Search

International audience; Background Allergic bronchopulmonary aspergillosis (ABPA) is an underestimated allergic disease due to Aspergillus fumigatus (AF). The main diagnostic criteria for ABPA rely on the evaluation of immunoglobulin (Ig) E and IgG responses to AF extracts, although these cannot discriminate AF-sensitization from ABPA. Objectives To evaluate the performance of cellular functional assays with extract and molecular AF allergens in ABPA. Methods A prospective cohort of 67 patients (6 ABPA) was investigated with basophil activation test (BAT) with AF extract. Twelve patients were further investigated for BAT responses to molecular AF components: Asp f 1, Asp f 2, Asp f 3, Asp f 4, and Asp f 6. Results BAT with AF extract with an optimized cutoff displayed 100% sensitivity and 77.6% specificity for ABPA diagnosis. Among patients with positive BAT to AF, BAT with Asp f 4 was significantly higher in ABPA patients at 10 ng/mL (mean basophil stimulation index 10.56 in ABPA vs. 1.24 in non-ABPA patients, p = 0.0002). Conclusion BAT with AF is a promising diagnostic biomarker in the context of suspected ABPA, which can be further improved with AF molecular allergens, especially Asp f 4.

International audience; Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).

International audience; Background: Allergic contact dermatitis (ACD) and photoallergic contact dermatitis (PACD) to benzophenone present in printing ink have been reported. However, precise chemical analyses and extended photo-patch tests have not been performed in these cases.Objectives: To determine which component present in a magazine cover are responsible for a patient's skin reaction, to determine the primary sensitizer, and precisely diagnose ACD and PACD.Methods: After initial photo-patch tests were performed on a patient with a history of reaction to magazine covers after sun exposure, gas chromatography-mass spectrometry and high-performance liquid chromatography analyses of the magazine covers, and additional photo-patch tests were performed.Results: The first photo-patch test results confirmed PACD to ketoprofen and fenofibrate and evoked PACD to the magazine covers. 4-methyl benzophenone (4-MBP) and 1-hydroxy-cyclohexyl-phenyl-ketone (1-HCPK) were found in the magazine cover. Additional photo-patch tests confirmed PACD to 1-HCPK and to benzophenone, and photo-aggravated ACD to 4-MBP. The primary sensitizer was ketoprofen.Conclusions: Benzophenones are present in a wide variety of products, without always being listed on the packaging. Patients previously sensitized to other ketones, such as ketoprofen, may react to benzophenones without being able to avoid contact with these molecules. New regulations may be needed for more efficient eviction advice.Highlights: Photoallergic contact dermatitis to covers of a magazine was diagnosed and thorough investigation was necessary to identify the haptens responsible. Chemical analyses of the covers revealed the presence of 4-methyl benzophenone (4-MBP) and 1-hydroxy-cyclohexyl-phenyl-ketone (1-HCPK) Photo-patch tests suggested photo-aggravation of contact dermatitis to 4-MBP and benzophenone, and photoallergy to 1-HCPK and ketoprofen. Ketoprofen was the most likely primary sensitizer.

OBJECTIVE The objective of this article was to conduct a systematic review of the treatment of moderate-to-severe asthma by administrating Dupilumab.METHODS A search on the online databases EBSCO, Scielo, PubMed, Medline Bireme, Lilacs, and The New England Journal of Medicine was conducted, publications from 2010 to 2018 were selected. The inclusion criteria were articles which contained control groups, tested the validity of Dupilumab, and verified the response of patients through controlled tests. For the search of such articles, the following keywords were used: “Dupilumab”, “asthma”, “Bronchial Asthma” AND “Asthma, Bronchial” AND their correspondent in Portuguese “asma”, “Asma brônquica” and “Asma brônquica”. The exclusion criteria were literature reviews, news, articles without control groups, articles on different subjects, Dupilumab studies on other diseases, articles concerning asthma without the use of Dupilumab, and repeated articles on the databases were discarded.RESULTS The literature considers that the medication shows a good response for the treatment of moderate-to-severe asthma and assists in the improvement of lung function, aside from resulting in few side effects. It presents good efficacy, safety, and tolerance by patients.CONCLUSIONS Dupilumab is promising for the treatment of asthma, whereas conventional therapy is deemed to be insufficient. More additional studies are needed to confirm the long-term safety and effectiveness., OBJETIVO Este artigo teve como objetivo fazer uma revisão sistemática sobre o tratamento da asma moderada a grave, administrando Dupilumabe.MÉTODOS Foi realizada uma busca nas plataformas on-line Ebsco, SciELO, PubMed, Medline Bireme, Lilacs e New England Journal of Medicine. Foram selecionadas publicações de 2010 a 2018 referentes a artigos que continham grupos controle, que testaram a validade de Dupilumabe e verificaram a resposta dos pacientes por meio de testes controlados. Para a busca desses artigos, foram utilizadas as seguintes palavras-chave: “Dupilumab”, “asthma”, “Bronchial Asthma” and “Asthma, Bronchial”. E o correspondente em português: “asma”, “Asma brônquica” and “Asma brônquica”. Os critérios de exclusão, revisões de literatura, notícias, artigos sem grupos de controle, artigos sobre diferentes assuntos, estudos de Dupilumabe sobre outras doenças, artigos sobre asma sem uso de Dupilumabe e artigos repetidos em plataformas de busca foram descartados. RESULTADOS A literatura aponta que a medicação apresenta boa resposta no tratamento da asma moderada a grave e auxilia na melhora da função pulmonar, além de resultar em poucos efeitos colaterais. Apresenta boa eficácia, segurança e tolerância pelos pacientes.CONCLUSÕES Dupilumabe é promissor para o tratamento da asma em que a terapia convencional se revela insuficiente. Maiores estudos adicionais são necessários para confirmar a segurança e a eficácia em longo prazo.

