Opposite to other immunoglobulin (Ig) classes and subclasses, there is no consensus on the definition of normal levels of serum total IgE. However, longitudinal studies on birth cohorts produced ...growth charts of total IgE levels in helminth-free and never atopic children and defining the normal ranges of total serum IgE concentration at the individual, rather than population, level. Accordingly, very 'low IgE producers' (i.e., children whose tIgE level belong to the lowest percentiles) became atopic while keeping their total IgE levels in a range considered 'normal' if compared to the general age-matched population but 'abnormally high' if projected on the tIgE growth chart against the trajectory of that child's own percentile levels. In 'low IgE producers', the IgE-specific activity, i.e., the ratio between allergen-specific and total IgE, is more important than the absolute specific IgE levels to confirm causality between allergen exposure and allergic symptoms. Patients with allergic rhinitis or peanut anaphylaxis but low or undetectable allergen-specific IgE levels must therefore be reconsidered considering their total IgE levels. Low IgE producers have been also associated with common variable immunodeficiency, lung diseases, and malignancies. A few epidemiological studies have shown a higher risk of malignancies in very low IgE producers, leading to a debated hypothesis proposing a novel, evolutionistic-relevant function for IgE antibodies for antitumor immune surveillance.
Strategies to improve patients’ adherence to treatment are essential to reduce the great health and economic burden of allergic rhinitis and asthma. Mobile phone applications (apps) for a better ...management of allergic diseases are growing in number, but their usefulness for doctors and patients is still debated. Controlled trials have investigated the feasibility, cost-effectiveness, security, and perspectives of the use of tele-medicine in the self-management of asthma. These studies focused on different tools or devices, such as SMS, telephone calls, automatic voice response system, mobile applications, speech recognition system, or cloud-computing systems. While some trials concluded that m-Health can improve asthma control and the patient’s quality of life, others did not show any advantage in relation to usual care. The only controlled study on allergic rhinitis showed an improvement of adherence to treatment among tele-monitored patients compared to those managed with usual care. Most studies have also highlighted a few shortcomings and limitations of tele-medicine, mainly concerning security and cost-efficiency. The use of smartphones and apps for a personalized asthma and allergy care needs to be further evaluated and optimized before conclusions on its usefulness can be drawn.
The use of mobile communication devices in health care is spreading worldwide. A huge amount of health data collected by these devices (mobile health data) is nowadays available. Mobile health data ...may allow for real-time monitoring of patients and delivering ad-hoc treatment recommendations. This paper aims at showing how this may be done by exploiting the potentialities of fuzzy clustering techniques. In fact, such techniques can be fruitfully applied to mobile health data in order to identify clusters of patients for diagnostic classification and cluster-specific therapies. However, since mobile health data are full of noise, fuzzy clustering methods cannot be directly applied to mobile health data. Such data must be denoised prior to analyzing them. When longitudinal mobile health data are available, functional data analysis represents a powerful tool for filtering out the noise in the data. Fuzzy clustering methods for functional data can then be used to determine groups of patients. In this work we develop a fuzzy clustering method, based on the concept of medoid, for functional data and we apply it to longitudinal mHealth data on daily symptoms and consumptions of anti-symptomatic drugs collected by two sets of patients in Berlin (Germany) and Ascoli Piceno (Italy) suffering from allergic rhinoconjunctivitis. The studies showed that clusters of patients with similar changes in symptoms were identified opening the possibility of precision medicine.
Background The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. Objectives We sought to characterize the evolutionary patterns of ...the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. Methods We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. Results One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Conclusions Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.
Background The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. Objective We aimed to determine early-life predictors of asthma ...incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. Methods In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). Results Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio HR, 0.66 95% CI, 0.47-0.93). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 95% CI, 1.67-3.02), started day care early or late (before 18 months: adjusted HR, 1.79 95% CI, 1.03-3.10; after 3 years: adjusted HR, 1.64 95% CI, 0.96-2.79), had mothers who smoked during pregnancy (adjusted HR, 1.79 95% CI, 1.20-2.67), had poor parents (adjusted HR, 1.55 95% CI, 1.09-2.22), and had parents with asthma (adjusted HR, 1.65 95% CI, 1.17-2.31). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. Conclusion Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.
