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Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost., Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DL NO and DL CO via a single-breath (sDL NO and sDL CO )., Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDL NO , sDL CO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC)., Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV 1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDL CO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDL CO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R 2 ), RV coupled with sDL CO or Vc proved the best predictors of emphysema., Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDL NO , sDL CO and Vc do enhance the predictive power of current spirometric measures substantially. sDL NO , sDL CO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Dal Negro et al.)

Purpose: To explore the effect of erdosteine on COPD exacerbations, health-related quality of life (HRQoL), and subjectively assessed COPD severity., Patients and Methods: This post-hoc analysis of the RESTORE study included participants with COPD and spirometrically moderate (GOLD 2; post-bronchodilator forced expiratory volume in 1 second [FEV 1 ] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV 1 30‒49% predicted; n = 191) who received erdosteine 300 mg twice daily or placebo added to usual maintenance therapy for 12 months. Antibiotic and oral corticosteroid use was determined together with patient-reported HRQoL (St George's Respiratory Questionnaire, SGRQ). Patient and physician subjective COPD severity scores (scale 0‒4) were rated at baseline, 6 and 12 months. Data were analyzed using descriptive statistics for exacerbation severity, COPD severity, and treatment group. Comparisons between treatment groups used Student's t -tests or ANCOVA as appropriate., Results: Among GOLD 2 patients, 43 of 126 erdosteine-treated patients exacerbated (7 moderate-to-severe exacerbations), compared to 62 of 128 placebo-treated patients (14 moderate-to-severe exacerbations). Among those with moderate-to-severe exacerbations, erdosteine-treated patients had a shorter mean duration of corticosteroid treatment (11.4 days vs 13.3 days for placebo, P = 0.043), and fewer patients required antibiotic treatment with/without oral corticosteroids (71.4% vs 85.8% for placebo, P < 0.001). Erdosteine-treated GOLD 2 patients who exacerbated showed significant improvements from baseline in SGRQ total scores and subjective disease severity scores (patient- and physician-rated), compared with placebo-treated patients regardless of exacerbation severity. Among GOLD 3 patients, there were no significant differences between treatment groups on any of these measures., Conclusion: Adding erdosteine to the usual maintenance therapy of COPD patients with moderate airflow limitation reduced the number of exacerbations, the duration of treatment with corticosteroids and the episodes requiring treatment with antibiotics. Additionally, treatment with erdosteine improved HRQoL and patient-reported disease severity., Competing Interests: P Calverley reports personal fees from Recipharm, during the conduct of the study; personal fees from Edmond Pharma, Novartis, Phillips Respironics, and Genentech, outside the submitted work. P Rogliani participated as a lecturer and advisor in scientific meetings sponsored by Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline (GSK), Menarini Group, MSD, Mundipharma, Novartis, Edmond Pharma and Roche. Her department was funded by Almirall, Boehringer Ingelheim, Chiesi Farmaceutici, Novartis, and Zambon. J Wedzicha reports grants from AstraZeneca, personal fees from Chiesi Farmaceutici, Novartis, grants, personal fees from GSK, grants from Boehringer Ingelheim, personal fees from Gilead, grants from Genentech, outside the submitted work. A Papi reports grants from Chiesi Farmaceutici, AstraZeneca, GSK, Boehringer Ingelheim, Teva, Sanofi, personal fees from Chiesi Farmaceutici, AstraZeneca, GSK, Novartis, Sanofi, IQVIA, Avillion, Elpen Pharmaceuticals, MSD, Boehringer Ingelheim, Menarini, Zambon, Mundipharma, Teva, Edmond Pharma, outside the submitted work. M Cazzola and C Page are consultants to Edmond Pharma who manufactures and markets erdosteine. C Page reports personal fees from Edmond Pharma, during the conduct of the study; equity from Verona Pharma, personal fees from Glycos Innovation, personal fees from Eurodrug, personal fees from worldwide clinical trial, outside the submitted work; and Non Executive Director of Epiendo Pharmaceuticals. AF Cicero reported personal fees from Edmond Pharma. The authors report no other conflicts of interest in this work., (© 2022 Calverley et al.)

