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1. Asthma severity: the patient’s point of view

Author

Gabriella Guarnieri, Bianca Olivieri, Manuela Latorre, Angela Rizzi, Francesco Blasi, Giorgio Walter Canonica, Enrico Heffler, Pierluigi Paggiaro, Gianenrico Senna, and Marco Caminati

Subjects
Severe asthma, mild asthma, oral corticosteroids, patient’s perspective, self reporting severity, Diseases of the respiratory system, RC705-779
Abstract

Objective Initiated by the Severe Asthma Network Italy (SANI), this study aims to explore asthma patients’ perceptions of disease severity, differentiating between mild and severe asthma. The objective is to identify factors influencing tailored treatment strategies for varying disease severities and to provide insights into asthma care in Italy.Methods Conducted between November 2020 and January 2021, a survey using Computer-Assisted Personal Interviewing (CAPI) collected data from 308 Italian adults, representing the population. A 25 item multiple choice questionnaire covered asthma diagnosis, symptoms, treatment approaches, associated conditions, and quality of life.Results Among participants, 83.8% reported having mild asthma, while 16.2% had severe asthma. Severe asthma patients had longer disease durations, more severe symptoms, frequent exacerbations, and higher hospital/ER visits. Although treatment adherence and symptom profiles generally aligned with international guidelines for self reported severe asthma, 22% of self identified mild asthmatics experienced severe respiratory symptoms. Oral corticosteroid (OCS) use was observed in 50% of severe cases and 22% of mild cases. Adherence was higher in severe asthma patients (76%) versus mild asthma patients (28%). Both groups experienced comorbidities, with 96% of severe asthmatics and 72% of mild asthmatics reporting impaired quality of life.Conclusion This study highlights the disparity between clinical categorization and patient perceptions of asthma severity. The prevalence of self reported severe asthma exceeds literature data. The burden of mild asthma remains significant, with treatment approaches not fully aligned, particularly regarding disproportionate OCS use. Addressing this gap requires enhancing patient education, improving diagnostic practices, and promoting adherence.

Published
2024
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2. Profiling severe asthma: Any relevance for age? An analysis from Severe Asthma Network Italy (SANI) cohort

Author

Marco Caminati, MD, Alessandro Marcon, PhD, Rachele Vaia, MD, Gianenrico Senna, MD, Matteo Maule, MD, Pierpaolo Marchetti, MD, Jessica Miotti, MD, Giuseppe Argentino, MD, Francesco Blasi, MD, PhD, Giorgio W. Canonica, MD, Enrico M. Heffler, MD, PhD, Pierluigi Paggiaro, MD, Andrea Vianello, MD, PhD, Gabriella Guarnieri, MD, Luisa Brussino, MD PhD, S.S.D.D.U, Cecilia Calabrese, MD PhD, Gianna Camiciottoli, MD, Giovanna E. Carpagnano, MD PhD, Stefano Centanni, MD PhD, Angelo G. Corsico, MD PhD, Maria T. Costantino, MD, Claudia Crimi, MD PhD, Alice D'adda, MD, Simona D'alo, MD, Maria D'amato, MD PhD, Stefano Del Giacco, MD, Fabiano Di Marco, MD PhD, Nicola C. Facciolongo, MD, Manuela Latorre, MD PhD, Eustachio Nettis, MD, Eleonora Nucera, MD, Giovanni Passalacqua, MD, Girolamo Pelaia, MD, Laura Pini, MD PhD, Luisa Ricciardi, MD, Luca Richeldi, MD, Erminia Ridolo, MD PhD, Pierachille Santus, MD PhD, Nicola Scichilone, MD, Giulia Scioscia, MD PhD, Giuseppe Spadaro, MD, Antonio Spanevello, MD PhD, and Paolo Tarsia, MD PhD

Subjects
Severe asthma, Aging, Comorbidities, Lung function, Asthma control, Immunologic diseases. Allergy, RC581-607
Abstract

Background: Aging implies changes in terms of lung function, immune system, and respiratory and extra-respiratory comorbidities. Few studies have specifically addressed the relevance of age on severe asthma burden and control. We aimed to evaluate whether age acts as an independent determinant of asthma severity, in terms of clinical, functional, and inflammatory profile, and to explore potential cofactors that contribute to a more difficult disease control in different age groups. Methods: Patients from Severe Asthma Network Italy (SANI) registry were retrospectively divided in subgroups according to their age. Cutoffs for age were established according to quartiles in order to obtain a comparable number of patients for each group, and then rounded for the sake of simplicity. Results: Overall, 1805 severe asthma patients were analyzed. Lung function represented the most important age-related variable. On the opposite the level of asthma control was not differently distributed among age ranges. In young people the presence of atopy-related comorbidities (allergic rhinitis, atopic dermatitis) predominated, whilst systemic-metabolic and degenerative comorbidities such as diabetes, cardiovascular diseases, anxious-depressive syndrome, and osteoporosis prevailed in elderly. Bronchiectasis and sleep disturbances were significantly associated with age. Conclusions: Despite that it cannot be considered a treatable trait, our study suggests that age should be evaluated within a personalized approach to severe asthma patients, in order to provide a better clinical profiling and a more tailored treatment strategy.

Published
2024
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4. Symptom exacerbation control: an evolution in GINA guidelines?

Author

Manuela Latorre, Riccardo Pistelli, Giovanna Elisiana Carpagnano, Alessandro Celi, Ilaria Puxeddu, Nicola Scichilone, Antonio Spanevello, Giorgio Walter Canonica, and Pierluigi Paggiaro

Subjects
Diseases of the respiratory system, RC705-779
Abstract

The article traces the concept of asthma control within GINA guidelines over the past 25 years. In the first 15 years after 1995, the main objective of asthma management was to obtain the control of all clinical and functional characteristics of asthma. A landmark study (GOAL) showed for the first time that a good control of asthma is a reasonable outcome that can be achieved in a large proportion of asthmatics with a regular appropriate treatment. In the following years, more emphasis was placed on the role of exacerbations as critical manifestations of poor asthma control, whose frequency is associated with excessive FEV1 decline and increased risk of death. Accordingly, the 2014 GINA report makes a clear distinction between the control of the day-by-day symptoms and the reduction in the risk of severe exacerbations, stating that both conditions should be obtained. The 2019 update included a significant change in the management of mild asthma, prioritizing the prevention of exacerbations to that of mild symptoms. This view was repeated in the 2021 update, where the prevention of exacerbations, together with an acceptable symptom control with a minimal use of rescue medication, appeared to be the real main goal of asthma management. While a discrepancy between current symptoms and exacerbations may be present in mild asthma, a significant relationship between these two features is observed in moderate-severe asthma: a persistent poor symptom control is a major risk factor for exacerbations, whereas achieving symptom control through regular treatment is associated with a reduction in exacerbation rate. Thus, the opinion that frequent symptoms are not important in the absence of acute exacerbations should be discouraged, whereas education of patients to a good symptom perception and to improve adherence to regular treatment should be implemented. Furthermore, the persistence of risk factors, such as increased airway inflammation, even in a patient with minor daily symptoms, should be considered for optimizing treatment.

Published
2023
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5. Long-Term Efficacy of Mepolizumab at 3 Years in Patients with Severe Asthma: Comparison with Clinical Trials and Super Responders

Author

Diego Bagnasco, Stefania Nicola, Elisa Testino, Luisa Brussino, Laura Pini, Marco Caminati, Federica Piccardo, Rikki Frank Canevari, Laura Melissari, Alessandro Ioppi, Luca Guastini, Carlo Lombardi, Manlio Milanese, Francesca Losa, Michela Robbiano, Laura De Ferrari, Anna Maria Riccio, Giuseppe Guida, Marco Bonavia, Donatella Fini, Francesco Balbi, Cristiano Caruso, Pierluigi Paggiaro, Francesco Blasi, Enrico Heffler, Giovanni Paoletti, Giorgio Walter Canonica, Gianenrico Senna, Giovanni Passalacqua, and on behalf of SANI

Subjects
severe asthma, eosinophils, mepolizumab, CRSwNP, IL-5, real life, Biology (General), QH301-705.5
Abstract

The efficacy mepolizumab in severe asthmatic patients is proven in the literature. Primarily to study the effect of mepolizumab on exacerbations, steroid dependence, and the continuation of efficacy in the long term. Secondarily to evaluate the effect of the drug on nasal polyps. Analyzing data from SANI (Severe Asthma Network Italy) clinics, we observed severe asthmatic patients treated with mepolizumab 100 mg/4 weeks, for a period of 3 years. 157 patients were observed. Exacerbations were reduced from the first year (−84.6%) and progressively to 90 and 95% in the second and third ones. Steroid-dependent patients decreased from 54% to 21% and subsequently to 11% in the second year and 6% in the third year. Patients with concomitant nasal polyps, assessed by SNOT-22, showed a 49% reduction in value from baseline to the third year. The study demonstrated the long-term efficacy of mepolizumab in a real-life setting.

Published
2023
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6. Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

Author

Giorgio Walter Canonica, Francesco Blasi, Nunzio Crimi, Pierluigi Paggiaro, Alberto Papi, Francesca Fanelli, Annalisa Stassaldi, and Gianluca Furneri

Subjects
Type 2 asthma, Dupilumab, Biomarkers, Italy, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.

Published
2021
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7. Severe asthma: One disease and multiple definitions

Author

Diego Bagnasco, MD, PhD, Pierluigi Paggiaro, MD, Manuela Latorre, MD, Chiara Folli, BS, Elisa Testino, MD, Arianna Bassi, MD, Manlio Milanese, MD, Enrico Heffler, MD, Andrea Manfredi, Anna Maria Riccio, BS, Laura De Ferrari, BS, Francesco Blasi, Rikki Frank Canevari, MD, Giorgio Walter Canonica, MD, Giovanni Passalacqua, MD, Gabriella Guarnieri, Vincenzo Patella, Foschino Barbaro Maria Pia, Giovanna Elisiana Carpagnano, Anna del Colle, Giulia Scioscia, Pelaia Gerolamo, Francesca Puggioni, Francesca Racca, Elisabetta Favero, Sandra Iannacone, Eleonora Savi, Marcello Montagni, Gianna Camiciottoli, Chiara Allegrini, Carlo Lombardi, Giuseppe Spadaro, Caterina Detoraki, Francesco Menzella, Carla Galeone, Patrizia Ruggiero, Monna Rita Yacoub, Alvise Berti, Nicola Scichilone, Carmen Durante, Maria Teresa Costantino, Chiara Roncallo, Mariachiara Braschi, Alice D’Adda, Erminia Ridolo, Massimo Triggiani, Roberta Parente, D’Amato Maria, Maria Vittoria Verrillo, Giovanni Rolla, Luisa Brussino, Agata Valentina Frazzetto, Zappa Maria Cristina, Marianna Lilli, Nunzio Crimi, Marco Bonavia, Angelo Guido Corsico, Amelia Grosso, Stefano Del Giacco, Margherita Deidda, Luisa Ricciardi, Stefania Isola, Francesca Cicero, Giuliana Amato, Federica Vita, Antonio Spanevello, Patrizia Pignatti, Francesca Cherubino, Dina Visca, Fabio Luigi Massimo Ricciardolo, Vitina Maria Anna Carriero, Francesca Bertolini, Pierachille Santus, Roberta Barlassina, Andrea Airoldi, Giuseppe Guida, Nucera Eleonora, Arianna Aruanno, Angela Rizzi, Cristiano Caruso, Stefania Colantuono, Gianenrico Senna, Marco Caminati, Alessandra Arcolaci, Andrea Vianello, Fulvia Chieco Bianchi, Maria Rita Marchi, Stefano Centanni, Simone Luraschi, Silvia Ruggeri, Rocco Rinaldo, Elena Parazzini, Cecilia Calabrese, Martina Flora, Lorenzo Cosmi, Linda Di Pietro, Enrico Maggi, Laura Pini, Luigi Macchia, Danilo Di Bona, Luca Richeldi, Carola Condoluci, Leonello Fuso, Matteo Bonini, Alessandro Farsi, Giulia Carli, Paolo Montuschi, Giuseppe Santini, Maria Elisabetta Conte, Elisa Turchet, Carlo Barbetta, Francesco Mazza, Simona D’Alo, Stefano Pucci, Maria Filomena Caiaffa, Elena Minenna, Luciana D'Elia, Carlo Pasculli, Vittorio Viviano, Paolo Tarsia, Joyce Rolo, Mariacarmela Di Proietto, and Salvatore Lo Cicero

Subjects
Severe asthma, Classification, Definition, Biological treatment, Immunologic diseases. Allergy, RC581-607
Abstract

Introduction: There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods: Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results: 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions: The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Published
2021
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8. Manifesto on the overuse of SABA in the management of asthma: new approaches and new strategies

Author

Giorgio Walter Canonica, Pierluigi Paggiaro, Francesco Blasi, Antonino Musarra, Luca Richeldi, Andrea Rossi, and Alberto Papi

Subjects
Diseases of the respiratory system, RC705-779
Abstract

The risks of overusing short-acting β 2 -agonists (SABA), including an increase in asthma-related deaths, are many and well known. The Global Initiative on Asthma (GINA) 2019 and 2020 updates recommend as-needed inhaled corticosteroid (ICS)/formoterol as the preferred rescue medication in mild asthma as monotherapy and also in moderate to severe asthma when the maintenance and reliever therapy (MART) strategy is used. Using SABA for symptom relief, however, was the standard of treatment for many years, and consequently this practice persists, particularly in patients not taking ICS regularly. Here, we examine the rationale for this shift from a long-standing recommendation for as-needed SABA treatment to the use of as-needed ICS/formoterol and consider clinical evidence on strategies for asthma treatment and patient management.

Published
2021
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9. Comorbidities are associated with different features of severe asthma

Author

Federica Novelli, Elena Bacci, Manuela Latorre, Veronica Seccia, Maria Laura Bartoli, Silvana Cianchetti, Federico Lorenzo Dente, Antonella Di Franco, Alessandro Celi, and Pierluigi Paggiaro

Subjects
Severe asthma, Comorbidities, Asthma control, Sputum eosinophils, Nasal polyps, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background According to ATS/ERS document on severe asthma (SA), the management of these patients requires the identification and proper treatment of comorbidities, which can influence the control of asthma. Methods The aim of this study was to assess the independent effect of different comorbidities on clinical, functional and biologic features of SA. Seventy-two patients with SA according to GINA guidelines were examined. We collected demographic data, smoking habit, asthma history, and assessment of comorbidities. Pulmonary function, inflammatory biomarkers, upper airway disease evaluation, asthma control and quality of life were carefully assessed. Results The mean age of patients was 59.1 years (65.3% female, 5.6% current smokers). Comorbidities with higher prevalence were: chronic rhinosinusitis with or without nasal polyps (CRSwNP or CRSsNP), obesity and gastro-esophageal reflux (GERD), with some overlapping among them. In an univariate analysis comparing patients with single comorbidities with the other ones, asthmatics with CRSwNP had lower lung function and higher sputum eosinophilia; obese asthmatics had worse asthma control and quality of life, and tended to have lower sputum eosinophils; asthmatics with GERD showed worse quality of life. In multivariate analysis, obesity was the only independent factor associated with poor asthma control (OR 4.9), while CRSwNP was the only independent factor associated with airway eosinophilia (OR 16.2). Lower lung function was associated with the male gender and longer duration of asthma (OR 3.9 and 5.1, respectively) and showed a trend for the association with nasal polyps (OR 2.9, p = 0.06). Conclusion Our study suggests that coexisting comorbidities are associated with different features of SA.

Published
2018
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10. Chronic obstructive pulmonary disease: moving from symptom relief to mortality reduction

Author

Alessandro Celi, Manuela Latorre, Pierluigi Paggiaro, and Riccardo Pistelli

Subjects
Therapeutics. Pharmacology, RM1-950
Abstract

Chronic obstructive pulmonary disease (COPD) has a 3-year mortality rate up to 37%, 2–6 times higher than the general population. We present evidence supporting pharmacological therapies to improve patient life expectancy, focusing on inhaled corticosteroids (ICSs) combined with long-acting bronchodilators (LABDs). A reduction in 3-year all-cause mortality (ACM) has been shown in patients with severe COPD treated with fluticasone propionate (an ICS) and salmeterol [long-acting beta-agonist (LABA)], compared with placebo. An observational study of elderly patients with severe COPD and multiple comorbidities suggested ICS+LABD reduce ACM compared with LABD monotherapy. Patients with symptomatic COPD at risk of exacerbations saw a mortality benefit with the ICS/long-acting muscarinic antagonist (LAMA)/LABA combinations fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR) versus UMEC/VI or GLY/FOR (LAMA/LABA combinations) in the IMPACT and ETHOS trials, respectively. Reduced risk of mortality may be due to modulation of airway inflammation, thereby reducing activation of proinflammatory mediators in the peripheral circulation. Importantly, estimated annual risk reduction for ACM with ICS/LAMA/LABA combinations in patients with COPD is of the same order of magnitude as for statins (patients with coronary disease) and angiotensin-converting enzyme inhibitors (patients with vascular disease). Based on the current data, the pharmacological treatment of COPD appears not only able to improve symptoms and reduce the frequency of exacerbations but is also very promising in improving patient prognosis in the long term.

