Respiratory Disease Research Articles

EVALUATION OF THE PREVALENCE MYCOPLASMA GALLISEPTICUM IN BROILER FARMS IN SAMARRA CITY.

This study was aimed to evaluate the extent of the spread for Mycoplasma gallisepticum in the broiler chicken flocks of the Samarra city. 202 samples were collected from eight meat chicken fields in the city of Samarra for the period from September to December 2022, as these samples showed respiratory symptoms. The collected specimens were dissected in order to obtain both the trachea and the air sacs; After isolating the causative agent on Pleuropneumonia - like organisms (PPLOs) medium, mycoplasma infection reached 32.2%. The result appeared in the form of colonies with a shape similar to that of a “fried egg.” The rates of mycoplasma infection at culture for each of the trachea were (41.1%), while in contrast to the air sac samples, which amounted to (22.1%). Polymerase Chain Reaction (PCR) results for the 16S rRNA gene also showed a positive result for Mycoplasma gallisepticum. The results were also disturbed by the appearance of respiratory signs, such as coughing and sneezing, along with the presence of ocular and nasal secretions. It was also noted that pathological changes were recorded in both the trachea and air sacs, represented by congestion of these organs.

Stress Can Induce Bovine Alpha-Herpesvirus 1 (BoHV-1) Reactivation from Latency

Bovine alpha-herpesvirus 1 (BoHV-1) is a significant problem for the cattle industry, in part because the virus establishes latency, and stressful stimuli increase the incidence of reactivation from latency. Sensory neurons in trigeminal ganglia and unknown cells in pharyngeal tonsils are importantsites for latency. Reactivation from latency can lead to reproductive problems in pregnant cows, virus transmission to young calves, suppression of immune responses, and bacterial pneumonia. BoHV-1 is also a significant cofactor in bovine respiratory disease (BRD). Stress, as mimicked by the synthetic corticosteroid dexamethasone, reproducibly initiates reactivation from latency. Stress-mediated activation of the glucocorticoid receptor (GR) stimulates viral replication and transactivation of viral promoters that drive the expression of infected cell protein 0 (bICP0) and bICP4. Notably, GR and Krüppel-like factor 15 (KLF15) form a feed-forward transcription loop that cooperatively transactivates immediate early transcription unit 1 (IEtu1 promoter). Two pioneer transcription factors, GR and KLF4, cooperatively transactivate the bICP0 early promoter. Pioneer transcription factors bind silent viral heterochromatin, remodel chromatin, and activate gene expression. Thus, wepredict that these novel transcription factors mediate early stages of BoHV-1 reactivation from latency.

Progranulin derivative attenuates lung neutrophilic infiltration from diesel exhaust particle exposure.

Air pollutants, such as diesel exhaust particles (DEPs), induce respiratory disease exacerbation with neutrophilic infiltration. Progranulin (PGRN), an epithelial cell and macrophage-derived secretory protein, is associated with neutrophilic inflammation. PGRN is digested into various derivatives at inflammatory sites and is involved in several inflammatory processes. PGRN and its derivatives likely regulate responses to DEP exposure in allergic airway inflammation. To investigate the role of PGRN and its derivatives in the regulation of responses to DEP exposure in allergic airway inflammation. A murine model of allergic airway inflammation was generated in PGRN-deficient mice, and they were simultaneously exposed to DEP followed by intranasal administration of full-length recombinant PGRN (PGRN-FL) and a PGRN-derived fragment (FBAC). Inflammatory status was evaluated by bronchoalveolar lavage fluid and histopathologic analyses. Human bronchial epithelial cells were stimulated with DEPs and house dust mites (HDMs), and the effect of FBAC treatment was evaluated by assessing various intracellular signaling molecules, autophagy markers, inflammatory cytokines, and intracellular oxidative stress. DEP exposure exaggerated neutrophilic inflammation, enhanced IL-6 and CXCL15 secretions, and increased oxidative stress in the murine model; this effect was greater in PGRN-deficient mice than in wild-type mice. The DEP-exposed mice with PGRN-FL treatment revealed no change in neutrophil infiltration and higher oxidative stress status in the lungs. On the contrary, FBAC administration inhibited neutrophilic infiltration and reduced oxidative stress. In human bronchial epithelial cells, DEP and HDM exposure increased intracellular oxidative stress and IL-6 and IL-8 secretion. Decreased nuclear factor erythroid 2-related factor 2 (Nrf2) expression and increased phosphor-p62 and LC3B expression were also observed. FBAC treatment attenuated oxidative stress from DEP and HDM exposure. FBAC reduced neutrophilic inflammation exaggerated by DEP exposure in a mouse model of allergic airway inflammation by reducing oxidative stress. PGRN and PGRN-derived proteins may be novel therapeutic agents in attenuating asthma exacerbation induced by air pollutant exposure.

