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The editorial "Addressing Oxidative Stress and Endothelial Dysfunction in Chronic Respiratory Diseases: The Role of Exercise and Multidisciplinary Rehabilitation" discusses the prevalence of chronic respiratory diseases (CRDs) and their impact on physical, psychological, and occupational health. The article highlights the common pathogenetic mechanisms of inflammation and oxidative stress in CRDs, emphasizing the systemic nature of these processes. It also explores the role of endothelial dysfunction in CRDs and the potential benefits of exercise-based approaches in improving endothelial function and managing cardiovascular comorbidities. The study suggests that exercise and pulmonary rehabilitation may play a crucial role in restoring endothelial function and addressing the cardiovascular risk associated with CRDs. [Extracted from the article]

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease characterized by chronic airflow limitation and persistent respiratory symptoms. It is a major cause of morbidity and mortality worldwide, significantly impacting healthcare systems with considerable socioeconomic consequences. The main risk factors include exposure to tobacco smoke, environmental pollutants, occupational dust, and genetic factors such as alpha-1 antitrypsin deficiency. COPD is often associated with extrapulmonary comorbidities, particularly psychiatric disorders like depression and anxiety, which worsen patients' quality of life and prognosis. The prevalence of these disorders in patients with COPD varies significantly but is always higher than in healthy controls. Psychiatric disorders can negatively influence COPD management and vice versa, creating a complex bidirectional interaction. Depression and anxiety are the most common psychiatric comorbidities in patients with COPD, influenced by factors such as social isolation, physical limitations, and fear of exacerbations. Diagnosis of these psychiatric disorders is complicated by the overlap of symptoms with those of COPD. However, some screening tools can facilitate early detection. The treatment of psychiatric disorders in patients with COPD in a rehabilitation setting requires a multidisciplinary approach involving pulmonologists, neurologists and psychologists. Pharmacological therapy with antidepressants shows mixed results in terms of efficacy and safety, with some studies reporting benefits on quality of life and others suggesting an increased risk of exacerbations and pneumonia. An integrated approach that includes the assessment and intervention of mental disorders is essential to improve the overall management of COPD and the quality of life of patients. This narrative review provides an overview of the main psychiatric comorbidities in COPD patients, aiming to fill gaps in the literature and suggest areas for future research. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods: Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results: A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23–4.45) in ICS users and 3.39% (IQR: 2.45–4.08) in ICS nonusers (p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23–4.45 to 4.77%; IQR: 3.25–5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45–4.08 to 5.04%; IQR: 3.98–6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions: Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy. [ABSTRACT FROM AUTHOR]

Background: Severe eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short-and middle-term effects are well described, no study has so far investigated its longlasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients. Methods: We conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20). Results: Of 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment. Conclusion: Mepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function. [ABSTRACT FROM AUTHOR]

Over the past 15 years, the paradigm of viewing the upper and lower airways as a unified system has progressively shifted the approach to chronic respiratory diseases (CRDs). As the global prevalence of CRDs continues to increase, it becomes evident that acknowledging the presence of airway pathology as an integrated entity could profoundly impact healthcare resource allocation and guide the implementation of pharmacological and rehabilitation strategies. In the era of precision medicine, endotyping has emerged as another novel approach to CRDs, whereby pathologies are categorized into distinct subtypes based on specific molecular mechanisms. This has contributed to the growing acknowledgment of a group of conditions that, in both the upper and lower airways, share a common type 2 (T2) inflammatory signature. These diverse pathologies, ranging from allergic rhinitis to severe asthma, frequently coexist and share diagnostic and prognostic biomarkers, as well as therapeutic strategies targeting common molecular pathways. Thus, T2 inflammation may serve as a unifying endotypic trait for the upper and lower airways, reinforcing the practical significance of the united airways model. This review aims to summarize the literature on the role of T2 inflammation in major CRDs, emphasizing the value of common biomarkers and integrated treatment strategies targeting shared molecular mechanisms. [ABSTRACT FROM AUTHOR]

