Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: Systematic review and meta-analysis of preclinical studies.
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ABSTRACT:
SUBMITTER: Brito JCM
PROVIDER: S-EPMC8250479 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe LRIs are a major cause of infant/child hospitalization and a risk factors for asthma pathogenisis. Innate immune interactions with microbial pathogens, esp. in early life, underpin risk. We aimed to characterize cord blood mononuclear cell (CBMC) responses to activation of micriobial recognition receptors (TLRs 3, 4, & 7) and identify response pattern variations associated withsLRI susceptibility in infancy.
2022-08-24 | GSE184383 | GEO
Project description:Background: Distinguishing between bacterial and viral lower respiratory tract infections (LRTI) in hospitalized patients remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods: We performed whole blood transcriptional analysis in a cohort of 118 adult patients (median [IQR] age, 61 [50-76] years) hospitalized with bacterial, viral or viral-bacterial LRTI, and 40 age-matched healthy controls (60 [46-70] years). We applied class comparisons, modular analysis and class prediction algorithms to identify distinct biosignatures for bacterial and viral LRTI, which were validated in an independent group of patients. Results: Patients were classified as bacterial (B, n=22), viral (V, n=71) and bacterial-viral LRTI (BV, n=25) based on comprehensive microbiologic testing. Compared with healthy controls statistical group comparisons (p<0.01; with multiple test corrections) identified 3,376 differentially expressed genes in patients with B-LRTI; 2,391 in V-LRTI, and 2,628 in BV-LRTI. Independent of etiologic pathogen, patients with LRTI demonstrated overexpression of innate immunity and underexpression of adaptive immunity genes. Patients with B-LRTI showed significant overexpression of inflammation (B>BV>V) and neutrophils (B>BV>V) while those with V-LRTI displayed significantly greater overexpression of interferon genes (V>BV>B). The K-Nearest Neighbors (K-NN) algorithm identified 10 classifier genes that discriminated patients with bacterial vs viral LRTI with 97% [95%CI: 84-100] sensitivity and 92% [77-98] specificity. In comparison, procalcitonin classified bacterial vs viral LRTI with 38% [18-62] sensitivity and 91% [76-98] specificity. Conclusions: Transcriptional profiling can be used as a helpful tool for the diagnosis of adults hospitalized with LRTI. 158 samples, no replicates; bacterial LRTI n=22, viral LRTI n=71, bacterial-viral coinfections n=25, and healthy controls n=40
2015-09-14 | E-GEOD-60244 | biostudies-arrayexpress
Project description:BackgroundViruses and bacteria from the nasopharynx are capable of causing community-acquired pneumonia (CAP), which can be difficult to diagnose. We aimed to investigate whether shifts in the composition of these nasopharyngeal microbial communities can be used as diagnostic biomarkers for CAP in adults.MethodsWe collected nasopharyngeal swabs from adult CAP patients and controls without infection in a prospective multicenter case-control study design. We generated bacterial and viral profiles using 16S ribosomal RNA gene sequencing and multiplex polymerase chain reaction (PCR), respectively. Bacterial, viral, and clinical data were subsequently used as inputs for extremely randomized trees classification models aiming to distinguish subjects with CAP from healthy controls.ResultsWe enrolled 117 cases and 48 control subjects. Cases displayed significant beta diversity differences in nasopharyngeal microbiota (P = .016, R2 = .01) compared to healthy controls. Our extremely randomized trees classification models accurately discriminated CAP caused by bacteria (area under the curve [AUC] .83), viruses (AUC .95) or mixed origin (AUC .81) from healthy control subjects. We validated this approach using a dataset of nasopharyngeal samples from 140 influenza patients and 38 controls, which yielded highly accurate (AUC .93) separation between cases and controls.ConclusionsRelative proportions of different bacteria and viruses in the nasopharynx can be leveraged to diagnose CAP and identify etiologic agent(s) in adult patients. Such data can inform the development of a microbiota-based diagnostic panel used to identify CAP patients and causative agents from nasopharyngeal samples, potentially improving diagnostic specificity, efficiency, and antimicrobial stewardship practices.
