Different skin prick test sensitization patterns do not influence the response to omalizumab in severe asthma

Exploring the relevance and extent of small airways dysfunction in asthma (ATLANTIS): baseline data from a prospective cohort study

BACKGROUND: Small airways dysfunction (SAD) is well recognised in asthma, yet its role in the severity and control of asthma is unclear. This study aimed to assess which combination of biomarkers, physiological tests, and imaging markers best measure the presence and extent of SAD in patients with asthma.METHODS: In this baseline assessment of a multinational prospective cohort study (the Assessment of Small Airways Involvement in Asthma [ATLANTIS] study), we recruited participants with and without asthma (defined as Global Initiative for Asthma severity stages 1-5) from general practices, the databases of chest physicians, and advertisements at 29 centres across nine countries (Brazil, Chi…

Overcoming Barriers to the Effective Management of Severe Asthma in Italy.

Pierluigi Paggiaro,1 Simona Barbaglia,2 Stefano Centanni,3,4 Davide Croce,5 Enrico Desideri,6 Saffi Giustini,7,8 Claudio Micheletto,9 Antonino Musarra,10 Nicola Scichilone,11 Ugo Trama,12 Maria Teresa Zedda,7,13 Giorgio Walter Canonica14 1Department of Surgery, Medicine, Molecular Biology, and Critical Care, University of Pisa, Pisa, Italy; 2Associazione Nazionale Pazienti “Respiriamo Insieme”, Padova, Italy; 3Department of Health Sciences, Università degli Studi di Milano, Milan, Italy; 4Respiratory Unit, ASST Santi Paolo e Carlo, Milan, Italy; 5Center for Health Economics, Social and Health Care Management, LIUC-Università Cattaneo, Castellanza, I…

Fluticasone propionate/formoterol: a fixed-combination therapy with flexible dosage.

International guidelines describe asthma control as the main outcome of asthma management. Prevention of symptoms, improved quality of life, and reduction of exacerbations are the main components, consequently decreasing health care costs. However, many of these objectives remain unmet in real life: several surveys show that a large proportion of asthmatic patients are not well controlled despite the efficacy of current available treatment. Several randomized controlled clinical trials indicate that combining inhaled corticosteroids and long-acting β2-agonists, by means of a single inhaler, greatly improves the management of the disease. The results of 9 multicenter phase III clinical studi…

Mepolizumab effectiveness on small airway obstruction, corticosteroid sparing and maintenance therapy step-down in real life

Background: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life. Methods: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV1%:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months). Results: FEV1% improved significantly after MEP. Mean FEF25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/μ…

Why use long acting bronchodilators in chronic obstructive lung diseases? An extensive review on formoterol and salmeterol

Abstract Long-acting β 2 -adrenoceptor agonists, formoterol and salmeterol, represent a milestone in the treatments of chronic obstructive lung diseases. Although no specific indications concerning the choice of one molecule rather than another are provided by asthma and COPD guidelines, they present different pharmacological properties resulting in distinct clinical employment possibilities. In particular, salmeterol has a low intrinsic efficacy working as a partial receptor agonist, while formoterol is a full agonist with high intrinsic efficacy. From a clinical perspective, in the presence of low β 2 -adrenoceptors availability, like in inflamed airways, a full agonist can maintain its b…

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

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 al…

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

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 oppos…

Differences in the efficacy and safety among inhaled corticosteroids (ICS)/long-acting beta2-agonists (LABA) combinations in the treatment of chronic obstructive pulmonary disease (COPD): Role of ICS

Inhaled corticosteroids (ICS) are frequently recommended for the treatment of asthma and COPD, often in combination with long-acting beta2-agonists (LABA), depending on the severity of the disease and/or on the specific phenotype. Several ICS/LABA combinations are currently available that differ in their pharmacokinetic characteristics and dose of both components. Thus, this review assesses differences in the efficacy and the safety profiles of the ICS components in the two more frequently used ICS/LABA combinations (budesonide/formoterol and fluticasone/salmeterol) for the management of COPD. Whereas the basic mechanism of action is similar for all ICS (binding with the intracellular gluco…

On-line Italian register for severe/non-controlled asthma

Background Severe/Non-controlled asthma (SNCA) is a crucial challenge for physicians and a socio-economic burden for National Health Services (NHS). In Italy more than 50% of costs for asthma (1-2% of total NHS expenditure) are due to SNCA and moreover, within the European Community Respiratory Health Survey, Italy was the country with the lowest % of ICS daily use (29%) and with the highest % of subjects with uncontrolled asthma despite treatment (67% vs an overall European mean of 47%). Despite few data from very selected centers, in our country a precise estimate of the epidemiological figures and the disease related costs for SNCA is not available. Thus, we aimed at instituting of an on…

