Hospitalization For Lower Respiratory Tract Infection Research Articles

Genetic predisposition to high BMI increases risk of early life respiratory infections and episodes of severe wheeze and asthma.

High BMI is an established risk factor for asthma, but the underlying mechanisms remain unclear.Objective: To increase understanding of the BMI-asthma relationship by studying the association between genetic predisposition to higher body mass index (BMI) and asthma, infections, and other asthma-traits during childhood. Data was obtained from the two ongoing COPSAC mother-child cohorts. Polygenic risk score (PRS) for adult BMI were calculated for each child. Replication was done in the large-scale iPSYCH cohort using data on hospitalization for asthma and infections. In the COPSAC cohorts (n=974), the adult BMI PRS was significantly associated with lower respiratory tract infections (LRTI) (IRR 1.20 95% CI 1.08-1.33, FDR=0.005) age 0-3 years and episodes of severe wheeze (IRR 1.30, 1.06-1.60, FDR=0.04) age 0-6 years. LRTI partly mediated the association between the adult BMI PRS and severe wheeze (proportion mediated: 0.59, 0.28-2.24, pACME 2E-16). In contrast, these associations were not mediated through the child's current BMI and the PRS was not associated with an asthma diagnosis or reduced lung function up to age 18. The associations were replicated in iPSYCH (n=114 283), where the adult BMI PRS significantly increased the risk of hospitalizations for LRTI and wheeze or asthma during childhood to age 18 years. Children with genetic predisposition to higher BMI had increased risk of LRTI and severe wheeze, independent of the child's current BMI. These results shed further light on the complex relationship between BMI and asthma.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol

ABSTRACT Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children’s wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6–24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023–377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea.

Lower respiratory tract infections (LRTI) during the first 2 years of life increase the risk of pediatric obstructive sleep apnea (OSA), but whether this risk varies by LRTI severity is unknown. We analyzed data from 2962 children, aged 0-5 years, with early-life LRTI requiring hospitalization (severe LRTI, n = 235), treated as outpatients (mild LRTI, n = 394) and without LRTI (reference group, n = 2333) enrolled in the Boston Birth Cohort. Kaplan-Meier survival estimates and Cox proportional hazards models adjusted by pertinent covariables were used to evaluate the risk of pediatric OSA. Compared to children without LRTI, those with mild LRTI were at a higher risk of having OSA (hazard ratio [HR] 1.44, 95% confidence interval [CI]: 1.01-2.05), and those with severe LRTI were at the highest risk (HR 2.06, 95% CI: 1.41-3.02), independently of relevant covariables (including maternal age, race, gestational age, and type of delivery). Additional risk factors linked to a higher risk of OSA included prematurity (HR 1.34, 95% CI 1.01-1.77) and maternal obesity (HR 1.82, 95% CI 1.32-2.52). The time elapsed between LRTI and OSA diagnosis was similar in mild and severe LRTI cases, with medians of 23 and 25.5 months, respectively (p = .803). Infants with severe early-life LRTI have a higher risk of developing OSA, and surveillance strategies to identify OSA need to be particularly focused on this group. OSA monitoring should continue throughout the preschool years as it may develop months or years after the initial LRTI hospitalization.

Risk of subsequent lower respiratory tract infection (LRTI) after hospitalization for COVID-19 LRTI and non-COVID-19 LRTI: a retrospective cohort study

