Bianca Beghè

Nowadays, the management of chronic obstructive airway diseases is shifting from traditional diagnostic labels toward a precision medicine approach based on “treatable traits.” Among these, blood eosinophilia is emerging as a biomarker of type 2 (T2) inflammation across asthma and chronic obstructive airway diseases (COPD), even if its role as diagnostic tool and therapeutic target remains debated. In this manuscript we presented a clinical case of a 60-year-old male, former mild smoker (5 p/y), initially diagnosed with severe COPD with persistent airflow limitation, frequent severe exacerbations and persistent eosinophilia, but a history of asthma and nasal polyposis. After six months with optimization of inhaled therapy and clinical reassessment, the diagnosis of “severe COPD” shifted to the diagnosis of “severe eosinophilic asthma”. Considering the new diagnosis, he was prescribed mepolizumab on top of triple inhaled therapy. After 1 year, the clinical response was excellent in terms of symptoms control, exacerbations reduction and OCS sparing, despite no improvement in lung function. Starting from this clinical case, the aim of this mini review is to describe the role of eosinophilic inflammation in asthma and COPD. While eosinophilic inflammation is a common feature of asthma, COPD is usually characterized by neutrophilic inflammation, even if, a subset of patients with COPD has eosinophilic inflammation. In this context, blood eosinophilia might represent a clinically actionable trait to guide diagnosis and personalized therapy in chronic airway diseases even if it should not be targeted in isolation but be integrated into a multidimensional assessment.

Asthma is a chronic, heterogeneous respiratory disease that affects more than 300 million individuals worldwide and is responsible for substantial morbidity, mortality and healthcare burden. Chronic airway inflammation plays a central role in symptom expression, disease progression, and response to therapy. Corticosteroids, both inhaled and systemic, are the cornerstone of asthma treatment. However, it is well known that the use and abuse of systemic corticosteroids is almost invariably associated to the development of significant acute and chronic adverse events. Epidemiological data report that despite the availability of new target therapy, e.g., biologics, in real practice systemic steroids are still overused, and in this review, we highlight strategies 1) to identify and screen patients at risk of developing corticosteroids adverse events and 2) to reduce them.

Background: Obesity‐related asthma (OBA) is a distinct asthma phenotype, with increased severity. Adipokine release from excessive adipose tissue is suggested to be a key feature of OBA pathophysiology. However, it is unclear how the clinical characteristics of severe asthma associate with adipokine mediators. We examined systemic adipokine levels and evaluated relationships with disease severity, weight, sex, and steroid treatment in asthma. Methods: A multiplex immunoassay for nine adipokines with proposed involvement in obesity‐related inflammation (adiponectin, adipsin, BAFF, chemerin, FGF‐21, leptin, lipocalin‐2/NGAL, osteonectin and resistin) was designed. Plasma adipokines were measured in 127 patients with mild‐to‐moderate asthma (MMA) or severe asthma (SA) from the European BIOAIR cohort at baseline and after a controlled 2‐week oral corticosteroid (OCS) intervention. Results: Leptin and chemerin were significantly increased in patients with SA vs. MMA. Leptin, adiponectin, adipsin, and NGAL were affected by sex, whereas leptin and adipsin were strongly affected by weight. OCS increased leptin and adiponectin, decreased adipsin and BAFF, and did not affect osteonectin, resistin, or chemerin. No adipokines showed positive associations with exhaled NO, blood or sputum eosinophils, although certain correlations with serum CRP, blood, and sputum neutrophils were observed. Conclusions: Overall, we observe variable relationships between the nine adipokines, obesity and asthma severity. There were no relationships between adipokine levels and type‐2 airway inflammation, yet associations with systemic neutrophilic inflammation were seen. Although one adipokine, chemerin, was independently associated with asthma severity, deciphering the role of adipokines in OBA is complex due to the influence of sex, BMI, and OCS.