Genetic evidence of bidirectional mendelian randomization study on the causality between gut microbiome and respiratory diseases contributes to gut-lung axis

Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10−4, OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10−3, OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10−4, OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome’s roles in respiratory diseases’ clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.

Testing the psychometric characteristics of EQ-5D-5L and respiratory bolt-ons using a sample of the Australian population.

The EQ-5D has been used to assess health related quality of life (HRQoL) in respiratory conditions. However, the core descriptive system may not be sensitive to all the HRQoL impacts of these conditions. To increase the sensitivity of the descriptive system, two respiratory specific bolt-ons, have been developed. Psychometric assessment of the bolt-ons in comparison to other validated instruments is required to facilitate their use. Therefore, the aim of this study is to test the psychometric characteristics of the EQ-5D-5L + R using a large dataset collected in Australia. A cross-sectional online survey was used to recruit adult respondents (≥ 18 years) representative of the Australian population. Descriptive and psychometric analyses were used to understand the performance of the EQ-5D-5L and bolt-ons in comparison to other validated instruments. The construct validity was estimated using correlations. Known-group validity was tested to determine the sensitivity of the instruments to differences across different severity groups. Overall 10,033 respondents (52% female) completed the survey, of which 300 had a respiratory condition. There were moderate to high correlation between bolt-ons with EQ-5D-5L and WHODAS. The EQ-5D-5L + bolt-ons slightly reduced the ceiling effect in comparison to the EQ-5D-5L. The effect size was larger for people with respiratory conditions than people who did not have a respiratory condition. The results show that adding the respiratory bolt-on to the EQ-5D-5L might slightly improve the instruments descriptive sensitivity. The choice of bolt-on may be driven by whether overall problems or limitations are being measured.

A case of squamous cell carcinoma of the lung misdiagnosed as tuberculosis. Is HPV infected by oral sex the causative agent?

BackgroundThe integration of high-risk human papilloma virus (HPV) DNA into the human genome has been implicated in cervical carcinogenesis and head and neck squamous cell cancer. However, its role in lung squamous cell carcinoma is not well understood. In addition, tuberculosis (TB) and lung cancer(LC) share similar clinical symptoms and imaging features, increasing the risk of misdiagnosis.Case PresentationThe patient presented with a 16-month history of hemoptysis, chest pain, and occasional fatigue, without fever, chills, or history of mechanical damage or autoimmune diseases. Examination revealed normal vital signs and laboratory parameters, except for a positive interferon-gamma release assay indicating tuberculosis infection. Bronchoscopic examinations identified congestion and edema of the tracheal wall, along with a tiny lesion in the right wall of the trachea. She had been misdiagnosed with tuberculosis. However, the diagnosis of squamous cell carcinoma was eventually confirmed by endoscopic biopsy. The patient’s macrogenomic second-generation sequencing (mNGS) of the bronchoscopic biopsy specimen was positive for HPV-16.The patient’s sex partner tested positive for HPV-16 in penile scrapings, indicating HPV transmission through oral sex.ConclusionsThis case highlights the potential for HPV infection acquired through oral sex to lead to lung squamous cell carcinoma. It emphasizes the importance of considering HPV-associated malignancies in patients with respiratory symptoms who engage in oral sexual behaviors.

Impenetrable Abdomen: A Case Report of Endoscopic Sleeve Gastroplasty Performed in Patient with Huge Paramedian Laparocele.

