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Viral Bronchiolitis in Children
Abstract
Few diseases have a greater effect on the health of young children than viral lower respiratory tract illness. Approximately 800,000 children in the United States, or approximately 20% of the annual birth cohort, require outpatient medical attention during the first year of life because of illness caused by respiratory syncytial virus (RSV).(1) Between 2% and 3% of all children younger than 12 months of age are hospitalized with a diagnosis of bronchiolitis, which accounts for between 57,000 and 172,000 hospitalizations annually.(1-4) Estimated nationwide hospital charges for care related to bronchiolitis in children younger than 2 years of age exceeded $1.7 billion in 2009.(5) Globally, in 2005, RSV alone was estimated to cause 66,000 to 199,000 deaths among children younger than 5 years of age, with a disproportionate number of these deaths occurring in resource-limited countries.(6,7) In the United States, by contrast, bronchiolitis due to RSV accounts for fewer than 100 deaths in young children annually.(8) This review describes the current understanding of bronchiolitis, including the increasing number of viruses that are known to cause it, the current understanding of its pathogenesis, the importance of environmental and host genetic factors, and the roles of season, race, and sex in bronchiolitis attack rates and subsequent episodes of wheezing. In addition, guidelines from the American Academy of Pediatrics regarding the diagnosis, management, and prevention of bronchiolitis are summarized.(9,10)
... Acute bronchiolitis is a viral infection of the lower respiratory tract in children and is one of the most common reasons for hospitalization in children aged 2 to 24 months (1). Respiratory Syncytial Virus (RSV) is the most common pathogen responsible for Acute bronchiolitis (1,2). ...
... According to American Academy of Pediatrics guidelines, the diagnosis of bronchiolitis is clinical, based on history and physical examination, signs, and symptoms (2). Symptoms include cough and coryza, shortness of breath, tachypnea, nasal flaring, chest retractions, wheezing, and/or crackles, followed by a viral upper respiratory infection (3,4). ...
... Acute bronchiolitis is one of the most common reasons for hospitalization in children 2-24 months of age (1,2). Unnecessary chest radiographs are taken in over 40% of cases (7,8), although chest X-ray (CXR) is only indicated in severe cases or cases with risks of pulmonary complications (1,2). ...
Background: This study was performed to determine the relationship between chest X-ray findings and the severity of bronchiolitis using the modified Tal score scale (MTS). Methods: This retrospective study was conducted among 999 children aged 2-24 months admitted to a referral teaching hospital in Isfahan, Iran. The severity of bronchiolitis was determined by MTS criteria, with scores ranging from 0 to 12. We considered scores 0-5 mild, 6-9 moderate, and 10-12 severe bronchiolitis. The patient's CXRs were also extracted from the hospital's picture archiving and communication system (PACS) and reported by an expert Pediatric radiologist. The radiologic findings were compared with the MTS criteria. Results: The mean (SD) of the MTS score in the patients was 4.58 ± 1.92. Overall, 757 patients (75.78%) had normal radiographies. The frequency of normal radiography was 75.3% in the group of mild bronchiolitis and 77.3% in the group of moderate bronchiolitis. Reports of 9 patients with severe disease showed that 6 of them had normal CXRs (66.7%), 2 had hyperinflation, and 1 had atelectasis. There was no statistically significant relationship between radiographic results and the severity of bronchiolitis, according to MTS criteria (P = 0.23). The agreement between radiographic results and the severity of bronchiolitis was very weak (0.004) without statistical significance (P = 0.632). Conclusion: Considering that 99.3% of children with bronchiolitis do not have significant findings in chest X-rays, routine chest X-ray is not recommended in these patients.
... [1,2] Respiratory syncytial virus (RSV) is the commonest cause of pneumonia (20 -40%) and bronchiolitis (40 -80%) in children, particularly those aged <1 year. [3][4][5][6][7] RSV is a single-stranded RNA virus in the Pneumoviridae family, exhibiting two antigenic types, RSV A and RSV B, which vary by season and region. [8] The RSV genome encodes 11 proteins (two non-structural and nine structural), each contributing to the virus's virulence. ...
... [12] Further management includes maintaining adequate hydration and avoidance of unnecessary antibiotics, steroids and nebulisation. [3] The immediate goal to reduce the RSV burden is prevention of severe RSV-LRTI and RSV-associated hospitalisation. Until recently, prevention of RSV-LRTI has largely been non-existent in LMIC ...
... [14,15] The American Academy of Pediatrics has recommended administration of palivizumab during the RSV season to infants aged <12 months who are at high risk of severe disease, i.e. those born before 29 weeks' gestation, and to children aged <2 years with haemodynamically significant congenital heart disease or chronic lung disease of prematurity. [3] In 2023, the US Food and Drug Administration and the European Medicines Agency (EMA) approved the use of a new-generation long-acting monoclonal antibody and a maternal RSV vaccine as strategies to reduce the burden of RSV-LRTI in infants, both of which are being considered for licensure in SA. Nirsevimab, a longacting monoclonal antibody with a half-life of ~71 days, is directed against site Ø of the RSV F protein. ...
... Preterm infants, having missed the third trimester maternal IgG transfer, face an increased risk of severe RSV infection (Meissner, 2016). Young children's smaller bronchial lumens and larger surface area-to-volume ratios increase their susceptibility to severe RSV infection (Griffiths et al., 2017). ...
... The inflammatory host immune response primarily causes airway damage in the bronchi and bronchioles (Meissner, 2016;Griffiths et al., 2017), leading to lower airway obstruction due to swelling, mucus, and cell debris instead of bronchospasm (Xing and Proesmans, 2019). ...
... Humoral immune response and Th1 cell-mediated response collaborate to generate neutralizing antibodies that prevent RSV infection, control viral replication, and promote clearance (Meissner, 2016;Griffiths et al., 2017). ...
Human respiratory syncytial virus (hRSV) remains a leading cause of morbidity and mortality in infants, young children, and older adults. hRSV infection's limited treatment and vaccine options significantly increase bronchiolitis' morbidity rates. The severity and outcome of viral infection hinge on the innate immune response. Developing vaccines and identifying therapeutic interventions suitable for young children, older adults, and pregnant women relies on comprehending the molecular mechanisms of viral PAMP recognition, genetic factors of the inflammatory response, and antiviral defense. This review covers fundamental elements of hRSV biology, diagnosis, pathogenesis, and the immune response, highlighting prospective options for vaccine development.
... Bronchiolitis is an acute viral inflammation of the bronchioles and is a leading cause of hospitalisations in young children. 1 Respiratory syncytial virus (RSV) is the most common causative agent of infection, accounting for 50-80% of bronchiolitis cases. 2 Approximately 2-3% of all children younger than 12 months of age are hospitalised with a diagnosis of bronchiolitis. 3 Bronchiolitis is associated with substantial morbidity in both inpatient and outpatient settings. 4 Most children hospitalised with acute bronchiolitis do not require further escalation of treatment, however, approximately 2-6% require admission to a paediatric intensive care unit (PICU), with 2-3% requiring invasive mechanical ventilation. ...
... [13][14][15][16] These serve as a guide for management; however, recommended treatments remain essentially supportive with emphasis placed on ensuring adequate hydration and oxygen supplementation as needed. 3,13 Despite evidence-based guidelines for the treatment of bronchiolitis, wide variations in practice remain, including marked variability in the inpatient management of bronchiolitis across different sites. 17 The aim of the present study was to systematically identify and characterise the current body of evidence available on the management options for patients with severe bronchiolitis who required escalation of treatment to a PICU setting. ...
