Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

Epidemiology of Medically Attended Respiratory Syncytial Virus Lower Respiratory Tract Infection in Japanese Children, 2011-2017.

BACKGROUND: The objective was to report critical respiratory syncytial virus (RSV)-related epidemiological and healthcare resource utilization measures among Japanese children stratified by gestational and chronological age groups. METHODS: The JMDC (formerly the Japan Medical Data Center) was used to retrospectively identify infants with or without RSV infection (beginning between 1 February 2011 and 31 January 2016, with follow-up through 31 December 2017). The incidence of RSV medically attended lower respiratory tract infection (MALRI) was captured by flagging hospitalizations, outpatient, and emergency department/urgent care visits with an RSV diagnosis code during the season. RESULTS: Of 113 529 infants and children identified, 17 022 (15%) had an RSV MALRI (14 590 during the season). The RSV MALRI and hospitalization rates in the first 5 months were 14.3/100 child-years (CY) and 6.0/100 CY, respectively (13.4/100 and 5.8/100 CY for full-term infants and 20/100 and 6.8/100 CY for late preterm infants, respectively). Among those with ≥1 type of MALRI event during the RSV season, >80% of children had it by 24 months of chronological age, although this observation differed by prematurity status. Sixty percent of healthcare resource utilization measures started in the outpatient setting. CONCLUSIONS: This study emphasizes the RSV burden in young children and critically highlights the data needed to make decisions about new preventive strategies.

Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage Fluid on Antimicrobial Stewardship in Patients With Lower Respiratory Tract Infections: A Retrospective Cohort Study.

BACKGROUND: The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown. METHODS: This retrospective cohort study included patients who had LRTIs diagnosed and underwent bronchoalveolar lavage between September 2019 and December 2020. Patients who underwent both mNGS and conventional microbiologic tests were classified as the mNGS group, while those with conventional tests only were included as a control group. A 1:1 propensity score match for baseline variables was conducted, after which changes in antimicrobial stewardship between the 2 groups were assessed. RESULTS: A total of 681 patients who had an initial diagnosis of LRTIs and underwent bronchoalveolar lavage were evaluated; 306 patients were finally included, with 153 in each group. mNGS was associated with lower rates of antibiotic escalation than in the control group (adjusted odds ratio, 0.466 [95% confidence interval, .237-.919]; P = .02), but there was no association with antibiotic de-escalation. Compared with the control group, more patients discontinued the use of antivirals in the mNGS group. CONCLUSIONS: The use of mNGS was associated with lower rates of antibiotic escalation and may facilitate the cessation of antivirals, but not contribute to antibiotic de-escalation in patients with LRTIs.

Analysis of the prevalence and clinical features of respiratory syncytial virus infection in a pediatric hospital in Zhejiang Province from 2019 to 2023.

The aim of this study was to investigate the epidemiological characteristics of respiratory syncytial virus (RSV) infections in children in Zhejiang from 2019 to 2023. Data from pediatric patients who visited the Children's Hospital of Zhejiang University School of Medicine for RSV infection between 2019 and 2023 were analyzed. Nasopharyngeal swabs were collected for RSV antigen detection, and relevant patient information was collected. Factors such as age were analyzed. A total of 673 094 specimens were included from 2019 to 2023, with a rate of positive specimens of 4.74% (31 929/673 094). The highest rate of positive specimens of 10.82%, was recorded in 2021, while the remaining years had a rate of approximately 3%-5%. In terms of seasonal prevalence characteristics, the rate of positive specimens in 2019, 2020, and 2022 peaked in the winter months at approximately 8% and decreased in the summer months, where the rate of positive specimens remained at approximately 0.5%. In contrast, summer is the peak period for RSV incidence in 2021 and 2023, with the rate of positive specimens being as high as 9%-12%. Based on the prevalence characteristics of gender and age, this study found that the detection rate of positive specimens was higher in boys than in girls in 2019-2023. In 2019-2022, among the different age groups, the highest rate of positive specimens was found in children aged 0 to <6 months, and it decreased with age. In 2023, the rate of positive specimens was above 8% in the 0 to <6 months, 6 to <12 months, and 1-2 years age groups, with the highest rate of positive specimens in the 1-2 years age group, and a gradual decrease in the rate of positive specimens with age for children over 3 years of age. Between 2019 and 2023, the epidemiological pattern of RSV changed. A summer peak was observed in 2021 and 2023.

