Diagnosis Of Lower Respiratory Tract Infections Research Articles

Integrated Host/Microbe Metagenomics Enables Accurate Lower Respiratory Tract Infection Diagnosis in Critically Ill Children.

Integrated Host/Microbe Metagenomics Enables Accurate Lower Respiratory Tract Infection Diagnosis in Critically Ill Children.

A dual-process of targeted and unbiased Nanopore sequencing enables accurate and rapid diagnosis of lower respiratory infections

Nanopore metagenomics has been used for infectious disease diagnosis for bacterial pathogens. However, this technology currently lacks comprehensive performance studies in clinical settings for simultaneous detection of bacteria, fungi, and viruses. We developed a dual-process of Nanopore sequencing for one sample, with unbiased metagenomics in Meta process and target enrichment in Panel process (Nanopore Meta-Panel process, NanoMP) and prospectively enrolled 450 respiratory specimens from multiple centers. The filter system of pathogen detection was established with machine learning and receiver operator characteristic (ROC) curve to optimize the detection accuracy based on orthogonal test of 21 species. Antimicrobial resistance (AMR) genes were identified based on the Comprehensive Antibiotic Resistance Database (CARD) and single-nucleotide polymorphism matrix. Our approach showed high sensitivity in Meta process, with 82.9%, 88.7%, and 75.0% for bacteria, fungi (except Aspergillus), and Mycobacterium tuberculosis groups, respectively. Moreover, target amplification improved the sensitivity of virus (>80.0% vs. 39.4%) and Aspergillus (81.8% vs. 42.3%) groups in Panel process compared with Meta process. Overall, NanoMP achieved 80.2% sensitivity and 98.8% specificity compared with the composite reference standard, and we were able to accurately detect AMR genes including blaKPC-2, blaOXA-23 and mecA and distinguish their parent organisms in patients with mixed infections. We combined metagenomic and enriched Nanopore sequencing for one sample in parallel. Our NanoMP approach simultaneously covered bacteria, viruses and fungi in respiratory specimens and demonstrated good diagnostic performance in real clinical settings. National Key Research and Development Program of China and National Natural Science Foundation of China.

Co-Circulation of SARS-CoV-2 and Other Respiratory Pathogens in Upper and Lower Respiratory Tracts during Influenza Season 2022-2023 in Lazio Region.

Lower respiratory tract infections (LRTIs) occur when there is a lower airway tract infection. They are well-known for increasing the susceptibility of patients to bacterial/fungal co-infections and super-infections. In this study, we present the results of our investigation, which involved 381 consecutive patients admitted to our hospital during the Influenza season from October 2022 to April 2023. Among the 381 specimens, 75 were bronchoalveolar (BAL), and 306 were nasopharyngeal swabs (NPSs). Notably, 34.4% of the examined samples tested positive for SARS-CoV-2. Of these, we observed that 7.96% of NPSs showed positivity only for other respiratory viruses, while a substantial percentage (77%) of BAL specimens exhibited positive results only for bacterial co-infections. The results of our study not only confirm the importance of co-infections in COVID-19 but also emphasize the significance of utilizing rapid diagnostic tests (RDTs) for the timely diagnosis of LRTIs. In fact, RDTs allow for the identification of multiple pathogens, providing clinicians with useful and timely information to establish effective therapy.

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

The impact of metagenomic next-generation sequencing (mNGS) on antimicrobial stewardship in patients with lower respiratory tract infections (LRTIs) is still unknown. 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. 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. 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.

All-cause and pathogen-specific lower respiratory tract infection hospital admissions in children younger than 5 years during the COVID-19 pandemic (2020–22) compared with the pre-pandemic period (2015–19) in South Africa: an observational study

Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015-19). Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67-0·74) and 13% lower in 2021 (0·87, 0·83-0·91), but 16% higher in 2022 (1·16, 1·11-1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45-0·58), influenza-associated LRTI (0·05, 0·02-0·11), and pulmonary tuberculosis (0·52, 0·41-0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95-1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92-1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65-0·94) and IPD (0·51, 0·24-0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19-0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97-1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03-1·58). The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. The Bill & Melinda Gates Foundation.