Bariatric surgical techniques have demonstrated scientific efficacy and interventional safety; however, these approaches are not universally appropriate for all patients. The term "impenetrable abdomen" refers to the inability to achieve surgical access to the abdominal cavity, a condition that may arise from several underlying factors. Endoscopic sleeve gastroplasty (ESG) is proposed as a safe and effective technique in this subgroup of patients with obesity. A 56-year-old Caucasian woman with an impenetrable abdomen due to the presence of a large left paramedian laparocele underwent ESG (Fig. 1) to our unit. An abdominal computed tomography (CT) scan revealed a substantial laparocele in the left paramedian region, involving the tenuous loops, mesentery, and part of the transverse colon. The patient body mass index (BMI) at presentation was 47.15 kg/m2 (116 kg per 1.57 m). Comorbidities included obstructive sleep apnea syndrome (OSAS), requiring nocturnal continuous positive airway pressure (CPAP) therapy, hepatic steatosis, hypertension, hypertriglyceridemia, and hypovitaminosis D. The case was discussed with our multidisciplinary board team (MDT), who agreed to proceed with the ESG. The endoscopic procedure was performed in the supine position, using the Overstitch device and lasted 58 min. No intraprocedural or post-procedural complications/adverse events have been observed. The patient resumed a liquid diet on the first postoperative day and was discharged from the hospital 24 h after the procedure in good clinical condition. Regular outpatient follow-up visits showed significant reduction of the BMI at 6 months post-procedure with a value of 34.9 kg/m2 compared with the initial value of 47.1 kg/m2. Additionally, the patient's use of nocturnal CPAP for OSAS was successfully discontinued suggesting an improvement in her respiratory condition as a result of weight loss. Moreover, there was a notable reduction in the pharmacological management required for arterial hypertension. These outcomes underscore the positive impact of selecting the most appropriate therapeutic strategy for each patient with obesity through a multidisciplinary team approach. In our experience, we confirm that endoscopic sleeve gastroplasty is both feasible and safe in patients presenting with an impenetrable abdomen. Despite the minimally invasive approach, this technique has proven effective in terms of body weight loss and reduction of obesity related compared with bariatric surgery.

Rural–Urban Divide of COVID-19 Fatalities in India—Investigating the Role of Lifestyle Disorder Diseases

AbstractUsing data on weekly COVID-19 infections and fatalities at the district level for 19 states and 4 union territories of India, we investigate the determinants of COVID-19 deaths focusing exclusively on the second wave of infections. We include several macroeconomic and structural indicators for districts namely, per capita district domestic product, the degree of urbanization, population density, percentage of aged population, share of agriculture, poverty, among several others. Our findings suggest that fatalities have a clear rural–urban divide. Rural agricultural districts with more poor people have experienced less cases and fatalities. Fatalities are more clustered in prosperous and dense industrial districts. Regions having higher COVID-19 fatalities also have a higher proportion of ageing population with urban life-style disorder related diseases such as obesity, diabetes, and hypertension. Prevalence of respiratory illnesses further aggravates the effects of some of these life-style disorder diseases on COVID-19 fatalities.

The Relationship Between Asthma and Food Allergies in Children

Asthma and food allergy are two complex allergic diseases with an increasing prevalence in childhood. They share risk factors, including atopic family history, atopic dermatitis, allergen sensitization, and T2 inflammatory pathways. Several studies have shown that in children with a food allergy, the risk of developing asthma, particularly in early childhood, is high. Food allergen intake or the inhalation of aerosolized allergens can induce respiratory symptoms such as bronchospasm. Patients with both conditions have an increased risk of severe asthma exacerbations, hospitalization, and mortality. The current management of clinical food hypersensitivity primarily involves the dietary avoidance of food allergens and the use of self-injectable adrenaline for severe reactions. Poorly controlled asthma limits the prescription of oral immunotherapy to foods, which has emerged as an alternative therapy for managing food allergies. Biological therapies that are effective in severe asthma have been explored for treating food allergies. Omalizumab improves asthma control and, either alone or in combination with oral immunotherapy, increases the threshold of allergen tolerance. Understanding the interplay between asthma and food allergy is crucial for developing successful treatment approaches and ameliorating patient results.

