Background: Exercise training improves exercise tolerance in chronic obstructive pulmonary disease (COPD). Tiotropium 18 μg once daily induces sustained bronchodilation throughout the day and reduces hyperinfl ation, 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 (FEV 1 ): 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 FEV 1 responses on all test days. At the end of and 12 weeks following PR, patients on tiotropium showed no statistically signifi cant 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 Ͻ 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 signifi cant. During the study period, there were fewer exacerbations and exacerbation days in the tiotropium group. Conclusion: Although signifi cant improvements were observed with perceived dyspnea, compared to placebo, the addition of tiotropium to pulmonary rehabilitation did not improve the 6MWT.

These data suggest that plasma OPN and serum OPN are not influenced by confounding factors such as age, smoking habits and asbestos exposure. Plasma and serum OPN may be useful markers in the diagnosis of epithelial MPM in addition to traditional radiological exams. However, in our opinion plasma OPN is preferable to serum OPN because it is more stable and measurements of OPN in serum are less reliable.

Background: Progress in management has improved hospital mortality of patients admitted to the intensive care units, but also the prevalence of those patients needing weaning from prolonged mechanical ventilation, and of ventilator assisted individuals. The result is a number of difficult clinical and organizational problems for patients, caregivers and health services, as well as high human and financial resources consumption, despite poor long-term outcomes. An effort should be made to improve the management of these patients. This narrative review summarizes the main concepts in this field. Main body: There is great variability in terminology and definitions of prolonged mechanical ventilation. There have been several recent developments in the field of prolonged weaning: ventilatory strategies, use of protocols, early mobilisation and physiotherapy, specialised weaning units. There are few published data on discharge home rates, need of home mechanical ventilation, or long-term survival of these patients. Whether artificial nutritional support improves the outcome for these chronic critically ill patients, is unclear and controversial how these data are reported on the optimal time of initiation of parenteral vs enteral nutrition. There is no consensus on time of tracheostomy or decannulation. Despite several individualized, non-comparative and non-validated decannulation protocols exist, universally accepted protocols are lacking as well as randomised controlled trials on this critical issue. End of life decisions should result from appropriate communication among professionals, patients and surrogates and national legislations should give clear indications. Conclusion: Present medical training of clinicians and locations like traditional intensive care units do not appear enough to face the dramatic problems posed by these patients. The solutions cannot be reserved to professionals but must involve also families and all other stakeholders. Large multicentric, multinational studies on several aspects of management are needed.

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