Struttura Complessa PNEUMOLOGIA Azienda Ospedaliero-Universitaria "Ospedali Riuniti di Trieste" Ospedale di Cattinara Strada di Fiume 447 34149 Trieste Italy
Abstract: 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.
Abstract: OBJECTIVE: During thoracotomy, positive end-expiratory pressure is applied to the dependent lung and continuous positive airway pressure (CPAP) inflates the nondependent lung to avoid hypoxemia. These methods do not allow the removal of produced secretions. We hypothesized that high-frequency percussive ventilation(HFPV) can improve both conditions and reduce hospital length of stay in these patients. DESIGN: Randomized prospective study. SETTING: University Hospital. PATIENTS: Fifty-three consecutive patients undergoing elective pulmonary partial resection were enrolled. Nine were excluded because of surgical reasons. INTERVENTIONS: The nondependent lung was ventilated with HFPV in 22 patients and other 22 received CPAP. In both groups,the dependent lung was ventilated with continuous mechanical ventilation. MEASUREMENT AND MAIN RESULTS: Cardiocirculatory variables and blood gas analysis were measured during surgery. Postoperatively,all patients underwent chest physiotherapy, and SpO2,body temperature, the amount of sputum produced, and chest radiography were recorded. Before nondependent lung re-expansion,HFPV patients presented higher PaO2 than CPAP group (p = 0.020). The amount of secretions was higher in chronic obstructive pulmonary disease patients treated with HFPV than in those who received CPAP (199 and 64 mL, respectively, p = 0.028). HFPV increased by 5.28 times the chance of sputum production by chronic obstructive pulmonary disease patients (chi(2) = 46.66, p < 0.0001; odds ratio = 5.28). A patient treated with HFPV had a 3.14-fold larger chance of being discharged earlier than a CPAP-treated subject (likelihood ratio = 11.5, p = 0.0007). CONCLUSIONS: Under the present settings, HFPV improved oxygenation in one-lung ventilation during pulmonary resection. Postoperatively, it decreased the length of stay and increased the removal of secretions in comparison with CPAP.
Abstract: BACKGROUND AND OBJECTIVE: Exacerbations of COPD are often characterized by increased mucus production that is difficult to treat and worsens patients' outcome. This study evaluated the efficacy of a chest physiotherapy technique (expiration with the glottis open in the lateral posture, ELTGOL) during acute exacerbations of COPD using as outcome measures sputum volume, length of hospitalization, reduction in dyspnoea (Borg score), improvement in quality of life (assessed by the St George Respiratory Questionnaire) and incidence of COPD exacerbations during follow up. METHODS: The study recruited 59 patients hospitalized for the treatment of acute exacerbation of COPD, who were randomly assigned to a control group and an intervention group. The control group was treated with standard medical therapy while the intervention group was treated with ELTGOL plus medical therapy. A subgroup of patients was followed for 6 months to verify the effects on COPD exacerbations and need for hospitalizations. RESULTS: At the time of hospital discharge there was no significant difference between the two groups in the outcome measures, with the exception of the Borg score, which was significantly improved in the ELTGOL group (4.3 +/- 1.5 in the control group vs 3.0 +/- 1.8 in the ELTGOL group, P = 0.004). After 6 months there was no significant difference in the other measured parameters between a subset of the groups available for follow up. During follow up, the ELTGOL group had numerically fewer exacerbations and less need for hospitalization though differences were not statistically significant. CONCLUSIONS: Chest physiotherapy using the ELTGOL technique has a limited role in patients with mild exacerbation of moderate to severe COPD with a tendency towards fewer exacerbations and hospitalizations.
Abstract: CONTEXT: The benefit of corticosteroids in severe sepsis and septic shock remains controversial. OBJECTIVE: We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. DATA SOURCES: We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. STUDY SELECTION: Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. DATA EXTRACTION: All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. RESULTS: We identified 17 randomized trials (n = 2138) and 3 quasi-randomized trials (n = 246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P = .05; I(2) = 53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P = .83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) (RR, 0.84; 95% CI, 0.72-0.97; P = .02). This treatment increased 28-day shock reversal (6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P = .02; I(2) = 4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P < .001; I(2) = 0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P = .50; I(2) = 0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P = .92; I(2) = 8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P = .58; I(2) = 30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P < .001; I(2) = 0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [19.2%]; P < .001; I(2) = 0%). CONCLUSIONS: Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality.
Abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and underdiagnosed disease characterized by progressive hypertension secondary to organized thrombi in pulmonary vessels. The arteriolar lesions of CTEPH are similar to those seen in idiopathic pulmonary arterial hypertension (PAH). Surgical disobliteration of the vessels by pulmonary endarterectomy is the therapy of choice but this is not suitable for all cases. To date, there is no licensed specific drug for CTEPH. Endothelin-1, a vasoconstrictor and promoter of cell proliferation, is involved in the pathogenesis of both CTEPH and PAH. Bosentan, the first oral dual endothelin receptor antagonist, has been shown to be effective in PAH. Preliminary uncontrolled and/or unblinded studies reported efficacy of bosentan in CTEPH, and the only randomized, controlled trials showed a positive hemodynamic effect but failed its other co-primary end point, namely the improvement of 6-min walking distance. Nevertheless, bosentan has been shown to be safe and the data from most literature encourage its use for inoperable CTEPH. However, further randomized controlled trials are needed to definitively establish bosentan as a standard drug for CTEPH.
Abstract: The development of the medical knowledge has became a multidisciplinary process that can be called life sciences. The new biotechnologies are changing the insight of pathology and medical therapy itself. So, the rule of the physician is changing together with the overwhelming centrality of the patient into the health system. Also, the evidence based medicine is no more considered a crucial task for the physician who cares the single ill person, albeit its importance is still high for health organizations. A genomic and post-genomic approach could indeed help to create an actual personalised medicine. Nevertheless, "omics" probably need the development of new bioinformatic tools capable to manage a huge amount of data by means of Grid computing. The development of the life sciences involves new formative and professional needs for the physician. The translational knowledge can be favoured by the closeness of clinical centres and basic science areas as suggested by several examples spreading all over the world. These experiences could open new exciting horizons for the medical science.
Abstract: The study of airways pH represents a new perspective in the comprehension of asthma pathogenesis. The effects of acidification may cause symptoms as cough, dyspnoea, wheezing and may be related to gastroesophageal reflux-induced asthma, inhaled acids (pollution, fog, professional exposure) and disregulation of acid-base homeostasis.
Abstract: This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.
Abstract: BACKGROUND AND AIM: Out-patient high-dose-rate endobronchial brachytherapy (HDREB) is a possible option in the palliation of symptoms in patients with advanced lung cancer, but literature data is limited and the technique is still under development in Italy. Our aim was to evaluate safety and effectiveness of out-patient HDREB for palliation of malignant endobronchial tumours in the context of a multidisciplinary approach. METHODS: Out-patient HDREB sessions were scheduled at weekly intervals (500-1000 cGy per session) with prior Diodi-laser resection in some cases. Response was assessed bronchoscopically, clinically and functionally at the end of treatment and one month after the last HDREB session. Inclusion criteria was: histological evidence of malignant tumour not susceptible to surgical treatment for extension or co-morbidity. RESULTS: 150 outpatient HDREB sessions were carried out on consecutive 35 patients (mean age 69 yrs, M/F 29/6) with symptoms due to central airway obstruction. A shortterm endoscopic response was observed in 15/28 patients. After delivering 2000 cGy dyspnoea decreased significantly. After one month cough decreased and haemoptysis disappeared. Palliation was obtained in all patients except one during. Lung function tests did not significantly improve after HDREB. No fatal complication occurred. A temporary radiation bronchitis was observed in six patients. CONCLUSIONS: This non-comparative, prospective observational study showed a palliative response of HDREB in most of patients with advanced endoluminal lung cancer. The safety of the procedure was good and the rate of non-fatal serious complications was very low.