Late-asthma onset and associated factors

Although asthma is usually considered to originate in childhood, adult-onset is being increasingly reported. Aim: to assess factors associated to early- (<18 yrs) and late-onset (≥18 yrs) asthma. Methods: Data from a web-based Italian severe/uncontrolled asthma (SUA) registry (released in 2014), including 577 SUA subjects from 6 clinical and epidemiological Italian centres (Pisa1, Perugia, Ancona, Verona, Palermo, Pisa2). Results: 77.5% of SUA subjects had a late-onset asthma. Among subjects with early-onset asthma there were higher frequencies of allergic asthma (92.1 vs 76.4%), asthma familiarity (52.8 vs 42.8%), seasonal symptoms (51.3 vs 27.6%), active smoking habits (8.5 vs 4.4%) and u…

WITHDRAWN: Scaling up strategies of the Chronic Respiratory Disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3 – Area 5)

Questionnaires, spirometry and PEF monitoring in epidemiological studies on elderly respiratory patients.

Questionnaires are the most used subjective instrument of measurement in respiratory epidemiology. The standardisation of the questionnaires aims to limit bias by maximising validity and reliability, and comparability. Within the European Union project BIOMED1, a compendium of respiratory standard questionnaires (CORSQ) was developed for adults covering 18 topics from general information to early life events, through environmental risk factors and respiratory symptoms and diseases. Reliable spirometry data needs a rigorous quality control programme, as in the "Salute Respiratoria nell'Anziano" (Sa.R.A.) project, Italian for "Respiratory Health in the Elderly". Reproducibility rates were 95.…

Validation of Murray sputum purulence scale in the Italian Registry of Bronchiectasis (IRIDE)

Introduction: Murray sputum colour chart stratifies patients according to the presence of mucous (M), muco-purulent (MP) or purulent (P) sputum, and has not been validated in Bx yet. We aimed to validate this scale across a large Italian cohort of Bx patients. Methods: A secondary analysis of the IRIDE database was conducted including adults with Bx and daily sputum production enrolled across 13 Italian centres between 2014 and 2017. M vs. MP vs. P sputum producers were identified and clinical, functional and microbiological data were collected. Clinical outcomes during a two-year follow up period were evaluated in the Monza and Milan cohorts. A sensitivity analysis excluding COPD patients …

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

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 conse…

The Severe Asthma Network in Italy: Findings and Perspectives

Background Severe Asthma Network in Italy (SANI) is a registry of patients recruited by accredited centers on severe asthma. Objective To analyze epidemiological, clinical, inflammatory, functional, and treatment characteristics of severe asthmatics from the SANI registry. Methods All consecutive patients with severe asthma were included into the registry, without exclusion criteria to have real-life data on demographics, asthma control, treatments (including biologics), inflammatory biomarkers, and comorbidities. Results A total of 437 patients (mean age: 54.1 years, 57.2% females, 70.7% atopics, 94.5% in Global Initiative for Asthma severity step V) were enrolled into the study. The mean …

Tiotropium Respimat® Add-On To Inhaled Corticosteroids Improves Lung Function In Patients With Symptomatic Mild Asthma: Results From A Phase III Trial

Inhalation therapy in the next decade

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Asthma management in a specialist setting: Results of an Italian Respiratory Society survey.

Abstract Background Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources. Aim to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting. Method: A quantitative research program was implemented. Data were collected…

Reply to: Kow CS et al. Are severe asthma patients at higher risk of developing severe outcomes from COVID-19?

Which factors affect the choice of the inhaler in chronic obstructive respiratory diseases?

Inhalation is the preferred route of drug administration in chronic respiratory diseases because it optimises delivery of the active compounds to the targeted site and minimises side effects from systemic distribution. The choice of a device should be made after careful evaluation of the patient's clinical condition (degree of airway obstruction, comorbidities), as well as their ability to coordinate the inhalation manoeuvre and to generate sufficient inspiratory flow. These patient factors must be aligned with the specific advantages and limitations of each inhaler when making this important choice. Finally, adherence to treatment is not the responsibility of the patient alone, but should …

Asthma control in severe asthmatics under treatment with omalizumab: A cross-sectional observational study in Italy

Few data are available on the proportion of asthmatics achieving a good asthma control (according GINA guidelines) and on the level of airway inflammation during omalizumab treatment. The aim of this cross-sectional national observational study was to assess the level of control (according to GINA guidelines) achieved in a group of asthmatics on omalizumab treatment, and to characterize the factors that influence the lack of control. We studied 306 asthmatics under omalizumab treatment for a median of 32 months (range 4-120). The level of control according to GINA was good in 25.2%, partial in 47.1% and poor in 24.5% of patients (data were missing for the remaining 3.2%). Comparison between…

