Search

Abstract Background A standardized and cost-effective molecular identification system is now an urgent need for Fungi owing to their wide involvement in human life quality. In particular the potential use of mitochondrial DNA species markers has been taken in account. Unfortunately, a serious difficulty in the PCR and bioinformatic surveys is due to the presence of mobile introns in almost all the fungal mitochondrial genes. The aim of this work is to verify the incidence of this phenomenon in Ascomycota, testing, at the same time, a new bioinformatic tool for extracting and managing sequence databases annotations, in order to identify the mitochondrial gene regions where introns are missing so as to propose them as species markers. Methods The general trend towards a large occurrence of introns in the mitochondrial genome of Fungi has been confirmed in Ascomycota by an extensive bioinformatic analysis, performed on all the entries concerning 11 mitochondrial protein coding genes and 2 mitochondrial rRNA (ribosomal RNA) specifying genes, belonging to this phylum, available in public nucleotide sequence databases. A new query approach has been developed to retrieve effectively introns information included in these entries. Results After comparing the new query-based approach with a blast-based procedure, with the aim of designing a faithful Ascomycota mitochondrial intron map, the first method appeared clearly the most accurate. Within this map, despite the large pervasiveness of introns, it is possible to distinguish specific regions comprised in several genes, including the full NADH dehydrogenase subunit 6 (ND6) gene, which could be considered as barcode candidates for Ascomycota due to their paucity of introns and to their length, above 400 bp, comparable to the lower end size of the length range of barcodes successfully used in animals. Conclusion The development of the new query system described here would answer the pressing requirement to improve drastically the bioinformatics support to the DNA Barcode Initiative. The large scale investigation of Ascomycota mitochondrial introns performed through this tool, allowing to exclude the introns-rich sequences from the barcode candidates exploration, could be the first step towards a mitochondrial barcoding strategy for these organisms, similar to the standard approach employed in metazoans.

Abstract Background Population genetics studies based on the analysis of mtDNA and mitochondrial disease studies have produced a huge quantity of sequence data and related information. These data are at present worldwide distributed in differently organised databases and web sites not well integrated among them. Moreover it is not generally possible for the user to submit and contemporarily analyse its own data comparing them with the content of a given database, both for population genetics and mitochondrial disease data. Results HmtDB is a well-integrated web-based human mitochondrial bioinformatic resource aimed at supporting population genetics and mitochondrial disease studies, thanks to a new approach based on site-specific nucleotide and aminoacid variability estimation. HmtDB consists of a database of Human Mitochondrial Genomes, annotated with population data, and a set of bioinformatic tools, able to produce site-specific variability data and to automatically characterize newly sequenced human mitochondrial genomes. A query system for the retrieval of genomes and a web submission tool for the annotation of new genomes have been designed and will soon be implemented. The first release contains 1255 fully annotated human mitochondrial genomes. Nucleotide site-specific variability data and multialigned genomes can be downloaded. Intra-human and inter-species aminoacid variability data estimated on the 13 coding for proteins genes of the 1255 human genomes and 60 mammalian species are also available. HmtDB is freely available, upon registration, at http://www.hmdb.uniba.it. Conclusion The HmtDB project will contribute towards completing and/or refining haplogroup classification and revealing the real pathogenic potential of mitochondrial mutations, on the basis of variability estimation.