Integrated host/microbe metagenomics enables accurate lower respiratory tract infection diagnosis in critically ill children.

BACKGROUNDLower respiratory tract infection (LRTI) is a leading cause of death in children worldwide. LRTI diagnosis is challenging because noninfectious respiratory illnesses appear clinically similar and because existing microbiologic tests are often falsely negative or detect incidentally carried microbes, resulting in antimicrobial overuse and adverse outcomes. Lower airway metagenomics has the potential to detect host and microbial signatures of LRTI. Whether it can be applied at scale and in a pediatric population to enable improved diagnosis and treatment remains unclear.METHODSWe used tracheal aspirate RNA-Seq to profile host gene expression and respiratory microbiota in 261 children with acute respiratory failure. We developed a gene expression classifier for LRTI by training on patients with an established diagnosis of LRTI (n = 117) or of noninfectious respiratory failure (n = 50). We then developed a classifier that integrates the host LRTI probability, abundance of respiratory viruses, and dominance in the lung microbiome of bacteria/fungi considered pathogenic by a rules-based algorithm.RESULTSThe host classifier achieved a median AUC of 0.967 by cross-validation, driven by activation markers of T cells, alveolar macrophages, and the interferon response. The integrated classifier achieved a median AUC of 0.986 and increased the confidence of patient classifications. When applied to patients with an uncertain diagnosis (n = 94), the integrated classifier indicated LRTI in 52% of cases and nominated likely causal pathogens in 98% of those.CONCLUSIONLower airway metagenomics enables accurate LRTI diagnosis and pathogen identification in a heterogeneous cohort of critically ill children through integration of host, pathogen, and microbiome features.FUNDINGSupport for this study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute (UG1HD083171, 1R01HL124103, UG1HD049983, UG01HD049934, UG1HD083170, UG1HD050096, UG1HD63108, UG1HD083116, UG1HD083166, UG1HD049981, K23HL138461, and 5R01HL155418) as well as by the Chan Zuckerberg Biohub.

Viral Identification Using Multiplex Polymerase Chain Reaction Testing Does Not Reduce Antibiotic Prescribing in Paediatric Intensive Care Units.

PCR tests for viral identification, performed on nasopharyngeal secretions, have experienced a major boom in the last few years. Their use is very frequent, but their indications are still not well defined, especially in Paediatric Intensive Care Units (PICU). These tests are used for the microbiological diagnosis of lower respiratory infections but can be used in other situations. The aim of the study was to investigate the effect of viral identification on antibiotic therapy management. We conducted a single-centre retrospective study from 1 October 2017 to 31 December 2019. This study included all consecutive FilmArray® Respiratory Panel tests performed in patients hospitalised in a PICU. Patients were identified using the microbiology laboratory prospective database and data were extracted from the medical record. 544 tests corresponding to 408 patients were included. The main reasons for testing were pneumonia (34%) and bronchiolitis (24%). In 70% of cases, at least one virus was identified, with Human Rhinovirus (56%) and Respiratory Syncytial Virus (28%) being the two predominant. Bacterial co-infection was present in 25% of cases. Viral identification was not associated with reduced antibiotic therapy. On multivariate analysis, antibiotic management was significantly associated with clinical gravity, CRP value or radiology findings regardless of virus identification. Viral identification has an epidemiological value, but antibiotic prescription relies on other factors.

