Cardiovascular Events During and After Bronchiectasis Exacerbations and Long-term Mortality.

BACKGROUND: Population-based and retrospective studies have shown that risk for cardiovascular events such as arrythmias, ischemic episodes, or heart failure, increase during and after bronchiectasis exacerbations. RESEARCH QUESTION: What are the risk factors for cardiovascular events (CVE) during and after bronchiectasis exacerbations and their impact on mortality? STUDY DESIGN AND METHODS: This was a post hoc retrospective analysis of a prospective observational study of 250 patients with bronchiectasis at two tertiary care hospitals. Only the first exacerbation was considered for each patient, collecting demographic, comorbidity, and severity data. The main outcomes were the appearance of CVE and mortality. Risk factors for CVE were analyzed using a semi-competing risks model. RESULTS: During a median follow-up of 35 months, 74 (29.6%) patients had a CVE and 93 (37.2%) died. Semi-competing risk analysis indicated that age, arterial hypertension, COPD, and potentially severe exacerbations significantly increased the risk for developing CVE. Compared with patients without CVE, those with CVE had higher mortality. INTERPRETATION: Demographic factors and comorbidities are risk factors for the development of CVE after an acute exacerbation of bronchiectasis. The appearance of CVE worsens long-term prognosis.

Incidence, risk factors, and thrombotic load of pulmonary embolism in patients hospitalized for COVID-19 infection.

OBJECTIVE: To determine the incidence, characteristics, and risk factors of pulmonary embolism (PE) among patients hospitalized for COVID-19. PATIENTS AND METHODS: We performed a prospective observational study of a randomly selected cohort of consecutive patients hospitalized for COVID-19 infection between March 8, 2020 through April 25, 2020. All eligible patients underwent a computed tomography pulmonary angiography independently of their PE clinical suspicion and were pre-screened for a baseline elevated D-dimer level. RESULTS: 119 patients were randomly selected from the 372 admitted to one tertiary hospital in Valencia (Spain) for COVID-19 infection during the period of study. Seventy-three patients fulfilled both the inclusion criteria and none of the exclusion criteria and were finally included in the study. Despite a high level of pharmacological thromboprophylaxis (89%), the incidence of PE was 35.6% (95% confidence interval [CI], 29.6 to 41.6%), mostly with a peripheral location and low thrombotic load (Qanadli score 18.5%). Multivariate analysis showed that heart rate (Hazard Ratio [HR], 1.04), room-air oxygen saturation (spO2) (HR, 0.87), D-dimer (HR, 1.02), and C-reactive protein (CRP) levels (HR, 1.01) at the time of admission were independent predictors of incident PE during hospitalization. A risk score was constructed with these four variables showing a high predictive value of incident PE (AUC-ROC: 0.86; 95% CI: 0.80 to 0.93). CONCLUSIONS: Our findings confirmed a high incidence of PE in hospitalized COVID-19 patients. Heart rate, spO2, D-dimer, and CRP levels at admission were associated with higher rates of PE during hospitalization.

Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa.

Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1ß, IL-6, IL 8; tumor necrosis factor-alpha (α)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1ß, IL-8, and tumor necrosis factor-α levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation.

Simultaneous Depression of Immunological Synapse and Endothelial Injury is Associated with Organ Dysfunction in Community-Acquired Pneumonia.

RATIONALE: A depressed expression of antigen presentation is, along with endothelial dysfunction, a recognized signature of severe community-acquired pneumonia (CAP). We aimed to evaluate the expression of a number of genes involved in the immunological synapse in non-critically ill CAP patients with or without organ dysfunction and to profile endothelial biomarkers such as proendothelin-1 (proET1) and proadrenomedullin (proADM). METHODS: A nested study in a prospective cohort in CAP patients was performed. Expression levels of major histocompatibility complex class II DR alpha (HLA-DRA), CD40 ligand (CD40LG), CD3E, CD28, and inducible T-cell costimulator (ICOS) were quantified by using droplet digital polymerase chain reaction and endothelial biomarkers by immunofluorescence. RESULTS: Ninety-four patients were included, 44.7% of whom had organ failure in one or more organs. A significant decrease in the expression of the five genes with increased levels of proadrenomedullin (proADM) and proendothelin-1 (proET1) was found in CAP with organ failure. The depressed expression of HLA-DRA (odds ratio (OR), 2.94), CD40LG (OR, 3.90), and CD28 (OR, 3.48) was independently associated with organ failure after adjustment for age, Charlson score, and severity. CONCLUSIONS: CAP with organ failure showed depressed expression of immunological synapse genes with increased levels of biomarkers denoting endothelial damage. Simultaneous profiling of immunological and endothelial signatures could help in the early identification of organ failure in CAP and in the implementation of personalized treatment.

Lymphopenic community-acquired pneumonia is associated with a dysregulated immune response and increased severity and mortality.

OBJECTIVES: Lymphopenic (<724 lymphocytes/µL) community-acquired pneumonia (L-CAP) is an immunophenotype with an increased risk of mortality. We aimed to characterize the l-CAP immunophenotype though lymphocyte subsets and the inflammatory response and its relationship with severity at presentation and outcome. METHODS: Prospective study of 217 immunocompetent patients hospitalized for CAP. Lymphocyte subsets (CD4+, CD8+, CD19+, and natural killer [NK] cells) and inflammatory cytokines were analyzed on days 1 and 4, and immunoglobulin subclasses were analyzed on day 1 in a nested group. RESULTS: 39% of patients showed l-CAP, with decreased levels of all lymphocyte subsets with a partial recovery of CD4+ and CD8+ cells by day 4. l-CAP patients exhibited higher initial severity and systemic levels of interleukin (IL)-8, IL-10, granulocyte colony-stimulating factor, and monocyte chemoattractant protein-1. Initial IgG2 levels were lower in patients with <724 lymphocytes/µL and positively correlated with ALC, CD4+, and CD19+ cell counts. Low CD4+ counts (<129 cells/µL) also independently predicted 30-day mortality after adjusting for age, gender, and the CURB-65 score. CONCLUSIONS: l-CAP is characterized by CD4+ depletion, a higher inflammatory response, and low IgG2 levels that correlated with greater severity at presentation and worse prognosis. l-CAP is an immunophenotype useful for rapidly recognizing severity.

Pulmonary venous thrombosis secondary to radiofrequency ablation of the pulmonary veins.

BACKGROUND: Pulmonary Vein Thrombosis (PVT) is a rare and underdiagnosed entity produced by local mechanical nature mechanisms, vascular torsion or direct injury to the vein. PVT has been described in clinical cases or small multicenter series mainly in relation to pulmonary vein stenosis, metastatic carcinoma, fibrosing mediastinitis, as an early surgical complication of lung transplantation lobectomy and radiofrequency ablation performed in patients with atrial fibrillation, although in some cases the cause is not known. CASE: We report the case of a 57 years old male with history of atrial fibrillation treated by radiofrequency ablation who was admitted in our center because of a two-week history of consistent pleuritic pain in the left hemithorax and low-grade hemoptysis and a lung consolidation treated as a pneumonia with antibiotic but not responding to medical therapy. In view of the poor evolution of the patient, computed tomography angiography was performed with findings of PVT and secondary venous infarction and anticoagulation therapy was optimized. At the end, pulmonary resection was performed due to hemorrhagic recurrence. CONCLUSION: PVT remains a rare complication of radiofrequency ablation and other procedures involving pulmonary veins. Clinical suspicion and early diagnosis is crucial because is a potentially life-threatening entity.