Aim
Systematically review the management of infants with severe bronchiolitis in a paediatric intensive care unit (PICU) setting with a focus on high-risk infants to identify gaps in evidence-based knowledge.
Methods
This systematic review utilised Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) to examine the literature on the PICU management of bronchiolitis in infants <24 months old. Three databases, Embase, PubMed and Medline, were searched and higher levels of evidence I, II and III were included.
Results
There were 455 papers reviewed and 26 met the inclusion criteria. Furthermore, 19 of these studied respiratory interventions such as positive airway pressure and oxygen delivery. The remaining 7 examined: erythropoietin, caffeine, dexamethasone, protein supplementation, ribavirin, respiratory syncytial virus immune globulin, or diuretic therapy. Of the 26 studies, 20 excluded infants with high-risk conditions. Therapies showing favourable outcomes included Heliox, prophylactic dexamethasone pre-extubation, protein supplementation, and diuretic use.
Conclusions
Clinical trials for bronchiolitis management frequently exclude high-risk children. Innovative study design in the future may improve access to clinical trials for the management of bronchiolitis in high-risk infants in a PICU setting.
Impact
Clinical trials for bronchiolitis management frequently exclude high-risk children.
We review the evidence base for the management of an under-investigated patient demographic in the setting of acute bronchiolitis.
Randomised controlled trials are needed to determine the efficacy of management strategies for bronchiolitis in high-risk infants in a paediatric intensive care setting.
... Viral respiratory tract infections affect young children worldwide, annually leading to high hospitalization rates, increased health-care burdens, and even death. 1,2 Vulnerable populations, such as premature infants-especially those born weighing less than 1000 gramsare at high risk for infection-related morbidities and mortality. 3 A significant burden for premature infants is their heightened susceptibility to respiratory viral infections, resulting in higher hospitalization and intensive care admission rates, prolonged hospital stays, and more invasive and extended respiratory support compared to term infants. ...
... Sloughed nasal cells are inhaled and carried into the lower airways, leading to bronchiolitis. 1,15 Thus, the nasal epithelium represents the "gatekeeper" in the progression of severe RSV. The nasal immune response to respiratory viruses in preterm infants appears to be altered, as evidenced by attenuated and imbalanced nasal cytokine responses, 16 rendering nasal epithelial cells a promising target for deciphering underlying molecular and cellular mechanisms. ...
Background and objectives
Viral respiratory infections significantly affect young children, particularly extremely premature infants, resulting in high hospitalization rates and increased health‐care burdens. Nasal epithelial cells, the primary defense against respiratory infections, are vital for understanding nasal immune responses and serve as a promising target for uncovering underlying molecular and cellular mechanisms.
Methods
Using a trans‐well pseudostratified nasal epithelial cell system, we examined age‐dependent developmental differences and antiviral responses to influenza A and respiratory syncytial virus through systems biology approaches.
Results
Our studies revealed differences in innate‐receptor repertoires, distinct developmental pathways, and differentially connected antiviral network circuits between neonatal and adult nasal epithelial cells. Consensus network analysis identified unique and shared cellular‐viral networks, emphasizing highly relevant virus‐specific pathways, independent of viral replication kinetics.
Conclusion
This research highlights the importance of nasal epithelial cells in innate antiviral immune responses and offers crucial insights that allow for a deeper understanding of age‐related differences in nasal epithelial cell immunity following respiratory virus infections.
... While bronchiolitis is generally considered as a self-limiting condition and the majority of children suffering from bronchiolitis can be treated as outpatients, an estimated 1-2% of all children require hospitalization due to bronchiolitis during their first 24 months of life, and furthermore, up to 10-15% of the overall hospitalizations of children under 24 months are directly linked to bronchiolitis [2]. Additionally, a significant portion of the global mortality in young children, particularly in infants, resulting from an acute respiratory tract infection, is attributed to viral bronchiolitis [2][3][4]. While the general infant mortality rate has decreased, the bronchiolitis-associated rate of mortality has remained relatively stable [2,5]. ...
... While the general infant mortality rate has decreased, the bronchiolitis-associated rate of mortality has remained relatively stable [2,5]. The risk of severe bronchiolitis has been associated with respiratory syncytial virus (RSV) infection, prematurity, ages under 6 months, exposure to tobacco smoke, congenital heart defects, and Down syndrome [4][5][6]. ...
Wheezing children infected with rhinovirus (RV) have a markedly increased risk of subsequently developing recurrencies and asthma. No previous studies have assessed the association between cytokine response and the severity of acute illness in the first wheezing episode in children infected with RV. Forty-seven children treated both as inpatients and as outpatients infected with RV only, aged 3–23 months, with severe first wheezing episodes were recruited. During acute illness, peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with anti-CD3/anti-CD28 in vitro. A multiplex ELISA was used to quantitatively identify 56 different cytokines. The mean age of the children was 17 months, 74% were males, 79% were hospitalized, and 33% were sensitized. In adjusted analyses, the inpatient group was characterized by decreased expressions of interferon gamma (IFN-γ), interleukin 10 (IL-10), macrophage inflammatory protein 1 alpha (MIP-1α), RANTES (CCL5), and tumor necrosis factor-alpha (TNF-α) and an increased expression of ENA-78 (CXCL5) compared to the outpatient group. The cytokine response profiles from the PBMCs were different between the inpatient and outpatient groups. Our results support that firmly controlled interplay between pro-inflammatory and anti-inflammatory responses are required during acute viral infection to absolve the initial infection leading, to less severe illness.
... Inclusion criteria were children aged < 12 months with a clinical diagnosis of bronchiolitis. Bronchiolitis was defined as an LRTI characterized by respiratory distress, cough, wheezing, and/or crackles [15]. For the purpose of our study, we included both the first and subsequent episodes of bronchiolitis. ...
Background: Bronchiolitis is the most common cause of lower respiratory tract infection (LRTI) in the first year of life. We analyzed the association between complete blood count (CBC), c-reactive protein (CRP), and novel inflammatory indexes (NLR, PLR, MLR, ELR, LMR, NPR, LPR, LNR, PNR, SII, SIRI) in predicting bronchiolitis severity at hospital admission. Methods: We retrospectively collected data from 95 infants hospitalized for bronchiolitis in a third-level hospital during three epidemic seasons. Five outcomes of severity were analyzed: BRAS; pediatric intensive care unit (PICU) admission; ventilatory support; intravenous (IV) rehydration; and length of stay (LOS). Results: Lower age and weight at admission were statistically associated with four of the five severity outcomes. Prolonged LOS (≥6 days) was associated with high values of total white blood cells, lymphocytes, and eosinophils. Only three inflammatory indexes (PLR, MLR, and PNR) showed a significant association with one outcome (prolonged LOS). A new index (RBC/AiW/1000) was statistically associated with each severity outcome for a value > 350. Conclusions: We proposed a comprehensive analysis of the association between CBC, CRP, and novel inflammatory indexes and bronchiolitis severity. RBC/AiW/1000 could represent a future predictive marker of disease severity at hospital admission in infants with bronchiolitis.
... Molecular biomarkers can also be used to phenotype viral LRTI in infants, often lumped together as "viral bronchiolitis" [131]. Distinct bronchiolitis phenotypes and endotypes have been identified based on the heterogeneity of clinical presentations, molecular immune signatures, and clinically relevant outcomes [132][133][134]. ...
