Lower Respiratory Infections Research Articles

Respiratory syncytial virus vaccination in older adults and patients with chronic disorders: A position paper from the Portuguese Society of Pulmonology, the Portuguese Association of General and Family Medicine, the Portuguese Society of Cardiology, the Portuguese Society of Infectious Diseases and Clinical Microbiology, the Portuguese Society of Endocrinology, Diabetes and Metabolism, and the Portuguese Society of Internal Medicine.

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection, hospitalisation and death in adults. Based on evidence regarding the impact of RSV on adult populations at risk for severe infection and the efficacy and safety of RSV vaccines, the Portuguese Society of Pulmonology, the Portuguese Association of General and Family Medicine, the Portuguese Society of Cardiology, the Portuguese Society of Infectious Diseases and Clinical Microbiology, the Portuguese Society of Endocrinology, Diabetes and Metabolism, and the Portuguese Society of Internal Medicine endorses this position paper with recommendations to prevent RSV-associated disease and its complications in adults through vaccination. The RSV vaccine is recommended for people aged ≥50 years with risk factors (chronic obstructive pulmonary disease, asthma, heart failure, coronary artery disease, diabetes, chronic kidney disease, chronic liver disease, immunocompromise, frailty, dementia, and residence in a nursing home) and all persons aged ≥60 years. If it cannot be made available to this population, then the vaccine should be prioritised for individuals aged ≥75 years and those aged ≥50 years with risk factors. The vaccine should preferably be given between September and November and can be co-administered with the influenza vaccine. Ongoing studies on RSV vaccines may justify extending these recommendations in the future.

Factors Associated with Mortality in Nosocomial Lower Respiratory Tract Infections: An ENIRRI Analysis

Background: Nosocomial lower respiratory tract infections (nLRTIs) are associated with unfavorable clinical outcomes and significant healthcare costs. nLRTIs include hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and other ICU-acquired pneumonia phenotypes. While risk factors for mortality in these infections are critical to guide preventive strategies, it remains unclear whether they vary based on their requirement of invasive mechanical ventilation (IMV) at any point during the hospitalization. Objectives: This study aims to identify risk factors associated with short- and long-term mortality in patients with nLRTIs, considering differences between those requiring IMV and those who do not. Methods: This multinational prospective cohort study included ICU-admitted patients diagnosed with nLRTI from 28 hospitals across 13 countries in Europe and South America between May 2016 and August 2019. Patients were selected based on predefined inclusion and exclusion criteria, and clinical data were collected from medical records. A random forest classifier determined the most optimal clustering strategy when comparing pneumonia site acquisition [ward or intensive care unit (ICU)] versus intensive mechanical ventilation (IMV) necessity at any point during hospitalization to enhance the accuracy and generalizability of the regression models. Results: A total of 1060 patients were included. The random forest classifier identified that the most efficient clustering strategy was based on ventilation necessity. In total, 76.4% of patients [810/1060] received IMV at some point during the hospitalization. Diabetes mellitus was identified to be associated with 28-day mortality in the non-IMV group (OR [IQR]: 2.96 [1.28–6.80], p = 0.01). The 90-day mortality-associated factor was MDRP infection (1.98 [1.13–3.44], p = 0.01). For ventilated patients, chronic liver disease was associated with 28-day mortality (2.38 [1.06–5.31] p = 0.03), with no variable showing statistical and clinical significance at 90 days. Conclusions: The risk factors associated with 28-day mortality differ from those linked to 90-day mortality. Additionally, these factors vary between patients receiving invasive mechanical ventilation and those in the non-invasive ventilation group. This underscores the necessity of tailoring therapeutic objectives and preventive strategies with a personalized approach.