Low Levels of RSV Testing Among Adults Hospitalized for Lower Respiratory Tract Infection in the United States.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection (LRTI)-related hospitalizations in older adults. Without RSV-specific treatment for adults, testing is uncommon, leading to potential underestimation of RSV incidence in real-world data studies. This study aimed to quantify the frequency of RSV testing during LRTI-related hospitalizations of older adults to inform interpretation of incidence estimates. Administrative and billing data for hospitalizations of adults aged≥65years with a primary or secondary diagnosis of LRTI during the 2016-2019 RSV seasons (October-April) were extracted from the US all-payer Premier Healthcare Database (PHD). Billing codes identified RSV tests administered during eligible hospitalizations. The proportion of LRTI-related hospitalizations with a billed RSV test was calculated for each hospital in PHD, and summarized descriptively by hospital bed size, teaching status, and population served. Most of the 937 study hospitals performed RSV testing infrequently during LRTI hospitalization; median percentage of LRTI hospitalizations with RSV testing was 4.3%, and 78.4% of hospitals performed RSV testing in less than 25% of LRTI-related hospitalizations. RSV testing varied extensively by hospital type. Median percentage tested was significantly higher for hospitals with≥200 beds (9.1%) versus<200 beds (1.6%), for teaching (11.0%) versus non-teaching (2.5%) hospitals, and in urban (7.4%) versus rural (0.7%) settings. The median percentage of RSV testing increased over time, from 0.8% to 6.3% between the 2016/17 and 2018/19 seasons. A small proportion of older adults hospitalized with LRTI are tested for RSV in US hospitals. Large variability occurs across hospital types. Consequently, retrospective database analyses likely result in a substantial underestimation of the true RSV-related hospitalization incidence. RSV incidence studies using real-world data need to assess for RSV testing frequency and adjust their results for under ascertainment associated with limited testing.

Advancing Microbe Detection for Lower Respiratory Tract Infection Diagnosis and Management with Metagenomic Next-Generation Sequencing.

Due to limitations of traditional microbiological methods and the presence of the oropharyngeal normal flora, there are still many pathogens that cause lower respiratory tract infections (LRTIs) cannot be detected. Metagenomic next-generation sequencing (mNGS) has the potential capacity to solve this problem. This retrospective study successively reviewed 77 patients with LRTI and 29 patients without LRTI admitted to Tianjin Medical University General Hospital, China from August 2020 to June 2021. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected adopting mNGS and traditional microbiological assays. The diagnostic performance of pathogens was compared between mNGS and BALF culture. The value of mNGS for aetiological and clinical impact investigation in LRTI was also evaluated. Among 77 patients with LRTI, 22.1%, 40.3%, and 65.0% of cases were detected as definite or probable pathogens by culture, all conventional microbiological tests, and mNGS, respectively. Using the final diagnosis as a gold standard, mNGS exhibited a sensitivity of 76.6% (95% confidence interval [CI], 65.6-85.5%), which was considerably superior to that of BALF culture (76.6% vs 18.2%; P < 0.01); specificity of 79.3% (95% CI, 60.3-92.0%), which was similar (79.3% vs 89.7%; P = 0.38); positive-predictive value of 90.8% (95% CI, 81.0-96.5%), and negative-predictive value of 56.1% (95% CI, 39.7-71.5%). According to our data, mNGS identified potential microorganisms in 66.7% (42/63) of culture-negative samples. Among 59 patients with pathogens identified by mNGS, conventional microbiological methods confirmed pathogenic infections in less than half (28/59) cases. Within the 77 patients, 34 (44.2%) patients received pathogen-directed therapy, 7 (9.1%) patients underwent antibiotic adjustment, and 3 (3.9%) patients stopped using antibiotics due to mNGS results. mNGS exhibits high accuracy in diagnosing LRTI, and combine with traditional microbiological tests, causative pathogens can be detected in approximately 70.0% of cases, thus yields a positive effect on antibiotic application.

Comparison of Third-Generation Sequencing Technology and Traditional Microbiological Detection in Pathogen Diagnosis of Lower Respiratory Tract Infection.