| S-EPMC8906706 | biostudies-literature
Project description:BackgroundLower respiratory tract infections (LRTIs) are a leading cause of childhood morbidity and mortality. Potentially pathogenic organisms are present in the respiratory tract in both symptomatic and asymptomatic children, but their presence does not necessarily indicate disease. We aimed to assess the concordance between upper and lower respiratory tract microbiota during LRTIs and the use of nasopharyngeal microbiota to discriminate LRTIs from health.MethodsFirst, we did a prospective study of children aged between 4 weeks and 5 years who were admitted to the paediatric intensive care unit (PICU) at Wilhelmina Children's Hospital (Utrecht, Netherlands) for a WHO-defined LRTI requiring mechanical ventilation. We obtained paired nasopharyngeal swabs and deep endotracheal aspirates from these participants (the so-called PICU cohort) between Sept 10, 2013, and Sept 4, 2016. We also did a matched case-control study (1:2) with the same inclusion criteria in children with LRTIs at three Dutch teaching hospitals and in age-matched, sex-matched, and time-matched healthy children recruited from the community. Nasopharyngeal samples were obtained at admission for cases and during home visits for controls. Data for child characteristics were obtained by questionnaires and from pharmacy printouts and medical charts. We used quantitative PCR and 16S rRNA-based sequencing to establish viral and bacterial microbiota profiles, respectively. We did sparse random forest classifier analyses on the bacterial data, viral data, metadata, and the combination of all three datasets to distinguish cases from controls.Findings29 patients were enrolled in the PICU cohort. Intra-individual concordance in terms of viral microbiota profiles (96% agreement [95% CI 93-99]) and bacterial microbiota profiles (58 taxa with a median Pearson's r 0·93 [IQR 0·62-0·99]; p<0·05 for all 58 taxa) was high between nasopharyngeal and endotracheal aspirate samples, supporting the use of nasopharyngeal samples as proxy for lung microbiota during LRTIs. 154 cases and 307 matched controls were prospectively recruited to our case-control cohort. Individually, bacterial microbiota (area under the curve 0·77), viral microbiota (0·70), and child characteristics (0·80) poorly distinguished health from disease. However, a classification model based on combined bacterial and viral microbiota plus child characteristics distinguished children with LRTIs from their matched controls with a high degree of accuracy (area under the curve 0·92).InterpretationOur data suggest that the nasopharyngeal microbiota can serve as a valid proxy for lower respiratory tract microbiota in childhood LRTIs, that clinical LRTIs in children result from the interplay between microbiota and host characteristics, rather than a single microorganism, and that microbiota-based diagnostics could improve future diagnostic and treatment protocols.FundingSpaarne Gasthuis, University Medical Center Utrecht, and the Netherlands Organization for Scientific Research.
| S-EPMC7172745 | biostudies-literature
Project description:Background: Distinguishing between bacterial and viral lower respiratory tract infections (LRTI) in hospitalized patients remains challenging. Transcriptional profiling is a promising tool for improving diagnosis in LRTI. Methods: We performed whole blood transcriptional analysis in a cohort of 118 adult patients (median [IQR] age, 61 [50-76] years) hospitalized with bacterial, viral or viral-bacterial LRTI, and 40 age-matched healthy controls (60 [46-70] years). We applied class comparisons, modular analysis and class prediction algorithms to identify distinct biosignatures for bacterial and viral LRTI, which were validated in an independent group of patients. Results: Patients were classified as bacterial (B, n=22), viral (V, n=71) and bacterial-viral LRTI (BV, n=25) based on comprehensive microbiologic testing. Compared with healthy controls statistical group comparisons (p<0.01; with multiple test corrections) identified 3,376 differentially expressed genes in patients with B-LRTI; 2,391 in V-LRTI, and 2,628 in BV-LRTI. Independent of etiologic pathogen, patients with LRTI demonstrated overexpression of innate immunity and underexpression of adaptive immunity genes. Patients with B-LRTI showed significant overexpression of inflammation (B>BV>V) and neutrophils (B>BV>V) while those with V-LRTI displayed significantly greater overexpression of interferon genes (V>BV>B). The K-Nearest Neighbors (K-NN) algorithm identified 10 classifier genes that discriminated patients with bacterial vs viral LRTI with 97% [95%CI: 84-100] sensitivity and 92% [77-98] specificity. In comparison, procalcitonin classified bacterial vs viral LRTI with 38% [18-62] sensitivity and 91% [76-98] specificity. Conclusions: Transcriptional profiling can be used as a helpful tool for the diagnosis of adults hospitalized with LRTI.