Viral lower respiratory tract infections (LRTI) are ubiquitous in early life. They are disproportionately severe in infants and toddlers (0–2 years), leading to more than 100,000 hospitalizations in the United States per year. The recent relative resilience to severe Coronavirus disease (COVID‐19) observed in young children is surprising. These observations, taken together, underscore current knowledge gaps in the pathogenesis of viral lower respiratory tract diseases in young children and respiratory developmental immunology. Further, early‐life respiratory viral infections could have a lasting impact on lung development with potential life‐long pulmonary sequelae. Modern molecular methods, including high‐resolution spatial and single‐cell technologies, in concert with longitudinal observational studies beginning in the prenatal period and continuing into early childhood, promise to elucidate developmental pulmonary and immunophenotypes following early‐life viral infections and their impact on trajectories of future respiratory health. In November 2019, under the auspices of a multi‐disciplinary Workshop convened by the National Heart Lung Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, experts came together to highlight the challenges of respiratory viral infections, particularly in early childhood, and emphasize the knowledge gaps in immune, virological, developmental, and clinical factors that contribute to disease severity and long‐term pulmonary morbidity from viral LRTI in children. We hope that the scientific community will view these challenges in clinical care on pulmonary health trajectories and disease burden not as a window of susceptibility but as a window of opportunity.
... Also, RSV infections may have short-term direct and indirect consequences such as an increased incidence of acute otitis media, pneumonia, and excessive antibiotic usage (3), or long-consequences such as early transient or recurrent wheezing, asthma, and impaired lung function (4). Respiratory Syncytial Virus (RSV) is estimated to be the causative agent in 80% and 40% of hospitalisations due to bronchiolitis and pneumonia, respectively, among children (5). Globally, it's projected that RSV accounts for a total of 55,000 to 200,000 annual fatalities and 3.2 million hospitalisations among children below 5 years old (6). ...
Introduction:
Respiratory syncytial virus is a leading cause of respiratory hospitalisations in infants. This systematic review (registration number: CRD42021248309) aims to synthesise the available evidence on Respiratory Syncytial Virus-related hospitalisations among children aged 0 to 6 years in Italy.
Methods:
The literature search was conducted on PubMed, Embase, Scopus, and International HTA, covering the period from January 2000 to July 2022, with a focus on studies that reported information on Respiratory Syncytial Virus-associated hospitalisation in children aged 0-6 years in Italy.
Results:
Eight articles were included after screening 20,845 records. These retrospective studies reported that most hospitalisations were among those <1 year (71.5%-88.8%), infants aged <1 year were also at higher risk of hospitalisation in intensive care unit. Respiratory Syncytial Virus infections typically peaked December-February, with an atypical early start in August 2021. Subtype analysis showed alternating prevalence of Respiratory Syncytial Virus-A and Respiratory Syncytial Virus-B across different seasons. Coinfections were not uncommon (1.1%-37.4%), with rhinovirus and bocavirus being the most frequent.
Conclusions:
All infants at their first Respiratory Syncytial Virus season showed an increased risk of severe infection and hospitalisation, regardless of the gestational age at birth, compared to older participants. This systematic review will enrich the understanding about Respiratory Syncytial Virus disease and help support decisions regarding prevention efforts in Italy.
... Nielenže sa podľa epidemiologických štúdií najčastejšie vyskytujú u detí do piatich rokov, ale sa aj významnou mierou podieľajú na rozvoji bronchiálnej astmy u vnímavých jedincov s predispozičnými faktormi. (5,6) Základné virologické a klinické charakteristiky týchto dvoch vírusov popisuje tabuľka 1. ...
Introduction: Respiratory viruses contribute significantly to respiratory morbidity in children with a high burden on
society.
Objectives: Retrospective analysis of the epidemiological characteristics of selected respiratory viruses detected in
often ill pediatric patients.
Materials and methods: Assessment of laryngeal swab outcomes. The results were examined using RT-PCR method
for a coherent group of 10 viruses: rhinovirus (RV), adenovirus (ADV), respiratory syncytial virus (RSV), human coronavirus (HCoV), parainfluenza virus (PIV 1-4), human bocavirus (HboV), and human metapneumovirus (HMPV). The
data collection period was established from January 2022 to June 2023. This period corresponded to the investigation of 722 samples. The variables analysed included age, sex, month of detection of the pathogen, and diagnosis of
acute respiratory infection. The average age of the children was 5.6 ± 4.3 years.
Results: Among all samples, more than half (373; 52%) were confirmed to contain a viral pathogen. The virus with
the highest prevalence was RV (184; 49%). ADV was the second most prevalent (47; 12%), closely followed by respiratory RSV (40; 11%). An analysis of virus detection over different months revealed typical epidemiological patterns,
with RV and ADV present throughout the year, and RSV, PIV 1-4, and HMPV showing seasonal patterns. The two
most common viruses, RV and RSV, exhibited a differential age-related presence in children.
Conclusion: This study found that the prevalence of specific respiratory viruses varies according to the season and
age of paediatric patients with acute respiratory infections. By identifying specific pathogens, we can enhance therapeutic management and prevent possible complications of viral respiratory infections.
Key words: respiratory viruses, children, acute respiratory infections, rhinovirus, respiratory syncytial virus, epidemiology
... 237 (Level II-2) About 50% of all respiratory tract infections were associated with RSV. 238 Mortality from a birth cohort study was 6.9 per 1 million births and highest amongst premature babies less than 29 weeks gestation. 239 In adults more than 60 years of age in a retrospective study, the mortality was ...
... Nearly all children experience an RSV infection by the age of 2 years [8,9]. Globally, RSV is a prevalent pathogen and the primary cause of bronchiolitis in infants and young children [10]. A systematic literature review published in 2019 estimated that RSV caused 33.0 million acute lower respiratory infection (ALRI), 3.6 million hospitalizations, and 101,400 deaths worldwide in children under five years of age [3]. ...
Background
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection and hospitalizations among infants, young children, and the elderly. This systematic literature review aimed to summarize the epidemiological and economic burden estimates of RSV infection at any age in Germany.
Methods
We conducted a systematic literature search to identify full-text articles published from 2003 to 2023 and reporting data on the epidemiological or economic burden of RSV in Germany. Based on pre-specified eligibility criteria, data on incidence, rates of hospital and intensive care unit (ICU) admission, clinical manifestation, underlying conditions, seasonality, health care resource use and costs were extracted.
Results
After screening 315 full-text articles, we included 42 articles in the review. The characteristics of the included studies were heterogenous regarding study population, setting, age groups and RSV-related outcome measures.
The most frequently reported epidemiological outcome measures were RSV detection rate (n = 33), followed by clinical manifestation (n = 19), seasonality (n = 18), and underlying conditions of RSV infection (n = 13). RSV detection rates were reported across heterogenous study populations, ranging from 5.2 to 55.4% in pediatric inpatient cases and from 2.9 to 14% in adult inpatient cases. All articles that reported RSV detection rates across several age groups demonstrated the highest burden in infants and young children. Few articles reported RSV-related outcome measures distinctively for the outpatient setting.
Health care resource use, such as hospital length of stay, ICU admission rate and treatment of patients with RSV infection were described in 23 articles, of which only one study quantified associated costs from 1999 to 2003 for children ≤ 3 years. In-hospital ICU admission rates varied between 3.6 and 45%, depending on population characteristics as age and underlying conditions.
