Vittorio Cardaci

Use of functional independence measure in rehabilitation of inpatients with respiratory failure

Most outcomes do not deeply express the degree of disability in patients with respiratory failure (RF) following inpatient pulmonary rehabilitation (IPR). The aim of our study was to evaluate the efficacy of an IPR in patients with confirmed COPD and RF using functional independence measure (FIM) that determines the degree of disability experienced by patients and the progress they make during rehabilitation. This scale includes several items: self care, mobility, locomotion, communication and social recognition. Twenty-two patients (age 70+/-2 years, PO(2) 58.18+/-7.63mmHg, PCO(2) 46.82+/-9.11mmHg) were prospectively observed and studied. IPR included respiratory and peripheral muscle training, mucus evacuation techniques, and energy conservation techniques. FIM, Medical Research Council dyspnoea scale (MRC), St. Georges Respiratory Questionnaire (SGRQ), and 6-min walking distance (6-MWD) were assessed on admission (pre) and discharge (post) from IPR. After IPR there was a statistically significant improvement (p<0.01) in all the FIM items (total score in self care, mobility, locomotion, social recognition) except for communication. Changes of MRC (pre 4.32+/-0.84; post 3.00+/-1.15, p<0.001), SGRQ (%) (pre 69.86+/-4.62; post 46.50+/-11.94, p<0.001), and 6-MWD (pre 164.54+/-98.63; post 214.32+/-97.64, p<0.001) paralleled those improvements. An inverse correlation between MRC and FIM (r=-0.5042, p=0.016) was observed. Our preliminary study has shown that the benefits of IPR in COPD with RF do not only translate in dyspnoea, exercise capacity and quality of life but also within neuromotor disabilities as assessed by FIM. Our results warrant future studies in pulmonary rehabilitation using FIM as an outcome measure.

Use of 6-min and 12-min walking test for assessing the efficacy of formoterol in COPD.

Exercise tolerance is an important outcome measure in patients with COPD, mostly because there is evidence that exercise testing is superior to other functional measurements obtained at rest in demonstrating the positive effect of a specific intervention. We assessed the effect of a 5-day treatment with formoterol 12 microg twice daily on lung function, exercise capacity and dyspnea in 22 stable COPD patients, and compared 6-MWT with 12-MWT in evaluating formoterol efficacy. All subjects entered a crossover design. They underwent 6-MWT or 12-MWT in a randomised order and soon after started the 5-day treatment. After a 3-day washout, patients who had first performed 6-MWT, underwent 12-MWT, and the contrary. Formoterol induced a progressively significant increase in pre-drug FEV1 and IC and also significant changes in these parameters 2 h after its inhalation at each test day. Moreover, it increased the walked distance by 53.6 m at the end of 6-MWT and 59.9 m at the end of 12-MWT. Formoterol also induced a significant change in Borg score for dyspnea caused by the 6-MWT when compared with the pre-treatment values, whereas it significantly changed dyspnea induced by 12-MWT only after the first dose. Our study not only strengthens the importance of walking tests as a useful tool for evaluating the impact of a bronchodilator on some COPD patient-centred outcomes, but also indicates that 6-MWT seems to be a more appropriate instrument than 12-MWT for assessing the exercise response to a bronchodilator in COPD.

Safety of inhaled corticosteroids for treating chronic obstructive pulmonary disease

Introduction: The frequent use of inhaled corticosteroids (ICSs), especially at higher doses, has been accompanied by concern about both systemic and local side effects. Patients suffering from chronic obstructive pulmonary disease (COPD) are more at risk from side effects, likely because of the use of higher doses of ICS in COPD to overcome corticosteroid unresponsiveness. Areas covered: There is considerable concern about increased incidence of pneumonia, osteoporosis and hyperglycemia in diabetic patients and cataracts. The local side effects of ICSs, such as hoarseness and pharyngeal discomfort, oral and oropharyngeal candidiasis, cough during inhalation, and a sensation of thirst, are not usually serious but are of clinical importance because they may lead to patients discontinuing therapy. Expert opinion: The possibility that ICSs induce adverse side effects should not lead us to avoid their use in patients in whom clinical evidence suggests that they may be helpful. However, clinicians should balance the potential benefits of ICSs in COPD against their potential side effects and always consider using the lowest possible dose to achieve the best possible management.

Rapid onset of bronchodilation with formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler as compared to formoterol alone in patients with COPD.