Background: The RESTORE study, a multi-national randomized, placebo-controlled study, showed that erdosteine - a muco-active antioxidant that modulates bacterial adhesiveness - reduced the rate and duration of exacerbations in moderate and severe COPD with a history of exacerbations. How much benefit patients with less severe disease experience when taking this drug remains unclear., Methods: This post hoc analysis of the 254 RESTORE participants with spirometrically-defined moderate COPD (post-bronchodilator forced expiratory volume in 1 second [FEV 1 ] 50‒79% predicted) examined exacerbation rate and duration, time to first exacerbation, and exacerbation-free time. Data were analyzed using descriptive statistics and comparisons between treatment groups used Wilcoxon rank-sum tests, Mann-Whitney U -tests, or log rank tests., Results: Patients with moderate COPD received erdosteine 300 mg twice daily (n=126) or placebo (n=128) added to usual COPD therapy for 12 months. During this time, there were 53 exacerbations in the erdosteine group and 74 in the placebo group, with 42.1% and 57.8% of patients, respectively, experiencing an exacerbation. There was a 47% reduction in the mean exacerbation rate with erdosteine compared to placebo (0.27 vs 0.51 exacerbations per-patient per-year, respectively, P =0.003), and a 58.3% reduction in the mild exacerbation rate (0.23 vs 0.53 mild exacerbations per-patient per-year, P =0.001). Mean duration of exacerbations was 26% shorter in erdosteine-treated patients (9.1 vs 12.3 days for placebo, P =0.022), with significant reductions in the duration of mild and moderate-to-severe exacerbations. Mean time to first exacerbation was prolonged by 7.7% (182 days for erdosteine vs 169 days for placebo, P <0.001) and the mean exacerbation-free time was increased by 51 days (279 days for erdosteine vs 228 days for placebo; P <0.001)., Conclusion: These results indicate that adding erdosteine to usual COPD maintenance therapy reduces the number of mild, and duration of all, exacerbations in patients with moderate COPD and a history of exacerbations., Competing Interests: EP is employed by Edmond Pharma. PC, CP, RDN, GF, MC, and AC report personal fees from Edmond Pharma. The authors report no other conflicts of interest in this work., (© 2019 Calverley et al.)