International audience; Gadolinium-based contrast agents (GCs), used for magnetic resonance imaging (MRI), are classically considered safer with regard to hypersensitivity (HS) reactions than iodinated radiocontrast media (iRCM). We conducted a retrospective analysis of 132 consecutive patients investigated for suspicions of GC HS (see this article’s Online Repository at www.jaci-inpractice.org). Among the 132 tested patients (83.3% female), 110 (83.3%) had a history of immediate HS (

International audience; Background: House dust mite (HDM) allergens constitute the most frequent cause of persistent allergic rhinitis and asthma. The symptoms vary throughout the year but typically peak in spring, autumn and (to a lesser extent) mid-winter.Methods: We performed a 13-month, observational, multicentre survey of adult patients with a self-reported history of moderate-to-severe, poorly controlled, physician-diagnosed HDM respiratory allergy in three European countries (France, Italy and Spain). After screening and inclusion, 28 detailed, fortnightly telephone interviews were used to gather extensive data on the participants' symptom prevalence and intensity, medical consultations, disease burden and medication use from late May 2012 to early July 2013. This report focuses on the disease burden.Results: Of the 22,995 screened participants, 313 met the inclusion criteria and completed the post-inclusion questionnaire (n = 114 in Italy, 92 in France and 107 in Spain). The median time since the first symptoms of HDM allergy was ≥ 13 years in each country. A relevant minority of the participants suffered from symptoms of HDM allergy every day or almost every day of the year (14% in Italy, 46% in France and 37% in Spain). According to the fortnightly telephone interviews, the most frequently impacted disease burden variables were sleep, daytime tiredness and irritability, with the highest values in spring 2012, autumn 2012 and spring 2013 (mirroring symptom intensities). Professional activities were more affected than social activities. The burden data were heterogeneous: around a quarter of participants were strongly or very strongly affected but most of the remaining participants were only rarely bothered or not bothered.Conclusions: In a 13-month, fortnightly survey of patients in France, Italy and Spain with a self-reported history of moderate-to-severe, poorly controlled, HDM-induced allergic rhinitis and asthma, we found that a relevant minority of participants regularly reported a severe or very severe impact of their allergy on tiredness, sleep and professional activities (including time off work). The disease burden peaked in autumn and late spring.

International audience; BACKGROUND: The management of iodinated contrast medium (ICM) hypersensitivity has been a matter of debate. Skin testing to identify a subgroup of ICM allergic patients has been proposed, in addition to complete avoidance, provocation testing, or premedication. OBJECTIVE: The objective of this study was to assess the negative predictive value (NPV) of skin testing for ICM. METHODS: Patients with a hypersensitivity reaction to ICM who underwent skin testing during a 13.5-year period at a single center were evaluated for re-exposure to a negatively skin-tested ICM. Premedication, consisting of second-generation H1-antihistamines twice a day 48 hours before the examination, was advised only for patients with mast cell disorder or chronic urticaria who had negative skin tests. RESULTS: A total of 597 patients tested for 423 (70.9%) immediate, 118 (19.7%) nonimmediate, and 56 (9.4%) hypersensitivity reactions with undetermined chronology were included. Eighty (13.4%) patients were skin test positive. Re-exposure to ICM occurred in 233 (39.0%) patients and was tolerated in 16 of 17 (94.1%) with at least 1 positive skin test and 201 of 216 (93.1%) with all negative skin tests. Reaction intensity was similar in 4, milder in 10, unknown in 1, and worse in 1 patient although this reaction was deemed to be nonallergic in hindsight. Premedication was administered in 20.7% of patients and associated with more reactions (19.4% vs 5.7%, P~= .01). The overall NPV of skin testing for ICM was 93.1% (95% confidence interval [CI] 89.1% to 96.0%), and for immediate and nonimmediate hypersensitivity reactions 94.2% (95% CI 89.6% to 97.2%) and 86.1% (95% CI 72.1% to 94.7%), respectively. We cannot exclude some challenges occurred with a different than the initial culprit ICM, possibly overestimating the NPV. CONCLUSIONS: Skin testing for potential ICM hypersensitivity can identify safe alternative(s) for ICM re-exposure especially in patients with an immediate hypersensitivity reaction and/or skin test-proven ICM drug allergy. Reactions on re-exposure were infrequent, mostly milder, and occurred in some patients despite premedication.