It is common to obtain a low detection rate and unsatisfactory detection results in complex infection or rare pathogen detection. This retrospective study aimed to illustrate the application value and prospect of the third-generation sequencing technology in lower respiratory tract infection disease. This study recruited 70 patients with lower respiratory tract infection (LRTI). Pathogen detection of bronchoalveolar lavage fluid (BALF) from all patients was performed using nanopore metagenomic sequencing technology and traditional culture. BALF culture combined with quantitiative PCR (qPCR) was used as a reference standard to analyze the sensitivity and specificity of nanopore sequencing technology. The current study also collected the examination results of enrolled samples using technical methods sputum culture, tuberculosis DNA (TB-DNA), and Xpert MTB/RIF and analyzed the detection efficiency of nanopore sequencing for Mycobacterium tuberculosis. The positive rates of pathogens in 70 BALF samples detected by conventional culture and nanopore sequencing were 25.71% and 84.29%, respectively. Among the 59 positive BALF cases using nanopore sequencing, a total of 31 pathogens were identified, of which the proportions of bacteria, fungi, viruses, and other pathogens were 50%, 17%, 32%, and 1%, respectively. Using the results combined with culture and qPCR detection methods as the standard, the pathogen detection of BALF using nanopore sequencing had a sensitivity of 70% and a specificity of 91.7%. Additionally, the positive rate of the detection of M. tuberculosis using nanopore sequencing was 33.3% (6/18). The clinical medication plans of 74.3% (52/70) of the patients were referred to the nanopore sequencing results, of which 31 cases changed their treatment strategy, 21 supported the previous treatment plans, and 90% (47/52) of the patients finally had clinical improvement. BALF detection using nanopore sequencing technology improves the process of detecting pathogens in patients with LRTI, especially for M. tuberculosis, fungi, and viruses, by reducing the report time from three days to six hours. The clinical application prospect of nanopore sequencing technology is promising in the pathogen diagnosis of LRTI.

Identification of Elderly Patients with Lower Respiratory Tract Infection by Artificial Intelligence Analysis of Cough Pattern Sounds.

Automatic recognition of cough sounds shows promise in the diagnosis of respiratory conditions. This study investigated the diagnostic value of cough sounds in elderly patients with lower respiratory tract infection (LRTI). We selected 83 elderly patients with suspected LRTI who sought medical advice at our hospital from January 2022 to September 2022, and grouped them into the infected and uninfected categories, according to their clinical traits. The cough sound of each subject was recorded and features were extracted using the Mel Frequency Cepstrum Coefficient. Four cough sound indexes, including the length of light or heavy cough time (T1), frequency of sound, decibels full scale (dBFs) and total length of cough time (T0) were compared between the two groups. The diagnostic efficacy of each index was analyzed using the receiver operating characteristic (ROC) curve. 22 patients were diagnosed with LRTI in the infected group including 15 males and 7 females, 13 were in the LRTI-free uninfected group, including 7 males and 6 females. Cough sound indexes were higher in the infected group compared with the uninfected group at T1 (p = 0.127), frequency of sound (p = 0.894), dBFs (p = 0.532) and T0 (p = 0.854). ROC curve analysis showed that the area under the curve (AUC) values of the above four indexes and the combined indexes for LRTI diagnosis were 0.680, 0.503, 0.577, 0.486 and 0.696, respectively. Cough sounds are correlated with LRTI. However, due to the small sample size of this study, the current results do not find that automatic recognition of cough has obvious diagnostic value, but its diagnostic potential in elderly patients with LRTI cannot be denied.

330. BioFire ® FilmArray® Pneumonia Panel (PN) Results Compared to Standard Microbiologic Testing and Clinical Adjudication in Adults Hospitalized with Respiratory Illness.

