Mariona Pinart

Designing and Reporting Clinical Trials on Treatments for Cutaneous Leishmaniasis

Cutaneous leishmaniasis is considered to be one of the most neglected and serious parasitic infectious skin diseases in many developing countries. We have assessed the design and reporting of randomized, controlled trials evaluating treatments included in 2 Cochrane systematic reviews on cutaneous leishmaniasis. The analysis of the methodological quality identified some potential bias that can make it difficult to determine whether truly effective therapies exist for this disease. We found important weaknesses in the adequacy and transparency of randomization, loss of participants, causative Leishmania species, outcome measures, and follow-up times. Given these distorting effects on the evidence base, we propose guidelines for authors who wish to conduct clinical trials aimed at the development of effective therapies in cutaneous leishmaniasis. The recommendations in this report will hopefully deserve the attention of the World Health Organization and assist in the planning and prioritization of global strategies for improving the interpretation and replication of clinical research on cutaneous leishmaniasis.

A systematic review of socioeconomic position in relation to asthma and allergic diseases

The role of socioeconomic position (SEP) in the development of asthma and allergies is unclear, with some pointing to the risks of low SEP and other research pointing in the direction of higher SEP being associated with higher prevalence rates. The aim of this systematic review is to clarify associations between SEP and the prevalence of asthma and allergies. Out of 4407 records identified, 183 were included in the analysis. Low SEP was associated with a higher prevalence of asthma in 63% of the studies. Research on allergies, however, showed a positive association between higher SEP and illness in 66% of studies. Pooled estimates for the odds ratio of disease for the highest compared with the lowest SEP confirmed these results for asthma (unadjusted OR 1.38, 95% CI 1.37–1.39), allergies in general (OR 0.67, 95% CI 0.62–0.72), atopic dermatitis (unadjusted OR 0.72, 95% CI 0.61–0.83) and allergic rhinoconjunctivitis (unadjusted OR 0.52, 95% CI 0.46–0.59). Sensitivity analyses with a subsample of high-quality studies led to the same conclusion. Evidence from this systematic review suggests that asthma is associated with lower SEP, whereas the prevalence of allergies is associated with higher SEP. Lower socioeconomic position associated with higher prevalence of asthma and lower prevalence of allergies http://ow.ly/Oroan

Paving the way of systems biology and precision medicine in allergic diseases

MeDALL (Mechanisms of the Development of ALLergy; EU FP7‐CP‐IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large‐scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy‐related diseases. To complement the population‐based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Phenotyping asthma, rhinitis and eczema in MeDALL population-based birth cohorts: an allergic comorbidity cluster

Asthma, rhinitis and eczema often co‐occur in children, but their interrelationships at the population level have been poorly addressed. We assessed co‐occurrence of childhood asthma, rhinitis and eczema using unsupervised statistical techniques.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen‐specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono‐ and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE‐mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re‐occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE‐mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention.

A systematic review on the development of asthma and allergic diseases in relation to international immigration: the leading role of the environment confirmed.

Background The prevalence of asthma and allergic diseases is rising worldwide. Evidence on potential causal pathways of asthma and allergies is growing, but findings have been contradictory, particularly on the interplay between allergic diseases and understudied social determinants of health like migration status. This review aimed at providing evidence for the association between migration status and asthma and allergies, and to explore the mechanisms between migration status and the development of asthma and allergies. Methods and Findings Systematic review on asthma and allergies and immigration status in accordance with the guidelines set by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled odds ratio (OR) of the prevalence of asthma in immigrants compared to the host population was 0.60 (95% CI 0.45–0.84), and the pooled OR for allergies was 1.01 (95% CI 0.62–1.69). The pooled OR for the prevalence of asthma in first generation versus second generation immigrants was 0.37 (95% CI 0.25–0.58). Comparisons between populations in their countries of origin and those that emigrated vary depending on their level of development; more developed countries show higher rates of asthma and allergies. Conclusions Our findings suggest a strong influence of the environment on the development of asthma and allergic diseases throughout the life course. The prevalence of asthma is generally higher in second generation than first generation immigrants. With length of residence in the host country the prevalence of asthma and allergic diseases increases steadily. These findings are consistent across study populations, host countries, and children as well as adults. Differences have been found to be significant when tested in a linear model, as well as when comparing between early and later age of migration, and between shorter and longer time of residence.