Society for Maternal-Fetal Medicine Statement: Clinical considerations for the prevention of respiratory syncytial virus disease in infants.

Respiratory syncytial virus is a leading cause of lower respiratory tract illness globally in children aged <5 years. Each year, approximately 58,000 hospitalizations in the United States are attributed to respiratory syncytial virus. Infants aged ≤6 months experience the most severe morbidity and mortality. Until recently, prevention with the monoclonal antibody, palivizumab, was only offered to infants with high-risk conditions, and treatment primarily consisted of supportive care. Currently, 2 products are approved for the prevention of respiratory syncytial virus in infants. These include the Pfizer bivalent recombinant respiratory syncytial virus prefusion F protein subunit vaccine, administered seasonally to the pregnant person between 32 0/7 and 36 6/7 weeks of gestation, and the monoclonal antibody, nirsevimab, administered to infants aged up to 8 months entering their first respiratory syncytial virus season. With few exceptions, administering both the vaccine to the pregnant person and the monoclonal antibody to the infant is not recommended. All infants should be protected against respiratory syncytial virus using one of these strategies. Key considerations for pregnant individuals include examining available safety and efficacy data, weighing accessibility and availability, and patient preferences for maternal vaccination vs infant monoclonal antibody treatment. It will be critical for maternal-fetal medicine physicians to provide effective and balanced counseling to aid patients in deciding on a personalized approach to the prevention of respiratory syncytial virus in their infants.

Utilizing metagenomic next-generation sequencing for pathogen detection and diagnosis in lower respiratory tract infections in real-world clinical practice.

BACKGROUND: Infectious etiologies of lower respiratory tract infections (LRTIs) by the conventional microbiology tests (CMTs) can be challenging. Metagenomic next-generation sequencing (mNGS) has great potential in clinical use for its comprehensiveness in identifying pathogens, particularly those difficult-to-culture organisms. METHODS: We analyzed a total of 205 clinical samples from 201 patients with suspected LRTIs using mNGS in parallel with CMTs. mNGS results were used to guide treatment adjustments for patients who had negative CMT results. The efficacy of treatment was subsequently evaluated in these patients. RESULTS: mNGS-detected microorganisms in 91.7% (188/205) of the clinical samples, whereas CMTs demonstrated a lower detection rate, identifying microorganisms in only 37.6% (77/205) of samples. Compared to CMT results, mNGS exhibited a detection sensitivity of 93.5% and 95.4% in all 205 clinical samples and 180 bronchoalveolar lavage fluid (BALF) samples, respectively. A total of 114 patients (114/201; 56.7%) showed negative CMT results, among which 92 received treatment adjustments guided by their positive mNGS results. Notably, 67.4% (62/92) of patients demonstrated effective treatment, while 25% (23/92) experienced a stabilized condition. Subgroup analysis of cancer patients revealed that 41.9% (13/31) exhibited an effective response to treatment, and 35.5% (11/31) maintained a stable condition following medication adjustments guided by mNGS. CONCLUSION: mNGS demonstrated great potential in identifying microorganisms of clinical significance in LRTIs. The rapid turnaround time and reduced susceptibility to the impact of antimicrobial administration make mNGS a valuable supplementary tool for diagnosis and treatment decision-making for suspected LRTIs in clinical practice.

Mycoplasma pneumoniae detections in children with lower respiratory infection before and during the COVID-19 pandemic: a large sample study in China from 2019 to 2022.

