Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life.

BACKGROUND: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life. METHODS: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months). RESULTS: FEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/µL (8.4 ± 5.2%) decreasing to 151 ± 384/µL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients. CONCLUSION: In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure.

Diagnosis of pulmonary embolism.

Conventional pulmonary arteriography for the diagnosis of pulmonary embolism (PE) bears several limitations in clinical practice, basically due to its invasiveness. On the other hand, no single noninvasive test is both sensitive and specific for the diagnosis of PE. Therefore, the choice of available noninvasive diagnostic tests guided by the clinical probability of PE is a good compromise at present. The first necessary step toward the diagnosis of PE is to raise the clinical suspicion, given that no diagnosis can be made if PE is not considered in the differential diagnosis of patients with acute cardiorespiratory symptoms. Second, empirical or standardized rules for predicting clinical probability may be combined with one or more noninvasive tests with the aim of increasing the accuracy of the noninvasive diagnosis. The strategy for the noninvasive diagnosis of PE varies among different centers according to the availability of each single technique that may be integrated with another and according to the characteristics of the population that refers to each single center. Therefore, spiral CT should not be used as a primary tool for the diagnosis of PE; its role needs to be re-evaluated in light of its sensitivity, feasibility, and radiation burden on the patients. In patients in whom the diagnosis of PE cannot be made at the end of the noninvasive pathway, the use of the invasive techniques must be taken into consideration. In our experience, however, such cases should not exceed 15 to 20% of the total patient population.

Elective surgery for giant bullous emphysema: a 5-year clinical and functional follow-up.

BACKGROUND: So far, very few studies in the literature have reported data on the long-term follow-up of patients who have undergone surgery for giant bullous emphysema (GBE), and much still needs to be known on the late fate of these patients. AIMS: To evaluate patients who have undergone elective surgery due to GBE, early and late mortality following surgery, the early and late reappearance of bullae, and the early and late modifications of clinical and functional data. SUBJECTS AND METHODS: Forty-one consecutive patients (36 men; mean [+/- SD] age, 48.4 +/- 14.8 years) who underwent elective surgery for GBE were enrolled in a prospective study, and were studied both before and after undergoing bullectomy for a 5-year-follow-up period. Analyses were performed on the whole population and on two subgroups of patients who were divided on the basis of the absence of underlying diffuse emphysema (group A; n = 23) or the presence of underlying diffuse emphysema (group B; n = 18). RESULTS: The early mortality rate was 7.3% (within the first year), and the late mortality rate was 4.9% (overall mortality rate at 5 years, 12.2%; mortality rate in group B, 27.8%). Bullae did not reappear and residual bullae did not become enlarged in any patients at the site of the bullectomy. During the follow-up, the dyspnea score was reduced significantly soon after bullectomy and up to the fourth year of follow-up; intrathoracic gas volume also was reduced significantly (average, 0.7 L). The same was true for the FEV1 percent predicted and the FEV1/vital capacity ratio, which kept increasing until the second year; then, from the third year of follow-up these values were reduced, yet remained above the prebullectomy values until the fifth year of follow-up. When considered separately, the patients in group B appeared to be the most impaired, clinically and functionally (eg, FEV1 showed a similar significant increase up to the second year in both groups after surgery, while a different mean annual decrease was appreciable from the second to the fifth year of follow-up: group A, 25 mL/year; group B, 83 mL/year. Furthermore, patients in group B were the only ones who contributed to the mortality rate, on the whole showing a behavior similar to that of patients who had undergone lung volume reduction surgery. CONCLUSIONS: In patients with GBE who were enrolled in the study prospectively and were investigated yearly during a 5-year-follow-up period, elective surgery appears to have been fairly safe, and allowed clinical and functional improvement for at least 5 years. Better results may be expected in patients without underlying diffuse emphysema.

[Geographical study on lung cancer mortality among residents in the neighbourhood of the coke plant in Piombino]. / Studio geografico sulla mortalità per tumore del polmone nei residenti a Piombino attorno alla locale cokeria.

OBJECTIVES: To evaluate a possible risk of lung cancer related to environmental pollutants in the population living in Piombino, Italy in the neighborhood of the local coke plant. DESIGN: Geographical study. SETTING AND PARTICIPANTS: Lung cancer deaths occurred in 1986-2000 in residents in Piombino were included in the study. MAIN OUTCOME MEASURES: Observed and expected number of cases for each census unit were computed using 4 different case distributions by residence in the area: at the time of death, 10 years before death, 15 years before death, and the longer residence in Piombino. For each census unit, the expected cases of male lung cancer death in 1986-2000 were calculated using the cause-, sex- and age-specific mortality rates of the entire area, obtained with the four case distributions. Data was analyzed and adjusted for an index ofsocial deprivation, using the Stone conditional test. RESULTS: A significant excess risk of lung cancer mortality, decreasing with distance from the plant, was observed only when the cases experiencing their longer residence in Piombino were included in the analysis. CONCLUSIONS: Smoking habits and occupation are the most important risk factors, nevertheless environmental pollutants might have played an additional role in the causation of the excess risk observed.