Abstract Background Inability to define microbial etiology of lower respiratory tract infection (LRTI) leads to unnecessary antibiotic use. Though multiplex PCR improves viral detection, bacterial LRTI diagnosis remains problematic. We evaluated the clinical utility of BioFire ® FilmArray ® Pneumonia (PN) Panel which detects 8 viruses, 3 atypical and 15 pathogenic bacteria by semi-quantitative PCR to inform bacterial diagnosis. Methods As part of a study to distinguish bacterial from non-bacterial LRTI in hospitalized adults, clinical, laboratory, and X-ray data were collected. Adequate sputa (&amp;lt; 10 Epithelial &amp; &amp;gt;25 PMNs) processed by Gram stain and culture were tested with FilmArray® PN. Microbial LRTI etiology (viral alone, bacterial with or without concomitant viruses, or indeterminate) was adjudicated by a four physician panel using all clinical data except bacterial PCR results. Bacterial PCR was compared to Gram stain and culture and clinical adjudication. Results From 737 illnesses evaluated, 423 sputa were collected and 201 deemed adequate and were tested with FilmArray® PN. Most common discharge diagnoses were pneumonia (24%), AECOPD (21%), viral illness (13%) and asthma exacerbations (9%). FilmArray® PN detected 155 typical bacteria, 9 atypical and 101 viruses. Most bacterial detections were monomicrobial (58%) often with concomitant viruses (43%). Compared to Gram stain and culture, FilmArray® PN detected more bacterial pathogens and was less affected by antibiotics. (Figure) Cases were adjudicated as viral Alone (37), bacterial (93) and indeterminate (71). Bacteria were detected by PCR in 41% of viral and 96% of bacterial cases, p=0.0001 and 76% of indeterminate cases. In cases with no bacteria detected by PCR, only 4 (9%) were adjudicated as bacterial; all deemed caused by anaerobic bacteria which are not included in the PCR panel. Comparing bacterial vs. non-bacterial (Viral + Indeterminate), FilmArray® PN bacterial PCR had 96% sensitivity, 36% specificity, 56% positive predictive value and 91% negative predictive value. Finally, sputum PCR detected 4 mycoplasma and 56 viral infections missed by standard of care testing. FigureRelationship of Gram Stain and Time on Antibiotics to Bacterial Culture and Bacterial PCR Results Conclusion Multiplex PCR testing of sputa for bacteria is useful to rule out bacterial infection with added value to detect viruses and atypical bacteria. Disclosures Ann R. Falsey, MD, BioFire Diagnostics: Grant/Research Support|Janssen: Grant/Research Support|Merck, Sharp and Dohme: Grant/Research Support|Novavax: Advisor/Consultant|Pfizer: Grant/Research Support Angela R. Branche, MD, Cyanvac: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Expert Testimony|Pfizer: Grant/Research Support Edward E. Walsh, MD, Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support.

Medically Attended Illness due to Respiratory Syncytial Virus Infection Among Infants Born in the United States Between 2016 and 2020.

BackgroundRespiratory syncytial virus (RSV) is a leading cause of infant hospitalization in the United States. Preterm infants and those with select comorbidities are at highest risk of RSV-related complications. However, morbidity due to RSV infection is not confined to high-risk infants. We estimated the burden of medically attended (MA) RSV-associated lower respiratory tract infection (LRTI) among infants in the United States.MethodsWe analyzed commercial (MarketScan Commercial [MSC], Optum Clinformatics [OC]), and Medicaid (MarketScan Medicaid [MSM]) insurance claims data for infants born between April 2016 and February 2020. Using both specific and sensitive definitions of MA RSV LRTI, we estimated the burden of MA RSV LRTI during infants’ first RSV season, stratified by gestational age, comorbidity status, and highest level of medical care associated with the MA RSV LRTI diagnosis.ResultsAccording to the specific definition 75.0% (MSC), 78.6% (MSM), and 79.6% (OC) of MA RSV LRTI events during infants’ first RSV season occurred among term infants without known comorbidities.ConclusionsTerm infants without known comorbidities account for up to 80% of the MA RSV LRTI burden in the United States during infants’ first RSV season. Future prevention efforts should consider all infants.

Comparison of tracheal aspirate and bronchoalveolar lavage samples in the microbiological diagnosis of lower respiratory tract infection in pediatric patients.

Bacterial cultures from tracheal aspirates (TA) and bronchoalveolar lavage (BAL) specimens can be used to assess patients with artificial airways for lower respiratory tract infections (LRTI). TA collection may be advantageous in situations of limited resources or critical illness. Literature comparing these diagnostic modalities in pediatric populations is scarce. Single-center, retrospective analysis of 52 pediatric patients with an artificial airway undergoing evaluation for LRTI. All patients had a TA specimen collected for semiquantitative Gram stain and culture followed by BAL within 48 h. Microbiologic diagnosis of LRTI was defined as a BAL sample with >25% neutrophils and growth of >104 colony-forming units/ml of one or more bacterial species. The test characteristics of TA were compared with these BAL results as the reference standard. Concordance in microorganism identification was also assessed. Overall, 24 patients (47%) met criteria for LRTI using BAL as the diagnostic standard. TA samples positive for an isolated organism had poor sensitivity for acute LRTI when compared with BAL, regardless of semiquantitative white blood cell (WBC) count by Gram stain. Using a TA diagnostic threshold of organism growth and at least "moderate" WBC yielded a specificity of 93%. Positive predictive value was highest when an organism was identified by TA. Negative predictive value was >70% for TA samples with no WBC by semiquantitative analysis, with or without growth of an organism. Complete concordance of cultured species was 58% for all patients, with a higher rate seen among those with endotracheal tubes. The role of cultures obtained by TA remains limited for the diagnosis of acute LRTI as demonstrated by the poor correlation to BAL results within our cohort. Optimal strategies for diagnosing LRTI across patient populations and airway types remain elusive.