BACKGROUND: Nonpharmaceutical interventions (NPIs) implemented to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have suppressed the spread of other respiratory viruses during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to explore the epidemiological trends and clinical characteristics of Mycoplasma pneumoniae (MP) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the COVID-19 pandemic, and investigate the long-term effects of China's NPIs against COVID-19 on the epidemiology of MP among inpatient children with LRTI. METHODS: Children hospitalised for LRTI at the Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between January 2019 and December 2022 were tested for common respiratory pathogens, including Mycoplasma pneumoniae (MP), Chlamydia trachomatis (CT) and other bacteria. Clinical data on age, sex, season of onset, disease spectrum, and combined infection in children with MP-induced LRTI in the past 4 years were collected and analysed. RESULTS: Overall, 15909 patients were enrolled, and MP-positive cases were 1971 (34.0%), 73 (2.4%), 176 (5.8%), and 952 (20.6%) in 2019, 2020, 2021, and 2022, respectively, with a significant statistical difference in the MP-positive rate over the 4 years (p <0.001). The median age of these children was preschool age (3-6 years), except for 2022, when they were school age (7-12 years), with statistical differences. Comparing the positive rates of different age groups, the school-age children (7-12 years) had the highest positive rate, followed by the preschoolers (3-6 years) in each of the 4 years. Compared among different seasons, the positive rate of MP in children with LRTI was higher in summer and autumn, whereas in 2020, it was highest in spring. The monthly positive rate peaked in July 2019, remained low from 2020 to 2021, and rebounded until 2022. Regarding the disease spectrum, severe pneumonia accounted for the highest proportion (46.3%) pre-pandemic and lowest (0%) in 2020. CONCLUSION: Trends in MP detection in children with LRTIs suggest a possible correlation between COVID-19 NPIs and significantly reduced detection rates. The positivity rate of MP gradually rose after 2 years. The epidemic season showed some differences, but school-age children were more susceptible to MP before and during the COVID-19 pandemic.

Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden.

BACKGROUND: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality. METHODS: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI. RESULTS: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves. CONCLUSION: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.

Cost of illness due to respiratory syncytial virus acute lower respiratory tract infection among infants hospitalized in Argentina.

BACKGROUND: Information is scarce regarding the economic burden of respiratory syncytial virus (RSV) disease in low-resource settings. This study aimed to estimate the cost per episode of hospital admissions due to RSV severe disease in Argentina. METHODS: This is a prospective cohort study that collected information regarding 256 infants under 12 months of age with acute lower respiratory tract infection (ALRTI) due to RSV in two public hospitals of Buenos Aires between 2014 and 2016. Information on healthcare resource use was collected from the patient's report and its associated costs were estimated based on the financial database and account records of the hospitals. We estimated the total cost per hospitalization due to RSV using the health system perspective. The costs were estimated in US dollars as of December 2022 (1 US dollar = 170 Argentine pesos). RESULTS: The mean costs per RSV hospitalization in infants was US$587.79 (95% confidence interval [CI] $535.24 - $640.33). The mean costs associated with pediatric intensive care unit (PICU) admission more than doubled from those at regular pediatric wards ($1,556.81 [95% CI $512.21 - $2,601.40] versus $556.53 [95% CI $514.59 - $598.48]). CONCLUSIONS: This study shows the direct economic impact of acute severe RSV infection on the public health system in Argentina. The estimates obtained from this study could be used to inform cost-effectiveness analyses of new preventive RSV interventions being developed.

Perinatal exposure to traffic related air pollutants and the risk of infection in the first six months of life: a cohort study from a low-middle income country.