International audience; Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction characterized by rapidly developing airway and/or circulation problems. It presents with very different combinations of symptoms and apparently mild signs and can progress to fatal anaphylactic shock unpredictably. The difficulty in recognizing anaphylaxis is due, in part, to the variability of diagnostic criteria, which in turn leads to a delay in administration of appropriate treatment, thus increasing the risk of death. The use of validated clinical criteria can facilitate the diagnosis of anaphylaxis. Intramuscular epinephrine (adrenaline) is the medication of choice for the emergency treatment of anaphylaxis. Administration of corticosteroids and H1-antihistamines should not delay the administration of epinephrine, and the management of a patient with anaphylaxis should not end with the acute episode. Long-term management of anaphylaxis should include avoidance of triggers, following confirmation by an allergology study. Etiologic factors suspected in the emergency department often differ from the real causes of anaphylaxis. Evaluation of patients with a history of anaphylaxis should also include an assessment of personal data, such as age and comorbidities, which may increase the risk of severe reactions. Special attention should also be paid to co-factors, as these may easily confound the cause of the anaphylaxis. Patients experiencing anaphylaxis should administer epinephrine as soon as possible. Education (including the use of Internet and social media), written personalized emergency action plans, and self-injectable epinephrine have proven useful for the treatment of further anaphylaxis episodes.

International audience; Drug-induced anaphylaxis (DIA) is a well-recognized risk factor for virtually all classes of medications. The incidence and specific risk factors vary widely depending on the class of drug and reported populations. This perspective addresses recent data reported on DIA and its impact on the understanding of the epidemiology, pathophysiology, and management of anaphylaxis.

Publisher's version (útgefin grein), Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS). Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age. We classified subjects into weight change profiles according to baseline body mass index (BMI) categories and weight change over 20 years. We estimated trajectories of lung function over time as a function of weight change profiles using population-averaged generalised estimating equations. Results: In individuals with normal BMI, overweight and obesity at baseline, moderate (0.25-1 kg/year) and high weight gain (>1 kg/year) during follow-up were associated with accelerated FVC and FEV 1 declines. Compared with participants with baseline normal BMI and stable weight (±0.25 kg/year), obese individuals with high weight gain during follow-up had -1011 mL (95% CI -1.259 to -763) lower estimated FVC at 65 years despite similar estimated FVC levels at 25 years. Obese individuals at baseline who lost weight (, Funding The present analyses are part of the ageing lungs in european cohorts (alec) study (www.alecstudy.org), which has received funding from the european Union’s horizon 2020 research and innovation programme under grant agreement no. 633212. The local investigators and funding agencies for the european community respiratory health survey are reported in the online supplement. isglobal is a member of the cerca Programme, generalitat de catalunya.

ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE vol:7 issue:3 pages:1081-1082 ispartof: location:United States status: published

International audience; This article is one of a series of international consensus documents developed from the International Drug Allergy Symposium held at the Joint Congress of the American Academy of Allergy, Asthma & Immunology/World Allergy Organization on March 1, 2018, in Orlando, Florida, USA. The symposium was sponsored by The Journal of Allergy and Clinical Immunology, The Journal of Allergy and Clinical Immunology: In Practice, and The World Allergy Organization Journal and chaired by Mariana Castells, MD, PhD, and Pascal Demoly, MD, PhD.

International audience; The bronchial epithelium mucociliary function ensuring the lung continuous clearance relies on mucus rheological properties and cilia beating coordination. We focus on two points: first, the biochemical and physical parameters affecting the mucus viscoelastic properties; secondly, the cilia coordination and its coupling with the mucus.We performed rheological experiments on mucus extracted from Air Liquid Interface cultures of bronchial epithelium reconstituted from bronchial biopsies. We combine standard macro-rheology to micro-rheology performed with optical tweezers, to quantify the mucus flowing behaviour at two scales: the mucus layer thickness and the cilia or bacteria scale. Macro- and micro-rheology give different results: an elastic plateau (1-2 Pa) at the macro-scale; a viscous flow (10-3-10-2 Pa) at the micro-scale but with an important adhesion and elasticity at the interfaces. We also perform original experiments using optical tweezers directly on the epithelium, to access the viscoelastic response in the various mucus layers. We obtain an increased elasticity in the vicinity to the epithelium.Finally, the study of the physical mucus properties coupled with the specific methodology we developed to quantify cilia activity, coordination and mucus velocity field, should help to evaluate the efficiency of the mucociliary function and to understand the mechanisms of clearance.