Purpose: Efficient management of COPD represents an international challenge. Effective management strategies within the means of limited health care budgets are urgently required. This analysis aimed to evaluate the cost-effectiveness of a home-based disease management (DM) intervention vs usual management (UM) in patients from the COPD Patient Management European Trial (COMET)., Methods: Cost-effectiveness was evaluated in 319 intention-to-treat patients over 12 months in COMET. The analysis captured unplanned all-cause hospitalization days, mortality, and quality-adjusted life expectancy. Costs were evaluated from a National Health Service perspective for France, Germany, and Spain, and in a pooled analysis, and were expressed in 2015 Euros (EUR). Quality of life was assessed using the 15D health-related quality-of-life instrument and mapped to utility scores., Results: Home-based DM was associated with improved mortality and quality-adjusted life expectancy. DM and UM were associated with equivalent direct costs (DM reduced costs by EUR -37 per patient per year) in the pooled analysis. DM was associated with lower costs in France (EUR -806 per patient per year) and Spain (EUR -51 per patient per year), but higher costs in Germany (EUR 391 per patient per year). Evaluation of cost per death avoided and cost per quality-adjusted life year (QALY) gained showed that DM was dominant (more QALYs and cost saving) in France and Spain, and cost-effective in Germany vs UM. Nonparametric bootstrapping analysis, assuming a willingness-to-pay threshold of EUR 20,000 per QALY gained, indicated that the probability of home-based DM being cost-effective vs UM was 87.7% in France, 81.5% in Spain, and 75.9% in Germany., Conclusion: Home-based DM improved clinical outcomes at equivalent cost vs UM in France and Spain, and in the pooled analysis. DM was cost-effective in Germany with an incremental cost-effectiveness ratio of EUR 2,541 per QALY gained. The COMET home-based DM intervention could represent an attractive alternative to UM for European health care payers., Competing Interests: Disclosure JB, IDZ, PC, DK, ST, JLV, RWDN, and RK were investigators in the COMET trial and have received honoraria from Air Liquide Healthcare, sponsors of the COMET trial. DG was an employee of Air Liquide Healthcare at the time when the study was conducted. SR is a director of HEVA HEOR, which received consulting fees from Air Liquide Healthcare to perform the health economic analysis described here. The authors report no other conflicts of interest in this work.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration.The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40-80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study.In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus 1.13 exacerbations·patient -1 ·year -1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient -1 ·year -1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient -1 ·year -1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation.In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Multidimensional scores were proposed for defining COPD outcomes, but without any incorporation of the economic COPD cost to clinical indices., Aim: using mortality as an outcome, the hypothesis that adding total health care cost to the BODE index would better predict mortality in COPD was investigated., Methods: 275 COPD patients were surveyed. Anthropometrics, lung function, the BODE and the Charlson Comorbidity Index were determined. History of exacerbations, ER visits, hospitalizations and mortality were also determined over the next three years, being their rates graded and added to the BODE index according to a simple algorithm. The novel PRO-BODE index ranged 0-10 points; its relationship to annual total COPD cost and survival was assessed by linear regression analysis., Results: total COD cost showed the highest relationship with survival (r = -0.58), even higher than that of age and of BODE index (r = -0.28 and r = -0.21, respectively). The integrated Pro-BODE score proved proportional to the cost of care and inversely proportional to the length of survival., Conclusions: Pro-BODE is a novel composite index which helps in predicting in real life the impact of COPD over three years, both in terms of patients' survival and of COPD economic burden., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Erdosteine (ER), a multimechanism, mucoactive agent with anti-oxidant and anti-inflammatory properties, has been shown to improve lung function, decrease plasma reactive oxygen species (ROS), and 8-isoprostane levels in patients with chronic obstructive pulmonary disease (COPD)., Aim: To assess vs. placebo the effect of ER on the exercise-induced oxidative stress by measuring and comparing the release of pro-inflammatory mediators in severe COPD patients., Methods: The double blind, placebo controlled study was carried out in 24 severe (GOLD Class III) COPD patients, aged >40 yr, randomized to receive either oral ER (600 mg/day, 8 males, mean age 70.5 yr) or placebo (9 males, mean age 70.8 yr) for 10 days. All patients performed a 6-min walking test (6MWT) before and after both treatments., Results: Mean ROS plasma levels increased significantly, but equally, in each group following the baseline 6MWT (p = ns). At the end of both treatments, a significant difference in mean plasma ROS increase from baseline became clear between the ER (+14.6% ± 2.7) and the placebo group (+24.4% ± 3.8) after the second 6MWT (p < 0.025). A similar significant trend was proved for the mean 8-isoprostane increase, which changed from baseline by +14.1% ± 2.6 in the ER, and by +26.3 ± 2.9 in the placebo group, respectively, after the second 6MWT (p < 0.006)., Conclusions: Data from the present study are suggesting that ER is effective in reducing the release of inflammatory mediators due to the exercise-induced oxidative stress in severe COPD patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with increased airway and systemic inflammation. There is evidence that erdosteine accelerates recovery from AECOPD by reducing airway inflammation., Aim: To investigate the dose-dependent antioxidant/anti-inflammatory activity of erdosteine in COPD patients., Methods: In this single-centre, double blind, double dummy study, patients with mild-to-moderate COPD (GOLD stage II-III), were randomised to receive either placebo or two dosages of oral erdosteine (300 mg tid or 300 mg bid + 1 capsule of indistinguishable placebo) for 28 days in addition to their standard treatment. Primary variables were plasma reactive oxygen species (ROS) and 8-isoprostane levels, while secondary variable was lung function (FEV1; FEV1/FVC; FEV1 short-term reversibility), all assessed in baseline; every two weeks during the study, and one week after the end of the study., Results: Baseline demographic characteristics, plasma ROS and 8-isoprostane levels and lung function were not significantly different in the 24 eligible patients (14 males, aged 38-75 years). At 2 weeks, there was a dose-dependent decrease in ROS in the erdosteine groups. By week 4 there were significant differences in ROS levels compared to baseline between patients receiving 900 mg/day (p < 0.003) and those receiving 600 mg/day (p < 0.04). This effect continued in the follow-up week (p < 0.021). Erdosteine also lowered 8-isoprostane plasma levels after 4 weeks (p < 0.01), and this effect lasted over the post-treatment week. Moreover, % FEV1 reversibility after salbutamol 400 mcg obtained after a 4 -week treatment of erdosteine 900 mg/day was significantly higher than that obtained after 600 mg/day (p < 0.01). Erdosteine was well tolerated and no treatment-related adverse event was reported., Conclusions: Results confirm the antioxidant dose- and time-dependent activity of erdosteine, and support the utility of including erdosteine it in the therapeutic strategy for the prevention and treatment of oxidative stress-induced inflammation, which frequently leads to AECOPD occurrence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) can affect cognition. The effects of other less severe chronic airway disorders on cognition remain to be clarified. This study aimed to measure and compare cognitive deterioration in subjects with COPD, subjects with chronic non-obstructive bronchitis (CNOB), and asymptomatic smokers (AS), and to relate the corresponding prevalence to several demographic and clinical variables and to normal reference values., Methods: Four hundred and two subjects (COPD n=229, CNOB n=127, and AS n=46) of comparable age were included in the study. Cognitive impairment was assessed using the Mini Mental Status test, the Clock Drawing test, and the Trail Making test A and B., Results: The extent and prevalence of cognitive deterioration was greater in COPD subjects, followed by CNOB subjects and AS (P<0.001). The Medical Research Council and COPD Assessment test scores, forced expiratory volume in the first second predicted, and arterial partial pressure of O2 and of CO2 were related to the extent and the prevalence of cognitive deterioration. COPD subjects, CNOB subjects, and AS aged 40-69 years showed the greatest cognitive impairment (P<0.01 compared to normal values). This was particularly clear in COPD subjects., Conclusion: Cognitive impairment may start at the early stages of chronic airway damage and progress with a worsening of the respiratory condition. Indeed, the greatest cognitive deterioration was seen in COPD subjects. Cognition impairment may contribute to explaining the insufficient adherence to therapeutic plans and strategies, and the increasing social costs in respiratory subjects.

Background: Most patients with chronic obstructive pulmonary disease (COPD) in Europe are treated in primary care, but perceptions on what guides primary care physicians (PCPs) in managing patients are lacking., Aims: To describe factors associated with the assessment by PCPs of COPD severity and those associated with impaired health status, as assessed by patient-reported outcomes., Methods: This cross-sectional study evaluated health-related quality of life (HRQL) in 2,294 COPD patients from five European countries. The severity of COPD was clinically judged by the PCPs and GOLD stage severity was calculated using spirometry data., Results: PCPs' categories of severity reflected a wider range of HRQL scores (St George's Respiratory Questionnaire (SGRQ) total score: mild 30.3; moderate 41.7; severe 55.0; very severe 66.1) than GOLD severity grading (Stage I 38.2; Stage II 41.1; Stage III 49.9; Stage IV 58.5). Multiple ordinal logistic regression models showed that factors most closely related to PCP-rated COPD severity were Medical Research Council (MRC) dyspnoea grade, forced expiratory volume in 1 second (FEV₁) percent predicted, HRQL score (either SGRQ or COPD Assessment Test (CAT)), and previous hospitalisations (model generalised R²=0.45 or 0.44 (SQRQ or CAT in model, respectively); all factors p<0.0001). Factors with the highest association with HRQL scores (SGRQ or CAT) were MRC dyspnoea grade, COPD severity (PCP-rated), sputum production, and number of co-morbidities (model R²=0.46 or 0.37 (SQRQ or CAT in multiple linear regression model, respectively); all factors p<0.0001)., Conclusions: PCPs successfully graded COPD severity clinically and appeared to have greater discriminative power for assessing severity in COPD than FEV₁-based staging. Their more holistic approach appeared to reflect the patients' HRQL rating and was consistent across five European countries.

