Garcia G.,University Paris - Sud |
Garcia G.,French Institute of Health and Medical Research |
Magnan A.,University of Nantes |
Magnan A.,French Institute of Health and Medical Research |
And 20 more authors.
Chest | Year: 2013
Background: While up to 50% of patients with severe asthma have no evidence of allergy, IgE has been linked to asthma, irrespective of atopic status. Omalizumab, an anti-IgE monoclonal antibody, is reported to signifi cantly benefi t a subset of patients with severe, persistent, allergic asthma. Therefore, we investigated whether omalizumab has biologic and clinical effects in patients with refractory nonatopic asthma. Methods: Forty-one adult patients who, despite daily treatment with or without maintenance oral corticosteroids, had severe, nonatopic, refractory asthma according to GINA (Global Initiative for Asthma) step 4, were randomized to receive omalizumab or placebo in a 1:1 ratio. The primary end point was the change in expression of high-affi nity IgE receptor (Fc RI) on blood basophils and plasmacytoid dendritic cells (pDC2) after 16 weeks. The impact of omalizumab on lung function and clinical variables was also examined. Results: Compared with placebo, omalizumab resulted in a statistically signifi cant reduction in FcεRI expression on basophils and pDC2 (P < .001). The omalizumab group also showed an overall increase in FEV 1 compared with baseline (1 250 mL, P = .032; 1 9.9%, P = .029). A trend toward improvement in global evaluation of treatment effectiveness and asthma exacerbation rate was also observed. Conclusions: Omalizumab negatively regulates Fc RI expression in patients with severe nonatopic asthma, as it does in severe atopic asthma. Omalizumab may have a therapeutic role in severe nonatopic asthma. Nonetheless, our preliminary fi ndings support further investigation to better assess the clinical effi cacy of omalizumab. © 2013 American College of Chest Physicians.
PubMed | Paris-Sorbonne University, Nancy University Hospital Center, Hopital Arnaud de Villeneuve, University Claude Bernard Lyon 1 and 7 more.
Type: Journal Article | Journal: PloS one | Year: 2015
Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non-genetic factors are chance findings or reflect true underlying mechanisms.
Price D.,University of Aberdeen |
Bosnic-Anticevich S.,University of Sydney |
Briggs A.,University of Glasgow |
Chrystyn H.,University of Huddersfield |
And 3 more authors.
Respiratory Medicine | Year: 2013
Whilst the inhaled route is the first line administration method in the management of asthma, it is well documented that patients can have problems adopting the correct inhaler technique and thus receiving adequate medication. This applies equally to metered dose inhalers and dry powder inhalers and leads to poor disease control and increased healthcare costs. Reviews have highlighted these problems and the recent European Consensus Statement developed a call to action to seek solutions. This review takes forward the challenge of inhaler competence by highlighting the issues and suggesting potential solutions to these problems. The opportunity for technological innovation and educational interventions to reduce errors is highlighted, as well as the specific challenges faced by children. This review is intended as a policy document, as most issues faced by patients have not changed for half a century, and this situation should not be allowed to continue any longer. Future direction with respect to research, policy needs and practice, together with education requirements in inhaler technique are described. © 2012 Published by Elsevier Ltd.
PubMed | McGill University, University of Quebec at Chicoutimi, University of Verona, Imperial College London and 6 more.
Type: Journal Article | Journal: The Journal of allergy and clinical immunology | Year: 2016
Asthma and allergic rhinitis (AR) are common allergic comorbidities with a strong genetic component in which epigenetic mechanisms might be involved.We aimed to identify novel risk loci for asthma and AR while accounting for parent-of-origin effect.We performed a series of genetic analyses, taking into account the parent-of-origin effect in families ascertained through asthma: (1) genome-wide linkage scan of asthma and AR in 615 European families, (2) association analysis with 1233 single nucleotide polymorphisms (SNPs) covering the significant linkage region in 162 French Epidemiological Study on the Genetics and Environment of Asthma families with replication in 154 Canadian Saguenay-Lac-Saint-Jean asthma study families, and (3) association analysis of disease and significant SNPs with DNA methylation (DNAm) at CpG sites in 40 Saguenay-Lac-Saint-Jean asthma study families.We detected a significant paternal linkage of the 4q35 region to asthma and allergic rhinitis comorbidity (AAR; P=7.210(-5)). Association analysis in this region showed strong evidence for the effect of the paternally inherited G allele of rs10009104 on AAR (P=1.110(-5), reaching the multiple-testing corrected threshold). This paternally inherited allele was also significantly associated with DNAm levels at the cg02303933 site (P=1.710(-4)). Differential DNAm at this site was found to mediate the identified SNP-AAR association.By integrating genetic and epigenetic data, we identified that a differentially methylated CpG site within the melatonin receptor 1A (MTNR1A) gene mediates the effect of a paternally transmitted genetic variant on the comorbidity of asthma and AR. This study provides a novel insight into the role of epigenetic mechanisms in patients with allergic respiratory diseases.
