European Respiratory Journal最新文献

Sleep disordered breathing (SDB) is considered a risk factor for cardiovascular disease (CVD). Obstructive sleep apnoea (OSA) can be treated with continuous positive airway pressure (CPAP), and central sleep apnoea (CSA), in patients with heart failure with reduced ejection fraction (HFrEF), by peak flow-triggered adaptive servo-ventilation. Presently, there is equipoise as to whether treating SDB prevents cardiovascular events. Some propose treatment for this indication, based on observational data, while others argue against because of the lack of randomised trial evidence. This review evaluates literature concerning the cardiovascular effects of treating SDB with PAP devices in individuals with and without CVDs. Nine observational studies report significantly lower cardiovascular event rates in those treated, than in those not treated, for SDB. Conversely, 12 randomised trials in which excessive daytime sleepiness was generally an exclusion criterion showed no reduction in cardiovascular event rates. The SERVE-HF trial showed an increase in mortality with use of minute ventilation-triggered adaptive servo-ventilation for CSA in patients with HFrEF. In the ADVENT-HF trial, treating HFrEF patients with coexisting OSA or CSA using peak flow-triggered adaptive servo-ventilation was safe and improved sleep structure and heart failure-related quality of life but did not reduce all-cause mortality or cardiovascular events. More evidence is required to determine whether treating CSA in patients with HFrEF prevents cardiovascular events and improves survival. Presently, the rationale for treating SDB with PAP remains improving sleep structure and quality of life, as well as relieving excessive daytime sleepiness, but not reducing cardiovascular events.

Background: Lung structure and cardiac structure and function are associated cross-sectionally. The classic literature suggests relationships of airways disease to cor pulmonale and emphysema to reduced cardiac output (CO) but longitudinal data are lacking.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study was a multicentre longitudinal COPD case-control study of participants 50-79 years with ≥10 pack-years smoking without clinical cardiovascular disease. Segmental airway wall area (WA) and percent emphysema were measured on computed tomography. Right and left ventricle parameters were assessed on cardiac magnetic resonance imaging (cMRI) in exams 6 years apart. Longitudinal and period cross-sectional associations were evaluated with mixed models adjusted for demographics, body size and smoking.

Results: The 187 participants with repeated cMRI were 67±7 years old; 42% had COPD; 22% currently smoked; and the race/ethnicity distribution was 54% White, 30% Black, 14% Hispanic and 3% Asian. Greater WA at enrolment was associated with longitudinal increase in right ventricular (RV) mass (3.5 (95% CI 1.1-5.9) g per 10 mm² WA). Greater percent emphysema was associated with stably lower left ventricular (LV) end-diastolic volume (-7.8 (95% CI -10.3- -3.0) mL per 5% emphysema) and CO (-0.2 (95% CI -0.4- -0.1) L·min^-1 per 5% emphysema).

Conclusion: Cardiac associations varied by lung structure over 6 years in this multi-ethnic study. Greater WA at enrolment was associated with longitudinal increases in RV mass, whereas greater percent emphysema was associated with stable decrements in LV filling and CO.

Background: Macrolide maintenance therapy (MMT) has demonstrated notable efficacy in reducing exacerbation in patients with bronchiectasis, which is a major risk factor for cardiovascular events. However, a comprehensive assessment of the cardiovascular benefits and safety profile of MMT in this population is lacking.

Methods: This territory-wide cohort study analyzed patients diagnosed with bronchiectasis in Hong Kong between 2001 and 2018. Patients were classified as MMT receivers or macrolide non-receivers based on the administration of MMT. Propensity score (PS) matching was employed for confounding factors adjustment. The primary outcome of interest was major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction and stroke. The safety outcome was the occurrence of ventricular arrhythmias or sudden cardiac death. Cox proportional hazard regression analysis was utilized to compare the incidence of outcomes across the two groups.