Simple Summary: COVID-19, with persistent and new onset of symptoms, such as fatigue, post-exertional malaise, and cognitive dysfunction that impact everyday functioning, is referred to as long-COVID under the general category of post-acute sequelae of the SARS-CoV-2 infection (PASC). It includes a wide range of signs and symptoms that can last weeks, months, or even years after infection, most of which are attributable to dysfunctions of the neurovegetative system. The causative mechanisms are still unknown, but autoimmunity and the production of autoantibodies targeting self-antigens via the molecular mimicry phenomenon seem to have a role. Here we evaluated the presence of autoantibodies against two proteins of vagal nuclei sharing a peptide with SARS-CoV-2 spike glycoprotein in sera from ongoing symptomatic COVID-19 patients (long-COVID) with cardiorespiratory symptoms, subjects vaccinated without a history of SARS-CoV-2 infection, and subjects not vaccinated without a history of SARS-CoV-2. Putative autoantibodies are present in both long-COVID-19 and vaccinated groups, suggesting that both viral infection and vaccination may trigger autoreactivity. However, the presence of autoantibodies is not sufficient for triggering autoimmunity, and other predisposing conditions must co-occur. Therefore, it is necessary to run further investigations to clarify the complex mechanisms involved in the development of long-COVID, providing knowledge which may offer further information for the prevention and treatment of the disease. As reported by the World Health Organization (WHO), about 10–20% of people have experienced mid- to long-term effects following SARS-CoV-2 infection, collectively referred to as post-COVID-19 condition or long-COVID, including some neurovegetative symptoms. Numerous findings have suggested that the onset of these neurovegetative symptoms upon viral infection may be caused by the production of autoantibodies through molecular mimicry phenomena. Accordingly, we had previously demonstrated that 22 of the human proteins sharing putatively immunogenic peptides with SARS-CoV-2 proteins are expressed in the dorsal motor nucleus and nucleus ambiguous. Therefore, if molecular mimicry occurs following severe forms of COVID-19, there could be transitory or permanent damage in some vagal structures, resulting in a lower vagal tone and all the related clinical signs. We investigated the presence of autoantibodies against two proteins of vagal nuclei sharing a peptide with SARS-CoV-2 spike glycoprotein using an immunoassay test on blood obtained from patients with cardiorespiratory symptoms in patients affected by ongoing symptomatic COVID-19 (long-COVID), subjects vaccinated without a history of SARS-CoV-2 infection, and subjects not vaccinated without a history of SARS-CoV-2 infection. Interestingly, putative autoantibodies were present in both long-COVID-19 and vaccinated groups, opening interesting questions about pathogenic mechanisms of the disease. [ABSTRACT FROM AUTHOR]

High-flow nasal cannula (HFNC) has recently emerged as a crucial therapeutic strategy for hypoxemic patients both in acute and chronic settings. Indeed, HFNC therapy is able to deliver higher fractions of inspired oxygen (FiO2) with a heated and humidified gas flow ranging from 20 up to 60 L per minute, in a more comfortable way for the patient in comparison with Conventional Oxygen Therapy (COT). In fact, the flow keeps the epithelium of the airways adequately moisturized, thus positively affecting the mucus clearance. Finally, the flow is able to wash out the carbon dioxide in the dead space of the airways; this is also enhanced by a modest positive end-expiratory pressure (PEEP) effect. Recent evidence has shown applications of HFNC in exercise training and chronic settings with promising results. In this narrative review, we explored how HFNC might contribute to enhancing outcomes of exercise training and pulmonary rehabilitation among patients dealing with chronic obstructive pulmonary disease, interstitial lung diseases, and lung cancer. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a short-lived gas molecule which has been studied for its role as a signaling molecule in the vasculature and later, in a broader view, as a cellular messenger in many other biological processes such as immunity and inflammation, cell survival, apoptosis, and aging. Fractional exhaled nitric oxide (FeNO) is a convenient, easy-to-obtain, and non-invasive method for assessing active, mainly Th2-driven, airway inflammation, which is sensitive to treatment with standard anti-inflammatory therapy. Consequently, FeNO serves as a valued tool to aid the diagnosis and monitoring of several asthma phenotypes. More recently, FeNO has been evaluated in several other respiratory and/or immunological conditions, including allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, atopic dermatitis, eosinophilic esophagitis, and food allergy. In this review, we aim to provide an extensive overview of the current state of knowledge about FeNO as a biomarker in type 2 inflammation, outlining past and recent data on the application of its measurement in patients affected by a broad variety of atopic/allergic disorders. [ABSTRACT FROM AUTHOR]

Diffuse lung disorders (DLDs) and interstitial lung diseases (ILDs) are pathological conditions affecting the lung parenchyma and interstitial network. There are approximately 200 different entities within this category. Radiologists play an increasingly important role in diagnosing and monitoring ILDs, as they can provide non-invasive, rapid, and repeatable assessments using high-resolution computed tomography (HRCT). HRCT offers a detailed view of the lung parenchyma, resembling a low-magnification anatomical preparation from a histological perspective. The intrinsic contrast provided by air in HRCT enables the identification of even the subtlest morphological changes in the lung tissue. By interpreting the findings observed on HRCT, radiologists can make a differential diagnosis and provide a pattern diagnosis in collaboration with the clinical and functional data. The use of quantitative software and artificial intelligence (AI) further enhances the analysis of ILDs, providing an objective and comprehensive evaluation. The integration of "meta-data" such as demographics, laboratory, genomic, metabolomic, and proteomic data through AI could lead to a more comprehensive clinical and instrumental profiling beyond the human eye's capabilities. [ABSTRACT FROM AUTHOR]

In line with a growing body of evidence, if some Th2-driven pathophysiological mechanisms are shared across multiple atopic/allergic disorders, it is possible to hypothesize that, by treating a single clinical condition in an individual with multiple Th2 diseases, a simultaneous improvement can be obtained. Patients with atopic/allergic disorders, including atopic dermatitis (AD), allergic rhino-conjunctivitis (AR), chronic rhinosinusitis with/without nasal polyps (CRSwNP/CRSsNP), bronchial asthma, food allergy, and eosinophilic esophagitis (EoE), often share a common genetic background, a type Th2 polarized immune response, and several environmental factors [[1]]. However, although the positive clinical response to biologics confirms the association between Th2-driven diseases, no biomarker with high specificity can anticipate the therapeutic response in either single or multiple Th2 conditions. The presence of several allergic disorders in the same individuals suggests that some subgroups of allergic diseases share the same subtype of health condition, namely the "endotype" variety, especially the Th2-driven endotype. [Extracted from the article]