Infants Hospitalized with Lower Respiratory Tract Infections Were More Likely to Develop Asthma.

Lower respiratory tract infections (LRTIs) have been reported to possibly initiate the development of asthma in children. However, the role of LRTIs in infantile asthma remains controversial. The goal of this study is to investigate whether LRTIs in hospitalized infants are involved in the development of asthma. The subjects were 251 infants under 2 years of age who were admitted to our hospital with an RTI (59 cases of upper RTI (URTIs) with upper respiratory tract inflammation and pharyngeal tonsillitis; 192 cases of LRTIs with bronchitis, pneumonia, and bronchiolitis). Pathogens of viral infections were examined at admission using viral antigen test kits that could be used in ordinary clinical practice in Japan. When the children reached the age of 3 years, a survey was conducted by mailing a questionnaire to determine the symptoms, diagnosis, and treatment of asthma. The mailed questionnaires were returned by 116 of the 251 subjects. On the questionnaire, the diagnosis of asthma and treatment for asthma were significantly higher in hospitalized infants with LRTIs than in those with URTIs. By diagnosis of LRTIs, infants with pneumonia and bronchiolitis were significantly more likely to develop asthma. However, on pathogen-specific examination, there was no difference in the development of asthma among infants with LRTIs. LRTI in infancy may be involved in the development of asthma. The severity of LRTI in hospitalized infants, but not the particular viral pathogen causing infection, may be associated with later asthma onset.

Incidence and Risk Factors for Hyponatremia in Hospitalized Children with Lower Respiratory Tract Infections

Lower respiratory tract infection (LRTI) is an important cause of hospitalization in pediatric population. Hyponatremia is frequently present in children hospitalized with pneumonia and bronchiolitis and is associated with poorer outcomes. We conducted a study to identify the risk factors for hyponatremia in hospitalized children with LRTI and to evaluate the relationship between serum sodium levels and severity of respiratory distress. A total of 147 patients between 2 months and 12 years of age, admitted with the diagnosis of LRTI at the Mahatma Gandhi Mission Hospital and Medical College, a tertiary hospital in Navi Mumbai, Maharashtra, India, between December 2017 and November 2019, were studied prospectively. Patients with any other comorbidities were excluded. The severity of respiratory distress at presentation was graded using the Clinical Respiratory score (CRS). Serum electrolytes were sent within 1 hour of hospital admission. Median age of enrolled patients was 14 months. Overall, 23 (16%) children had mild respiratory distress, 97 (66%) had moderate respiratory distress, and 26 (18%) had severe distress. The incidence of hyponatremia in children admitted with LRTI was 66% and majority of them (70%) had mild hyponatremia. The incidence, as well as severity of hyponatremia differed significantly with etiology (p &lt; 0.05). An inverse correlation was found between serum sodium levels and CRS at presentation (r = − 0.26, p = 0.001). In multivariate analyses, parenchymal disease was an independent risk factor for development of hyponatremia (adjusted odds ratio [aOR] = 5.64 (2.52–12.59), p &lt; 0.001). Incidence and severity of hyponatremia in children with LRTI increased with severity of respiratory distress and presence of parenchymal disease.

Comparison of Clinical, Demographic Features, and Costs in Respiratory Syncytial Virus, Rhinovirus, and Viral Co-infections in Children Hospitalized with Viral Infections of the Lower Respiratory Tract.