Background: Pulmonary Rehabilitation ("Rehabilitation") can improve both lung function and quality of life in patients suffering from chronic obstructive pulmonary disease (COPD) even if only a very small proportion of patients have access to Rehabilitation. Supplementation of Essential Amino Acids (EAAs) might allow COPD patients to achieve some typical Rehabilitation outcomes such as a better physical performance and an improved health status., Methods: 88 COPD out-patients (GOLD class 3-4) with a body mass index (BMI) < 23 Kg/m2 were randomised to receive EAAs (n = 44) or placebo (n = 44) for twelve weeks. Primary outcome measures were changes in both physical activities in daily life (measured by Sense Wear Armband in terms of mean steps walked in one week) and in quality of life (measured by the St George's Respiratory Questionnaire, SGRQ)., Results: After 12 weeks, the physical performance was significantly increased vs baseline only in patients who received EAAs (1140.33 +/- 524.69 and 638.68 +/- 662.1 steps/day, respectively; p = 0.02), being also the comparison vs the placebo group highly significant (p = 0.003). Similarly, the SGRQ score improved significantly only in EAA patients (69.35 +/- 9.51 vs baseline 72.04 +/- 8.62; p < 0.01), and changes were significantly different from those measured in the placebo group (p < 0.001). Furthermore, when compared to those who received placebo, EAAs patients significantly increased their fat-free mass (p = 0.04), muscle strength (p < 0.01), saturation of oxygen (p = 0.05), serum albumin (p < 0.001), and also ameliorated their original cognitive dysfunction (p = 0.02)., Conclusions: Oral supplementation with EAAs contribute to improve the daily-life performance in domiciliary severe COPD patients who can not enter any Rehabilitation programme, together with their quality of life; nutritional and cognitive status, and muscle strength.

Introduction: Chronic obstructive pulmonary disease (COPD) is a disease characterized by an airflow limitation that is not fully reversible. β(2)-agonists and anticholinergics represent the most effective therapeutic options. Optoelectronic plethysmography (OEP) is a novel technology, which provides noninvasive steady-state measurements of chest wall kinematics, together with the assessment of the relative contribution of all different thoracic and abdominal compartments to tidal volume., Objectives: The aim of this pilot study was to investigate the changes in quiet breathing due to different long-acting bronchodilators (namely, formoterol and tiotropium) administered to COPD patients of different severity., Methods: Eight moderate-to-severe COPD patients were studied according to a randomized crossover design. All subjects received both the long-acting bronchodilators: formoterol (long-acting β(2)-agonist, 24 µg) and tiotropium (long-acting anticholinergic bronchodilator, 18 µg). The effect of bronchodilators on quiet breathing was evaluated by means of OEP at base conditions, and 2 and 7 hours after inhalation., Results: Both bronchodilators caused changes in the quiet breathing pattern in COPD patients that had previously reported only negligible changes in FEV(1) (ΔFEV(1) = 2.6% after salbutamol). The main changes were observed in increased ventilation per minute, inspiratory and expiratory flow, and decreased breath-by-breath variability. Formoterol induced its main effects during the first 2 hours after inhalation, while tiotropium caused improvements between 2 and 7 hours., Conclusion: Even though a greater cohort of COPD patients is needed in order to confirm the present results, this pilot study reports a novel piece of evidence concerning the effects of bronchodilators on quiet breathing pattern in severe and very severe COPD patients.

Aims: To understand the needs of people with asthma and COPD, and to identify opportunities for improved care., Methods: Quantitative questionnaire-based survey performed in five European countries on patients with asthma and COPD. Questionnaires were administered to patients using Computer Assisted Web Interview methodology., Results: 1022 patients with asthma (UK [n=190]; Germany [n=214]; France [n=200]; Italy [n=222]; Spain [n=196]) and 719 patients with COPD (UK [n=153]; Germany [n=147]; France [n=145]; Italy [n=140]; Spain [n=134]) were enrolled in the study. 32% of those with asthma and 67% of those with COPD considered that their condition had a significant effect on their quality of life, and stigma and emotional distress was common. Many expressed concern regarding potential medication side effects or that medicines might lose their effect with time. Major discrepancies between expectations and patient satisfaction with the doctor-patient relationship were observed, including a need to be consulted in the choice of inhalers. Consultations were infrequent, and 75% of respondents sought additional information beyond that received during consultations - commonly from the internet., Conclusions: Patient satisfaction was high but information needs were not addressed and the emotional burden of disease is underappreciated.