In the present study, we examined whether there is a difference in the onset of bronchodilatation between formoterol/beclomethasone 12/200 μg Modulite and formoterol/budesonide 9/320 μg Turbuhaler in patients with COPD. We enrolled 28 patients with stable COPD. Both formoterol/beclomethasone and formoterol/budesonide elicited a larger mean FEV₁-AUC₀₋₁₅min than formoterol alone, whereas there was no significant difference between their FEV₁-AUC₀₋₁₅min. Also the change in FEV₁ 15 min after inhalation of formoterol/beclomethasone combination or formoterol/budesonide combination was greater than that induced by formoterol alone. This study confirms the rapid effect of the inhaled corticosteroid component when combined with formoterol and indicates that the onset of bronchodilation of formoterol/beclomethasone Modulite and formoterol/budesonide Turbuhaler are similar and greater than formoterol alone in patients with COPD.

Farnesyltransferase Inhibitors and Human Malignant Pleural Mesothelioma: A First-Step Comparative Translational Study

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor α (TGF-α), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-α, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non–small cell lung cancer cells A459. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS-214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-α secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin.

Pulmonary rehabilitation following radical chemo-radiation in locally advanced non surgical NSCLC: Preliminary evidences

pulmonary rehabilitation (PR) has been fully included in the trategy for treatment of lung cancer [1]. Evidences from ranomised controlled trials (RCTs) are scarce and limited to the ost-surgical setting [2] but a systematic review on the topic as recently concluded that “(rehabilitative) interventions preperatively or post-cancer treatment are associated with positive enefits on exercise capacity, symptoms and some domains of RQoL” [3]. We have a long-standing interest in this approach [4–6] nd the positive results in our everyday clinical practice, based n extensive multidisciplinary cooperation, have prompted us to xplore its further application beyond the strictly “peri-surgical” etting. We have therefore offered to patients with locally advanced SCLC who are not suitable for surgical treatment an inpatient Pulonary Rehabilitation protocol (iPR), comprehensively described n [4] and summarised below. According to oncological guideines, these patients undergo concurrent chemo-radiation (CTRT) dministered with radical intent where pulmonary toxicity is one f the most important adverse effect limiting the delivered radition dose (and plausibly the overall cure rate). We report here ur preliminary findings, in a setting not matched with a control roup, on the feasibility and efficacy of this approach. Following nformed consent and communication to the local ethical comittee, according to national guidelines and regulations the iPR s routinely prescribed and performed on the basis of the pulonary functionality of patients. Following the chemo-radiation

Metabolic Disorder in Chronic Obstructive Pulmonary Disease (COPD) Patients: Towards a Personalized Approach Using Marine Drug Derivatives

Metabolic disorder has been frequently observed in chronic obstructive pulmonary disease (COPD) patients. However, the exact correlation between obesity, which is a complex metabolic disorder, and COPD remains controversial. The current study summarizes a variety of drugs from marine sources that have anti-obesity effects and proposed potential mechanisms by which lung function can be modulated with the anti-obesity activity. Considering the similar mechanism, such as inflammation, shared between obesity and COPD, the study suggests that marine derivatives that act on the adipose tissues to reduce inflammation may provide beneficial therapeutic effects in COPD subjects with high body mass index (BMI).

Chronic obstructive pulmonary disease (COPD) and erectile dysfunction (ED): Results of the BRED observational study

Most patients with chronic obstructive pulmonary disease (COPD) share many risk factors and similar aetiological agents with erectile dysfunction (ED). Both conditions also cause serious interference with quality of life and sexual relationships. In general, ageing and chronic illness decrease sexual interest, sexual function, and testosterone levels. This observational study included 66 male patients referred to our centre with different grades of COPD. We studied the different correlations between COPD and ED. The data collected from each patient regarded the following features: demographic and social condition; smoking status; clinical status; spirometric measurements. In this group, COPD was diagnosed in 78.8% and ED was present in 83.3% with increased severity in presence of LUTS and nicotinism.

Cognitive Impairment in Chronic Obstructive Pulmonary Disease (COPD): Possible Utility of Marine Bioactive Compounds

Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and is associated with COPD severity and comorbidities. Cognitive impairment in COPD enhances the assistance requirement in different aspects of daily living, treatment adherence, and effectual self-management.This review describes various bioactive compounds of natural marine sources that modulate different targets shared by both COPD and cognitive impairment and hypothesizes a possible link between these two syndromes.

Flavonoids and Reduction of Cardiovascular Disease (CVD) in Chronic Obstructive Pulmonary Disease (COPD)

BACKGROUND Chronic obstructive pulmonary disease (COPD) and cardiovascular diseases (CV) often coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it is hypothesizable that treatment of cardiovascular co-morbidities may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight secondary metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point to an important effects on CVD risk prevention. OBJECTIVE This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk. CONCLUSIONS Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD.