The Additional Value of Lower Respiratory Tract Sampling in the Diagnosis of COVID-19: A Real-Life Observational Study.

Background: Since December 2019, SARS-CoV-2 has been causing cases of severe pneumonia in China and has spread all over the world, putting great pressure on health systems. Nasopharyngeal swab (NPS) sensitivity is suboptimal. When the SARS-CoV-2 infection is suspected despite negative NPSs, other tests may help to rule out the infection. Objectives: To evaluate the yield of the lower respiratory tract (LRT) isolation of SARS-CoV-2. To evaluate the correlations between SARS-CoV-2 detection and clinical symptoms, and laboratory values and RSNA CT review scores in suspect patients after two negative NPSs. To assess the safety of bronchoscopy in this scenario. Method: A retrospective analysis of data from LRT sampling (blind nasotracheal aspiration or bronchial washing) for suspected COVID-19 after two negative NPS. Chest CT scans were reviewed by two radiologists using the RSNA imaging classification. Results: SARS-CoV-2 was detected in 14/99 patients (14.1%). A correlation was found between SARS-CoV2 detection on the LRT and the presence of a cough as well as with typical CT features. Typical CT resulted in 57.1% sensitivity, 80.8% accuracy and 92.3% NPV. Neither severe complications nor infections in the personnel were reported. Conclusions: In suspect cases after two negative swabs, CT scan revision can help to rule out COVID-19. In selected cases, with consistent CT features above all, LRT sampling can be of help in confirming COVID-19.

Gender specific airway gene expression in COPD sub-phenotypes supports a role of mitochondria and of different types of leukocytes.

Chronic obstructive pulmonary disease (COPD) is a destructive inflammatory disease and the genes expressed within the lung are crucial to its pathophysiology. We have determined the RNAseq transcriptome of bronchial brush cells from 312 stringently defined ex-smoker patients. Compared to healthy controls there were for males 40 differentially expressed genes (DEGs) and 73 DEGs for females with only 26 genes shared. The gene ontology (GO) term "response to bacterium" was shared, with several different DEGs contributing in males and females. Strongly upregulated genes TCN1 and CYP1B1 were unique to males and females, respectively. For male emphysema (E)-dominant and airway disease (A)-dominant COPD (defined by computed tomography) the term "response to stress" was found for both sub-phenotypes, but this included distinct up-regulated genes for the E-sub-phenotype (neutrophil-related CSF3R, CXCL1, MNDA) and for the A-sub-phenotype (macrophage-related KLF4, F3, CD36). In E-dominant disease, a cluster of mitochondria-encoded (MT) genes forms a signature, able to identify patients with emphysema features in a confirmation cohort. The MT-CO2 gene is upregulated transcriptionally in bronchial epithelial cells with the copy number essentially unchanged. Both MT-CO2 and the neutrophil chemoattractant CXCL1 are induced by reactive oxygen in bronchial epithelial cells. Of the female DEGs unique for E- and A-dominant COPD, 88% were detected in females only. In E-dominant disease we found a pronounced expression of mast cell-associated DEGs TPSB2, TPSAB1 and CPA3. The differential genes discovered in this study point towards involvement of different types of leukocytes in the E- and A-dominant COPD sub-phenotypes in males and females.

[Community-acquired pneumonia: outcomes and costs]. / Le polmoniti acquisite in comunità: considerazioni cliniche e farmaco-economiche.

The number of patients admitted with community acquired pneumonias (CAP) varies greatly from one hospital to another. Prognostic models for CAP can help physicians decide which cases to treat on an outpatients basis. Our aims were: a) to validate a model for predicting low-risk CAP, and b) to estimate savings that would have resulted if the low-risk patients identified by the model had been treated at home rather than in hospital. The prediction rule of Fine et al. was used to classify retrospectively 260 CAP patients. Mortality in each category was compared with the mortality predicted. Patients in the lowest risk categories were considered to have been inappropriately admitted. The predictive model used has been found useful for identifying patients at very low-risk of dying from CAP. Application of the model can lead to savings.

[Clinical policy for management and risk stratification of community-acquired pneumonia in patients hospitalized on the basis of conventional admission criteria]. / Condotta clinica e stratificazione del rischio in pazienti ospedalizzati secondo criteri convenzionali per polmonite acquisita in comunità.