Unlabelled: Chronic obstructive pulmonary disease (COPD) is a complex and progressive respiratory disease characterized by incompletely reversible bronchial obstruction. The effects of current therapeutic options in early stages of COPD have been poorly investigated in the past, being this specific topic revamped by the results of recent secondary analyses from large international trials., Aim: To measure and monitor in real life the changes in main clinical outcomes and health care resources in patients suffering from mild-to-moderate and severe COPD treated with only tiotropium br. for twenty-four months., Methods: The population sample of the present observational retrospective study consists of 319 COPD subjects (214 males; average age 71.7 years ± 06 se) automatically extracted from the DataBase of the Health Care Institution. Inclusion criteria were: age ≥ 40 y; basal FEV1 < 80% predicted and FEV1/FVC < 70%; regular treatment with only 18 mcg tiotropium br. for the following two years. All subjects were divided into two subsets according to their FEV1 basal value: (Group A ≤ 50%, and Group B >50% predicted). Lung function; n. exacerbations; n. hospitalizations; absenteeism; n. GP's visits, and use of systemic steroids or antibiotics were checked during the observational period and mean values compared in both subsets with those of the twelve months preceding tiotropium br. (such as during other therapeutic strategies). T test was used for checking the comparability of groups, while ANOVA--Duncan test was used to compare the trends of all variables over time; p < 0.05 was accepted., Results: Group A, 154 individuals (104 males; mean age 72.1 years ± 0.51 se) had a mean FEV1 value of 45.4% pred. ± 0.61 se, while the remaining 165, Group B (111 males; mean age 71.4 years ± 0.60 se) had a mean FEV1 value of 65.5% pred. ± 5.7 se (p < 0,01). The two subsets were well matched for gender, age, and previous use of systemic steroids, but significantly different in terms of basal lung function, COPD morbidity, and antibiotic use. Basically, the impact of COPD confirmed higher in severe patients even if it was unexpectedly remarkable in mild-to-moderate individuals in terms of consumption of health care resources. The overall reduction in COPD morbidity was significant in both groups, but the improvement in FEV1 and in other main long-term outcomes observed in subjects with mild-to-moderate COPD was particularly significant and substantial (p < 0.001), these subjects confirming to be worth of earlier therapeutic attention., Conclusions: 18 mcg tiotropium br. monotherapy for twenty-four months on a regular daily basis enables a significant minimization of COPD impact, and consents the progressive lung function recovery also in mild-to-moderate individuals, thus suggesting a possible role of tiotropium br. in affecting the natural history of COPD., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A short, easy-to-use health status questionnaire is needed in the multidimensional assessment of chronic obstructive pulmonary disease (COPD) in routine practice. The performance of the eight-item COPD assessment test (CAT) was analysed in 1,817 patients from primary care in seven European countries. The CAT has a scoring range of 0-40 (high score representing poor health status). Mean CAT scores indicated significant health status impairment that was related to severity of airway obstruction, but within each Global Initiative for Obstructive Lung Disease stage (I to IV) there was a wide range of scores (I: 16.2 ± 8.8; II: 16.3 ± 7.9; III: 19.3 ± 8.2; and IV: 22.3 ± 8.7; I versus II, p = 0.88; II versus III, p<0.0001; III versus IV, p = 0.0001). CAT scores showed relatively little variability across countries (within ± 12% of the mean across all countries). Scores were significantly better in patients who were stable (17.2 ± 8.3) versus those suffering an exacerbation (21.3 ± 8.4) (p<0.0001); and in patients with no (17.3 ± 8.1) or one or two (16.6 ± 8.2) versus three or more (19.7 ± 8.5) comorbidities (p<0.0001 for both). The CAT distinguished between classes of other impairment measures and was strongly correlated with the St George's Respiratory Questionnaire (r = 0.8, p<0.0001). The CAT is a simple and easy-to-use questionnaire that distinguishes between patients of different degrees of COPD severity and appears to behave the same way across countries.