Background/Objectives: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder classically associated with emphysema and COPD. However, emerging evidence indicates that its clinical spectrum extends to airway-predominant diseases such as bronchiectasis and asthma, where protease–antiprotease imbalance and neutrophilic inflammation may drive tissue injury. This narrative review aims to synthesize current evidence on the relationship between AATD and airway diseases beyond emphysema, focusing on epidemiological patterns, underlying mechanisms, diagnostic strategies, and therapeutic implications. Methods: A narrative synthesis of the literature was performed, integrating data from registries, with observational and translational studies addressing the prevalence, pathobiology, and therapeutic implications of AATD in bronchiectasis, asthma, and severe asthma. Epidemiologic and mechanistic insights were analyzed to identify overlapping pathways and evidence gaps. Results: Evidence supports a non-negligible prevalence of bronchiectasis and asthma among AATD individuals, particularly in severe or heterozygous genotypes. Neutrophil elastase overactivity, impaired mucociliary clearance, and chronic neutrophilic inflammation emerge as shared mechanisms promoting bronchial remodeling and airflow limitation. In asthma, AATD appears linked to T2-low, steroid-resistant phenotypes and persistent obstruction, whereas in severe asthma cohorts, up to 20% may carry non-PiMM SERPINA 1 variants. No randomized trials have evaluated augmentation therapy and standardized screening algorithms are lacking. Conclusions: AATD represents a systemic disorder with clinically relevant airway manifestations beyond COPD and emphysema. Targeted testing should be considered in patients with idiopathic bronchiectasis or severe asthma. Future genotype-stratified, prospective studies are required to clarify causality, define biomarkers of disease activity, and evaluate the potential role of anti-protease-based therapeutic strategies.

Background: Sarcoidosis is a multisystem inflammatory disease characterized by the immune-mediated formation of non-necrotizing epithelioid granulomas. Several commonly used medications can induce similar granulomatous reactions, known as drug-induced sarcoid-like reactions (DISRs), which closely mimic sarcoidosis. Despite their specificity in targeting molecular pathways, certain therapies—particularly targeted treatments—have increasingly been linked to DISRs. Methods: This narrative review was based on a PubMed search using the terms “SARCOID LIKE REACTION” and “DRUG”. A cross-check was performed with “SARCOID” combined with each identified drug to identify misclassified cases. Drugs with limited evidence or weak pathogenetic plausibility were excluded, leaving only molecularly targeted therapies for consideration. Sources included case reports, case series, and reviews selected based on their clinical and scientific relevance, without any restrictions on time or language. Results: In light of the available data, five main pharmacological groups were found to be associated to DISR: immune checkpoint inhibitors, TNF-α antagonists, BRAF inhibitors, monoclonal antibodies, and miscellaneous agents. Each group has distinct mechanisms of action and clinical indications, which likely affect the frequency, presentation, and timing of DISRs. Conclusions: Diagnosing DISRs is challenging, and a structured approach is crucial for differentiating them from other conditions. To support clinicians, we propose a diagnostic algorithm to guide decision-making in suspected cases. Management should be individualized, as most DISRs either resolve spontaneously or improve after the discontinuation of the causative drug. Important factors influencing therapeutic decisions include the severity of the underlying disease, the availability of alternative treatments, and the extent of DISR manifestations.

In recent years, several studies have examined the impact of sleep-disordered breathing (SBD) on the quality of life and prognosis of patients with idiopathic pulmonary fibrosis (IPF). Among these disorders, obstructive sleep apnea (OSA) and nocturnal hypoxemia (NH) are the most prevalent and extensively studied, whereas central sleep apnea (CSA) has only been documented in recent research. The mechanisms underlying the relationship between IPF and SBDs are complex and remain an area of active investigation. Despite growing recognition of SBDs in IPF, no standardized guidelines exist for their management and treatment, particularly in a population characterized by distinct structural pulmonary abnormalities. This review outlines the pathophysiological connections between sleep-breathing disorders (SBDs) and idiopathic pulmonary fibrosis (IPF), as well as current therapeutic options. A comprehensive literature search using PubMed identified relevant studies, confirming the efficacy of CPAP in treating severe OSA and CSA. While high-flow oxygen therapy has not been validated in this patient cohort, it may offer a potential solution for select patients, particularly the elderly and those with low compliance. Conventional oxygen therapy, however, is limited to cases of isolated nocturnal hypoxemia or mild central sleep apnea.