BackgroundRespiratory pathogens, including SARS-CoV-2, can cause pulmonary structural damage and physiologic impairment, which may increase the risk of subsequent lower respiratory tract infections (LRTI). Prior hospitalization for any reason is a risk factor for LRTI, but data on the risk of subsequent new-onset LRTI following hospitalization for COVID-19 LRTI or non-COVID-19 LRTI are needed to inform strategies for immunizations targeting respiratory pathogens.MethodsWe conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) among adults hospitalized from 3/1/2020 to 5/31/2022, excluding labor and delivery. We categorized individuals into 3 mutually exclusive baseline exposure groups: those hospitalized for COVID-19 LRTI, those hospitalized for non-COVID-19 LRTI, and those hospitalized for all other causes without LRTI or COVID-19 (“non-LRTI”). Following hospital discharge, patients were followed up for new-onset LRTI, beginning 30 antibiotic-free days after hospital discharge until 8/31/2022. We used multivariable cause-specific Cox regression with time-varying covariates to estimate hazard ratios (HR) of new-onset LRTI comparing those hospitalized for COVID-19 LRTI or non-COVID-19 LRTI to those hospitalized for non-LRTI, adjusting for demographic and clinical characteristics.ResultsThe study included 22,417 individuals hospitalized for COVID-19 LRTI, 12,795 individuals hospitalized for non-COVID-19 LRTI, and 176,788 individuals hospitalized for non-LRTI. Individuals hospitalized for non-COVID-19 LRTI were older and had more comorbidities than those hospitalized for COVID-19 LRTI or non-LRTI. Incidence rates per 1,000 person-years (95% CI) of new-onset LRTI were 52.5 (51.4–53.6) among individuals hospitalized for COVID-19 LRTI, 253.5 (243.7–263.6) among those hospitalized for non-COVID-19 LRTI, and 52.5 (51.4–53.6) among those hospitalized for non-LRTI. The adjusted hazard of new-onset LRTI during follow-up was 20% higher among individuals hospitalized for COVID-19 LRTI (HR 1.20 [95% CI: 1.12–1.28]) and 301% higher among individuals hospitalized for non-COVID-19 LRTI (HR 3.01 [95% CI: 2.87–3.15]) compared to those hospitalized for non-LRTI.ConclusionThe risk of new-onset LRTI following hospital discharge was high, particularly among those hospitalized for non-COVID-19 LRTI, but also for COVID-19 LRTI. These data suggest that immunizations targeting respiratory pathogens, including COVID-19, should be considered for adults hospitalized for LRTI prior to hospital discharge.

Optimizing next-generation RSV prevention in Mali: A cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis.

Respiratory syncytial virus (RSV) is the most common cause of early childhood lower respiratory tract infection (LRTI) in low- and middle-income countries (LMICs). Maternal vaccines, birth-dose extended half-life monoclonal antibodies (mAbs), and pediatric vaccines are under development for prevention of respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in young children. We analyzed the health and economic impact of RSV interventions used alone or in combinations in Mali. We modeled age-specific and season-specific risks of RSV LRTI in children through three years, using WHO Preferred Product Characteristics and data generated in Mali. Health outcomes included RSV LRTI cases, hospitalizations, deaths, and disability-adjusted life-years (DALYs). We identified the optimal combination of products across a range of scenarios. We found that mAb delivered at birth could avert 878 DALYs per birth cohort at an incremental cost-effectiveness ratio (ICER) of $597 per DALY averted compared to no intervention if the product were available at $1 per dose. Combining mAb with pediatric vaccine administered at 10/14 weeks, 1947 DALYs would be prevented. The ICER of this combination strategy is $1514 per DALY averted compared to mAb alone. Incorporating parameter uncertainty, mAb alone is likely to be optimal from the societal perspective at efficacy against RSV LRTI above 66%. The optimal strategy was sensitive to economic considerations, including product prices and willingness-to-pay for DALYs. For example, the combination of mAb and pediatric vaccine would be optimal from the government perspective at a willingness-to-pay above $775 per DALY. Maternal vaccine alone or in combination with other interventions was never the optimal strategy, even for high vaccine efficacy. The same was true for pediatric vaccine administered at 6/7 months. At prices comparable to existing vaccine products, extended half-life RSV mAbs would be impactful and efficient components of prevention strategies in LMICs such as Mali.

Association of ambient carbon monoxide exposure with hospitalization risk for respiratory diseases: A time series study in Ganzhou, China.