Pan-European data on health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) are lacking. This cross-sectional epidemiological study evaluated health status in 1817 COPD patients from an 'all-comers' primary care population in seven European countries (87% stable disease; 13% with current exacerbation) using: St George's Respiratory Questionnaire-COPD specific (SGRQ-C), the short form health survey (SF-12) and the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale. Mean total score for SGRQ was 44.7 ± 19.4 showing marked impairment of HRQL. Scores differed little between countries (range 39.2-50.1). Impairment was associated with the severity of airway obstruction, but within each GOLD stage the variation (SD) was wide [Stage I: 38.5 ± 19.3 (n = 223); Stage II: 40.4 ± 18.1 (n = 868); Stage III: 50.2 ± 18.6 (n = 551); Stage IV: 58.6 ± 17.7 (n = 144)]. Patients suffering an exacerbation had a worse SGRQ score (54.9 ± 19.3) than those with stable disease (43.3 ± 19.0). The presence of ≥3 co-morbidities (CM) was also associated with a significantly worse score (49.9 ± 19.1) vs. 1-2 CM (42.1 ± 19.1) or no CM (42.3 ± 18.6). Findings with the SF-12 and FACIT-F results were consistent with those from the SGRQ-C. This large observational primary care study shows that health status is significantly impaired in COPD patients of all severities, even in those with mild airway obstruction. Within each GOLD stage of severity there is considerable heterogeneity in HRQL impairment among patients. (Study number: 111749)., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Unlabelled: Oxidant-antioxidant imbalance and lipid peroxidation are known to activate the 5-LO pathway with increased expression of inflammatory eicosanoids. Erdosteine has recently shown important anti-oxidant properties, including the ability to reduce 8-isoprostane in COPD patients., Aim: To assess the effects of erdosteine (E) on eicosanoids, and to compare the time-course of effect with that of E anti-oxidant activity., Methods: 12 moderate COPD patients (9 males, 60 - 78 y) randomly received E 300 mg b.i.d. or placebo (P) for 10 days in a double-blind, controlled design. Blood ROS (Fort/Units); serum LTB4 and urine LTE4 (pg/ml) were measured at baseline and after 1, 3, 5 and 10 days of treatment. Analysis of covariance (ANCOVA) was performed., Results: In COPD patients, both LTB4 and LTE4 dropped significantly during the 10-day treatment with E: s-LTB4 from 136.0 ± 35.4 SD to 54.5 ± 31.2 SD; u-LTE4 from 267.0 ± 91.5 SD to 84.0 ± 64.7 SD, p < 0.001 vs. p from Days 5 and 3, respectively. Moreover, a significant decrease of blood ROS was confirmed in patients using E. FEV1 values slightly increased during erdosteine treatment, whereas a trend to decrease was observed in the placebo group, with a significant difference in favor of erdosteine after 10 days of treatment (p = 0.0088)., Conclusions: 1) The scavenging and anti-inflammatory effects of Erdosteine were both confirmed; 2) erdosteine proved to affect eicosanoids significantly; 3) this novel effect underlines the important anti-inflammatory potentialities of the drug in COPD; 4) further investigation is needed in order to assess the capability of Erdosteine in controlling ongoing inflammation in chronic respiratory diseases.

Aim: Aim of the study was to investigate whether or not oral supplementation of essential amino acids (EAAs) may improve body composition, muscle metabolism, physical activity, cognitive function, and health status in a population of subjects with severe chronic obstructive pulmonary disease (COPD) and sarcopenia., Methods: Thirty-two patients (25 males) (FEV1/FVC < 40% predicted), age 75 +/- 7 years, were randomised (n = 16 in both groups) to receive 4 gr/bid EAAs or placebo according to a double-blind design. When entered the study (T0), after four (T4), and after twelve (T12) weeks of treatments, body weight, fat free-mass (FFM), plasma lactate concentration (micromol/l), arterial PaCO2 and PaO2, physical activity (n degree steps/day), cognitive function (Mini Mental State Examination; MMSE), health status (St. George's Respiratory Questionnaire; SGRQ) were measured., Results: EAAs supplemented, but not patients assuming placebo, progressively improved all baseline variables overtime. In particular, at T12 of EAAs supplementation, body weight (BW) increased by 6 Kg (p = 0.002), FFM by 3.6 Kg (p = 0.05), plasma lactate decreased from 1.6 micromol/l to 1.3 micromol/l (p = 0.023), PaO2 increased by 4.6 mmHg (p = 0.01), physical activity increased by 80% (p = 0.01). Moreover, the score for cognitive dysfunction improved from 19.1 scores to 20.8 (p = 0.011), while the SRGQ score also improved from 723 to 69.6 even though this trend did not reach the statistical significance. CONCLUSIONS. A three-month EAAs supplementation may have comprehensive effects on nutritional status; muscle energy metabolism; blood oxygen tension, physical autonomy; cognitive function, and perception of health status in patients with severe COPD and secondary sarcopenia.

Background: The use of inhaled corticosteroids (ICS) and long-acting beta(2) adrenergics (LABA) in fixed combination (ICS/LABA) was recently extended to COPD patients with a baseline FEV(1) 50-60% predicted, thus broadening the original guideline indications (GOLD 2006) that limited their use only to stages III and IV., Method: The present study was carried out to assess the clinical profile of this new subset of patients, with a view to providing data for future studies on the impact of this novel extension of ICS/LABA use in COPD., Results: Data from the present observational cross-sectional study suggest that COPD patients with FEV(1) 50-60% predicted depict a dichotomic condition: actually, even though resembling milder patients in terms of frequency and severity of their respiratory symptoms, they are much more similar to severer patients in terms of rate of hospital admissions and resource consumption (p50.01). In other words, this subset of patients seems to represent a peculiar condition in the evolutional phase of COPD during which therapeutic treatment should be intensified in order to slow down the disease progression effectively. Nevertheless, independently of the severity, the general therapeutic approach to COPD was found to be greatly inadequate when compared to GOLD guidelines, particularly in terms of appropriateness., Conclusions: These findings should pave the way for future studies aimed to long-term monitoring of main outcomes and to evaluate the overall impact of earlier ICS/LABA use on disease progression and lung function decline in COPD.