Intrinsic and extrinsic factors, such as bioerosion at nesting sites, regulate population dynamics and are relevant for the long-term conservation of penguins. Colony trends (between 2004-2022) were studied in a Magellanic penguin colony on Martillo Island, Beagle Channel, Argentina and compared between zones with contrasting degrees of erosion (high, medium, low). Individuals from each zone were characterized for foraging ecology, stress, and reproductive performance during the 2017-2018 breeding season to better understand the colony dynamics. Changes in nest abundance varied in magnitude between nesting zones with different characteristics of occupation time, density and erosion. Declines in nest abundance in the densest, most eroded and longest occupied zone suggests that environmental degradation may be limiting the colony's carrying capacity. A higher percentage of late breeders (probably younger breeders) occupied the less eroded and more recently occupied zone. Foraging, breeding and stress barely differed between zones. New individuals recruiting into the breeding colony select less-eroded zones, either to reduce competition for nests or to avoid other effects of erosion and high-density areas. If this is the mechanism behind the shift in numbers throughout the island, we expect the island to be progressively occupied to the west. If competition or other density dependent factors are at play, a time will come when the vacant east side will begin to be recolonized by younger individuals. However, if erosion or other long-term effects spread throughout the island, recolonization may not occur and the colony may ultimately be abandoned as individuals search for new breeding grounds. Erosion at the breeding site may be a key factor in regional population trends of this burrow nesting species, by following an extinction / colonization of new sites process., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Scioscia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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. The TT strategy, which considers behavioral/risk factors, as well as pulmonary and extrapulmonary traits, has shown to be a promising strategy in COPD management. This work reviews the TT strategy in COPD, giving special attention to the most relevant pulmonary traits, such as frequent productive cough, chronic bronchitis, type 2 inflammation, neutrophilic inflammation, lung hyperinflation, bronchiectasis, exacerbations and non-reversible airflow limitation. N-acetylcysteine (NAC), a widely used mucolytic agent, might be a major player in this strategy. Indeed, through a thorough review of the literature, it has been possible to highlight that, besides being essential in the treatment of frequent productive cough, NAC could bring benefits in case of airflow limitations, airways inflammation, exacerbations and bronchiectasis. A clinical case in which the TT strategy was able to reduce symptoms and improve lung function and quality of life, minimizing unnecessary medication and side effects, is also presented. The identification of TTs and their proper treatment through personalized medicine remarkably ameliorates COPD management. Of note, the mucolytic, antioxidant, and anti-inflammatory activities of NAC might have beneficial effects on several TTs., Competing Interests: Declaration of Competing Interest ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Giulia Scioscia reports financial support and writing assistance were provided by Zambon Italy Srl. Giulia Scioscia reports a relationship with Zambon Italy Srl that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

This study identifies two distinct subgroups of patients with severe eosinophilic asthma who respond differently to mepolizumab. Cluster analysis reveals that patients with a family history of asthma, positive skin prick tests and higher baseline lung function have better treatment outcomes, highlighting the value of personalised treatment strategies., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Severe asthma presents significant management challenges, often requiring advanced treatments to control symptoms and reduce exacerbations. The use of monoclonal antibodies has revolutionized the clinical course of patients with severe asthma, showing a significant impact on exacerbations reduction, oral corticosteroids (OCS) cessation and on the improvement of lung function and quality of life. Tezepelumab, an anti-thymic stromal lymphopoietin (TSLP) monoclonal antibody, has emerged as a potential therapeutic option for these patients., Methods: We conducted an observational, prospective, multicenter study including 20 patients with confirmed severe asthma according to ERS guidelines and GINA recommendations. Patients received Tezepelumab 210 mg every 4 wk due to uncontrolled asthma despite maximal inhalation treatment with ICS/LABA. Data were collected before treatment initiation (T0) and after three months from the first administration (T3)., Results: After three months of Tezepelumab treatment, we reported significant improvements in asthma symptoms and quality of life, as well as a consistent reduction in exacerbations and OCS use. We found no statistically meaningful differences among main clinical and functional outcomes according to inflammatory biomarkers, while lung function improved significantly in patients with less allergic sensitization. No serious adverse event was reported during the follow up, while the rates of mild adverse effects were comparable to those from registration trials., Conclusion: Tezepelumab demonstrated short-term efficacy in improving asthma control and quality of life, showing a favorable safety profile. Further studies with larger sample sizes and longer follow-up would confirm these findings and identify predictors of response to Tezepelumab.