OBJECTIVE: There is limited study from low-and-middle income countries on the effect of perinatal exposure to air pollution and the risk of infection in infant. We assessed the association between perinatal exposure to traffic related air pollution and the risk of infection in infant during their first six months of life. METHODS: A prospective cohort study was performed in Jakarta, March 2016-September 2020 among 298 mother-infant pairs. PM2.5, soot, NOx, and NO2 concentrations were assessed using land use regression models (LUR) at individual level. Repeated interviewer-administered questionnaires were used to obtain data on infection at 1, 2, 4 and 6 months of age. The infections were categorized as upper respiratory tract (runny nose, cough, wheezing or shortness of breath), lower respiratory tract (pneumonia, bronchiolitis) or gastrointestinal tract infection. Logistic regression models adjusted for covariates were used to assess the association between perinatal exposure to air pollution and the risk of infection in the first six months of life. RESULTS: The average concentrations of PM2.5 and NO2 were much higher than the WHO recommended levels. Upper respiratory tract infections (URTI) were much more common in the first six months of life than diagnosed lower respiratory tract or gastro-intestinal infections (35.6%, 3.5% and 5.8% respectively). Perinatal exposure to PM2.5 and soot suggested increase cumulative risk of upper respiratory tract infection (URTI) in the first 6 months of life per IQR increase with adjusted OR of 1.50 (95% CI 0.91; 2.47) and 1.14 (95% CI 0.79; 1.64), respectively. Soot was significantly associated with the risk of URTI at 4-6 months age interval (aOR of 1.45, 95%CI 1.02; 2.09). All air pollutants were also positively associated with lower respiratory tract infection, but all CIs include unity because of relatively small samples. Adjusted odds ratios for gastrointestinal infections were close to unity. CONCLUSION: Our study adds to the evidence that perinatal exposure to fine particles is associated with respiratory tract infection in infants in a low-middle income country.

Surveillance of infections of surgical sites and lower respiratory tracts should be combined: experiences from the German surveillance module for operated patients (OP-KISS), 2018 to 2022.

BackgroundSurveillance of lower respiratory tract infections (LRTI) of operated patients conventionally focuses on intubated patients in intensive care units (ICU). Post-operative immobilisation increases the risk of LRTI not associated with ventilators. Operated patients, however, have thus far not been a primary target for LRTI surveillance.AimWe aimed to describe the applied LRTI surveillance method in the German surveillance module for operated patients (OP-KISS) and to report data between 2018 and 2022.MethodsSurveillance of LRTI can be performed voluntarily in addition to surgical site infection (SSI) surveillance in OP-KISS. We calculated LRTI rates per 100 operations for all procedures combined, as well as for individual surgical groups and procedures. Additionally, a combined post-operative infection rate (SSI and LRTI) was calculated.ResultsSurveillance of LRTI was performed in 4% of all participating OP-KISS departments and for 2% (23,239 of 1,332,438) of all procedures in the OP-KISS database. The pooled LRTI rate was 0.9 per 100 operations, with marked differences between different types of surgery (3.6 for lobectomies, 0.1 for traumatology and orthopaedics). The share of LRTI among all post-operative infections was highly variable. For lobectomies, the LRTI rate was higher than the SSI rate (3.6 vs 1.5 per 100 operations).ConclusionSurveillance of post-operative LRTI is not yet widely adopted by German hospitals. Based on the data in this study, lobectomies represent a prime target for post-operative LRTI surveillance.

Targeting the gut-lung axis by synbiotic feeding to infants in a randomized controlled trial.

BACKGROUND: Formula-fed infants are at increased risk of infections. Due to the cross-talk between the mucosal systems of the gastrointestinal and respiratory tracts, adding synbiotics (prebiotics and probiotics) to infant formula may prevent infections even at distant sites. Infants that were born full term and weaned from breast milk were randomized to prebiotic formula (fructo- and galactooligosaccharides) or the same prebiotic formula with Lactobacillus paracasei ssp. paracasei F19 (synbiotics) from 1 to 6 months of age. The objective was to examine the synbiotic effects on gut microbiota development. RESULTS: Fecal samples collected at ages 1, 4, 6, and 12 months were analyzed using 16S rRNA gene sequencing and a combination of untargeted gas chromatography-mass spectrometry/liquid chromatography-mass spectrometry. These analyses revealed that the synbiotic group had a lower abundance of Klebsiella, a higher abundance of Bifidobacterium breve compared to the prebiotic group, and increases in the anti-microbial metabolite d-3-phenyllactic acid. We also analyzed the fecal metagenome and antibiotic resistome in the 11 infants that had been diagnosed with lower respiratory tract infection (cases) and 11 matched controls using deep metagenomic sequencing. Cases with lower respiratory tract infection had a higher abundance of Klebsiella species and antimicrobial resistance genes related to Klebsiella pneumoniae, compared to controls. The results obtained using 16S rRNA gene amplicon and metagenomic sequencing were confirmed in silico by successful recovery of the metagenome-assembled genomes of the bacteria of interest. CONCLUSIONS: This study demonstrates the additional benefit of feeding specific synbiotics to formula-fed infants over prebiotics only. Synbiotic feeding led to the underrepresentation of Klebsiella, enrichment of bifidobacteria, and increases in microbial degradation metabolites implicated in immune signaling and in the gut-lung and gut-skin axes. Our findings support future clinical evaluation of synbiotic formula in the prevention of infections and associated antibiotic treatment as a primary outcome when breastfeeding is not feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT01625273 . Retrospectively registered on 21 June 2012.