Results: A total of 22 895 patients with bronchiectasis were identified. Following 1:2 PS matching, the final cohort consisted of 3137 individuals, with 1123 MMT receivers and 2014 macrolide non-receivers. MMT administration was associated with a significant reduced risk of MACE (16.38 versus 24.11 events per 1000 person years; HR 0.68; 95% CI 0.52-0.90). Importantly, the use of MMT was not associated with elevated risk of ventricular arrhythmias or sudden cardiac death (7.17 versus 7.67 events per 1000 person years; HR 0.93; 95% CI 0.60-1.44).

Conclusions: The administration of MMT in patients with bronchiectasis was associated with a significant reduction in the risk of MACE, without any evidence suggesting an increased risk of severe arrhythmia-related adverse events.

Background: Primary ciliary dyskinesia is a rare genetic disorder caused by insufficient mucociliary clearance leading to chronic airway infections. The diagnostic guideline of the European Respiratory Society primarily recommends an evaluation of the clinical history (e.g. by the PICADAR prediction tool), nasal nitric oxide production rate measurements, high-speed videomicroscopy analysis of ciliary beating and an assessment of ciliary axonemes via transmission electron microscopy. Genetic testing can be implemented as a last step.

Aims: In this study, we aimed to characterise primary ciliary dyskinesia with a defective C1d projection of the ciliary central apparatus and we evaluated the applicability of the European Respiratory Society diagnostic guideline to this primary ciliary dyskinesia type.

Methods: Using a high-throughput sequencing approach of genes encoding C1d components, we identified pathogenic variants in the novel primary ciliary dyskinesia genes CFAP46 and CFAP54, and the known primary ciliary dyskinesia gene CFAP221. To fully assess this primary ciliary dyskinesia type, we also analysed individuals with pathogenic variants in CFAP74.

Results: Careful evaluation revealed that C1d-defective primary ciliary dyskinesia is associated with normal situs composition, normal nasal nitric oxide production rates, normal ciliary ultrastructure by transmission electron microscopy and normal ciliary beating by high-speed videomicroscopy analysis. Despite chronic respiratory disease, PICADAR does not reliably detect this primary ciliary dyskinesia type. However, we could show by in vitro ciliary transport assays that affected individuals exhibit insufficient ciliary clearance.

Conclusions: Overall, this study extends the spectrum of primary ciliary dyskinesia genes and highlights that individuals with C1d-defective primary ciliary dyskinesia elude diagnosis when using the current diagnostic algorithm. To enable diagnosis, genetic testing should be prioritised in future diagnostic guidelines.

Streptococcus pneumoniae is the most common causative agent of community-acquired pneumonia worldwide. A key pathogenic mechanism that exacerbates severity of disease is the disruption of the alveolar-capillary barrier. However, the specific virulence mechanisms responsible for this in the human lung are not yet fully understood. In this study, we infected living human lung tissue with Strep. pneumoniae and observed a significant degradation of the central junctional proteins occludin and vascular endothelial cadherin, indicating barrier disruption. Surprisingly, neither pneumolysin, bacterial hydrogen peroxide nor pro-inflammatory activation were sufficient to cause this junctional degradation. Instead, pneumococcal infection led to a significant decrease of pH (∼6), resulting in the acidification of the alveolar microenvironment, which was linked to junctional degradation. Stabilising the pH at physiological levels during infection reversed this effect, even in a therapeutic-like approach. Further analysis of bacterial metabolites and RNA sequencing revealed that sugar consumption and subsequent lactate production were the major factors contributing to bacterially induced alveolar acidification, which also hindered the release of critical immune factors. Our findings highlight bacterial metabolite-induced acidification as an independent virulence mechanism for barrier disruption and inflammatory dysregulation in pneumonia. Thus, our data suggest that strictly monitoring and buffering alveolar pH during infections caused by fermentative bacteria could serve as an adjunctive therapeutic strategy for sustaining barrier integrity and immune response.