014

Background: Allergen immunotherapy (AIT) has proven to be effective. However, no biomarkers capable of predicting the clinical response to AIT have been detected. The aim of the present study was to determine a cutoff value for serum specific IgE that could be associated with effective AIT. Methods: We evaluated 174 allergic patients (83 males) with ages ranging between 6 and 77 years. All patients were monsensitized and received sublingual immunotherapy (SLIT) for at least 3 years with a single allergen extract. Symptom severity was assessed using the visual analog scale (VAS). Drug use was also evaluated. A responder was defined as a patient whose VAS score fell by at least 30% over baseline. Results: The response to SLIT was considered effective in 145 patients (83.3%). The use of allergen-specific IgE levels >9.74 kUA/L as a biomarker of effective SLIT yielded a sensitivity value of 96.4%, specificity of 100%, and an area under the receiver operator characteristic curve of 0.987. Conclusions: Assessment of serum specific-IgE before AIT could be a useful biomarker for predicting response to AIT. © 2014 Esmon Publicidad.


Savarino E.,University of Padua | Zentilin P.,IRCCS AOU San Martino | Mastracci L.,University of Genoa | Dulbecco P.,IRCCS AOU San Martino | And 7 more authors.
Journal of Gastroenterology | Year: 2013

Background Microscopic esophagitis (ME) is common in patients with non-erosive reflux disease (NERD), and dilation of intercellular spaces (DIS) has been regarded as the potential main mechanism of symptom generation. We aimed to compare these histological abnormalities in healthy volunteers (HVs) and patients with erosive esophagitis (EE), NERD, and functional heartburn (FH). Methods Consecutive patients with heartburn prospectively underwent upper endoscopy and impedance-pH off-therapy. Twenty EE patients and fifty-seven endoscopy- negative patients (NERD), subclassified as 22 with pH-POS (positive for abnormal acid exposure), 20 with hypersensitive esophagus (HE; normal acid/symptom association probability [SAP]+ or symptom index [SI]+), and 15 with FH (normal acid/SAP-/SI-/ proton pump inhibitor [PPI] test-), were enrolled. Twenty HVs were also included. In each patient/control, multiple specimens (n = 5) were taken from the distal esophagus and histological alterations were evaluated. ME was diagnosed when the global histological score was > 0.35. Results The prevalence of ME was higher (p<0.0001) in EE (95 %), pH-POS (77 %), and HE (65 %) NERD patients than in FH patients (13 %) and HVs (15 %). Also, basal cell hyperplasia (p<0.0023), DIS (p<0.0001), and papillae elongation (p<0.0002) showed similar rates of prevalence in the above populations (p<0.0001). ME, including each histological lesion, had similar low frequencies in FH and HVs (p = 0.9990). Considering the histological abnormalities together, they permitted us to clearly differentiate EE and NERD from FH and HVs (p<0.0001 and p<0.0001, respectively). Conclusions The lack of ME in the esophageal distal biopsies of FH patients indicates a limited role of these histological abnormalities in symptom generation in them. ME can be considered as an accurate and reliable diagnostic marker for distinguishing FH patients from GERD patients and has the potential to be used to guide the correct therapy. © Springer 2012.


PubMed | IRCCS AOU San Martino and Instituto Giannina Gaslini
Type: Journal Article | Journal: Allergologia et immunopathologia | Year: 2016

Respiratory allergy is characterised by an IgE-mediated reaction. The immune system functions, including IgE production, progressively decline over time with growing up and ageing. Molecular-based allergy diagnostic defines sensitisation profile. This study aimed to evaluate the impact of age on serum allergen-specific IgE to molecular component levels in a large sample of subjects.Serum IgE to: rCor a11, rPru p3, nJug r3, rAra h8, rGly m4, rCor a8, nPen m1, nAct d8, Bos d 8, and nGal d2 were assessed by ISAC method. Sera from 2795 patients, 1234 males (44.1%) and 1561 females (55.9%), median age 23 years (1st and 3rd quartiles: 9.7-43.7 years; age range: 1 month-103 years) were analysed.The number of positive tests (i.e. sensitisation) tended to increase between birth and school-age until young adulthood and then decreased. A similar age-dependent trend was observed considering the levels of each allergen components: the levels of each allergen component tended to increase until early adulthood, but Gal d 2 and Bos d 8 (rapidly diminishing), and then to decrease over time. However, the pattern is significantly dependent on each single tested food.Allergen-specific IgE production to food molecular components tend to reduce with ageing, but with differences between allergens. This phenomenon should be adequately evaluated managing allergic patients.


PubMed | IRCCS AOU San Martino, San Bortolo Hospital of Vicenza, Hospital of Lucca, University of Siena and Hospital of Grosseto
Type: | Journal: Internal and emergency medicine | Year: 2016

Acute heart failure is a common condition among adults presenting with dyspnea in the Emergency Department (ED), still the diagnosis is challenging as objective standardized criteria are lacking. First line work-up, other then clinical findings, is nowadays made with lung ultrasound imaging study, chest X-ray study and brain natriuretic peptide (BNP) level determination; however, it is not clear which is the best diagnostic test to be used and whether there is any real benefit for clinical judgement. We set up this study to compare the performances of these three diagnostic tools; furthermore, we combined them to find the best possible approach to dyspneic patients. This is a prospective observational study based in the ED. We enrolled adults presenting with dyspnea not trauma-related, they underwent lung ultrasound, and chest X-ray studies, and NT pro-BNP level determination. Then we compared the results with the diagnosis of acute heart failure established by an independent panel of experts. 236 patients were enrolled in the study. We find sensitivity and specificity for lung ultrasound of 57.73 and 87.97%, for chest X-ray 74.49 and 86.26%, for NT pro-BNP 97.59 and 27.56%, respectively. Combining together the chest X-ray and lung ultrasound, we find the best overall performance with 84.69% sensitivity, 77.69% specificity and 87.07% negative predictive value. From our results, we could not identify the best test to diagnose acute heart failure in an emergency setting, although we could suggest that a stepwise workup combining chest X-ray and lung ultrasound at first, then for those negative, a determination of NT pro-BNP assay would be a reasonable approach to the dyspneic patient.


PubMed | IRCCS AOU San Martino and University of Bari
Type: Journal Article | Journal: Journal of biological regulators and homeostatic agents | Year: 2017

Allergic rhinitis (AR) and upper airway respiratory infections are frequent in children, and both have a relevant impact on some social aspects, including school attendance and performance, sleep, quality of life (also of the parents), and costs. Saline nasal irrigation is widely employed to reduce nasal congestion and mucopurulent secretion, to stimulate cleansing of the nasal and paranasal cavities, and to induce restoration of mucociliary clearance. The present study evaluated the effects of nasal irrigation on nasal cytology, using the new device Nasir in 66 children (40 males, 26 females, mean age 7.311.7 years, age range 4-17 years) with allergic rhinitis. The patients were treated with nasal irrigation with warm (36C) Nasir (250 mL sacs of premixed solution): one sac twice daily for 12 days. Nasal irrigation significantly reduced the neutrophilic infiltrate (baseline median value 2.80.7; post treatment value 20.5; p less than 0.05). In addition, there was a reduction of eosinophil infiltrate (T0= 3.21.1; T1= 2.61.2; p= less than 0.05). There was no significant change with regard to bacteria (T0= 2.70.9; T1= 2.31.02; p= 0.17). In conclusion, this pilot study reports that nasal irrigation with Nasir might be useful to attenuate upper airway inflammation.

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