Costs and healthcare utilisation due to respiratory syncytial virus disease in paediatric patients in Italy: a systematic review.

OBJECTIVES: Respiratory syncytial virus (RSV) is a frequent cause of acute lower respiratory infection in children, imposing a substantial economic burden on healthcare systems. This systematic review aimed to assess the economic burden and healthcare utilisation of RSV in children aged 0-59 months in Italy. STUDY DESIGN: Systematic review. METHODS: A systematic search of PubMed, Embase, Scopus, and the International HTA Database, including studies published in English or Italian, was conducted between January 2000 and July 2022. Inclusion criteria required studies to be conducted in Italy and provide data on the economic costs and healthcare resource utilisation related to RSV infections. RESULTS: Out of 20,845 records screened, 18 articles met the inclusion criteria. Only one study provided comprehensive data on RSV disease costs, including hospitalisation, diagnostic tests, and medical procedures for infants with RSV-bronchiolitis. The mean cost per inpatient was higher for RSV-positive children (€5753.43 ± €2041.62) than that for RSV-negative children. Additionally, five studies reported a median length of hospital stay of 5 days for RSV-infected children, and four studies indicated a higher frequency of intensive care unit admissions for RSV-infected children than for those with other viral infections. CONCLUSIONS: This is the first systematic review to examine the economic burden and healthcare utilisation of RSV in children aged 0-59 months in Italy. While limited data were available, the findings underscore the urgency to conduct further research and gather additional evidence on the costs and healthcare resource utilisation associated with RSV infections. Such efforts are essential for informing the development of effective prevention strategies for paediatric RSV infections in Italy.

Clinical Profiles, Laboratory Biomarkers, and Mortality in Cancer Patients with Lower Respiratory Tract Infections: A Prospective Cohort Study.

Respiratory tract infections (RTIs) pose a substantial health burden worldwide, especially among immunocompromised groups like cancer patients. The aim of this prospective cohort study was to explore lower respiratory tract infections in cancer patients. We followed 107 cases with clinically or radiologically suspected lower respiratory tract infections until discharge or death, comprising 65 males and 42 females across diverse age groups. Clinical evaluations, including patient history, examination, and malignancy diagnosis, were conducted. Nasopharyngeal swabs (NPSs), sputum samples, and blood samples were collected within 24 h of symptom onset. Multiplex Real-Time PCR allowed for the simultaneous detection of viral, bacterial, and fungal infections, while conventional microbiological culture methods were used for bacterial and fungal analysis. SARS-CoV-2 infection was excluded in all of the enrolled patients using real-time RT-PCR. Hematological and biochemical analyses included hemoglobin, lymphocyte, neutrophil, and platelet counts, along with ALT, AST, creatinine, and CRP levels. Significant differences were noted in clinical presentations, management outcomes, and prognostic markers among patients with different hematological malignancies. Distinct clinical profiles were identified for leukemia, lymphoma, and solid tumors, with variations in age distribution and symptom prevalence. ICU admission rates varied significantly, with solid tumor patients exhibiting higher rates. The hematological and biochemical biomarkers differed across malignancies, with notable associations between lymphopenia, thrombocytopenia, and mortality following respiratory episodes. This study highlights the critical role of rapid pathogen detection and infection control measures in safeguarding vulnerable cancer patients from nosocomial transmission.

Burden of Lower Respiratory Tract Infections Preventable by Adult Immunization With 15- and 20-Valent Pneumococcal Conjugate Vaccines in the United States.

BACKGROUND: Updated recommendations of the US Advisory Committee on Immunization Practices indicate that all adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. METHODS: We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California from 2016 through 2019. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against LRTI to model potential direct effects of PCV15/20 by age group and risk status. RESULTS: Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval, 41.3-131.8) and 108.6 (50.4-159.1) medically attended LRTI cases; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths, each per 10 000 person-years. Among at-risk adults aged <65 years, use of PCV15 and PCV20 could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically attended LRTI cases per 10 000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10 000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10 000 person-years. CONCLUSIONS: Our findings suggest recent recommendations, including PCV15/20 within adult pneumococcal vaccine series, may substantially reduce LRTI burden.

High incidence of the virus among respiratory pathogens in children with lower respiratory tract infection in northwestern China.

Lower respiratory tract infection (LRTI) is one of the major reasons for childhood mortality that threaten the health of the public. We aimed to investigate the epidemiological pathogens and their infection analysis among children with LRTI. Sputum specimens were collected for polymerase chain reaction detection and microbiological tests to identify the viral infection and bacterial infection. The serological specimens were separated from venous blood using for Mycoplasma pneumoniae and Chlamydia pneumoniae detection. The virus was confirmed in 86.2% of the children. Human rhinovirus (38.3%), respiratory syncytial virus (32.1%), and parainfluenza virus type 3 (27.2%) were the most frequently identified pathogens. Patients with viral and bacterial coinfection showed younger age (p = 0.032), a higher proportion of wheezing rales (p = 0.032), three depressions sign (p = 0.028), and tachypnea (p = 0.038), and more likely associated with severe pneumonia (p = 0.035). Additionally, older children were more susceptible to viral-atypical bacterial coinfection (p = 0.032). Vomiting (p = 0.011) and fever (p = 0.003) were more likely to occur in children with viral-atypical bacterial coinfection. Attention should be paid to the virus infection of LRTI, as viral-bacterial coinfection and viral-atypical bacterial co-infection may have a detrimental impact on the gravity of LTRI.

Modulation of autophagy and mTOR signaling pathway genes in respiratory epithelium by respiratory syncytial virus (RSV) in children suffering from acute lower respiratory tract infections.

The study was planned to carry out the molecular characterization of the respiratory syncytial virus (RSV) circulating strains and to elucidate the gene expression of autophagy and mammalian target of rapamycin (mTOR) signaling pathways in children with acute lower respiratory tract infection (ALRTI). Nasopharyngeal aspirate (NPA) samples (n = 145) from children suffering from ALRTI were subjected to the detection of RSV. Of them, 31 RSV positive strains were subjected for sequencing. Semi-quantitative gene expression analysis for mTOR signaling and autophagy pathway genes was performed in respiratory tract epithelial cells using 25 RSV positive cases, and 10 age and sex matched healthy control subjects. Five representative genes were selected for each pathway and subjected to SYBR green real-time polymerase chain reaction. RSV was positive in 69 (47.6%) samples and the representative (n = 31) RSV strains belonged to RSV-A. Thirty-one strains of RSV-A on phylogenetic analysis clustered with the novel ON1 genotype having 72 bp nucleotide duplicationby targeting the ecto-domain portion of the G gene. Further, the stains belonged to lineage 1 (51.6%), followed by lineage 3 (29%) and lineage 2 (19.4%). Autophagy gene expression analysis revealed significant upregulation in NPC1 and ATG3 autophagy genes. mTOR, AKT1, and TSC1 genes of the mTOR pathway were significantly downregulated in RSV positive patients. Thus, RSV infection inducing autophagy pathway genes (NPC1 and ATG3) and suppressing mTOR signaling pathway genes (AKT1, mTOR, and TSC1) to possibly evade the host immune system through dysregulating these pathways for its way of survival within the host.