Background: Interstitial lung diseases (ILD) is a group of lung disorders characterized by interstitial lung thickening due to inflammatory and fibrotic processes. Krebs von den Lungen-6 (KL-6) is a molecule secreted by damaged type II alveolar pneumocytes in the alveolar space. The goal of the present study was to compare two detection methods of KL-6 in both bronchoalveolar lavage (BAL) and serum from ILD patients at the moment of diagnosis., Methods: Patients with suspicious of ILD and followed at two Italian referral centres for rare lung diseases were included in the study. BAL fluid and serum were collected and analysed by chemiluminescent enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) methods provided by Tosoh Biosciences., Results: A total of 158 (mean age ± standard deviation, 61.5 ± 13.7, 65 females) patients were enrolled. A total of, 36 had diagnosis of idiopathic pulmonary fibrosis (IPF), 74 sarcoidosis, 15 connective tissue disease-ILD (CTD-ILD) and 33 other ILD. Diagnostic agreement between two methods was demonstrated for both BAL (r = 0.707, p < 0.0001) and serum (r = 0.816, p < 0.0001). BAL KL-6 values were lower than serum (p < 0.0001). IPF patients had higher serum KL-6 concentration than other ILDs (p = 0.0294), while BAL KL-6 values were lower in IPF than in non-IPF (p = 0.0023)., Conclusion: This study explored KL-6 concentrations through the CLEIA method in serum and BAL of patients with various ILDs, showing significant differences of biomarkers concentrations between IPF and other non-IPF ILDs. Our findings are promising as they provided further knowledge concerning KL-6 expression across different ILDs and may suggest its utility in differential diagnosis., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background and Objective: Several randomized controlled trials (RCTs) have shown that benralizumab is characterized by a good profile of efficacy and safety, thereby being potentially able to elicit clinical remission on-treatment of severe eosinophilic asthma (SEA). The main goal of this multicentre observational study was to verify the effectiveness of benralizumab in inducing a sustained remission on-treatment of SEA in patients with or without comorbid chronic rhinosinusitis with nasal polyps (CRSwNP)., Methods: Throughout 2 years of treatment with benralizumab, a four-component evaluation of sustained remission of SEA was performed, including the assessment of SEA exacerbations, use of oral corticosteroids (OCSs), symptom control and lung function., Results: The present study recruited 164 patients suffering from SEA. After 24 months of add-on biological therapy with benralizumab, 69 (42.1%) achieved the important target of sustained remission on-treatment (exacerbation rate = 0, OCS dose = 0, pre-bronchodilator FEV 1 ≥80% pred., ACT score ≥ 20). During the same period, a persistent improvement of CRSwNP (SNOT-22 < 30, NP recurrence = 0) was observed in 33 (40.2%) out of 82 subjects with concomitant NP. The latter comorbidity and post-bronchodilator reversibility of airflow limitation were two independent predictors of sustained remission on-treatment (OR = 2.32, p < 0.05 and OR = 5.59, p < 0.01, respectively)., Conclusion: Taken together, the results of this real-life clinical investigation indicate that benralizumab can induce a sustained remission on-treatment of SEA, especially in those patients with comorbid CRSwNP and reversible airflow limitation., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Introduction: Patients with chronic obstructive pulmonary disease (COPD) frequently have cardiovascular comorbidities, increasing the risk of hospitalised COPD exacerbations (H-ECOPDs) or death. This pragmatic study examined the effects of adding an inhaled corticosteroid (ICS) to long-acting bronchodilator(s) (LABDs) in patients with COPD and cardiac comorbidities who had a recent H-ECOPD., Methods: Patients >60 years of age with COPD and ≥1 cardiac comorbidity, within 6 months after discharge following an H-ECOPD, were randomised to receive LABD(s) with or without ICS, and were followed for 1 year. The primary outcome was the time to first rehospitalisation and/or all-cause death., Results: The planned number of patients was not recruited (803/1032), limiting the strength of the conclusions. In the intention-to-treat population, 89/403 patients (22.1 %) were rehospitalised or died in the LABD group (probability 0.257 [95 % confidence interval 0.206, 0.318]), vs 85/400 (21.3 %) in the LABD+ICS group (0.249 [0.198, 0.310]), with no difference between groups in time-to-event (hazard ratio 1.116 [0.827, 1.504]; p = 0.473). All-cause and cardiovascular mortality were lower in patients receiving LABD(s)+ICS, with relative reductions of 19.7 % and 27.4 %, respectively (9.8 % vs 12.2 % and 4.5 % vs 6.2 %), although the groups were not formally statistically compared for these endpoints. Fewer patients had adverse events in the LABD+ICS group (43.0 % vs 50.4 %; p = 0.013), with 4.9 % vs 5.4 % reporting pneumonia adverse events., Conclusions: Results suggest addition of ICS to LABDs did not reduce the time-to-combined rehospitalisation/death, although it decreased all-cause and cardiovascular mortality. ICS use was not associated with an increased risk of adverse events, particularly pneumonia., Competing Interests: Declaration of competing interest In addition to the medical writing support disclosed below, the authors have the following conflicts of interest. Alberto Papi reports grants to his institution from Chiesi, AstraZeneca, GlaxoSmithKline and Sanofi, consulting fees from Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, Moderna, and Roche, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, AstraZeneca, GlaxoSmithKline, Menarini, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, Sanofi, and