Published
2021
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11. Economic impact of mepolizumab in uncontrolled severe eosinophilic asthma, in real life

Author

Diego Bagnasco, Massimiliano Povero, Lorenzo Pradelli, Luisa Brussino, Giovanni Rolla, Marco Caminati, Francesco Menzella, Enrico Heffler, Giorgio Walter Canonica, Pierluigi Paggiaro, Gianenrico Senna, Manlio Milanese, Carlo Lombardi, Caterina Bucca, Andrea Manfredi, Rikki Frank Canevari, Giovanni Passalacqua, Gabriella Guarnieri, Vincenzo Patella, Foschino Barbaro Maria Pia, Elisiana Carpagnano, Anna del Colle, Giulia Scioscia, Pelaia Gerolamo, Manuela Latorre, Francesca Puggioni, Francesca Racca, Elisabetta Favero, Sandra Iannacone, Eleonora Savi, Marcello Montagni, Gianna Camiciottoli, Chiara Allegrini, Giuseppe Spadaro, Caterina Detoraki, Carla Galeone, Patrizia Ruggiero, Monna Rita Yacoub, Alvise Berti, Gisella Colombo, Nicola Scichilone, Carmen Durante, Maria Teresa Costantino, Chiara Roncallo, Mariachiara Braschi, Francesco Blasi, Alice D'Adda, Erminia Ridolo, Massimo Triggiani, Roberta Parente, D'Amato Maria, Maria Vittoria Verrillo, Zappa Maria Cristina, Marianna Lilli, Nunzio Crimi, Marco Bonavia, Angelo Guido Corsico, Amelia Grosso, Stefano Del Giacco, Margherita Deidda, Luisa Ricciardi, Stefania Isola, Francesca Cicero, Giuliana Amato, Federica Vita, Antonio Spanevello, Patrizia Pignatti, Francesca Cherubino, Dina Visca, Eleonora Aletti, Fabio Luigi Massimo Ricciardolo, Vitina Maria Anna Carriero, Francesca Bertolini, Pierachille Santus, Roberta Barlassina, Andrea Airoldi, Giuseppe Guida, Nucera Eleonora, Arianna Aruanno, Angela Rizzi, Cristiano Caruso, Stefania Colantuono, Alessandra Arcolaci, Andrea Vianello, Fulvia Chieco Bianchi, Maria Rita Marchi, Stefano Centanni, Simone Luraschi, Silvia Ruggeri, Rocco Rinaldo, Elena Parazzini, Cecilia Calabrese, Martina Flora, Lorenzo Cosmi, Linda Di Pietro, Enrico Maggi, Laura Pini, Luigi Macchia, Danilo Di Bona, Luca Richeldi, Carola Condoluci, Leonello Fuso, Matteo Bonini, Alessandro Farsi, Giulia Carli, Paolo Montuschi, Giuseppe Santini, Maria Elisabetta Conte, Elisa Turchet, Carlo Barbetta, Francesco Mazza, Simona D'Alo, Stefano Pucci, Maria Filomena Caiaffa, Elena Minenna, Luciana D'Elia, Carlo Pasculli, Vittorio Viviano, Paolo Tarsia, Joyce Rolo, Mariacarmela Di Proietto, and Salvatore Lo Cicero

Subjects
Severe asthma, Mepolizumab, Anti IL-5, Pharmacoeconomics, OCS, Comorbidities, Immunologic diseases. Allergy, RC581-607
Abstract

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Published
2021
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12. Upper and lower airway inflammation in severe asthmatics: a guide for a precision biologic treatment

Author

Manuela Latorre, Elena Bacci, Veronica Seccia, Maria Laura Bartoli, Cristina Cardini, Silvana Cianchetti, Ludovica Cristofani, Antonella Di Franco, Mario Miccoli, Ilaria Puxeddu, Alessandro Celi, and Pierluigi Paggiaro

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Background and aims: Severe asthma may require the prescription of one of the biologic drugs currently available, using surrogate markers of airway inflammation (serum IgE levels and allergic sensitization for anti-IgE, or blood eosinophils for anti-IL5/IL5R). Our objective: to assess upper and lower airway inflammation in severe asthmatics divided according to the eligibility criteria for one of the target biologic treatments. Methods: We selected 91 severe asthmatics, uncontrolled despite high-dose ICS-LABA, and followed for >6 months with optimization of asthma treatment. Patients underwent clinical, functional and biological assessment, including induced sputum and nasal cytology. They were then clustered according to the eligibility criteria for omalizumab or mepolizumab/benralizumab. Results: Four clusters were selected: A (eligible for omalizumab, n = 23), AB (both omalizumab and mepolizumab, n = 26), B (mepolizumab, n = 22) and C (non-eligible for both omalizumab and mepolizumab, n = 20). There was no difference among clusters for asthma control (Asthma Control Test and Asthma Control Questionnaire 7), pre-bronchodilator forced expiratory volume in 1 s, serum IgE and fractional exhaled nitric oxide levels. Sputum eosinophils were numerically higher in clusters AB and B, in agreement with the higher levels of blood eosinophils. Allergic rhinitis was more frequent in clusters A and AB, while chronic rhinosinusitis with nasal polyps prevalence increased progressively from A to C. Eosinophils in nasal cytology were higher in clusters AB, B and C. Conclusion: Eosinophilic upper and lower airway inflammation is present in the large majority of severe asthmatics, independently from the prescription criteria for the currently available biologics, and might suggest the use of anti-IL5/IL5R or anti IL4/13 also in patients without blood eosinophilia. The reviews of this paper are available via the supplemental material section .

Published
2020
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13. Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI)

Author

Giorgio Walter Canonica, Francesco Blasi, Pierluigi Paggiaro, Gianenrico Senna, Giovanni Passalacqua, Antonio Spanevello, Stefano Aliberti, Diego Bagnasco, Marco Bonavia, Matteo Bonini, Luisa Brussino, Caterina Bucca, Maria F. Caiaffa, Cecilia Calabrese, Gianna Camiciottoli, Marco Caminati, Giovanna E. Carpagnano, Cristiano Caruso, Stefano Centanni, Maria E. Conte, Angelo G. Corsico, Lorenzo Cosmi, Maria T. Costantino, Nunzio Crimi, Simona D’Alò, Maria D'Amato, Stefano Del Giacco, Alessandro Farsi, Elisabetta Favero, Maria P. Foschino Barbaro, Gabriella Guarnieri, Giuseppe Guida, Manuela Latorre, Salvatore Lo Cicero, Carlo Lombardi, Luigi Macchia, Francesco Mazza, Francesco Menzella, Manlio Milanese, Marcello Montagni, Paolo Montuschi, Eleonora Nucera, Roberta Parente, Vincenzo Patella, Girolamo Pelaia, Laura Pini, Francesca Puggioni, Luisa Ricciardi, Fabio L.M. Ricciardolo, Luca Richeldi, Erminia Ridolo, Giovanni Rolla, Pierachille Santus, Nicola Scichilone, Giuseppe Spadaro, Andrea Vianello, Vittorio Viviano, Mona R. Yacoub, Maria C. Zappa, and Enrico Heffler

Subjects
Severe asthma, Biologics, Oral corticosteroids, Real-life, Registr, Immunologic diseases. Allergy, RC581-607
Abstract

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

Published
2020
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15. Biologics in Severe Eosinophilic Asthma: Three-Year Follow-Up in a SANI Single Center

Author

Paolo Solidoro, Stefania Nicola, Irene Ridolfi, Giorgio Walter Canonica, Francesco Blasi, Pierluigi Paggiaro, Enrico Heffler, Diego Bagnasco, Filippo Patrucco, Fulvia Ribolla, Caterina Bucca, Giovanni Rolla, Carlo Albera, and Luisa Brussino

Subjects
severe eosinophilic asthma, biologics, T2-high asthma, SANI registry, IL-5, IL-4, Biology (General), QH301-705.5
Abstract

Introduction: Biologic drugs have dramatically improved severe eosinophilic asthma (SEA) outcomes. Our aim was to evaluate the long-term efficacy of biological therapy in SEA in a real-life setting and to identify the predictors for switching to another biological drug in patients with poor asthma control. The outcomes for efficacy were decreased annual exacerbations (AE) and improved asthma control test (ACT). Methods: In 90 SEA patients being treated with a biological drug, clinical examination, ACT, blood eosinophils count and spirometry were assessed before (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36 (T4) months from the start of biological therapy. Patients were considered responders (R) or non-responders (NR) to biologics depending on whether or not they had less than two AE and a 20% increase in the ACT after 12 months of treatment. Results: 75% of the patients were R, 25% NR. In R patients, biological therapy add-on was followed by significant improvement in AE and ACT throughout the whole follow-up period. The percentage of patients on oral corticosteroids (OCS) dropped from 40% to 12%. By contrast, the NR patients were shifted to another biological drug after 12 months of therapy, as they still had high AE and nearly unchanged ACT; 40% of them still needed OCS treatment. The predictors of switching to another biological drug were three or more AE, ACT below 17, nasal polyposis and former smoking (p < 0.05). In NR, the shift to another biological drug was followed by a significant decrease in AE and an increase in the ACT. Discussion: This real-life study confirms the long-term efficacy of biologics in most SEA patients and indicates that even in non-responders to a first biological drug, it is worth trying a second one. It is hoped that the availability of additional biologics with different targets will help improve the personalization of SEA therapy.

Published
2022
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16. Asthma control in primary care: the results of an observational cross-sectional study in Italy and Spain

Author

Maria Sandra Magnoni, Manuela Latorre, Germano Bettoncelli, M. Guadalupe Sanchez-Herrero, Araceli Lopez, Eduardo Calvo, Andrea Rizzi, Marco Caminati, Gianenrico Senna, and Pierluigi Paggiaro

Subjects
Asthma, Control, ACT, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Background Poor asthma control observed in several surveys may be related to a lack of systematic assessment by physicians and/or to patient underestimation of symptoms. Along this line, the purpose of this study was to investigate the level of asthma control in patients attending the GP office for different reasons, either for renewal of drug prescription or for worsening of asthma symptoms. Methods Each of the 145 General Practitioners (GP) in Italy and Spain selected at least eight asthmatic patients attending their office for a renewal of drug prescription (Group A) or for worsening of asthma symptoms (Group B), between May and December 2009. Asthma Control Test (ACT) and other clinical information (including SF-12 questionnaire) were collected. Results Data from 1375 patients with moderate-severe asthma were analysed (mean age: 47.2 years; female: 59%; smokers or ex-smokers: 35.4%); 57% were on treatment with ICS-LABA combination. ACT score

Published
2017
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17. Distinct profile of inflammatory and remodelling biomarkers in sputum of severe asthmatic patients with or without persistent airway obstruction

Author

Silvana Cianchetti, Cristina Cardini, Ilaria Puxeddu, Manuela Latorre, Maria Laura Bartoli, Matteo Bradicich, Federico Dente, Elena Bacci, Alessandro Celi, and Pierluigi Paggiaro

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background: Both inflammatory and remodelling processes are associated with irreversible airway obstruction observed in severe asthma. Our aim was to characterize a group of severe asthmatic patients with or without persistent airway obstruction in relation to specific sputum inflammatory and remodelling biomarkers. Methods: Forty-five patients under regular high-dose inhaled corticosteroid/ß-2agonist treatment were studied, after a follow-up period of at least 2 years, with a minimum of 4 visits. Periostin, TGF-ß, RANTES, IL-8, GM-CSF, FGF-2, and cell counts were measured in induced sputum. Serum periostin was also measured. Results: Sputum induction was successfully performed in all but 5 patients. There were no significant differences in demographic and clinical data between patients with non-persistent obstruction (NO: FEV1/VC>88%pred.) and those with persistent obstruction (O: a not completely reversible obstruction with FEV1/VC103.3 pg/ml: median value) showed an absolute number of sputum eosinophils significantly higher than patients with low sputum periostin; this behavior was unobserved when serum periostin was considered. Conclusions: Only periostin and TGF-ß identified a subgroup of severe asthmatic patients with persistent airway obstruction. Sputum periostin was also inversely associated with FEV1 and proved to be a more sensitive biomarker than serum periostin to identify severe asthmatics with higher sputum eosinophilia. Keywords: Severe asthma, Remodelling, Airway inflammation, Biomarkers, Induced sputum

Published
2019
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18. Shadow cost of oral corticosteroids-related adverse events: A pharmacoeconomic evaluation applied to real-life data from the Severe Asthma Network in Italy (SANI) registry

Author

Giorgio Walter Canonica, Giorgio Lorenzo Colombo, Giacomo Matteo Bruno, Sergio Di Matteo, Chiara Martinotti, Francesco Blasi, Caterina Bucca, Nunzio Crimi, Pierluigi Paggiaro, Girolamo Pelaia, Giovanni Passalaqua, Gianenrico Senna, Enrico Heffler, Aliberti Stefano, Bagnasco Diego, Barbuto Sarah, Camiciottoli Gianna, Caminati Marco, Colombo Giselda, Costantino Maria Teresa, Crimi Claudia, Crivellaro Mariangiola, D'Amato Mariella, Favero Elisabetta, Foschino Maria Pia, Guarnieri Gabriella, Latorre Manuela, Lombardi Carlo, Francesco Menzella, Patella Vincenzo, Puggioni Francesca, Ridolo Erminia, Rolla Giovanni, Savi Eleonora, Scichilone Nicola, Solidoro Paolo, Spadaro Giuseppe, and Triggiani Massimo

Subjects
Immunologic diseases. Allergy, RC581-607
Abstract

Background: Asthma is one of the most common non-communicable respiratory diseases, affecting about 6% of the general population. Severe asthma, even if afflicts a minority of asthmatics, drives the majority of costs of the disease. The aim of this study is to create a pharmacoeconomic model to predict the costs of corticosteroid-related adverse events in severe asthmatics and applying it to the first published epidemiologic data from the Severe Asthma Network in Italy (SANI) registry. Methods: The analysis was conducted from the perspective of the Italian National Healthcare System (INHS). Model inputs, derived from literature, included: asthma epidemiology data, frequency of adverse events, percentage of severe asthma treated with OCS and adverse event cost (Diagnosis-Related Group (DRG) national tariffs). We estimated costs per different patient groups: non-asthma controls, mild/moderate and severe asthmatics. Final results report estimated direct cost per patient and total direct cost for overall target population, showing economic impact related to corticosteroid complication. Results: Based on epidemiological data input, in Italy, asthmatic subjects resulted about 3,999,600, of which 199,980 with severe asthma. The number of patients with severe asthma OCS-treated was estimated at 123,988. Compared to the non-asthma control cohort and to that with moderate asthma annual cost per severe asthmatic patient resulted respectively about €892 and €606 higher, showing a corticosteroids shadow cost ranging from 45% to 30%.Applying the cost per patient to the target population identified for Italy, the budget impact model estimated a total annual cost related to OCS-related adverse events of €242.7 million for severe asthmatics. In respect with non-asthmatic and moderate population, an incremental expenditure of about € 110.6 million and €75.2, respectively, were shown. Conclusions: Our study provides the first estimates of additional healthcare costs related to corticosteroid induced adverse events in severe asthma patient. Budget impact model results highlighted the relevant economic impact of OCS-related adverse events in severe asthma patients. The future extrapolation of additional data from SANI registry will support the development of a model to investigate the role of corticosteroids sparing drugs. Keywords: Severe asthma, Oral corticosteroids, Adverse events, Pharmacoeconomy, Costs, Diabetes, Glaucoma, Obesity, Bone fracture, Chronic kidney disease

Published
2019
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19. Cell-derived microparticles and the lung

Author

Dario Nieri, Tommaso Neri, Silvia Petrini, Barbara Vagaggini, Pierluigi Paggiaro, and Alessandro Celi

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Cell-derived microparticles are small (0.1–1 μm) vesicles shed by most eukaryotic cells upon activation or during apoptosis. Microparticles carry on their surface, and enclose within their cytoplasm, molecules derived from the parental cell, including proteins, DNA, RNA, microRNA and phospholipids. Microparticles are now considered functional units that represent a disseminated storage pool of bioactive effectors and participate both in the maintenance of homeostasis and in the pathogenesis of diseases. The mechanisms involved in microparticle generation include intracellular calcium mobilisation, cytoskeleton rearrangement, kinase phosphorylation and activation of the nuclear factor-κB. The role of microparticles in blood coagulation and inflammation, including airway inflammation, is well established in in vitro and animal models. The role of microparticles in human pulmonary diseases, both as pathogenic determinants and biomarkers, is being actively investigated. Microparticles of endothelial origin, suggestive of apoptosis, have been demonstrated in the peripheral blood of patients with emphysema, lending support to the hypothesis that endothelial dysfunction and apoptosis are involved in the pathogenesis of the disease and represent a link with cardiovascular comorbidities. Microparticles also have potential roles in patients with asthma, diffuse parenchymal lung disease, thromboembolism, lung cancer and pulmonary arterial hypertension.

Published
2016
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20. Nasal Cytology: A Comparative Study of Two Different Techniques of Processing—Smeared versus Cytocentrifuged Slides

Author

Maria Laura Bartoli, Lodovica Cristofani-Mencacci, Mariella Scarano, Andrea Nacci, Manuela Latorre, Elena Bacci, Pierluigi Paggiaro, and Veronica Seccia

Subjects
Pathology, RB1-214
Abstract

Nasal cytology is a precious tool to study nasal disorders, but in current literature, there is no consensus on the standardization of the processing procedure of the obtained samples. Therefore, we decided to test on specimens obtained by nasal scraping, a common way of nasal specimen sampling, two different processing techniques, smear and cytocentrifugation, and compare them in terms of inflammatory cell content, quality of slides, and validity on clinical assessment. We analyzed 105 patients with suspected sinonasal diseases, and in each patient, we performed nasal cytology with both techniques. Our analysis showed a good correlation between the two techniques for neutrophil and eosinophil percentages, both returned well-preserved cells, and showed higher neutrophil percentage in males and in smokers and higher eosinophil percentage in patients with polyposis, with a good concordance with clinical symptoms, as measured by a specific disease-related questionnaire (Sino-Nasal Outcome Test-22). Technically speaking, smeared slides were easier to prepare, with no need of dedicated equipment, but cell distribution was better in cytocentrifuged slides allowing shorter reading time. In conclusion, both techniques can be considered superimposable and worthy to be used.