Vitamin D supplementation and lower respiratory tract infection in infants: a nested case-control study.

PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.

The value of modified Ross score in the evaluation of children with severe lower respiratory tract infection admitted to the pediatric intensive care unit.

Heart failure (HF) represents an important cause of morbidity and mortality in children. It is mostly caused by congenital heart disease (CHD) and cardiomyopathy. The Ross HF classification was developed to assess severity in infants and has subsequently been modified to apply to all pediatric ages. The modified Ross classification for children provides a numeric score comparable with the New York Heart Association (NYHA) HF classification for adults. The aim of this work is to investigate the role of modified Ross score in the evaluation of children with severe lower respiratory tract infection admitted to the pediatric intensive care unit (PICU). One hundred and sixty-four children with severe LRTI admitted to the PICU were enrolled in this prospective cohort study, which was carried out at Assiut University Children Hospital, from the start of July 2021 up to the end of December 2021. Sixty patients (36.6%) of studied cases with severe LRTI admitted to PICU had HF. Out of these, 37 (61.7%) had mild HF; 17 (28.3%) had moderate HF, while six cases (10%) had severe HF according to the modified Ross score. The value of modified Ross score was significantly higher in children with heart failure with sensitivity and specificity 100% with cutoff value of 2. Admission to NICU, history of previous ventilation, and prematurity were higher in patients who developed HF. Patients with pulmonary hypertension (PH) and those with raised neutrophil lymphocyte ratio were significantly higher in the group of patients with moderate and severe degree of HF.   Conclusion: Modified Ross score is a simple clinical score which may help in assessing and predicting children with severe LRTI. What is Known: • Hear failure is common complication to lower respiratory tract infection. • Modified Ross score was used to predict and classify heart failure in adult with lower respiratory infection. What is New: • Modified Ross score found to be of value in prediction of heart failure in children with lower respiratory tract infection.

Comparative analysis of clinical features of lower respiratory tract infection with respiratory syncytial virus and influenza virus in adults: a retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This retrospective study aims to delineate and compare the clinical manifestations of adult RSV and influenza virus infections in the lower respiratory tract, thereby enhancing awareness of RSV lower respiratory tract infection and providing strategic insights for its prevention and treatment. METHODS: Clinical data from January 2019 to December 2020 were analyzed for 74 patients with RSV and 129 patients with influenza A/B virus lower respiratory tract infections who were admitted to respiratory or intensive care units. All patients had complete clinical data with positive IgM and negative IgG viral antibodies. Comparison parameters included onset timing, baseline data, clinical manifestations, supplementary examination results, treatment methods, and prognosis, while logistic regression was employed to ascertain the correlation of clinical features between the two patient groups. RESULTS: In comparison to the influenza group, the RSV group presented less frequently with fever at admission but exhibited a higher incidence of dyspnea and wheezing on pulmonary auscultation (P < 0.01). RSV infection was more prevalent among patients with underlying diseases, particularly chronic obstructive pulmonary disease (COPD) and demonstrated a higher probability of co-infections, most notably with Mycoplasma (P < 0.01). The RSV group had significantly higher lymphocyte counts (P < 0.01) and exhibited more incidences of pleural thickening, pulmonary fibrosis, and emphysema (P < 0.05). The use of non-invasive mechanical ventilation was more common, and hospital stays were longer in the RSV group compared to the influenza group (P < 0.05). Logistic multivariate regression analysis further revealed that age and tachypnea incidence were significantly higher in the RSV group (P < 0.05). CONCLUSION: Compared to influenza virus infection, adults with COPD are more susceptible to RSV infection. Moreover, RSV infection elevates the risk of co-infection with Mycoplasma and may lead to conditions such as pleural thickening, pulmonary fibrosis, and emphysema. The requirement for non-invasive mechanical ventilation is higher in RSV-infected patients, who also tend to have longer hospital stays. Therefore, greater awareness and preventive strategies against RSV infection are imperative.