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