European Respiratory Journal最新文献

Background: Prior exacerbation history is used to guide initial maintenance therapy in COPD; however, the recommendations were derived from patients already diagnosed and treated.

Methods: We assessed the rates of moderate (i.e. treated with antibiotics and/or systemic corticosteroids) and severe (i.e. hospitalised) exacerbations in the year following diagnosis in patients newly diagnosed with COPD according to their prior history of exacerbations, blood eosinophil count (BEC) and whether maintenance therapy was started. Data were extracted from the Optimum Patient Care Research Database.

Results: 73 189 patients were included. 61.9% had no exacerbations prior to diagnosis, 21.5% had 1 moderate, 16.5% had ≥2 moderate and 0.3% had ≥1 severe. 50% were started on maintenance therapy. In patients not started on maintenance therapy the rates of moderate exacerbations in the year after diagnosis in patients with no, 1 moderate, ≥2 moderate and ≥1 severe prior exacerbations were 0.34 (95% CI 0.33-0.35), 0.59 (95% CI 0.56-0.61), 1.18 (95% CI 1.14-1.23) and 1.21 (95% CI 0.73-1.69), respectively. Similar results were seen in patients started on maintenance therapy. BEC did not add significantly to the prediction of future exacerbation risk.

Conclusions: A single moderate exacerbation in the year prior to diagnosis increases the risk of subsequent exacerbations, and more frequent or severe exacerbations prior to diagnosis are associated with a higher risk.

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 Chronic Obstructive Pulmonary Disease (COPD) Study was a multi-center 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 (RV, LV) parameters were assessed on magnetic resonance imaging (MRI) in exams six 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 MRI 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 enrollment was associated with longitudinal increase in RV mass (3.5 g per 10mm² WA, 95% CI: 1.1, 5.9). Greater percent emphysema was associated with stably lower LV end diastolic volume (-7.8 mL per 5% emphysema, 95% CI: -10.3, -3.0) and CO (-0.2 L·min^-1 per 5% emphysema, 95% CI: -0.4, -0.1).

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

Background: House dust mite is the most frequent trigger of allergic asthma, with innate and adaptive immune mechanisms playing critical roles in outcomes. We recently identified the nucleotide-binding oligomerisation domain 1 (NOD1)/receptor-interacting serine/threonine protein kinase 2 (RIPK2) signalling pathway as a relevant contributor to murine house dust mite-induced asthma. This study aimed to evaluate the effectiveness of a pharmacological RIPK2 inhibitor administered locally as a preventive and therapeutic approach using a house dust mite-induced asthma model in wild-type and humanised NOD1 mice harbouring an asthma-associated risk allele, and its relevance using air-liquid interface epithelial cultures from asthma patients.

Methods: A RIPK2 inhibitor was administered intranasally either preventively or therapeutically in a murine house dust mite-induced asthma model. Airway hyperresponsiveness, bronchoalveolar lavage composition, cytokine/chemokine expression and mucus production were evaluated, as well as the effect of the inhibitor on precision-cut lung slices. Furthermore, the inhibitor was tested on air-liquid interface epithelial cultures from asthma patients and controls.

Results: While local preventive administration of the RIPK2 inhibitor reduced airway hyperresponsiveness, eosinophilia, mucus production, T-helper type 2 cytokines and interleukin 33 (IL-33) in wild-type mice, its therapeutic administration failed to reduce the above parameters, except IL-33. By contrast, therapeutic RIPK2 inhibition mitigated all asthma features in humanised NOD1 mice. Results in precision-cut lung slices emphasised an early role of thymic stromal lymphopoietin and IL-33 in the NOD1-dependent response to house dust mite, and a late effect of NOD1 signalling on IL-13 effector response. RIPK2 inhibitor downregulated thymic stromal lymphopoietin and chemokines in house dust mite-stimulated epithelial cultures from asthma patients.

Conclusion: These data support that local interference of the NOD1 signalling pathway through RIPK2 inhibition may represent a new therapeutic approach in house dust mite-induced asthma.