Biomarker Biosample Biosample Biosample Biosample Biosample Biosample Biosample Advantage Limitation Utility Ref
Sputum Blood BALF Biopsies/brushings EBCs Nasal secretions Nasal cells
Ezrin
+
+
+
+
Present in multiple biosamples Useful in early diagnosis Variable expression level Predicts greater decline in lung function Indicates early epithelial injury Indicates asthma control
[70,72]
Claudin 4
+
+
A major claudin expressed in ECs A selective sodium barrier protein Mechanistic role unclear Correlates with eosinophils, total IgE and lung function Predicts inflammation and asthma severity
[105]
Claudin 18
+
Only lung-specific TJ protein Reduced in IgE-high and eosinophilic T2high asthma Mechanistic role unclear Indicates epithelial permeability
[106]
CCSP16
+
+
+
Correlates with disease duration Easy to detect in the circulation Secreted by nonciliated terminal bronchiolar epithelial cells Not applicable in all lung diseases Some conflicting results Predicts impaired lung function in adults Marker of progressive airway damage
[67,68]
Sec14l3
+
+
Specifically expressed in airway epithelium Difficult to obtain in clinical setting Reflects ciliated epithelial cell integrity Predicts airway inflammation
[121]
Osteopontin
+
+
+
+
+
Associated with eosinophils Correlated with disease severity Multicellular sources Mechanistic role unclear In consistency of results Measures disease onset and treatment Important indicator of childhood asthma
[107-109,118]
YKL-40
+
+
+
+
+
+
Indicative of severe, non-T2 asthma Related to disease severity and decline in lung function Requires replication in multicenter cohorts and longitudinal studies Not a biomarker of asthma severity in children Asthma diagnosis and prognosis Distinguishes ACO and COPD Distinguishes Asthma from COPD and healthy controls
[77-79]
Fibrinogen
+
+
Associated with airway geometry Related to asthma severity and airway inflammation Asthma severity and treatment response
[114, 115]
IL-33
+
+
+
+
+
+
+
Genetic associations with asthma risk Related to the asthma severity Lack of sensitive and specific assay in serum Predicts asthma risk Disease onset and asthma prevention Response to environment and treatment
[34, 110, 111]
IL-25
+
+
+
+
+
+
Related to asthma severity and airway inflammation Associated with lung function Inconsistent between upper and lower airways Multicellular sources Defines asthma phenotypes Response to ICS therapy
[112, 113]
MMP-9
+
+
+
+
+
+
+
Related to airway remodeling, inflammation and lung function Susceptible to many factors Multicellular sources Difficult to detect Response to glucocorticoid treatment [119, 120]
Periostin
+
+
+
+
+
+
+
Used in phase 2/3 studies of lebrikizumab Associated with persistent airflow limitation serum levels that change with age inconsistency of results Increased expression in various disease Phenotyping of severe asthma – T2high Response to ICS therapy Indicates omalizumab efficacy in asthma
[52-59,62]
TSLP
+
+
+
+
+
+
+
Genetic risk for asthma Correlated with airflow obstruction Inconsistent between upper and lower airways Multicellular sources Predicts asthma risk Prevents remodeling
[110, 116, 117]