Efficacy of Streptococcus salivarius Blis K12 in the Prevention of Upper Respiratory Tract Infections in Physically Active Individuals: A Randomized Controlled Trial

This study investigates the efficacy of Streptococcus salivarius K12 in preventing upper respiratory tract infections (URTIs) in healthy adults. URTIs are a common issue, particularly in physically active individuals, leading to significant disruptions in daily life. Probiotics, such as S. salivarius K12, have emerged as a potential preventive strategy for these infections. This research was conducted as a randomized, double-blind, placebo-controlled trial involving 112 participants aged between 19 and 25. Participants were randomly divided into two groups: one group received a daily dose of S. salivarius K12, marketed as Bactoblis®, while the other received a placebo. The trial lasted for four months, during which adherence to the treatment protocol was closely monitored. The primary goal was to measure the incidence of URTIs using the Jackson Scale and the Wisconsin Upper Respiratory Symptom Survey (WURSS-11). The results indicated that higher adherence to the S. salivarius K12 treatment was associated with an increased number of days without URTI symptoms. Although the overall severity of symptoms did not differ significantly between the treatment and control groups, those with high adherence to S. salivarius K12 (greater than 90%) reported more days free from illness. In conclusion, S. salivarius K12 demonstrated potential as a preventive measure against URTIs, especially in individuals who adhered strictly to the treatment regimen. However, further research involving larger populations and longer follow-up periods is needed to fully confirm these findings and better understand the role of S. salivarius K12 in preventing respiratory infections.

Psychiatric Disorders in Patients with Chronic Obstructive Pulmonary Disease: Clinical Significance and Treatment Strategies

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.

Real-World and Patient-Reported Outcomes of Dupilumab and Other Biological Drugs for Chronic Obstructive Pulmonary Disease—A Systematic Review

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three “real-world” case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients’ self-perceived drug effects, and none evaluated patients’ perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients’ experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials.

The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin

The TMEM16A chloride channel is proposed as a therapeutic target in cystic fibrosis, where activation of this ion channel might restore airway surface hydration and mitigate respiratory symptoms. While TMEM16A is associated with increased mucin production under stimulated or pro-inflammatory conditions, its role in baseline mucin production, secretion and/or maturation is less well understood. Here, we use the Xenopus tadpole skin mucociliary surface as a model of human upper airway epithelium to study Tmem16a function in mucus production. We found that Xenopus tropicalis Tmem16a is present at the apical membrane surface of tadpole skin small secretory cells that express canonical markers of mammalian “goblet cells” such as Foxa1 and spdef. X. tropicalis Tmem16a functions as a voltage-gated, calcium-activated chloride channel when transfected into mammalian cells in culture. Depletion of Tmem16a from the tadpole skin results in dysregulated mucin maturation post-secretion, with secreted mucins having a disrupted molecular size distribution and altered morphology assessed by sucrose gradient centrifugation and electron microscopy, respectively. Our results show that in the Xenopus tadpole skin, Tmem16a is necessary for normal mucus barrier formation and demonstrate the utility of this model system to discover new biology relevant to human mucosal biology in health and disease.

Therapeutic efficacy and pharmacological mechanism of Bailing capsule on chronic obstructive pulmonary disease: a meta-analysis and network pharmacology

Context Bailing capsule, derived from Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae), has shown potential in the treatment of chronic obstructive pulmonary disease (COPD), a prevalent respiratory disorder. Objective This study elucidates the efficacy and mechanism of action of the use of Bailing capsules in the treatment of COPD using meta-analysis and network pharmacology. Materials and methods A meta-analysis of randomized controlled trials (RCTs) was performed. The treatment group received Bailing capsules alongside standard therapy, while the control group received standard therapy or in combination with other traditional Chinese medicines. Efficacy outcomes included lung function, exercise tolerance, acute exacerbation risk, and quality of life. Network pharmacology and molecular docking identified key targets of Bailing capsules. Results The meta-analysis of 27 RCTs showed significant improvements in the treatment group for forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, and the 6-min walk test (6MWT). Additionally, there was a marked reduction in acute COPD attacks and an improvement in quality of life. Meanwhile, network pharmacological analysis identified SRC, HIF1A, NFKB1, HDAC2, and PRKACA, as the potential core targets for Bailing capsules in the treatment of COPD. Discussion and conclusion Bailing capsules have shown promising results in the treatment of stable COPD. Future studies should focus on large-scale, multicenter RCTs to confirm the long-term benefits and safety of Bailing capsules.