International audience; The mucociliary function of the bronchial epithelium ensures the continuous clearance of the respiratory system. This function relies on two main elements: mucus and cilia beating. We perform here a rheological characterization of mucus samples extracted from ALI (Air-liquid interface) cultures of bronchial epithelium. Our approach combines macro- and micro-rheology techniques with the aim of quantifying the mucus viscoelastic properties at different length scales (from the size of bronchial cilia up to the scale on which mucus is transported). In addition, this methodology allows us to compare the rheological behavior of mucus samples corresponding to different pathologies.

International audience; The mucociliary function of the bronchial epithelium ensures the continuous clearance of the respiratory system. This function relies on two main elements: mucus properties and cilia beating coordination. We work on high speed optical microscopy videos of Human bronchial epithelium from ALI (Air-liquid interface) cultures. We present here a technique based on the tracking of each cilium and on the spatiotemporal analysis of the obtained trajectories. To relate each cilium to its corresponding cell, a clustering method is used. The spatiotemporal coordination can than be quantified both, inside and in-between ciliated cells. In addition the physical parameters can be mapped to observe the heterogeneity of the cilia activity and compare different pathologies.

National audience; The bronchial epithelium mucociliary function ensuring the lung continuous clearance relies on mucus rheological properties and cilia beating coordination. Our biophysical approach aims at understanding two points. First, the biochemical and physical parameters affecting the mucus viscoelastic properties and evaluating its use as a marker for the diagnosis of respiratory diseases. Secondly the cilia coordination and its coupling with the mucus.We performed rheological experiments on mucus extracted from Air Liquid Interface (ALI) cultures of bronchial epithelium reconstituted from bronchial biopsies. Our approach consists in combining standard macro-rheology to micro-rheology performed with optical tweezers, in order to quantify the mucus flowing behavior at different scales, from the cilia up to the mucus layer length scales.Macro- and micro-rheology give different results. At the macro-scale, we obtain an elastic plateau (1 to 2 Pa), a shear-thinning behaviour and a very low yield stress (0.05-0.2 Pa). While at the micro-scale, we obtain a viscous flow, with a very low viscoelastic modulus (10-3-10-2 Pa). Nevertheless, by applying local forces at the interfaces, we observe an important adhesion and elasticity. Mucus adhesion should be taken into account to understand the differences between these different length scales and more generally to characterize the mucus properties. We also perform original experiments using optical tweezers directly on the epithelium, to access the viscoelastic response in the various mucus layers. We obtain an increased elasticity in the vicinity to the epithelium. Moreover, comparison of physical properties of mucus from the culture and directly extracted from patient lungs, provides an additional validation of the ALI model.Finally, the specific methodology we developed to quantify cilia activity and coordination, allows us to map, the cilia spatial distribution, the beating frequency and orientation of each cilium, and their standard deviation within a cilia cluster (cell). Local quantification of the cilia activity coupled to the measurement of the mucus velocity field, should help to evaluate the efficiency of the mucociliary function and to understand the mechanisms of clearance.

Publisher's version (útgefin grein), Background Mothers’ smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers’ smoking may have a similar effect, and biological plausibility that fathers’ smoking during adolescence may influence offspring’s health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma. Methods Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents’ (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines. Results Fathers’ smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01–2.01] and mothers’ smoking during pregnancy (RRR = 1.27, 95% CI: 1.01–1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers’ smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17–2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02–1.55). Conclusions Fathers’ smoking during early adolescence and grandmothers’ and mothers’ smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception., The present analyses are part of the Ageing Lungs in European Cohorts (ALEC) Study [www.alecstudy.org], which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 633212. The coordination of the European Community Respiratory Health Survey (ECRHS) was supported by the European Commission (phases 1 and 2) and the Medical Research Council (phase 3). Local funding agencies for the ECRHS are reported in the Supplementary Appendix, available as Supplementary data at IJE online. Conflict of interest: J.W.H. reports grants from the European Union’s Horizon 2020 programme (633212), the Medical Research Council UK (MC_PC_15078) and the National Institutes of Health USA (R01 AI091905, R01 AI121226) during the conduct of the study. R.J. reports grants from the Estonian Research Council (personal grant No. 562) during the conduct of the study, grants/grants pending from the Estonian Research Council (personal research grant No. 562), personal fees for consulting and lecturing from GlaxoSmithKline, Boehringer and Novartis and travel/accommodation/meeting expenses paid by GlaxoSmithKline and Boehringer, outside the submitted work. C.R. reports personal fees for consulting and lecturing from ALK, Astra Zeneca, GSK, Boheringer and Novartis, outside the submitted work. A.G.C. reports grants from Chiesi Farmaceutici and GlaxoSmithKline Italy, during the conduct of the study. P.D. reports personal fees for consulting and lecturing from ALK and Stallergenes Greer and personal fees for consulting from Circassia, Chiesi Farmaceutici, ThermofisherScientific and Menarini, outside the submitted work. D.J. reports grants from the Medical Research Council and the European Union’s Horizon 2020 programme, during the conduct of the study. All other authors declare no competing interests.