How likely is it that a virus or bacteria is causing a patient’s symptoms? A new approach to interpret the outcome from multi-pathogen PCR

Background Whether a detected virus or bacteria is a pathogen that may require treatment, or is merely a commensal ‘passenger’, remains confusing for many infections. This confusion is likely to increase with the wider use of multi-pathogen PCR. Objectives To propose a new statistical procedure to analyse and present data from case-control studies clarifying the probability of causality. Methods We conducted a case-control study in US outpatient settings that enrolled patients aged 18 to 75 years with acute lower respiratory tract infection and controls without respiratory symptoms. Patients underwent multi-pathogen PCR testing. The positive etiologic predictive value was calculated to estimate the probability that each potential pathogen was the cause of symptoms. The outcome was illustrated using a modified forest plot and by classifying pathogens into five categories clarifying the probability for causality. Results We enrolled 618 adult cases and 497 asymptomatic controls. The modified forest plot and the classification of risk for causality aimed to facilitate understanding. Pathogens likely to be causative when present included influenza A and B, SARS-CoV-2, rhinovirus, and parainfluenza viruses, while Staphylococcus aureus is almost always commensal. Broad confidence intervals for the positive etiologic predictive value made it difficult to draw conclusions for potential pathogens with low prevalence. Conclusion This pilot study shows that the proposed statistical approach is likely to be practical for analysing larger case-control studies or for a meta-analysis of multiple studies. This method may help when interpreting the results from multi-pathogen PCR.

Impact of COVID-19 pandemic restrictions and relaxation on pediatric respiratory virus hospitalizations in Southwest China: a retrospective study

BackgroundResearch from multiple regions indicates that Coronavirus disease of 2019 (COVID-19) pandemic has altered the epidemiological characteristics of respiratory viruses.MethodsThis single-center retrospective study included children hospitalized for lower respiratory tract infections (LRTIs) from 2017 to mid-2024. Data on respiratory syncytial virus (RSV), adenovirus (ADV), influenza A virus (IAV), influenza B virus (IBV), and parainfluenza virus (PIV)—were collected and analyzed across pre-pandemic, pandemic, and post-pandemic periods.ResultsA total of 59173 children were included. Detection rates were 34.97% (8553/24459) pre-pandemic, 21.93% (4621/21067) during the pandemic, and 21.64% (2953/13647) post-pandemic. Mixed infections rates significantly decreased during the pandemic (0.78%) and post-pandemic (0.78%) compared to pre-pandemic levels (1.63%) (P < 0.001). RSV was the most prevalent virus across all periods (P < 0.001). Following non-pharmaceutical interventions (NPIs) in 2020, detection rates declined significantly. After restrictions eased in 2021, RSV, PIV, and IBV surged, while IAV continued to decline until its resurgence in spring 2023 (P < 0.001). Certain viruses showed altered seasonal patterns: during the spring and summer of 2021, RSV detection rates exceeded those of previous years, while the expected winter 2022 peak was delayed by approximately six months. IAV peaks disappeared during winters of 2020 and 2021, peaking in spring 2023. IBV peaked in autumn 2021 and winter 2023. PIV had an unusual rise in summer 2020, peaking in autumn, delayed by about five months. The peak in the first half of 2024 returned to its normal timing. ADV appeared to be unaffected, with increased detection in 2022, and decreased in 2023 and 2024.ConclusionEpidemiological patterns of respiratory viruses have been altered by multiple influencing factors. The significance of vaccination, hygiene practices, public health interventions and etc. was emphasized in addressing pandemics. Additionally, ongoing dynamic monitoring is essential due to the evolving epidemiology.

Association of Influenza Vaccination During Pregnancy with Health Outcomes in Mothers and Children: A Population-Based Cohort Study.

