Proteins as biomarkers:
Hoang et al. showed that seed storage proteins (Ara h 1, 2, 3, 6), uteroglobin from cat (Fel d 1), and lipocalin from dog (Can f 1) demonstrated the strongest linkage to clinical markers of asthma severity. These results suggest their potential contribution as biomarkers in preschool asthma.141
A study in the Spanish population was identified serum biomarkers for allergic or non-allergic asthma by using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics. It indicates that increasing levels of plasma insulin-like growth factor-binding protein acid labile subunit, which has a role in the regulation of insulin-like growth factor pathway, could act as a potential biomarker for defining severity of allergic asthma, whereas the proteins of the complement ficolin-2 and mannan-binding lectin serine peptidase 1 levels seems increased in non-allergic individuals.142
Exhaled Biomarkers: Measurement of biomarkers in exhaled breath (i.e. FeNO) and exhaled breath condensate (i.e. volatile organic compounds) are non-invasive and safe. FeNO is a widely accepted biomarker for type 2 driven airway inflammation. Recently, a new subgroup of patients with high FeNO levels (>25 ppb) and low blood eosinophils (<300 cells/μL) was described. These patients showed a significantly higher number of sensitizations against aeroallergens compared to patients with low FeNO subgroups.114 FeNO is also associated with increased risk of asthma exacerbations and a beneficial effect of ICS. Pavord et al. investigated whether these biomarkers have prognostic value or predict the effects of regular or as-needed ICS on exacerbations in patients with mild asthma.143 The open label, randomized controlled trial showed that the effects of as-needed budesonide-formoterol are independent of biomarker profile.143 Dupilumab improves asthma control, quality of life, and FEV1 are improved and use of rescue medication is reduced above the minimally important clinical difference threshold only in patients with high blood eosinophils and high FeNO (blood eosinophils > 300/μL and/or FeNO > 50 ppb).130
The non‐T2 endotype covers both patients with a neutrophilic and a pauci-granulocytic airway inflammatory pattern. Childhood asthma comprises more different phenotypes with complex pathophysiology. Su et al. showed that neutrophil‐predominant asthma is the most severe asthma phenotype in children with a poor corticosteroid response.127 Less is known about biomarkers for pauci-granulocytic asthma. The role of biomarkers in the non‐type 2 endotype has yet to be fully elucidated.
AIT is an allergen tolerance-inducing treatment for allergic diseases. There are no biomarkers that sufficiently predict response to AIT. The Allergen Immunotherapy User’s Guide summarized the potential biomarkers for monitorization of the clinical efficacy of AIT as follows: a) IgE (total IgE, specific IgE (sIgE) /total IgE ratio), b) subclasses of IgG (allergen-specific IgG, IgG1 and sIgG4, sIgE/IgG4 ratio), c) IgE serum inhibitory activity for IgE (IgEFAB), d) basophil activation, e) chemokines and cytokines, f) cell markers such as Tregs, Bregs, and DCs, and g) in vivo biomarkers including provocation tests.144,145
Digital asthma biomarkers: Exhaled breath analysis using an electronic nose (eNose) is a new technique. This tool has the potential to assess asthma control and tailoring asthma treatment.146,147 In a study including participants between 6 and 18 years of age, Cavaleiro Rufo et al. showed that the exhaled breath condensate volatilome analysis by an eNose has good accuracy for asthma identification being able to distinguish individuals with diagnosed pediatric asthma from those without the disease.148 Farraia et al. demonstrated that the analysis of the exhaled volatile organic compounds profiles using an eNose could be used as a fast and non-invasive complementary assessment tool for the detection of uncontrolled asthma.146Moreover, the eNose was able to identify individuals with persistent asthma under prescribed corticosteroid therapy, supporting the diagnostic ability of this method to identify individuals in need of corticosteroid therapy.148
Mobile Airways Sentinel Network [MASK] is an information technology-based tool that developed through ARIA studies, which can inform patient decisions based on a self-care plan proposed by the health care providers, and can increase self-medication and share decision making in rhinitis and asthma multimorbidity.149. Using the MASK-air app, 14,189 users and 205,904 days, a visual analogue scale (VAS) days, have been recorded. VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS profile has potential for prevention, for the assessment of allergic rhinitis severity and progression, and for monitoring the drug effects in patients.150 Another study has determined the importance of mobile technologies in rhinitis control by using allergic rhinitis and its impact on asthma (ARIA) score.151Subsequent to this study, Bousquet et al. examined the use of mobile technology to get information in the change management of allergic rhinitis and asthma multimorbidity, with the aim of providing an active and healthy lifestyle for these patients.149 The European Innovation Partnership on Active and Healthy Ageing transferred innovation from the “Allergy Diary” to 22 Reference Sites or regions across Europe, aiming to compare the phenotypic characteristics of rhinitis and asthma multimorbidity in adults and the elderly, to assess the percentage of accepting the Allergy Diary in adults and elderly, understand the phenotypic characteristics and follow-up treatment over 1-year of rhinitis and asthma multimorbiditiy.152