Conclusions
This systematic review revealed that RSV imposes substantial disease burden in infants, young children, and the elderly in Germany, whereby infants are particularly affected. To date, there has been limited exploration of the impact of RSV infection on healthy children or the elderly in Germany. Given their notably high reported burden in studies, the medical and economic RSV burden in these groups should move more into focus.
... Essa afecção costuma se manifestar durante o inverno com um quadro clínico inicial de 2 a 4 dias que pode abranger aceleração do ritmo respiratório, tosse, febre com valores menores que 39 ºC, vias nasais com excesso de secreção, maior empenho respiratório. Sibilos expiratórios são característicos na ausculta médica (Meissner, 2016 (Ralston et al, 2014e Pimentel et al, 2017. ...
As doenças respiratórias agudas são importante causa de hospitalizações e grande desafio para a Saúde Pública. A Bronquite Aguda e Bronquiolite Aguda, são infecções que afetam as vias aéreas inferiores. A bronquiolite aguda se dá por lesões nos bronquíolos provocadas pelo agente causador viral, grande parte dos casos tem desfecho sem gravidade, em situações agravantes pode ocorrer sofrimento respiratório. A bronquite aguda é causada por alterações inflamatórias nos brônquios, com quadro clínico que varia de sintomas leves, como tosse, a graves, como falta de ar. O objetivo deste estudo é conhecer o perfil epidemiológico da morbimortalidade hospitalar da Bronquite Aguda e Bronquiolite Aguda em crianças menores de 5 anos. Nesse sentido, o estudo proposto é uma pesquisa epidemiológica, transversal, quantitativa e descritiva de série temporal de 2017 a 2021, com dados secundários advindos do DATASUS - MS. Os dados coletados serão analisados estatisticamente pelo Programa Bioestat 5.3. e os resultados serão expostos em gráficos e tabelas. Ocorreram, no período em estudo, um elevado número de internações por tais patologias com n=224.754, houve um aumento nas internações por Bronquite Aguda e Bronquiolite Aguda no Brasil até 2019, seguido por uma queda em 2020 e novo aumento em 2021, principalmente na região Sudeste. A maioria das internações ocorreu em crianças com menos de 1 ano, especialmente no sexo masculino e entre crianças pardas. Houve 1.733 óbitos, com a região Sudeste liderando em números, e as taxas de mortalidade variaram regionalmente, com a região Norte apresentando a taxa mais alta. Esses resultados podem ser utilizados para ajudar a comunidade e a assistência à saúde do país como um todo, desde a gestão até os profissionais, na diminuição dos casos de agravamento e de morte dessas doenças.
The resurgence of respiratory syncytial virus (RSV) infection among Japanese infants during the coronavirus disease 2019 pandemic might be due to a decrease in cord blood anti-RSV immunoglobulin G (IgG) positivity resulting from reduced maternal RSV exposure. This study examined changes in the positivity before and during the pandemic to clarify the relationship between this positivity and infantile/severe RSV infections. Data from a prospective cohort study conducted in Tokyo, Japan, involving mother–child pairs of infants born between February 2019 and August 2022 were reanalyzed. Cord blood anti-RSV IgG levels measured by enzyme-linked immunosorbent assay were classified as positive, gray zone, and negative. We examined the relationship between antibody positivity and infantile (≤12 months old) and/or severe RSV infections as diagnosed by pediatricians. A total of 319 families participated. There was a significant decrease in cord blood anti-RSV IgG positivity from 65.1% in 2019 to 50.9% in 2022 ( P = .02). Among infants followed up until their 2nd birthday, 43 (33.1%) were diagnosed with RSV infections. Of these cases, 5 were infantile/severe and occurred among the 50 infants classified as negative or gray zone, while none were observed among the 80 infants classified as positive ( P = .004). Infantile/severe RSV infection was identified in 4 (16.7%) born during the pandemic, representing a significantly higher rate than 1 (0.9%) born before the pandemic ( P < .001). This study revealed an association between lower cord blood anti-RSV IgG positivity during the coronavirus disease 2019 pandemic compared to before the pandemic, and an increased risk of subsequent infant/severe RSV infections.
Objective
To investigate the effect of viral co‐infections on treatment length and treatment failure in children with lower respiratory tract infections (LRTI) supported with continuous positive airway pressure (CPAP) or high‐flow nasal cannula oxygenation therapy (HFNC).
Methods
Patients aged 0–5 years hospitalized with viral LRTI and in need of respiratory support between August 1 and December 31, 2021, were retrospectively evaluated by patient chart audits.
Results
A total of 148 children (median age 10.1 [IQR 2.2–17.6] months) were included. Of this, 98 children were treated with HFNC and 50 with CPAP. Five children were transferred to the pediatric intensive care unit. In 17 children, HFNC treatment failed, leading to a shift to CPAP. The median treatment length was 90.6 (IQR 61–136) h. A total of 93 children were mono‐infected: 66 with respiratory syncytial virus (RSV), 14 with rhino/enterovirus (REV), 11 with metapneumovirus (MPV), 1 with adenovirus (AV), and 1 with coronavirus. Fourteen children were co‐infected with either RSV, REV or MPV and AV or parainfluenza virus (PIV). A total of 41 children were infected with both RSV and REV, RSV and MPV, MPV and REV, or all three viruses. Co‐infections with RSV, MPV, and/or REV were independent predictors of treatment failure with HFNC ( p < 0.05) and length of treatment ( p < 0.01), whereas co‐infections with AV or PIV had no effect.
Conclusion
In children with viral LRTI, the combination of RSV/REV/MPV had an impact on treatment length and failure with HFNC, whereas co‐infections with either RSV, REV or MPV, and AV or PIV had not.
Aim
High flow nasal cannula (HFNC) therapy is a form of respiratory support used in children with bronchiolitis. A national guideline for the use of HFNC was published in The Netherlands in 2020. We studied the implementation and use of this guideline.
Methods
We performed a multicentre observational study amongst all hospitals in the North‐West part of The Netherlands referring to the same paediatric intensive care unit (PICU). This study consisted of two parts: a comparison of local HFNC protocols to the national guideline and a survey about the use of HFNC amongst paediatricians in the participating centres.
Results
We observed considerable variations between the local protocols and the national protocol, especially regarding criteria to initiate HFNC treatment and weaning practices. Survey results showed that expectations of HFNC widely varied, while the clinical use of HFNC deviated from both the national guideline as well as local protocols, especially for weaning practices and the use of pCO 2 as a parameter for initiation and evaluation of the effect of HFNC.
Conclusion
Implementation of the national guideline for HFNC therapy in bronchiolitis was inefficacious, leading to non‐uniform clinical practice.
Lower respiratory tract infection (LRTI) is a major cause of neonatal morbidity and mortality worldwide. Maternal vaccination is an effective strategy in protecting young infants from LRTI, particularly in the first few months after birth when infant is most vulnerable, and most primary childhood vaccinations have not been administered. Additionally, maternal vaccination protects the mother from illness during pregnancy and the postnatal period, and the developing fetus from adverse outcomes such as stillbirth and prematurity. In this paper, we review the safety, efficacy, and effectiveness of maternal vaccines against LRTIs, such as pertussis, influenza, coronavirus disease 2019, and respiratory syncytial virus.