Abstract: RATIONALE: Acidification of the airways seems to be involved in asthma pathophysiology, but its assessment might be difficult. OBJECTIVES: The aim of our study is to assess the feasibility and validity of airway acidification measurement by induced sputum and its clinical significance in asthma. METHODS: Induced-sputum samples were obtained in 57 outpatients with asthma. The between-sample repeatability after 48 hours was measured in an independent population of 14 patients with asthma. pH was measured using a pH meter. The control of asthma was established by the Asthma Control Questionnaire. MEASUREMENTS AND MAIN RESULTS: The pH measurement was feasible in all samples and repeatable both within (intraclass correlation coefficient [ICC], 0.96) and between samples (ICC, 0.621). The mean pH was significantly different between healthy subjects and patients with asthma, including in those with controlled (mean pH: 7.54 in healthy subjects vs. 7.28 in subjects with controlled asthma; p = 0.0105) and uncontrolled disease (mean pH: 7.54 in healthy subjects vs. 7.06 in subjects with uncontrolled disease; p < 0.0001), and between patients with stable asthma and those with poorly controlled asthma (7.28 vs. 7.06, respectively; p = 0.0134). The validity of the method was assessed with the receiver operating characteristic curves and induced-sputum lower pH values (with a cutoff value of 7.3; sensitivity, 72.1%; specificity, 100%). CONCLUSIONS: Patients with asthma show lower pH than healthy subjects. Patients with poorly controlled asthma seem to have the lowest induced-sputum pH, independent of the GINA (Global Initiative for Asthma) severity level. In conclusion, induced sputum is a feasible, repeatable, noninvasive method to measure airway pH. The pH in induced sputum may reflect a different aspect of asthma from sputum eosinophils and be related to different pathophysiologic factors.
Abstract: Despite advances in antimicrobial therapy and supportive measures, mortality for patients with severe community-acquired pneumonia admitted to the intensive care unit remains high, especially in case of development of sepsis with its complications. So, the early detection of the severity of pneumonia is crucial to achieve an optimal monitoring and treatment of the patients. Studies of serum and lung cytokines levels in patients with pneumonia show a compartimentalized response, that rarely appears in the serum. In case of severe community-acquired pneumonia inflammation spill over from the lungs, particularly there is a persistent increase of IL-6 and CRP in serum, and this is associated with a worst prognosis and possible development of sepsis-related complications. Hydrocortisone and other glucorticoid agents have a powerful modulating effect on inflammation and balance between pro- and anti-inflammatory factors. Recent randomized controlled clinical trials on patients with severe community acquired pneumonia support the use of prolonged infusion of low doses of hydrocortisone to accelerate the resolution of the pneumonia and prevent the development of complications due to sepsis. Moreover, this therapeutic approach seems to be associated with a significant reduction in duration of mechanical ventilation, in length of hospital stay and mortality in hospital.
Abstract: 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).
Abstract: INTRODUCTION: To assess whether respiratory intermediate care units (RICUs) are cost effective alternatives to intensive care units (ICUs) for patients with exacerbation of chronic obstructive pulmonary disease (COPD). PATIENTS AND METHODS: Multi-centre, prospective, bottom-up cost study performed in 15 ICUs and 6 RICUs. COPD patients staying longer than 48 h were recruited; those coming from other ICUs/RICUs, with immune-deficiency or stroke, were excluded. After the ICU sample was standardised to the RICU distribution of the reason-for-admission and infusion of a vasoactive drug on admission, 60 ICU patients and 65 RICU patients remained, of the original 164 recruited. For each patient, besides clinical data on admission and discharge, daily information about the resources consumed were recorded and analysed in terms of their costs. RESULTS: Total cost per patient was lower in RICUs than in ICUs (754 vs. 1507 Euro; P < 0.0001). In all items, except drugs and nutrition, we found a significant lower cost in RICUs. Dead patients were noticeably different in terms of disease severity between ICUs and RICUs, while surviving ones were not. CONCLUSIONS: Our study suggests that some COPD patients, less severe and with pure respiratory failure, could be successfully and less costly treated in RICUs.
