Advocacy of Precision Allergy Molecular Diagnosis in Decision Making for the Eligibility of Customized Allergen Immunotherapy.

Allergen immunotherapy (AIT) with aeroallergens is the only disease-modifying treatment for patients with different allergic conditions. Despite the effectiveness of AIT having been proven in both randomized controlled trials and real-world studies, it remains underused in less than 10% of subjects with allergic rhinitis (AR) and/or asthma (A). We aimed to determine the current eligibility for house dust mite (HDM) AIT by means of a precision allergy molecular diagnosis (PAMD@) model in a selected cohort of youngsters with different allergic phenotypes according to the available evidence. A complex response to both HDM and storage mite allergens was depicted regardless of the subjects' basal atopic condition. No solely specific IgE-binding responses to Der p 1, Der p 2, and/or Der p 23 were found in the studied cohort. Despite the patients with A and atopic dermatitis showing significantly higher serum titers to six mite allergens than subjects with AR, no specific molecular profile was regarded as disease specific. Given the increasing complexity of specific IgE responses to the local prevailing aeroallergens, the identification and presence of such molecules are needed in commercially available AIT in the era of precision medicine.

Allergic Asthma in the Era of Personalized Medicine.

Allergic asthma is the most common asthma phenotype and is characterized by IgE sensitization to airborne allergens and subsequent typical asthmatic symptoms after exposure. A form of type 2 (T2) airway inflammation underlies allergic asthma. It usually arises in childhood and is accompanied by multimorbidity presenting with the occurrence of other atopic diseases, such as atopic dermatitis and allergic rhinitis. Diagnosis of the allergic endotype is based on in vivo (skin prick tests) and/or in vitro (allergen-specific IgE levels, component-resolved diagnosis (CRD)) documentation of allergic sensitization. Biomarkers identifying patients with allergic asthma include total immunoglobulin E (IgE) levels, fractional exhaled nitric oxide (FeNO) and serum eosinophil counts. The treatment of allergic asthma is a complex procedure and requires a patient-tailored approach. Besides environmental control involving allergen avoidance measurements and cornerstone pharmacological interventions based on inhaled drugs, allergen-specific immunotherapy (AIT) and biologics are now at the forefront when it comes to personalized management of asthma. The current review aims to shed light on the distinct phenotype of allergic asthma, ranging over its current definition, clinical characteristics, pathophysiology and biomarkers, as well as its treatment options in the era of precision medicine.

Allergic Endotypes and Phenotypes of Asthma.

Allergic asthma is defined as asthma associated with sensitization to aeroallergens, which leads to asthma symptoms and airway inflammation. Allergic asthma is the most common asthma phenotype. The onset of allergic asthma is most often in childhood and is usually accompanied by other comorbidities including atopic dermatitis and allergic rhinitis. It is often persistent although there is a wide variation in disease severity. It is a TH2-driven process. Biomarkers have been identified to distinguish patients with allergic asthma, particularly serum IgE levels, tests to indicate sensitization to aeroallergens such as specific IgE or skin prick test positivity, blood and sputum eosinophil levels, fraction of exhaled nitric oxide, and periostin. Treatments for allergic asthma include environmental control measures, allergen immunotherapy, and glucocorticoids. Biologics, targeting the TH2 pathway, have been shown to be effective in the treatment of allergic asthma.

Metabolomics strategies to discover new biomarkers associated to severe allergic phenotypes.

In the last decades have emerged new technological platforms that allow evaluation of genes, transcripts, proteins, or metabolites of a living being, so-called omics sciences. More importantly, new technics for their integration have provided access to a complete set of information of the current conditions and features of a specific biological sample in a precise moment. Thus, omic sciences are now considered an essential tool for patient stratification in base to their severity, to understand disease progression and to identify new biomarkers. Severe patients, that are out of control, provide an excellent model to understand disease evolution and to identify new intervention and biomarkers strategies. Here we discuss the use of metabolomics to understand severity in allergic diseases in a strategy that opens new insights as well as identify new biological systems relevant for allergy progression. Metabolomics strategies are based in parallel evaluation of different allergy severity models by mean of untargeted analysis that allows the identification of potential biomarkers. Overlapping of different biomarkers in multiple models, provides information of general as well as specific biological systems involved in each model. Later a selected panel of biomarkers will be used in a target method to explore the diagnosis potential to stratify allergic patients.

Metabolomics strategies to discover new biomarkers associated to severe allergic phenotypes

In the last decades have emerged new technological platforms that allow evaluation of genes, transcripts, proteins, or metabolites of a living being, so-called omics sciences. More importantly, new technics for their integration have provided access to a complete set of information of the current conditions and features of a specific biological sample in a precise moment. Thus, omic sciences are now considered an essential tool for patient stratification in base to their severity, to understand disease progression and to identify new biomarkers. Severe patients, that are out of control, provide an excellent model to understand disease evolution and to identify new intervention and biomarkers strategies. Here we discuss the use of metabolomics to understand severity in allergic diseases in a strategy that opens new insights as well as identify new biological systems relevant for allergy progression. Metabolomics strategies are based in parallel evaluation of different allergy severity models by mean of untargeted analysis that allows the identification of potential biomarkers. Overlapping of different biomarkers in multiple models, provides information of general as well as specific biological systems involved in each model. Later a selected panel of biomarkers will be used in a target method to explore the diagnosis potential to stratify allergic patients.