Unlabelled: Anti-oxidant interventions consist in reduction of direct oxidant damage by removing oxidant agents and/or by supplementing reducing agents with anti-oxidant effects., Aim: Aim of the present study was to investigate the anti-oxidant effects of erdosteine, a recent drug currently used in chronic obstructive pulmonary disease (COPD) for its rheological activity. At present, no data are available on current smokers with COPD to our knowledge., Methods: Two groups of 10 persons matched for sex; age (65.0 yr+/-8.4 S.D. and 65.3 yr+/-6.5 S.D.); basal FEV1 (88.7% pred +/-6.8 S.D. and 85.2% pred +/-5.8 S.D.); and cigarette consumption (25.4 pack/yr+/-3.5 S.D. and 28.1 pack/yr+/-2.3 S.D.) entered a controlled, double blind, parallel groups study. They were randomized to receive erdosteine 600 mg daily or placebo for 10 days. IL-6; IL-8; TNFalpha were measured in bronchial secretions in bsln, after 4, 7, and 10 days of Erdosteine or placebo; e-NO and both ROS and 8-Isoprostane in blood were also measured at the same experimental times., Statistics: ANOVA: a t-test with Bonferroni correction; p<0.05 was accepted., Results: Blood ROS and IL-8 in bronchial secretions dropped significantly following erdosteine starting from day 4 (both p<0.01), while 8-isoprostane drop was significant only after day 10 (p<0.02), and the e-NO decrease proved evident but not significant. No significant changes were observed in the placebo group., Conclusions: Erdosteine affects substantially some pro-inflammatory cytokines specifically involved in oxidative stress in current smokers with mild COPD. Effects appeared differently time-dependent. Further long-term studies are needed to confirm these pilot data and to assess their long-term clinical relevance.

Chronic respiratory diseases affect a large number of subjects in Italy and are characterized by high socio-health costs. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and costs generated in 1 year by a population of patients with chronic obstructive pulmonary disease (COPD) in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data from COPD patients who reported spontaneously to pneumological centers participating in the study, the corresponding economic outcomes being assessed at baseline and after a 1-year survey. A total of 748 COPD patients were enrolled, of whom 561 [408 m, mean age 70.3 years (SD 9.2)] were defined as eligible by the Steering Committee. At the baseline visit, the severity of COPD (graded according to GOLD 2001 guidelines) was 24.2% mild COPD, 53.7% moderate and 16.8% severe. In the 12 months prior to enrollment, 63.8% visited a general practitioner (GP); 76.8% also consulted a national health service (NHS) specialist; 22.3% utilized Emergency Care and 33% were admitted to hospital, with a total of 5703 work days lost. At the end of the 1-year survey, the severity of COPD changed as follows: 27.5% mild COPD, 47.4% moderate and 19.4% severe. Requirement of health services dropped significantly: 57.4% visited the GP; 58.3% consulted an NHS specialist; 12.5% used Emergency Care and 18.4% were hospitalized. Compared to baseline, the mean total cost per patient decreased by 21.7% (p<0.002). In conclusion, a significant reduction in the use of health resources and thus of COPD-related costs (both direct and indirect costs) was observed during the study, likely due to a more appropriate care and management of COPD patients.

Background and Aim: Subjects with airway obstruction are strongly recommended to monitor their lung function, which is particularly variable in asthma. Unlike PEFR, other personal measurements (such as FEV1) are still difficult to perform. PIKO-1 is the first electronic device for both PEFR and FEV1 personal check, but its precision has not yet been assessed. The aim of this study was to compare PEFR and FEV1 values from PIKO-1 and from a conventional spirometer in subjects with airway obstruction., Methods: In total, 352 subjects (217 men; 47.6 +/- 19.0 years; 72.6 +/- 15.0 kg; 168.1 +/- 11.9 cm) performed sequential measurements using a PIKO-1 device and a spirometer. Wilcoxon signed-rank test and sign test were used as statistical tests., Results: Mean FEV1 values from the spirometer and PIKO-1, respectively, were 2.9 L +/- 1.1 and 3.0 L +/- 1.1, and mean PEFR values were 466.1 L/min +/- 164.5 SD and 426.3 L/min +/- 151.6 SD. PIKO-1 proved to overestimate FEV1 values by 4% (p<0.0001) and to underestimate PEFR values by 8% (p<0.000) systematically., Conclusions: The precision of both PIKO-1 measurements (such as FEV1 and PEFR) have been assessed. PEFR and FEV1 measures should be reset by two different constants. Nevertheless, PIKO-1 is a suitable and reliable device for the personal monitoring of obstructive patients in real life.