Publisher's version (útgefin grein), Life course data on obesity may enrich the quality of epidemiologic studies analysing health consequences of obesity. However, achieving such data may require substantial resources. We investigated the use of body silhouettes in adults as a tool to reflect obesity in the past. We used large population-based samples to analyse to what extent self-reported body silhouettes correlated with the previously measured (9–23 years) body mass index (BMI) from both measured (European Community Respiratory Health Survey, N = 3 041) and self-reported (Respiratory Health In Northern Europe study, N = 3 410) height and weight. We calculated Spearman correlation between BMI and body silhouettes and ROC-curve analyses for identifying obesity (BMI ≥30) at ages 30 and 45 years. Spearman correlations between measured BMI age 30 (±2y) or 45 (±2y) and body silhouettes in women and men were between 0.62–0.66 and correlations for self-reported BMI were between 0.58–0.70. The area under the curve for identification of obesity at age 30 using body silhouettes vs previously measured BMI at age 30 (±2y) was 0.92 (95% CI 0.87, 0.97) and 0.85 (95% CI 0.75, 0.95) in women and men, respectively; for previously self-reported BMI, 0.92 (95% CI 0.88, 0.95) and 0.90 (95% CI 0.85, 0.96). Our study suggests that body silhouettes are a useful epidemiological tool, enabling retrospective differentiation of obesity and non-obesity in adult women and men., The project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 633212. The co-ordination of ECRHS I and ECRHS I was supported by the European Commission. The co-ordination of ECRHS III was supported by the Medical Research Council (Grant Number 92091). The co-ordination of the RHINE study is led by Professor C. Janson at the Uppsala University. The funding sources for the local ECRHS and RHINE studies are provided in the on-line supplement.

OBJECTIVE: We assessed associations between physical activity and lung function, and its decline, in the prospective population-based European Community Respiratory Health Survey cohort. METHODS: FEV1 and FVC were measured in 3912 participants at 27-57 years and 39-67 years (mean time between examinations=11.1 years). Physical activity frequency and duration were assessed using questionnaires and used to identify active individuals (physical activity ≥2 times and ≥1 hour per week) at each examination. Adjusted mixed linear regression models assessed associations of regular physical activity with FEV1 and FVC. RESULTS: Physical activity frequency and duration increased over the study period. In adjusted models, active individuals at the first examination had higher FEV1 (43.6 mL (95% CI 12.0 to 75.1)) and FVC (53.9 mL (95% CI 17.8 to 89.9)) at both examinations than their non-active counterparts. These associations appeared restricted to current smokers. In the whole population, FEV1 and FVC were higher among those who changed from inactive to active during the follow-up (38.0 mL (95% CI 15.8 to 60.3) and 54.2 mL (95% CI 25.1 to 83.3), respectively) and who were consistently active, compared with those consistently non-active. No associations were found for lung function decline. CONCLUSION: Leisure-time vigorous physical activity was associated with higher FEV1 and FVC over a 10-year period among current smokers, but not with FEV1 and FVC decline. This project has received funding from the european Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-curie individual Fellowship scheme (elaine Fuertes, H2020- MSca-iF-2015; proposal number 704268). the present analyses are part of the ageing lungs in european cohorts (alec) Study (www.alecstudy.org), which has also received funding from the european Union's Horizon 2020 research and innovation programme under grant agreement no 633212. the local investigators and funding agencies for the european community respiratory Health Survey (ecrHS ii and ecrHS iii) are reported in the online supplementary file.

BACKGROUND: Anaphylaxis hospitalisations are increasing in many countries, in particular for medication and food triggers in young children. Food-related anaphylaxis remains an uncommon cause of death, but a significant proportion of these are preventable. AIM: To review published epidemiological data relating to food-induced anaphylaxis and potential risk factors of fatal and/or near-fatal anaphylaxis cases, in order to provide strategies to reduce the risk of severe adverse outcomes in food anaphylaxis. METHODS: We identified 32 published studies available in MEDLINE (1966-2017), EMBASE (1980-2017), CINAHL (1982-2017), using known terms and synonyms suggested by librarians and allergy specialists. RESULTS: Young adults with a history of asthma, previously known food allergy particularly to peanut/tree nuts are at higher risk of fatal anaphylaxis reactions. In some countries, cow's milk and seafood/fish are also becoming common triggers of fatal reactions. Delayed adrenaline injection is associated with fatal outcomes, but timely adrenaline alone may be insufficient. There is still a lack of evidence regarding the real impact of these risk factors and co-factors (medications and/or alcohol consumption, physical activities, and mast cell disorders). CONCLUSIONS: General strategies should include optimization of the classification and coding for anaphylaxis (new ICD 11 anaphylaxis codes), dissemination of international recommendations on the treatment of anaphylaxis, improvement of the prevention in food and catering areas and, dissemination of specific policies for allergic children in schools. Implementation of these strategies will involve national and international support for ongoing local efforts in relationship with networks of centres of excellence to provide personalized management (which might include immunotherapy) for the most at-risk patients. This article is protected by copyright. All rights reserved.