Immunization rates of maternal influenza vaccination during pregnancy remain suboptimal, with concerns about potential harm to the mothers and their offspring. We conducted a population-based cohort study, using mother-child linked database in Korea: (a) maternal cohort between December 2019, and March 2022; (b) neonatal cohort between September 2020, and June 2021. Exposure was defined as influenza vaccination during pregnancy. Study outcomes included gestational outcomes, vaccine-related adverse events, and other health outcomes in mothers and childbirth and immune-related health outcomes in children. After 1-to-1 propensity score matching using diverse potential confounders, effect estimates with 95% confidence intervals were estimated using the log-binomial model for cumulative outcomes and the Cox proportional model for time-to-event outcomes. After 1-to-1 propensity score matching, we identified 174,008 and 53,344 pairs for the maternal and neonatal cohorts, respectively. In the maternal cohort, influenza vaccination during pregnancy was not associated with preeclampsia, antenatal bleeding, and various adverse outcomes, including neurological, vascular, blood, and lymphatic system disorders, except for marginally elevated risks of gestational diabetes mellitus (effect estimate 1.06, 95% confidence interval 1.05 to 1.08) and postpartum hemorrhage (1.05, 1.01 to 1.08). In the neonatal cohort, maternal influenza vaccination did not increase risks of childbirth (e.g., preterm/low birth weight, congenital malformations, mortality) and immune-related outcomes, except for a slightly increased risk of lower respiratory tract infection (1.06, 1.007 to 1.12). In this population-based cohort study, influenza vaccination during pregnancy was not associated with an increased risk of a range of adverse outcomes in mothers and their offspring.

Hypervirulent Klebsiella pneumoniae have better clinical outcomes than classical Klebsiella pneumoniae for lower respiratory tract infection patients

BackgroundThe clinical outcomes and microbiological features of lower respiratory tract infections (LRTIs) caused by hypervirulent Klebsiella pneumoniae (hvKp) and classical Klebsiella pneumoniae (cKp) have not been well understood.MethodsThis study collected 287 non-repetitive Klebsiella pneumoniae isolates from 287 LRTI patients. All these strains underwent annotation for resistance and virulence factors, with 141 strains undergoing mouse infection experiments to assess their virulence. The primary clinical outcomes of these patients were evaluated, including intensive care unit (ICU) admission and in-hospital mortality rates.ResultsA total of 46 capsule serotypes were identified. Among these isolates subjected to mouse infection experiments, the proportions of strains exhibiting hypervirulent phenotypes were 92.6% (25/27), 92.1% (35/38), 80% (4/5), 25% (1/4), 10.5% (2/19), and 7.1% (1/14) for K2, K1, K20, K54, K47, and K25, respectively. Therefore, K1, K2, and K20 K. pneumoniae were defined as hvKp. In addition, the rates of ICU admission and in-hospital mortality for hvKp-infected patients were significantly lower than those of cKp-infected patients (51.4% vs. 65.9%, χ2 = 4.722, p = 0.03 and 8.6% vs. 29%, χ2 = 12.133, p < 0.001). Notably, among the cKp group, the cKp-ST11 subgroup had higher rates of ICU admission (77% vs. 58.5%, χ2 = 7.981, p = 0.005) and in-hospital mortality (44.8% vs. 18.5%, χ2 = 17.585, p < 0.001) than cKp-nonST11 subgroup.ConclusionsThese findings suggest that capsule serotype is a more accurate factor for the prediction of the virulence phenotype, while hvKp have better clinical outcomes than cKp for LRTI patients. Furthermore, the cKp-ST11 subgroup has the worst prognosis than cKp-nonST11 subgroup.

The effect of azithromycin treatment on respiratory morbidity in children with down syndrome

BackgroundChildren with Down syndrome (DS) often experience recurrent and prolonged hospitalizations from respiratory infections. While Azithromycin has been increasingly used for lower-respiratory tract infections (LRTIs) in children, its potential benefits for DS patients are unexplored. This study evaluates the effect of chronic azithromycin treatment on respiratory morbidity in children with DS.MethodsIn this retrospective cohort study, we analyzed data from children with DS aged 0–6 years treated with Azithromycin for at least 6 weeks (10 mg/kg, thrice weekly). Respiratory morbidity indicators, such as primary care visits, medication consumption, emergency department visits, hospitalizations, and hospital length of stay (LOS), were assessed and compared six months before and after the Azithromycin treatment.ResultsTwenty-three episodes of Azithromycin treatment (≥ 6 weeks) in eighteen children with DS (mean age of 2.3 years, 78% males) during 2016–2023 were included. A significant reduction in mean respiratory LOS was observed (13.6 vs. 4.7 days, p = 0.05) when comparing pre to post-Azithromycin treatment. Other secondary respiratory outcomes showed no significant differences.ConclusionThe significant reduction in respiratory LOS suggests the potential benefits of Azithromycin in children with DS, and emphasizes the need for larger clinical trials to determine optimal use and long-term effects in this vulnerable population.