2015-09-14 | GSE60244 | GEO
Project description:Background: Little is known about the interaction between the nasopharyngeal bacterial profile and the nutritional status in children. In this study, our main goal was to evaluate the associations between overnutrition and the presence of four potentially pathogenic bacteria in the nasopharynx of infants with viral lower respiratory tract infections (LRTI). In addition, we determined whether changes in the nasopharyngeal bacterial profile were associated with mucosal and serum proinflammatory cytokines and with clinical disease severity. Methods: We enrolled 116 children less than 2 years old hospitalized for viral LRTI during two consecutive respiratory seasons (May 2016 to August 2017); their nutritional status was assessed, and nasopharyngeal and blood samples were obtained. S. aureus, S. pneumoniae, H. influenzae, M. catarrhalis, and respiratory viruses were identified in nasopharyngeal samples by qPCR. Cytokine concentrations were measured in nasopharyngeal and blood samples. Disease severity was assessed by the length of hospitalization and oxygen therapy. Results: Nasopharyngeal pathogenic bacteria were identified in 96.6% of the enrolled children, and 80% of them tested positive for two or more bacteria. The presence and loads of M. catarrhalis was higher (p = 0.001 and p = 0.022, respectively) in children with overnutrition (n = 47) compared with those with normal weights (n = 69). In addition, the detection of >2 bacteria was more frequent in children with overnutrition compared to those with normal weight (p = 0.02). Multivariate regression models showed that the presence and loads of S. pneumoniae and M. catarrhalis were associated with higher concentrations of IL-6 in plasma and TNF-α in mucosal samples in children with overnutrition. Conclusions: The nasopharyngeal profile of young children with overnutrition was characterized by an over representation of pathogenic bacteria and proinflammatory cytokines.
| S-EPMC9317356 | biostudies-literature
Project description:BackgroundLower respiratory tract infections (LRTI) are responsible for a considerable number of deaths among children, particularly in developing countries. In Egypt and the Middle East region, there is a lack of data regarding the viral causes of LRTI. In this study, we aimed to identify the relative prevalence of various respiratory viruses that contribute to LRTIs in young children. Although, nucleic acid-based methods have gained importance as a sensitive tool to determine the viral infections, their use is limited because of their prohibitive cost in low-income countries. Therefore, we applied three different laboratory methods, and presented the different virus prevalence patterns detected by each method.MethodsWe collected nasopharyngeal aspirate samples, demographic data and, clinical data from 450 children under five years of age who presented with LRTI at Abou El Reesh hospital in Cairo during a one-year period. To identify the viral causes of the LRTI we used direct fluorescence assay, real-time reverse-transcriptase polymerase chain reaction (rt-RT-PCR), and shell vial culture. We tested for eight major respiratory viruses.ResultsTwo hundred sixty-nine patients (59.9%) had a viral infection, among which 10.8% had a co-infection with two or more viruses. By all three methods, respiratory syncytial virus (RSV) was the most predominant, and parainfluenza virus type 2 (HPIV-2), influenza B virus (FLUBV) were the least predominant. Other viral prevalence patterns differed according to the detection method used. The distribution of various viruses among different age groups and seasonal distribution of the viruses were also determined.ConclusionsRSV and human adenovirus were the most common respiratory viruses detected by rt-RT-PCR. Co-infections were found to be frequent among children and the vast majority of co-infections were detected by nucleic acid-based detection assays.