Increased Lipocalin 2 detected by RNA sequencing regulates apoptosis and ferroptosis in COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a complex respiratory condition influenced by environmental and genetic factors. Using next-generation sequencing, we aimed to identify dysregulated genes and potential therapeutic targets for COPD.MethodsPeripheral blood leukocyte RNA profiles from COPD patients and healthy controls were analyzed using next-generation sequencing. Key genes involved in COPD pathogenesis were identified through protein–protein interaction network analysis. In vitro, bronchial epithelial cells treated with cigarette smoke extract (CSE) were used to study the effects on gene expression, cell viability, apoptosis, and ferroptosis. Additionally, Lipocalin 2 (LCN2) inhibition experiments were conducted to elucidate its role in COPD-related cellular processes.ResultsAnalysis of RNA profiles revealed consistent downregulation of 17 genes and upregulation of 21 genes across all COPD groups. Among these, Cathelicidin Antimicrobial Peptide(CAMP), Defensin Alpha 4(DEFA4), Neutrophil Elastase(ELANE), LCN2 and Lactotransferrin(LTF) were identified as potentially important players in COPD pathogenesis. Particularly, LCN2 exhibited a close association with COPD and was found to be involved in cellular processes. In vitro experiments demonstrated that CSE treatment significantly increased LCN2 expression in bronchial epithelial cells in a concentration-dependent manner. Moreover, CSE-induced apoptosis and ferroptosis were observed, along with alterations in cell viability, Glutathione content, Fe2 + accumulation, ROS: Reactive Oxygen Species and Malondialdehyde levels, Lactate Dehydrogenase(LDH) release and Glutathione Peroxidase 4(GPX4) expression. Inhibition of LCN2 expression partially reversed these effects, indicating the pivotal role of LCN2 in COPD-related cellular processes.ConclusionOur study identified six candidate genes: CAMP, DEFA4, ELANE, LCN2, and LTF were upregulated, HSPA1B was downregulated. Notably, LCN2 emerges as a significant biomarker in COPD pathogenesis, exerting its effects by promoting apoptosis and ferroptosis in bronchial epithelial cells.

A multivalent RSV vaccine based on the modified vaccinia Ankara vector shows moderate protection against disease caused by RSV in older adults in a phase 3 clinical study

Respiratory syncytial virus (RSV) causes a significant disease burden in older adults. The live recombinant vaccine based on a nonreplicating modified vaccinia Ankara (MVA-BN) poxvirus, MVA-BN-RSV, encoding for multiple proteins of RSV subtypes A and B, was assessed for efficacy against respiratory disease caused by RSV.Adults aged ≥60 years, with or without underlying chronic conditions, were enrolled and randomized in a 1:1 ratio to receive a single dose of vaccine or placebo and were followed for disease caused by RSV infection during the 2022–2023 season. The 2 primary endpoints were RSV-associated lower respiratory tract disease (LRTD) with ≥3 and ≥ 2 symptoms; acute respiratory disease (ARD) was a key secondary endpoint. The humoral RSV-specific immune response was assessed at baseline and 14 days post-vaccination. Safety was evaluated by collection of solicited adverse events (AEs) and unsolicited AEs for 7 and 28 days post-vaccination respectively, and SAEs for the entire study period.In total, 18,348 participants were included in the final efficacy and safety analyses. Vaccine efficacy was 42.9 % (95 % CI: −16.1; 71.9) against RSV-associated LRTD with ≥3 symptoms, 59.0 % (95 % CI: 34.7; 74.3) against LRTD with ≥2 symptoms, and 48.8 % (95 % CI: 25.8; 64.7) against ARD. The primary objective was not met for LRTD with ≥3 symptoms since the lower bound of the 95 % CI was below 20 %, the prespecified success criterion. The vaccine-elicited immune response showed mean fold-increases of 1.7 for RSV A and B neutralizing antibodies and 2.9 and 4.3 for RSV-specific IgG and IgA, respectively. The vaccine displayed mild to moderate reactogenicity, and no safety concerns were identified.MVA-BN-RSV induced suboptimal protection against RSV-associated LRTD, likely due to suboptimal neutralizing antibody response. The vaccine had an acceptable safety profile and confirmed immunogenicity, overall showing promise for MVA-BN-vectored constructs targeting other diseases.Trial Registration:Clinicaltrials.gov Identifier NCT05238025 (Registered February 14, 2022).

