Search Results (56)

In respiratory patients, limited adherence to and misuse of devices hinder the effectiveness of inhalation therapy. Switching inhalers for non-clinical reasons poses a risk of deterioration of respiratory disease and/or promotes poor adherence to therapy. The objective of this work was to explore the impact of device changes for non-clinical reasons on clinical outcomes (primary) and costs (secondary), including carbon emissions in Spain. After a comprehensive literature search, the increased use of resources following worsening outcomes was apportioned using Spanish cost data and following the recommended pathways for care. We calculated the cost of re-training these patients and attributed carbon emissions in metric tons of CO₂ equivalent (tCO₂eq) to the excess resource use. In Spain, the impact of uncontrolled switching for non-clinical reasons in COPD has an annual estimated cost of EUR 923/patient, leading to an excess annual expenditure of more than EUR 216 million. For asthma patients, the annual impact is almost EUR 263/patient, representing an additional EUR 118 million excess annual expenditure. The environmental consequence of both conditions can be equated to almost 45 thousand tCO₂eq. Training all these patients on the new device would cost around EUR 35 million and would generate an extra impact reduction of about 2.6 thousand tCO₂eq in carbon emissions levy. Full article

Cardiovascular diseases remain the leading cause of death worldwide, highlighting the urgent need for novel therapeutic strategies. The Mediterranean diet is renowned for its cardiovascular benefits, largely attributed to extra virgin olive oil (EVOO) and its phenolic compounds, particularly hydroxytyrosol (HT). HT, a potent antioxidant and anti-inflammatory agent, has demonstrated significant therapeutic potential in mitigating myocardial damage following acute myocardial infarction (AMI). However, there is a notable lack of published evidence regarding the effects of HT administration in the context of acute ischemia/reperfusion (I/R) injury, making this study a novel contribution to the field. This study aimed to evaluate the cardioprotective effects of HT using the Langendorff technique in an isolated mouse heart ischemia/reperfusion (I/R) model. Mice were administered a single intraperitoneal dose of HT (10 mg/kg) 24 h prior to the I/R protocols, and parameters such as the infarct size, mitochondrial function, and redox balance were assessed. The results revealed a remarkable 57% reduction in infarct size in HT-treated mice compared to untreated controls. HT treatment also improved mitochondrial bioenergetics, as evidenced by the increased membrane potential (ΔΨm), enhanced oxygen consumption, and reduced hydrogen peroxide (H₂O₂) production. Furthermore, HT restored the activity of the mitochondrial respiratory complexes, notably Complex I, even under I/R conditions. These findings highlight the efficacy of HT in reducing oxidative stress and preserving mitochondrial function, critical factors in cardiac disease. In conclusion, HT emerges as a promising therapeutic agent for ischemic heart disease, demonstrating both preventive and restorative potential. Future research should explore its clinical applicability to advance cardiovascular disease management. Full article

Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article

Background: Tuberculosis and COVID-19 co-infection poses significant clinical challenges, with pulmonary TB (PTB) and extrapulmonary TB (extraPTB) potentially influencing disease progression and outcomes differently. This study aims to compare the clinical manifestations, inflammatory markers, and outcomes between PTB and extraPTB patients with SARS-CoV-2 co-infection. Methods: A retrospective, cross-sectional study was conducted on 55 hospitalized adults with TB-COVID-19 co-infection from March 2020 to March 2022. Patients were divided into PTB (n = 32) and extraPTB (n = 23) groups. Demographic, clinical, laboratory, and imaging data were collected and analyzed using statistical models, including ANCOVA, LASSO regression, and Random Forest classification, to identify key predictors of hospitalization duration and mortality. Results: PTB patients had significantly lower BMI, worse oxygenation status, and greater lung involvement on CT compared to extraPTB patients. CRP was elevated in PTB, while IL-6 levels were higher in extraPTB. Hospitalization duration was primarily influenced by inflammatory and coagulation markers (IL-6, D-dimer, neutrophil count, systemic inflammatory index), while higher BMI was associated with shorter stays. Mortality risk was strongly correlated with oxygenation impairment (worst SpO₂, SpO₂ at diagnosis), inflammatory burden (CRP, LDH), and CT severity score, rather than TB localization. Conclusions: TB localization did not independently affect hospitalization duration or mortality risk. Instead, severe lung involvement, systemic inflammation, and hypoxemia were the strongest predictors of poor outcomes. These findings emphasize the importance of early risk stratification based on respiratory and inflammatory markers to optimize patient management. Further research is needed to clarify the long-term impact of TB-COVID-19 co-infection, particularly in extraPTB cases. Full article