Published
2018
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21. Divergent effects of Nitric oxide on airway epithelial cell activation

Author

Tommaso Neri, Ilaria Conti, Chiara Cerri, Laura Tavanti, Pierluigi Paggiaro, and Alessandro Celi

Subjects
Adhesion molecules, Airway inflammation, Alveolar Epithelium, Chemok Nes, Nitric Oxide, Biology (General), QH301-705.5
Abstract

Nitric oxide (NO*) is a gaseous mediator synthesized by Nitric oxide sinthases. NO* is involved in the modulation of inflammation, but its role in airway inflammation remains controversial. We investigated the role of NO* in the synthesis of the chemok Nes Interleukin-8 and Monocyte Chemotactic Protein-1, and of Intercellular Adhesion Molecule-1 by human airway epithelial cells. normal human bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used. Neterleukin-8 (IL-8) and Monocyte Chemotactic Protein-1 (MCP-1) secretion and Intercellular Adhesion Molecule-1 (ICAM-1) expression were measured by ELISA. mRNA was assessed by semiquantitative RTI-PCR. Neterleukin-8 secretion was significantly reduced after 24h incubation with the NO* donor, sodium nitroprusside. The effect was dose-dependent. Similar results were obta Ned with S-Nitroso-N-D,L-penicillam Ne and S-Nitroso-L-glutathione. Inhibition of endogenous NO* with the Nitric oxide synthase inhibitor N-Nitro-L-arg N Ne-methyl-esther caused an increase in IL-8 secretion by lypopolisaccharide- and cytok Ne-stimulated BEAS-2B cells. Sodium nitroprusside also caused a reduction in Monocyte Chemotactic Protein-1 secretion by both cell types. In contrast, Intercellular Adhesion Molecule-1 expression was upregulated by sodium NItroprusside. RTI-PCR results indícate that the modulation of protein levels was paralleled by modification in mRNA levels. NO* has divergent effects on the synthesis of different inflammatory mediators in human bronchial epithelial cells.

Published
2010

22. Neutrophilic Bronchial Inflammation Correlates with Clinical and Functional Findings in Patients with Noncystic Fibrosis Bronchiectasis

Author

Federico L. Dente, Marta Bilotta, Maria Laura Bartoli, Elena Bacci, Silvana Cianchetti, Manuela Latorre, Laura Malagrinò, Dario Nieri, Maria Adelaide Roggi, Barbara Vagaggini, and Pierluigi Paggiaro

Subjects
Pathology, RB1-214
Abstract

Background. Neutrophilic bronchial inflammation is a main feature of bronchiectasis, but not much is known about its relationship with other disease features. Aim. To compare airway inflammatory markers with clinical and functional findings in subjects with stable noncystic fibrosis bronchiectasis (NCFB). Methods. 152 NFCB patients (62.6 years; females: 57.2%) underwent clinical and functional cross-sectional evaluation, including microbiologic and inflammatory cell profile in sputum, and exhaled breath condensate malondialdehyde (EBC-MDA). NFCB severity was assessed using BSI and FACED criteria. Results. Sputum neutrophil percentages inversely correlated with FEV1 (P

Published
2015
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23. Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

Author

Federica Novelli, Tommaso Neri, Laura Tavanti, Chiara Armani, Concettina Noce, Fabio Falaschi, Maria Laura Bartoli, Federica Martino, Antonio Palla, Alessandro Celi, and Pierluigi Paggiaro

Subjects
Medicine, Science
Abstract

Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p

Published
2014
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24. Contribution by polymorphonucleate granulocytes to elevated gamma-glutamyltransferase in cystic fibrosis sputum.

Author

Alessandro Corti, Maria Franzini, Silvana Cianchetti, Gabriella Bergamini, Evelina Lorenzini, Paola Melotti, Aldo Paolicchi, Pierluigi Paggiaro, and Alfonso Pompella

Subjects
Medicine, Science
Abstract

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by a chronic neutrophilic airways inflammation, increasing levels of oxidative stress and reduced levels of antioxidants such as glutathione (GSH). Gamma-glutamyltransferase (GGT), an enzyme induced by oxidative stress and involved in the catabolism of GSH and its derivatives, is increased in the airways of CF patients with inflammation, but the possible implications of its increase have not yet been investigated in detail. PRINCIPAL FINDINGS: The present study was aimed to evaluate the origin and the biochemical characteristics of the GGT detectable in CF sputum. We found GGT activity both in neutrophils and in the fluid, the latter significantly correlating with myeloperoxidase expression. In neutrophils, GGT was associated with intracellular granules. In the fluid, gel-filtration chromatography showed the presence of two distinct GGT fractions, the first corresponding to the human plasma b-GGT fraction, the other to the free enzyme. The same fractions were also observed in the supernatant of ionomycin and fMLP-activated neutrophils. Western blot analysis confirmed the presence of a single band of GGT immunoreactive peptide in the CF sputum samples and in isolated neutrophils. CONCLUSIONS: In conclusion, our data indicate that neutrophils are able to transport and release GGT, thus increasing GGT activity in CF sputum. The prompt release of GGT may have consequences on all GGT substrates, including major inflammatory mediators such as S-nitrosoglutathione and leukotrienes, and could participate in early modulation of inflammatory response.

Published
2012
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25. Effect of Dupilumab on Blood Eosinophil Counts in Patients With Asthma, Chronic Rhinosinusitis With Nasal Polyps, Atopic Dermatitis, or Eosinophilic Esophagitis

Author

Michael E, Wechsler, Amy D, Klion, Pierluigi, Paggiaro, Parameswaran, Nair, Delphine, Staumont-Salle, Amr, Radwan, Robert R, Johnson, Upender, Kapoor, Faisal A, Khokhar, Nadia, Daizadeh, Zhen, Chen, Elizabeth, Laws, Benjamin, Ortiz, Juby A, Jacob-Nara, Leda P, Mannent, Paul J, Rowe, and Yamo, Deniz

Subjects
Adult, Adolescent, Granulomatosis with Polyangiitis, Eosinophilic Esophagitis, Churg-Strauss Syndrome, Antibodies, Monoclonal, Humanized, Asthma, Enteritis, Dermatitis, Atopic, Eosinophils, Nasal Polyps, Gastritis, Chronic Disease, Eosinophilia, Humans, Immunology and Allergy, Sinusitis, Rhinitis
Abstract

Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials.To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis.Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (1,500 cells/μL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented.Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/μL; week 4: 515-578 cells/μL), CRSwNP (baseline: 440-448 cells/μL; week 16: 595 cells/μL), and atopic dermatitis (baseline: 434-600 cells/μL; week 4: 410-710 cells/μL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/μL; week 4: 230 cells/μL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy.Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms.

Published
2022

26. ROSE: radiology, obstruction, symptoms and exposure – a Delphi consensus definition of the association of COPD and bronchiectasis by the EMBARC Airways Working Group

Author

Stefano Aliberti, Michal Shteinberg, Joseph Jacob, Sebastian Ferri, Miguel Ángel Martínez-García, Letizia Traversi, John R. Hurst, Jens Vogel-Claussen, Marc Miravitlles, Katerina Dimakou, Apostolos Bossios, James D. Chalmers, Pierluigi Paggiaro, Sabine Dettmer, Eva Polverino, Georgios Hillas, Institut Català de la Salut, [Traversi L] Dept of Medicine and Surgery, Respiratory Diseases, Università dell’Insubria, Varese-Como, Italy. Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Miravitlles M] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. CIBER de Enfermedades Respiratorias, Barcelona, Spain. [Martinez-Garcia MA] CIBER de Enfermedades Respiratorias, Barcelona, Spain. Respiratory Dept, La Fe University and Polytechnic Hospital, Valencia, Spain. [Shteinberg M] Pulmonology Institute and Cystic Fibrosis Center, Carmel Medical Center, and the Technion – Israel Institute of Technology, the B. Rappaport Faculty of Medicine, Haifa, Israel. [Bossios A] Dept of Respiratory Medicine and Allergy, Karolinska University Hospital and Dept of Medicine, Karolinska Institutet, Stockholm, Sweden. [Dimakou K] 5th Respiratory Department, 'SOTIRIA' Hospital for Chest diseases, Athens, Greece. [Polverino E] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Pulmonary and Respiratory Medicine, Spirometry, medicine.medical_specialty, Respiratory Tract Diseases::Bronchial Diseases::Bronchiectasis [DISEASES], Delphi method, MEDLINE, Enquestes, FEV1/FVC ratio, Medicine, Pulmonologists, Bronquièctasi, Response rate (survey), COPD, Bronchiectasis, Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Obstructive::Pulmonary Disease, Chronic Obstructive [DISEASES], medicine.diagnostic_test, Pulmons - Malalties obstructives, business.industry, COPD and bronchiectasis, medicine.disease, respiratory tract diseases, enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares obstructivas::enfermedad pulmonar obstructiva crónica [ENFERMEDADES], Ciencias de la información::análisis de sistemas::técnica Delfos [CIENCIA DE LA INFORMACIÓN], Family medicine, Original research articles, Information Science::Systems Analysis::Delphi Technique [INFORMATION SCIENCE], enfermedades respiratorias::enfermedades bronquiales::bronquiectasia [ENFERMEDADES], business
Abstract

Introduction The coexistence of COPD and bronchiectasis seems to be common and associated with a worse prognosis than for either disease individually. However, no definition of this association exists to guide researchers and clinicians. Methods We conducted a Delphi survey involving expert pulmonologists and radiologists from Europe, Turkey and Israel in order to define the “COPD– [bronchiectasis] BE association”. A panel of 16 experts from EMBARC selected 35 statements for the survey after reviewing scientific literature. Invited participants, selected on the basis of expertise, geographical and sex distribution, were asked to express agreement on the statements. Consensus was defined as a score of ≥6 points (scale 0 to 9) in ≥70% of answers across two scoring rounds. Results 102 (72.3%) out of 141 invited experts participated in the first round. Their response rate in the second round was 81%. The final consensus definition of “COPD–BE association” was: “The coexistence of (1) specific radiological findings (abnormal bronchial dilatation, airways visible within 1 cm of pleura and/or lack of tapering sign in ≥1 pulmonary segment and in >1 lobe) with (2) an obstructive pattern on spirometry ([forced expiratory volume in 1 s] FEV1/[forced vital capacity] FVC, A group of experts from EMBARC has generated a consensus definition of COPD and bronchiectasis association based on the coexistence of radiological findings, bronchial obstruction, compatible symptoms and exposure to smoke or toxic agents (ROSE criteria) https://bit.ly/3g3cdld

Published
2021

27. Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO

Author

Kenneth R. Chapman, Steven W. Yancey, David B Rubin, Stephanie Harris, Ian D. Pavord, Eric S. Bradford, Frank C. Sciurba, Bhabita Mayer, Pierluigi Paggiaro, and Mona Bafadhel

Subjects
medicine.medical_specialty, Exacerbation, International Journal of Chronic Obstructive Pulmonary Disease, Antibodies, Monoclonal, Humanized, Placebo, Pulmonary Disease, Chronic Obstructive, exacerbation, Maintenance therapy, Internal medicine, medicine, Clinical endpoint, COPD, Humans, eosinophil, Original Research, Randomized Controlled Trials as Topic, business.industry, Hazard ratio, mepolizumab, General Medicine, Eosinophil, medicine.disease, Eosinophils, medicine.anatomical_structure, Disease Progression, Quality of Life, business, Mepolizumab, medicine.drug
Abstract

Background A pre-specified meta-analysis of individual patient data from the 52-week METREX and METREO trials, which investigated mepolizumab for chronic obstructive pulmonary disease (COPD) in patients with blood eosinophil counts ≥150 cells/µL (screening) or ≥300 cells/µL (prior year) and frequent exacerbations, enables more robust characterization of mepolizumab efficacy in COPD and exploration of the relationship between blood eosinophil count and treatment responses. Methods In METREX (117106/NCT02105948) and METREO (117113/NCT02105961), randomized patients received mepolizumab or placebo added to existing inhaled corticosteroid (ICS)–based triple maintenance therapy. The annual rate of moderate/severe exacerbations (primary endpoint) was compared between subcutaneous (SC) mepolizumab 100 mg versus placebo (primary comparison of interest) and all doses (100 mg and 300 mg SC) versus placebo in patients with blood eosinophil counts ≥150 cells/µL at screening or ≥300 cells/µL in the prior year. Secondary/other endpoints included time to first moderate/severe exacerbation, exacerbations leading to emergency department visit/hospitalization and health-related quality of life (HRQoL). A predictive model of the relationship between screening blood eosinophil counts and exacerbation rates included data from all randomized patients. Results In total, 1510 patients were randomized in METREX and METREO and 1136 patients were included in the pre-specified meta-analysis. From the meta-analysis, mepolizumab 100 mg SC significantly reduced annual moderate/severe exacerbation rates versus placebo by 18% (rate ratio: 0.82; 95% confidence interval: 0.71, 0.95; p=0.006) and delayed time to first moderate/severe exacerbation (hazard ratio: 0.80 [0.68, 0.94]; p=0.006). Mepolizumab 100 mg SC versus placebo numerically reduced exacerbations leading to ED visits/hospitalization and improved HRQoL. A modelling approach demonstrated increasing efficacy for moderate/severe exacerbations with increasing screening blood eosinophil count; this relationship was more pronounced for exacerbations requiring oral corticosteroids (post hoc). The all-doses comparison had similar results. Conclusion Mepolizumab reduces exacerbations in patients with eosinophil-associated COPD. Results suggest that blood eosinophil counts (≥150 cells/µL at screening or ≥300 cells/µL in the prior year) allow for identification of patients with COPD who experience exacerbations while treated with maximal ICS-based triple maintenance therapy who are likely to benefit from mepolizumab., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/YCq1mqQ5Xl4

Published
2021

28. Differential outcomes following 4 weeks of aclidinium/formoterol in patients with COPD: a reanalysis of the ACTIVATE study

Author

Maud Koopman, Frits ME Franssen, Swetlana Gaffron, Henrik Watz, Thierry Troosters, Judith Garcia-Aymerich, Pierluigi Paggiaro, Eduard Molins, Miguel Moya, Lindy van Burk, Dieter Maier, Esther Garcia Gil, Emiel FM Wouters, Lowie EGW Vanfleteren, Martijn A Spruit, Pulmonologie, and RS: NUTRIM - R3 - Respiratory & Age-related Health

Subjects
Male, Respiratory System, physical activity, Hyperinflation, Muscarinic Antagonists, International Journal of Chronic Obstructive Pulmonary Disease, PULMONARY, DISEASE, LUNG HYPERINFLATION, Pulmonary Disease, Chronic Obstructive, Double-Blind Method, Forced Expiratory Volume, Formoterol Fumarate, Humans, COPD, Adrenergic beta-2 Receptor Agonists, INDACATEROL, Science & Technology, Physical activity, EXERCISE TOLERANCE, General Medicine, STANDARDIZATION, hyperinflation, Bronchodilator Agents, Drug Combinations, PHYSICAL-ACTIVITY, Female, Life Sciences & Biomedicine, TIOTROPIUM, Tropanes, RESPONSES
Abstract

Maud Koopman,1– 3 Frits ME Franssen,1– 3 Swetlana Gaffron,4 Henrik Watz,5 Thierry Troosters,6,7 Judith Garcia-Aymerich,8– 10 Pierluigi Paggiaro,11 Eduard Molins,12 Miguel Moya,12 Lindy van Burk,13 Dieter Maier,14 Esther Garcia Gil,12 Emiel FM Wouters,1,3,15 Lowie EGW Vanfleteren,16 Martijn A Spruit1– 3 1Department of Research and Development, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands; 2NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; 4Viscovery Software GmbH, Vienna, Austria; 5Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Grosshansdorf, Germany; 6Department of Rehabilitation Sciences, KU Leuven – University of Leuven, Leuven, Belgium; 7Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; 8Barcelona Institute for Global Health (ISGlobal), Barcelona, Spain; 9Universitat Pompeu Fabra (UPF), Barcelona, Spain; 10CIBER Epidemiología y Salud Publica (CIBERESP), Madrid, Spain; 11Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy; 12AstraZeneca, Barcelona, Spain; 13AstraZeneca, Den Haag, the Netherlands; 14Biomax Informatics AB, Planegg, 82152, Germany; 15Ludwig Boltzmann Institute for Lung Health, Vienna, Austria; 16COPD Center, Sahlgrenska University Hospital, Institute of Medicine, University of Gothenburg, Gothenburg, SwedenCorrespondence: Maud Koopman, CIRO+, Center of Expertise for Chronic Organ Failure, Hornerheide 1, Horn, 6085 NM, the Netherlands, Email maudkoopman@gmail.comRationale: It is difficult to predict the effects of long-acting bronchodilators (LABD) on lung function, exercise capacity and physical activity in patients with chronic obstructive pulmonary disease (COPD). Therefore, the multidimensional response to LABD was profiled in COPD patients participating in the ACTIVATE study and randomized to LABD.Methods: In the ACTIVATE study, patients were randomized to aclidinium bromide/formoterol fumarate (AB/FF) or placebo for four weeks. The primary outcomes included (1) lung function as measured by functional residual capacity (FRC), residual volume (RV), and spirometric outcomes; (2) exercise performance as measured by a constant work rate cycle ergometry test (CWRT); and (3) physical activity (PA) using an activity monitor. Self-organizing maps (SOMs) were used to create an ordered representation of the patients who were randomly assigned to four weeks of AB/FF and cluster them into different outcome groups.Results: A total of 250 patients were randomized to AB/FF (n = 126) or placebo (n = 124). Patients in the AB/FF group (39.6% women) had moderate-to-severe COPD, static hyperinflation (FRC: 151.4 (27.7)% predicted) and preserved exercise capacity. Six clusters with differential outcomes were identified. Patients in clusters 1 and 2 had significant improvements in lung function compared to the remaining AB/FF-treated patients. Patients in clusters 1 and 3 had significant improvements in CWRT time, and patients in clusters 2, 3 and 6 had significant improvements in PA compared to the remaining AB/FF-treated patients.Conclusion: Individual responses to 4 weeks of AB/FF-treatment in COPD are differential and the degree of change differs across domains of lung function, exercise capacity and PA. These results indicate that clinical response to LABD therapy is difficult to predict and is non-linear, and show doctors that it is important to look at multiple outcomes simultaneously when evaluating the clinical response to LABD therapy.Clinical Trial Registration: The original ACTIVATE study was registered on ClinicalTrials.gov, registration number NCT02424344.Keywords: COPD, hyperinflation, physical activity

Published
2022

29. Relevance of Smoking Habit in Severe Asthma Patients: Evidence from the Severe Asthma Network in Italy (SANI) Registry

Author

Marco Caminati, Gabriella Guarnieri, Pierluigi Paggiaro, Andrea Vianello, Ernesto Crisafulli, Rachele Vaia, and Gianenrico Senna

Subjects
severe asthma, Severe Asthma Network in Italy, cigarette smoking, lung function, General Medicine, eosinophils
Abstract