International audience; The mucociliary function of the bronchial epithelium ensures the continuous clearance of the respiratory system, which relies on two main elements: mucus and cilia beating coordination.We perform here a rheological characterization of mucus samples extracted from ALI (Air-liquid interface) cultures of bronchial epithelium. Our approach combines macro- and micro-rheology techniques with the aim of quantifying the mucus viscoelastic properties at different length scales (from the size of bronchial cilia up to the scale on which mucus is transported). This specific methodology allows us to compare samples corresponding to different patient pathologies.In addition, we will describe our method to quantitatively characterize the coordination between cilia and how density and spatial distribution influences this coordination and consequently the mucus motion, required for the mucoliary clearance.

Telomere shortening is associated with COPD and impaired lung function in cross-sectional studies, but there is no longitudinal study. We used data from 448 participants recruited as part of the French follow-up of the European Community Respiratory Health Survey. We found no relationship between telomere length at baseline and FEV1 decline after 11 years of follow-up. However, heavy smoking was associated with an accelerated FEV1 decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08). Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.

International audience; The mucociliary function of the bronchial epithelium ensures the continuous clearance of the respiratory system. This function relies on two main elements: mucus and cilia beating. We perform here a rheological characterization of mucus samples extracted from ALI (Air-liquid interface) cultures of bronchial epithelium. Our approach combines macro- and micro-rheology techniques with the aim of quantifying the mucus viscoelastic properties at different length scales (from the size of bronchial cilia up to the scale on which mucus is transported). In addition, this methodology allows us to compare the rheological behavior of mucus samples corresponding to different pathologies

National audience; La fonction mucociliaire de l'épithélium bronchique assure le nettoyage continu des voies respiratoires afin d’éviter toutes infections et inflammations par les éléments présents dans l’air que nous respirons. L'efficacité de la clairance mucociliaire repose sur deux éléments principaux : les propriétés rhéologiques du mucus et la coordination du battement ciliaire. Dans cette communication, nous décrirons spécifiquement nos résultats sur la rhéologie du mucus. Notre approche biophysique vise à comprendre les paramètres biochimiques et physiques affectant les propriétés viscoélastiques du mucus et à évaluer l 'utilisation des propriétés viscoélastiques du mucus comme marqueur du diagnostic de maladie respiratoire (BPCO, maladie pulmonaire obstructive chronique ...).Des études sur la rhéologie du mucus ont déjà été réalisées, mais essentiellement sur le crachat ou le mucus reconstitué. Nous avons effectué des expériences rhéologiques sur le mucus extrait des cultures ALI (Air Liquid Interface) de l'épithélium bronchique reconstitué à partir d'une biopsie bronchique. Notre approche consiste à combiner une expérience de macro-rhéologie standard et une micro-rhéologie réalisée avec des pinces optiques afin de quantifier les propriétés viscoélastiques du mucus et de comprendre son comportement d'écoulement à différentes échelles, de l'échelle des cils jusqu'à l'échelle de longueur sur laquelle le mucus est transporté.Nos résultats montrent le comportement d'amincissement par cisaillement et la nature élastique du mucus avec un petit module élastique G 'compris entre 1 et 2 Pa. On observe également la rupture du gel de mucus à très faible taux de cisaillement et même pour la déformation oscillatoire réalisée À des fréquences inférieures à la fréquence de battement des cils (~ 15 Hz), probablement en raison de la structure complexe et hétérogène du mucus. Néanmoins, la structure du mucus et les propriétés viscoélastiques sont récupérées en 5 minutes. La macro et la micro-rhéologie indiquent deux comportements différents : on observe un plateau élastique à la macro-échelle et un comportement visqueux à la micro-échelle, avec une viscoélasticité très faible de l'ordre de 10-3 à 10-2 Pa et proportionnelle À la fréquence de ω0,9 dans la même plage de fréquence. En appliquant des forces locales grâce à des pinces optiques, comme le montre la figure 1, nous montrons que l'adhérence du mucus est impliquée et doit être prise en compte pour comprendre les différences entre les propriétés mécaniques mesurées à ces différentes échelles de longueur et plus généralement pour caractériser les propriétés du mucus.Cette approche biophysique et méthodologie spécifique nous permet de comparer des échantillons correspondant à différentes pathologies du patient et pourrait être appliquée avec succès à l'hypersécrétion de mucus de patients atteints de fibrose kystique. Ce travail s'inscrit dans le cadre d'un projet de plus grande envergure impliquant une étude de physique statistique sur la coordination des cils et son couplage avec la viscoélasticité du mucus.