Regeneron, and participation on advisory boards for Chiesi, AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, Iqvia, Avillion, Elpen Pharmaceuticals, and Moderna. All are outside the scope of the current manuscript. Giacomo Forini has no other conflicts to disclose. Mauro Maniscalco declares grants or contracts (with payments to Istituti Clinici Scientifici Maugeri IRCCS) from GlaxoSmithKline and AstraZeneca, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GlaxoSmithKline, AstraZeneca, and Chiesi. All are outside the scope of the current manuscript. Elena Bargagli has no other conflicts to disclose. Claudia Crimi received honoraria for lectures from Fisher & Paykel, ResMed, AstraZeneca, Sanofi, GlaxoSmithKline, and Vitalaire. All are outside the scope of the current manuscript. Pierachille Santus declares research grants from AstraZeneca, Edmondpharma, GlaxoSmithKline, and Novartis (payments were made to the Department of Biomedical and Clinical Sciences of University of Milan), consulting fees from GlaxoSmithKline, Sanofi, Edmondpharma, Dompè, Valeas, and Neopharmed, and honoraria for lectures from AstraZeneca, Sanofi, GlaxoSmithKline, Berlin Chemie, Edmondpharma, and Zambon Brasil. All are outside the scope of the current manuscript. Antonio Molino has no other conflicts to disclose. Valeria Bandiera is an employee of Alira Health SrI, which received funding from the Università degli Studi di Ferrara to provide biometrics services to the study. Federico Baraldi received a short-term research fellowship from the European Respiratory Society, outside the scope of the current manuscript Silvestro Ennio D'Anna has no other conflicts to disclose. Mauro Carone received honoraria as speaker from GlaxoSmithKline and AstraZeneca, and honoraria for participation in speaker bureaus from Boehringer Ingelheim, support for attending meetings and travel from the Associazione Italiana Pneumologi Ospedalieri – Italian Thoracic Society (AIPO-ITS/ETS), and an unpaid role as the National President of the AIPO-ITS/ETS. All are outside the scope of the current manuscript. Maurizio Marvisi has no other conflicts to disclose. Corrado Pelaia received honoraria for lectures from AstraZeneca, GlaxoSmithKline, and Sanofi, all outside the scope of the current manuscript. Giulia Scioscia has no other conflicts to disclose. Vincenzo Patella has no other conflicts to disclose. Maria Aliani has no other conflicts to disclose. Leonardo M Fabbri received consulting fees from Alfasigma, AstraZeneca, Chiesi, GlaxoSmithKline, ICON, Menarini, Novartis, and Verona Pharma, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chiesi, GlaxoSmithKline, Glenmark, Lusofama, and Novartis, support for attending meetings and/or travel from the Italian Society of Allergy, Asthma and Clinical Immunology and the Menarini Foundation, and participated in a data safety monitoring board or advisory board for Novartis, Chiesi, and ICON. All are outside the scope of the current manuscript., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

This study investigates volatile organic compound (VOC) profiles in the exhaled breath of normal subjects under different oxygenation conditions-normoxia (FiO2 21%), hypoxia (FiO2 11%), and hyperoxia (FiO2 35%)-using an electronic nose (e-nose). We aim to identify significant differences in VOC profiles among the three conditions utilizing principal component analysis (PCA) and canonical discriminant analysis (CDA). Our results indicate distinct VOC patterns corresponding to each oxygenation state, demonstrating the potential of e-nose technology in detecting physiological changes in breath composition (cross-validated accuracy values: FiO2 21% vs. FiO2 11% = 63%, FiO2 11% vs. FiO2 35% = 65%, FiO2 21% vs. FiO2 35% = 71%, and p < 0.05 for all). This research underscores the viability of breathomics in the non-invasive monitoring and diagnostics of various respiratory and systemic conditions.

Introduction: The relationship between obstructive sleep apnea (OSA) and cancer has been recognized for some time now. However, little is known about the mechanisms by which sleep apnea promotes tumorigenesis and the impact of OSA on survival after cancer diagnosis. In the last few years, research has focused on the exploration of different biomarkers to understand the mechanisms underlying this relationship and miRNAs, non-coding single strands of about 22 nucleotides that post-transcriptionally regulate gene expression, have emerged as possible actors of this process.The aim of the study was to evaluate the impact of OSA on survival of metastatic colorectal cancer (mCRC) patients based on the expression of specific miRNAs., Methods: The expression of 6 miRNAs, respectively miR-21, miR-23b, miR-26a, miR-27b, miR-145 and miR-210, was analyzed by qRT-PCR in patients' sera. Response to first-line therapy, Kaplan-Meier curves of overall and progression-free survival were used to evaluate survival in mCRC patients with and without OSA stratified for the expression of miRNAs., Results: The expression of miR-21, miR-23b, miR-26a and miR-210 was significantly upregulated in mCRCs with OSA compared to no OSA. In mCRC patients with OSA and increasing expression of miR-21, miR-23b, miR-26a and miR-210 risk of progression after first-line therapy was higher and both overall and progression-free survival were significantly worst. Conversely, as miR-27b and miR-145 expression increased, the life expectancy of patients diagnosed with OSA and mCRC improved markedly., Conclusions: This study highlights the relevance of specific miRNAs on OSA in mCRCs and their significance as non-invasive biomarkers in predicting the prognosis in patients with mCRC and OSA., (© 2024 The Authors.)

