Queens Beat One-Eyed Jacks, but Nobody’s Played the Ace Yet. Adipokines as Chronic Obstructive Pulmonary Disease Biomarkers

Curtis, Jeffrey L.

doi:10.1513/annalsats.201505-256ed

Cited by 2 publications

(1 citation statement)

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“…In addition, the lower leptin levels observed in malnourished populations are associated with dysfunctional cell-mediated immunity and increased susceptibility to infections 41,43 . In COPD, elevated leptin concentrations have been reported in the plasma and airways in some [44][45][46][47][48] , but not all studies 49 , and has been identified as a potential biomarker of emphysema progression 50,51 . Our results suggest that "high disease activity" or "severe disease risk" subtype individuals might exhibit humoral and cytokine profiles similar to those seen in malnourished individuals with increased susceptibility to infections.…”

Section: Moll Et Almentioning

confidence: 99%

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes

Moll,

Hecker,

Platig

et al. 2024

Preprint

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Rationale: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. Objectives: Define high-risk COPD subtypes using both genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. Methods: We defined high-risk groups based on PRS and TRS quantiles by maximizing differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein-protein interaction networks and drug repurposing analyses between high-risk groups. Measurements and Main Results: We examined two high-risk omics-defined groups in non-overlapping test sets (n=1,133 NHW COPDGene, n=299 African American (AA) COPDGene, n=468 ECLIPSE). We defined 'High activity' (low PRS/high TRS) and 'severe risk' (high PRS/high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signaling processes compared to a low-risk (low PRS, low TRS) reference subgroup. 'High activity' but not 'severe risk' participants had greater prospective FEV1 decline (COPDGene: -51 mL/year; ECLIPSE: -40 mL/year) and their proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Conclusions: Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection.

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