The Role of Galectins in Asthma Pathophysiology: A Comprehensive Review.

Galectins are a group of ß-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot-Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma.

Managing Small Airway Disease in Patients with Severe Asthma: Transitioning from the "Silent Zone" to Achieving "Quiet Asthma".

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed "Quiet Asthma".

Can Galectin-3 be a reliable predictive biomarker for post-COVID syndrome development?

BACKGROUND AND OBJECTIVES: Reliable biomarkers able to predict post-COVID syndrome development are still lacking. The aim of the study was to evaluate the relationship between Galectin-3 blood concentrations and the development of post-COVID syndrome. METHODS: We performed a single-center, prospective, observational study, enrolling 437 consecutive patients attending our outpatient clinic for the post-COVID assessment. For each patient, we recorded the main clinical, functional and radiological findings. We also dosed several blood biomarkers which have been related to COVID-19 disease, including Galectin-3. We performed Receiver Operating Characteristic (ROC) and multivariate regression analysis to evaluate the predictive performance of Galectin-3 for post-COVID syndrome development. RESULTS: Among the blood biomarkers tested, Galectin-3 resulted the only one correlated with the outcome, although the insufficient performance of the Cox regression model from a statistical standpoint. Correlation coefficients and ROC curves analysis revealed the close relationship between Galectin-3 levels and the time passed from the acute phase of COVID-19 disease, suggesting a possible predictive role for this biomarker when dosed from 60 to 120 days after the infection. CONCLUSIONS: Galectin-3 could play an important role as predictive biomarker for COVID-19 sequelae, but its evaluation must be carefully planned along the follow up to avoid misinterpretations.

The Predictors of Long COVID in Southeastern Italy.

INTRODUCTION: Long COVID is now recognized as a common consequence of the SARS-CoV-2 infection, but we are still far from fully understanding its pathogenesis and predictive factors. Many pathophysiological factors have been studied, including ethnicity. To our knowledge, the risk factors for Long COVID have not been studied in Southeastern Italy. AIMS: The aim of this study was to evaluate the predictive factors of Long COVID in a cohort of patients from Southeastern Italy. METHODS: We conducted a retrospective longitudinal study, enrolling inpatients and outpatients diagnosed with COVID-19 from June 2021 to March 2022. A total of 436 subjects were evaluated in an outpatient setting 12 weeks after a SARS-CoV-2 infection, recording comorbidities, symptoms, therapy, and clinical information. Univariate and multivariate binomial logistic regression analyses were performed on different risk factors to define the probability of developing Long COVID. RESULTS: A total of 71.8% of patients (313) developed Long COVID, while the remaining 123 (28.3%) had a complete remission of symptoms 3 months after acute infection. During the acute phase of COVID-19, 68.3% of patients experienced respiratory failure and 81.4% received corticosteroid therapy. In a multivariate analysis, the female sex (SEX M ODD 0.513) and corticosteroids (ODD 2.25) were maintained as predictive values. CONCLUSIONS: From our data and in line with other studies, the female sex emerges as a risk factor for Long COVID in the population of Southeastern Italy. Corticosteroid therapy administered in the acute phase also appears to be associated with an increased risk of Long COVID. Although indications for the prescription of corticosteroid therapy in the acute phase were indicated by the presence of pneumonia complicated by respiratory insufficiency, there was an over-prescription of corticosteroid therapy in the real life of our cohort, with 64% of patients having respiratory insufficiency and 81% having corticosteroid therapy. We hypothesize that a synergistic link between viral infection and the side effects of corticosteroid therapy may arise in selected cases.

Severe asthma clinical remission after biologic treatment with anti-IL4/IL13: A real-life experience.

INTRODUCTION: Dupilumab, a fully human anti-interleukin-4/interleukin-13 monoclonal antibody, has shown efficacy in many aspects of Type-2 severe asthma management. Currently, we lack real-life studies addressing the achievment of clinical remission in patients treated with this biologic. MATERIALS AND METHODS: We performed a prospective study enrolling 18 patients with severe asthma treated with Dupilumab. We assessed main clinical, functional and biological severe asthma features at baseline (T0) and after a 1-year course of treatment (T12). Clinical remission was defined at T12 in patients without asthma exacerbations, no oral corticosteroid (OCS) use, ACT ≥ 20 and FEV1 improvement ≥ 100 ml from baseline. RESULTS: Among total population, 38.9% of patients achieved clinical remission at T12. Anti IL-4/IL-13 treatment significantly reduced asthma exacerbations and OCS use in the overall cohort, with a more pronounced ACT improvement in the remission group. Patients achieving clinical remission went through a step down of the inhalation therapy, suspending long-acting anti-muscarinics administration at T12. CONCLUSIONS: Treatment with anti-IL4/IL13 can induce clinical remission in patients with T2 severe asthma.

The impact of healthcare setting on post-COVID mood disorders: a single-centre perspective from Southern Italy Respiratory Intensive Care Unit.

BACKGROUND AND OBJECTIVES: Post-COVID syndrome includes several clinical identities, with both physical and mental alterations lasting several months from the acute phase of COVID-19 disease. However, to date, data concerning the relationship between healthcare settings during COVID-19 disease and post-COVID mood disorders are lacking. METHODS: We performed a prospective study enrolling 440 patients with post-COVID syndrome. Each patient underwent a complete clinical evaluation, along with blood and functional tests. Patients were divided according to the healthcare setting needed during COVID-19 disease. RESULTS: Patients admitted to RICU were more prone to develop mental alterations, even when compared to ICU-admitted patients. Other risk factors for mood disorders included female gender and some post-COVID symptoms. CONCLUSIONS: Healthcare needs during COVID-19 can explain the higher incidence of mood disorders in post-COVID syndrome. RICU arises as an important but underexplored risk factor for post-COVID psychic sequelae.

A glimpse in post-COVID pathophysiology: the role of exhaled breath condensate pH as an early marker of residual alveolar inflammation.

BACKGROUND: Residual alveolar inflammation seems to be paramount in post-COVID pathophysiology. Currently, we still lack a reliable marker to detect and track alveolar phlogosis in these patients. Exhaled Breath Condensate (EBC) pH has robust evidences highlighting its correlation with lung phlogosis in various diseases. We aim to define the reliability of alveolar and bronchial EBC pH in the assessment and in the follow up of post-COVID-related inflammation. RESEARCH DESIGN AND METHODS: We enrolled 10 patients previously hospitalized due to COVID-19 pneumonia. We performed a complete follow-up after 3 months and 6 months from discharge. Each visit included routine blood tests, arterial blood gas analysis, 6-minute walking test, spirometry, diffusing capacity and body plethysmography. Finally, bronchial and alveolar EBC were collected at the end of each visit. RESULTS: Alveolar EBC pH was significantly lower than bronchial EBC pH at T1, alveolar EBC pH tended to be more acid after 3 months from hospital discharge compared to the same sample 6 months later. Serum inflammatory biomarkers showed no significant differences from T1 to T2. Alveolar EBC pH was positively correlated with neutrophil-lymphocyte ratio. CONCLUSIONS: Collecting EBC pH could help to understand pathophysiologic mechanism as well as monitoring alveolar inflammation in the post-COVID syndrome.