Ambient carbon monoxide (CO) exposure is associated with increased mortality and hospitalization risk for total respiratory diseases. However, evidence on the risk of hospitalization for specific respiratory diseases from ambient CO exposure is limited. Data on daily hospitalizations for respiratory diseases, air pollutants, and meteorological factors from January 2016 to December 2020 were collected in Ganzhou, China. A generalized additive model with the quasi-Poisson link and lag structures was used to estimate the associations between ambient CO concentration and hospitalizations of total respiratory diseases, asthma, chronic obstructive pulmonary disease (COPD), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), and influenza-pneumonia. Possible confounding co-pollutants and effect modification by gender, age, and season were considered. A total of 72,430 hospitalized cases of respiratory diseases were recorded. Significant positive exposure-response relationships were observed between ambient CO exposure and hospitalization risk from respiratory diseases. For each 1 mg/m3 increase in CO concentration (lag0-2), hospitalizations for total respiratory diseases, asthma, COPD, LRTI, and influenza-pneumonia increased by 13.56 (95% CI: 6.76%, 20.79%), 17.74 (95% CI: 1.34%, 36.8%), 12.45 (95% CI: 2.91%, 22.87%), 41.25 (95% CI: 18.19%, 68.81%), and 13.5% (95% CI: 3.41%, 24.56%), respectively. In addition, the associations of ambient CO with hospitalizations for total respiratory diseases and influenza-pneumonia were stronger during the warm season, while women were more susceptible to ambient CO exposure-associated hospitalizations for asthma and LRTI (all P < 0.05). In brief, significant positive exposure-response relationships were found between ambient CO exposure and hospitalization risk for total respiratory diseases, asthma, COPD, LRTI, and influenza-pneumonia. Effect modification by season and gender was found in ambient CO exposure-associated respiratory hospitalizations.

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.

94. Pooled analysis of nirsevimab resistance through 150 days post dose in preterm and term infants

Abstract Background Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection (LRTI) and hospitalization in infants. In two global pivotal placebo-controlled studies, nirsevimab, a monoclonal antibody to the RSV prefusion (F) protein with extended half-life, reduced medically attended (MA) RSV LRTI versus placebo throughout the RSV season (MELODY (Primary Cohort)/Study 3 (Proposed Dose) Pool, 79.5% efficacy). Here we summarize resistance analyses of all RT-PCR-confirmed RSV isolates from healthy term and preterm infants through 150 days post dose. Methods Infants were randomized 2:1 to receive one intramuscular injection of nirsevimab or placebo, prior to their first RSV season. RT-PCR-confirmed RSV isolates were reflexed for genotypic analyses of RSV F and phenotypic analyses of identified substitutions in a recombinant RSV neutralization susceptibility assay. Results In the pooled proposed dose analysis of Study 3 (50 mg nirsevimab if &amp;lt; 5 kg at dosing) and MELODY (50 or 100 mg nirsevimab if &amp;lt; 5 kg or ≥5 kg at dosing, respectively), no subject with MA RSV LRTI had an RSV isolate containing nirsevimab resistance-associated substitutions in either treatment group (nirsevimab, RSV A: 0/14 and RSV B: 0/5; placebo, RSV A: 0/35 and RSV B: 0/16). In Study 3 (50 mg nirsevimab if ≥5 kg at dosing), 2/18 subjects in the nirsevimab group and 0/20 subjects in the placebo group with MA RSV LRTI had an RSV isolate harbouring nirsevimab binding site substitutions I64T+K68E+I206M+Q209R (&amp;gt;447-fold) or N208S (&amp;gt;387-fold) that conferred reduced susceptibility to nirsevimab neutralization (nirsevimab, RSV A: 0/9 and RSV B: 2/9; placebo, RSV A: 0/10 and RSV B: 0/10). Subjects with RSV isolates harboring F protein sequence variations that maintained susceptibility to nirsevimab neutralization were balanced between treatment groups with no association with RSV disease severity. No subjects with non-protocol defined MA RSV LRTI cases or hospitalization due to any RSV respiratory illness had an RSV isolate conferring nirsevimab resistance. Conclusion Lack of nirsevimab resistance following immunization at the proposed dose supports efficacy and neutralization activity of nirsevimab against both RSV A and B strains throughout the RSV season. Disclosures Michael E. Abram, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Bahar Ahani, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds David E. Tabor, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Fiona Fernandes, PhD, AstraZeneca: Stocks/Bonds Deidre Wilkins, BSC, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Anastasia A. Aksyuk, PhD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Kevin M. Tuffy, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Hong Ji, BSc, AstraZeneca: Stocks/Bonds Christine Blaze, BSc, AstraZeneca: Stocks/Bonds Tyler Brady, MS, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Pamela Griffin, MD, AstraZeneca: Stocks/Bonds Amanda Leach, MD, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Tonya L. Villafana, PhD, MPH, AstraZeneca: Employee|AstraZeneca: Stocks/Bonds Mark T. Esser, PhD, AstraZeneca: Stocks/Bonds.