Mechanisms of the Development of Allergy (MeDALL): Introducing novel concepts in allergy phenotypes

&NA; Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE‐associated and non–IgE‐associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7‐CP‐IP; project no: 261357; 2010‐2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including in vivo and in vitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow‐ups between pregnancy and age 20 years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. A microarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome‐wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), and transcriptomic (723) studies. Using classical epidemiology and machine‐learning methods in 16,147 children aged 4 years and 11,080 children aged 8 years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

Childhood asthma prediction models: a systematic review

Early identification of children at risk of developing asthma at school age is crucial, but the usefulness of childhood asthma prediction models in clinical practice is still unclear. We systematically reviewed all existing prediction models to identify preschool children with asthma-like symptoms at risk of developing asthma at school age. Studies were included if they developed a new prediction model or updated an existing model in children aged 4 years or younger with asthma-like symptoms, with assessment of asthma done between 6 and 12 years of age. 12 prediction models were identified in four types of cohorts of preschool children: those with health-care visits, those with parent-reported symptoms, those at high risk of asthma, or children in the general population. Four basic models included non-invasive, easy-to-obtain predictors only, notably family history, allergic disease comorbidities or precursors of asthma, and severity of early symptoms. Eight extended models included additional clinical tests, mostly specific IgE determination. Some models could better predict asthma development and other models could better rule out asthma development, but the predictive performance of no single model stood out in both aspects simultaneously. This finding suggests that there is a large proportion of preschool children with wheeze for which prediction of asthma development is difficult.

The development of the MeDALL Core Questionnaires for a harmonized follow-up assessment of eleven European birth cohorts on asthma and allergies.

Background: Numerous birth cohorts have been initiated in the world over the past 30 years using heterogeneous methods to assess the incidence, course and risk factors of asthma and allergies. The aim of the present work is to provide the stepwise proceedings of the development and current version of the harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used prospectively in 11 European birth cohorts. Methods: The harmonization of questions was accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages and (iv) implementation of the harmonized follow-up. Results: Three harmonized MeDALL-CQs (2 for parents of children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed and used for a harmonized follow-up assessment of 11 European birth cohorts on asthma and allergies with over 13,000 children. Conclusions: The harmonized MeDALL follow-up produced more comparable data across different cohorts and countries in Europe and will offer the possibility to verify results of former cohort analyses. Thus, MeDALL can become the starting point to stringently plan, conduct and support future common asthma and allergy research initiatives in Europe.

Sex-Related Allergic Rhinitis Prevalence Switch from Childhood to Adulthood: A Systematic Review and Meta-Analysis

Background: A sex-related switch in the prevalence of asthma from childhood (male predominance) to adulthood (female predominance) has been described, but for allergic rhinitis this remains unclear. We aimed to examine sex- and age-group-specific differences in allergic rhinitis prevalence by systematically evaluating studies from across the globe. Methods: A systematic search of MEDLINE and Embase for population-based cross-sectional studies was performed regardless of the language of publication. The search was restricted to the present millennium (2000 to June 2014). Study quality was defined by the sampling method, response rate, sample size, and data collection method. To assess sex differences in the prevalence of self- or parent-reported symptoms of rhinitis, calculated pooled estimates of the male-female ratio (MFR) were obtained using random-effects model meta-analyses due to heterogeneity. A meta-regression analysis was also performed. Results: Out of 6,539 publications identified, 67 cross-sectional population-based studies (291,726 males and 301,781 females) were included in our meta-analysis. In children (<11 years of age) significantly more boys than girls had rhinitis symptoms (MFR 1.21, 95% CI 1.17-1.25), whereas in adolescents (11 to <18 years of age) males were significantly less often affected than females (MFR 0.90, 95% CI 0.85-0.95). No sex-specific prevalence difference was observed in adults (MFR 0.96, 95% CI 0.83-1.17). These findings were consistent in all continents except in Asia, where the male predominance remained beyond childhood. Conclusions: The male predominance of rhinitis prevalence in childhood changed towards a female predominance in adolescence across the globe, except in Asia. Longitudinal studies are needed to confirm these cross-sectional data and examine possible determinants and underlying mechanisms.