In times of “Precision Medicine” it is fundamental to identify the individual disease phenotype in order to provide an individualized therapy for every patient. This concept is also becoming ...increasingly important for the treatment of allergic diseases. Thanks to the biological engineering of recombinant and native allergens for the assessment of allergen-specific IgE antibodies, it is now possible to easily obtain the individual sensitization profile of a patient. This allows the allergist to precisely identify the primary elicitor of an IgE response and, based on this knowledge, to choose the best treatment option. Several studies have observed the longitudinal evolution of sensitization profiles and identified a phenomenon termed “molecular spreading,” which describes a broadening of the recognized allergen spectrum from a source over time. Additionally, the identification of marker proteins, which can trigger an IgE response or correlate with an increased risk for certain clinical symptoms, helps to establish an individual risk profile. This information may not only affect the decision-making concerning immunotherapy, but also opens up avenues for future investigations with regard to prevention strategies. We provide here an overview on the role of individual sensitization patterns and their predictive value.
Background
There is a need to establish the effectiveness, cost‐effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease.
Methods
Two reviewers independently ...screened nine international biomedical databases. Studies were quantitatively synthesized using random‐effects meta‐analyses.
Results
A total of 32 studies satisfied the inclusion criteria. Overall, meta‐analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04–2.09) and no randomized controlled evidence was found in relation to its longer‐term effects for this outcome. There was, however, a reduction in the short‐term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30–0.54), with this finding being robust to a pre‐specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31–1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24–2.18. There was no clear evidence of any longer‐term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08–2.77. AIT appeared to have an acceptable side effect profile.
Conclusions
AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short‐term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost‐effectiveness of AIT.
Clinical decision support systems (CDSS) aid health care professionals (HCP) in evaluating large sets of information and taking informed decisions during their clinical routine. CDSS are becoming ...particularly important in the perspective of precision medicine, when HCP need to consider growing amounts of data to create precise patient profiles for personalized diagnosis, treatment and outcome monitoring. In allergy care, several CDSS are being developed and investigated, mainly for respiratory allergic diseases. Although the proposed solutions address different stakeholders, the majority aims at facilitating evidence-based and shared decision-making, incorporating guidelines, and real-time clinical data. We offer here an overview on existing tools, new developments and novel concepts and discuss the potential of digital CDSS in improving prevention, diagnosis and monitoring of allergic diseases.
Background IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis. Objective We sought to investigate the evolution at the molecular level and the preclinical predictive ...value of IgE responses against grass pollen. Methods The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen–related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively. Results One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% 95% CI, 50% to 82%; negative predictive value, 84% 95% CI, 80% to 87%). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset. Conclusions The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a “molecular spreading” process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage.
Background Allergen-specific subcutaneous immunotherapy (SCIT) of seasonal allergic rhinitis (SAR) is usually considered a “second-line,” slow-acting, disease-modifying treatment. Objective We sought ...to test whether SCIT is as effective as antisymptomatic treatment in the control of symptoms in patients with SAR in the first year of treatment. Methods We reviewed meta-analyses with 5 or more randomized, double-blind, placebo-controlled trials of SCIT or antisymptomatic treatment in patients with SAR. We then selected trials measuring the total nasal symptom score (TNSS), the total symptom score (TSS), or both during the first pollen season after treatment initiation. Efficacy was determined as the percentage reduction in TSSs and TNSSs obtained with active treatment compared with placebo (relative clinical impact RCI) and the standardized mean difference (SMD) of treatment verses placebo (effect size ES). Results The weighted mean RCI of SCIT on TNSSs (−34.7% ± 6.8%) was higher than those of mometasone (−31.7% ± 16.7%, P < .00001) and montelukast (−6.3% ± 3.0%, P < .00001). The weighted mean RCI of SCIT on TSSs (−32.9% ± 12.7%) was higher than that of desloratadine (−12.0% ± 5.1%, P < .00001). The overall ES of SCIT in terms of TNSSs (SMD, −0.94; 95% CI, −1.45 to −0.43) was similar to that of mometasone (SMD, −0.47; 95% CI, −0.63 to −0.32; P > .05) and higher than that of montelukast (SMD, −0.24; 95% CI, −0.33 to −0.16; P < .05). The overall ES of SCIT in terms of TSSs (SMD, −0.86; 95% CI, −1.17 to −0.55) was comparable with that of desloratadine (SMD, −1.00; 95% CI, −1.68 to −0.32; P > .05). Conclusions Our data provide indirect but consistent evidence that SCIT is at least as potent as pharmacotherapy in controlling the symptoms of SAR as early as the first season of treatment.
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