Effect of the COVID-19 Pandemic on Lower Respiratory Tract Infection Determinants in Thai Hospitalized Children: National Data Analysis 2015-2020.

Background: The COVID-19 outbreak emerged in January 2020 and remains present in 2022. During this period, nonpharmaceutical interventions (NPIs) have been used to reduce the spread of COVID-19 infection. Nationwide data analysis should be pushed as the new standard to demonstrate the impact of COVID-19 infection on other respiratory illnesses and the reliability of NPIs during treatment. Objective: This study aims to identify and compare the incidence of lower respiratory tract infections (LRTIs) among children in Thailand before and after the emergence of COVID-19. Methods: A retrospective study was carried out in hospitalized children under the age of 18 in Thailand from October 2015 to September 2020. The International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification, was used to identify patient diagnoses (ICD-10-TM). The data were extracted from the Universal Coverage Health Security Scheme Database. Results: A total of 1,610,160 admissions were attributed to LRTIs. The most common diagnosis was pneumonia (61.9%). Compared to the 2019 fiscal year, the number of hospitalizations due to LRTIs decreased by 33.9% in the 2020 fiscal year (COVID-19 period) (282,590 vs. 186,651). The incidence of all three diagnostic groupings was substantially lower in the pre- and post-COVID-19 eras, with a decrease of 28% in the pneumonia group (incidence rate ratio (IRR) = 0.72; 95% confidence interval (CI): 0.71 to 0.72), 44% in the bronchiolitis group (IRR = 0.56; 95% CI: 0.55 to 0.57), and 34% in the bronchitis group (IRR = 0.66; 95% CI: 0.65 to 0.67). Between fiscal years 2019 and 2020, the overall monthly cost of all hospitalizations for LRTIs decreased considerably (p value < 0.001). Conclusions: NPIs may decrease the number of pediatric hospitalizations related to LRTIs. All policies designed to prevent the spread of COVID-19 must be continually utilized to maintain the prevention of LRTIs.

Risk Factors of Very Severe RSV Infections in a Multicenter Cohort of Very Preterm and Extreme Preterm Babies Receiving or Not Palivizumab.

IntroductionPreterm infants are at risk of lower respiratory tract infections (LRTI), including Respiratory Syncytial Virus (RSV) associated bronchiolitis, for which palivizumab prophylaxis can be proposed. Our aim was to determine risk factors of very severe RSV disease in children born before 34 weeks of gestation.MethodsAmong 2,101 infants born before 34 weeks of gestation in 3 maternity wards between 2012 and 2017, the laboratory confirmed RSV-infected patients requiring hospitalization before 12 months of corrected age were retrospectively included. We collected data about the neonatal period, the palivizumab prophylaxis and the hospitalization for a RSV-related LRTI. LRTI was considered as very severe (VS-LRTI) when patients required invasive or non-invasive positive pressure ventilation.ResultsAmong 86 included patients, 31 met the criteria of VS-LRTI. The VS-LRTI patients had a higher birth gestational age and weight but less heart disease and bronchopulmonary dysplasia. They received palivizumab prophylaxis less frequently than the other patients but the difference was not significant. At the onset of infection, VS-LRTI patients had a younger corrected age for prematurity and presented more frequently with apnea, bradycardia, life-threatening event, hemodynamic failure, hypercapnia. Using logistic regression, the main factor associated with VS-LRTI was a younger corrected age for prematurity at the onset of infection [Odd ratio for each month of corrected age = 0.77 (0.62; 0.93), p = 0.012].ConclusionInfants at the highest risk of VS-LRTI were infants with a younger corrected age for prematurity. Therefore, a better targeting of infants requiring palivizumab prophylaxis and early interventions at hospital discharge could limit VS-LRTI in these infants.

