Hair Analysis as an Objective Biomarker for Medication Adherence to Inhaled Corticosteroid/Long-Acting β₂-Agonist Therapy in Asthma: A Systematic Review

Abstract

Background: Poor adherence to inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy remains a leading, modifiable cause of poor asthma control, exacerbations and excess healthcare expenditure, yet the tools routinely used to measure it are either subjective and prone to overestimation or logistically demanding for long-term outpatient use.

Objective: To synthesise the published evidence on hair analysis as an objective, minimally invasive biomarker of medication exposure, to describe the biological and analytical basis for its application to inhaled respiratory medications, and to critically evaluate its potential role and limitations as a measure of ICS/LABA adherence in asthma.

Methods: A structured systematic review was conducted, informed by the principles of the PRISMA statement for transparent reporting. Peer-reviewed literature indexed in PubMed/MEDLINE-linked sources and other academic databases was searched using combinations of terms relating to asthma, ICS/LABA adherence, medication-adherence measurement, hair analysis, drug incorporation into hair, and hair glucocorticoid/bronchodilator quantification, supplemented by hand-searching of reference lists and authoritative guideline documents. Because the available evidence in this specific application is heterogeneous in design and outcome reporting, findings were synthesised narratively rather than pooled statistically.

Results: Adherence to ICS/LABA therapy is estimated at well below 80% in routine care, and is associated with a two- to three-fold increase in exacerbations, hospitalisation and healthcare cost. Conventional adherence measures (self-report, pill/canister counts, pharmacy refill ratios, electronic monitoring) each carry recognised biases. Hair analysis, already validated for antiretroviral, antihypertensive and immunosuppressant therapy, offers a centimeter-by-centimeter retrospective record of systemic drug exposure spanning weeks to months from a single, low-burden sample. Direct evidence for inhaled respiratory medications is still emerging, constrained by low and variable systemic drug incorporation, analytical sensitivity requirements, and confounding by hair colour, cosmetic treatment and external contamination.

Conclusion: Hair analysis is analytically feasible and clinically promising as a complementary, objective adherence biomarker for ICS/LABA therapy, but current evidence is insufficient to support its use as a stand-alone measure. Well-designed pharmacokinetic and validation studies, of the type proposed in ongoing institutional doctoral research, are needed before clinical translation.