Alfredo Potena

Association between markers of emphysema and more severe chronic obstructive pulmonary disease

Background: The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. Methods: Twenty six outpatients with COPD and eight healthy non-smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. Results: Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9, and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). Conclusions: These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema.

Patient Satisfaction With Conscious Sedation for Bronchoscopy

STUDY OBJECTIVE Bronchoscopic technique is not standardized. Controversies exist with regard to premedication with sedatives before the test. To evaluate safety and efficacy of conscious sedation, we studied 100 randomized patients undergoing diagnostic bronchoscopy; patients received premedication with lidocaine spray and atropine sulfate i.m. (nonsedation group; 50 patients) or lidocaine spray, atropine i.m. and diazepam i.v. (sedation group; 50 patients). METHODS AND RESULTS Monitoring during flexible fiberoptic bronchoscopy included continuous ECG and pulse oximetry. The procedure could not be completed in six patients. None received premedication with diazepam; among the patients who ended the examination, tolerance to the examination (visual analogue scale, 0 to 100; 0 = excellent; 100 = unbearable) was better in the sedation group. Low anxiety, male sex, but not age were also associated with improved patient tolerance to the test. Oxygen desaturation occurred in 17% of patients, and it was not more frequent after diazepam treatment. CONCLUSIONS In our study, sedation had a beneficial effect on patient tolerance and rarely induced significant alterations in cardiorespiratory monitoring parameters.

Last 3 months of life in home-ventilated patients: the family perception

We studied the familys perception of care in patients under home mechanical ventilation during the last 3 months of life. In 11 respiratory units, we submitted a 35-item questionnaire to relatives of 168 deceased patients exploring six domains: symptoms, awareness of disease, family burden, dying, medical and technical problems. Response rate was 98.8%. The majority of patients complained respiratory symptoms and were aware of the severity and prognosis of the disease. Family burden was high especially in relation to money need. During hospitalisation, 74.4% of patients were admitted to the intensive care unit (ICU). 78 patients died at home, 70 patients in a medical ward and 20 in ICU. 27% of patients received resuscitation manoeuvres. Hospitalisations and family economical burden were unrelated to diagnosis and mechanical ventilation. Families of the patients did not report major technical problems on the use of ventilators. In comparison with mechanical invasively ventilated patients, noninvasively ventilated patients were more aware of prognosis, used more respiratory drugs, changed ventilation time more frequently and died less frequently when under mechanical ventilation. We have presented good points and bad points regarding end-of-life care in home mechanically ventilated patients. Noninvasive ventilation use and diagnosis have impact on this burden.

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.

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.

Pulmonary infections in lung cancer patients at diagnosis

We carried out a prospective study involving 96 consecutive lung cancer patients at diagnosis, in order to determine through quantitative cultures of the bronchoalveolar lavage (BAL) fluid, the prevalence of pulmonary infections; we also evaluated the relationship between a patients performance status, immunocompetence, lung cancer stage, histotype and the occurrence of respiratory infections. The patients (81 males, 15 females) had a mean age of 64 +/- 9 years. Of these, 62 were smokers, 30 were ex-smokers and four had never smoked. Sixty-seven patients had a prior history of chronic bronchitis. A total of 42 micro-organisms were cultured from the BAL fluids of 33 patients (34.3%). Fifty percent of these micro-organisms were gram-negative, 33.3% were gram-positive and the remaining 16.7% were other micro-organisms. The bacilli most often isolated were the Haemophilus species, accounting for 38.8% of all gram-negative bacilli. The most frequently isolated gram-positive pathogen was the Staphylococcus aureus. We have not found a significant relationship between the presence of a respiratory infection and the different cell types separately analyzed, nor with SCLC and NSCLC patient groups, nor with the stage of the disease. The performance status, the immunoregulatory ratio and the lymphocyte subsets were not significantly different in patients with or without a pulmonary infection. We think that the identification of a definite etiologic agent is of great importance for a rational anti-microbial treatment of pulmonary infections.

Bronchial hyperreactivity in systemic sclerosis patients: influence of associated Sjögren's syndrome.

OBJECTIVE--To determine the frequency and relative risk of bronchial hyperreactivity to methacholine in systemic sclerosis patients with or without associated Sjögrens syndrome. METHODS--A prospective study of 56 patients with systemic sclerosis (42 with the diffuse and 14 with the limited variant; 24 with associated Sjögrens syndrome), 57 with primary Sjögrens syndrome, and 61 healthy controls. RESULTS--Bronchial hyperreactivity (BH) was present in 6.5% of the healthy controls, 25% of the systemic sclerosis patients without associated Sjögrens syndrome, 42.2% of those with primary Sjögrens syndrome, and in 50% of those with systemic sclerosis with associated Sjögrens syndrome. The presence of BH did not correlate with age, disease duration, chest radiograph abnormalities, respiratory, and immunological data. The subgroup of subjects with the limited variant of systemic sclerosis more frequently had associated BH than did those with the diffuse variant of the disease; coexisting Sjögrens syndrome further increased this frequency. CONCLUSIONS--In agreement with previous studies, we have confirmed the high prevalence of bronchial hyperreactivity in primary Sjögrens syndrome; systemic sclerosis likewise appears to be associated with an increased frequency of bronchial hyperreactivity compared with healthy control subjects. There is evidence also that the coexistence of Sjögrens syndrome and systemic sclerosis further increases the frequency and the calculated relative risk of developing bronchial hyperreactivity.

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.

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

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.

Reduced expression of macrophage-associated antigens on alveolar mononuclear phagocytes from acquired immunodeficiency syndrome

SummaryIn this study we evaluated the phenotype of alveolar mononuclear phagocytes recovered from the bronchoalveolar lavage fluid of 24 patients with human immunodeficiency virus infection (AIDS-related complex 8 patients, AIDS 16 patients) and 8 healthy individuals by using a panel of monoclonal antibodies known to react with tissue macrophages, in combination with a flow cytometer. The results showed that 90% of patients with AIDS present a marked reduction in the expression of several antigenic determinants (in descreasing order: CD68, CD36, CR1, CD11c, HLA-DR). The levels of antigen expression by flow cytometry seem to decline with disease progression, showing the most dramatic perturbations in patients with full-blown AIDS associated with pulmonary infections (especiallyPneumocystis carinii pneumonia) and lower peripheral CD4 lymphocyte counts. In contrast, patients with AIDS-related complex or AIDS without histological or cultural evidence of pulmonary involvement showed, respectively, only minimal or medium antigenic decreases. However, only a minor proportion (16%, 20%, 20%, 25%, and 25% respectively) of human immunodeficiency virus infected patients (mostly with AIDS) had a significant reduction of the levels of CD4, CD14, CD45R, CD11b, and CD16 antigens in the alveolar macrophages. Since macrophages play a central role in the pathogenesis of AIDS, it may be postulated that the loss of various phenotypic markers on alveolar mononuclear phagocytes (some of them known for their important immunoregulatory actions) could have an important part in the pathogenesis of human immunodeficiency virus induced immunosuppression, and thereby condition the abnormal susceptibility to pulmonary diseases typical of human immunodeficiency virus-infected patients.