Respirology最新文献

Background and objective: The impact of lipid abnormalities on right heart function and outcomes in pre-capillary pulmonary hypertension (precPH) remains unclear. This study investigates how lipid profile alterations influence right heart function, strain, and prognosis in precPH patients.

Methods: From June 2013 to December 2023, 394 precPH patients were prospectively enrolled. Clinical data, cardiac MRI-derived right heart systolic function, and strain parameters were compared among groups based on lipid profiles. The optimal cut-off values of lipid profiles were determined using the maximally selected rank statistics. Prognostic analyses were conducted using Cox regression and Kaplan-Meier survival methods.

Results: During a median follow-up of 36 months, 18.8% of patients died. Low-density lipoprotein cholesterol (LDL-C) < 1.93 mmol/L and high-density lipoprotein cholesterol (HDL-C) < 0.82 mmol/L were associated with increased mortality risks (2.51-fold and 2.65-fold, respectively). Multivariate analysis confirmed decreased LDL-C (HR 1.853, 95% CI 1.102-3.115, p = 0.02) and decreased HDL-C (HR 2.019, 95% CI 1.131-3.603, p = 0.02) as independent prognostic indicators. A decrease in either cholesterol subtype predicted worse outcomes (Log-rank p = 0.003). Incorporation of LDL-C and HDL-C enhanced prognostic accuracy of the ESC model (χ²: 50.8 to 60.5, p = 0.007; 50.8 to 66.0, p < 0.001) and ESC-CMR model (χ²: 59.3 to 66.0, p = 0.04; 59.3 to 72.7, p = 0.001). HDL-C < 0.82 mmol/L was associated with impaired right ventricular global longitudinal strain (p < 0.001), RV free wall strain (p < 0.001), and right atrial phasic strain (all p < 0.05).

Conclusions: Decreased HDL-C and LDL-C levels independently predict increased mortality in precPH patients. Notably, low HDL-C significantly associates with impaired right heart function and strain.

Trial registration: Chinese Clinical Trial Registry (https://www.

Clinicaltrials: gov; ID: ChiCTR1800019314 and ChiCTR1900025518).

Background and objective: Despite improved respiratory symptoms after smoking cessation, patients with chronic obstructive pulmonary disease (COPD) remain susceptible to exacerbations and persistent airway inflammation, wherein the underlying mechanisms for sustained inflammation remain unclear. To address this knowledge gap, we investigated the persistence of airway epithelial barrier dysfunction in ex-smokers with COPD and examined the relationship between goblet cell hyperplasia and barrier dysfunction.

Methods: We analysed differentiated primary bronchial epithelial cells from never smokers with normal lung function, ex-smokers (> 10-year cessation), and current smokers with COPD using RNA sequencing, ATAC sequencing, and single-cell analyses to examine barrier function and cell differentiation.

Results: Genes associated with ciliary formation and motility were progressively downregulated from never smokers to ex-smokers to current smokers with COPD. The expression of junction-associated molecules was decreased in both ex-smokers and current smokers, showing a significant inverse correlation with the proportion of MUC5AC-positive cells. Single-cell analyses revealed distinct alterations in cell differentiation trajectories, particularly persistent goblet cell hyperplasia associated with increased expression of the transcription factor SPDEF, linked to epigenetic changes in the NKX2-1 gene regulatory regions.

Conclusion: Epigenetic mechanisms maintain persistent alterations in airway epithelial differentiation after smoking cessation, leading to mucus-producing cell hyperplasia through dysregulation of the NKX2-1/SPDEF axis. This hyperplasia correlates with reduced junction-associated molecule expression and subsequent barrier dysfunction. Therapeutic strategies targeting epithelial barrier restoration and/or normalisation of epigenetic dysregulation may benefit patients with COPD, even after smoking cessation.