Ischemic Heart Disease and Chronic Obstructive Pulmonary Disease Hospitalizations in Japan Before and After the Introduction of a Heated Tobacco Product.

To substantiate the beneficial effects of switching from cigarette smoking to heated tobacco products (HTP), this study conducted a time-trend analysis using data from the Japanese Medical Data Center (JMDC) database. Specifically, we assessed hospitalization numbers for chronic obstructive pulmonary disease (COPD) exacerbations and acute ischemic heart disease (IHD) before and after the introduction of HTPs in the Japanese market. This study replicated a previous study using a different Japanese real-world data source (Medical Data Vision). We retrieved the number of hospitalizations associated with the International Classification of Diseases-10 codes for COPD and IHD from 2010 to 2019−5 years before to 4 years after introducing HTPs in the Japanese market—from the JMDC database. Then, we used interrupted time-series analyses to test the hypothesis that the introduction of HTPs is associated with a reduction in hospitalizations for COPD (all codes), COPD exacerbation, COPD exacerbation plus lower respiratory tract infections (LRTI), and IHD, adjusting for age, sex, seasonality, and flu vaccination rates. Analysis of all available data from the JMDC database revealed a significant reduction in the number of hospitalizations for COPD (all codes; P = 0.0001) and IHD using Diagnosis Procedure Combination data on causative disease flags (P < 0.00001). We also observed a non-significant reduction in hospitalizations for COPD plus LRTI as well as IHD after HTP introduction in Japan. This study confirmed the findings of our previous study where a decrease in hospitalizations due to COPD exacerbation after the introduction of HTPs in Japan was also shown. Nevertheless, these findings warrant further research to evaluate the impact of HTPs on the health of populations in other countries where these products have been introduced.

Incidence and Estimated Vaccine Effectiveness Against Hospitalizations for All-Cause Pneumonia Among Older US Adults Who Were Vaccinated and Not Vaccinated With 13-Valent Pneumococcal Conjugate Vaccine

Following routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in children in 2010, invasive pneumococcal disease rates have decreased substantially in children and adults. In 2014, the Advisory Committee for Immunization Practices recommended routine use of PCV13 among adults aged 65 years or older; previously only 23-valent pneumococcal polysaccharide vaccine (PPV23) was recommended. To estimate the association between the incidence of hospitalized all-cause pneumonia and lower respiratory tract infections (LRTI) and PCV13 vaccination among older adults at Kaiser Permanente Northern California (KPNC). This retrospective cohort study included adults at KPNC aged 65 years or older between July 1, 2015, and June 30, 2018, born after 1936 with no known history of PPV23 or PCV13 receipt before age 65. The study took place at an integrated health care system with an annual membership more than 4 million individuals, approximately 15% of whom are 65 years or older and broadly representative of the region. Data analysis took place from July 2018 to December 2021, and data collection took place from November 2016 to June 2018. PCV13 vaccination status was ascertained from the electronic medical record (EMR). Individuals were considered vaccinated 14 days following immunization. First hospitalized all-cause pneumonia was identified in the EMR using primary/secondary discharge diagnosis International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. First hospitalized LRTI was identified using pneumonia codes and acute bronchitis codes. Relative risk (RR) of first pneumonia or LRTI hospitalization of individuals who were PCV13 vaccinated vs PCV13 unvaccinated was estimated using Poisson regressions adjusted for sex, race, ethnicity, age, influenza vaccine receipt, PPV23 receipt since age 65, pneumonia risk factors, health care use, and season. Vaccine effectiveness (VE) was estimated as (1-RR) × 100%. Of 192 061 adults, 107 957 (56%) were female and 139 024 (72%) were White individuals. PCV13 coverage increased from 0 in 2014 to 135 608 (76.9%) by 2018. There were 3488 individuals with 3766 pneumonia hospitalizations and 3846 individuals with 4173 LRTI hospitalizations. PCV13 was associated with an adjusted VE of 10.0% (95% CI, 2.4-17.0; P = .01) against hospitalized pneumonia and 9.4% (95% CI, 2.1-16.1; P = .01) against hospitalized LRTI. In the context of a robust pediatric PCV13 immunization program, PCV13 vaccination of adults aged 65 years or older was associated with significant reductions in hospitalizations for all-cause pneumonia and LRTI. Vaccinating older adults with PCVs may provide broader public health benefit against pneumonia hospitalizations.