Konstan M.W.,Case Western Reserve University |
Flume P.A.,Medical University of South Carolina |
Kappler M.,Ludwig Maximilians University of Munich |
Chiron R.,Hopital Arnaud de Villeneuve |
And 6 more authors.
Journal of Cystic Fibrosis | Year: 2011
Background: A light-porous-particle, dry-powder formulation of tobramycin was developed, using PulmoSphere® technology, to improve airway delivery efficiency, substantially reduce delivery time, and improve patient convenience and satisfaction. We evaluated the safety, efficacy and convenience of tobramycin inhalation powder (TIP™) versus tobramycin inhalation solution (TIS, TOBI®) for treating Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients aged ≥ 6 years. Methods: In this open-label study, 553 patients were randomized 3:2 to TIP (total 112. mg tobramycin) via the Novartis T-326 Inhaler or TIS 300. mg/5. mL via PARI LC® PLUS nebulizer twice daily for three treatment cycles (28. days on-drug, 28. days off-drug). Safety, efficacy, and treatment satisfaction outcomes were evaluated. Results: TIP was generally well-tolerated; adverse events were similar in both groups. The rate of cough suspected to be study drug related was higher in TIP-treated patients (TIP: 25.3%; TIS: 4.3%), as was the overall discontinuation rate (TIP: 26.9%; TIS: 18.2%). Increases in FEV1% predicted from baseline to Day 28 of Cycle 3 were similar between groups; the mean reduction in sputum P. aeruginosa density (log10 CFU/g) on Day 28 of Cycle 3 was also comparable between groups. Administration time was significantly less for TIP (mean: 5.6 versus 19.7min, p<0.0001). Treatment satisfaction was significantly higher for TIP for effectiveness, convenience, and global satisfaction. Conclusions: TIP has a safety and efficacy profile comparable with TIS, and offers a far more convenient treatment option for pseudomonas lung infection in CF. © 2010 European Cystic Fibrosis Society.
Radioguided occult lesion localization plus sentinel node biopsy (SNOLL) versus wire-guided localization plus sentinel node detection: A case control study of 129 unifocal pure invasive non-palpable breast cancers
Giacalone P.L.,Oncology Unit |
Bourdon A.,Hopital Arnaud de Villeneuve |
Trinh P.D.,Oncology Unit |
Taourel P.,Hopital Arnaud de Villeneuve |
And 5 more authors.
European Journal of Surgical Oncology | Year: 2012
Aims: We compared histological patterns after lumpectomy for non-palpable breast cancers preoperatively localized by radioguided occult lesion localization plus sentinel node localization (SNOLL) versus wire-guided localization. Methods: To ensure a homogeneously treated cohort and rigorous comparisons, only patients with invasive cancer and measurable opacity by imaging were included. Exclusion criteria were one or more parameters that could interfere with localization and/or the surgical procedure. Forty-three SNOLL were compared with 86 WGL plus sentinel node (SN) localization. Cancer localization effectiveness was based on careful assessment of histological data from only the first resected glandular specimen, as any additional resection specimens were guided by intraoperative histological examination. Results: Reexcisions to ensure free tissue margins were performed during the same procedure in 13.9% of SNOLL versus 31.3% of WGL; p = 0.02. Significantly more women in SNOLL (53.4%) also had free nearest margins of >9 mm after the first procedure compared with WGL (33.7%); p = 0.03. The median centricity ratio after the first procedure was better in SNOLL (2.8, range 1.3-14) than WGL (5, range 1-50); p = 0.008. The median number of SN detected by lymphoscintigraphy was the same in SNOLL and WGL (1, range 0-9, vs. 1, range 0-8). Intraoperative SN detection by blue dye and/or gamma probe was successful for 97.6% of SNOLL versus 93% of WGL. Conclusion: In this study, SNOLL was effective and safe, and this procedure significantly improved the rate of negative margins in the first specimen and the rate of reexcision for positive margins compared with WGL. © 2011 Elsevier Ltd. All rights reserved.
Pellestor F.,French Institute of Health and Medical Research |
Puechberty J.,Hopital Arnaud de Villeneuve |
Weise A.,Institute of Human Genetics and Anthropology |
Lefort G.,Hopital Arnaud de Villeneuve |
And 3 more authors.