Background: Post COVID-19 syndrome is a frequent disabling outcome, leading to a delay in social reintegration and return to working life., Study Design: This was a prospective observational cohort study. The main objective was to explore the effectiveness of a Spa rehabilitation treatment on the improvement of post COVID-19 dyspnoea and fatigue, also analyzing the relationship between such symptoms. Additionally, it was assessed if different clinical characteristics could predispose patients in experiencing post COVID-19 symptoms or could influence the effectiveness of a Spa intervention., Methods: From July to November 2021, 187 post COVID-19 patients were enrolled in the study. All the patients complained persi-sting dyspnoea, whose impact on daily activities was assessed using the modified Medical Research Council dyspnoea scale. 144 patients (77.0%) reported also fatigue. The Spa treatment was started at least 3 months after COVID-19 acute phase. At the end of the treatment, patients were asked to rate the improvement in the dyspnoea and fatigue sensation. 118 patients also underwent the modified Borg Dyspnoea Scale for severity estimation of Exertion Dyspnoea and the Barthel index for severity estimation of Physical Limitation., Results: 165 out of 187 patients (88.2%) reported an improvement in dyspnoea, while 116 out 144 patients (80.6%) reported an improvement in both dyspnoea and fatigue. On a total of 118 subjects, a clinically significant improvement in the modified Borg Dyspnoea Scale (i.e. Delta Borg equal or more than -2.0 points) was reached by the 50.8% of patients, while a clinically significant improvement in the Barthel index (i.e. Delta Barthel equal or more than +10.0 points) was reached by the 51.7% of them. The 31.4% of patients reached a minimal clinically important improvement in both the modified Borg Dyspnoea Scale and the Barthel index. No risk factors were associated to a clinically impacting dyspnoea at entry, while a BMI>30 Kg/m2 was the main risk factor for chronic fatigue. Presence of respiratory comorbidities, obesity and severe acute COVID-19 (phenotype 4) configured risk factors for the lack of improvement of dyspnoea after the treatment, while no risk factors were associated to a lack of improvement for fatigue. Older age, obesity and comorbidities seemed to make more difficult to reach a clinically meaningful improvement in the modified Borg Dyspnoea Scale and the Barthel index after treatment. Female gender may imply more physical limitation at entry, while male patients seem to show less improvement in the Barthel index after treatment., Conclusions: Dyspnoea and fatigue were confirmed to be important post COVID-19 symptoms even in younger subjects of wor-king age and subjects with absent or modest pulmonary alterations at distance from acute COVID-19. A Spa health resort seems to be an effective "low-intensity" setting for a rehabilitation program of such patients. There is a strong relationship in terms of improvement between dyspnoea and fatigue, even if risk factors for their occurrence appear to be different. The improvement in exertion dyspnoea and physical limitation seemed to be less mutually related, probably due to a greater complexity in the asses-sment questionnaires. Some risk factors may predict a lack of improvement in symptoms after treatment.