Background House dust mite (HDM) allergens constitute the leading trigger for the symptoms of persistent respiratory allergies (such as allergic rhinitis and asthma). However, the fluctuating, pernicious nature of the symptoms has given rise to a perception that HDM-induced respiratory allergy is not a “real” disease. Methods In order to assess the self-reported disease profile and behaviour of adult patients with a self-reported history of severe, poorly controlled, physician-diagnosed HDM respiratory allergy, we performed an observational, international, multicentre survey in three European countries (France, Italy and Spain). Participants were included in the survey if they passed a short Internet-based screening questionnaire. Following completion of a detailed post-inclusion questionnaire, 28 fortnightly telephone interviews were used to gather extensive data on the participants’ symptom prevalence and intensity, medical consultations, disease burden, quality of life, and medication use from late May 2012 to early July 2013. Results Twenty-two thousand nine hundred ninety five individuals completed the Internet screening questionnaire and 339 respondents (67 % female) met all the inclusion criteria. 313 of the 339 (92 %) completed the post-inclusion questionnaire (n = 114 in Italy, 92 in France and 107 in Spain). The median time since the first symptoms of HDM allergy was over 13 years in all three countries. The response rate for the fortnightly interviews averaged 75 % (range: 29 to 97 %). The reported fortnightly prevalence of nasal and ocular symptoms peaked in the autumn (September to November) and spring (March to May). These peaks in prevalence coincided with increased reports of symptom worsening and higher physician consultation rates. In participants not allergic to pollen, the autumn and spring peaks were accompanied by a third peak in late December 2012. Very few participants reported that their symptoms had never improved (4 %) or never worsened (11 %) during the survey period. Conclusions In a survey in France, Italy and Spain, patients with severe HDM-induced respiratory allergies experienced a complex set of changing, troublesome symptoms throughout the year, with peaks in spring, autumn and (to a lesser extent) mid-winter. Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0246-9) contains supplementary material, which is available to authorized users.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing. ispartof: Clinical and Translational Allergy vol:6 issue:1 pages:41-47 ispartof: location:England status: published

International audience; BackgroundChildhood interstitial lung disease (chILD) is a heterogeneous group of rare disorders characterized by abnormal imaging findings, impaired gas exchange; and is associated with substantial morbidity and mortality. Neuroendocrine cell hyperplasia (NEHI) is a unique sub-group, which is more prevalent in infants and children younger than 2 years of age, and typically manifests with chronic tachypnea, retractions, hypoxemia and failure to thrive. NEHI insidiously appears in the first year of life, subtly masquerading as one of the more common lung diseases of childhood. Therefore, the diagnosis of NEHI is challenging and requires a systematic approach.Case presentationWe report a case of an infant, with a history of recurrent respiratory infections and wheezing, who presented with persistent hypoxemia (PaO2 88 mmHg) and chronic respiratory symptoms, that prompted an extensive diagnostic work up for chILD; eventually a diagnosis of NEHI was made.ConclusionNEHI is a rare chILD disorder presenting in the first 2 years of life with common but challenging key clinical features. Increased awareness among pediatricians and prompt recognition of the clinical presentation may enable timely diagnosis and improve disease management and prognosis.

Background: Disease stratification, using phenotypic characterization performed either by hypothesis- or data-driven methods, was developed to improve clinical decisions. However, cluster analysis has not been used for allergic rhinitis. Objective: To define clusters in allergic rhinitis and to compare them with ARIA (Allergic Rhinitis and Its Impact on Asthma), a hypothesis-driven approach. Methods: A French observational prospective multicenter study (EVEIL: Echelle visuelle analogique dans la rhinite allergique) was carried out on 990 patients consulting general practitioners for allergic rhinitis and treated as per clinical practice. In this study, changes in symptom scores, visual analogue scales and quality of life were measured at baseline and after 14 days of treatment. A post hoc analysis was performed to identify clusters of patients with allergic rhinitis - using Ward's hierarchical method - and to define their clinical relevance at baseline and after 14 days of treatment. The cluster approach was compared to the ARIA approach. Results: Patients were clustered into 4 phenotypes which partly followed the ARIA classes. These phenotypes differed in their disease severity including symptoms and quality of life. Physicians in real-life practice prescribed medication regardless of the phenotype and severity, with the exception of patients with ocular symptoms. Prescribed treatments were comparable in hypothesis- and data-driven analyses. The prevalence of uncontrolled patients during treatment was similar in the 4 clusters, but was significantly different according to the ARIA classes. Conclusion: Cluster analysis using demographic and clinical parameters only does not appear to add relevant information for disease stratification in allergic rhinitis.