Background: Studies have highlighted long-term respiratory muscle dysfunction in COVID-19 survivors, although the underlying risk factors remain unclear. This single-centre study assessed respiratory muscle function and individual associated factors at follow-up in patients hospitalised with COVID-19 and related acute respiratory failure. Methods: Data were collected for consecutive patients, aged ≥ 18 years, at the post-COVID outpatient service of Hospital Policlinico in Modena (Italy) in the time frame of 3 to 6 months after discharge. Data were analysed using single and multiple logistic regression models. Correlations among MIP/MEP, hand-grip values, and lung function were further explored. Results: Out of 223 patients (mean age 67 years, 69% male) 121 (54.3%) exhibited MIP or MEP dysfunction, which was found to be associated with the use of non-invasive ventilation (aOR = 1.91 [1.07–3.49], p = 0.04) and female gender (aOR = 1.76 [1.09–4.16], p = 0.03) as independent risk factors. A positive correlation was observed between MIP dysfunction and hand-grip strength (p = 0.03 and 0.01), whereas both MIP and MEP were significantly associated with FEV₁, FVC, TLC, and DLCO. Conclusions: Respiratory muscle dysfunction is consistently prevalent and parallels peripheral muscle weakness and the lung function level in patients at follow-up after severe COVID-19. The need for non-invasive ventilation during the acute phase and female gender might represent risk factors. MIP/MEP assessment should be recommended to observe respiratory muscle dysfunction in severe post-COVID survivors.

Background/Objectives: 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. Methods: 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. The safety endpoints focused on the frequency and nature of adverse events and the likelihood that they were induced by benralizumab. The efficacy endpoints focused on lung function, asthma exacerbations and control, and oral corticosteroid use. Results: Benralizumab, consistent with its mechanism of action, led to the rapid and nearly complete depletion of eosinophils. In total, 26 adverse events (21.1%) were observed, with 1.6% related to the treatment and 0.8% categorized as serious (vagal hypotension). Bronchitis was the most common unrelated adverse event (15.4%), occurring between months 36 and 38. Importantly, benralizumab effectiveness and safety were maintained consistently across the 48-month duration, resulting in significant improvements in lung function and reductions in oral corticosteroid use and exacerbation frequency. Conclusions: Benralizumab demonstrated a favorable safety profile, comparable to previously published studies, with perdurable effectiveness in controlling SEA and reducing oral corticosteroid use. Finally, this study provides evidence that near-complete eosinophil depletion does not increase long-term safety risks and supports benralizumab as a reliable treatment option for SEA patients.

Background: Studies have highlighted long-term respiratory muscle dysfunction in COVID-19 survivors, although the underlying risk factors remain unclear. This single-center study assessed respiratory muscle function and individual associated factors at follow-up in patients hospitalised with COVID-19 and related acute respiratory failure. Methods: Data were collected for consecutive patients, aged ≥18 years, at the post-COVID outpatient service of Hospital Policlinico in Modena (Italy) in the time frame of 3 to 6 months after discharge. Data were analysed using single and multiple logistic regression model. Correlation between MIP/MEP, hand-grip values and lung function were further explored. Results: Out of 223 patients (mean age 67 years, 69% male) 121 (54.3%) exhibited MIP or MEP dysfunction which was found to be associated with use of non-invasive ventilation (OR=1.93 [1.08–3.52], p=0.03) and female gender (OR=1.96 [1.1–3.57], p=0.03) as indipendent risk factors. A positive correlation was observed between MIP dysfunction and hand-grip strength (p=0.03 and 0.01), whereas both MIP and MEP were significantly associated with FEV1, FVC, TLC, and DLCO. Conclusions: Respiratory muscle dysfunction is consistently prevalent and parallels peripheral muscle weakness and lung fuction level in patients at follow up after severe COVID-19. The need for non-invasive ventilation during the acute phase and female gender might represent risk factors. MIP/MEP assessment should be recommended to observe respiratory muscle dysfunction in severe post-COVID survivors.