Viruses are the most common cause of lower respiratory tract infections (LRTIs) in children. Our study aimed to shed light on co-infection by comparing it with the most common single agents, such as respiratory syncytial virus (RSV) and rhinovirus (RV), in terms of epidemiological, clinical, laboratory findings, and cost. This retrospective study analyzed medical records pertaining to infants aged below 5 years, hospitalized with a diagnosis of LRTI with RSV, RV, or co-infection. The study group consisted of 199 children, RSV was detected in 116 patients (58.3%), RV in 46 (23.1%), and co-infections in 37 (18.6%). The average age of patients infected with RV was higher (P = 0.006), and the length of hospital stay of patients infected with RSV was longer (P = 0.03) than that with other agents. There was no significant difference between the groups in terms of oxygen requirement, intensive care unit admission, intubation, and development of complications. The cost was significantly higher in the RSV group (P = 0.02) compared to the other groups. Viral co-infections, RSV, and RV constitute an important part of the etiology in patients aged below 5 years; co-infections do not cause more severe clinical findings compared to single viral agents.

ASSESSMENT OF CASES ADMITTED TO THE NEONATAL INTENSIVE CARE UNIT WITH LOWER RESPIRATORY TRACT INFECTION

OBJECTIVE: The purpose of this study is to assess the clinical features, laboratory findings, diagnosis and treatments of neonates in the neonatal intensive care unit with a diagnosis of lower respiratory tract infection (LRTI).MATERIAL AND METHODS: The data of neonates hospitalized in the neonatal intensive care unit of our hospital between 2017 and 2019 with a diagnosis of LRTI was retrospectively obtained from the file records. Demographical features, diagnosis and treatments were analyzed.RESULTS: A total of 57 patients diagnosed with LRTI were included in the study. The mean gestational age of the patients was 36.8 ± 3 weeks and their mean birth weight was 2864 ± 787 g. The 67% (n = 38) of them were term infants and the 33% (n = 19) of them were preterm infants. When the symptoms, examination findings and chest radiographs of the cases were examined at the time of admission, tachypnea, prolonged expiration, and nutritional difficulty in 67% of cases (n = 38), cough in 26% (n = 15) of the cases, fever in 20% (n = 12) of the cases, vomiting in 12% (n = 7) of the cases, apnea in 7% (n = 4)of the cases, and increased aeration in lung imaging in 21% (n = 12) of the cases were detected. Respiratory panel using Polymenase Chain Reaction (PCR) method was investigated in nasopharyngeal swab samples of 61% (n = 35) of the patients, respiratory syncytial virus (RSV) in 57% (n = 20), rhinovirus in 14% (n = 5), and metapneumovirus in 3% (n = 1) of the cases were observed. The 47% of the patients (n = 27) received high-flow oxygen, 26% (n= 15) nasal CPAP, 58% (n=33) antibiotics, 63% (n= 36) inhaler bronchodilator and hypertonic saline treatment.CONCLUSIONS: In accordance with the literature, a high rate of RSV infection was detected in neonates with LRTI in the neonatal intensive care unit of our hospital. Early diagnosis is important to prevent unnecessary use of antibiotics and to prevent nosocomial infections.

Evaluation of children diagnosed with a lower respiratory tract infection due to Human metapneumovirus.

Human metapneumovirus (hMPV) is one of the leading causes of acute respiratory infections and bronchiolitis in infants. A history of prematurity and chronic diseases such as congenital heart disease or asthma/reactive airway disease (RAD) increases the risk of severe lower respiratory tract infection (LRTI) due to hMPV. In this cross-sectional study, we aimed to analyze the clinical outcome and risk factors for severe disease in children with LRTI due to hMPV. The current cross-sectional study included children between 28 days and 18 years of age with the diagnosis of hMPV-associated LRTI hospitalizations, over two years from January 2016 to September 2018 in Health Science University Dr. Behçet Uz Child Disease and Pediatric Surgery Training and Research Hospital. hMPV virus was detected by the multiplex polymerase chain test (PCR) (Commercial Multiplex Real-Time PCR: FTD Respiratory 21 plus, Fast Track Diagnostics, Luxembourg) from a nasopharyngeal swab. Patients who had positive results in multiplex PCR tests with other viral agents simultaneously were not included in the study. Data were retrospectively collected from the computerized hospital system. In this cross-sectional study, 62 patients who were hospitalized with the diagnosis of LRTI due to hMPV infection were included. Thirty-five (55.7%) of the patients were male. The median age was one year (2 months-15 years). Fifty-one (82.2%) patients were younger than two years. The median hospital length of stay was found to be 10 days (2-33 days) in patients with an underlying disease and 7,5 days (ranging from 2 to 20 days) in the patients without an underlying disease, this difference was significant (p=0.031). Clinicians should consider hMPV as an important pathogen of LRTI even in healthy children, although we expect a poor course of disease in children with an underlying disease.