Patients with rheumatoid arthritis (RA) have an increased risk of infections. This may be linked to disease-related factors, immunosuppressive therapy and the presence of comorbidities. Background/Objectives: In an unselected group of RA patients, our aims were to assess the following: (a) the incidence and (b) features of diseases and (c) the predictive factors of severe respiratory infection (SRI). Methods: An observational and retrospective study of all patients with RA included in the vaccination program of our hospital between October 2011 and October 2018 was conducted. The follow-up continued until December 2020. Patients with SRI, defined as those that required hospitalization or at least one dose of intravenous antibiotic treatment in the emergency room, were (a) compared with those not requiring hospital admission and (b) studied for predictive factors of SRI (multivariate analysis adjusted for age and sex). The vaccination program in our hospital includes vaccination against influenza, S. pneumoniae and H. influenzae. Information on the patients, infections and hospitalizations was retrospectively retrieved from the hospital and general physician records. Results: We studied 528 RA patients (409 women/119 men) with a mean age of 58.9 ± 13.2 years. A total of 55 patients (10.4%) suffered 89 SRIs. The median [IQR] number of hospitalizations per patient was 1.5 [1–2]. Patients with an SRI were older, had had RA for longer and had more comorbidities (hypertension, hypercholesterolemia, diabetes and interstitial lung disease). These patients had more ACPA positivity, more extra-articular manifestations and high disease activity at the time of their vaccination. Treatment with glucocorticoids, methotrexate and leflunomide was seen in a higher number of patients. Predictive factors for SRI were age; time of evolution of RA; associated comorbidities, especially hypertension and diabetes; extra-articular manifestations, especially interstitial lung disease; and treatment with glucocorticoids, methotrexate and leflunomide. Conclusions: Despite being included in a vaccination program, about 10% of our patients required hospitalization due to an SRI. The main predictive factors were certain comorbidities, interstitial lung disease and treatment with glucocorticoids. Predicting SRI in RA patients remains an unmet need. Full article

In patients with aspirin-exacerbated respiratory disease (AERD), there is disparate regulation of prostaglandin E2 (PGE₂) and prostaglandin D₂ (PGD₂). Both prostanoids are synthesised by cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). However, while the basal synthesis of PGE₂ tends to decrease, that of PGD₂ increases in patients with AERD. Furthermore, both behave differently in response to the inhibitory action of NSAIDs on COX-1: PGE₂ levels decrease while PGD₂ increases. Increased PGD₂ release correlates with nasal, bronchial, and extra-pulmonary symptoms caused by aspirin in AERD. The proposed hypothesis establishes that the answer to this paradoxical dissociation can be found in the airway epithelium. This is based on the observation that reduced COX-2 mRNA and/or protein expression is associated with reduced PGE₂ synthesis in cultured fibroblast and epithelial cells from AERD compared to patients with asthma who are aspirin-tolerant and healthy subjects. The low production of PGE₂ by the airway epithelium in AERD results in an excessive release of alarmins (TSLP, IL-33), which in turn contributes to activating group 2 innate lymphoid cells (ILC2s) and PGD₂ synthesis by mast cells and eosinophils. Aspirin, by further increasing the diminished PGE₂ regulation capacity in AERD, leads to respiratory reactions associated with the surge in PGD₂ from mast cells and eosinophils. In summary, the downregulation of COX-2 and the subsequent low production of PGE₂ by airway cells account for the apparently paradoxical increased production of PGD₂ by mast cells and eosinophils at the baseline and after aspirin provocation in patients with AERD. A better understanding of the role of the airway epithelium would contribute to elucidating the mechanism of AERD. Full article