Clinical characteristics of infants with respiratory syncytial virus infection under 3 months of age before, during, and after the SARS-CoV-2 pandemic

Objectives: To assess the changes in epidemiologic and clinical characteristics of respiratory syncytial virus (RSV) infection among inpatient under 3 months of age with lower respiratory tract infection (LRTI) in different stages of the SARS-CoV-2 pandemic. Methods: A retrospective cohort study was conducted. Clinical data on general condition and laboratory tests were collected from 3 144 RSV-positive LRTI infants less than 3 months of age hospitalized at Children's Hospital, Zhejiang University School of Medicine from January 2017 to January 2024. Based on the admission date, all patients were categorized into three groups: pre-SARS-CoV-2 infection, during SARS-CoV-2 infection and after SARS-CoV-2 infection. Clinical data from three groups of patients were compared using ANOVA or chi-square test or Kruskal Wallis text to assess the impact of the SARS-CoV-2 infection on the epidemiological and clinical characteristics of RSV. Results: Among the 3 144 RSV-positive children, there were 1 872 males and 1 272 females, with an age of 42 (24, 61) d. The pre-SARS-CoV-2 infection, during SARS-CoV-2 infection and after SARS-CoV-2 infection in 1 224, 1 173 and 747 cases respectively. There were statistically significant differences in RSV infection in winter, summer and autumn (all P<0.001). Compared with the pre-SARS-CoV-2 pandemic and during the SARS-CoV-2 pandemic, children with RSV infection in the post-SARS-CoV-2 pandemic had higher hospitalization costs (8 831.3 (5 925.0, 12 887.6) vs.7 153.8 (4 918.0, 9 834.2) vs. 7 842.0 (4 920.0, 11 414.2) yuan, H=57.57, P<0.001), lower admission oxygen saturation (0.95 (0.94,0.97) vs. 0.97 (0.95,0.98) vs. 0.97 (0.95,0.98), H=143.96, P<0.001), an increased rate of intravenous glucocorticosteroid application (56.8% (424/747) vs. 35.9% (439/1 224) vs. 29.9% (351/1 173), χ2=144.58, P<0.001), immunoglobulin application (27.7% (207/747) vs. 16.2% (198/1 224) vs. 14.6% (171/1 173), χ2=58.41, P<0.001), respiratory support (45.5% (340/747) vs. 38.9% (476/1 224) vs. 36.7% (431/1 173), χ2=15.03, P=0.001), and intensive care unit admission (3.9% (29/747) vs. 1.3% (16/1 224) vs. 3.0% (35/1 173), χ2=13.86, P=0.001). Conclusions: During the post-SARS-CoV-2 pandemic, there were off-season outbreaks of RSV, with peaks occurring in the summer and fall. RSV-positive infants in the post-SARS-CoV-2 infection period had lower oxygen saturation on admission and higher rates of intravenous glucocorticosteroids, immunoglobulin application, respiratory support, and admission to the intensive care unit.

The role of IFN-γ/CXCL10 axis in Mycoplasma pneumonia infection

Mycoplasma pneumoniae caused lower respiratory tract infection in children and can exacerbate these infections through the production of various inflammatory factors, with chemokines playing a key role. However, the pathogenesis of this infection is complicated and thus has not been thoroughly studied. We clarified that cytokine expression levels were analyzed in both peripheral blood and bronchoalveolar lavage fluid (BALF), and in vitro assays were conducted using THP-1 macrophages. We discovered that, compared to control children, M. pneumoniae pneumonia (MPP) patients expressed significantly higher levels of CXCL10 both in the peripheral blood and BALF. Moreover, numbers of macrophages, predominantly with a M1 phenotype, were significantly increased in BALFs of children of MPP. In vitro, coculture with IFN-γ or activated CD4+ Th1 cells significantly promoted CXCL10 expressions in THP-1 derived macrophages, which was largely reversed by siRNA-mediated down regulation of STAT1. In addition, IFN-γ-stimulated macrophages greatly promoted the trans-migration of Th1 cells. our data show that Th1 cells-derived IFN-γ augments CXCL10 production in macrophages via the JAK-STAT1 pathway, which subsequently recruits more immune cells like Th1 cells into the infection sites, thereby constituting a positive feedback loop and aggravating the type I inflammatory responses in MPP patients.