Background
The first post-COVID-19 pandemic year demonstrated an unusual bronchiolitis epidemic in both hemispheres and has been attributed to the removal of barriers implemented during SARS-CoV-2 infection. Several countries reported an increase in respiratory syncytial virus (RSV) bronchiolitis, with more hospitalizations and a greater need for respiratory support. We aimed to evaluate the consequences of the COVID-19 pandemic on the epidemiology and management of severe bronchiolitis in pediatric intensive care units (PICUs) in Italy.
Methods
Multicenter, retrospective, cohort database analysis. All children younger than 24 months admitted to 7 PICUs from October 2017 to April 2023 diagnosed with bronchiolitis were included. We compared patients from pre-COVID and post-COVID eras, excluding patients from the 2020–2021 season due to low numbers. Logistic regression models were used to assess the impact of the pre-/post-COVID period on the need for invasive ventilation.
Results
Seven hundred fifteen patients were admitted to PICU during the study period, 451 patients pre-COVID and 251 patients post-COVID. Patients in the post-COVID group were older, had more comorbidities, and had higher Pediatric Index of Mortality scores at admission but the need for respiratory support was not significantly different. There was high variability in bronchiolitis management across centers. Presenting pre-COVID was protective against the risk of mechanical ventilation, adjusted for age and disease severity at admission (OR 0.38, 95% CI 0.16–0.89), while RSV infection increased the risk of intubation (OR 2.49, 95% CI 1.1–5.63).
Conclusions
PICUs have faced an unexpected peak of significantly more severe cases of bronchiolitis after the COVID-19 pandemic, which did not require increased respiratory support.
Introdução: O Vírus Sincicial Respiratório (VSR) é uma das principais causas de hospitalizações por doenças respiratórias agudas em crianças menores de um ano, sendo uma preocupação significativa em regiões com recursos limitados. Recentemente, a vacina contra o VSR foi aprovada pela ANVISA no Brasil, representando um avanço importante na proteção das crianças. Objetivo: Este artigo visa descrever a situação atual e as perspectivas da imunização durante a gravidez contra o VSR, com foco na proteção dos recém-nascidos nos primeiros meses de vida no Brasil. Metodologia: Realizou-se uma revisão integrativa da literatura nas bases de dados Scielo e Pubmed, selecionando artigos em inglês e português publicados entre 2013 e 2023. Inicialmente, foram obtidos 80 resultados, que foram analisados por dois revisores de forma independente, resultando em 13 artigos revisados integralmente. Resultados: A vacina contra o VSR demonstrou conferir proteção ao feto por meio da transmissão transplacentária de anticorpos neutralizantes. As evidências indicam um perfil de segurança favorável, com reações leves a moderadas e eventos adversos graves similares aos do placebo. Estudos mostram uma redução de 81,8% nos casos de doença grave nos primeiros três meses de vida e de 69,4% aos seis meses após o nascimento entre as gestantes vacinadas. Conclusão: A vacina Pfizer, aprovada pela ANVISA em abril deste ano, será administrada em dose única durante o segundo ou terceiro trimestre de gestação, mostrando-se promissora na prevenção de doenças respiratórias graves relacionadas ao VSR, reduzindo internações e necessidade de cuidados médicos em bebês menores de seis meses de idade.
Aim
Examine the trends and epidemiological features of acute hospitalized bronchiolitis cases among children aged 28 days to 2 years, both before and after the COVID‐19 pandemic. Furthermore, evaluate their need for intensive care unit (ICU) admission and identify primary risk factors associated with severe bronchiolitis.
Methods
A retrospective analysis was conducted on the medical records of paediatric patients admitted to Meyer Children's Hospital in Florence (Italy) from September 2019 to March 2023, with the diagnosis of bronchiolitis.
Results
Between 2019 and 2023, bronchiolitis hospitalizations grew by 76%, going from 131 to 230 cases, after the historical minimum of 14 cases in the 2020–2021 season. Respiratory syncytial virus (RSV) infection emerged as the predominant etiological agent, contributing to 76% of hospitalizations in both 2021–2022 and 2022–2023 seasons. Coinfection cases increased fivefold from 2019 to 2023, accounting for 23% of hospitalizations in 2022–2023. In addition, the ICU admission rate increased from 13% in 2019–2020 to 31% of bronchiolitis hospitalizations in 2022–2023. Univariate and multivariate analysis data show that infants below 2 months of age, preterm births, comorbidities and RSV infections were correlated with a higher risk for ICU admission.
Conclusion
The growing trend in ICU admissions for acute bronchiolitis in hospitalized children represents a substantial health challenge. Addressing the bronchiolitis epidemic necessitates a strategic focus on RSV prevention through interventions such as vaccines and monoclonal antibodies. Urgent implementation of preventive initiatives, together with continuous surveillance and the establishment of national databases, is imperative and cannot be further deferred.
Background
Respiratory syncytial virus (RSV) prophylaxis using palivizumab effectively reduces RSV-associated morbidity in preterm infants. In Korea, national insurance coverage for palivizumab was implemented in October 2016 for moderate-to-late preterm (MLPT) infants born during the RSV season (October-March) who have older siblings. However, no large-scale studies have investigated the changes in the incidence and risk of severe acute lower respiratory infections (ALRIs) after insurance coverage implementation for MLPT infants.
Methods
This large-scale retrospective cohort study used data from the Korean National Health Insurance Service between October 2013 and December 2019. MLPT infants (32 0/7–35 6/7 weeks of gestation) with older siblings were stratified into pre-insurance period (PIP; October 2013–September 2016) and insurance period (IP; October 2016–March 2019) groups based on the date of birth with respect to initial insurance palivizumab implementation. Severe ALRI outcomes (hospitalization, respiratory support, and intensive care unit admission) were evaluated up to 1 year of age using multivariable logistic regression models.
Results
Of the 11,722 MLPT infants included in the study, 6,716 and 5,006 infants were included in the IP and PIP groups, respectively. The incidences of ALRI-hospitalization and ALRI-respiratory support were significantly lower in the IP group than that in PIP group (24.0% vs. 26.0% and 3.1% vs. 4.0%, respectively). Additionally, ALRI-respiratory support risk was significantly lower in the IP group (adjusted odds ratio 0.771, 95% confidence interval 0.626–0.949, P = 0.014) than that in the PIP group. Among infants born during the RSV season, the risk of ALRI-hospitalization and ALRI-respiratory support were significantly lower in the IP group than that in the PIP group. However, no significant differences were observed between the IP and PIP groups for infants born during the non-RSV season.
Conclusion
The risks of severe ALRI outcomes decreased in Korea following the 2016 insurance implementation of palivizumab prophylaxis for MLPT infants born during the RSV season with older siblings.
Respiratory syncytial virus (RSV) is an enveloped, negative-sense, single-stranded RNA virus of the Orthopneumovirus genus of the Pneumoviridae family in the order Mononegavirales . RSV can cause acute upper and lower respiratory tract infections, sometimes with extrapulmonary complications. The disease burden of RSV infection is enormous, mainly affecting infants and older adults aged 75 years or above. Currently, treatment options for RSV are largely supportive. Prevention strategies remain a critical focus, with efforts centered on vaccine development and the use of prophylactic monoclonal antibodies. To date, three RSV vaccines have been approved for active immunization among individuals aged 60 and above. For children who are not eligible for these vaccines, passive immunization is recommended. A newly approved prophylactic monoclonal antibody, Nirsevimab, which offers enhanced neutralizing activity and an extended half-life, provides exceptional protection for high-risk infants and young children. This review provides a comprehensive and detailed exploration of RSV’s virology, immunology, pathogenesis, epidemiology, clinical manifestations, treatment options, and prevention strategies.
