Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis.

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease," coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis." This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases.

Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study.

BACKGROUND: Diagnosing atopic dermatitis (AD) in infants is challenging. OBJECTIVES: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. METHODS: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. RESULTS: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22-0·48] or 12 months (OR 0·49, 95% CI 0·32-0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3-43·6) or two (OR 6·5, 95% CI 4·3-9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. CONCLUSIONS: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.

Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

An update on prevalence and risk of snus and nicotine replacement therapy during pregnancy and breastfeeding.

AIM: In parallel with falling smoking rates, use of the oral moist tobacco product snus increases among women in reproductive age. We report an update on prevalence and effects of maternal use of snus and nicotine replacement therapy (NRT) during pregnancy and breastfeeding. METHODS: A literature search of human studies in Medline, PubMed and EMBASE was conducted from September 2016 to May 2018, with stepwise screening of abstracts and subsequent relevant full-text papers for inclusion in Scandinavian and English languages. RESULTS: Based on three studies, the prevalence of snus use in pregnancy was up to 3.4% in the first trimester and 2.1% in the third trimester. In 12 studies, we found increased risk of several adverse effects, especially preterm delivery, stillbirth and small for gestational age associated with maternal snus use during pregnancy. Knowledge on effects of NRT during pregnancy was conflicting and inconclusive in 10 studies. We did not identify any studies on prevalence or potential health effects of snus or NRT during breastfeeding. CONCLUSION: Few studies with updated data on the prevalence and adverse health effects of maternal use of snus and NRT during pregnancy were found. No studies during breastfeeding were identified.

Predicting reactivity threshold in children with anaphylaxis to peanut.

BACKGROUND: Peanut allergy necessitates dietary restrictions, preferably individualized by determining reactivity threshold through an oral food challenge (OFC). However, risk of systemic reactions often precludes OFC in children with severe peanut allergy. OBJECTIVE: We aimed to determine whether clinical and/or immunological characteristics were associated with reactivity threshold in children with anaphylaxis to peanut and secondarily, to investigate whether these characteristics were associated with severity of the allergic reaction during OFC. METHODS: A double-blinded placebo-controlled food challenge (DBPCFC) with peanut was performed in 96 5- to 15-year-old children with a history of severe allergic reactions to peanut and/or sensitization to peanut (skin prick test [SPT] ≥3 mm or specific immunoglobulin E [s-IgE] ≥0.35 kUA/L). Investigations preceding the DBPCFC included a structured interview, SPT, lung function measurements, serological immunology assessment (IgE, IgG and IgG4 ), basophil activation test (BAT) and conjunctival allergen provocation test (CAPT). International standards were used to define anaphylaxis and grade the allergic reaction during OFC. RESULTS: During DBPCFC, all 96 children (median age 9.3, range 5.1-15.2) reacted with anaphylaxis (moderate objective symptoms from at least two organ systems). Basophil activation (CD63+ basophils ≥15%), peanut SPT and the ratio of peanut s-IgE/total IgE were significantly associated with reactivity threshold and lowest observed adverse events level (LOAEL) (all P < .04). Basophil activation best predicted very low threshold level (<3 mg of peanut protein), with an optimal cut-off of 75.8% giving a 93.5% negative predictive value. None of the characteristics were significantly associated with the severity of allergic reaction. CONCLUSION AND CLINICAL RELEVANCE: In children with anaphylaxis to peanut, basophil activation, peanut SPT and the ratio of peanut s-IgE/total IgE were associated with reactivity threshold and LOAEL, but not with allergy reaction severity.

Mechanisms of exercise-induced bronchoconstriction in athletes: Current perspectives and future challenges.

The evidence of exercise-induced bronchoconstriction (EIB) without asthma (EIBwA ) occurring in athletes led to speculate about different endotypes inducing respiratory symptoms within athletes. Classical postulated mechanisms for bronchial obstruction in this population include the osmotic and the thermal hypotheses. More recently, the presence of epithelial injury and inflammation in the airways of athletes was demonstrated. In addition, neuronal activation has been suggested as a potential modulator of bronchoconstriction. Investigation of these emerging mechanisms is of major importance as EIB is a significant problem for both recreational and competitive athletes and is the most common chronic condition among Olympic athletes, with obvious implications for their competing performance, health and quality of life. Hereby, we summarize the latest achievements in this area and identify the current gaps of knowledge so that future research heads toward better defining the etiologic factors and mechanisms involved in development of EIB in elite athletes as well as essential aspects to ultimately propose preventive and therapeutic measures.

Prenatal exposure to perfluoralkyl substances (PFASs) associated with respiratory tract infections but not allergy- and asthma-related health outcomes in childhood.

