Franco Pasqua

Change in asthma and COPD prescribing by Italian general practitioners between 2006 and 2008.

AIMS To explore the trend in prescribing of drugs classified within the R03 therapeutic pharmacological subgroup (drugs for obstructive airway diseases) of the Anatomical Therapeutic Chemical (ATC) classification. METHODS Comparison of GP-collected data on physician-patient contacts and drug prescriptions for asthma and COPD in 2006 and 2008. RESULTS Compared to 2006, in 2008 patients with COPD were prescribed more long-acting bronchodilators; use of tiotropium increased, whilst use of long-acting β2-agonists (LABAs) and short-acting antimuscarinic agents decreased. However, 55.9% of patients in 2006, and 47.8% in 2008, received an inhaled corticosteroid (ICS), mainly as a LABA/ICS fixed combination inhaler. Compared to 2006, in 2008 there were increased prescriptions of LABA/ICS fixed combination inhalers for asthma, but only 54.5% of all prescriptions included an ICS. This could explain the large use of short-acting β2-agonists, a marker of poor asthma control. Remarkably, LABA/ICS fixed combination inhalers were prescribed more frequently in COPD than in asthma. CONCLUSIONS Our data indicate that adherence to guidelines is still low. Patients with asthma and COPD are undertreated by Italian GPs, with a trend to a change in COPD prescribing likely driven by new scientific information.

A systems medicine clinical platform for understanding and managing non- communicable diseases

Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.

Combining triple therapy and pulmonary rehabilitation in patients with advanced COPD: A pilot study

BACKGROUND The synergistic interactions between pharmacotherapy and pulmonary rehabilitation has been provided, but it remains to be established whether this may also apply to more severe patients. OBJECTIVES We have examined whether tiotropium enhances the effects of exercise training in patients with advanced COPD (FEV(1)</=60% predicted, hypoxemia at rest corrected with oxygen supplementation, and limitations of physical activity). METHODS We enrolled 22 patients that were randomised to tiotropium 18mug or placebo inhalation capsules taken once daily. Both groups (11 patients in each group) underwent an in patient pulmonary rehabilitation program and were under regular treatment with salmeterol/fluticasone twice daily. Each rehabilitation session was held 5 days per week (3h/day) for a total of 4 weeks. RESULTS Compared to placebo, tiotropium had larger impact on pulmonary function (FEV(1)+0.164L, FVC +0.112L, RV -0.544L after tiotropium, FEV(1)+0.084L, FVC -0.039L, RV -0.036L after placebo). The addition of tiotropium allowed a longer distance walked in 6min (82.3m vs. 67.7m after placebo) and reduced dyspnoea (Borg score) (-0.4 vs. +0.18 after placebo) when compared with baseline (pre pulmonary rehabilitation program). The changes in SGRQ from baseline to the end of treatment were: total score -28.3U, activity -27.8U, impact -14.5U, and symptoms -33.4U in the placebo group; and total score -19.1U, activity -18.9U, impact -16.4U, and symptoms -33.8U in the tiotropium group. CONCLUSIONS Our study clearly indicates that there is an advantage in combining pulmonary rehabilitation with an aggressive drug therapy in more severe patients.

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.

Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery

OBJECTIVE We have analyzed short- and long-term variations of pulmonary function in locally advanced non-small cell lung cancer after induction chemoradiotherapy. METHODS Twenty-seven patients with stage IIIA (N2) non-small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. RESULTS A 22.80% decrease of diffusing capacity of the lung for carbon monoxide (P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, -20.50% (P < .001); forced vital capacity, -22.50% (P < .001); forced expiratory volume in 1 second, -23.00% (P < .001); peak expiratory flow, -29.0 (P < .001); forced expiratory flow 25% to 75%, -13.7% (P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% (P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase (P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. CONCLUSIONS An impairment of respiratory function is evident in the immediate postoperative setting in patients with non-small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only.

COPD: maximization of bronchodilation.

The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient’s functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.

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.

A prospective multicentric study of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease and different clinical phenotypes.

Background: Recently, it has been proposed that different clinical phenotypes can be recognized in patients with chronic obstructive disease (COPD), namely predominant airway disease or parenchymal destructive changes. Objectives: The aim of this prospective multicenter study was to evaluate whether these two phenotypes may influence outcomes following a pulmonary rehabilitation program (PRP). Methods: We have prospectively evaluated 364 consecutive COPD patients (70 ± 8 years, 76.3% males) admitted to a standard hospital-based PRP in 6 Italian centers. According to their phenotype, the study cohort was divided into two groups: patients with airway obstructive (group 1, n = 208) or parenchymal destructive COPD (group 2, n = 156). Before and after PRP, values of 6-min walking distance, perceived breathlessness (Medical Research Council), health-related quality of life (St. Georges Respiratory Questionnaire) and respiratory muscle function (maximal inspiratory and expiratory pressure) were recorded. Results: PRP resulted in significant improvements in all outcome measures without any significant differences between groups. Conclusions: Our study confirms that COPD patients may benefit from pulmonary rehabilitation independent of their clinical phenotype.

BODE index and pulmonary rehabilitation in chronic respiratory failure.

To the Editors: We read with interest the article by Cote and Celli 1 regarding the beneficial effects induced by pulmonary rehabilitation (PR) on the BODE (body mass index (BMI), degree of airway obstruction, dyspnoea, exercise capacity) index (BI) in patients with chronic obstructive pulmonary disease (COPD). In an observational study, Cote and Celli 1 showed that the response to outpatient PR can be objectively measured using the BI, whose change provides information regarding ultimate survival, and that participation in a PR is associated with a decrease in the number of hospitalisations. This multidimensional 10-point scale has been previously shown to predict the death risk in COPD patients 2 …