Aberer W.,Medical University of Graz |
Maurer M.,Charité - Medical University of Berlin |
Reshef A.,Clinical Immunology and Angioedema Unit |
Longhurst H.,Barts and the London Hospital |
And 5 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2014
Background: Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered icatibant in patients with HAE type I or II. Secondary objectives included patient convenience and clinical efficacy of self-administration. Methods: In this phase IIIb, open-label, multicenter study, adult patients were trained to self-administer a single 30-mg icatibant subcutaneous injection to treat their next attack. Icatibant-naïve patients were treated by an HCP prior to self-administration. Evaluations included adverse event (AE) reporting, a validated questionnaire for convenience, and visual analog scale for efficacy. Results: A total of 151 patients were enrolled; 104 had an attack requiring treatment during the study, and 97 patients (19 naïve) were included in the self-administration cohort. Recurrence or worsening of HAE symptoms (22 of 97) was the most commonly reported AE; rescue medications including icatibant (N = 3) and C1-inhibitor concentrate (N = 6) were used in 13 cases. Overall, 89 of 97 patients used a single injection of icatibant. No serious AEs or hospitalizations were reported. Most patients (91.7%) found self-administration preferable to administration in the clinic. The median time to symptom relief (3.8 h) was comparable with results from controlled trials of icatibant. Conclusions: With appropriate training, patients were successfully able to recognize HAE attacks and decide when to self-administer icatibant. This, coupled with the patient-reported high degree of satisfaction, convenience and ease of use supports the adoption of icatibant self-administration in clinical practice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Villalta D.,Allergy and Immunology Unit |
Tonutti E.,Allergy and Immunopathology Unit |
Prause C.,University of Leipzig |
Koletzko S.,Ludwig Maximilians University of Munich |
And 11 more authors.
Clinical Chemistry | Year: 2010
BACKGROUND: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD in patients with IgA deficiency. METHODS: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. AntidGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays. RESULTS: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2% (95% CI 76.3%-97.7%) according to age-specific cutoffs and 82.4% (66.1%-92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8% (58.8%-87.4%) and the sensitivity of IgG-anti-dGli was 88.2% (72.8%-95.9%) according to both cutoffs. CONCLUSIONS: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.
Quirce S.,Hospital Universitario La Paz |
Quirce S.,CIBER ISCIII |
Lemiere C.,Hopital du Sacre Coeur |
De Blay F.,University of Strasbourg |
And 9 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2010
The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of 'united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued. © 2009 John Wiley & Sons A/S.
Zanini A.,IRCCS Rehabilitation Institute of Tradate |
Cherubino F.,IRCCS Rehabilitation Institute of Tradate |
Zampogna E.,IRCCS Rehabilitation Institute of Tradate |
Croce S.,Allergy and Immunology Unit |
And 2 more authors.
International Journal of COPD | Year: 2015
Background: Bronchial hyperresponsiveness (BHR), sputum eosinophilia, and bronchial reversibility are often thought to be a hallmark of asthma, yet it has been shown to occur in COPD as well. Objectives: To evaluate the relationship between BHR, lung function, and airway inflammation in COPD patients. Methods: Thirty-one, steroid-free patients with stable, mild and moderate COPD were studied. The following tests were carried out: baseline lung function, reversibility, provocative dose of methacholine causing a 20% fall in forced expiratory volume in 1 second, a COPD symptom score, and sputum induction. Results: Twenty-nine patients completed the procedures. About 41.4% had BHR, 31.0% had increased sputum eosinophils, and 37.9% had bronchial reversibility. Some of the patients had only one of these characteristics while others had two or the three of them. Patients with BHR had higher sputum eosinophils than patients without BHR (P=0.046) and those with sputum eosinophils ≥3% had more exacerbations in the previous year and a higher COPD symptom score than patients with sputum eosinophils <3% (P=0.019 and P=0.031, respectively). In patients with BHR, the cumulative dose of methacholine was negatively related to the symptom score and the number of exacerbations in the previous year. When patients with bronchial reversibility were considered, bronchodilation was positively related to sputum eosinophils. Conclusion: Our study showed that BHR, sputum eosinophilia, and bronchial reversibility were not clustered in one single phenotype of COPD but could be present alone or together. Of interest, BHR and airway eosinophilia were associated with clinical data in terms of exacerbations and symptoms. Further investigation is needed to clarify this topic. © 2015 Zanini et al.
Dykewicz M.S.,Allergy and Immunology Unit |
Hamilos D.L.,Harvard University
Journal of Allergy and Clinical Immunology | Year: 2010
Rhinitis and sinusitis are among the most common medical conditions and are frequently associated. In Western societies an estimated 10% to 25% of the population have allergic rhinitis, with 30 to 60 million persons being affected annually in the United States. It is estimated that sinusitis affects 31 million patients annually in the United States. Both rhinitis and sinusitis can significantly decrease quality of life, aggravate comorbid conditions, and require significant direct medical expenditures. Both conditions also create even greater indirect costs to society by causing lost work and school days and reduced workplace productivity and school learning. Management of allergic rhinitis involves avoidance, many pharmacologic options, and, in appropriately selected patients, allergen immunotherapy. Various types of nonallergic rhinitis are treated with avoidance measures and a more limited repertoire of medications. For purposes of this review, sinusitis and rhinosinusitis are synonymous terms. An acute upper respiratory illness of less than approximately 7 days' duration is most commonly caused by viral illness (viral rhinosinusitis), whereas acute bacterial sinusitis becomes more likely beyond 7 to 10 days. Although the mainstay of management of acute bacterial sinusitis is antibiotics, treatment of chronic sinusitis is less straightforward because only some chronic sinusitis cases have an infectious basis. Chronic rhinosinusitis (CRS) has been subdivided into 3 types, namely CRS without nasal polyps, CRS with nasal polyps, and allergic fungal rhinosinusitis. Depending on the type of CRS present, a variety of medical and surgical approaches might be required. © 2010 American Academy of Allergy, Asthma & Immunology.
Ponvert C.,University of Paris Descartes |
Perrin Y.,Allergy and Immunology Unit |
Le Bourgeois M.,University of Paris Descartes |
Karila C.,University of Paris Descartes |
And 3 more authors.
Pediatric Allergy and Immunology | Year: 2011
Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p<0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p<0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspected betalactam hypersensitivity. © 2011 John Wiley & Sons A/S.
Rotondi M.,Laboratory for Endocrine Disruptors |
Coperchini F.,Laboratory for Endocrine Disruptors |
Pignatti P.,Allergy and Immunology Unit |
Magri F.,Laboratory for Endocrine Disruptors |
Chiovato L.,Laboratory for Endocrine Disruptors
Journal of Clinical Endocrinology and Metabolism | Year: 2015
Context: Metformin displays both direct and indirect anti-tumor effects. CXCL8 is a crucial down-stream mediator of Nuclear-Factor-κB signaling related to the growth and progression of thyroid cancers. Targeting CXCL8 results in prolonged survival and reduced metastatic spread in in-vivo animal models of thyroid tumors. Objective: This study aimed to evaluate whether metformin inhibits the secretion of CXCL8 induced by Tumor-Necrosis-Factor-α (TNF-α) in primary cultures of normal and tumor human thyroid cells as well as in thyroid cancer cell lines. Methods: Normal human thyrocytes, papillary thyroid cancer cells, and thyroid cancer cell lines (TPC-1 and BCPAP) were stimulated with TNF-α (10 ng/mL) alone or in combination with metformin (0.01, 0.1, 1, 2.5, 5, and 10mM). CXCL8 levels were measured in the cell supernatants after 24 hours. Results: Metformin significantly and dose-dependently inhibited the TNF-α-induced CXCL8 secretion in both normal thyrocytes (ANOVA: F = 42.04; P < .0001) and papillary thyroid cancer cells (ANOVA: F = 21.691; P < .0001) but not in TPC-1 and BCPAP cell lines. Conclusion: Metformin inhibits the TNF-α-induced CXCL8 secretion in primary cultures of normal thyroid cells and differentiated thyroid cancer cells at least of the most frequent poorly aggressive phenotype. The recruitment of neutrophils within the thyroid gland is a crucial metastasis-promoting factor, and it depends on the amount of CXCL8 produced by both tumor cells and by the more abundant normal thyroid cells exposed to TNF-α. Thus, the here-reported inhibiting effect of metformin on TNF-α-induced CXCL8 secretion could be considered as a further indirect anticancer property of the drug. Copyright © 2015 by the Endocrine Society.