Background Allergy and hypersensitivity can affect people of any age and manifest with problems in a range of organ systems. Moreover, they can have a significant impact on the quality of life of patients and their families. Although once rare, there is presently an epidemic of allergic disorders with associated considerable societal consequences.Our understanding of the pathophysiology of these disorders has changed substantially over the last 20 years. In the light of these developments, the Joint Allergy Academies have made concerted efforts to ensure that these are reflected in the current definitions and concepts used in clinical allergy and to ensure these are reflected in the forthcoming International Classification of Diseases-11 (ICD-11).Objective In this review, we seek to provide an update on the current definitions and concepts in relation to allergic disorders.Results Once the new section has been built in the ICD-11 to address allergic and hypersensitivity conditions, we have been moving actions to try to support awareness by disseminating updated concepts in the field. Aligned with the ICD and the WAO philosophy of being global, this document presents fundamental and broad allergy concepts to strengthen the understanding by different health professionals worldwide, besides to support the formation of in training students.Conclusion This current review intends to be accepted and used universally by all health professionals involved in diseases’ classification and coding and, therefore, contribute to improve care and outcomes in this increasing sub-section of the world’s population. Keywords: Allergy, Hypersensitivity, Allergic conditions, Hypersensitivity conditions, Sensitization

The occurrence of a late reaction following exercise induced asthma is questionable and its relationship with the non specific bronchial hyperreactivity is poorly known. In this study, nine patients (age 15-21 years) underwent an exercise challenge in order to (a) determine the incidence of immediate and late phase reaction and (b) analyse the modifications of non specific bronchial hyperreactivity. Study design was a follow; day-3: determination of bronchial responsiveness to metacholine; day 0: control day with FEV1 measurements every hour for 11 hours; day 1: exercise challenge followed by a careful observation of change in FEV1; day 2: new determination of bronchial responsiveness to metacholine. An immediate exercise induced bronchial obstruction was observed in 5 patients. A late phase reaction (6th hour) with a fall of FEV1 equal to or more than 20% has been demonstrated in two patients. For the former, the change in FEV1 did not differ from the value of the control day. For the second, the FEV1 changed spontaneously during the control day so that decreases of FEV1 during control and challenge days were parallel. Thus, no late phase reaction were observed (F = 0.46; ns). There was no modification of bronchial responsiveness to metacholine (pre-exercise: 1,784 +/- 1,970 [SD]; post-exercise 1,827 +/- 2,231 micrograms [SD]). The lack of true late phase reaction when the post-exercise change in FEV1 is compared to the one of a control day and the absence of modification of non specific bronchial hyperreactivity weaken the hypothesis of an inflammatory mechanism of exercise induced asthma.

In order to define the role of individualized training intensity in a conditioning program for asthmatic children, we have trained seven asthmatics (age = 11.4 +/- 1.8 years) at their ventilatory threshold (VTh) intensity level for a three-month period (aerobic training) and at maximal intensity also for three months (high intensity training). VTh is the point at which a nonlinear increase of VE occurs. Another group of seven asthmatics (age = 11.4 +/- 1.5) served as control subjects. Cardiopulmonary fitness was determined on a cycle ergometer before and after each training session. This study demonstrated that aerobic training, correctly adapted to the child's physical ability, induces the following: (1) a rapid and marked cardiovascular fitness increase; and (2) a decrease in VE over a given work range so that VTh is increased. This is of great importance because hyperventilation is a major determinant of exercise-induced bronchospasm. In contrast, even if high intensity training is well tolerated in an indoor swimming pool, the long-term effects are unsuitable for asthmatic children because the decrease of VTh will involve an increase of hyperventilation, even when exercise is performed at submaximal intensity.

There have been few works studying the effects of training in asthmatics and there does not yet exist any study utilising the idea of the individualization of training. This is why the aim of this study was to assess the value of the effects of individualised aerobic training on cardio-respiratory aptitude in the asthmatic child. This study was carried out on two populations of asthmatics, swimmers and non-swimmers matched for age, height, degree of bronchial obstruction during a remission and baseline of physical fitness. Each child in the swimming group was trained to a metabolic level corresponding to the ventilatory threshold. After a period of 3 months a second cardio-respiratory evaluation was carried out. A clear cut improvement (20%) of VO2 max was observed as well as a proportional elevation of the ventilatory threshold in the swimming group. The VE max, the VT max, the VT/Timax, the FC max and the maximal oxygen uptake were also recorded. On the other hand aerobic training seems to be without effect on resting pulmonary function, even if the clinical state of the children improved. In conclusion this study shows that aerobic training closely adapted to the level of each child, obtains an important and rapid gain in cardio-respiratory fitness which leads to a better exercise adaptation. In addition the progression of the ventilatory threshold implies an increased capacity for work without the appearance of hyperventilation. This enables an understanding of how aerobic training is generally accompanied in the asthmatic with a better respiratory comfort and argues in favour of the perfect efficacy of this type of reconditioning in the re-adaptation to effort in these patients.