Background: Tuberculosis remains one of the biggest global public health problems today. The objective of this study was to evaluate the diagnostic methods, clinical outcomes, patient compliance, and mortality rates in patients diagnosed with extrarespiratory tuberculosis. Methods: 105 cases of extrarespiratory tuberculosis were analyzed over a five-year period (2018–2023). Data from medical records were reviewed and processed. Diagnostic methods included Ziehl–Nielsen staining, Löwenstein–Jensen cultures, GeneXpert, and histopathological analysis. Diagnosis was supplemented by a specialist organ examination and, in cases with concurrent pulmonary involvement, by a chest X-ray and sputum examination. For negative cases, a probabilistic diagnosis was made. Results: Most patients presented pleural TB (38%), osteo-articular TB (26.67%), and ganglionary TB (19%). Patients were mostly men (56.19%), in the 18–40 years-old category (40%), and lived in rural areas (61%). In total, 94.29% were newly diagnosed and most observed comorbidites were chronic smoking (11.37%), chronic lung diseases (10.20%), and malnutrition (9.02%). Moreover, 68% had a negative microscopic examination, while 55% had negative cultures on Löwenstein–Jensen. Conclusions: This study highlights the importance of a multi-modal approach to diagnosing extrarespiratory tuberculosis, especially in negative bacteriological and histopathological results. Imaging, combined with clinical and epidemiological data, is critical for a probabilistic diagnosis. GeneXpert proved useful in difficult cases. This study emphasizes the need for a comprehensive diagnostic strategy to effectively manage extrarespiratory tuberculosis. Full article

Asbestos research, identification, and quantification have been performed over the years, and the relationship between fiber inhalation and lung disease development is well defined. The same cannot be said for the gastroenteric system: the International Agency for Research on Cancer (IARC) believes that colorectal cancer (CRC) could be associated with asbestos exposure, but research has not demonstrated a casual nexus between exposure and CRC, despite highlighting an association tendency. The combination of scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) is the most applied technique in asbestos fiber identification in tissues and intestinal mucosa. In this study, SEM/EDS was applied to evaluate the presence of asbestos fibers and bodies (ABs) inside the tissue of eleven patients affected by CRC who had undergone environmental exposure due to living in an asbestos-polluted area where an Eternit plant had been active in the past. This technique was coupled with optical microscopy (OM) to verify whether the latter could be applied to evaluate the presence of these mineral phases, with the goal of understanding its suitability for identifying fibers and ABs in colon tissues. In addition to verifying the presence of fibers, this study allowed us to identify the deposition site of said fibers within the sample and possibly detect associated tissue reactions using OM, over a shorter time and at lower costs. Despite being a preliminary and descriptive work, the obtained results allowed us to propose a method involving first-sample OM observation to identify regulated (fibers with a length ≥ 5 μm, a thickness ≤ 3 μm, and a length/thickness ratio > 3) asbestos phases and ABs in the extra-respiratory system. In fact, OM and SEM/EDS provided similar information: no asbestiform morphology or ABs were found, but phyllosilicates and other inorganic materials were identified. This research needs to be continued using higher-resolution techniques to definitively rule out the presence of these fibers inside tissues whilst also increasing the number of patients involved. Full article

In the last few years, an increasing interest has developed regarding the application of different techniques for the identification of pollutants inside the tissues deriving from patients affected by benign or neoplastic diseases. Particular attention was paid to neoplasia linked to particular exposures, e.g., heavy metals, carbon dusts, silica, asbestos. As regards the last pollutant, a wide body of scientific literature has been collected, considering the severe effects caused by mineral fibers on human health. Optical and electronic microscopies were widely applied to identify the fibers in respiratory and extra-respiratory organs to detect the minerals and to link their presence to an exposure source and to understand their role in cancer development. The main advantage of electron microscopy lies in the possibility of coupling the microscopes with energy dispersive spectrometers and also collecting data on the elemental composition of various inorganic phases. In term of sample preparation and time of analysis, the most utilized microscope technique is Scanning Electron Microscopy with an annexed energy dispersive spectrometer (SEM/EDS), allowing for the morphological and chemical characterization of the observed particles/fibers. Moreover, this technique is envisaged by Italian Law for asbestos identification in air and bulk samples. On the other hand, this technique does not allow a reliable identification of the mineral phase in the case of polymorphs with the same chemical formula but different crystal structures. In this work, the coupling of a spectroscopical technique—micro-Raman spectroscopy—to SEM/EDS is proposed for a sure phase identification of particles, showing EDS spectra with ambiguous phase identification, observed in samples of tissues from patients affected by colorectal cancer and living in an asbestos-polluted area. In these tissues, different particles with EDS spectra that do not allow a sure identification of the phase—in particular calcium-rich particles and titanium oxides—were successively analyzed by micro-Raman spectroscopy. Thanks to this last technique, it was possible to ascribe the mineral phases associated to these particles to “aragonite” (a calcium carbonate polymorph) and to “anatase” (a Ti dioxide polymorph). Full article