Age Differences and Prevalence of Comorbidities for Death and Survival in Patients with COVID-19: A Single-Center Observational Study in a Region of Southern Italy

The SARS-CoV-2 outbreak has resulted in a considerable number of deaths worldwide. The virus damages the pulmonary artery endothelium, leading to a condition known as microvascular pulmonary inflammatory thrombotic syndrome (MPITS), which can be fatal and cause multiple organ failure. The presence of preexisting comorbidities has been shown to significantly impact the severity and prognosis of patients with SARS-CoV-2 infection. The objective of this study was to compare the age groups of patients with coronavirus disease 2019 (COVID-19) and to identify the prevalence of comorbidities associated with death and survival in an area of southern Italy. The data set consisted of 1985 patients with confirmed cases of SARS-CoV-2 infection who were admitted to the A.O.U. San Giovanni di Dio e Ruggi d’Aragona Hospital in Salerno between January 2021 and December 2022. The results were presented for the overall population and stratified by outcome and age group. All analyses were performed using the XLSTAT (Lumivero, 2024, Paris, France) and STATA software (release 16.1, StataCorp LLG, College Station, TX, USA, 2019) packages. In the study, population, 636 cases (32%) resulted in death, with a higher prevalence in the 60–79 age group, followed by the ≥80 and 30–59 age groups. The most prevalent diseases among deceased and surviving patients with confirmed cases of SARS-CoV-2 infection were those affecting the circulatory system (61.5% vs. 55.5%), the respiratory system (55.8% vs. 26.2%), and the metabolic system (25.9% vs. 25.4%). In patients aged 30–79, respiratory diseases were the primary cause of mortality, whereas in those aged ≥80, circulatory system diseases were more prevalent. Among survivors, cardiovascular diseases were the most common comorbidities across all age groups, followed by respiratory diseases and endocrine, metabolic, and immune disorders. Moreover, these comorbidities were associated with an elevated risk of mortality. The study emphasizes the substantial influence of age and comorbidities on the mortality associated with SARS-CoC-2 infection. These findings highlight the necessity for targeted interventions to manage comorbid conditions in patients with SARS-CoV-2 infection, particularly in older adults.

Updated insights into adverse events associated with mepolizumab: a disproportionality analysis from the FDA adverse event reporting system database

BackgroundMepolizumab, a monoclonal antibody targeting interleukin-5, is used to treat severe eosinophilic asthma and other eosinophilia-related conditions. Given its growing use, there is a pressing need for the latest data to improve the understanding and management of its adverse events (AEs). This study aimed to investigate the safety of mepolizumab by analyzing the pharmacovigilance database of the US Food and Drug Administration.MethodsThe AE signals associated with mepolizumab from 2015 to 2024 were analyzed and the correlations using reporting ratios (RORs) quantified. Subgroup analyses were conducted to understand AEs in individuals ≤ 18 years of age. We also used time-to-onset (TTO) analysis to examine AE occurrence patterns.ResultsIn total, 82,478 AE reports linked to mepolizumab therapy were included. Our analysis, involving 24,156 patients, revealed a predominance of female patients, with the highest incidence of AEs occurring in those aged 18–65 years. Disproportionality analyses revealed significant signals across various system organ classifications (SOCs), most prominently respiratory, thoracic, and mediastinal disorders (ROR = 5.12, 95% confidence intervals [CI] 5.03–5.21), infections and infestations (ROR = 1.86, 95% CI 1.81–1.90), and immune system disorders (ROR = 1.14, 95% CI 1.08–1.21). The highest ROR was found for asthma crisis (ROR = 104.90, 95% CI 95.31–115.44) at the preferred term (PT) level, and the other notables were coronavirus infection (ROR = 7.33, 95% CI 6.05–8.88) and coronavirus disease 2019 (COVID-19) (ROR = 1.34, 95% CI 1.23–1.47). A subgroup analysis of patients ≤ 18 years old identified four significant SOC signals, with the highest ROR in respiratory, thoracic, and mediastinal disorders (ROR = 5.28, 95% CI 4.17–6.68). PT analysis revealed significant AEs, such as wheezing, bronchospasm, and chest discomfort. TTO analysis revealed that 18.5% of AEs occurred within the first 30 days of treatment. The Weibull shape parameter indicated an “early failure-type” pattern for mepolizumab-associated AEs, underscoring the need for vigilant monitoring during the initial stages of therapy.ConclusionOur study highlights the importance of post-market surveillance for monitoring the safety of mepolizumab, which revealed significant AE signals, particularly for respiratory diseases, infections, and immune system complications. The association with opportunistic infections, including COVID-19, highlights the need for vigilant surveillance and further research.

