Publications by authors named "Micheletto C"

Mucus hypersecretion is a trait of chronic obstructive pulmonary disease (COPD) associated with poorer outcomes. As it may be present before airway obstruction, its early treatment may have a preventive role. This narrative review of the literature presents the role of mucus dysfunction in COPD, its pathophysiology, and the rationale for the use of N-acetylcysteine (NAC).

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Benralizumab is an anti-IL-5 receptor alpha monoclonal antibody that induces the near-complete depletion of eosinophils. This study aimed to evaluate the long-term safety and effectiveness of benralizumab in patients with severe eosinophilic asthma (SEA) over an extended 48-month follow-up period, offering one of the longest real-world perspectives available. This was a single-arm, retrospective, observational, multicenter study involving 123 SEA patients treated with benralizumab at a dosage of 30 mg every 4 weeks for the first 3 doses and then every 8 weeks.

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Chronic obstructive pulmonary disease (COPD) is a progressive lung condition and a leading cause of physical decline and death. COPD prevalence is expected to increase steadily in the coming years, and as a result, the healthcare and social burden of this condition will intensify. In this scenario, a patient-centric approach, the treatable trait (TT) strategy, based on the identification of traits that are clinically relevant, identifiable, monitorable and treatable, has emerged.

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Airways hyperresponsiveness (AHR) is a pathognomonic event of asthma in which the airways are reactive to various bronchoconstrictor stimuli at 'doses' that normally have no bronchoconstrictor effect in non-asthmatics. AHR is an objective measure of clinical efficacy, and the introduction of biologics revived interest as a marker of disease and its pathophysiologic mechanism. This article aims to discuss the mechanisms of AHR, focusing on the role of epithelial damage and TSLP production, and promote its correct assessment for the evaluation of patients with severe asthma, to predict the risk of exacerbations and outcomes, and the eligibility for treatment with an anti-TSLP agent.

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Article Synopsis
  • Predictors of severe COVID-19 cases, specifically the ROX index, were analyzed in a study involving 227 patients hospitalized in Italy during the second pandemic wave, focusing on its ability to predict treatment failures like intubation or death.
  • The study found that older age, history of smoking, cardiovascular diseases, and a lower PaO2/FiO2 ratio at admission were linked to a higher likelihood of treatment failure.
  • The predictive value of the ROX index improved by the third day of hospitalization, with a critical cut-off value of 8.53 indicating a greater risk of treatment failure in patients on days 1 to 3.
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Background: Chronic obstructive pulmonary disease (COPD) represents an important health challenge, despite being preventable and manageable thanks to up-to-date recommendations. In Italy, the pharmaceutical care of COPD patients is still ill-timed and inaccurate. This study aimed to describe the treatment of COPD patients in Italy and possible switches following an exacerbation.

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Background: The management of chronic obstructive pulmonary disease (COPD) lacks standardization due to the diverse clinical presentation, comorbidities, and limited acceptance of recommended approaches by physicians. To address this, a multicenter study was conducted among Italian respiratory physicians to assess consensus on COPD management and pharmacological treatment.

Methods: The study employed the Delphi process using the Estimate-Talk-Estimate method, involving a scientific board and expert panel.

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Background: COPD management and therapy have been periodically revised to support a more patient-specific approach. Several concerns remain in primary care, such as the proper choice of initial treatment, medication adherence, and missing values for spirometry investigations. These concerns may be exacerbated by inconsistencies between the GOLD23 report and reimbursement criteria, as per the Italian NOTA99, especially for what concerns the assessment of disease severity and related treatment choice.

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Article Synopsis
  • Hypereosinophilic syndromes (HES) are rare immune conditions marked by high levels of eosinophils in the blood, with the idiopathic subtype (I-HES) being particularly hard to diagnose due to varied symptoms and overlap with other diseases.
  • Diagnosing HES is complicated by the lack of specific tests, the need for referrals to various specialists, and the absence of a standard treatment approach, highlighting the need for better clinician awareness.
  • The review emphasizes the importance of increasing understanding among healthcare providers and proposes a new multidisciplinary model to improve patient care and address the challenges faced in managing HES.
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Objective: Achieving remission in severe asthma holds paramount importance in elevating patient quality of life and reducing both individual and societal burdens associated with this chronic condition. This study centers on identifying pivotal patient-relevant endpoints through standardized, reproducible methods, while also developing a patient-centric definition of remission, essential for effective disease management.

