Poor adherence to guidelines for long-term oxygen therapy (LTOT) in two Italian university hospitals.

Long-term oxygen therapy (LTOT) improves survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. Adherence to LTOT guidelines is problematic, both because efficacy has been demonstrated only in specific groups of COPD patients, and because it implies high costs. Introduces treatment high costs. The aim of our study was to examine retrospectively the adherence to LTOT guidelines in a sample of medical records of patients prescribed LTOT between January 2005 and December 2006 in two Italian university hospitals (Ferrara and Modena). Out of a total of 191 medical records of patients prescribed LTOT, only 157 had adequate clinical data considering the three main criteria for appropriateness (arterial blood gas and/or pulse oximetry measurement, oxygen administration, smoking status). Out of these 157 patients, only 73 (46.5 %) fulfilled all three criteria recommended by the guidelines. Adherence was higher for LTOT prescribed by pulmonologists compared to internists. This survey showed that the adherence to LTOT guidelines in a sample of medical records of patients prescribed LTOT is poor. Considering the high costs and the impact on the patients' quality of life of LTOT, these results suggest that the adherence should be carefully monitored.

Plasma sRAGE and N-(carboxymethyl) lysine in patients with CHF and/or COPD.

BACKGROUND: Knowledge of the role of the receptor for advanced glycation end products (RAGE), particularly its soluble form (sRAGE), and of its advanced glycation end product (AGE) ligand, N-(carboxymethyl)lysine adducts (CML), is limited in chronic heart failure (CHF) and in chronic obstructive pulmonary disease (COPD). We evaluated whether the AGE/RAGE system is activated in stable CHF and COPD, and whether plasma sRAGE and CML levels are affected by clinical and functional parameters. MATERIALS AND METHODS: We measured plasma levels of sRAGE and CML using a sandwich enzyme-linked immunosorbent assay (ELISA) in 143 subjects, aged ≥ 65 years, divided into five groups: 58 with CHF, 23 with COPD, 27 with CHF+COPD and 35 controls (17 healthy smokers and 18 healthy nonsmokers). Individuals with diabetes were excluded from the study. RESULTS: Plasma levels of sRAGE and CML were higher in CHF patients than in controls [sRAGE: 0.48 (0.37-0.83) vs. 0.42 (0.29-0.52) ng/mL, P = 0.01; CML: 1.95 (1.58-2.38) vs. 1.68 (1.43-2.00) ng/mL, P = 0.01]. By contrast, sRAGE and CML were not different between both COPD and CHF+COPD patients and controls (P > 0.05). N-terminal pro-brain natriuretic peptide (Nt-pro BNP) correlated with sRAGE, but not with CML, in the patient groups: CHF (r = 0.43, P < 0.001), COPD (r = 0.77, P < 0.0001) and CHF/COPD (r = 0.43, P = 0.003). CONCLUSIONS: Plasma levels of sRAGE and CML are increased in CHF, but not in COPD patients. The robust association between NT-pro BNP, a diagnostic and prognostic marker in CHF, and sRAGE concentrations might suggest a possible BNP pathway of amplification of inflammation via the AGE/RAGE system.

Occurrence and impact of chronic obstructive pulmonary disease in elderly patients with stable heart failure.

BACKGROUND AND OBJECTIVE: The coexistence of chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) increases with age. The occurrence, prognosis and therapeutic implications of concurrent COPD in elderly patients with CHF were investigated. METHODS: One hundred and eighteen consecutive patients, ≥ 65 years old with ≥ 10 pack/years of smoking and with a verified diagnosis of CHF in stable condition, were enrolled. They were followed for a mean of 1029 (range 758-1064) days. All patients had spirometry and the diagnosis and classification of COPD were made according to Global Initiative for Chronic Obstructive Lung Disease guidelines. RESULTS: The mean occurrence of COPD was 30% (90% confidence interval: 24-37%). At baseline in patients with CHF and COPD, there was a shorter 6-min walk distance, lower arterial oxygen tension, glomerular filtration rate and higher N-terminal pro-B-type natriuretic peptide (all P < 0.05). The prescription of CHF therapies, including ß-blockers, was similar in the two groups. After follow up, the presence of COPD in patients with CHF did not appear to influence survival. CONCLUSIONS: COPD is relatively frequent in elderly patients with CHF. COPD did not alter survival.

The EvA study: aims and strategy.

The EvA study is a European Union-funded project under the Seventh Framework Programme (FP7), which aims at defining new markers for chronic obstructive pulmonary disease (COPD) and its subtypes. The acronym is derived from emphysema versus airway disease, indicating that the project targets these two main phenotypes of the disease. The EvA study is based on the concept that emphysema and airway disease are governed by different pathophysiological processes, are driven by different genes and have differential gene expression in the lung. To define these genes, patients and non-COPD controls are recruited for clinical examination, lung function analysis and computed tomography (CT) of the lung. CT scans are used to define the phenotypes based on lung density and airway wall thickness. This is followed by bronchoscopy in order to obtain samples from the airways and the alveoli. These tissue samples, along with blood samples, are then subjected to genome-wide expression and association analysis and markers linked to the phenotypes are identified. The population of the EvA study is different from other COPD study populations, since patients with current oral glucocorticoids, antibiotics and exacerbations or current smokers are excluded, such that the signals detected in the molecular analysis are due to the distinct inflammatory process of emphysema and airway disease in COPD.

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.

Pathophysiology of viral-induced exacerbations of COPD.

Inflammation of the lower airways is a central feature of chronic obstructive pulmonary disease (COPD). Inflammatory responses are associated with an increased expression of a cascade of proteins including cytokines, chemokines, growth factors, enzymes, adhesion molecules and receptors. In most cases the increased expression of these proteins is the result of enhanced gene transcription: many of these genes are not expressed in normal cells under resting conditions but they are induced in the inflammatory process in a cell-specific manner. Transcription factors regulate the expression of many pro-inflammatory genes and play a key role in the pathogenesis of airway inflammation. Many studies have suggested a role for viral infections as a causative agent of COPD exacerbations. In this review we will focus our attention on the relationship between common respiratory viral infections and the molecular and inflammatory mechanisms that lead to COPD exacerbation.

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).

[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.

[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.