| S-EPMC3538156 | biostudies-literature
Project description:Viral lower respiratory tract infection (VLRTI) is the most common cause of hospital admission among small children in high-income countries. Guidelines to identify children in need of admission are lacking in the literature. In December 2012, our hospital introduced strict guidelines for admission. This study aims to retrospectively evaluate the safety and efficacy of the guidelines. We performed a single-center retrospective administrative database search and medical record review. ICD-10 codes identified children < 24 months assessed at the emergency department for VLRTI for a 10-year period. To identify adverse events related to admission guidelines implementation, we reviewed patient records for all those discharged on primary contact followed by readmission within 14 days. During the study period, 3227 children younger than 24 months old were assessed in the ED for VLRTI. The proportion of severe adverse events among children who were discharged on their initial emergency department contact was low both before (0.3%) and after the intervention (0.5%) (p=1.0). Admission rates before vs. after the intervention were for previously healthy children > 90 days 65.3% vs. 53.3% (p<0.001); for healthy children ≤ 90 days 85% vs. 68% (p<0.001); and for high-risk comorbidities 74% vs. 71% (p=0.5).Conclusion: After implementation of admission guidelines for VLRTI, there were few adverse events and a significant reduction in admissions to the hospital from the emergency department. Our admission guidelines may be a safe and helpful tool in the assessment of children with VLRTI. What is Known: • Viral lower respiratory tract infection, including bronchiolitis, is the most common cause of hospitalization for young children in the developed world. Treatment is mainly supportive, and hospitalization should be limited to the cases in need of therapeutic intervention. • Many countries have guidelines for the management of the disease, but the decision on whom to admit for inpatient treatment is often subjective and may vary even between physicians in the same hospital. What is New: • Implementation of admission criteria for viral lower respiratory tract infection may reduce the rate of hospital admissions without increasing adverse events.
| S-EPMC8285352 | biostudies-literature
Project description:The human respiratory tract is heavily exposed to microorganisms. Viral respiratory tract pathogens, like RSV, influenza and rhinoviruses cause major morbidity and mortality from respiratory tract disease. Furthermore, as viruses have limited means of transmission, viruses that cause pathogenicity in other tissues may be transmitted through the respiratory tract. It is therefore important to chart the human virome in this compartment. We have studied nasopharyngeal aspirate samples submitted to the Karolinska University Laboratory, Stockholm, Sweden from March 2004 to May 2005 for diagnosis of respiratory tract infections. We have used a metagenomic sequencing strategy to characterize viruses, as this provides the most unbiased view of the samples. Virus enrichment followed by 454 sequencing resulted in totally 703,790 reads and 110,931 of these were found to be of viral origin by using an automated classification pipeline. The snapshot of the respiratory tract virome of these 210 patients revealed 39 species and many more strains of viruses. Most of the viral sequences were classified into one of three major families; Paramyxoviridae, Picornaviridae or Orthomyxoviridae. The study also identified one novel type of Rhinovirus C, and identified a number of previously undescribed viral genetic fragments of unknown origin.
| S-EPMC3280267 | biostudies-literature
Project description:BackgroundPreventing severe complications of influenza such as hospitalization is a public health priority; however, estimates of influenza vaccine effectiveness (VE) against influenza-associated acute lower respiratory tract infection (LRTI) hospitalizations are limited. We examined influenza VE against influenza-associated LRTIs in hospitalized adult patients.MethodsWe retrospectively analyzed data from a randomized trial of oseltamivir treatment in adults hospitalized with LRTI in Louisville, Kentucky, from 2010 to 2013. Patients were systematically tested for influenza at the time of enrollment. We estimated VE as 1 - the adjusted odds ratio (aOR) of antecedent vaccination in influenza-positives vs negatives × 100%. Vaccination status was obtained by patient self-report. Using logistic regression adjusting for age, sex, season, timing of illness, history of chronic lung disease, and activities of daily living, we estimated VE against hospitalized influenza-associated LRTIs and community-acquired pneumonia (CAP) with radiographic findings of infiltrate.ResultsOf 810 patients with LRTI (median age, 62 years), 184 (23%) were influenza-positive and 57% had radiographically confirmed CAP. Among influenza-positives and -negatives, respectively, 61% and 69% were vaccinated. Overall, 29% were hospitalized in the prior 90 days and >80% had comorbidities. Influenza-negatives were more likely to have a history of chronic obstructive pulmonary disease than influenza-positives (59% vs 48%; P = .01), but baseline medical conditions were otherwise similar. Overall, VE was 35% (95% CI, 4% to 56%) against influenza-associated LRTI and 51% (95% CI, 13% to 72%) against influenza-associated radiographically confirmed CAP.ConclusionsVaccination reduced the risk of hospitalization for influenza-associated LRTI and radiographically confirmed CAP. Clinicians should maintain high rates of influenza vaccination to prevent severe influenza-associated complications.
| S-EPMC7372707 | biostudies-literature