BACKGROUND: Prenatal exposure to perfluoralkyl substances (PFASs) has been reported to be associated with immunosuppression in early childhood, but with contradictory findings related to atopic and lung diseases. AIM: We aimed to determine if prenatal exposure to PFASs is associated with asthma or other allergic diseases or respiratory tract infections in childhood. METHODS: Nineteen PFASs were measured in cord blood available from 641 infants in the Environment and Childhood Asthma (ECA) prospective birth cohort study. The six most abundant PFASs were perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonamide (PFOSA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA). Health outcomes were assessed at two and ten years of age, and included reported obstructive airways disease (wheeze by 10 years; asthma by 2 and 10 years; reduced lung function at birth; allergic rhinitis by 10 years), atopic dermatitis (AD) by 2 and 10 years, allergic sensitization by 10 years, and episodes of common respiratory tract infections (common cold by 2 years, lower respiratory tract infections (LRTI) by 10 years). The associations between exposure and health outcomes were examined using logistic and Poisson regression. RESULTS: The number of reported airways infections were significantly associated with cord blood concentrations of PFAS; common colds by two years with PFUnDA (ß = 0.11 (0.08-0.14)) and LRTIs from 0 to 10 years of age with PFOS (ß = 0.50 (0.42-0.57)), PFOA (ß = 0.28 (0.22-0.35)), PFOSA (ß = 0.10 (0.06-0.14)), PFNA (ß = 0.09 (0.03-0.14)) and PFUnDA (ß = 0.18 (0.13-0.23)) concentrations. Neither reduced lung function at birth, asthma, allergic rhinitis, AD nor allergic sensitization were significantly associated with any of the PFASs. CONCLUSION: Although prenatal exposure to PFASs was not associated with atopic or lung manifestations by 10 years of age, several PFASs were associated with an increased number of respiratory tract infections in the first 10 years of life, suggesting immunosuppressive effects of PFASs.

Sequels to tattoo removal by caustic products.

BACKGROUND: Caustic products are used as affordable alternatives to laser removal of tattoos. OBJECTIVE: Describe a series of patients with sequels after tattoo removal by caustic products. METHODS: 11 patients with complications referred from 2013 to 2017 were studied. Objective findings, sequels, corrective treatments, cost and psychological aspects were obtained. Numeric Rating Scale (NRS, score 10 extremely dissatisfied) was used to describe patient satisfaction with tattoos before and after removal. RESULTS: Scarring and residual tattoo pigments were detected in all patients. Chronic itching (73%), redness (73%) and swelling (64%) were frequent. Patients were less satisfied with their tattoo after removal attempts; Average NRS prior to removal was 7.5 (range 5-10), and afterwards 8.9 (range 4.5-10), t test non-significant. Removal was performed by medical professionals (82%) and cosmetologists (18%), involving the marketed injection brands Tatt2Away and Rejuvi. Ten patients had corrections eg. laser, plastic surgery or cover-up tattoos. Private expense for corrections was mean 1.953 EUR, not including consultations provided by the Hospital. CONCLUSION: Tattoo removal by caustic products can cause severe and chronic sequels with dissatisfaction despite therapeutic interventions to correct disfiguring changes. Removal by caustic products is freely permitted. Products are obscured and liability and consumer protection is unacceptable; limitation is needed.

Conjunctival provocation test in diagnosis of peanut allergy in children.

BACKGROUND: Peanut allergy frequently causes severe allergic reactions. Diagnosis includes detection of IgE to peanuts in serum or by skin prick tests. While children may have allergic sensitization without having clinical peanut allergy, oral peanut challenge is often required for accurate diagnosis. The conjunctival provocation test is used for diagnosis and evaluation of treatment effect in inhalant allergies, but it has not been evaluated as a tool for diagnosing peanut allergy. OBJECTIVE: To investigate whether the conjunctival provocation tests may be feasible, accurate and safe in diagnosing clinically relevant peanut allergy in patients with suspected peanut allergy. METHODS: This cross-sectional case-control study in children with clinical or laboratory suspected peanut allergy included 102 children recruited from the regional paediatric departments and specialist practices during one year from April 2011. A peanut-tolerant control group of 28 children of similar age was recruited locally. A double-blind placebo-controlled conjunctival provocation test with peanut extract was performed in all children, while oral peanut provocation was performed as double-blind placebo-controlled challenge in children with suspected peanut allergy and as an open challenge in the control children. RESULTS: All 81 children with a positive double-blind placebo-controlled oral food challenge (OFC) also had a positive conjunctival provocation test. None of the children with negative conjunctival provocation test had a positive OFC. The sensitivity and the specificity of the conjunctival provocation test were 0.96 and 0.83, respectively. No children had severe adverse reaction caused by the conjunctival provocation test, whereas 23 children suffered an anaphylactic reaction to the OFC. CONCLUSION AND CLINICAL RELEVANCE: Conjunctival allergen challenge appears to be feasible, accurate and safe in diagnosing children referred for suspected peanut allergy.