Viral bronchiolitis is the most common pediatric acute respiratory infection leading to hospitalization, and it causes a significant healthcare burden worldwide. Current guidelines recommend supportive management after many clinical trials on specific therapies failed to demonstrate benefits. However, several
studies in the past decade have revealed that bronchiolitis may not be a homogeneous disease, but instead may constitute an umbrella comprised of different ‘‘endotypes” and ‘‘phenotypes” based on patient characteristics, etiology, pathophysiological mechanisms, and clinical presentation.
In this extensive review, we summarize the current evidence that several different types of bronchiolitis (‘‘bronchiolitides”) coexist, with different short- and long-term consequences on respiratory health and the risk of asthma development. Disease pathobiology, immune response, and clinical characteristics may differ between the two most prevalent viral agents, respiratory syncytial virus and rhinovirus.
Recent randomized trials have shown that some subgroups of children may benefit from the use of systemic corticosteroids and/or bronchodilators. These findings also suggest that some children may benefit from individualized therapeutical approaches for viral bronchiolitis rather than following broad recommendations for treating all patients uniformly using only supportive management.
Background
In the last decades none of the medical therapies investigated have shown clear efficacy in the treatment of bronchiolitis, and literature agrees on a general de‐implementation of pharmacological therapies, recognizing an effective role only to nutritional support and oxygen therapy. High‐flow nasal cannulas (HFNC) has become increasingly popular in the last decade, despite its lack of clear efficacy. Recent randomized controlled trials (RCT) comparing standard oxygen therapy (SOT) and HFNC did not demonstrate significant benefit of HFNC. To acquire more clinical data on HFNC efficacy we performed a retrospective, quasi‐experimental analysis of patients admitted for bronchiolitis in the epidemic seasons 2021–2022 and 2022–2023.
Methods
To assess the efficacy of SOT and HFNC we used a pragmatic approach, a fuzzy regression discontinuity design, which is a quasi‐experimental test. Unlike RCTs, this process is not a true randomization, but may be interpreted as quasi‐randomization in an observational setting.
Results
HFNC did not reduce length of oxygen therapy (LOO) nor length of hospitalization (LOS) (respectively, p: 0.383 and p: 0.454). Treatment failure was not significantly different in the treatment groups (p: 0.354).
Conclusions
It is crucial to perform additional RCTs with uniform protocols to determine the efficacy of HFNC more accurately in the treatment of bronchiolitis. HFNC does not reduce LOO, suggesting that early use of HFNC does not change the course of disease in moderate bronchiolitis. In view of the greater complexity and higher cost, HFNC should not be routinely used as first‐line treatment in children with moderate respiratory distress and mild hypoxemia.
Background: The first post-COVID-19 pandemic year demonstrated an unusual bronchiolitis epidemic in both hemispheres and has been attributed to the removal of barriers implemented during SARS-CoV-2 infection. Several countries reported an increase in respiratory syncytial virus (RSV) bronchiolitis, with more hospitalizations and greater need for respiratory support. We aimed to evaluate the consequences of the COVID-19 pandemic on the epidemiology and management of severe bronchiolitis in Pediatric Intensive Care Units (PICUs) in Italy.
Methods: multicenter, retrospective, cohort database analysis. All children younger than 24 months admitted to 7 PICUs from October 2017 to April 2023 diagnosed with bronchiolitis were included. We compared patients from Pre-COVID and Post-COVID eras, excluding patients from the 2020-2021 season due to low numbers. Logistic regression models were used to assess the impact of Pre/Post-COVID period on the need for invasive ventilation.
Results: 715 patients were admitted to PICU during the study period, 451 patients Pre-COVID and 251 patients Post-COVID. Patients in the Post-COVID group were older, had more comorbidities and higher Pediatric Index of Mortality score at admission but the need for respiratory support was not significantly different. There was high variability in bronchiolitis management across Centers. Presenting Pre-COVID was protective against the risk of mechanical ventilation, adjusted for age and disease severity at admission (OR 0.38, 95% CI 0.16-0.89), while RSV infection increased the risk of intubation (OR 2.49, 95% CI 1.1-5.63).
Conclusions: PICUs have faced an unexpected peak of significantly more severe cases of bronchiolitis after the COVID-19 pandemic, but this didn’t require increased respiratory support.
Resumo Objetivo Avaliar a distribuição longitudinal do número de hospitalizações pediátricas por bronquiolite viral aguda no Sistema Único de Saúde e os gastos com internações correspondentes a cada macrorregião, no âmbito nacional brasileiro. Métodos Estudo quantitativo, observacional, ecológico, tendo por base uma análise retrospectiva e longitudinal de dados do Departamento de Informática do Sistema Único de Saúde no período de 2012 a 2021, por meio de estatística descritiva e teste pareado de Tukey. Resultados Houve diferença estatística significante quanto aos gastos das internações nas macrorregiões no âmbito nacional ao longo dos anos (p=0,017), porém as comparações múltiplas de Tukey indicaram que não houve diferença significante entre 2 anos consecutivos, quando comparados os anos de 2020 e 2021 e o valor médio de internações por regiões. As proporções médias dos números de internações nas macrorregiões nos 10 anos do estudo foram de 461,1 no Centro-Oeste, 528,27 no Norte, 1.026 no Sul, 1.127 no Nordeste e 3.044 no Sudeste, considerando que a maior incidência quanto à média de internação esteve no Sudeste e houve diferença estatística significante do número de internações ao longo dos anos (p=0,001). Conclusão Houve aumento significativo da ocorrência de internações dos casos de bronquiolite viral aguda em crianças menores de 4 anos, especialmente em lactentes, o qual se mostrou crescente a incidência de internações nessa faixa etária e os gastos hospitalares no Brasil na maioria das macrorregiões, principalmente na Sudeste.
Objective To assess the longitudinal distribution of the number of pediatric hospitalizations for acute viral bronchiolitis in the Brazilian Health System and the expenses with hospitalizations corresponding to each macro-region at the Brazilian national level. Methods This is a quantitative, observational, ecological study based on a retrospective and longitudinal analysis of data from the Brazilian Health System Information Technology Department from 2012 to 2021, using descriptive statistics and Tukey’s paired test. Results There was a statistically significant difference regarding hospitalization costs in macro-regions at the national level over the years (p=0.017), but Tukey’s multiple comparisons indicated that there was no significant difference between 2 consecutive years, when comparing the years 2020 and 2021 and the mean value of hospitalizations by regions. The mean proportions of the number of hospitalizations in the macro-regions in the 10 years of study were 461.1 in the Midwest, 528.27 in the North, 1,026 in the South, 1,127 in the Northeast and 3,044 in the Southeast, considering that the highest incidence in terms of the mean of hospitalization was in the Southeast and there was a statistically significant difference in the number of hospitalizations over the years (p=0.001). Conclusion There was a significant increase in the occurrence of hospitalizations for cases of acute viral bronchiolitis in children under 4 years old, especially in infants, which showed an increasing incidence of hospitalizations in this age group and hospital expenses in Brazil in most macro-regions, mainly in the Southeast.
There are meaningful differences and similarities in the prevalence, associated risks, and prevention of healthcare-associated infections (HAI) in pediatric/neonatal intensive care units (ICUs) when compared to adult care areas.