Smoking habit is still fairly common among asthmatics. So far, the impact of smoke on severe asthma burden has not been specifically investigated. We aimed to estimate the frequency of smoking habit among severe asthma patients, their clinical features, and the impact of smoke on asthma outcomes. The Severe Asthma Network in Italy (SANI) registry was analyzed. Demographic, clinical, and functional features of smokers, never and former smokers were compared. Data from 1194 patients were explored. Smokers were younger, with a lower asthma onset age. Atopy, BMI and respiratory/systemic comorbidities were equally distributed. In former smokers pre- and post-FEV1/FVC was significantly lower; no other significant differences were detected. Similar findings were confirmed when stratifying the former smokers by pack-years and length of smoking cessation. Among former smokers, lymphocytes and neutrophils were higher in the

Published
2022

30. Biologics in Severe Eosinophilic Asthma: Three-Year Follow-Up in a SANI Single Center

Author

Paolo Solidoro, Stefania Nicola, Irene Ridolfi, Giorgio Walter Canonica, Francesco Blasi, Pierluigi Paggiaro, Enrico Heffler, Diego Bagnasco, Filippo Patrucco, Fulvia Ribolla, Caterina Bucca, Giovanni Rolla, Carlo Albera, and Luisa Brussino

Subjects
IL-5, Severe eosinophilic asthma, IL-4, Medicine (miscellaneous), Benralizumab, Omalizumab, Biologics, Dupilumab, ACT, F, E, NO, IL-13, Lung function tests, Mepolizumab, Real-life setting, SANI registry, T2-high asthma, General Biochemistry, Genetics and Molecular Biology, severe eosinophilic asthma, biologics, omalizumab, mepolizumab, benralizumab, dupilumab, FENO, lung function tests, real-life setting
Abstract

Introduction: Biologic drugs have dramatically improved severe eosinophilic asthma (SEA) outcomes. Our aim was to evaluate the long-term efficacy of biological therapy in SEA in a real-life setting and to identify the predictors for switching to another biological drug in patients with poor asthma control. The outcomes for efficacy were decreased annual exacerbations (AE) and improved asthma control test (ACT). Methods: In 90 SEA patients being treated with a biological drug, clinical examination, ACT, blood eosinophils count and spirometry were assessed before (T0) and after 6 (T1), 12 (T2), 24 (T3) and 36 (T4) months from the start of biological therapy. Patients were considered responders (R) or non-responders (NR) to biologics depending on whether or not they had less than two AE and a 20% increase in the ACT after 12 months of treatment. Results: 75% of the patients were R, 25% NR. In R patients, biological therapy add-on was followed by significant improvement in AE and ACT throughout the whole follow-up period. The percentage of patients on oral corticosteroids (OCS) dropped from 40% to 12%. By contrast, the NR patients were shifted to another biological drug after 12 months of therapy, as they still had high AE and nearly unchanged ACT; 40% of them still needed OCS treatment. The predictors of switching to another biological drug were three or more AE, ACT below 17, nasal polyposis and former smoking (p < 0.05). In NR, the shift to another biological drug was followed by a significant decrease in AE and an increase in the ACT. Discussion: This real-life study confirms the long-term efficacy of biologics in most SEA patients and indicates that even in non-responders to a first biological drug, it is worth trying a second one. It is hoped that the availability of additional biologics with different targets will help improve the personalization of SEA therapy.

Published
2021

31. Impact of baseline patient characteristics on dupilumab efficacy in type 2 asthma

Author

Yuji Tohda, Jo A Douglass, Pierluigi Paggiaro, Nami Pandit-Abid, Benjamin Ortiz, Xavier Muñoz, William W. Busse, Nadia Daizadeh, Thomas B. Casale, G. Walter Canonica, and Mario Castro

Subjects
Pulmonary and Respiratory Medicine, American Lung Association, business.industry, Patient demographics, Patient characteristics, Stock options, macromolecular substances, Antibodies, Monoclonal, Humanized, Dupilumab, Medical writing, Research Letters, Asthma, Management, respiratory tract diseases, Disease severity, immune system diseases, Medicine, Humans, business, Production team, Agora
Abstract

Severe asthma affects an estimated 5–10% of the total asthma patient population [1]. Various demographic factors, such as sex, age, obesity and age of onset, have been associated with asthma disease severity [2, 3], and the efficacy of asthma treatments has previously been found to vary depending on patient demographics [4, 5]., Dupilumab treatment versus placebo improved exacerbation rate and lung function outcomes in patients with uncontrolled moderate-to-severe asthma and high type 2 biomarkers at baseline, regardless of baseline characteristics in the phase 3 QUEST study https://bit.ly/3yR7MlD

Published
2021

32. Mild/Moderate Asthma Network in Italy (MANI): a long-term observational study

Author

Fulvio, Braido, Francesco, Blasi, Giorgio Walter Canonica, Pierluigi, Paggiaro, Bianca, Beghè, Matteo, Bonini, Giovanna Elisiana Carpagnano, Stefano Del Giacco, Federico, Lavorini, Manlio, Milanese, Vincenzo, Patella, Pierachille, Santus, Marco, Contoli, Mani, Network, Chiara, Allegrini, Ilaria, Baiardini, Laura, Bonzano, Maria Filomena Caiaffa, Paolo, Castelnuovo, Angelo Guido Corsico, Lorenzo, Cosmi, Maria Teresa Costantino, Marcello, Cottini, Nunzio, Crimi, Maria Angiola Crivellaro, Simona, D'Alò, Ilenia, Folletti, Dario, Fornari, Maria Pia Foschino-Barbaro, Laura, Franceschini, Domenico, Gargano, Kim Lokar Oliani, Mauro, Maniscalco, Laura, Melissari, Marcello, Montagni, Paolo, Montuschi, Nicola, Murgia, Alessandro, Pannofino, Alberto, Papi, Roberta, Parente, Girolamo, Pelaia, Pini, Laura, Francesca, Puggioni, Nolita, Pulerà, Onofrio, Resta, Luisa, Ricciardi, Erminia, Ridolo, Eleonora, Savi, Francesca, Savoia, Guglielmo, Scala, Gianenrico, Senna, Salvatore, Tripodi, Alessandro, Vatrella, Maria Teresa Ventura, Vittorio Maria Viviano, and Mona-Rita, Yacoub

Subjects
Pulmonary and Respiratory Medicine, Pediatrics, medicine.medical_specialty, Moderate asthma, registry, immune system diseases, Cross-sectional, Administration, Inhalation, medicine, Immunology and Allergy, Humans, Anti-Asthmatic Agents, Prospective Studies, Prospective cohort study, patient-reported outcomes, prospective cohort study, health care economics and organizations, Asthma, business.industry, medicine.disease, respiratory tract diseases, Term (time), Cross-Sectional Studies, Pediatrics, Perinatology and Child Health, Disease Progression, Quality of Life, Observational study, business
Abstract

The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences.This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844).Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease.MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Published
2021

33. The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study

Author

Monica Kraft, Matthew Richardson, Brian Hallmark, Dean Billheimer, Maarten Van den Berge, Leonardo M Fabbri, Thys Van der Molen, Gabriele Nicolini, Alberto Papi, Klaus F Rabe, Dave Singh, Chris Brightling, Salman Siddiqui, Emilio Pizzichini, Alberto Cukier, Rafael Stelmach, Ronald Olivenstein, Qingling Zhang, Philipp Badorrek, Christian Gessner, Nicola Scichilone, Alfredo Chetta, Pierluigi Paggiaro, Stefano Milleri, Mariella D'Amato, Antonio Spanevello, Maria Pia Foschino, Willem Germen Boersma, Marielle Broeders, J Sebastiaan Vroegop, Vicente Plaza Moral, Ratko Djukanovic, Omar Usmani, Robert Schilz, Richard Martin, Nicola Hanania, and Groningen Research Institute for Asthma and COPD (GRIAC)

Subjects
Pulmonary and Respiratory Medicine, Male, DISTAL AIRWAYS, Respiratory System, Middle Aged, Asthma, Pulmonary Disease, Chronic Obstructive, Spirometry, Forced Expiratory Volume, Oscillometry, Quality of Life, Humans, Female, Longitudinal Studies, ALVEOLAR TISSUE, IMPULSE OSCILLOMETRY
Abstract

Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0·20-0·25, p0·0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations.Chiesi Farmaceutici.

Published
2021

34. DUPILUMAB IMPROVES PATIENT-REPORTED BREATHING IN ORAL CORTICOSTEROID-DEPENDENT SEVERE ASTHMA

Author

Siddhesh Kamat, Nadia Daizadeh, Robert R. Wolfe, Benjamin Ortiz, Camille Taillé, Pierluigi Paggiaro, Lawrence Sher, Nami Pandit-Abid, Santiago Quirce, Asif Khan, Giovanni Passalacqua, and Lauren Cohn

Subjects
Pulmonary and Respiratory Medicine, medicine.drug_class, business.industry, Severe asthma, Anesthesia, medicine, Breathing, Corticosteroid, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine, business, Dupilumab
Published
2020

35. Is adherence to treatment influenced by the ability to use inhaled devices in patients with COPD correctly?

Author

Manuela Latorre, Giulia Parri, and Pierluigi Paggiaro

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Psychometrics, MEDLINE, Aptitude, Pulmonary disease, Pulmonary Disease, Chronic Obstructive, Patient Education as Topic, Adrenal Cortex Hormones, Administration, Inhalation, Humans, Medicine, In patient, Intensive care medicine, COPD, Portugal, Inhalation, business.industry, Nebulizers and Vaporizers, Disease progression, medicine.disease, Bronchodilator Agents, Treatment Adherence and Compliance, Observational Studies as Topic, Disease Progression, business
Published
2020

36. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials

Author

Anders Cervin, Heribert Staudinger, M. Zhang, Xin Lu, Leon S. Greos, George D. Yancopoulos, Chunpeng Fan, Naimish Patel, Gianluca Pirozzi, Steven Draikiwicz, Neil M.H. Graham, G. Walter Canonica, Pierluigi Paggiaro, Claus Bachert, Joaquim Mullol, Heidi Olze, Stella E. Lee, Joseph K. Han, Tanya M. Laidlaw, Neil Stahl, Nikhil Amin, Asif Khan, Wytske Fokkens, Seong H. Cho, Claire Hopkins, Shigeharu Fujieda, Marcella Ruddy, Siddhesh Kamat, John V. Bosso, Peter Hellings, Jorge Maspero, David M. Weinreich, Leda Mannent, Martin Desrosiers, Ear, Nose and Throat, and AII - Inflammatory diseases

Subjects
Adult, Male, medicine.medical_specialty, Injections, Subcutaneous, Population, 030204 cardiovascular system & hematology, Nasal congestion, Antibodies, Monoclonal, Humanized, Placebo, Severity of Illness Index, Placebos, 03 medical and health sciences, Nasal Polyps, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, medicine, Humans, Nasal polyps, 030212 general & internal medicine, Sinusitis, Adverse effect, education, Asthma, education.field_of_study, business.industry, Antibodies, Monoclonal, General Medicine, Atopic dermatitis, Middle Aged, medicine.disease, Dupilumab, Treatment Outcome, Chronic Disease, Quality of Life, Female, medicine.symptom, business
Abstract

Background: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) generally have a high symptom burden and poor health-related quality of life, often requiring recurring systemic corticosteroid use and repeated sinus surgery. Dupilumab is a fully human monoclonal antibody that inhibits signalling of interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, and has been approved for use in atopic dermatitis and asthma. In these two studies, we aimed to assess efficacy and safety of dupilumab in patients with CRSwNP despite previous treatment with systemic corticosteroids, surgery, or both. Methods: LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52 were two multinational, multicentre, randomised, double-blind, placebo-controlled, parallel-group studies assessing dupilumab added to standard of care in adults with severe CRSwNP. SINUS-24 was done in 67 centres in 13 countries, and SINUS-52 was done in 117 centres in 14 countries. Eligible patients were 18 years or older with bilateral CRSwNP and symptoms despite intranasal corticosteroid use, receiving systemic corticosteroids in the preceding 2 years, or having had sinonasal surgery. Patients in SINUS-24 were randomly assigned (1:1) to subcutaneous dupilumab 300 mg or placebo every 2 weeks for 24 weeks. Patients in SINUS-52 were randomly assigned (1:1:1) to dupilumab 300 mg every 2 weeks for 52 weeks, dupilumab every 2 weeks for 24 weeks and then every 4 weeks for the remaining 28 weeks, or placebo every 2 weeks for 52 weeks. All patients were randomly assigned centrally with a permuted block randomisation schedule. Randomisation was stratified by asthma or non-steroidal anti-inflammatory drug-exacerbated respiratory disease status at screening, previous surgery at screening, and country. Patients with or without comorbid asthma were included. Coprimary endpoints were changes from baseline to week 24 in nasal polyp score (NPS), nasal congestion or obstruction, and sinus Lund-Mackay CT scores (a coprimary endpoint in Japan), done in an intention-to-treat population. Safety was assessed in a pooled population of both dupilumab groups in SINUS-52 up to week 24 and the dupilumab group in SINUS-24 and the placebo groups in both studies until week 24. The trials are complete and registered at ClinicalTrials.gov, NCT02912468 and NCT02898454. Findings: Between Dec 5, 2016, and Aug 3, 2017, 276 patients were enrolled in SINUS-24, with 143 in the dupilumab group and 133 in the placebo group receiving at least one study drug dose. Between Nov 28, 2016, and Aug 28, 2017, 448 patients were enrolled in SINUS-52, with 150 receiving at least one dose of dupilumab every 2 weeks, 145 receiving at least one dose of dupilumab every 2 weeks for 24 weeks and every 4 weeks until week 52, and 153 receiving at least one dose of placebo. Dupilumab significantly improved the coprimary endpoints in both studies. At 24 weeks, least squares mean difference in NPS of dupilumab treatment versus placebo was −2·06 (95% CI −2·43 to −1·69; p

Published
2019

37. Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis

Author

Annalisa Stassaldi, Nunzio Crimi, Francesco Blasi, Gianluca Furneri, Francesca Fanelli, Giorgio Walter Canonica, Pierluigi Paggiaro, and Alberto Papi

Subjects
0301 basic medicine, Allergy, medicine.medical_specialty, Immunology, Population, Socio-culturale, Disease, Dupilumab, Immunoglobulin E, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Immunology and Allergy, Type 2 asthma, education, Molecular Biology, Asthma, Biomarkers, dupilumab, Italy, type 2 asthma, education.field_of_study, biology, business.industry, Research, RC581-607, medicine.disease, respiratory tract diseases, 030104 developmental biology, Italy, 030228 respiratory system, Exhaled nitric oxide, biology.protein, Biomarker (medicine), Immunologic diseases. Allergy, business, Biomarkers
Abstract

Background Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status. Methods A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab). Results According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population). Conclusions There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.

Published
2021

38. Chronic obstructive pulmonary disease: moving from symptom relief to mortality reduction

Author

Riccardo Pistelli, Manuela Latorre, Pierluigi Paggiaro, and Alessandro Celi

Subjects
Budesonide, medicine.medical_specialty, Population, Medicine (miscellaneous), Review, RM1-950, Placebo, Fluticasone propionate, chronic obstructive pulmonary disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, bronchodilator agents, steroids, Internal medicine, medicine, 030212 general & internal medicine, education, COPD, education.field_of_study, business.industry, medicine.disease, 030228 respiratory system, chemistry, Vilanterol, Salmeterol, Formoterol, Therapeutics. Pharmacology, business, medicine.drug
Abstract

Chronic obstructive pulmonary disease (COPD) has a 3-year mortality rate up to 37%, 2–6 times higher than the general population. We present evidence supporting pharmacological therapies to improve patient life expectancy, focusing on inhaled corticosteroids (ICSs) combined with long-acting bronchodilators (LABDs). A reduction in 3-year all-cause mortality (ACM) has been shown in patients with severe COPD treated with fluticasone propionate (an ICS) and salmeterol [long-acting beta-agonist (LABA)], compared with placebo. An observational study of elderly patients with severe COPD and multiple comorbidities suggested ICS+LABD reduce ACM compared with LABD monotherapy. Patients with symptomatic COPD at risk of exacerbations saw a mortality benefit with the ICS/long-acting muscarinic antagonist (LAMA)/LABA combinations fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) or budesonide/glycopyrrolate/formoterol (BUD/GLY/FOR) versus UMEC/VI or GLY/FOR (LAMA/LABA combinations) in the IMPACT and ETHOS trials, respectively. Reduced risk of mortality may be due to modulation of airway inflammation, thereby reducing activation of proinflammatory mediators in the peripheral circulation. Importantly, estimated annual risk reduction for ACM with ICS/LAMA/LABA combinations in patients with COPD is of the same order of magnitude as for statins (patients with coronary disease) and angiotensin-converting enzyme inhibitors (patients with vascular disease). Based on the current data, the pharmacological treatment of COPD appears not only able to improve symptoms and reduce the frequency of exacerbations but is also very promising in improving patient prognosis in the long term.