Google Trends terms reporting rhinitis and related topics differ in European countries.

Google Trends (GT) searches trends of specific queries in Google and reflects the real-life epidemiology of allergic rhinitis. We compared Google Trends terms related to allergy and rhinitis in all European Union countries, Norway and Switzerland from 1 January 2011 to 20 December 2016. The aim was to assess whether the same terms could be used to report the seasonal variations of allergic diseases. Using the Google Trend 5-year graph, an annual and clear seasonality of queries was found in all countries apart from Cyprus, Estonia, Latvia, Lithuania and Malta. Different terms were found to demonstrate seasonality depending on the country - namely 'hay fever', 'allergy' and 'pollen' - showing cultural differences. A single set of terms cannot be used across all European countries, but allergy seasonality can be compared across Europe providing the above three terms are used. Using longitudinal data in different countries and multiple terms, we identified an awareness-related spike of searches (December 2016).

Tattoo removal by Q-switched yttrium aluminium garnet laser: client satisfaction.

BACKGROUND: Tattoo removal by Q-switched yttrium aluminium garnet (YAG) lasers is golden standard; however, clients' satisfaction with treatment is little known. OBJECTIVE: To determine clients' satisfaction with tattoo removal. METHODS: One hundred and fifty-four tattoo removal clients who had attended the private clinic 'Centre for Laser Surgery', Hellerup, Denmark, from 2001 to 2013 completed a questionnaire concerning outcome expectations, level of pain experiences and satisfaction with tattoo removal. The laser surgeon and his team were blinded from data handling. The study design included a minimum 2-year postlaser treatment observation period from 2013 to 2015. RESULTS: Overall, clients were satisfied with their laser treatment; 85% assessed their treatment and results to be acceptable to superb, while 15% assessed their treatment and results to be inferior to unacceptable. Effectiveness relative to colour of tattoo on a scale from 0 (no effect) to 10 (complete removal) scored a mean of blue 9.5, black 9.4, yellow 8.9, red 8.8 and green 6.5. Clients were dissatisfied with green pigment remnants, which could mimic bruising. One hundred and twenty-nine clients (84%) experienced moderate to extreme pain during treatment. Twenty-eight (20%) developed minor scarring. There were many reasons for tattoo removal; e.g. stigmatisation (33%), conspicuousness (29%) and poor artistic quality (22%). One hundred and two clients had expected complete removal of tattoos without a blemish, expectations that were only partly fulfilled. During the treatment period, clients adjusted expectations and adapted more realistic views of outcomes. CONCLUSION: The majority of clients were satisfied with Q-switched YAG laser removal of tattoos despite high pretreatment expectations which were only partly met. The study supports YAG lasers for tattoo removal as acceptable therapy of today, with room for new approaches.

Asthma and dietary intake: an overview of systematic reviews.

Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, anti-allergic and anti-inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

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.

Vitamin D levels and atopic eczema in infancy and early childhood in Norway: a cohort study.

BACKGROUND: Epidemiological data and the effect of sun exposure on atopic eczema (AE) suggest that vitamin D (vitD) may be involved in the pathogenesis. OBJECTIVES: To investigate if vitD levels were associated with the presence or severity of AE in the first 2 years of life in children living in south-east Norway. METHODS: Infants, recruited to a clinical trial on acute bronchiolitis (n = 404) and from the general population (n = 240), were examined at 1-13 months (first visit) and at 2 years of age (second visit). Caregivers were interviewed using a structured questionnaire. AE was diagnosed clinically, based on well-established criteria. Disease severity was assessed using the SCORing Atopic Dermatitis index. Blood samples were taken for vitD measurements, using liquid chromatography-tandem mass spectrometry and for common filaggrin mutation analyses. Complete data on AE and vitD were available in 596 and 449 children at the first and second visit, respectively. RESULTS: Atopic eczema was diagnosed in 67 children (11%) at the first visit and in 103 children (23%) at the second. Mean vitD levels were 58·2 nmol L(-1) at the first visit and 66·9 nmol L(-1) at the second. Using vitD level tertiles in multivariate regression analysis, there was no association between vitD levels and AE at either visit, regardless of filaggrin mutation. In children without AE at the first visit, vitD levels did not predict AE at the second. CONCLUSIONS: In this cohort of young children in Norway, we found no association between vitD levels and the presence or severity of AE.

Allergic reactions in red tattoos: Raman spectroscopy for 'fingerprint' detection of chemical risk spectra in tattooed skin and culprit tattoo inks.