COVID-19 is an airborne respiratory disease that mainly affects the lungs. To date, COVID-19 has infected 580 million people with a mortality of approximately 7 million people worldwide. The emergence of COVID-19 has also affected the infectivity, diagnosis, and disease outcomes of existing diseases such as influenza, TB, and asthma in human populations. These are airborne respiratory diseases with symptoms and mode of transmission similar to those of COVID-19. It was speculated that the protracted nature of the COVID-19 pandemic coupled with vaccination could impact other respiratory diseases and mortality. In this study, we analyzed the impact of COVID-19 on flu, tuberculosis (TB), and asthma. Our analyses suggest that COVID-19 has a potential impact on the mortality of flu, TB, and asthma. These impacts vary across before the COVID-19 era, during the peak period of the pandemic, and after vaccinations/preventive measures were implemented, as well as across different regions of the world. Overall, the spread of flu generally reduced during the pandemic, resulting in a reduced expenditure on flu-related hospitalizations, although there were sporadic spikes at setting times. In contrast, TB deaths generally increased perhaps due to the disruption in access to TB services and reduction in resources. Asthma deaths, on the other hand, only marginally varied. Collectively, the emergence of COVID-19 added extra cost to the overall expenditure on some respiratory infectious diseases, while the cost for other infectious diseases was either reduced or somewhat unaffected. Full article

Actinobacillus pleuropneumoniae (APP) is a major cause of lung infections in pigs. An experimental mouse has the edge over pigs pertaining to the ease of experimental operation, disease study and therapy, abundance of genetic resources, and cost. However, it is a challenge to introduce APP into a mouse lung due to the small respiratory tract of mice and bacterial host tropism. In this study, an effective airborne transmission of APP serovar 1 (APP1) was developed in mice for lung infection. Consequently, APP1 infected BALB/c mice and caused 60% death within three days of infection at the indicated condition. APP1 seemed to enter the lung and, in turn, spread to other organs of the mice over the first 5 days after infection. Accordingly, APP1 damaged the lung as evidenced by its morphological and histological examinations. Furthermore, ampicillin fully protected mice against APP1 as shown by their survival, clinical symptoms, body weight loss, APP1 count, and lung damages. Finally, the virulence of two extra APP strains, APP2 and APP5, in the model was compared based on the survival rate of mice. Collectively, this study successfully established a fast and reliable mouse model of APP which can benefit APP research and therapy. Such a model is a potentially useful model for airway bacterial infections. Full article

Background: As the SARS-CoV-2 virus remains one of the main causes of severe respiratory system infections, the Food and Drug Administration strongly advises the continuation of current vaccination programs, including the distribution of updated boosters, especially in high-risk groups of patients. Therefore, there is an unceasing need for further research on the safety and, no less importantly, the clinical effectivity of the vaccines, with an extra focus on cohorts of patients with underlying health problems. This study aimed to assess the efficacy of the SARS-CoV-2 vaccine in possibly immunocompromised children with rheumatic disease while utilizing the interferon-gamma release assay (IGRA) as a marker for COVID-19 immunity in the study follow-up. Methods: This prospective study was performed in a group of 55 pediatric patients diagnosed with juvenile idiopathic arthritis. Eight participants were immunized with the Comirnaty mRNA vaccine before the research commenced, while the rest of the group (n = 47) had not been vaccinated against SARS-CoV-2. At the study baseline, the cellular response to the virus antigen was measured using a specific quantitative IGRA in whole blood; subsequently, the anti-SARS-CoV-2 test was performed, marking the antibodies’ levels in serum. Around four months after the enrollment of the last patient in the study, a follow-up survey regarding the events of COVID-19 infection within the cohort was conducted. Results: The study confirmed that all the vaccinated children developed specific T-cell (p = 0.0016) and humoral (p = 0.001 for IgA antibodies, p = 0.008 for IgG antibodies) responses to the inoculation, including those receiving biological treatment and those on conventional disease-modifying anti-rheumatic drugs. The study also showed the different patterns of immunity elicited both after infection and post-vaccination, with higher levels of antibodies and T-cell response after inoculation than after natural exposure to the pathogen. According to the follow-up survey, six children developed PCR-confirmed SARS-CoV-2 infection, whereas the additional 10 patients admitted to having COVID-like symptoms with no laboratory verification. Conclusions: SARS-CoV-2 vaccinations elicit valid immune responses in pediatric rheumatic patients. Including the assessment of T-cell immunity in the evaluation of inoculation-induced immunization can enhance the accuracy of sole humoral response assays. Full article