Published
2021

39. Severe asthma: One disease and multiple definitions

Author

Maria Teresa Costantino, Luigi Macchia, Angelo Corsico, Andrea Airoldi, Carla Galeone, Zappa Maria Cristina, Paolo Tarsia, Foschino Barbaro Maria Pia, Silvia Ruggeri, Pierluigi Paggiaro, Lorenzo Cosmi, A. Farsi, Vitina Maria Anna Carriero, Arianna Bassi, Francesca Bertolini, Giovanni Passalacqua, Fulvia Chieco Bianchi, Carlo Lombardi, Salvatore Lo Cicero, Giovanni Rolla, Carmen Durante, Rocco Rinaldo, Elena Parazzini, Arianna Aruanno, Maria Rita Marchi, Chiara Folli, Alessandra Arcolaci, Carlo Pasculli, Fabio Luigi Massimo Ricciardolo, Vittorio Viviano, Alvise Berti, Stefano Del Giacco, Andrea Manfredi, Roberta Barlassina, Agata Valentina Frazzetto, Pierachille Santus, Luisa Brussino, Anna del Colle, Marco Bonavia, Dina Visca, Nicola Scichilone, Patrizia Pignatti, Enrico Heffler, Francesca Racca, Giuseppe Santini, Nucera Eleonora, Giovanna Elisiana Carpagnano, Linda Di Pietro, Stefano Centanni, Maria Elisabetta Conte, Vincenzo Patella, Monna Rita Yacoub, Diego Bagnasco, Nunzio Crimi, Anna Maria Riccio, Stefania Isola, Margherita Deidda, Gabriella Guarnieri, Giuseppe Guida, Elena Minenna, Manuela Latorre, Gianna Camiciottoli, Maria Vittoria Verrillo, Luca Richeldi, Marcello Montagni, Francesca Cicero, Maria Filomena Caiaffa, Antonio Spanevello, Cecilia Calabrese, Carlo Barbetta, Elisabetta Favero, Gianenrico Senna, Giuliana Amato, Amelia Grosso, Federica Vita, Francesco Blasi, Luisa Ricciardi, Carola Condoluci, Massimo Triggiani, Enrico Maggi, Mariacarmela Di Proietto, Giulia Carli, Roberta Parente, Eleonora Savi, Chiara Roncallo, Paolo Montuschi, Luciana D'Elia, Francesco Mazza, Simona D’Alo, Patrizia Ruggiero, Francesca Puggioni, Matteo Bonini, Simone Luraschi, Francesco Menzella, Leonello Fuso, Marco Caminati, Martina Flora, Mariachiara Braschi, Cristiano Caruso, Angela Rizzi, Sandra Iannacone, Rikki Frank Canevari, Andrea Vianello, D’Amato Maria, Manlio Milanese, Stefania Colantuono, Giorgio Walter Canonica, Giulia Scioscia, Laura Pini, Elisa Testino, Erminia Ridolo, Joyce Rolo, Elisa Turchet, Pelaia Gerolamo, Danilo Di Bona, Laura De Ferrari, Francesca Cherubino, Alice D’Adda, Marianna Lilli, Giuseppe Spadaro, Stefano Pucci, Caterina Detoraki, Chiara Allegrini, Bagnasco, D., Paggiaro, P., Latorre, M., Folli, C., Testino, E., Bassi, A., Milanese, M., Heffler, E., Manfredi, A., Riccio, A. M., De Ferrari, L., Blasi, F., Canevari, R. F., Canonica, G. W., Passalacqua, G., Guarnieri, G., Patella, V., Maria Pia, F. B., Carpagnano, G. E., Colle, A. D., Scioscia, G., Gerolamo, P., Puggioni, F., Racca, F., Favero, E., Iannacone, S., Savi, E., Montagni, M., Camiciottoli, G., Allegrini, C., Lombardi, C., Spadaro, G., Detoraki, C., Menzella, F., Galeone, C., Ruggiero, P., Yacoub, M. R., Berti, A., Scichilone, N., Durante, C., Costantino, M. T., Roncallo, C., Braschi, M., D'Adda, A., Ridolo, E., Triggiani, M., Parente, R., Maria, D. A., Verrillo, M. V., Rolla, G., Brussino, L., Frazzetto, A. V., Cristina, Z. M., Lilli, M., Crimi, N., Bonavia, M., Corsico, A. G., Grosso, A., Del Giacco, S., Deidda, M., Ricciardi, L., Isola, S., Cicero, F., Amato, G., Vita, F., Spanevello, A., Pignatti, P., Cherubino, F., Visca, D., Massimo Ricciardolo, F. L., Anna Carriero, V. M., Bertolini, F., Santus, P., Barlassina, R., Airoldi, A., Guida, G., Eleonora, N., Aruanno, A., Rizzi, A., Caruso, C., Colantuono, S., Senna, G., Caminati, M., Arcolaci, A., Vianello, A., Bianchi, F. C., Marchi, M. R., Centanni, S., Luraschi, S., Ruggeri, S., Rinaldo, R., Parazzini, E., Calabrese, C., Flora, M., Cosmi, L., Di Pietro, L., Maggi, E., Pini, L., Macchia, L., Di Bona, D., Richeldi, L., Condoluci, C., Fuso, L., Bonini, M., Farsi, A., Carli, G., Montuschi, P., Santini, G., Conte, M. E., Turchet, E., Barbetta, C., Mazza, F., D'Alo, S., Pucci, S., Caiaffa, M. F., Minenna, E., D'Elia, L., Pasculli, C., Viviano, V., Tarsia, P., Rolo, J., Di Proietto, M., Lo Cicero, S., Bagnasco D., Paggiaro P., Latorre M., Folli C., Testino E., Bassi A., Milanese M., Heffler E., Manfredi A., Riccio A.M., De Ferrari L., Blasi F., Canevari R.F., Canonica G.W., Passalacqua G., Guarnieri G., Patella V., Maria Pia F.B., Carpagnano G.E., Colle A.D., Scioscia G., Gerolamo P., Puggioni F., Racca F., Favero E., Iannacone S., Savi E., Montagni M., Camiciottoli G., Allegrini C., Lombardi C., Spadaro G., Detoraki C., Menzella F., Galeone C., Ruggiero P., Yacoub M.R., Berti A., Scichilone N., Durante C., Costantino M.T., Roncallo C., Braschi M., D'Adda A., Ridolo E., Triggiani M., Parente R., Maria D.A., Verrillo M.V., Rolla G., Brussino L., Frazzetto A.V., Cristina Z.M., Lilli M., Crimi N., Bonavia M., Corsico A.G., Grosso A., Del Giacco S., Deidda M., Ricciardi L., Isola S., Cicero F., Amato G., Vita F., Spanevello A., Pignatti P., Cherubino F., Visca D., Massimo Ricciardolo F.L., Anna Carriero V.M., Bertolini F., Santus P., Barlassina R., Airoldi A., Guida G., Eleonora N., Aruanno A., Rizzi A., Caruso C., Colantuono S., Senna G., Caminati M., Arcolaci A., Vianello A., Bianchi F.C., Marchi M.R., Centanni S., Luraschi S., Ruggeri S., Rinaldo R., Parazzini E., Calabrese C., Flora M., Cosmi L., Di Pietro L., Maggi E., Pini L., Macchia L., Di Bona D., Richeldi L., Condoluci C., Fuso L., Bonini M., Farsi A., Carli G., Montuschi P., Santini G., Conte M.E., Turchet E., Barbetta C., Mazza F., D'Alo S., Pucci S., Caiaffa M.F., Minenna E., D'Elia L., Pasculli C., Viviano V., Tarsia P., Rolo J., Di Proietto M., Lo Cicero S., Bagnasco, D, Paggiaro, P, Latorre, M, Folli, C, Testino, E, Bassi, A, Milanese, M, Heffler, E, Manfredi, A, Riccio, A, De Ferrari, L, Blasi, F, Frank Canevari, R, Canonica, G, Passalacqua, G, Guarnieri, G, Patella, V, Foschino Barbaro, M, Carpagnano, G, del Colle, A, Scioscia, G, Gerolamo, P, Puggioni, F, Racca, F, Favero, E, Iannacone, S, Savi, E, Montagni, M, Camiciottoli, G, Allegrini, C, Lombardi, C, Spadaro, G, Detoraki, C, Menzella, F, Galeone, C, Ruggiero, P, Yacoub, R, Verrillo, M, Rolla, G, and Lo Cicero, S

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Severe asthma, Immunology, Nice, Disease, Settore MED/10 - Malattie Dell'Apparato Respiratorio, Article, Pulmonary function testing, Internal medicine, Biological treatment, Classification, Definition, medicine, Immunology and Allergy, Respiratory function, computer.programming_language, Biological therapies, business.industry, Settore MED/09 - MEDICINA INTERNA, RC581-607, Severe asthma, Classification, Definition, Biological treatment, Biological treatment, Classification, Definition, Severe asthma, Immunologic diseases. Allergy, business, computer
Abstract

Introduction There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Published
2021

40. Circulating extracellular vesicles are associated with disease severity and interleukin-6 levels in copd: A pilot study

Author

Giovanna De Cusatis, Pierluigi Paggiaro, Tommaso Neri, Sabrina Santerini, Marina Saetta, Alessandro Celi, Manuel G. Cosio, Dario Nieri, Barbara Vagaggini, Marta Daniele, Erica Bazzan, and Stefania Lombardi

Subjects
Endothelium, Population, Inflammation, Disease, Systemic inflammation, Article, chronic obstructive pulmonary disease, extracellular vesicles, systemic inflammation, endothelium, medicine, education, Interleukin 6, COPD, education.field_of_study, biology, business.industry, Chronic obstructive pulmonary disease, Interleukin, General Medicine, Extracellular vesicles, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Immunology, biology.protein, Medicine, medicine.symptom, business
Abstract

Chronic obstructive pulmonary disease (COPD) is a complex condition in which systemic inflammation plays a role in extrapulmonary manifestations, including cardiovascular diseases: interleukin (IL)-6 has a role in both COPD and atherogenesis. The 2011 GOLD document classified patients according to FEV1, symptoms, and exacerbations history, creating four groups, from A (less symptoms/low risk) to D (more symptoms/high risk). Extracellular vesicles (EV) represent potential markers in COPD: nevertheless, no studies have explored their value in association to both disease severity and inflammation. We conducted a pilot study to analyze circulating endothelial-(E) and monocyte-derived (M) EV levels in 35 COPD patients, who were grouped according to the 2011 GOLD document, the relationship between EV and plasmatic markers of inflammation was analyzed. We found a statistically significant trend for increasing EEV, MEV, IL-6, from group A to D, and a significant correlation between EEV and IL-6. The associations between both EEV and MEV and disease severity, and between EEV and IL-6, suggest a significant interplay between pulmonary disease and inflammation, with non-respiratory cells (endothelial cells and monocytes) involvement, along with the progression of the disease. Thus, EV might help identify a high-risk population for extrapulmonary events, especially in the most severe patients.

Published
2021

41. Shadow cost of oral corticosteroids-related adverse events: A pharmacoeconomic evaluation applied to real-life data from the Severe Asthma Network in Italy (SANI) registry

Author

Giovanni Rolla, Pierluigi Paggiaro, Marco Caminati, Girolamo Pelaia, Claudia Crimi, Pia Foschino Maria, Vincenzo Patella, Sarah Barbuto, Gianenrico Senna, Stefano Aliberti, Nunzio Crimi, Manuela Latorre, Giselda Colombo, Giorgio L Colombo, Giuseppe Spadaro, Teresa Costantino Maria, Nicola Scichilone, Giovanni Passalaqua, Mariangiola Crivellaro, Massimo Triggiani, Enrico Heffler, Caterina Bucca, Francesco Menzella, Sergio Di Matteo, Eleonora Savi, Elisabetta Favero, Chiara Martinotti, Diego Bagnasco, Gabriella Guarnieri, Gianna Camiciottoli, Francesco Blasi, M D'Amato, GM Bruno, Francesca Puggioni, Paolo Solidoro, Carlo Lombardi, Giorgio Walter Canonica, Erminia Ridolo, Giorgio Walter, Canonica, Giorgio Lorenzo, Colombo, Giacomo Matteo, Bruno, Sergio Di, Matteo, Chiara, Martinotti, Francesco, Blasi, Caterina, Bucca, Nunzio, Crimi, Pierluigi, Paggiaro, Girolamo, Pelaia, Giovanni, Passalaqua, Gianenrico, Senna, Enrico, Heffler, Aliberti, Stefano, Bagnasco, Diego, Barbuto, Sarah, Camiciottoli, Gianna, Caminati, Marco, Colombo, Giselda, Costantino Maria, Teresa, Crimi, Claudia, Crivellaro, Mariangiola, D'Amato, Mariella, Favero, Elisabetta, Foschino Maria, Pia, Guarnieri, Gabriella, Latorre, Manuela, Lombardi, Carlo, Menzella, Francesco, Patella, Vincenzo, Puggioni, Francesca, Ridolo, Erminia, Rolla, Giovanni, Savi, Eleonora, Scichilone, Nicola, Solidoro, Paolo, Spadaro, Giuseppe, and Triggiani, Massimo

Subjects
Pulmonary and Respiratory Medicine, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Severe asthma, Immunology, Population, Disease, Article, Pharmacoeconomy, Chronic kidney disease, Health care, Epidemiology, Oral corticosteroids, medicine, Immunology and Allergy, Obesity, Adverse effect, education, Asthma, education.field_of_study, business.industry, Diabetes, Adverse events, Bone fracture, Costs, Glaucoma, medicine.disease, Emergency medicine, Cohort, business, Complication, lcsh:RC581-607
Abstract

Background: Asthma is one of the most common non-communicable respiratory diseases, affecting about 6% of the general population. Severe asthma, even if afflicts a minority of asthmatics, drives the majority of costs of the disease. The aim of this study is to create a pharmacoeconomic model to predict the costs of corticosteroid-related adverse events in severe asthmatics and applying it to the first published epidemiologic data from the Severe Asthma Network in Italy (SANI) registry. Methods: The analysis was conducted from the perspective of the Italian National Healthcare System (INHS). Model inputs, derived from literature, included: asthma epidemiology data, frequency of adverse events, percentage of severe asthma treated with OCS and adverse event cost (Diagnosis-Related Group (DRG) national tariffs). We estimated costs per different patient groups: non-asthma controls, mild/moderate and severe asthmatics. Final results report estimated direct cost per patient and total direct cost for overall target population, showing economic impact related to corticosteroid complication. Results: Based on epidemiological data input, in Italy, asthmatic subjects resulted about 3,999,600, of which 199,980 with severe asthma. The number of patients with severe asthma OCS-treated was estimated at 123,988. Compared to the non-asthma control cohort and to that with moderate asthma annual cost per severe asthmatic patient resulted respectively about €892 and €606 higher, showing a corticosteroids shadow cost ranging from 45% to 30%.Applying the cost per patient to the target population identified for Italy, the budget impact model estimated a total annual cost related to OCS-related adverse events of €242.7 million for severe asthmatics. In respect with non-asthmatic and moderate population, an incremental expenditure of about € 110.6 million and €75.2, respectively, were shown. Conclusions: Our study provides the first estimates of additional healthcare costs related to corticosteroid induced adverse events in severe asthma patient. Budget impact model results highlighted the relevant economic impact of OCS-related adverse events in severe asthma patients. The future extrapolation of additional data from SANI registry will support the development of a model to investigate the role of corticosteroids sparing drugs. Keywords: Severe asthma, Oral corticosteroids, Adverse events, Pharmacoeconomy, Costs, Diabetes, Glaucoma, Obesity, Bone fracture, Chronic kidney disease