Fertility and Sterility | Year: 2011
Objective: To directly study the meiotic segregation of a complex reciprocal translocation (CCR) as well as the occurrence of an interchromosomal effect. Design: In situ sperm fluorescence in situ hybridization (FISH) analysis. Setting: Department of Cytogenetics and INSERM research center. Patient(s): A male carrier of a balanced complex reciprocal translocation t(5;13;14)(q23;q21;q31). Intervention(s): Sperm samples from the carrier and direct FISH analysis on sperm slide preparations. Main Outcome Measure(s): Meiotic segregation pattern determined on sperm nuclei and estimation of the incidence of unbalanced spermatozoa and an interchromosomal effect (ICE). Result(s): Only 27% of spermatozoa displayed a normal or balanced chromosome complement. The rate of unbalanced sperm was 69.4%, including different types of 3:3, 4:2, and 5:1 segregations. There was no evidence for the occurrence of an interchromosomal effect in autosomal chromosomes, but the gonosomes displayed a statistically significant increase in disomy rates. Conclusion(s): These results are consistent with the formation of a hexavalent configuration at the pachytene stage of meiosis and a high prevalence of imbalance production. The mechanisms of formation of CCRs must be examined with regard to these direct results and new molecular data on the formation of genomic rearrangements. © 2011 by American Society for Reproductive Medicine.
Bourdin A.,Hopital Arnaud de Villeneuve |
Bourdin A.,Montpellier University |
Molinari N.,Montpellier University |
Molinari N.,Montpellier University Hospital Center |
And 7 more authors.
Journal of Allergy and Clinical Immunology | Year: 2014
Background Cross-sectional severe asthma cluster analysis identified different phenotypes. We tested the hypothesis that these clusters will follow different courses. Objective We aimed to identify which asthma outcomes are specific and coherently associated with these different phenotypes in a prospective longitudinal cohort. Methods In a longitudinal cohort of 112 patients with severe asthma, the 5 Severe Asthma Research Program (SARP) clusters were identified by means of algorithm application. Because patients of the present cohort all had severe asthma compared with the SARP cohort, homemade clusters were identified and also tested. At the subsequent visit, we investigated several outcomes related to asthma control at 1 year (6-item Asthma Control Questionnaire [ACQ-6], lung function, and medication requirement) and then recorded the 3-year exacerbations rate and time to first exacerbation. Results The SARP algorithm discriminated the 5 clusters at entry for age, asthma duration, lung function, blood eosinophil measurement, ACQ-6 scores, and diabetes comorbidity. Four homemade clusters were mostly segregated by best ever achieved FEV1 values and discriminated the groups by a few clinical characteristics. Nonetheless, all these clusters shared similar asthma outcomes related to asthma control as follows. The ACQ-6 score did not change in any cluster. Exacerbation rate and time to first exacerbation were similar, as were treatment requirements. Conclusion Severe asthma phenotypes identified by using a previously reported cluster analysis or newly homemade clusters do not behave differently concerning asthma control-related outcomes, which are used to assess the response to innovative therapies. This study demonstrates a potential limitation of the cluster analysis approach in the field of severe asthma. © 2014 American Academy of Allergy, Asthma & Immunology.
Brucker C.,Klinikum Nurnberg Nord |
Hedon B.,Hopital Arnaud de Villeneuve |
The H.S.,St. Antonius Ziekenhuis |
Hoschen K.,Grunenthal GmbH |
And 2 more authors.
Contraception | Year: 2010
Objective: This study was conducted to assess the long-term efficacy and safety of a low-dose monophasic combined oral contraceptive (COC) containing 0.02 mg ethinylestradiol (EE) and 2 mg chlormadinone acetate (CMA) in a novel regimen administered daily for 24 days followed by a 4-day placebo interval. Study Design: In this multicenter, uncontrolled, Phase III trial, 1665 subjects took the COC 0.02 mg EE/2 mg CMA for up to 21 cycles. The overall Pearl Index was the primary end point; cycle control, safety, effect on acne and seborrhea, and changes in body weight and libido were secondary end points. Results: Contraceptive efficacy was analyzed for 1653 subjects completing 21,495 cycles. Six pregnancies occurred during trial duration with one attributable to method failure. The overall Pearl Index for the first year of use was 0.33 (95% confidence interval, 0.09-0.85). The mean number of bleeding/spotting days during six 90-day reference periods (RPs) decreased from 17.0 (RP 1) to 11.7 (RP 6), and the number of bleeding episodes per RP decreased from 3.8 (RP 1) to 2.7 (RP 6). Among subjects who presented with acne at the baseline visit, a decrease of papules/pustules and comedones was observed during the course of the trial. The most common "at least possibly related" adverse events were headache, breast discomfort and nausea. The tolerability and well-being was reported as being excellent or good in the majority of trial subjects (84.6% and 80.2%, respectively). Conclusions: The low-dose COC 0.02 mg EE/2 mg CMA administered daily for 24 days followed by a 4-day placebo interval provides high contraceptive efficacy combined with an adequate cycle control and safety profile, beneficial effects on acne, and is well tolerated. © 2010 Elsevier Inc. All rights reserved.
Dechanet C.,Hopital Arnaud de Villeneuve |
Anahory T.,Hopital Arnaud de Villeneuve |
Mathieu Daude J.C.,Hopital Lapeyronie |
Quantin X.,Hopital Arnaud de Villeneuve |
And 4 more authors.
Human Reproduction Update | Year: 2011
Background: Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. Methods: We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. Results: Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. Conclusions: All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology. © The Author 2010. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.