Search

Roberto W Dal Negro,1 Paola Turco,1 Massimiliano Povero2 1National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology - CESFAR, Verona, Italy; 2AdRes Health Economics and Outcomes Research, Turin, ItalyCorrespondence: Massimiliano Povero, Email m.povero@adreshe.comBackground: 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 DLNO and DLCO via a single-breath (sDLNO and sDLCO).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 sDLNO, sDLCO 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”. FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO 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 R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema.Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO 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.Keywords: COPD, parenchymal destruction, emphysema, lung capillary blood volume, simultaneous single-breath NO and CO diffusing capacity, precision medicine

Peter MA Calverley,1 Alberto Papi,2 Clive Page,3 Paola Rogliani,4 Roberto W Dal Negro,5 Mario Cazzola,4 Arrigo F Cicero,6 Jadwiga A Wedzicha7 1Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK; 2Respiratory Medicine, University of Ferrara, Ferrara, Italy; 3Sackler Institute of Pulmonary Pharmacology, Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King’s College, London, UK; 4Respiratory Medicine Unit, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy; 5National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 6Medical and Surgical Department, University of Bologna, Bologna, Italy; 7Respiratory Division, National Heart and Lung Institute, Imperial College London, London, UKCorrespondence: Peter MA Calverley, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK, Tel +44 1515295886, Fax +44 1515295888, Email pmacal@liverpool.ac.ukPurpose: 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 [FEV1] 50‒79% predicted; n = 254), or severe airflow limitation (GOLD 3; post-bronchodilator FEV1 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.Keywords: antibiotic, chronic obstructive pulmonary disease, erdosteine, COPD exacerbation, health-related quality of life, systemic corticosteroid

Calverley PMA, Papi A, Page C, et al. 2022;17:1909–1920. The authors wish to correct Figure 1 on page 1912 after it came to their attention an error had been made in the second box of the last row (moderate-to-severe exacerbations), the correct number is 7 not 36. The corrected Figure 1 is shown below: The authors affirm that this error does not affect the results, discussion, and conclusions of the reported study and apologize for any inconvenience caused to the readers.

Peter MA Calverley,1 Clive Page,2 Roberto W Dal Negro,3 Giovanni Fontana,4 Mario Cazzola,5 Arrigo F Cicero,6 Edoardo Pozzi7,†, Jadwiga A Wedzicha8 1Department of Medicine, Clinical Sciences Centre, University Hospital Aintree, Liverpool, UK; 2Faculty of Life Sciences and Medicine, King’s College, London, UK; 3Lung Unit, National Centre for Respiratory Pharmacoeconomics and Pharmacoepidemiology, Verona, Italy; 4Pulmonology Department, Cough Centre, Careggi University Hospital, Firenze, Italy; 5Department of Systems Medicine, Chair of Respiratory Medicine, University of Rome ‘Tor Vergata’, Rome, Italy; 6Medical and Surgical Department, University of Bologna, Bologna, Italy; 7Medical Affairs Department, Edmond Pharma, Paderno, Italy; 8Respiratory Division, National Heart And Lung Institute, Imperial College London, London, UK†Dr Pozzii passed away on 9th July, 2019Correspondence: Peter MA CalverleyDepartment of Medicine, University Hospital Aintree, Lower Lane, Liverpool, Merseyside, UKTel +44 1515295886Fax +44 1515295888Email pmacal@liverpool.ac.ukBackground: 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 [FEV1] 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

Jean Bourbeau,1 Denis Granados,2 Stéphane Roze,3 Isabelle Durand-Zaleski,4 Pere Casan,5 Dieter Köhler,6 Silvia Tognella,7 Jose Luis Viejo,8 Roberto W Dal Negro,9 Romain Kessler10 1Department of Medicine, Division of Experimental Medicine, Respiratory Epidemiology and Clinical Research Unit, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 2Medical R&D – Real World & Clinical Evidence, Air Liquide Santé International, Gentilly, France; 3Department of Health Economics, HEVA HEOR, Lyon, France; 4URCEco Ile de France Hôpital de l’Hotel Dieu, Paris, France; 5Department of Pneumology, Asturias University Hospital, Oviedo, Spain; 6Department of Internal Medicine, Kloster Grafschaft Specialised Hospital, Schmallenberg, Germany; 7Department of Pneumology, Bussolengo General Hospital, Bussolengo, Italy; 8Department of Pneumology, Burgos University Hospital, Burgos, Spain; 9Department of Pneumology, Bussolengo Hospital, Bussolengo, Italy; 10Department of Pneumology, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France 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. Keywords: cost-effectiveness, France, Spain, Germany, home-based disease management, COPD

Roberto W Dal Negro,1 Luca Bonadiman,1 Silvia Tognella,2 Fernanda P Bricolo,3 Paola Turco31National Center for Respiratory Pharmacoeconomics and Pharmacoepidemiology (CESFAR), Verona, Italy; 2Lung Division, Bussolengo General Hospital, Bussolengo, Italy; 3Research and Clinical Governance, Verona, Italy 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