For the prevention of central line-associated blood stream infections (CLABSI) and catheter-associated urinary tract infections (CAUTI), many pediatric hospitals use the successful insertion and maintenance bundles developed by the Solutions for Patient Safety (SPS) collaborative as well as other complementary initiatives including the utilization of line teams and midlines.
Control mechanisms beyond contact isolation for multidrug-resistant organisms, such as methicillin resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and multidrug-resistant Gram-negative bacilli, include the growing adoption of daily chlorhexidine bathing typically for children above a certain weight and/or age, and antibiotic stewardship programs.
The national reporting of pediatric ventilator-associated pneumonia (VAP) is transitioning to the newer pediatric ventilator-associated events (PedVAE) definition with pediatric ICUs able to utilize either and neonatal ICUs using only PedVAE. Thus far there are no well-established PedVAE prevention bundles.
Hospital-acquired respiratory infections occur in nearly one in every 1000 pediatric patient days. Screening via viral testing is typically limited to only symptomatic patients and visitors. Besides employing the Centers for Disease Control and Prevention’s recommended precautions for infected patients, many pediatric hospitals strategically place alcohol-based sanitizers and cough-etiquette posters, ban young visitors during the viral season, and encourage staff influenza vaccination.
Nosocomial diarrheal illnesses, typically secondary to Clostridioides difficile and rotavirus, account for 15–35% of all pediatric hospital-acquired infections. Prevention strategies for both infections include patient isolation, contact precautions, and pathogen appropriate hand washing and room cleaning techniques.
Pediatric cardiac patients besides having higher central line and ventilator days per ICU admission, those with delayed sternal closure have increased rates of surgical sites infection causing many hospitals to develop sternal wound care prevention protocols.
Background
Paediatric acute bronchiolitis normally occurs from October to April in the temperate northern hemisphere, peaking in January. Nonpharmacological measures to control the spread of COVID-19 resulted in a decrease in the number of cases of bronchiolitis during the 2020–21 season. The discontinuation of these measures created an uncertain scenario.
Aim
To describe the epidemiological evolution of acute bronchiolitis seasons and the changes in the demographics of the affected population before, during, and after the implementation of nonpharmacological interventions for COVID-19 in Spain.
Methods
This was a multicentre and descriptive study. A total of 6,334 infants aged up to 12 months who were diagnosed with acute bronchiolitis were recruited from sixteen Spanish hospitals. We collected data from participants from September 1st, 2021, through August 31st, 2023, as part of the ECEALHBA research project. The study periods were before (P1), during (P2), and after (P3) the COVID-19 pandemic.
Findings
In P2 and after the discontinuation of nonpharmacological interventions, an unexpected increase in the number of acute bronchiolitis cases was observed from June–August 2021, resulting in an out-of-season peak. A subsequent peak was observed in November 2021, earlier than expected for the 2021-22 season. In the 2022-23 season, admissions followed a historical trend, with a greater number of cases than in the two previous seasons. Statistically significant differences in the length of stay (p<0.001), number of RSV infections (p=0.021), and number of paediatric intensive care unit admissions (p<0.001) were observed among the periods.
Conclusions
Two out-of-season peaks in the number of acute bronchiolitis cases were observed in 2020–2021 and 2021–2022. However, following the relaxation of nonpharmacological intervention measures, the peak observed in 2022–2023, although occurring 2–6 weeks earlier, was more similar to the peaks observed in the prepandemic seasons. Additionally, increased case severity was observed during these periods.
Background
Acute viral bronchiolitis is a major cause of infant hospitalizations worldwide. Childhood bronchiolitis is considered a risk factor for asthma, suggesting shared genetic factors and biological pathways. Genetic risk loci may provide new insights into disease pathogenesis.
Methods
We conducted a genome-wide association study (GWAS) to examine the genetic contributions to bronchiolitis susceptibility in the FinnGen project data. We analyzed 1,465 infants hospitalized for bronchiolitis <2 years of age and 356,404 individuals without a history of acute lower respiratory infections (LRIs).
Results
GWAS identified associations (p<5×10-8) for variants in gasdermin B (GSDMB) and a missense variant in cadherin-related family member 3 (CDHR3). Children with bronchiolitis in infancy were more likely to develop asthma later in life compared to controls. The two associated loci were previously linked to asthma and susceptibility to wheezing illness by other causative agents than RSV. The identified loci associated with overall bronchiolitis, with larger effects in non-RSV than RSV-induced infection.
Conclusion
Our results suggest that genetic variants in CDHR3 and GSDMB modulate susceptibility to bronchiolitis, especially when caused by viruses other than RSV. Severe bronchiolitis in infancy may trigger the development of asthma in genetically susceptible individuals, or it could be a marker of genetic predisposition to asthma.
Background
A bronchiolitis integrated care pathway (BICP) achieved an 87% reduction in the use of medications in our regional health service (RHS) during the 2019–2020 season.
Aim
This study aimed to assess the sustainability of the changes in bronchiolitis management over 3 years after implementation of the BICP.
Methods
A prospective observational study on rates of medications prescribing in children diagnosed with bronchiolitis in 135 primary care (PC) centres and eight hospital emergency departments (EDs) in the Basque Country, Spain, was conducted during the four bronchiolitis seasons between 2019 and 2023. Over this period, the deployment of BICP-related actions continued in our RHS. In addition, a strategy was designed to enhance the sustainability of the results. The main endpoint was the percentage of children prescribed salbutamol.
Results
Over the 2019–2020 to 2022–2023 epidemic waves, 12 966 infants were diagnosed with bronchiolitis in PC, and 6676 infants in EDs. Rates of salbutamol use over the four waves were 5.04%, 10.54%, 8.51% and 6.05%, respectively, in PC and 3.36%, 10.02%, 7.62% and 5.77% in EDs. Rates of concomitant administration of other medications in EDs over the four waves were 3.2%, 0.2%, 1.0% and 1.9% for epinephrine and 0.4%, 0.7%, 0.3% and 0.4% for corticosteroids, respectively. In PC, prescribing rates were 5.1% and 1.8%, 10.3% and 4.1% for antibiotics and 7.8% and 4.5%, 5.7% and 2.5% for corticosteroids, respectively.
Conclusions
Reductions in the use of medications for bronchiolitis achieved in 2019 through the implementation of our integrated clinical pathway have been sustained over the three subsequent waves.
Background and Objectives
Respiratory syncytial virus (RSV) is responsible for most cases of acute viral bronchiolitis (AVB) in childhood. The association of factors such as RSV subtype, viral load, and viral coinfection with severe disease is controversial. The objective is to describe the viral load dynamics of RSV in children under 2 years with AVB, including the first viral load, peak viral load, viral decay, and any possible association with severe disease.
Methods
73 inpatients with AVB and confirmed RSV infection were included. Viral load was obtained through nasal swab samples daily during hospitalization and weekly after discharge until absence of detection.
Results
44 of the patients were male, the mean age was 5.76 months, and comorbidities were found in 15 (20.5%) of the patients. 54 (74%) of the patients had the peak viral load between the 4th and the 7th day of symptom onset. The mean duration of viral detection was 12.5 days. There was no association between the first and peak viral load with markers of severe disease. However, association was found between viral persistence exceeding 10 days and the following factors: longer hospitalization period (p=0.009), length of ventilation support (p=0.044), length of invasive mechanical ventilation (p=0.035), prolonged requirement of nutritional support (p=0.038), and a longer course of antibiotic treatment (p=0.024). Age was inversely correlated with most of the severity outcomes.
