Publications by authors named "S I Rennard"
Among tobacco-exposed persons with preserved spirometry (TEPS), we previously demonstrated that different lung volume indices, specifically elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity-to-TLC (FRC/TLC), identify different lung disease characteristics in the COPDGene cohort. Determine differential disease characteristics and trajectories associated with the lung volume indices among TEPS in the SPIROMICS cohort. We categorized TEPS (n=814) by tertiles (low, intermediate, high) of TLC or residual volume-to-TLC (RV/TLC) derived from baseline CT images, and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]) versus high RV/TLC without high TLC ([RV/TLC]).
View Article and Find Full Text PDFBackground: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using 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 maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets.
Article Synopsis
- Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder mainly caused by a specific mutation, leading to severe lung and liver issues, which increase mortality rates.
- The E342K mutation alters the AAT protein, causing its accumulation in the liver and reducing its secretion, which results in lung damage due to unopposed protease activity.
- New treatments, particularly genomic medicines like RNA editing, show promise for correcting the mutation and restoring normal AAT levels for better management of both lung and liver conditions.
Quantitating exercise ventilatory and gas exchange dynamics affords insights into physiological control processes and cardiopulmonary dysfunction. We designed a novel waveform, the chirp waveform, to efficiently extract moderate-intensity exercise response dynamics. In the chirp waveform, work rate fluctuates sinusoidally with constant amplitude as sinusoidal period decreases progressively from ∼8.
View Article and Find Full Text PDFRationale: 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.