Pharmacogenomic Evidence and Factors Influencing Treatment Response in Asthma and COPD
Keywords:
Pharmacogenomics, Asthma, Chronic obstructive pulmonary disease, Genetic variants, Drug response, Precision medicineAbstract
Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous respiratory diseases in which treatment response varies substantially among individuals. Pharmacogenomics investigates how genetic variation may contribute to differences in drug efficacy and clinical outcomes. This narrative mini-review summarizes evidence on pharmacogenetic and pharmacogenomic associations with responses to commonly used respiratory medications in asthma and COPD, distinguishes candidate-gene findings from genome-wide and genotype-stratified trial evidence, examines limitations affecting clinical translation, and discusses research priorities. In asthma, the best-studied associations involve inhaled corticosteroids (ICS; GLCCI1, CRHR1, FCER2), β2-agonists (ADRB2), and leukotriene modifiers. A genome-wide study identified GLCCI1 rs37972 as associated with ICS response, and a systematic review found the most consistent candidate-gene evidence for FCER2 rs28364072, yet replication has been limited overall and even replicated variants explain only a small fraction of response variability. Two prospective genotype-stratified trials of ADRB2 Arg16Gly gave different clinical signals depending on the treatment regimen. In COPD, research is less developed, and a meta-analysis found no consistent association between the examined ADRB2 variants and β2-agonist response. Differences in populations, phenotypes, treatment regimens, and outcome definitions further limit comparisons. Although pharmacogenomics may eventually contribute to precision respiratory medicine, routine treatment decisions are not currently guided by most candidate pharmacogenomic markers in asthma or COPD. Larger and ancestrally diverse studies, independent replication, standardized response outcomes, and prospective evaluation of clinical utility are needed before broader implementation.
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