Unlabelled: Exacerbations often complicate the progressive course of chronic obstructive pulmonary disease (COPD), mainly due to infectious agents. The precise role of bacterial infections in the course and the pathogenesis of COPD has been a source of controversy for decades. Also viruses and other non-infectious causes of exacerbation play a relevant role and also contribute to persisting airway inflammation. Usually, the etiologic identification of the infective causes of COPD require considerable time and costs. The development of more rapid, reliable, and widely applicable methods to promptly define the etiology of COPD exacerbations should represent a relevant issue in devising earlier and more specific strategies for their effective therapeutic control., Aim: Of the study was to assess the predictive role of some pro-inflammatory cytokines measured in spontaneous bronchial secretions in discriminating the main infectious causes of COPD exacerbations., Methods: 124 subjects with moderate COPD (51-79 y; mean basal FEV1 = 49.6% pred. +/- 4.6 sd; FEV1 reversibility +3.9% from baseline +/- 4.8 sd after salbutamol 200 mcg) were studied during acute exacerbation. Respiratory viruses were isolated from bronchial secretions in 21 cases; common bacteria (CFU > or = 10(6)/ml) in 28 cases; Pseudomonas Aeruginosa (Ps.Ae.; CFU > or = 10(6)/ml) in 20 cases. The cytokines IL1beta, IL8, and TNFalpha (pg/ml; Immulite; Diagnostic Product Corp, Los Angeles, CA, USA), and neutrophils (% total count) were measured in bronchial secretions of all patients., Statistics: A two-stage logistic model was chosen for discriminating the different causes of COPD exacerbations (such as: non-infectious, or viral, bacterial, or due to Ps.Ae.)., Results: At the first decisional step, the two-stage logistic model proved that TNFalpha levels in bronchial secretions recognise clearly patients belonging to the Ps.Ae. group from those of all other groups (Area under ROC curve = 0.96; 95% CI = 0.91-0.99), and that, at the second decisional step, IL8 + IL10 levels discriminate patients with bacterial causes (such as all bacteria) from the non-infected ones and from those with a viral cause of exacerbation (Area under ROC curve = 0.87; 95% CI = 0.77-0.94). Neutrophil percent count did not support any contribution in discriminating the different subgroups of COPD subjects., Conclusions: When exacerbated, COPD subjects express different patterns of pro-inflammatory mediators in bronchial secretions, which appear modulated according to the etiological cause of the exacerbation. In particular, TNFalpha concentration per se enables recognition of COPD exacerbations due to Ps.Ae., while IL8 + IL1beta levels prove helpful in discriminating those to common bacteria from those to viral agents and to non-infectious causes. When present data are further confirmed, the use of a decisional rule based on cytokine measurements might be regarded as a helpful predictive tool. As measures of pro-inflammatory cytokines are low-cost, simple, and faster to perform, they could support rapid clinical decision making at the bedside regarding therapeutic strategy for COPD exacerbations, in particular when they are needed for severe COPD patients.

Unlabelled: Bronchodilator agents are central to the symptomatic management of Chronic Obstructive Pulmonary Disease (COPD), and long-acting inhaled bronchodilators are regarded as more convenient. The role of inhaled corticosteroids still remains controversial, but there is increasing evidence that they may improve FEV(1) and symptoms in the long-term., Aim: of the present small pilot study was to compare Salmeterol & Fluticasone (SM&FP) 50/250 microg bid via a single Diskus inhaler with SM 50 microg bid alone, and with placebo (P) in the treatment of moderate COPD., Methods: Eighteen moderate COPD patients (53-77 yr, mean basal FEV(1)=49.1% pred.+/-5.0 s.d.; mean FEV(1) reversibility=3.6% bsln+/-3.8 s.d.) treated with theophylline 400 mg/day and beta(2) short acting prn, were divided into three matched groups of six subjects according to a double-blind design, and treated with SM&FP 50/250 microcg, or SM 50 microcg alone, or P via Diskus inhaler bid for 52 weeks. In bsln, after 4, 12, 24, 36 and 52 weeks, FEV(1) (% pred), morning PEF (l/s), the daily symptom score, and the number of exacerbations (compared with the previous year) were considered. Statistics. t-test, anova in each treatment group, and anova among basal values and among the 52 week values were used, being p<0.05 accepted. Also changes (DeltaFEV(1)) from baseline were compared at different control times., Results: The mean number of exacerbations/yr decreased from 3.5+/-0.8 to 1.16+/-0.75 s.d. exacerbation/yr in the SM&FP group (t-test p<0.001); from 3.0+/-0.89 to 2.3+/-0.81 s.d. in the SM group (t-test p=ns); and from 3.16+/-1.16 to 4.16+/-0.75 s.d. in the P group (t-test p=ns). Patients receiving SM&FP showed the highest mean improvement in FEV(1) (+7.3%+/-3.3 s.d.) over the baseline pre-treatment value after 36 weeks of treatment (anova p<0.001), being FEV(1) unchanged after 52 weeks of treatment in SM group (+0.33%+/-2.4 s.d.) and with a substantial decrease following P (-2.6%+/-1.2 s.d.) (anova p<0.001). Morning PEF (l/min) increased in subjects treated with SM&FP (anova p<0.001), while it remained unchanged in SM and P group (in both, anova p=ns). After 52 weeks of treatment, only subjects treated with SM&FP showed a reduction of the daily symptoms score from 3.6+/-0.7 to 2.0+/-0.2 s.d. (anova p=0.008). Daily beta(2) short acting prn consumption was reduced only in SM&FP group from 4.2+/-0.81 to 2.2+/-1.2 s.d. after 52 weeks (anova p<0.001)., Conclusions: SM&FP 50/250 microcg regularly assumed in combination via a single Diskus inhaler for a 52 week period improves respiratory function (such as FEV(1), morning PEF), and and symptom score significantly in moderate COPD previously treated with theophylline, and at an higher extent than SM alone or P. The use of beta(2) short acting prn is also reduced, together with the number of exacerbations.