To identify discrepancies between Pneumonia Severity Index (PSI) risk class and the conventional criteria for deciding the site of care we performed a prospective observational study on 229 patients hospitalized for community-acquired pneumonia. PSI classes and corresponding mortality rates were as following: class I, 41 patients (0%); class II, 20 (0%); class III, 58 (1.7%); class IV, 86 (8.1%); class V, 24 (33.3%). Overall, 119 patients (52%) who were hospitalized according to conventional criteria were assigned to low-risk classes (I-III). Among these low risk patients, 58 (49%) had complications as respiratory failure, pleural effusion, hypotension or shock; among remaining patients, no reasons for admission were found. This latter group deserves prospective evaluation in randomized studies comparing in-hospital versus outpatient management.

Bosentan for patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease leading to worsening functional status and reduced survival for those patients who cannot undergo pulmonary endarterectomy (PEA). Pharmacotherapy with novel drugs for pulmonary hypertension may be useful in treating patients who are poor candidates for surgery, but there are still few clinical data on medical therapy for CTEPH. The aim of this prospective open-label, multicenter, study is to compare the efficacy of 1-year bosentan treatment to standard drugs in nonoperated patients with CTEPH. PATIENTS AND METHODS: Thirty-four nonoperated patients with CTEPH were enrolled. Functional assessment included 6 minute walk test (6MWT), Borg index, WHO classification, arterial blood gases and echocardiography systolic pulmonary artery pressure (sPAP). Seventeen patients received bosentan (62.5 mg b.i.d. for 4 weeks and then 125 mg b.i.d.); 17 patients were treated with standard therapy alone. RESULTS: At admission sPAP was 76.18+/-5.96 mmHg in bosentan group and 71.48+/-3.71 mmHg in controls, p(a)O(2) 64.68+/-2.25 mmHg in bosentan group, and 59.52+/-2.05 mmHg in controls, 6MWT 297.53+/-34.25 mt in bosentan group, and 268.47+/-36.54 mt in controls. After 12 months there were significant differences between the groups in the 6MWT (+57.24+/-22.21 m vs -73.13+/-21.23 m, p<0.001), dyspnoea index (Borg score 4.29+/-0.49 vs 7.06+/-0.32, p<0.001) and oxygenation (p(a)O(2) 65.93+/-3.76 mmHg vs 48.48+/-1.31 mmHg, p<0.001). The sPAP was stable after 12 months of bosentan (76.18+/-5.96 mmHg vs 71.00+/-5.41 mmHg, p=0.221) in contrast to controls (71.48+/-3.71 mmHg vs 80.44+/-4.70 mmHg, p=0.029). CONCLUSION: The data of this open-label study in nonoperated CTEPH patients suggest an improvement in functional outcomes adding Bosentan to diuretics and oral anticoagulants. No improvement was observed using only standard drugs after 1-year.

Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study.

We hypothesize that hydrocortisone infusion in severe community-acquired pneumonia attenuates systemic inflammation and leads to earlier resolution of pneumonia and a reduction in sepsis-related complications. In a multicenter trial, patients admitted to the Intensive Care Unit (ICU) with severe community-acquired pneumonia received protocol-guided antibiotic treatment and were randomly assigned to hydrocortisone infusion or placebo. Hydrocortisone was given as an intravenous 200-mg bolus followed by infusion at a rate of 10 mg/hour for 7 days. Primary end-points of the study were improvement in Pa(O(2)):FI(O(2)) (Pa(O(2)):FI(O(2)) > 300 or >/= 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and reduction in delayed septic shock. Forty-six patients entered the study. At study entry, the hydrocortisone group had lower Pa(O(2)):FI(O(2)), and higher chest radiograph score and C-reactive protein level. By Study Day 8, treated patients had, compared with control subjects, a significant improvement in Pa(O(2)):FI(O(2)) (p = 0.002) and chest radiograph score (p < 0.0001), and a significant reduction in C-reactive protein levels (p = 0.01), MODS score (p = 0.003), and delayed septic shock (p = 0.001). Hydrocortisone treatment was associated with a significant reduction in length of hospital stay (p = 0.03) and mortality (p = 0.009).