Background: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. Although mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission., Objective: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months., Methods: The REMIssion in Severe Eosinophilic Asthma Treated with Mepolizumab (REMI-M) is a retrospective, real-world, multicenter study that analyzed 303 patients with severe eosinophilic asthma who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroid (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period., Results: Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% and 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastroesophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent., Conclusions: This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background : Pneumothorax (PNX) represents a common clinical condition in emergency departments (EDs), requiring prompt recognition and treatment. The role of transthoracic ultrasounds (TUSs) in the diagnosis of PNX is still debated. We aimed to prospectively evaluate the accuracy of TUSs in the detection of spontaneous PNX in EDs. Methods : A total of 637 consecutive adult patients who presented to the EDs of four Italian hospitals complaining of acutely onset chest pain and dyspnoea were included in the study. Exclusion criteria were previous traumatic events, cardiogenic causes of pain/dyspnoea and suspected tension PNX. The absence of "lung sliding" (B-mode) and the "bar-code" sign (M-mode) were considered indicative of PNX in a TUS. Accuracy, sensitivity, specificity, and positive and negative predictive values (PPVs, NPVs) were calculated using a chest CT scan as reference. Results : Spontaneous PNX occurred in 93 patients: of those, 83 (89.2%) were correctly identified by TUSs. However, 306 patients with suspected PNX at TUS were not confirmed by chest CTs. The diagnostic accuracy of both the absence of "lung sliding" and "bar-code" sign during TUS was 50.4% (95% CI: 46.4-54.3), sensitivity was 89.2% (95% CI: 81.1-94.7), specificity was 43.8% (95% CI: 39.5-48.0), the PPV was 21.3% (95% CI: 19.7-23.1) and the NPV was 96.0% (95% CI: 92.9-97.7). Conclusions : TUS showed high sensitivity but low specificity in the identification of PNX in EDs. Relying exclusively on TUSs results for patients' management in ED settings is neither suitable nor recommendable. TUS examination can be useful to strengthen the clinical suspicion of PNX, but its results should be confirmed by a chest X-ray or CT scan.

Recent advancements in asthma management include non-invasive methodologies such as sputum analysis, exhaled breath condensate (EBC), and fractional exhaled nitric oxide (FeNO). These techniques offer a means to assess airway inflammation, a critical feature of asthma, without invasive procedures. Sputum analysis provides detailed insights into airway inflammation patterns and cellular composition, guiding personalized treatment strategies. EBC collection, reflecting bronchoalveolar lining fluid composition, provides a non-invasive window into airway physiology. FeNO emerges as a pivotal biomarker, offering insights into eosinophilic airway inflammation and aiding in asthma diagnosis, treatment monitoring, and the prediction of exacerbation risks. Despite inherent limitations, each method offers valuable tools for a more comprehensive assessment of asthma. Combining these techniques with traditional methods like spirometry may lead to more personalized treatment plans and improved patient outcomes. Future research is crucial to refine protocols, validate biomarkers, and establish comprehensive guidelines in order to enhance asthma management with tailored therapeutic strategies and improved patient outcomes.

Purpose: Asthma, obstructive sleep apnea (OSA), rhinosinusitis, and esophageal reflux are conditions that may overlap, forming a syndrome known as CORE. Whenever clinical remission of severe asthma (SA) is not achieved, it is essential to investigate the presence of comorbidities, in particular the presence of OSA that may lead to the diagnosis of CORE syndrome., Methods: The study was conducted on naive patients with SA and concomitant rhinosinusitis and esophageal reflux, referred to our institute since 2018. Patients who did not experience clinical remission were investigated for OSA through a home sleep apnea test. Subsequently, for those diagnosed with OSA, continuous positive airway pressure (CPAP) was proposed and was re-evaluated after 12 months., Results: Six patients with CORE syndrome were enrolled. The mean apnea-hypopnea index (AHI) was 33.25 ± 20.13 events/h, oxygen desaturation index (ODI) was 28.95 ± 19.95 events/h, and time in bed with SaO2 < 90% (T 90 ) was 26.40 ± 27.22% for which continuous positive airway pressure (CPAP) treatment was proposed but only 3 out of 6 patients accepted. After 12 months, all CPAP-treated patients manifested a significant reduction in daytime sleepiness (ESS score was 6.33 ± 3.8), an improvement in ACT score (+ 8 (+ 32%), + 9 (+ 36%), and + 14 (+ 56%) points), a discontinuation of oral corticosteroids (OCS), an absence of exacerbations, and an improvement of lung function leading to clinical remission of asthma., Conclusion: Whenever facing SA patients, non-responders to therapy, it is important to suspect the presence of CORE syndrome; in particular, the detection and subsequent treatment of OSA would seem to improve the outcome of such patients., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) ( p < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; p < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; p < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; p < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Background: Interstitial lung diseases (ILDs) encompass a diverse group of disorders affecting the lung interstitium, leading to inflammation, fibrosis, and impaired respiratory function. Currently, the identification of new diagnostic and prognostic biomarkers for ILDs turns out to be necessary. Several studies show the role of KL-6 in various types of interstitial lung disease and suggest that serum KL-6 levels can be used as a prognostic marker of disease. The aim of this study was to analyze KL-6 expression either in serum or bronchoalveolar lavage samples in order to: (i) make a serum vs. BAL comparison; (ii) better understand the local behavior of fibrosis vs. the systemic one; and (iii) evaluate any differences in patients with progressive fibrosis (PPF) versus patients with non-progressive fibrosis (nPPF). Methods: We used qRT-PCR to detect KL-6 expression both in serum and BAL samples. Mann-Whitney's U test was used to compare the differential expression between groups. Results: In serum, KL-6 is more highly expressed in PPF than in non-progressive fibrosis ( p = 0.0295). This difference is even more significant in BAL ( p < 0.001). Therefore, it is clear that KL-6 values are related to disease progression. Significant differences were found by making a comparison between BAL and serum. KL-6 was markedly higher in serum than BAL ( p = 0.0146). Conclusions: This study identifies KL-6 as a promising biomarker for the severity of the fibrosing process and disease progression in ILDs, with significantly higher levels observed in PPF compared to nPPF. Moreover, the marked difference in KL-6 levels between serum and BAL emphasizes its potential diagnostic and prognostic relevance, providing enlightening insights into both the local and systemic aspects of ILDs.