AIM: The aim of this study was to assess the feasibility of Raman spectroscopy as a screening technique for chemical characterisation of tattoo pigments in pathologic reacting tattoos and tattoo ink stock products to depict unsafe pigments and metabolites of pigments. MATERIALS/METHODS: Twelve dermatome shave biopsies from allergic reactions in red tattoos were analysed with Raman spectroscopy (A 785-nm 300 mW diode laser). These were referenced to samples of 10 different standard tattoo ink stock products, three of these identified as the culprit inks used by the tattooist and thus by history the source of the allergy. Three primary aromatic amine (PAA) laboratory standards (aniline, o-anisidine and 3,3'-dichlorobenzidine) were also studied. RESULTS: Application of Raman spectroscopy to the shave biopsies was technically feasible. In addition, all ten inks and the three PAA standards could be discriminated. 10/12 shave biopsies provided clear fingerprint Raman signals which differed significantly from background skin, and Raman spectra from 8/12 biopsies perfectly matched spectra from the three culprit ink products. The spectrum of one red ink (a low cost product named 'Tattoo', claimed to originate from Taiwan, no other info on label) was identified in 5/12 biopsies. Strong indications of the inks 'Bright Red' and 'Crimson Red' were seen in three biopsies. The three PAA's could not be unambiguously identified. CONCLUSION: This study, although on a small-scale, demonstrated Raman spectroscopy to be feasible for chemical analysis of red pigments in allergic reactions. Raman spectroscopy has a major potential for fingerprint screening of problematic tattoo pigments in situ in skin, ex vivo in skin biopsies and in tattoo ink stock products, thus, to eliminate unsafe ink products from markets.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Early risk factors for pubertal asthma.

BACKGROUND: Early life risk factors are previously described for childhood asthma, but less is known related to asthma in adolescence. We aimed to investigate early risk factors (before 2 years) for pubertal asthma and secondarily for pubertal asthma phenotypes based upon allergic comorbidities. METHODS: Based on data from 550 adolescents in the prospective birth cohort 'Environment and Childhood Asthma' study, subjects were categorized by recurrent bronchial obstruction (rBO) 0-2 years, asthma 2-10 years, and pubertal asthma from 10 to 16 years including incident asthma in puberty and asthma in remission from 10 to 16 years or as never rBO/asthma 0-16 years. Asthma in puberty was further classified based on the comorbidities atopic dermatitis and allergic rhinitis (AR) from 10 to 16 years. Twenty-three common asthma risk factors identified by 2 years of age, including frequency and persistence of bronchial obstruction (severity score), were analysed by weighted logistic regression for each phenotype. RESULTS: In adjusted models, the risk of pubertal asthma increased significantly with higher severity score, parental rhinitis, being the firstborn child, and familial stress around birth. Pubertal asthma in remission was significantly associated with severity score and number of lower respiratory tract infections and inversely associated with breastfeeding beyond 4 months. Pubertal incident asthma was more common among firstborn children. All asthma phenotypes with allergic diseases were significantly associated with severity score, whereas familial perinatal stress increased the risk of asthma only. Asthma combined with AR was associated with parental asthma and being firstborn, whereas the risk of asthma with both atopic dermatitis and AR increased with higher paternal education, atopic dermatitis, being firstborn, and familial perinatal stress. CONCLUSION AND CLINICAL RELEVANCE: Important early risk factors for pubertal asthma were early airways obstruction, parental rhinitis, being the firstborn child, and perinatal familial stress.

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

BACKGROUND: 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. METHODS: We included 17 209 children at 4 years and 14 585 at 8 years from seven European population-based birth cohorts (MeDALL project). At each age period, children were grouped, using partitioning cluster analysis, according to the distribution of 23 variables covering symptoms 'ever' and 'in the last 12 months', doctor diagnosis, age of onset and treatments of asthma, rhinitis and eczema; immunoglobulin E sensitization; weight; and height. We tested the sensitivity of our estimates to subject and variable selections, and to different statistical approaches, including latent class analysis and self-organizing maps. RESULTS: Two groups were identified as the optimal way to cluster the data at both age periods and in all sensitivity analyses. The first (reference) group at 4 and 8 years (including 70% and 79% of children, respectively) was characterized by a low prevalence of symptoms and sensitization, whereas the second (symptomatic) group exhibited more frequent symptoms and sensitization. Ninety-nine percentage of children with comorbidities (co-occurrence of asthma, rhinitis and/or eczema) were included in the symptomatic group at both ages. The children's characteristics in both groups were consistent in all sensitivity analyses. CONCLUSION: At 4 and 8 years, at the population level, asthma, rhinitis and eczema can be classified together as an allergic comorbidity cluster. Future research including time-repeated assessments and biological data will help understanding the interrelationships between these diseases.

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.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.