Published
2019

42. Benralizumab for the Prevention of COPD Exacerbations

Author

Criner, G. J., Celli, B. R., Brightling, C. E., Agusti, A., Papi, A., Singh, D., Sin, D. D., Vogelmeier, C. F., Sciurba, F. C., Bafadhel, M., Backer, V., Kato, M., Ramirez-Venegas, A., Wei, Y. -F., Bjermer, L., Shih, V. H., Jison, M., O'Quinn, S., Makulova, N., Newbold, P., Goldman, M., Martin, U. J., GALATHEA Study Investigators, TERRANOVA Study Investigators, Otto, Burghuber, Bernhard, Forstner, Gerhard, Köberl, Bernd, Lamprecht, Judith, Löffler-Ragg, Horst, Olschewski, Michael, Studnicka, Francois, Beaucage, Guy, Chouinard, Anthony, Dechant, Anthony, Dowell, Jacques, Hebert, Sohail, Khattak, Kieran, Killian, William, Killorn, Andy, Lam, Francois, Maltais, Darcy, Marciniuk, Lyle, Melenka, Bonavuth, Pek, Jeremy, Road, Donald, Sin, Alain, Vaugeois, Brandie, Walker, Tomas, Dvorak, Stanislav, Holub, Otakar, Hokynar, Vitezslav, Kolek, Daniela, Kopecka, Jan, Krepelka, Jaroslav, Mares, Josef, Veverka, Vladimir, Zindr, Sabine, Ballenberger, Rolf, Dichmann, Christian, Geßner, Margret, Jandl, Claus, Keller, Joachim, Kirschner, Marc, Kornmann, Petra, Mikloweit, Ingomar, Naudts, Axel, Overlack, Isabelle, Schenkenberger, Volker, Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan, Zielen, István, Albert, Beatrix, Bálint, Mária Csilla Hangonyi, Teréz, Kecskés, Anikó, Kurucz, Balázs, Medgyasszay, Lajos, Molnár, János, Mucsi, Márta, Papp, Magdolna, Póczi, Éva, Radeczky, Zsolt Pápai Székely, Csilla, Szabó, Gyöngyi, Szabó, Melinda, Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio, Donazzan, Federica, Meloni, Elisabetta, Pace, Pierluigi, Paggiaro, Alberto, Papi, Ricciardolo, Fabio Luigi Massimo, Antonio, Spanevello, Fumiaki, Aoki, Ryosuke, Eda, Takeo, Endo, Yasushi, Fukushima, Kenichi, Gemba, Naoki, Hagimoto, Hiromasa, Harada, Yasuko, Harada, Norihiko, Hata, Osamu, Hataji, Nobuo, Hatakeyama, Takahiko, Horiguchi, Gen, Ideura, Motoyasu, Iikura, Azusa, Ikegami, Shirou, Imokawa, Yoshikazu, Inoue, Takeshi, Isobe, Ryoji, Ito, Susumu, Iwata, Tadashi, Kamei, Motokazu, Kato, Hideki, Katsura, Yuji, Kawarada, Norio, Kihara, Masaharu, Kinoshita, Takashi, Kinoshita, Tomoo, Kishaba, Hideo, Kita, Arihiro, Kiyosue, Shigeru, Komatsu, Kazuki, Konishi, Sekiya, Koyama, Makoto, Kudo, Kazuhiko, Machida, Hironi, Makita, Hiroto, Matsuse, Naoki, Miyazawa, Hiroyuki, Nakamura, Yuji, Nakatani, Kazuyuki, Nishimura, Takashi, Nishimura, Junichi, Ogawa, Hiroyuki, Ohbayashi, Tetsuro, Ohdaira, Tsukasa, Ohnishi, Kazuhiko, Oki, Masahiko, Saito, Kenji, Sakamoto, Osamu, Sakamoto, Hisakuni, Sekino, Noriharu, Shijubo, Masaharu, Shinkai, Hideo, Soto, Yoshitaka, Sugawara, Noriaki, Suko, Hisaho, Takahashi, Masamitsu, Takahashi, Tsuneyuki, Takahashi, Hiroshi, Tanaka, Hiroyuki, Taniguchi, Tadayuki, Terada, Takao, Tochigi, Kazuyo, Tohyama, Hirokazu, Tokuyasu, Keisuke, Tomii, Tomomasa, Tsuboi, Mitsuyoshi, Utsugi, Katsumaru, Yamamoto, Michiko, Yamamoto, Shuichi, Yano, Makoto, Yoshida, Frank, Custers, Richard, Dekhuijzen, Remco, Djamin, Jan Willem Van Dan Berg, Lowie, Vanfleteren, Pascal, Wielders, Bogusława, Cimoszko, Anna, Doboszyńska, Andrzej, Dyczek, Andrzej, Fal, Krystyna, Folcik, Łukasz, Goliński, Marek, Jutel, Andrzej, Kolczyński, Piotr, Kuna, Ewa, Łączyńska, Wojciech, Machowiak, Maciej, Marczak, Joanna, Markiewicz, Janusz, Milanowski, Grzegorz, Mincewicz, Maria, Nittner-Marszalska, Wojciech, Papiewski, Małgorzata, Pawlukiewicz, Witold, Pomiećko, Barbara, Rewerska, Cezary, Rybacki, Wojciech, Skucha, Ewa, Trębas-Pietraś, Ewa, Uhryn, Małgorzata, Żurowska-Gębala, Laurentia, Andrei, Traian, Mihaescu, Stefan, Mihaicuta, Eniko Vera Pall, Ioan, Petrui, Angelica, Savu, Claudia, Toma, Ana, Trailescu, Vladimir, Abrosimov, Nataliya, Astafyeva, Evgenyi, Bazdyrev, Nadezhda, Berdnikova, Laura, Bolieva, Ekaterina, Bukreeva, Valery, Chistyakov, Anna, Galustyan, Halida, Gantseva, Svetlana, Goncharova, Sergey, Grigoriev, Galina, Ignatova, Inna, Ilyashevich, Nadezhda, Izmozherova, Magomed, Kamalov, Yaroslava, Khovaeva, Natalia, Kuzubova, Lyudmila, Kvitkova, Liudmila, Lenskaya, Igor, Leshchenko, Olga, Magnitskaya, Boris, Molotilov, Artem, Molotkov, Svetlana, Myasoedova, Sergey, Nedogoda, Vladimir, Nosov, Marina, Osipenko, Andrey, Peskov, Veronika, Popova, Oksana, Ratushnay, Irina, Ryzhova, Olga, Shangina, Natalia, Shaporova, Evgeny, Shmelev, Lybov, Shpagina, Alexander, Shutkin, Yuri, Shvarts, Mikhail, Smirnov, Irina, Stitsenko, Maksim, Vasilev, Arkadiy, Vertkin, Elena, Vishneva, Alexander, Vizel, Anna, Zateyschikova, Mohamed, Abdool-Gaffar, Ismail, Abdullah, Axel, Bruning, Nyda, Fourie, Michael, Greenblatt, Mohammed, Tayob, Venter, K, An Soo Jang, Kwan Ho Lee, Sang Haak Lee, Sook Young Lee, Suk Joong Yong, Kwang Ha Yoo, Soo Taek Uh, Ramón Agüero Balbín, David Ramos Barbón, Álvar Agustí García-Navarro, José Luis Velasco Garrido, Sergi Pascual Guardia, Eduard Monso Molas, Luis De Teresa Parreño, Borja García-Cosio Piqueras, German Peces-Barba Romero, Myriam Calle Rubio, Fernando Sánchez-Toril López, Alicia Marín Tapia, Heidi Martin Braschler, Martin, Brutsche, Michael, Grob, Jörg, Leuppi, Daiana, Stolz, Alexander, Turk, Nawar, Bakerley, Mona, Bafadhel, Christopher, Brightling, Rekha, Chaudhuri, Gourab, Choudhury, Graham, Devereux, Imran, Hussain, Kai, Lee, William, Macnee, Ravindran, Mahadeva, Matthew, Masoli, Monica, Nordstrom, Manish, Patel, Allan, Reid, Dinesh, Saralaya, Tariq, Sethi, Sukh Dave Singh, Anthony, G de Soyza, Tom, Wilkinson, Alice, Turner, Helen, Ward, Chandar, Abboy, Ivan, Ackerman, Idalia, Acosta, Arun, Adlakha, Bassil, Aish, Mohamed, Ali, Charles, Andrews, Robby, Ayoub, Anil, Badhwar, Dennis, Bassetti, Sherif El Bayadi, Richard, Beasley, Shashi, Bellam, Jonathan, Bernstein, Maria, Blahey, Scott, Bloom, Eugene, Bleecker, Wesley, Bray, Johnathan, Brewer, Robert, Buynak, William, Calhoun, Edward, Campbell, Anthony, Captain, Birjis, Chinoy, Kenneth, Chinsky, Geoffrey, Chupp, Arsenio, Columbie, Clinton, Corder, Gerard, Criner, Humberto, Cruz, Edward, Cullen, Kevin, Deboer, Michael, Denenberg, Mark, Dransfield, Leonard, Dunn, Miles, Elmore, David, Erb, Faisal, Fakih, Gary, Ferguson, Charles, Fogarty, Mark, Freed, Stephen, Fritz, David, Fuentes, Shariar, Cohen-Gadol, Robert, Garver, John, Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert, Gordon, Gregory, Gottschlich, Donald, Graham, David, Grant, Gary, Greenwald, James, Greenwald, Kenneth, Haft, Gregory, Hammond, Nadia, Hansel, Jeffrey, Harris, Humberto, Hernandez, Marvin, Heuer, Albrecht, Heyder, David, Hill, Willis, Holloway, Octavian, Ioachimescu, Richard, Jackson, Ajay, Jain, Nan, Jiang, Thomas, Kaelin, Adolfo, Kaplan, Mitchell, Kaye, Akram, Khan, Yekaterina, Khronusova, Ryan, Klein, Joel, Kline, Firas, Koura, Ritsu, Kuno, Ware, Kuschner, Jean Claude Labissiere, David Laman Jr, John, Lee, Mitchell, Lee, Lawrence, Levinson, Njira, Lugogo, Mador, M, Nathaniel, Marchetti, Rafael, Martinez, Richard, Martinez, Peter, Mattar, David, Maybee, Dennis, Mcgraw, Michael, Mcguire, Curtis, Mello, Aaron, Milstone, John, Mitchell, Wendy, Moore, Timothy, Moriarty, Cheta, Nand, Brooke, Nevins, Ikeadi, Ndukwu, Rachel, Nisbet, David, Nyanjom, Maria, Nualart, Thomas, O'Brien, Mikhail, Palatnik, Gnyandev, Patel, Amit, Patel, Guido, Perez, Christopher, Perry, Michael, Pfeffer, Krishna, Pudi, Marina, Raikhel, Murali, Ramaswamy, Joe, Ramsdell, Donato, Ricci, Gary, Richmond, Eugene, Ryan, Fadi, Saba, Boris, Sagalovich, C Andrew Schroeder, Timothy, Scialla, Frank, Sciurba, Amit, Shah, Nirav, Shah, Zeeshan, Shaikh, Akhtar, Siddiqui, Barry, Sigal, Thomas, Siler, Howard, Silverboard, William, Sims, Clyde, Southwell, Selwyn, Spangenthal, Peruvemba, Sriram, James, Stocks, Tony, Su, John, Suen, Robert, Sussman, Horia, Tatu, Antonio, Terrelonge, Alan, Thomas, Mario, Torres, Rodolfo, Trejo, Miguel, Trevino, Banks, Turner, Manuel, Villareal, Janine, Vintch, Neal, Warshoff, Jan, Westerman, Philip, Wexler, Thomas, Yunger, Amir, Zeki, Mariano Fernandez Acquier, Norma, Aramayo, German, Arce, Juan, Belloni, Víctor, Cambursano, Carlos De La Vega, Fernando Rodriguez Chariarse, Pedro, Elias, Marcelo, Fernández, Ana, Lopez, Andrea, Medina, María, Otaola, Maria Salazan Saez, Maria De Salvo, Fernando, Scherbovsky, Ana, Stok, Jorge, Taborda, Alberto, Tolcachier, Fernando, Verra, Carlos, Victorio, Rita Gisela Delgado Vizcarra, Philip, Bardin, Peter, Bremner, Martin, Phillips, John, Upham, Peter, Wark, Antoine, Bolly, Alain, Delobbe, Peter, Driesen, Eduard, Janssens, Wim, Janssens, Olivier, Michel, Bernard, Vandooren, Martti, Antila, Jussara, Fiterman, Carlos, Fritscher, Jorge, Hetzel, Jose, Jardim, Waldo De Mattos, Rafael, Martins, Maria Eunice De Oliveira, Andreia, Pez, Maria, Sales, Rafael, Stelmach, Priscila, Wolff, Svetla, Andreeva, Reneta, Antonova, Ana, Dancheva, Yuliya, Ivanova, Slavcho, Ivanov, Hristo, Metev, Iveta, Naydenova, Tatyana, Petkova, Galina, Petrova, Kostadinka, Sotirova, Mariyana, Stoyanova, Rumen, Tiholov, Iliyana, Valkanova, Oleg, Yakov, Rosa, Feijoo, Juana, Pavie, Patricia, Schönffeldt, Absalon, Silva, Victor, Martinez, David, Espinosa, Alejandro, Londono, Dora, Molina, Gonzalo, Prada, Andrés, Rico, Gregorio Sanchez Vallejo, Alvaro, Urbina, Ana, Vanegas, Maria, Villegas, Josip, Aralica, Gordana, Stjepanovic, Vibeke, Backer, Uffe, Bødtger, Christian, Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid, Titlestad, Nathalie, Bautin, Arnaud, Bourdin, Pascal, Chanez, Francis, Couturaud, Antoine, Cuvelier, Gilles, Devouassoux, Pierre-Olivier, Girodet, Jean-François, Muir, Jean-Louis, Pépin, Alain, Proust, Azzedine, Yaici, Yochai, Adir, Gershon, Fink, Zvi, Fridlender, Gabriel, Izbicki, Mordechai, Kramer, Yehuda, Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra, Ramirez-Venegas, Paul, Dawkins, Syed, Hussain, Benedict, Brockway, John, Richmond, Colin, Helm, Catherina, Chang, Jørn, Ahlqvist, Terje, Tollåli, Tadeusz, Tomala, Socorro, Castro, William, Chavez, Octavio, Cubas, Rolando, Estrella, Efrain, Felix, Ronal, Gamarra, Alfredo, Guerreros, Alberto, Matsuno, Danilo, Salazar, Miguel, Tsukayama, Albert Albay Jr, Teresita, Aquino, Tito, Atienza, Joven Roque Gonong, Ronnie, Samoro, Joel, Santiaguel, Beata, Asankowicz-Bargiel, Ewa, Pisarczyk-Bogacka, Renata, Bijata-Bronisz, Marta, Chełmińska, Małgorzata, Dobryniewska, Anna, Olech-Cudzik, Tomasz, Fijołek, Krzysztof, Filipek, Agata, Kot, Bożena, Kucińska, Krzysztof, Lis, Elżbieta, Rybicka-Liszewska, Marzenna, Tarnowska-Matusiak, Robert, Mróz, Piotr, Napora, Wojciech, Naumnik, Artur, Niemiec, Władysław, Pierzchała, Grzegorz, Przybylski, Katarzyna, Styka, Danuta, Wrońska, Branislava, Milenkovic, Dobrivoje, Novkovic, Matijaz, Flezar, Niksa, Segota, Snezana Ulcar Kostic, Albert, Klobucar, Leif, Bjermer, Dan, Curiac, Christer, Janson, Pekka, Koskinen, Lundback, Bo, Åke, Olsson, Shih-Lung, Cheng, Ming-Lin, Ho, Jeng-Yuan, Hsu, Wu-Huei, Hsu, Ping-Hung, Kuo, Chin-Chou, Wang, Yu-Feng, Wei, Kuang-Yao, Yang, Watchara, Boonsawat, Somchai, Chantarothorn, Warangkana, Keeratichananont, Kittipong, Maneechotesuwan, Kanok, Pipatvech, Piamlarp, Sangsayunh, Sibel, Arinc, Sermin, Borekci, Arzu Kaner Erturk, Filiz, Kosar, Hakan, Gunen, Ismail, Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel, Nayci, Serir Aktogu Ozkan, Abdullah, Sayiner, Esra, Uzaslan, Viktor, Blazhko, Volodymyr, Gavrysyuk, Olena, Golub, Liudmyla, Iashyna, Tetiana, Ilashchuk, Volodymyr, Koshlia, Olena, Krakhmalova, Vitali, Kryvenko, Lesia, Kuryk, Olena, Levchenko, Yuriy, Mostovoy, Mykola, Ostrovskyy, Tetyana, Pertseva, Olena, Piura, Nadiya, Rudnytska, Ganna, Stupnytska, Nataliia, Velychko, Oleh, Yakovenko, Lilia Rodriguez Ables, Roger, Abrahams, Jose, Alvarez, Fernando, Arencibia, Chander, Arora, Samir, Arora, Francis, Averill, Kwabena, Ayesu, Stephen, Basheda, Steven, Bauer, Jose, Bautista, Matthew, Beacom, Hernando, Bernal, Subodh, Bhuchar, J'Cinda, Bitters, John, Burk, Elizabeth, Burkett, James, Cain, Robert, Call, Christopher, Chappel, Bartolome, Celli, Tom, Christensen, Jeremy, Cole, Jerome, Daniel, Nguyen, Dang, Enrique, Davis, Samuel, Deleon, Robert, Deluca, Ernesto, Diaz, Anthony, Dimarco, Calvin, Dixon, Ankur, Doshi, Hugh, Durrence, Alain, Eid, John, Elsen, Herbon, Fleming, May, Flores, Scott, Franczek, Gregory, Funk, Stuart, Garay, Bernard, Garcia, Joseph, Graif, Carl, Griffin, Yamirka Duardo Guerra, David, Headley, Mitzie, Hewitt, Susan, Hole, Robert, Holladay, Ira, Horowitz, Yu-Luen, Hsu, Jonathan, Ilowite, Stephen, Jones, Ravindra, Kashyap, Edward, Kerwin, Ahtaram, Khan, Nicole, Kimzey, James, Krainson, Flory, Kreutter, Kannappan, Krishnaswamy, Shahrukh, Kureishy, Albert, Lai, Alex, Lechin, Daria, Lee, Marcus, Lee, Williams, Leeds, Joseph, Lillo, Edward, Lisberg, Lawrence, Madoff, Narendra, Maheskwari, Mujibur, Majumder, Sashi, Makam, Douglas, Mapel, Matthew, Mardiney, Jennifer, Martin, Isaac, Melamed, Elvin, Mendez, Stuart, Millstone, Joseph, Montes, Lee, Morrow, Frank, Murphy, Dany, Obeid, France, Occy, Godson, Oguchi, Juan, Ortiz, Francisco, Padron, Ward, Paine, James, Pearle, Enrique, Pelayo, Vandely, Perez, David, Pham, Carlos, Piniella, Kevin, Pritchett, Padmashri, Rastogi, Stephen, Ryan, Syed, Rehman, Jackson, Rhudy, Eustace, Riley, James, Riser, Clifford, Risk, Emory, Robinette, Christopher, Roney, Gary, Ruoff, David, Russian, Mercedes, Samson, Jay, Sandberg, Jose, Santiago, William, Sargeant, Alan, Schecter, Jeffrey, Scott, Ilia, Segal, Sudhir, Sehgal, Frederic, Seifer, Sudhir, Sekhsaria, Richard, Sellman, Paul, Shapero, Jeffrey, Shea, Lawrence, Sher, John, Sibille, Jawed, Siddiqui, Toniya, Singh, Deren, Sinkowitz, Denise, Smyth, Daniel, Soteres, Daniel, Sousa, Ralph, Steele, Thomas, Stern, Jose, Suarez, Sever, Surdulescu, Ricardo, Tan, Tonny, Tanus, Raymond, Tidman, Aurelio, Torres-Consuegra, Barry, Troyan, John, Updegrove, Sanjay, Vadgama, Armando, Pineda-Velez, Eduardo, Viera, Andrew, Wachtel, Ralph, Wade, Jimin, Wang, Dave, Webster, Paul, Weinberg, Terry, Wells, Jeffrey, White, Bram, Wieskopf, Hugh, Windom, Patrick, Wright, David, Wyatt, Bassam, Yousef, Zahid, Zafar, Chau, Ngo, Huong, Le, Lan, Nguyen, Thanh, Nguyen, Nhung, Nguyen, SALAS, Danielle, Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Harvard Medical School [Boston] (HMS), University of Leicester, University of Barcelona, Università degli Studi di Ferrara = University of Ferrara (UniFE), University of Manchester [Manchester], St. Paul’s Hospital - University of British Columbia [Vancouver, BC, Canada] (SPH-UBC), Philipps Universität Marburg = Philipps University of Marburg, University of Pittsburgh School of Medicine, University of Oxford, Bispebjerg University Hospital [Copenhagen, Denmark] (BUH), Kishiwada City Hospital [Osaka, Japan] (KCH), Instituto Nacional de Enfermedades Respiratorias [México, Mexico], I-Shou University [Kaohsiung, Taiwan] (ISU), Lund University [Lund], AstraZeneca [Gaithersburg, MD, USA] (AZ), Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), and Otto Burghuber, Bernhard Forstner, Gerhard Köberl, Bernd Lamprecht, Judith Löffler-Ragg, Horst Olschewski, Michael Studnicka, Francois Beaucage, Guy Chouinard, Anthony Dechant, Anthony Dowell, Jacques Hebert, Sohail Khattak, Kieran Killian, William Killorn, Andy Lam, Francois Maltais, Darcy Marciniuk, Lyle Melenka, Bonavuth Pek, Jeremy Road, Donald Sin, Alain Vaugeois, Brandie Walker, Tomas Dvorak, Stanislav Holub, Otakar Hokynar, Vitezslav Kolek, Daniela Kopecka, Jan Krepelka, Jaroslav Mares, Josef Veverka, Vladimir Zindr, Sabine Ballenberger, Rolf Dichmann, Christian Geßner, Margret Jandl, Claus Keller, Joachim Kirschner, Marc Kornmann, Petra Mikloweit, Ingomar Naudts, Axel Overlack, Isabelle Schenkenberger, Volker Schlegel, Lutz Von Versen, Claus Franz Vogelmeier, Stefan Zielen, István Albert, Beatrix Bálint, Mária Csilla Hangonyi, Teréz Kecskés, Anikó Kurucz, Balázs Medgyasszay, Lajos Molnár, János Mucsi, Márta Papp, Magdolna Póczi, Éva Radeczky, Zsolt Pápai Székely, Csilla Szabó, Gyöngyi Szabó, Melinda Szabó, Alfredo Antonio Chetta, Giuseppe Di Maria, Giulio Donazzan, Federica Meloni, Elisabetta Pace, Pierluigi Paggiaro, Alberto Papi, Fabio Luigi, Massimo Ricciardolo, Antonio Spanevello, Fumiaki Aoki, Ryosuke Eda, Takeo Endo, Yasushi Fukushima, Kenichi Gemba, Naoki Hagimoto, Hiromasa Harada, Yasuko Harada, Norihiko Hata, Osamu Hataji, Nobuo Hatakeyama, Takahiko Horiguchi, Gen Ideura, Motoyasu Iikura, Azusa Ikegami, Shirou Imokawa, Yoshikazu Inoue, Takeshi Isobe, Ryoji Ito, Susumu Iwata, Tadashi Kamei, Motokazu Kato, Hideki Katsura, Yuji Kawarada, Norio Kihara, Masaharu Kinoshita, Takashi Kinoshita, Tomoo Kishaba, Hideo Kita, Arihiro Kiyosue, Shigeru Komatsu, Kazuki Konishi, Sekiya Koyama, Makoto Kudo, Kazuhiko Machida, Hironi Makita, Hiroto Matsuse, Naoki Miyazawa, Hiroyuki Nakamura, Yuji Nakatani, Kazuyuki Nishimura, Takashi Nishimura, Junichi Ogawa, Hiroyuki Ohbayashi, Tetsuro Ohdaira, Tsukasa Ohnishi, Kazuhiko Oki, Masahiko Saito, Kenji Sakamoto, Osamu Sakamoto, Hisakuni Sekino, Noriharu Shijubo, Masaharu Shinkai, Hideo Soto, Yoshitaka Sugawara, Noriaki Suko, Hisaho Takahashi, Masamitsu Takahashi, Tsuneyuki Takahashi, Hiroshi Tanaka, Hiroyuki Taniguchi, Tadayuki Terada, Takao Tochigi, Kazuyo Tohyama, Hirokazu Tokuyasu, Keisuke Tomii, Tomomasa Tsuboi, Mitsuyoshi Utsugi, Katsumaru Yamamoto, Michiko Yamamoto, Shuichi Yano, Makoto Yoshida, Frank Custers, Richard Dekhuijzen, Remco Djamin, Jan Willem Van Dan Berg, Lowie Vanfleteren, Pascal Wielders, Bogusława Cimoszko, Anna Doboszyńska, Andrzej Dyczek, Andrzej Fal, Krystyna Folcik, Łukasz Goliński, Marek Jutel, Andrzej Kolczyński, Piotr Kuna, Ewa Łączyńska, Wojciech Machowiak, Maciej Marczak, Joanna Markiewicz, Janusz Milanowski, Grzegorz Mincewicz, Maria Nittner-Marszalska, Wojciech Papiewski, Małgorzata Pawlukiewicz, Witold Pomiećko, Barbara Rewerska, Cezary Rybacki, Wojciech Skucha, Ewa Trębas-Pietraś, Ewa Uhryn, Małgorzata Żurowska-Gębala, Laurentia Andrei, Traian Mihaescu, Stefan Mihaicuta, Eniko Vera Pall, Ioan Petrui, Angelica Savu, Claudia Toma, Ana Trailescu, Vladimir Abrosimov, Nataliya Astafyeva, Evgenyi Bazdyrev, Nadezhda Berdnikova, Laura Bolieva, Ekaterina Bukreeva, Valery Chistyakov, Anna Galustyan, Halida Gantseva, Svetlana Goncharova, Sergey Grigoriev, Galina Ignatova, Inna Ilyashevich, Nadezhda Izmozherova, Magomed Kamalov, Yaroslava Khovaeva, Natalia Kuzubova, Lyudmila Kvitkova, Liudmila Lenskaya, Igor Leshchenko, Olga Magnitskaya, Boris Molotilov, Artem Molotkov, Svetlana Myasoedova, Sergey Nedogoda, Vladimir Nosov, Marina Osipenko, Andrey Peskov, Veronika Popova, Oksana Ratushnay, Irina Ryzhova, Olga Shangina, Natalia Shaporova, Evgeny Shmelev, Lybov Shpagina, Alexander Shutkin, Yuri Shvarts, Mikhail Smirnov, Irina Stitsenko, Maksim Vasilev, Arkadiy Vertkin, Elena Vishneva, Alexander Vizel, Anna Zateyschikova, Mohamed Abdool-Gaffar, Ismail Abdullah, Axel Bruning, Nyda Fourie, Michael Greenblatt, Mohammed Tayob, K Venter, An Soo Jang, Kwan Ho Lee, Sang Haak Lee, Sook Young Lee, Suk Joong Yong, Kwang Ha Yoo, Soo Taek Uh, Ramón Agüero Balbín, David Ramos Barbón, Álvar Agustí García-Navarro, José Luis Velasco Garrido, Sergi Pascual Guardia, Eduard Monso Molas, Luis De Teresa Parreño, Borja García-Cosio Piqueras, German Peces-Barba Romero, Myriam Calle Rubio, Fernando Sánchez-Toril López, Alicia Marín Tapia, Heidi Martin Braschler, Martin Brutsche, Michael Grob, Jörg Leuppi, Daiana Stolz, Alexander Turk, Nawar Bakerley, Mona Bafadhel, Christopher Brightling, Rekha Chaudhuri, Gourab Choudhury, Graham Devereux, Imran Hussain, Kai Lee, William MacNee, Ravindran Mahadeva, Matthew Masoli, Monica Nordstrom, Manish Patel, Allan Reid, Dinesh Saralaya, Tariq Sethi, Sukh Dave Singh, Anthony G de Soyza, Tom Wilkinson, Alice Turner, Helen Ward, Chandar Abboy, Ivan Ackerman, Idalia Acosta, Arun Adlakha, Bassil Aish, Mohamed Ali, Charles Andrews, Robby Ayoub, Anil Badhwar, Dennis Bassetti, Sherif El Bayadi, Richard Beasley, Shashi Bellam, Jonathan Bernstein, Maria Blahey, Scott Bloom, Eugene Bleecker, Wesley Bray, Johnathan Brewer, Robert Buynak, William Calhoun, Edward Campbell, Anthony Captain, Birjis Chinoy, Kenneth Chinsky, Geoffrey Chupp, Arsenio Columbie, Clinton Corder, Gerard Criner, Humberto Cruz, Edward Cullen, Kevin Deboer, Michael Denenberg, Mark Dransfield, Leonard Dunn, Miles Elmore, David Erb, Faisal Fakih, Gary Ferguson, Charles Fogarty, Mark Freed, Stephen Fritz, David Fuentes, Shariar Cohen-Gadol, Robert Garver, John Given, Luis Ramos Gonez, Raul Ebran Gonzalez, Robert Gordon, Gregory Gottschlich, Donald Graham, David Grant, Gary Greenwald, James Greenwald, Kenneth Haft, Gregory Hammond, Nadia Hansel, Jeffrey Harris, Humberto Hernandez, Marvin Heuer, Albrecht Heyder, David Hill, Willis Holloway, Octavian Ioachimescu, Richard Jackson, Ajay Jain, Nan Jiang, Thomas Kaelin, Adolfo Kaplan, Mitchell Kaye, Akram Khan, Yekaterina Khronusova, Ryan Klein, Joel Kline, Firas Koura, Ritsu Kuno, Ware Kuschner, Jean Claude Labissiere, David Laman Jr, John Lee, Mitchell Lee, Lawrence Levinson, Njira Lugogo, M Mador, Nathaniel Marchetti, Rafael Martinez, Richard Martinez, Peter Mattar, David Maybee, Dennis McGraw, Michael McGuire, Curtis Mello, Aaron Milstone, John Mitchell, Wendy Moore, Timothy Moriarty, Cheta Nand, Brooke Nevins, Ikeadi Ndukwu, Rachel Nisbet, David Nyanjom, Maria Nualart, Thomas O'Brien, Mikhail Palatnik, Gnyandev Patel, Amit Patel, Guido Perez, Christopher Perry, Michael Pfeffer, Krishna Pudi, Marina Raikhel, Murali Ramaswamy, Joe Ramsdell, Donato Ricci, Gary Richmond, Eugene Ryan, Fadi Saba, Boris Sagalovich, C Andrew Schroeder, Timothy Scialla, Frank Sciurba, Amit Shah, Nirav Shah, Zeeshan Shaikh, Akhtar Siddiqui, Barry Sigal, Thomas Siler, Howard Silverboard, William Sims, Clyde Southwell, Selwyn Spangenthal, Peruvemba Sriram, James Stocks, Tony Su, John Suen, Robert Sussman, Horia Tatu, Antonio Terrelonge, Alan Thomas, Mario Torres, Rodolfo Trejo, Miguel Trevino, Banks Turner, Manuel Villareal, Janine Vintch, Neal Warshoff, Jan Westerman, Philip Wexler, Thomas Yunger, Amir Zeki, Mariano Fernandez Acquier, Norma Aramayo, German Arce, Juan Belloni, Víctor Cambursano, Carlos De La Vega, Fernando Rodriguez Chariarse, Pedro Elias, Marcelo Fernández, Ana Lopez, Andrea Medina, María Otaola, Maria Salazan Saez, Maria De Salvo, Fernando Scherbovsky, Ana Stok, Jorge Taborda, Alberto Tolcachier, Fernando Verra, Carlos Victorio, Rita Gisela Delgado Vizcarra, Philip Bardin, Peter Bremner, Martin Phillips, John Upham, Peter Wark, Antoine Bolly, Alain Delobbe, Peter Driesen, Eduard Janssens, Wim Janssens, Olivier Michel, Bernard Vandooren, Martti Antila, Jussara Fiterman, Carlos Fritscher, Jorge Hetzel, Jose Jardim, Waldo De Mattos, Rafael Martins, Maria Eunice De Oliveira, Andreia Pez, Maria Sales, Rafael Stelmach, Priscila Wolff, Svetla Andreeva, Reneta Antonova, Ana Dancheva, Yuliya Ivanova, Slavcho Ivanov, Hristo Metev, Iveta Naydenova, Tatyana Petkova, Galina Petrova, Kostadinka Sotirova, Mariyana Stoyanova, Rumen Tiholov, Iliyana Valkanova, Oleg Yakov, Rosa Feijoo, Juana Pavie, Patricia Schönffeldt, Absalon Silva, Victor Martinez, David Espinosa, Alejandro Londono, Dora Molina, Gonzalo Prada, Andrés Rico, Gregorio Sanchez Vallejo, Alvaro Urbina, Ana Vanegas, Maria Villegas, Josip Aralica, Gordana Stjepanovic, Vibeke Backer, Uffe Bødtger, Christian Meyer, Læge Sven Nielsen, Anders Loekke Ottesen, Ingrid Titlestad, Nathalie Bautin, Arnaud Bourdin, Pascal Chanez, Francis Couturaud, Antoine Cuvelier, Gilles Devouassoux, Pierre-Olivier Girodet, Jean-François Muir, Jean-Louis Pépin, Alain Proust, Azzedine Yaici, Yochai Adir, Gershon Fink, Zvi Fridlender, Gabriel Izbicki, Mordechai Kramer, Yehuda Schwartz, Juan Moreno Hoyos Abril, Ricardo Campos Cerda, Efraín Montaño Gonzalez, Ricardo Ramirez Terrones, Rodolfo Posadas Valay, Alejandra Ramirez-Venegas, Paul Dawkins, Syed Hussain, Benedict Brockway, John Richmond, Colin Helm, Catherina Chang, Jørn Ahlqvist, Terje Tollåli, Tadeusz Tomala, Socorro Castro, William Chavez, Octavio Cubas, Rolando Estrella, Efrain Felix, Ronal Gamarra, Alfredo Guerreros, Alberto Matsuno, Danilo Salazar, Miguel Tsukayama, Albert Albay Jr, Teresita Aquino, Tito Atienza, Joven Roque Gonong, Ronnie Samoro, Joel Santiaguel, Beata Asankowicz-Bargiel, Ewa Pisarczyk-Bogacka, Renata Bijata-Bronisz, Marta Chełmińska, Małgorzata Dobryniewska, Anna Olech-Cudzik, Tomasz Fijołek, Krzysztof Filipek, Agata Kot, Bożena Kucińska, Krzysztof Lis, Elżbieta Rybicka-Liszewska, Marzenna Tarnowska-Matusiak, Robert Mróz, Piotr Napora, Wojciech Naumnik, Artur Niemiec, Władysław Pierzchała, Grzegorz Przybylski, Katarzyna Styka, Danuta Wrońska, Branislava Milenkovic, Dobrivoje Novkovic, Matijaz Flezar, Niksa Segota, Snezana Ulcar Kostic, Albert Klobucar, Leif Bjermer, Dan Curiac, Christer Janson, Pekka Koskinen, Bo Lundback, Åke Olsson, Shih-Lung Cheng, Ming-Lin Ho, Jeng-Yuan Hsu, Wu-Huei Hsu, Ping-Hung Kuo, Chin-Chou Wang, Yu-Feng Wei, Kuang-Yao Yang, Watchara Boonsawat, Somchai Chantarothorn, Warangkana Keeratichananont, Kittipong Maneechotesuwan, Kanok Pipatvech, Piamlarp Sangsayunh, Sibel Arinc, Sermin Borekci, Arzu Kaner Erturk, Filiz Kosar, Hakan Gunen, Ismail Hanta, Pinar Akin Kabalak, Tunc Alp Demir, Sibel Nayci, Serir Aktogu Ozkan, Abdullah Sayiner, Esra Uzaslan, Viktor Blazhko, Volodymyr Gavrysyuk, Olena Golub, Liudmyla Iashyna, Tetiana Ilashchuk, Volodymyr Koshlia, Olena Krakhmalova, Vitali Kryvenko, Lesia Kuryk, Olena Levchenko, Yuriy Mostovoy, Mykola Ostrovskyy, Tetyana Pertseva, Olena Piura, Nadiya Rudnytska, Ganna Stupnytska, Nataliia Velychko, Oleh Yakovenko, Lilia Rodriguez Ables, Roger Abrahams, Bassil Aish, Jose Alvarez, Fernando Arencibia, Chander Arora, Samir Arora, Francis Averill, Kwabena Ayesu, Stephen Basheda, Steven Bauer, Jose Bautista, Matthew Beacom, Richard Beasley, Hernando Bernal, Subodh Bhuchar, J'Cinda Bitters, John Burk, Elizabeth Burkett, James Cain, Robert Call, Christopher Chappel, Bartolome Celli, Tom Christensen, Jeremy Cole, Jerome Daniel, Nguyen Dang, Enrique Davis, Samuel Deleon, Robert DeLuca, Ernesto Diaz, Anthony DiMarco, Calvin Dixon, Ankur Doshi, Hugh Durrence, Alain Eid, John Elsen, Herbon Fleming, May Flores, Charles Fogarty, Scott Franczek, Stephen Fritz, Gregory Funk, Stuart Garay, Bernard Garcia, Luis Ramos Gonez, Gregory Gottschlich, Joseph Graif, Carl Griffin, Yamirka Duardo Guerra, David Headley, Mitzie Hewitt, Susan Hole, Robert Holladay, Ira Horowitz, Yu-Luen Hsu, Jonathan Ilowite, Stephen Jones, Ravindra Kashyap, Edward Kerwin, Ahtaram Khan, Nicole Kimzey, James Krainson, Flory Kreutter, Kannappan Krishnaswamy, Shahrukh Kureishy, Albert Lai, Alex Lechin, Daria Lee, Marcus Lee, Williams Leeds, Joseph Lillo, Edward Lisberg, Lawrence Madoff, Narendra Maheskwari, Mujibur Majumder, Sashi Makam, Douglas Mapel, Matthew Mardiney, Jennifer Martin, David Maybee, Isaac Melamed, Elvin Mendez, Stuart Millstone, Joseph Montes, Lee Morrow, Frank Murphy, Dany Obeid, France Occy, Godson Oguchi, Juan Ortiz, Francisco Padron, Ward Paine, James Pearle, Enrique Pelayo, Vandely Perez, David Pham, Carlos Piniella, Kevin Pritchett, Padmashri Rastogi, Stephen Ryan, Syed Rehman, Jackson Rhudy, Eustace Riley, James Riser, Clifford Risk, Emory Robinette, Christopher Roney, Gary Ruoff, David Russian, Mercedes Samson, Jay Sandberg, Jose Santiago, William Sargeant, Alan Schecter, Frank Sciurba, Jeffrey Scott, Ilia Segal, Sudhir Sehgal, Frederic Seifer, Sudhir Sekhsaria, Richard Sellman, Paul Shapero, Jeffrey Shea, Lawrence Sher, John Sibille, Jawed Siddiqui, William Sims, Toniya Singh, Deren Sinkowitz, Denise Smyth, Daniel Soteres, Daniel Sousa, Ralph Steele, Thomas Stern, Jose Suarez, Sever Surdulescu, Ricardo Tan, Tonny Tanus, Raymond Tidman, Aurelio Torres-Consuegra, Barry Troyan, John Updegrove, Sanjay Vadgama, Armando Pineda-Velez, Eduardo Viera, Andrew Wachtel, Ralph Wade, Jimin Wang, Dave Webster, Paul Weinberg, Terry Wells, Jeffrey White, Bram Wieskopf, Hugh Windom, Patrick Wright, David Wyatt, Bassam Yousef, Zahid Zafar, Chau Ngo, Huong Le, Lan Nguyen, Thanh Nguyen, Nhung Nguyen

