Tiotropium and exercise training in COPD patients: Effects on dyspnea and exercise tolerance

Nicolino Ambrosino1, Katia Foglio2, Gianni Balzano2, Pier Luigi Paggiaro1, Patrizia Lessi3, Steven Kesten3 On behalf of the Tiotropium Multicentric Italian Study Group1Cardio-Thoracic Department, University Hospital, Pisa, Italy; 2S Maugeri Foundation IRCCS, Italy; 3Boehringer Ingelheim, GmbH, Milan, ItalyBackground: Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinflation, one of the pathophysiological factors contributing to exertional dyspnea in COPD patients.Aim: To determine whether tiotropium enhances the effects of exercise training in patients with COPD.Design: Multicenter, 25 week randomized, double-blind, placebo-controlled, parallel-group study.Setting: Twelve Italian Pulmonary Units practicing pulmonary rehabilitation.Patients and intervention: Two hundred thirty four COPD patients (196 males; mean age: 67.4 ± 7.6; forced expiratory volume at 1 second (FEV1): 41.4 ± 13.0% predicted) were randomised to tiotropium 18 μg or placebo inhalation capsules taken once daily. Both groups underwent a 8 week pulmonary rehabilitation program (PR) consisting of 3 exercise training session per week.Measurements: Baseline, at the end of PR and after 12 weeks, patients completed pulmonary function testing, six minute walking test (6MWT), the Baseline and Transition Dyspnea Index (BDI and TDI), and the St. George’s Respiratory Questionnaire (SGRQ).Results: Relative to placebo, tiotropium had larger trough and post-study drug FEV1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically significant differences in 6MWT compared to patients on placebo. Compared to the period immediately prior to PR, the mean improvement in 6MWT was only 29.7 meters (7.1%) for the combined cohort. Mean TDI focal scores at the end of PR were 3.60 for tiotropium and 2.25 for placebo (p < 0.01). At 12 weeks after PR, TDI focal scores were 2.71 for tiotropium and 2.11 for placebo (p = 0.16). Reduction in all four SGRQ component scores, indicating an improvement in health-related quality of life, was observed for the tiotropium group over the duration of the study compared to placebo but the differences were not statistically significant. During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group.Conclusion: Although significant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT.Keywords: bronchodilators, pulmonary rehabilitation, health-related quality of life, hyperinflation, dyspne

Multicenter Observational Retrospective Study on Febrile Events in Patients with Acute Myeloid Leukemia Treated with Cpx-351 in "Real-Life": The SEIFEM Experience

: In the present study, we aimed to evaluate the absolute risk of infection in the real-life setting of AML patients treated with CPX-351. The study included all patients with AML from 30 Italian hematology centers of the SEIFEM group who received CPX-351 from July 2018 to June 2021. There were 200 patients included. Overall, 336 CPX-351 courses were counted: all 200 patients received the first induction cycle, 18 patients (5%) received a second CPX-351 induction, while 86 patients (26%) proceeded with the first CPX-351 consolidation cycle, and 32 patients (10%) received a second CPX-351 consolidation. A total of 249 febrile events were recorded: 193 during the first or second induction, and 56 after the first or second consolidation. After the diagnostic work-up, 92 events (37%) were classified as febrile neutropenia of unknown origin (FUO), 118 (47%) were classifiable as microbiologically documented infections, and 39 (17%) were classifiable as clinically documented infections. The overall 30-day mortality rate was 14% (28/200). The attributable mortality-infection rate was 6% (15/249). A lack of response to the CPX-351 treatment was the only factor significantly associated with mortality in the multivariate analysis [p-value: 0.004, OR 0.05, 95% CI 0.01-0.39]. Our study confirms the good safety profile of CPX-351 in a real-life setting, with an incidence of infectious complications comparable to that of the pivotal studies; despite prolonged neutropenia, the incidence of fungal infections was low, as was infection-related mortality

Clinical variables associated with treatment changes in Parkinson\u2019s disease: results from the longitudinal phase of the REASON study

To assess over a period of 9\ua0months in a sample of Italian Parkinson\u2019s disease (PD) patients reasons leading the neurologist to modify dopaminergic treatment and patients\u2019 causes of dissatisfaction with ongoing therapy. To evaluate the influence of disease severity on therapy persistence. A disease severity balanced sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was enrolled and evaluated every 3\ua0months. Patients requiring APD treatment modifications were discontinued from the study. The probability to modify APD treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS score) severity. Both from neurologist\u2019s and patient\u2019s perspective, motor symptoms were the main determinants underlying APD treatment modifications. Non-motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52\ua0% of the patients, while only 36\ua0% of the neurologists considered these as valid reasons for therapy change. REASON is the first study in PD patients that prospectively examined reasons driving APD treatment changes. Results show that the disease severity significantly increases the probability of APD treatment change. Patients attribute greater relevance than neurologists to non-motor symptoms as reason requiring treatment changes. This confirms that patient and neurologist perceptions only partially overlap

Linkage disequilibrium between intra-locus variants in the aminopeptidase n gene and test of their association with coeliac disease

Coeliac disease (CD) is a multigenic and multifactorial enteropathy triggered by gluten-composing proteins. A possible involvement of the intestinal Aminopeptidase N (APN) was investigated by an association analysis. SSCP analysis detected four variants at position 281, 378, 956 and 2957 (referred to no. g178535, GenBank) that were studied in 193 Italian CD families. The haplotypic combinations were determined from family segregation and pairwise linkage disequilibria (D' = D/Dmax) between the polymorphic sites were calculated. Significant D' values ranged between 0.78 and 0.31. Association with CD was tested by TDT (Transmission Disequilibrium Test) utilizing as markers the nucleotide substitutions and their haplotypic combinations. No statistically significant transmission distortion to the probands or to their clinically silent sibs was observed. Our data exclude an involvement in CD of the tested markers and of further undetected variation in strong linkage disequilibrium (D' approximately equal to 1) with them. The power of the test was not adequate to detect an association with an unknown polymorphism which is not in complete linkage disequilibrium with those analysed