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.

1346. The Risk of Readmission after RSV Hospitalization Among Children Younger than 5 Years

Abstract Background Respiratory Syncytial Virus (RSV) is one of the most common causes of childhood lower respiratory tract infection (LRTI) leading to hospitalization worldwide. Readmissions following viral LRTI hospitalization are common, however rates, timing and causes of readmission following RSV LRTI hospitalization are understudied. We evaluated readmissions occurring during 1-year post-discharge of RSV hospitalization. Methods We prospectively identified children &amp;lt; 5 years of age hospitalized with laboratory-confirmed RSV LRTI at Primary Children’s and Riverton hospitals in Salt Lake City, Utah during the 2019-2020 RSV season. An electronic alert system identified all-cause readmission between November 2019 and April 2021. Discharge diagnoses of readmissions were reviewed by two pediatricians. We calculated the incidence rate of all-cause and respiratory-related readmission. Results A total of 297 children had laboratory-confirmed RSV LRTI hospitalizations during the 2019-2020 RSV season, with 24% admitted to the intensive care unit (ICU) during index RSV hospitalization and 24% having a chronic medical condition. During the 1-year follow-up period, 59 readmissions occurred among 47 patients (Table 1). The incidence rate of all-cause and respiratory-related readmission was 19.9 (95%CI 15.5-24.9) and 13.1 (95%CI 9.5-17.5) per 100 patients, respectively. Median age of readmitted patients was 11 months (interquartile range 5.9-11 months). Median number of readmissions was 1 (range: 1-4), with initial readmissions occurring within 28 days (median) of index admission; most (74%) due to a respiratory-related illness. Second and 3rd admissions were less common and occurred at 67 (median) and 160 (median) days respectively. During all readmissions, 19% of children required ICU admission and 25% had chronic medical conditions. Conclusion All cause and respiratory readmission after Initial hospitalization with RSV LRTI commonly occurred among children &amp;lt; 5 years. These data support the need for RSV vaccines and immunoprophylaxis to prevent RSV hospitalization. A further study with a control group is needed to determine the role of RSV in readmission. Disclosures Yoonyoung Choi, PhD, MS, RPh, Merck (Employee) Lyn Finelli, DrPH, MS, Merck (Employee)

Epidemiology of acute lower respiratory tract infection hospitalizations in Thai children: A 5-year national data analysis.

BackgroundLower respiratory tract infections (LRTIs) are the most common cause for hospitalization in pediatric patients. Pediatric patients with LRTIs are at an increased risk of morbidity and mortality. The national data analysis of epidemiologic variations facilitates awareness and develops solutions to prevent these conditions in the future.ObjectiveThis study aims to evaluate the epidemiology, causative pathogens, morbidity, and mortality of LRTIs in pediatric patients of Thailand from 2015 to 2019.MethodsThis was a retrospective study among pediatric patients aged between 0 and 18 years old admitted in hospitals due to LRTIs in Thailand from January 2015 to December 2019. The data were extracted from National Health Security Office using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification; ICD‐10‐TM of J09 to J22.ResultsA total of 1,423,509 children hospitalized due to LRTIs were identified. Most of the patients were of age 1–5 years. Pneumonia was the most common LRTI (876,557 children, 61.58%) in hospitalized children. Respiratory syncytial virus (RSV) is the main etiologic pathogen of bronchiolitis, which presents in approximately 10.86% of all episodes. Influenza viruses were found predominantly in children with pneumonia (15.52%). The mortality rate since 2015–2019 was highest in pneumonia under 1 year old (P < 0.001). Pneumonia in children under 5 years old had the highest mortality rate, which accounted for 11.85 per 100,000 children in 2019.ConclusionsLRTIs had a high incidence rate of hospitalization and mortality, especially in children under 5 years old. Influenza virus was the most common pathogen of pneumonia.