In order to limit the spread of the novel betacoronavirus (SARS-CoV-2), it is necessary to detect positive cases as soon as possible and isolate them. For this purpose, machine-learning algorithms, as a field of artificial intelligence, have been recognized as a promising tool. The aim of this study was to assess the utility of the most common machine-learning algorithms in the rapid triage of children with suspected COVID-19 using easily accessible and inexpensive laboratory parameters. A cross-sectional study was conducted on 566 children treated for respiratory diseases: 280 children with PCR-confirmed SARS-CoV-2 infection and 286 children with respiratory symptoms who were SARS-CoV-2 PCR-negative (control group). Six machine-learning algorithms, based on the blood laboratory data, were tested: random forest, support vector machine, linear discriminant analysis, artificial neural network, k-nearest neighbors, and decision tree. The training set was validated through stratified cross-validation, while the performance of each algorithm was confirmed by an independent test set. Random forest and support vector machine models demonstrated the highest accuracy of 85% and 82.1%, respectively. The models demonstrated better sensitivity than specificity and better negative predictive value than positive predictive value. The F1 score was higher for the random forest than for the support vector machine model, 85.2% and 82.3%, respectively. This study might have significant clinical applications, helping healthcare providers identify children with COVID-19 in the early stage, prior to PCR and/or antigen testing. Additionally, machine-learning algorithms could improve overall testing efficiency with no extra costs for the healthcare facility. Full article

Amyloidosis is a complex disorder characterized by deposited insoluble fibrillar proteins which misfold into β-pleated sheets. The pathogenesis of amyloidosis can vary but can be the result of immune dysregulation that occurs from sustained high inflammatory states, often known as AA amyloidosis. Multi-organ involvement including hepatic, gastrointestinal, renal, cardiac and immunological pathological manifestations has been observed amongst individuals presenting with amyloidosis. The recent global pandemic of severe acute respiratory syndrome coronavirus 2, also referred to as coronavirus 2019 (COVID-19), has been shown to be associated with multiple health complications, many of which are similar to those seen in amyloidosis. Though COVID-19 is recognized primarily as a respiratory disease, it has since been found to have a range of extra-pulmonary manifestations, many of which are observed in patients with amyloidosis. These include features of oxidative stress, chronic inflammation and thrombotic risks. It is well known that viral illnesses have been associated with the triggering of autoimmune conditions of which amyloidosis is no different. Over the recent months, reports of new-onset and relapsed disease following COVID-19 infection and vaccination have been published. Despite this, the exact pathophysiological associations of COVID-19 and amyloidosis remain unclear. We present a scoping review based on our systematic search of available evidence relating to amyloidosis, COVID-19 infection and COVID-19 vaccination, evaluating current perspectives and providing insight into knowledge gaps that still needs to be addressed going forward. Full article

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolysis and thrombosis and is associated with significant morbidity and mortality. Although complement inhibitors have significantly changed the outcomes in PNH patients, breakthrough hemolysis (BTH) may still occur as a response to stress factors such as pregnancy, surgery, and infections. Despite the well-described association between bacterial infections and hemolysis in PNH patients, little is known about the effect of respiratory viruses on triggering hemolytic episodes. This is the first study, to our knowledge, addressing this question. We retrospectively analyzed 34 patients with PNH disease between 2016 and 2018, who were on eculizumab treatment and who presented with respiratory symptoms and were subsequently tested for 10 respiratory viruses (influenza A, influenza B, parainfluenza, respiratory syncytial virus, adenovirus, rhinovirus, and human metapneumovirus). NTS+ patients had higher inflammatory markers, with the majority requiring antibiotics. Acute hemolysis, along with a significant drop in hemoglobin, was noted in the NTS+ group, with three of them requiring a top-up transfusion and two requiring an extra dose of eculizumab. Furthermore, the time from the last eculizumab dose was longer in the NTS+ patients who had BTH, than those who did not. Our data indicate that respiratory virus infections pose a significant risk for BTH in PNH patients on complement inhibitor treatment, underlining the need for regular screening and close monitoring of patients with respiratory symptoms. Furthermore, it implies a higher risk for patients who are not established on complement inhibitors, suggesting the necessity for greater vigilance in these patients. Full article