PubMed | University of Pavia, Allergy and Immunology Unit, Laboratory for Endocrine Disruptors and Molecular Cardiology Unit
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016
The chemokine receptor CCR6, selectively bound by CCL20, is involved in the metastatic spread of cancer cells. Tumor necrosis factor- (TNF-) displays a complex pro-tumorigenic actions, but it is unknown whether this cytokine could modulate the expression of chemokine receptors in thyroid tumors. The membrane expression of CCR6 was assessed by flow cytometry and immunofluorescence, in primary cultures of normal human thyroid (NHT) cells and in thyroid cancer cell lines (TPC-1 and BCPAP), both in basal conditions and after stimulation with TNF-. In basal conditions, CCR6+ cells were virtually absent in NHT cells (0.40.4%), while they were detected in TPC-1 (23.66.6%) and in BCPAP (12.99.4%) tumor cells (ANOVA F: 10.534; p<0.005). The incubation with TNF- significantly increased the percentage of CCR6+ cells in TPC-1 (23.66.6% vs. 33.18.7; p<0.033) and in BCPAP (12.99.4% vs. 18.111.5; p<0.030), but not in NHT (0.40.4% vs. 0.20.3; NS) cells. The magnitude of the TNF- effect was similar for TPC-1 and BCPAP (40% vs. baseline) cells. TPC-1 cells were characterized by a greater amount of CCR6 per cell as compared with BCPAP cells, both in basal conditions (148.333.7 fluorescence intensity vs. 102.522.1 p<0.016) and after TNF- stimulation (147.846.3 fluorescence intensity vs. 95.318.5; p<0.025). Cell migration assays showed that TNF- treatment significantly increased the rate of migrated cells in those cells in which it also increased the membrane expression of CCR6 (TPC-1 and BCPAP) as compared to basal condition (p<0.05 for both TPC-1 and BCPAP cells). No effect was observed in NHT cells in which TNF- stimulation had no effect in terms of CCR6 expression. We first report that TNF- enhances the expression of CCR6 in thyroid tumor cells, thus providing evidence that TNF- increases the metastatic potential of thyroid tumors.
PubMed | University of Pavia, Allergy and Immunology Unit, Tufts University and University of Jordan
Type: | Journal: Mediators of inflammation | Year: 2016
CXCL8 displays several tumor-promoting effects. Targeting and/or lowering CXCL8 concentrations within the tumor microenvironment would produce a therapeutic benefit. Aim of this study was to test the effect of IFN on the basal and TNF-stimulated secretion of CXCL8 in TCP-1 and BCPAP thyroid cancer cell lines (harboring RET/PTC rearrangement and BRAF V600e mutation, resp.). Cells were incubated with IFN (1, 10, 100, and 1000U/mL) alone or in combination with TNF- (10ng/mL) for 24 hours. CXCL8 and CXCL10 concentrations were measured in the cell supernatants. IFN inhibited in a dose-dependent and significant manner both the basal (ANOVA F: 22.759; p < 0.00001) and the TNF-stimulated (ANOVA F: 15.309; p < 0.00001) CXCL8 secretions in BCPAP but not in TPC-1 cells (NS). On the other hand, IFN and IFN + TNF- induced a significant secretion of CXCL10 in both BCPAP (p < 0.05) and TPC-1 (p < 0.05) cells. Transwell migration assay showed that (i) CXCL8 increased cell migration in both TPC-1 and BCPAP cells; (ii) IFN significantly reduced the migration only of BCPAP cells; and (iii) CXCL8 reverted the effect of IFN. These results constitute the first demonstration that IFN inhibits CXCL8 secretion and in turn the migration of a BRAF V600e mutated thyroid cell line.
Weiler Z.,Pulmonary Unit |
zeldin Y.,Allergy and Immunology Unit |
Magen E.,Barzilai Medical Center |
Zamir D.,Barzilai Medical Center |
Kidon M.I.,Allergy and Immunology Unit
Respiratory Medicine | Year: 2010
Background: At the population level, asthma has been associated with chronic systemic inflammation as well as adverse cardiovascular outcomes. Objectives: The aim of this study was to investigate peripheral vascular hemodynamic variables of arterial stiffness (AS) and their relationship to pulmonary function tests in asthmatic patients. Methods: Young asthmatic patients from the tertiary center for pulmonary diseases at the Barzilai Medical Center underwent pulmonary function evaluation and non-invasive radial artery hemodynamic profiling, pre- and post-exercise. Results were compared to age matched, non-asthmatic controls. Results: 23 young asthmatics and 41 controls, completed all evaluation points. Pulmonary flow parameters were significantly reduced in the asthma group at all points. There were no differences between groups in BMI, blood pressure, pulse rate or measurements of AS at baseline or after bronchodilation. The % predicted forced expiratory volume in the first second at baseline (FEV1%) in asthmatics was positively correlated with the small arteries elasticity index (SAEI) and negatively correlated with the systemic vascular resistance (SVR) in these patients. These correlations were not observed in non-asthmatic controls. In multifactorial regression FEV1 remained the major factor associated with measurements of AS in asthmatic patients, while gender was the only significant factor in non-asthmatic controls. Conclusions: Significant correlations between measurements of AS and FEV1 in young asthmatics, suggest the presence of a common systemic, most likely inflammatory pathway involving both the cardiovascular and respiratory systems. © 2009.