Lower respiratory tract infection hospitalizations among American Indian/Alaska Native adults, Indian Health Service and Alaska Region, 1998–2014

Objectives: This study describes the changes in lower respiratory tract infection (LRTI) rates from 1998 to 2014 among hospitalized American Indian/Alaska Native (AI/AN) adults residing in Alaska and other Indian Health Service (IHS) regions.Methods: Age-adjusted hospital discharge rates and rate ratios were calculated from the IHS Direct and Contract Health Services Inpatient Dataset, IHS National Patient Information Reporting System for AI/AN adults ≥18 years, hospitalized at an IHS-operated, tribally operated, or contract hospital with an LRTI-associated diagnosis during 1998–2014.Results: Overall, there were 13 733 LRTI-associated hospitalizations in Alaska (1998–2014), with an age-adjusted rate of 13.7/1000 adults. Among non-Alaska (non-AK) AI/AN, there were a total of 79 170 hospitalizations, with a rate of 8.6/1000 adults. In the pre-PCV7 and pre-PCV13 periods, LRTI rates were higher in Alaska (AK) AI/AN (12.4 and 14.1, respectively) when compared to non-AK AI/AN (10.1 and 9.1, respectively) (P < 0.0001). In the post-PCV7 and post-PCV13 periods, LRTI rates were also higher in AK (13.5 and 15.0, respectively) compared to non-AK (9.2 and 7.3, respectively) (P < 0.0001).Conclusions: Over the study period, a 26% increase in rates of LRTI among adult AI/AN residing in AK compared with a 38% decrease in rates among AI/AN residing in non-AK were observed. This disparity is likely due to a variety of factors such as tobacco use, crowding, etc. Strategies to reduce LRTI in AI/AN adults are needed.

Serious infections and cardiovascular complications among patients with chronic lymphocytic lymphoma treated with first-line ibrutinib or bendamustine/rituximab.

e19503 Background: Clinical trials have shown positive outcomes associated with ibrutinib monotherapy (IM) and bendamustine / rituximab combination (BR) therapy in patients with chronic lymphocytic lymphoma (CLL) compared to other standard treatments, but limited real-world data exist. This study evaluated serious infections and cardiovascular complications in CLL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients were diagnosed with CLL, treatment naïve, and continuously enrolled for ≥12 months prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions between the treatment groups were tested. Multivariate logistic regression models for lower respiratory tract infection (LRTI) and atrial fibrillation (AF) were also conducted to determine the adjusted odds of hospitalization. Results: Of 2,138 CLL patients, 810 had IM and 512 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older and more likely to have had an LRTI during baseline compared to BR patients, otherwise both groups had similar baseline characteristics. Hospitalization for serious infections was more common during follow-up among IM patients than BR patients (17.7% vs. 13.1%; p = 0.027). Specifically, 10.2% of IM patients had a bacterial infection hospitalization compared to 5.7% of BR patients (p = 0.004) and 10.7% of IM patients had a LRTI hospitalization compared to 6.6% of BR patients (p = 0.012). After adjusting for baseline characteristics, IM patients did not have significantly higher odds of a LRTI hospitalization (OR = 1.51; p = 0.069). Hospitalization for cardiovascular complications was more common during follow-up among IM patients than BR patients (18.3% vs. 11.9%; p = 0.002). Specifically, 8.4% of IM patients had an AF-related hospitalization versus 2.7% of BR patients (p &lt; 0.001). After adjusting for baseline characteristics, IM patients were more likely to have a hospitalization for AF versus BR patients (OR = 3.89; p &lt; 0.001). Conclusions: In a real-world setting, serious infections and cardiovascular complications were more common among CLL patients treated with first-line IM compared to BR during 12 months of follow-up. IM patients were more likely than BR patients to have an inpatient admission due to AF after adjusting for other patient characteristics.