Exploring the potential mediating role of systemic antibiotics in the association between early-life lower respiratory tract infections and asthma at age 5 in the CHILD study

Exploring the potential mediating role of systemic antibiotics in the association between early-life lower respiratory tract infections and asthma at age 5 in the CHILD study

KRT9 is required for GBP5 suppression of human respiratory syncytial virus.

RSV causes severe acute lower respiratory tract infections, which have posed serious health and safety risks to children and older adults worldwide. Although some RSV interventions are available, the longer-lasting monoclonals, which are expensive, are required to be injected before RSV infection, and their protection is observed only up to one RSV infection season; vaccines are currently only available to the elderly but are not suitable for application in infants and young children. As specific drug treatments are absent, a systematic and in-depth mechanism for research is essential. In our study, KRT9 was identified to play an important role in the GBP5 anti-RSV process for the first time. This investigation improved the interaction mechanism between GBP5 and RSV, provided new evidence for the synergistic effect between keratin transport and innate immunity, and opened a new research direction with GBP5 and the keratin transport system as the main subjects.

Performance of multiplex PCR-based targeted next-generation sequencing in bronchoalveolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients.

Multiplex polymerase chain reaction (PCR)-based targeted next-generation sequencing (tNGS) is a promising tool for distinguishing lower respiratory tract infections (LRTIs) in clinical practice, and its detectable pathogen spectrum can cover more than 95% of clinical cases. but there is limited information on systematic evaluation of the clinical use of multiplex PCR-based tNGS (mp-tNGS) in IPA cases. We aim to assess mp-tNGS in bronchoalveolar lavage fluid (BALF) for Aspergillus detection in suspected IPA patients, and to provide a reliable basis for initiating antifungal therapy without microbiological or histopathological evidence. We prospectively enrolled a cohort of consecutive patients suspected of IPA, all of them had undergone serum/BALF galactomannan antigen (GM), BALF mp-tNGS, and traditional tests (direct smear and culture of respiratory specimens), EORTC/MSGERC and FUDICU criteria were used for IPA diagnosis. Thirty-two patients were diagnosed with IPA and 42 with non-IPA. Compared with the final diagnosis, the sensitivity of BALF mp-tNGS was 87.5%, while the sensitivity of traditional tests, serum GM and BALF GM assay was 43.8%, 21.9%, and 62.5%, respectively; the specificity of BALF mp-tNGS was 90.5%, which was similar to traditional tests. The average turnaround time (TAT) for Aspergillus detection by BALF mp-tNGS was 22.10±2.49h, which was significantly faster than that by traditional tests. BALF mp-tNGS showed good performance in identification of Aspergillus in non-neutropenic IPA patients. Importantly, positive mp-tNGS in BALF can provide a basis for early antifungal therapy before microbiological evidence is available.

Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a novel LPP-delivered mRNA vaccine that expresses the respiratory syncytial virus prefusion protein (RSV pre-F) to evaluate its immunogenicity and protective effect in a mouse model. We synthesized mRNAs with gene modification for RSV pre-F and prepared mRNA vaccines using the LPP delivery platform, referred to as RSV pre-F LPP-mRNA. RSV pre-F protein expression in mRNA vaccines was characterized in vitro. Then, we evaluated the effects of the immune response and protection of this mRNA vaccine in mice up to 24 weeks post-vaccination. Following booster immunization, robust and long-lasting RSV pre-F-specific IgG antibodies were detected in the serum of mice, which exhibited Th1/Th2 balanced IgG response and cross-neutralizing antibodies against different subtypes (RSV A2, B18537, and clinical isolate hRSV/C-Tan/BJ 202301), with a clear dose-response relationship observed. RSV pre-F-specific IgG antibodies were maintained in the mice for an extended period, lasting up to 18 weeks post-immunization. Concurrently, multifunctional RSV F-specific CD8+ T cells (IFN-γ, IL-2, and TNF-α) were detected in the mice. After RSV A2 challenge, the RSV pre-F LPP-mRNA vaccine led to a significant reduction in viral replication, while reduced pathological damage was observed in lung tissue. The LPP-delivered mRNA vaccine expressing RSV pre-F induces a robust and long-lasting immune response and protection, indicating good prospects for further development and application.

Establishment of a 3D-Printed Tissue-on-a-Chip Model for Live Imaging of Bacterial Infections.

Despite advances in healthcare, bacterial pathogens remain a severe global health threat, exacerbated by rising antibiotic resistance. Lower respiratory tract infections, with their high death toll, are of particular concern. Accurately replicating host-pathogen interactions in laboratory models is crucial for understanding these diseases and evaluating new therapies. In this communication, we briefly present existing in vivo models for cystic fibrosis and their limitations in replicating human respiratory infections. We then present a novel, 3D-printed, cytocompatible microfluidic lung-on-a-chip device, designed to simulate the human lung environment, and with possible use in recapitulating general infectious diseases.Our device enables the colonisation of fully differentiated lung epithelia at an air-liquid interface with Pseudomonas aeruginosa, a key pathogen in many severe infections. By incorporating dynamic flow, we replicate the clearance of bacterial toxins and planktonic cells, simulating both acute and chronic infections. This platform supports real-time monitoring of therapeutic interventions, mimics repeated drug administrations as in clinical settings, and facilitates the analysis of colony-forming units and cytokine secretion over time. Our findings indicate that this lung-on-a-chip device has significant potential for advancing infectious disease research, in optimizing treatment strategies against infections and in developing novel treatments.

The effect of a general practitioner's perception of a patient request for antibiotics on antibiotic prescribing for respiratory tract infections: secondary analysis of a point prevalence audit survey in 18 European countries.

Illness severity, comorbidity, fever, age and symptom duration influence antibiotic prescribing for respiratory tract infections (RTI). Non-medical determinants, such as patient expectations, also impact prescribing. To quantify the effect of general practitioners' (GPs') perception of a patient request for antibiotics on antibiotic prescribing for RTI and investigate effect modification by medical determinants and country. Prospective audit in 18 European countries. Consultation data were registered of 4982 patients presenting with acute cough and/or sore throat. A mixed-effect logistic regression model analysed the effect of GPs' perception of a patient request for antibiotics. Two-way interaction terms assessed effect modification. Relevant clinical findings were added to subgroups of lower RTI (LRTI), throat infection, and influenza-like-illness (ILI). GPs who perceived a patient request for antibiotics were four times more likely to prescribe antibiotics (OR: 4.4, 95%CI: 3.4-5.5). This effect varied by country: lower in Spain (OR: 0.06), Ukraine (OR: 0.15), and Greece (OR: 0.22) compared to the lowest prescribing country. The effect was higher for ILI (OR: 13.86, 95%CI: 5.5-35) and throat infection (OR: 5.1, 95%CI: 3.1-8.4) than for LRTI (OR: 2.9, 95%CI: 1.9-4.3). For ILI and LRTI, GPs were more likely to prescribe antibiotics with abnormal lung auscultation and/or increased/purulent sputum and for throat infection, with tonsillar exudate and/or swollen tonsils. GPs' perception of an antibiotic request and specific clinical findings influence antibiotic prescribing. Incorporating exploration of patient expectations, point-of-care testing and discussing watchful waiting into the decision-making process will benefit appropriate prescribing of antibiotics.