Abstract: We analyzed 795 sputa from 315 patients (233 males, mean age 69.3+/-8.8 years, mean number of exacerbations 2.52/patient) with acute exacerbations of moderate-to-severe chronic obstructive pulmonary disease (COPD) (mean steady-state FEV1 42.5+/-7.8% of predicted). 581/795 sputa were considered adequate. Sputum was analyzed by a quali-quantitative colorimetric scale allowing both color distinction and color degree of intensity. Quantitative culture was then performed (threshold: >10(6)CFU/mL). Samples were distinguished in mucoid (145) and purulent (436) sputa. Absence of bacterial growth was observed in 22% and 5% of mucoid and purulent sputa, respectively. Among mucoid sputa, Gram positive bacterial growth occurred more commonly compared to Gram negative and Pseudomonas aeruginosa/Enterobacteriaceae (56%, 24%, 20%, respectively). In purulent sputa, Gram positives were found in 38% of cases, Gram negatives in 38%, and P. aeruginosa/Enterobacteriaceae in 24%. We evaluated whether functional impairment (FEV1) orientates as to the infectious etiology of exacerbations. Significant differences were observed in the distribution of pathogens. Gram negative and P. aeruginosa/Enterobacteriaceae were isolated more frequently in the sputum when FEV1 was <35%. Our study indicates that purulent sputum is strongly associated with bacterial growth in COPD exacerbations. Deepening sputum color (from yellowish to brownish) was associated with increased yield of Gram negative and P. aeruginosa/Enterobacteriaceae.
Abstract: Knowing the likelihood of failure of noninvasive positive pressure ventilation (NPPV) in patients with exacerbation of chronic obstructive pulmonary disease (COPD) could indicate the best choice between NPPV and endotracheal intubation instituted earlier. For this purpose, two risk charts were designed (at admission and after 2 h of NPPV) that included all relevant measurable clinical prognostic indicators derived from a population representing the patients seen routinely in clinical practice. Risk stratification of NPPV failure was assessed in 1,033 consecutive patients admitted to experienced hospital units, including two intensive care units, six respiratory intermediate care units, and five general wards. NPPV was successful in 797 patients. Patients with a Glasgow Coma Score <11, acute physiology and chronic health evaluation (APACHE) II > or =29, respiratory rate > or =30 breaths x min(-1) and pH at admission <7.25 have a predicted risk of failure >70%. A pH <7.25 after 2 h greatly increases the risk (>90%). The risk charts were validated on an independent group of 145 consecutive COPD patients treated with NPPV due to an acute ventilatory failure episode. To identify patients with a probability of failure >50%, the sensitivity and specificity were 33% and 96.7% on admission and 52.9% and 94.1% after 2 h of NPPV, respectively. The prediction chart, based on data from the current study, can function as a simple tool to predict the risk of failure of noninvasive positive pressure ventilation and thus improve clinical management of patients tailoring medical intervention.
Abstract: BACKGROUND: Cardiovascular complications are frequently observed in patients with chronic obstructive pulmonary disease (COPD) admitted to respiratory intensive care units and may affect the prognosis. The aims of this study were to evaluate a) the prevalence of cardiovascular complications in patients with COPD exacerbation admitted to respiratory intensive care units, b) which parameters detected at admission were predictive of cardiovascular complications, and c) the prognostic role of cardiovascular complications. METHODS: A series of 278 consecutive patients with COPD admitted to 11 Italian respiratory intensive care units between November 1997 and January 1998 has been retrospectively analyzed. All cardiovascular complications were recorded. RESULTS: One hundred and ten patients (39.6%) developed cardiovascular complications: congestive heart failure 49 (17.6%), arrhythmias 40 (14.4%), shock 13 (4.7%), and hypotension 11 (4%). Multivariate analysis showed that the APACHE II score, ECG abnormalities (supraventricular ectopic beats, right and/or left ventricular hypertrophy) and digoxin therapy were independent predictors of cardiovascular complications. The overall mortality was 9% being 4.7% in patients without and 15.5% in patients with cardiovascular complications (p = 0.0044). Multivariate analysis showed that the APACHE II score, respiratory rate, pneumonia and end-stage respiratory diseases were independent predictors of mortality. CONCLUSIONS: Cardiovascular complications occurred in many patients with COPD exacerbation admitted to respiratory intensive care units, and identify a subset of patients with higher mortality.