Real-world incidence and costs of serious infections and cardiovascular complications among patients with indolent non-Hodgkin lymphoma treated with first-line ibrutinib or bendamustine/rituximab.

e19528 Background: Patients with Indolent non-Hodgkin lymphoma (iNHL) have shown positive outcomes with ibrutinib monotherapy (IM) as well as bendamustine/rituximab combination (BR) therapy, but no studies have reported on patient outcomes using real-world data. The current analysis evaluated serious infections and cardiovascular complications in iNHL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients included in the study were diagnosed with iNHL, were treatment naïve, and were continuously enrolled for ≥12 months both prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) and associated inpatient costs were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions and costs (reported per patient per month [PPPM]) between the groups were tested. Results: Of 1,948 iNHL patients, 147 had IM and 1,058 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older, more often male, and more likely to have had a lower respiratory tract infection (LRTI) or atrial fibrillation (AF) during baseline compared to BR patients, otherwise the groups had similar baseline characteristics. Hospitalization for serious infections was similar for IM and BR patients during the follow-up period (17.0% vs. 14.4%; p = 0.397); among hospitalized patients, the IM and BR groups incurred similar PPPM inpatient costs ($2,839 vs. $3,954; p = 0.188). Specifically, 7.5% of IM patients had a bacterial infection hospitalization and incurred $2,561 PPPM vs 7.6% of BR patients who incurred $3,975 PPPM (both p &gt; 0.05); 8.8% of IM patients had a LRTI hospitalization and incurred $3,629 PPPM vs 6.1% of BR patients who incurred $4,980 PPPM (both p &gt; 0.05). Hospitalization for cardiovascular complications was similar during follow-up for IM and BR patients (15.6% vs. 12.2%; p = 0.237); among hospitalized patients, the IM and BR groups incurred similar PPPM costs ($3,777 vs. $3,862; p = 0.948). Specifically, 7.5% of IM patients had a hospitalization for AF and incurred $4,481 PPPM vs 3.6% of BR patients who incurred $4,860 PPPM (p = 0.025 and p = 0.875, respectively). Conclusions: In a real-world setting, serious infections and cardiovascular complications requiring hospitalization, including associated costs, were similar among iNHL patients treated with first-line IM or BR over 12 months, although IM patients were more likely to have an AF-related complication.

Incidence, risk factors, and viral etiology of community-acquired acute lower respiratory tract infection among older adults in rural north India.

BackgroundThere are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries.MethodsWe established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls.ResultsWe followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively.ConclusionIn this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

Does seafarers' limited access to health care increase risk for community-acquired pneumonia requiring hospital care? A longitudinal register-based analysis.

Limited access to medical care can be considered as an occupational risk of seafaring and it may predispose to developing community-acquired pneumonia (CAP) requiring hospital care. We sought to investigate the risk for CAP and other lower respiratory tract infections (LRTI) requiring hospital care among seafarers. We examined the length of hospital stay (LOS) as a proxy for severity of illness. The study population in this panel data analysis were all seafarers and a 20% random sample of economically active individuals aged 18-65 years who were residing in Denmark in 1997-2016, constituting more than 11 million person-years of follow-up. Annually-registered socio-demographic and work characteristics were linked to data on cause of hospital admissions. We used fixed-effects and zero-truncated Poisson regression to estimate the rate ratios of hospitalization for CAP and other LRTI, and compared LOS across the two populations. The adjusted incident rate ratio (IRR) for CAP in seafarers compared to the economically active population was 1.42 (95% confidence interval [CI]: 1.15-1.77), whereas the IRR was 0.73 (95% CI: 0.38-1.42) for other LRTI. For LOS, the IRRs for CAP and other LRTI in seafarers were 1.08 (95% CI: 1.04-1.12) and 0.92 (95% CI: 0.83-1.01), respectively. Our findings indicate that seafaring was associated with an increased risk for CAP requiring hospital care. Limited access to health care may be an important contributing factor.