Subjects
Male, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Anti-asthmatic Agent, law.invention, Pulmonary Disease, Chronic Obstructive, Leukocyte Count, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Monoclonal, Receptors, Medicine, Anti-Asthmatic Agents, 030212 general & internal medicine, Humanized, COPD Exacerbations, benralizumab, clinical trials, COPD, Subcutaneous, General Medicine, Middle Aged, anti–IL-5Rα, Benralizumab, Pulmonary Disease, Chronic Obstructive/drug therapy, [SDV] Life Sciences [q-bio], Female, Antibodies, Monoclonal, Humanized/administration & dosage, Chronic Obstructive, Benralizumab COPD exacerbations, Injections, Subcutaneous, Socio-culturale, Aged, Antibodies, Monoclonal, Humanized, Double-Blind Method, Eosinophils, Humans, Patient Acuity, Receptors, Interleukin-5, Antibodies, chronic obstructive pulmonary disease, Injections, Pulmonary Disease, 03 medical and health sciences, Phase III, Anti-Asthmatic Agents/administration & dosage, In patient, business.industry, Eosinophils/metabolism, medicine.disease, Clinical trial, Receptors, Interleukin-5/antagonists & inhibitors, chemistry, Multicenter study, randomized controlled trial, Immunology, Interleukin-5, business
Abstract