The role of gender factors influencing multiple dimensions of somatic symptoms in major depressive disorder patients with suicidal ideation: insights from the Chinese NSSD study

BackgroundThe study aimed to explore the influence of gender on the prevalence of various somatic symptoms and their associations with suicidal ideation (SI) among patients with major depressive disorder (MDD).MethodsWe recruited 3,275 patients with MDD from the National Survey on Symptomatology of Depression (NSSD), among whom 1,745 patients had SI. The clinical characteristics and the prevalence of somatic symptoms across 20 dimensions in MDD patients with SI were compared between male and female patients. Spearman correlation analysis and logistic regression analysis were used to explore the relationship between somatic symptoms and SI.ResultsIn patients with SI, 32.2% of female participants attributed the onset of MDD to physical concerns, whereas 27% of male patients held a similar perspective (P = 0.032). Female patients exhibited a higher prevalence of early insomnia (64.6% vs. 70.2%) and a lower prevalence of hypersomnia (17.2% vs. 12.9%) and urinary system symptoms (25.0% vs. 17.8%). Logistic regression analysis indicated that female patients displayed a broader range of somatic symptoms identified as risk factors for SI, including increased appetite, respiratory symptoms, circulatory system symptoms, limb pain, and various others.ConclusionThis study unveils gender-specific patterns in somatic symptoms among MDD patients with SI, highlighting the clinical significance of these symptoms in diagnosis and intervention. Understanding how physical concerns contribute to MDD, especially among females, underscores the need for tailored clinical approaches. Recognizing and addressing these symptoms could guide more effective suicide prevention strategies and enhance MDD management in clinical practice.

A smartphone app for preschool wheezing and reliability of medical history collection

BackgroundThe use of mobile applications helps improving self-management in adolescents with asthma. However, no evidence is available for children with preschool wheezing. In addition, we have no data on the reliability of medical history collected at visits. The first aim was to assess the feasibility of a smartphone app in the management of preschool wheezing; secondly we aimed to evaluate the reliability of anamnestic data collected during face-to-face medical interviews.MethodsChildren with recurrent wheezing, age between 25 and 72 months, were randomly assigned to the intervention group, provided with a smartphone app for symptoms monitoring and asthma attack treatment, or to the control group, with a written action plan. At follow-up medical history was collected and the asthma control test and a clinical questionnaire were completed. App acceptability was also explored. Respiratory symptoms, medication and utilization of healthcare resources were collected. Plus, medical information obtained from the paper questionnaires was compared with data daily recorded by the app.ResultsWe enrolled 85 preschool children with recurrent wheezing: 43 assigned to the intervention and 42 to the control group. The average (SD) adherence to e-Diary compilation was 60 (15)%. The acceptance and usability of the intervention was favorable as 70% and 93% of participants in the intervention arm described the app as ‘’simple and intuitive’’ at Visit1 (after 3 months from enrollement) and Visit2 (3 months later than Visit1), respectively and 95% and 98% found it useful in symptoms management. There were no significant differences between the two groups in clinical outcomes. At Visit1, the cACT median score (IQR) was 23,5 (21–25) for the control group (42 patients) and 23 (21–24) for the intervention group (43 patients). At Visit2 (41 controls and 42 in the intervention group) it was 25 (24–25) and 24 (24–25), respectively. Secondary analysis of data from the intervention group showed higher incidence of daily symptoms recorded by the app in comparison with the paper questionnaire, suggesting that collection of retrospective medical history may not be completely reliable.ConclusionsThe smartphone app is usable and acceptable by families of preschool wheezers. Future controlled trial are needed to prove an impact on clinical outcomes or its efficacy in a telemedicine program. Finally a daily questionnaire could provide physicians with a more reliable clinical picture as reflected better daily asthma symptoms than the written retrospective questionnaire filled at clinical visit.