Introduction: Clinical remission (CliR) achievement has been recognized as a new potential outcome in severe asthma. Nevertheless, we still lack a detailed profile of what features could better identify patients undergoing clinical remission. In this study, we aim to address this issue, tracing a possible identikit of patients fulfilling remission criteria., Methods: We enrolled 266 patients with severe eosinophilic asthma (SEA) treated with a 12-month course of anti-IL5/IL5 receptor (IL5r) monoclonal antibodies. Patients with no exacerbation, OCS withdrawal, ACT ≥ 20 and FEV 1 ≥ 80% after 1 year of biologic treatment were classified as in clinical remission., Results: 30.5% of the enrolled patients achieved remission after biologic administration. CliR group showed a lower number of baseline asthma exacerbations and better lung function parameters, with a trend for higher ACT scores and a less frequent history of a positive skin prick test. CliR achievement was unlikely in presence of a higher BMI, a positive skin prick test, an increased number of asthma exacerbations before biologic treatment, anti-muscarinic administration, and a previous diagnosis of EGPA, bronchiectasis or osteoporosis. In contrast, a better lung function, an increased blood eosinophilic count, the presence of chronic rhinosinusitis with nasal polyps and a more frequent use of reliever therapy predicts remission development. Changes in exacerbations number, OCS use, ACT scores and FEV 1 % between remittent and non-remittent patients arise at specific follow up timepoints and are positively associated with CliR achievement., Discussion: anti-IL5/IL5r biologics can induce CliR in a proportion of patients with SEA. Patients achieving remission demonstrate specific clinical, functional and inflammatory features, as well as a specific moment of improvement in all the CliR items., Competing Interests: GC reported grants or contracts from Astrazeneca, Chiesi, GlaxoSmithKline, Sanofi, Grifols; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Sanofi; support for attending meetings and/or travel from Astrazeneca, Menarini, Chiesi. AP reported payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Chiesi, Sanofi. AD reported payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Sanofi, Novartis, Lofarma. GS reported payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Sanofi. GV reported payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from GlaxoSmithKline, Sanofi. MD reported consulting fees from Astrazeneca, GlaxoSmithKline, Sanofi; payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Sanofi, Novartis; participation on Data Safety Monitoring Board or Advisory Board from Astrazeneca, GlaxoSmithKline, Sanofi. MT reported consulting fees from Astrazeneca, GlaxoSmithKline, Novartis. Nicola Scichilone reported payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Chiesi, Sanofi. CCr reported payment or honoraria for lectures, presentations, speakers, bureaus, manuscript writing or educational events from Astrazeneca, GlaxoSmithKline, Sanofi, Menarini, ResMed, Fisher&Paykel. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Carpagnano, Portacci, Nolasco, Detoraki, Vatrella, Calabrese, Pelaia, Montagnolo, Scioscia, Valenti, D’Amato, Caiaffa, Triggiani, Scichilone and Crimi.)