Correlation between physical activity and acute respiratory infections in preschool children

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim&amp;lt;/strong&amp;gt; To analyse a correlation between physical activity (PA) and acute respiratory infections (ARIs) in preschool children aged 5 to 7 years.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods&amp;lt;/strong&amp;gt; Data on both ARIs, sedentary behaviour (SB) and PA were obtained through specially created questionnaires for this study and relationships between them were examined.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results&amp;lt;/strong&amp;gt; A total of 129 children with an average age of 72.2&amp;amp;plusmn;4.2 months, with a slightly higher number of males, 65 (50.4%), have participated in the study. Upper respiratory tract infections (URTIs) were in a significantly negative correlation with the frequency of training on weekdays (p=0.041) and weekends (p=0.005). Lower respiratory tract infections (LRTIs) had a significantly positive correlation with the frequency of usage of electronic gaming devices on weekdays (p=0.034), and a significant negative correlation with the frequency of spending time in nature on weekends (p=0.036). ARIs in total were in a significant negative correlation with the frequency of training on weekdays (p=0.025) and weekends (p=0.005).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion&amp;lt;/strong&amp;gt; An increase of SB and reduced PA level showed a negative impact on the ARIs increase. It is recommended to introduce programs to increase PA among young children.&amp;lt;/p&amp;gt;

Comparison of two point-of-care lung ultrasound techniques and their associated outcomes for bronchiolitis in the pediatric emergency department

BackgroundAcute bronchiolitis (AB) is the most common lower respiratory tract infection in infants. Clinician diagnosis and management vary due to limited objective assessment tools. Point-of-care lung ultrasound (LUS) offers a promising diagnostic and prognostic tool in the emergency department (ED), however, the time to perform LUS is of concern in the emergency setting.MethodsInfants ≤ 12 months diagnosed with AB in the emergency department were enrolled. Two LUS techniques were performed sequentially: a 12-segment “lawnmower” approach and a posterior paravertebral “waterfall” technique. LUS were scored (0–36 for lawnmower; 0–6 for waterfall). Respiratory support (RS) was categorized into three levels: no RS (room air), low RS (wall O2 or heated high flow nasal cannula < 1L/kg), and high RS (heated high flow nasal cannula ≥ 1L/kg or positive pressure). Clinical data, including RS at 12 and 24 h, maximum RS, disposition, and length of stay, were extracted via chart review and compared to mean LUS scores for each technique. Calculated areas under the curve (AUC) were compared using the Youden Index (J).Results82 infants were enrolled. The mean waterfall scanning time was 1.65 min (SD 0.55) compared to the lawnmower’s 7.65 min (SD 1.45). The difference between mean LUS scores for the waterfall technique was statistically significant for all disposition comparisons and nearly all RS comparisons. While the lawnmower AUC was greater than the waterfall AUC for all RS and disposition comparisons, the Youden Index (J) was statistically significantly different for only two of the eight comparisons.ConclusionThe posterior-only LUS technique is faster than the lawnmower technique, provides comparable information for disposition, and has a stronger association with LOS, but is less associated with RS. The waterfall technique may be a suitable alternative to more time-intensive, thorough techniques.

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI. We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.S. PICUs from October through December 2022. We assigned CPS-Ped (0=discharged home at respiratory baseline to 8=death) at admission, days 2-7,10, and 14. We identified predictors of clinical improvement (CPS-Ped≤2 or 3-point decrease) by day 7 using multivariable log-binomial regression models and estimated the sample size (80% power) to detect 15% between-group clinical improvement with CPS-Ped versus hospital length of stay (LOS). Of 585 hospitalized infants, 138 (23.6%) received invasive mechanical ventilation (IMV). Of the 49 (8.4%) infants whose CPS-Ped score worsened by 2 points after admission, one died. Failure to clinically improve by day 7 occurred in 205 (35%) infants and was associated with age <3 months, prematurity, underlying respiratory condition, and IMV in the first 24 hours in the multivariable analysis. The estimated sample size per arm required for detecting a 15% clinical improvement in a potential study was 584 using CPS-Ped clinical improvement versus 2,031 for hospital LOS. CPS-Ped can be used to capture a range of disease severity and track clinical improvement in infants who develop RSV-related critical illness and could be useful for evaluating therapeutic interventions for RSV.