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Published
2019

43. Aspergillus-related diseases in a cohort of patients with severe asthma: A SANI single-center report

Author

Irene Ridolfi, Luisa Brussino, Giorgio Walter Canonica, Stefania Nicola, Enrico Heffler, Giovanni Rolla, Paolo Solidoro, Francesco Blasi, Caterina Bucca, Pierluigi Paggiaro, and Diego Bagnasco

Subjects
medicine.medical_specialty, Aspergillus, Bronchiectasis, biology, business.industry, Severe asthma, Aspergillosis, Allergic Bronchopulmonary, Allergic Bronchopulmonary, biology.organism_classification, Single Center, medicine.disease, Asthma, Aspergillus fumigatus, Cohort Studies, Humans, Internal medicine, Cohort, medicine, Aspergillosis, Immunology and Allergy, business, Cohort study
Published
2020

44. Asthma as a co-morbidity and cause of bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)

Author

Apostolos Bossios, Federico L. Dente, Katerina Dimakou, Antonio Spanevello, Letizia Traversi, Stefano Aliberti, Eva Polverino, Pierluigi Paggiaro, James D. Chalmers, Michal Shteinberg, Sebastian Ferri, Yochaid Adir, Miguel Ángel Martínez-García, and George Ghillas

Subjects
medicine.medical_specialty, Bronchiectasis, business.industry, Disease, medicine.disease, Lower risk, Respiratory symptom, Quality of life, Internal medicine, medicine, Co morbidity, Clinical significance, business, Asthma
Abstract

Introduction: asthma is frequently reported in patients with bronchiectasis but its clinical significance is unclear. Methods: The European Bronchiectasis Registry (EMBARC) was studied from Jan 2015 to June 2019. Severity of disease was evaluated using the Bronchiectasis severity index (BSI) and FACED. Quality of life using the QOL-B questionnaire. Asthma was reported by the investigator. Results: Of 13512 patients included in the analysis, asthma was reported in 4119 (30.5%) making it the most common co-morbidity in bronchiectasis. Despite similar age (mean 63 vs 65 years,p=0.3) and similar P. aeruginosa infection rates (21% vs 20%,p=0.005), patients with comorbid asthma had milder severity (BSI 7.6 vs 7.8,p Conclusions: Co-existing asthma in bronchiectasis is associated with increased exacerbations, respiratory symptom and, surprisingly, lower risk of NTM but reasons are unclear.

Published
2020

45. The hidden burden of severe asthma: from patient perspective to new opportunities for clinicians

Author

Catherine M. Hawrylowicz, Robert H. Brown, Todor A. Popov, Pierachille Santus, Stefano Centanni, Paolo Solidoro, Maria Gabriella Matera, Angelo Corsico, Andrea Matucci, Enrico Heffler, Gaetano Caramori, Pierluigi Paggiaro, Mina Gaga, Giorgio Walter Canonica, Alberto Papi, Alkis Togias, Paola Rogliani, Fabiano Di Marco, Louis-Philippe Boulet, Antonella Cianferoni, Nicola Scichilone, Alida Benfante, Battaglia S, Mario Cazzola, Peter J. Barnes, Giuseppe De Carlo, Scichilone, Nicola, Barnes, Peter John, Battaglia, Salvatore, Benfante, Alida, Brown, Robert, Canonica, Giorgio Walter, Caramori, Gaetano, Cazzola, Mario, Centanni, Stefano, Cianferoni, Antonella, Corsico, Angelo, De Carlo, Giuseppe, Di Marco, Fabiano, Gaga, Mina, Hawrylowicz, Catherine, Heffler, Enrico, Matera, Maria Gabriella, Matucci, Andrea, Paggiaro, Pierluigi, Papi, Alberto, Popov, Todor, Rogliani, Paola, Santus, Pierachille, Solidoro, Paolo, Togias, Alki, and Boulet, Louis-Philippe

Subjects
severe asthma, medicine.medical_specialty, Severe asthma, precision medicine, Acknowledgement, lcsh:Medicine, Socio-culturale, Review, Disease, biomarkers, patient’s perspective, precision medicine, severe asthma, Medical care, 03 medical and health sciences, Therapeutic approach, 0302 clinical medicine, Medicine, 030212 general & internal medicine, ddc:610, Intensive care medicine, business.industry, lcsh:R, Perspective (graphical), General Medicine, Research opportunities, Biomarkers, patient’s perspective, precision medicine, severe asthma, Biomarkers, Patient’s perspective, Precision medicine, patient’s perspective, Natural history, 030228 respiratory system, business
Abstract

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the “International Course on Severe Asthma” that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient’s needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach.

Published
2020

46. Real-life Mepolizumab effectiveness in severe eosinophilic asthmatics with nasal polyposis

Author

Pierachille Santus, Elena Bargagli, Manuela Latorre, Gianna Camiciottoli, Angelo Corsico, Pierluigi Paggiaro, Bruno Sposato, Stefano Baglioni, Simonetta Masieri, Corrado Pelaia, Antonino Musarra, Carlo Cavaliere, Nicola Murgia, Girolamo Pelaia, Mauro Maniscalco, Paola Rogliani, Alberto Ricci, Marco Scalese, Giovanna Elisiana Carpagnano, Amelia Grosso, and Ilenia Folletti

Subjects
Pulmonary and Respiratory Medicine, Mepolizumab, Nasal polyposis, Outcomes, Real-life, Severe eosinophilic asthma, medicine.medical_specialty, business.industry, Antibodies, Monoclonal, Humanized, Dermatology, Asthma, NO, Nasal Polyps, Mepolizumab, Severe eosinophilic asthma, Nasal polyposis, Outcomes, Real-life, Eosinophilic, Medicine, Humans, business, medicine.drug
Published
2020

47. Mepolizumab effectiveness and allergic status in real life

Author

Carlo Cavaliere, Giovanna Elisiana Carpagnano, Mauro Maniscalco, Simonetta Masieri, Alberto Ricci, Bruno Sposato, Pierachille Santus, Amelia Grosso, Ilenia Folletti, Pierluigi Paggiaro, Corrado Pelaia, Antonino Musarra, Angelo Corsico, Elena Bargagli, Stefano Baglioni, Manuela Latorre, Paola Rogliani, Marco Scalese, Gianna Camiciottoli, Nicola Murgia, Girolamo Pelaia, Sposato, B., Scalese, M., Camiciottoli, G., Carpagnano, G. E., Pelaia, C., Santus, P., Maniscalco, M., Corsico, A., Grosso, A., Baglioni, S., Murgia, N., Folletti, I., Pelaia, G., Masieri, S., Cavaliere, C., Musarra, A., Bargagli, E., Ricci, A., Latorre, M., Paggiaro, P., and Rogliani, P.

Subjects
severe asthma, medicine.medical_specialty, Severe asthma, Immunology, Eosinophilic asthma, allergic, Antibodies, Monoclonal, Humanized, Immunoglobulin E, medicine.disease_cause, outcomes, Severity of Illness Index, Gastroenterology, NO, Diagnosis, Differential, Allergen, real life, Internal medicine, Anti-Allergic Agents, Eosinophilic, Hypersensitivity, Odds Ratio, medicine, Settore MED/10, Humans, Immunology and Allergy, In real life, Retrospective Studies, biology, business.industry, eosinophilic, mepolizumab, General Medicine, Asthma, Mepolizumab, Severe asthma, Eosinophilic, Allergic, Outcomes, Real life, Respiratory Function Tests, Discontinuation, Eosinophils, Treatment Outcome, biology.protein, business, Mepolizumab, Biomarkers, medicine.drug
Abstract

Background: It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. Objective: We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. Method: We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; n: 97–72.4%), and nonallergic, with no prick test results and normal IgE levels n: 37–27.6%). They had taken mepolizumab for at least 6 months. Results: After 10.9 ± 3.7 months, improvements in FEV1%, FEF25–75%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting β2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5–9]) than in SAEA (5 [2.5–8.5]; p = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV1 >80%, FEF25–75 >65%, exacerbations ≤2, BE 1% (β = −0.110; p = 0.266), FEF25–75% (β = −0.228; p = 0.06), BE counts (β = −0.012; p = 0.918), FENO (β = 0.234; p = 0.085), ACT (β = 0.046; p = 0.660), and exacerbations (β = −0.070; p = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV1 >80%: OR = 1.04 [95% CI: 0.43–2.55], p = 0.923; FEF25–75 >65%: OR = 0.41 [95% CI: 0.08–2.03], p = 0.272) were detected. Neither all other parameters, such as ACT >20 (OR = 0.73 [95% CI: 0.32–1.63], p = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55–3.27], p = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40–3.39], p = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40–29.27], p = 0.258), were differently associated with 1 or the other phenotype. Conclusion: Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life.

Published
2020

48. Characterization of Occupational Eosinophilic Bronchitis in a Multicenter Cohort of Subjects with Work-Related Asthma Symptoms

Author

Marta Wiszniewska, Perrine Dellis, Vera van Kampen, Hille Suojalehto, Xavier Munoz, Jolanta Walusiak-Skorupa, Irmeli Lindström, Rolph Merget, Christian Romero-Mesones, Joaquin Sastre, Santiago Quirce, Paola Mason, Catherine Rifflart, Julien Godet, Frédéric de Blay, Olivier Vandenplas, Pavlina Klusackova, David Sherson, Katri Suuronen, Pirjo Hölttä, Paula Kauppi, Laura Hurdubaea, Nicolas Migueres, Rolf Merget, Alexandra M. Preisser, Volker Harth, Piero Maestrelli, Gianna Moscato, Patrizia Pignatti, Pierluigi Paggiaro, Donatella Talini, Marco dell’Omo, Ilenia Foletti, Cecilie Svanes, Jorunn Kirkeleit, Agnieszka Lipińska-Ojrzanowska, Mar Fernandez-Nieto, David Loli, Paul Cullinan, Julie Cannon, Sherwood Burge, Vicky Moore, Jennifer Hoyle, UCL - (MGD) Service de pneumologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, and UCL - SSS/IREC/PNEU - Pôle de Pneumologie, ORL et Dermatologie

Subjects
medicine.medical_specialty, Eosinophilic bronchitis, Occupational disease, Nitric Oxide, Gastroenterology, 03 medical and health sciences, Specific inhalation challenge, FEV1/FVC ratio, 0302 clinical medicine, stomatognathic system, Internal medicine, medicine, Humans, Immunology and Allergy, 030212 general & internal medicine, Asthma, Occupational, Bronchitis, Retrospective Studies, Asthma, Occupational diseases, business.industry, Sputum, medicine.disease, Occupational, respiratory tract diseases, Eosinophils, 030228 respiratory system, Exhalation, Bronchial hyperresponsiveness, Cohort, Exhaled nitric oxide, medicine.symptom, business
Abstract

Background Occupational eosinophilic bronchitis (OEB) has been described only as anecdotal case reports. Objective We investigated the clinical and inflammatory characteristics of subjects with OEB identified in a cohort of subjects who completed a specific inhalation challenge (SIC) with occupational agents. Methods In this retrospective multicenter study, OEB was defined by (1) a fall in FEV1 less than 15% during the SIC and the absence of nonspecific bronchial hyperresponsiveness both before and after the SIC and (2) a postchallenge increase of 3% or more in sputum eosinophils. The subjects who fulfilled these criteria were compared with 226 subjects with a negative SIC and 30 subjects with a positive SIC who failed to show baseline nonspecific bronchial hyperresponsiveness. Results An isolated increase in postchallenge sputum eosinophils was documented in 33 of 259 subjects (13%) with a negative SIC. These subjects reported significantly more often an isolated cough at work compared with the negative and positive SIC controls. When compared with positive SIC controls, the subjects with OEB experienced less frequently work-related wheezing and reported a shorter duration of symptoms at work. The sensitivity of the post-SIC increase in fractional exhaled nitric oxide in identifying OEB among subjects with a negative SIC was low, ranging from 43% to 24% using cutoff values of 8 ppb to 17.5 ppb, whereas the specificity was high (90%-97%). Conclusions This study highlights the relevance of induced sputum analysis in the investigation of work-related asthma symptoms to identify isolated increases in sputum eosinophils that are consistent with a diagnosis of OEB.

Published
2020

49. What drives inhaler prescription for asthma patients? Results from a real-life retrospective analysis

Author

Pierluigi Paggiaro, Fulvio Braido, A. Gentile, Federico Lavorini, A. Soldi, V. Pegoraro, Nicola Scichilone, F. Di Marco, Paola Rogliani, Girolamo Pelaia, G.W. Canonica, A. Bianco, Angelo Corsico, Pierachille Santus, Francesco Blasi, Lavorini, F., Bianco, A., Blasi, F., Braido, F., Corsico, A. G., Di Marco, F., Gentile, A., Paggiaro, P. L., Pegoraro, V., Pelaia, G., Rogliani, P., Santus, P., Scichilone, N., Soldi, A., Canonica, G. W., Lavorini F., Bianco A., Blasi F., Braido F., Corsico A.G., Di Marco F., Gentile A., Paggiaro P.L., Pegoraro V., Pelaia G., Rogliani P., Santus P., Scichilone N., Soldi A., and Canonica G.W.

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Multivariate analysis, Settore MED/10 - Malattie Dell'Apparato Respiratorio, General practitioner, 03 medical and health sciences, dry powder inhaler, 0302 clinical medicine, Inhalers, Adrenal Cortex Hormones, Adrenergic beta-2 Receptor Antagonists, Asthma control, General practitioners, Administration, Inhalation, Retrospective analysis, Medicine, 030212 general & internal medicine, Metered Dose Inhalers, Medical prescription, Asthma, Retrospective Studies, business.industry, Inhaler, dry powder inhalers, Odds ratio, medicine.disease, Confidence interval, Pressurised metered-dose inhaler, Pressurised metered-dose inhalers, Respiratory specialists, Prescriptions, 030228 respiratory system, Inhalation, Delayed-Action Preparations, Emergency medicine, Administration, business, Dry Powder Inhalers
Abstract

Background The choice of inhaler device for asthma patients depends upon multiple attributes. We investigated factors that may drive general practitioners (GPs) and respiratory specialists in the prescription of inhaler devices for asthma patients who initiated inhalation therapy. Methods We retrospectively analysed prescriptions by GPs and respiratory specialists to asthma patients commencing inhaled corticosteroid/long-acting β2-agonist combination therapy available as both pressurised metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs). Patient characteristics were compared by device and multivariate analysis was used to model the likelihood of receiving a pMDI as opposed to a DPI in order to identify drivers for prescription. A sample of the respiratory specialists completed an ad-hoc survey of their perceived success in achieving asthma control in their patients and barriers to attaining full control. Results Prescription of a particular inhaler device was unrelated to the characteristics of the patients. Multivariate analysis revealed that the main driver for the choice of inhaler device choice was the medication (Odds Ratio and 95% Confidence Interval, respectively for GPs and specialists: 0.19 [0.16–0.23]; 0.17 [0.08–0.37]). Specialists perceived asthma as being inadequately controlled in 41% of their patients, and considered patients' difficulties in using DPIs and pMDIs as instrumental in this, citing a need for a novel, more effective inhaler technology. Conclusion Physicians choose inhaler devices according to the prescribed drugs and not to the characteristics of the individual patient. This may reflect a lack of confidence in existing inhaler devices and underlines the need for technologies, which are more reliable and easier to use by patients.

Published
2020

50. Fluticasone furoate, umeclidinium bromide, and vilanterol as a combination therapy for chronic obstructive pulmonary disease

Author

Dario Nieri, Maria Adelaide Roggi, Alessandro Celi, Barbara Vagaggini, Pierluigi Paggiaro, and Giulia Parri

Subjects
Pulmonary and Respiratory Medicine, Quinuclidines, medicine.medical_specialty, Combination therapy, medicine.drug_class, Pulmonary disease, Chronic obstructive pulmonary disease (COPD), macromolecular substances, Umeclidinium bromide, Chlorobenzenes, Gastroenterology, Fluticasone propionate, fluticasone furoate, triple therapy, Immunology and Allergy, Public Health, Environmental and Occupational Health, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Adrenal Cortex Hormones, Internal medicine, Administration, Inhalation, medicine, Humans, 030212 general & internal medicine, Benzyl Alcohols, biology, business.industry, Environmental and Occupational Health, Lama, biology.organism_classification, Fluticasone-Salmeterol Drug Combination, Bronchodilator Agents, Androstadienes, 030228 respiratory system, chemistry, Quality of Life, Corticosteroid, Drug Therapy, Combination, Public Health, Vilanterol, business, hormones, hormone substitutes, and hormone antagonists, medicine.drug
Abstract

Introduction: Triple therapy with two bronchodilators (LABA plus LAMA) and an inhaled corticosteroid (ICS) is recommended for patients suffering from severe chronic obstructive pulmonary di...

Published
2018

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