Factors reducing omalizumab response in severe asthma

Background: Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics. Methods: 340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab. Results: Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. O…

Corrigendum to “Which factors affect the choice of the inhaler in chronic obstructive respiratory diseases?” [YPUPT 31C (2015) 63–67]

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Severe asthma: One disease and multiple definitions

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,…

COVID-19 in Severe Asthma Network in Italy (SANI) patients: Clinical features, impact of comorbidities and treatments

To the Editor Since the end of February 2020 Italy, first non- Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200,000 confirmed Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infected subjects and resulted in more than 34000 deaths (data updated to June 19th, 20201).Patients with asthma are potentially more severely affected by by SARS-CoV-2 infection 2 and it is well established that respiratory viral infections are associated with severe adverse outcomes in patients with asthma, including increased risk of asthma exacerbation episodes 3. Nonetheless, according to the epidemiological studies publishe…

The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial.

BackgroundTiotropium, a once-daily long-acting anticholinergic bronchodilator, has demonstrated efficacy in patients with asthma who were symptomatic despite treatment with medium- to high-dose inhaled corticosteroids (ICS).ObjectiveThe objective of this study was to evaluate the efficacy and safety of once-daily tiotropium Respimat (5 μg or 2.5 μg), compared with placebo Respimat, as add-on therapy to low- to medium-dose ICS for adults with symptomatic asthma.MethodsA phase III, double-blind, placebo-controlled trial was conducted (NCT01316380). Adults with symptomatic asthma receiving low- to medium-dose ICS (200-400 μg budesonide or equivalent dose) and a pre-bronchodilator forced expira…

P260 Tiotropium Respimat(R) Add-on To Inhaled Corticosteroids Improves Lung Function In Patients With Symptomatic Mild Asthma: Results From A Phase Iii Trial

Background Despite currently available therapies and detailed guidelines, many people with mild asthma remain symptomatic; it is important to establish the efficacy and safety of new treatments in this group. Methods A Phase III, randomised, double-blind, parallel-group trial (GraziaTinA-asthma ® ; NCT01316380) evaluated the efficacy and safety of once-daily tiotropium 5 µg or 2.5 µg versus placebo (all delivered via the Respimat ® SoftMist™ inhaler) for 12 weeks in patients with symptomatic asthma on low-dose inhaled corticosteroids (200–400 µg budesonide or equivalent). The primary end point was peak forced expiratory volume in 1 second (FEV 1 ) within 3 h of dosing (0–3h) response (chang…

Tiotropium reduces airflow obstruction in asthma patients, independent of body mass index

P149 Once-daily tiotropium Respimat® add-on to at least ICS in adult patients with symptomatic asthma: pooled safety analysis: Abstract P149 Table 1

Background A high proportion of patients with asthma are symptomatic despite at least ICS maintenance therapy. Five trials aimed to evaluate the safety of tiotropium Respimat® compared with placebo Respimat®, each as add-on to at least ICS in adult patients with symptomatic asthma. Methods Five Phase III and one Phase II randomised, double-blind, placebo-controlled, parallel-group trials. PrimoTinA-asthma® (48 weeks): tiotropium Respimat® 5 µg add-on to ICS + LABA (≥800 µg budesonide or equivalent); MezzoTinA-asthma® (24 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on to ICS (400–800 µg budesonide or equivalent); GraziaTinA-asthma® (12 weeks): tiotropium Respimat® 5 µg or 2.5 µg add-on t…

Can the response to Omalizumab be influenced by treatment duration? A real-life study

Objective It is unknown whether Omalizumab effectiveness changes over the course of time. Our retrospective real-life study tried to analyze whether Omalizumab response may be influenced by treatment duration. Methods 340 severe asthmatics treated with Omalizumab for different periods of time were recruited. They were subdivided into 4 groups according to the Omalizumab treatment length: 60 months. Omalizumab treatment results (FEV1, exacerbations, ACT, SABA use, asthma control levels, medications used e and ICS doses) were compared. Results ACT, exacerbations, GINA control levels, ICS doses and SABA use were similar in all groups with different Omalizumab treatment durations. Using a linea…

Randomized Controlled Trials and real life studies. Approaches and methodologies: a clinical point of view.

Randomized Controlled Trials (RCTs) are the "gold standard" for evaluating treatment outcomes providing information on treatments "efficacy". They are designed to test a therapeutic hypothesis under optimal setting in the absence of confounding factors. For this reason they have high internal validity. The strict and controlled conditions in which they are conducted, leads to low generalizability because they are performed in conditions very different from real life usual care. Conversely, real life studies inform on the "effectiveness" of a treatment, that is, the measure of the extent to which an intervention does what is intended to do in routine circumstances. At variance to RCTs, real …

Economic impact of mepolizumab in uncontrolled severe eosinophilic asthma, in real life

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 workin…