1337. Medically Attended (MA) Illness Due to Respiratory Syncytial Virus (RSV) Infection among Infants in the United States during the 2016–17, 2017–18, 2018–19, and 2019–20 RSV Seasons: The Need for All-Infant Protection

Abstract Background RSV-associated lower respiratory tract infection (LRTI) is the leading cause of infant hospitalization. Most studies of RSV have focused on infants with underlying comorbidities, including prematurity. The purpose of this analysis is to describe the burden of RSV LRTI across all medical settings and in all infants experiencing their first RSV season. Methods Using de-identified claims data from two commercial (MarketScan Commercial, MSC; Optum Clinformatics, OC) and one public (MarketScan Medicaid, MSM) insurance database, we estimated the prevalence of MA RSV LRTI among infants born between April 1, 2016 and June 30, 2019 in their first RSV season. Estimates were made by gestational age, presence/absence of comorbidities, and setting (inpatient, emergency department and outpatient). Due to limited laboratory testing, we defined MA RSV LRTI using two sets of ICD-10-CM diagnosis codes: a specific definition (identifying RSV explicitly) and a sensitive definition that included unspecified bronchiolitis. The first specific diagnosis triggered a search for another MA RSV LRTI diagnosis (either specific or sensitive) within the next 7 days. In the sensitive analysis, the first diagnosis was allowed to meet the sensitive definition. Setting was recorded as the highest level of care attached to a MA RSV LRTI diagnosis within this 7-day period. Results Using the specific (sensitive) definitions, 4.2% (12.2%), 6.8% (16.8%), and 2.7% (7.2%) of newborns had an MA RSV LRTI diagnosis during their first respiratory season across the MSC, MSM, and OC datasets (Table 1). Term infants without comorbidities accounted for 77% (83%), 79% (86%), and 80 (81%) of all MA RSV LRTI, and 21% (10%), 19% (10%), and 21% (10%) of all infants with MA RSV LRTI had an inpatient hospital stay (Table 2). Term infants without comorbidities accounted for 69% (68%), 67% (79%), and 73% (73%) of all MA RSV LRTI inpatients (Table 2). Conclusion In commercial and public claims data, during their first RSV season, term infants without comorbidities accounted for a sizable majority of inpatient, emergency room, and outpatient encounters for RSV LRTI in the US. To address the burden of RSV LRTI, future RSV prevention efforts should target all infants. Funding Sanofi Pasteur, AstraZeneca Disclosures Jason Gantenberg, MPH, Sanofi Pasteur (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Nicole Zimmerman, MS, IBM Watson Health (Employee, Nicole Zimmerman is an employee of IBM, which was compensated by Sanofi to complete this work.)Sanofi (Other Financial or Material Support, Nicole Zimmerman is an employee of IBM, which was compensated by Sanofi to complete this work.) Andrew R. Zullo, PharmD, PhD, ScM, Sanofi Pasteur (Grant/Research Support, Research Grant or Support) Brendan Limone, PharmD, PharmD, Sanofi Pasteur (Other Financial or Material Support, IBM was contracted by Sanofi to perform analysis) Clarisse Demont, n/a, Sanofi Pasteur (Employee, Shareholder) Sandra S. Chaves, MD, MSc, Sanofi Pasteur (Employee) William V. La Via, MD, AstraZeneca (Shareholder)Sanofi Pasteur (Employee) Christopher Nelson, PhD, Epidemiology, Sanofi Pasteur (Employee) Christopher Rizzo, MD, Sanofi (Employee) David A. Savitz, PhD, Sanofi Pasteur (Grant/Research Support) Robertus Van Aalst, MSc, Sanofi Pasteur (Employee, Shareholder)