Methods: A discrete choice experiment (DCE) was conducted to assess patients' perceptions on the four primary criteria for defining severe asthma remission, as outlined by the SANI survey.

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Article Synopsis
  • - Benralizumab effectively manages severe eosinophilic asthma (SEA), showing a significant 89% reduction in exacerbation rates and a 440 mL increase in forced expiratory volume (FEV) over 36 months in a study of 108 Italian patients.
  • - The treatment led to notable improvements in asthma control and sinonasal symptoms for patients with chronic rhinosinusitis with nasal polyposis, with 84.31% achieving partial or complete clinical remission.
  • - Results indicate benralizumab may act as a long-term disease-modifying drug for SEA, with most patients able to reduce or stop their oral corticosteroids, but further research is needed to evaluate its long-term safety and effectiveness.
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Background: Chronic obstructive pulmonary disease (COPD) is the fourth most important cause of death in high-income countries. Inappropriate use of COPD inhaled therapy, including the low adherence (only 10 %-40 % of patients reporting an adequate compliance) may shrink or even nullify the proven benefits of these medications. As such, an accurate prediction algorithm to assess at national level the risk of COPD exacerbation might be relevant for general practictioners (GPs) to improve patient's therapy.

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Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13.

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Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up.

Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period.

Setting: Ten Italian academic secondary- and tertiary-care centers.

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Dupilumab is currently approved for the treatment of Type 2 severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Few studies have specifically reported on dupilumab efficacy on asthma outcomes as a primary objective in a real-life setting, in patients with and without CRSwNP. Our study aimed to explore the efficacy of dupilumab on functional, inflammatory, and patient-reported outcomes in asthma patients across different disease phenotypes and severity, including mild-to-moderate asthma coexisting with CRSwNP.

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Introduction: Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha subunit, effectively blocks both IL-4 and IL-13 mediated pathways. Its introduction has represented a significant advancement in the treatment of severe asthma and other Type 2 (T2) conditions, including nasal polyps, atopic dermatitis, and eosinophilic esophagitis. To date, Dupilumab has demonstrated optimal efficacy and safety profile.

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Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. According to the available real-life evidence mepolizumab 300 mg and 100 mg, licensed for severe eosinophilic asthma, are comparable in terms of drug efficacy. However, the clinical rationale for selecting one dose or the other has not been explored.

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Asthma affects millions of people worldwide, with a subgroup suffering from severe asthma (SA). Biologics have revolutionized SA treatment, but challenges remain in managing different patient traits. This study analyzed data from the Italian Registry on Severe Asthma (IRSA) to investigate changes in SA characteristics and effectiveness of treatments after one year of follow-up, and to identify factors associated with response to treatments in a real-world setting.

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Background: Since the SARS-CoV-2 pandemic emerged, antimicrobial stewardship (AS) activities need to be diverted into COVID-19 management.

Methods: In order to assess the impact of COVID-19 on AS activities, we analyzed changes in antibiotic consumption in moderate-to-severe COVID-19 patients admitted to four units in a tertiary-care hospital across three COVID-19 waves. The AS program was introduced at the hospital in 2018.

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Chronic obstructive pulmonary disease (COPD) is a condition with a relevant clinical and economic burden. Only 10% to 40% of COPD patients reporting a regular use of respiratory medications, including those who suffered from severe disease being prescribed with triple combination therapy, nominally long-acting beta agonist (LABA), long-acting muscarinic antagonist (LAMA) and inhaled corticosteroid (ICS). The recent market launch of fixed-triple LABA/LAMA/ICS therapy might contribute to improve medications adherence and costs containment, given the use of a single instead of two or three inhalers.

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Bronchial asthma is a chronic inflammatory disease of the respiratory tract that varies in terms of clinical presentations (phenotypes) and distinct underlying pathophysiological mechanisms (endotypes). The definition of phenotype/endotype is crucial, given the availability of novel biologic agents for patients who do not respond to conventional therapies. Although patients with type 2 severe asthma benefit significantly from treatment with biologics, nonresponders have been identified.

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Objective: Growing interest is directed to the outcomes of COVID-19 in survivors, both in the convalescent period and in the long-term, which are responsible for morbidity and quality of life deterioration. This article aims to describe the mechanisms supporting the possible use of NAC as an adjuvant treatment for post-COVID-19 pulmonary fibrosis.

Materials And Methods: A search was performed in PubMed/MEDLINE.

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