Development and evaluation of a recombinant monoclonal human antibody with virus-neutralizing activity against the F glycoprotein of respiratory syncytial virus

Introduction. Respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections in children. RSV also poses a serious threat to the elderly and immunocompromised patients. Developing a therapy based on recombinant human antibodies to block the RSV fusion (F) glycoprotein is urgent to reduce the incidence of RSV infections and prevent associated complications. Aim. To design plasmid vectors for efficient production of the recombinant monoclonal antibody FM1 in a eukaryotic expression system targeting the RSV fusion (F) glycoprotein and to evaluate its activity against RSV subtypes A and B in vitro. Materials and methods. Constructs encoding the recombinant antibody FM1 were designed using genetic engineering. Recombinant antibodies were produced in the CHO-K1 cell line through transient expression. Antibody specimens were purified from the culture supernatant using affinity chromatography, with a modified protein A as the ligand. The virus-neutralizing activity of the antibody was evaluated in a microneutralization assay using several RSV strains on a Vero cell monolayer culture. Results. We developed a two-plasmid vector system to produce the recombinant FM1 antibody targeting the RSV F glycoprotein, using CHO cells as transient producers. The antibody was successfully produced, purified, and characterized, with its biological activity confirmed. The FM1 antibody demonstrated enhanced virus-neutralizing activity against reference and seasonal RSV strains of subtypes A and B compared to the control drug palivizumab. Conclusion. A recombinant FM1 antibody-based drug could address the import substitution challenge for protective measures against RSV infection. The authors are currently developing a stable FM1 producer clone with high productivity and viability and investigating the therapeutic efficacy of this antibody in a sublethal RSV infection mouse model.

The Role of Bronchoalveolar Lavage in Therapeutic Antimicrobial Choices for Hematologic Patients with Pulmonary Infiltrates.

Background and Objectives: Lower respiratory tract infections are particularly frequent in hematological patients; their early diagnosis and the timely start of targeted therapy are essential. Bronchoalveolar lavage (BAL) can provide a microbiological sample from the lower airways in a minimally invasive way. This study aimed to determine the diagnostic yield of BAL in hematological patients for microbiological purposes and its influence on modifying the therapeutic strategy. Material and Methods: This multicenter, retrospective, observational study included data from 193 consecutive patients from two centers from January 2020 to October 2022. The patients underwent a bronchoscopy with BAL in cases of pulmonary infiltrates suspicious of pulmonary infection. The demographic data, presenting symptoms, level of immunosuppression, chest CT changes, BAL sampling results, and antimicrobiological drug administration were analyzed. Results: Of the 193 procedures, 143 (74.1%) were performed on hospitalized patients, while 50 were performed on outpatients. In 53.9% of the cases, the BAL isolated at least one germ; in particular, if the procedure was carried out within 72 h of presenting symptoms, the probability of isolating the germ increased significantly (74.3%, p = 0.04). Among the isolated germs, 59.4% were viruses, 28.6% were bacteria, and 12% were fungi. The patients with higher immunosuppression and the febrile ones underwent BAL earlier than the patients with mild immunosuppression (p = 0.01) and those with other presenting symptoms (p = 0.0001). BAL positivity led to a change in empirical antimicrobial therapy in 79 out of 104 cases (77% vs. 36.3%; p < 0.001); these data were also confirmed among the hospitalized patients (81% vs. 44%; p < 0.001). The isolation of a pathogen through BAL and the degree of patient immunosuppression negatively influenced patient survival (p < 0.05 and p < 0.01, respectively). Conclusions: BAL is confirmed as a valid approach for evaluating pulmonary infiltrates in hematological patients, given the excellent clinical impact and high diagnostic yield, mainly if performed early after symptom presentation. However, ongoing antimicrobial treatments at the time of BAL may have potentially affected the diagnostic yield of the procedure.