Background. Nowadays, highly selective biological drugs offer the possibility of treating severe type 2 asthma. However, in the real-life setting, it is crucial to confirm the validity of the chosen biological treatment by evaluating the achievement of clinical remission. Study purpose. The main aims of this real-life study were to evaluate the efficacy of dupilumab in terms of clinical, functional, and inflammatory outcomes at 6, 12, 18, and 24 months of treatment and to estimate the percentage of patients achieving partial or complete clinical remission at 12 and 24 months of treatment. In addition, we attempted to identify whether baseline clinical characteristics of patients could be associated with clinical remission at 24 months of treatment. Materials and methods. In this observational prospective study, 20 outpatients with severe uncontrolled eosinophilic asthma were prescribed dupilumab and followed-up after 6, 12, 18, and 24 months of treatment. At each patient visit, the need for oral corticosteroids (OCS) and corticosteroid required dose, number of exacerbations during the previous year or from the previous visit, asthma control test (ACT) score, pre-bronchodilator forced expiratory volume in the 1st second (FEV 1 ), fractional exhaled nitric oxide at a flow rate of 50 mL/s (FeNO 50 ), and blood eosinophil count were assessed. Results. The number of OCS-dependent patients was reduced from 10 (50%) at baseline to 5 (25%) at one year (T12) and 2 years (T24). The average dose of OCS required by patients demonstrated a significant reduction at T12 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.015), remaining significant even at T24 (12.5 ± 13.75 mg vs. 2.63 ± 3.94 mg, p = 0.016). The number of exacerbators showed a statistically significant decrease at T24 (10 patients, 50% vs. 3 patients, 15%, p = 0.03). The mean number of exacerbations demonstrated a statistically significant reduction at T24 (1.45 ± 1.58 vs. 0.25 ± 0.43, p = 0.02). The ACT score improved in a statistically significant manner at T12 (15.30 ± 4.16 vs. 21.40 ± 2.35, p < 0.0001), improving further at T24 (15.30 ± 4.16 vs. 22.10 ± 2.59, p < 0.0001). The improvement in pre-bronchodilator FEV 1 values reached statistical significance at T24 (79.5 ± 14.4 vs. 87.7 ± 13.8, p = 0.03). The reduction in flow at the level of the small airways (FEF 25-75% ) also demonstrated an improvement, although it did not reach statistical significance either at T12 or T24. A total of 11 patients (55%) showed clinical remission at T12 (6 complete + 5 partial) and 12 patients (60%) reached clinical remission at T24 (9 complete + 3 partial). Only obesity was associated with a negative odds ratio (OR) for achieving clinical remission at T24 (OR: 0.03, 95% CI: 0.002-0.41, p = 0.004). No other statistically significant differences in baseline characteristics emerged between patients who reached clinical remission at T24 and the group of patients who did not achieve this outcome. Conclusion. Dupilumab appears to be an effective drug in promoting achievement of clinical remission in patients with severe uncontrolled eosinophilic asthma. The achievement of clinical remission should be continuously evaluated during treatment. Further studies are needed to clarify whether certain baseline clinical characteristics can help predict dupilumab favorable outcomes.

Wildlife tourism is increasing worldwide and monitoring the impact of tourism on wild populations is of the utmost importance for species conservation. The Magellanic penguin Spheniscus magellanicus colony at Martillo Island, Argentina, was studied in the 2016-2020 breeding seasons. In all seasons, adults and chicks belonged to: (i) an area close to or within the tourist trail or (ii) an area far from the tourist trail and out of sight of the tourists. Blood samples were taken for carbon and nitrogen stable isotope composition, in order to estimate trophic niches, and for smears that were made in situ and were then stained in the laboratory where leucocyte counts and differentiation were made under optical microscope. Heterophil to lymphocyte ratios were used as proxies of stress. Repeated sampling showed individual stress levels reduced while wintering. In 2017, stress levels and trophic values were lower than 2018 for the same individuals. Trophic levels did not differ between tourism and no tourism areas within each season, and differed between 2017 and the remaining seasons, indicating a possible diet shift that year. Stress levels were higher for the tourism area than the no tourism area for adults and chicks in all years except for 2020, when stress levels in the tourism area were lower and similar to the no tourism area that year and previous years. Vessel transit within the Beagle Channel and tourist visitation to the penguin colony was greatly reduced in 2020 due to the Covid-19 pandemic. A combination of internal characteristics and external factors may be affecting the stress physiology of individuals. Therefore, future research should include sampling of multiple aspects of penguin physiology, behaviour and environmental context in order to evaluate each effect on Magellanic penguin stress and, ultimately, inform the conservation of this iconic species in time., Competing Interests: The authors have no conflicts to declare., (© The Author(s) 2023. Published by Oxford University Press and the Society for Experimental Biology.)