Conclusion
Despite the lack of association between RSV viral load values and disease severity, prolonged viral shedding was associated with several adverse outcomes, which can contribute to a better understanding of RSV disease, particularly as several interventions are anticipated to become available in the coming years.
Childhood asthma is a common chronic disease of the airways that results from host and environment interactions. Most risk factor studies of asthma point to the first year of life as a susceptibility window of mucosal exposure that directly impacts the airway epithelium and airway epithelial cell development. The development of the airway epithelium, which forms a competent barrier resulting from coordinated interactions of different specialized cell subsets, occurs during a critical time frame in normal postnatal development in the first year of life. Understanding the normal and aberrant developmental trajectory of airway epithelial cells is important in identifying pathways that may contribute to barrier dysfunction and asthma pathogenesis. Respiratory viruses make first contact with and infect the airway mucosa. Human rhinovirus (HRV) and respiratory syncytial virus (RSV) are mucosal pathogens that are consistently identified as asthma risk factors. Respiratory viruses represent a unique early life exposure, different from passive irritant exposures which injure the developing airway epithelium. To replicate, respiratory viruses take over the host cell transcriptional and translational processes and exploit host cell energy metabolism. This takeover impacts the development and differentiation processes of airway epithelial cells. Therefore, delineating the mechanisms through which early life respiratory viral infections alter airway epithelial cell development will allow us to understand the maturation and heterogeneity of asthma and develop tools tailored to prevent disease in specific children. This review will summarize what is understood about the impact of early life respiratory viruses on the developing airway epithelium and define critical gaps in our knowledge.
Background
Respiratory syncytial virus (RSV) is the leading cause of lower-respiratory-tract infection in children. Nirsevimab, a monoclonal antibody against RSV, was implemented in a few countries in September 2023. However, its post-license effectiveness in ambulatory care settings is unknown. We aimed to assess the effectiveness of nirsevimab against RSV-bronchiolitis in outpatients aged <12 months.
Methods
We conducted a test-negative case–control study based on a national ambulatory surveillance system. We included all infants aged <12 months who had bronchiolitis and results of an RSV rapid antigen test performed, visiting a network of 107 ambulatory paediatricians from September 15, 2023, to February 1, 2024. Case patients were infants with bronchiolitis and a rapid antigen test positive for RSV. Control patients were infants with bronchiolitis and a rapid antigen test negative for RSV. Effectiveness was assessed by a logistic regression model adjusted for potential confounders. A range of sensitivity analyses were conducted to assess the robustness of the findings.
Findings
We included 883 outpatients who had bronchiolitis and results of an RSV rapid antigen test (453 were case patients, and 430 were control patients). Overall, 62/453 (13.7%) case patients and 177/430 (41.2%) control patients had been previously immunised for nirsevimab. The adjusted effectiveness of nirsevimab against RSV-bronchiolitis was 79.7% (95% CI 67.7–87.3). Sensitivity analyses gave similar results.
Interpretation
This post-license study indicates that nirsevimab was effective in preventing RSV-bronchiolitis in ambulatory care settings.
Funding
The study was supported by Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV), French Pediatrician Ambulatory Association (AFPA) and unrestricted grants from GSK, 10.13039/100030732MSD, 10.13039/100004319Pfizer and 10.13039/100004339Sanofi.
Background
Respiratory syncytial virus (RSV) causes serious illness in children. The Ad26.RSV.preF vaccine candidate was immunogenic with acceptable safety in a phase 1/2a study of RSV-seropositive children. Here, we assessed its safety and immunogenicity in RSV-seronegative children.
Methods
In this randomized, observer-blinded, placebo-controlled phase 1/2a study (NCT03606512; https://www.clinicaltrials.gov/ct2/show/NCT03606512), RSV-seronegative toddlers aged 12-24 months received Ad26.RSV.preF (2.5×1010 vp) or placebo on Days 1, 29, and 57 (a meningococcal vaccine [Nimenrix] could substitute for Day 57 placebo). Primary endpoints were solicited local and systemic adverse events (AEs; 7 days post each vaccination), unsolicited AEs (28 days postvaccination), and serious AEs (SAEs; first vaccination until study end). Participants were monitored for RSV-respiratory tract infection (RTI) to assess infection rates and for severe RSV-lower respiratory tract infection (RSV-LRTI) as an indication of enhanced disease. RSV-A2 neutralizing, RSV (A and B) preF binding, and RSV postF immunoglobulin G binding antibodies were evaluated on Days 1 (pre-dose), 8, and 85, and post–RSV season 1.
Results
Thirty-eight participants were enrolled and vaccinated (Ad26.RSV.preF, n=20; placebo, placebo/Nimenrix, n=18). Solicited AEs were more common following Ad26.RSV.preF than placebo; most were mild/moderate. No vaccine-related SAEs were reported. Five of 19 participants receiving Ad26.RSV.preF and 2/18 receiving placebo or placebo/Nimenrix had confirmed RSV-RTI or RSV-associated otitis media; none were considered severe. At the final season 1 study visit, most Ad26.RSV.preF recipients had ≥2-fold increases from baseline in RSV-A2 neutralizing, RSV A and B preF binding, and RSV postF antibodies.
Conclusions
Ad26.RSV.preF was well tolerated and immunogenic in RSV-seronegative toddlers.
Respiratory syncytial virus (RSV) is the most predominant viral pathogen worldwide in children with lower respiratory tract infections. The Coronavirus disease 2019 (COVID-19) pandemic and resulting nonpharmaceutical interventions perturbed the transmission pattern of respiratory pathogens in South Africa. A seasonality shift and RSV resurgence was observed in 2020 and 2021, with several infected children observed. Conventional RSV-positive nasopharyngeal swabs were collected from various hospitals in the Free State province, Bloemfontein, South Africa, from children suffering from respiratory distress and severe acute respiratory infection between 2020 to 2021. Overlapping genome fragments were amplified and complete genomes were sequenced using the Illumina MiSeq platform. Maximum likelihood phylogenetic and evolutionary analysis were performed on both RSV-A/-B G-genes with published reference sequences from GISAID and GenBank. Our study strains belonged to the RSV-A GA2.3.2 and RSV-B GB5.0.5a clades. The upsurge of RSV was due to pre-existing strains that predominated in South Africa and circulating globally also driving these off-season RSV outbreaks during the COVID-19 pandemic. The variants responsible for the resurgence were phylogenetically related to pre-pandemic strains and could have contributed to the immune debt resulting from pandemic imposed restrictions. The deviation of the RSV season from the usual pattern affected by the COVID-19 pandemic highlights the need for ongoing genomic surveillance and the identification of genetic variants to prevent unforeseen outbreaks in the future.
RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2–6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children’s hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period.
Conclusion: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis.What Is Known:
• Bronchiolitis is the most common viral infection of the lower respiratory tract in infants.
• It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world.
What Is New:
• In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain.
• Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.
Introduction
The American Academy of Pediatrics (AAP) Committee on Infectious Diseases issued updated guidance on respiratory syncytial virus (RSV) prophylaxis in 2014. This report models the potential impact of the new guidance on RSV outcomes in preterm infants 29–34 weeks’ gestational age (wGA) without chronic lung disease in the United States.
Methods
The number of preterm infants was estimated using 2012 natality data. Palivizumab utilization prior to the 2014 guidance update was estimated using 2013–2014 specialty pharmacy utilization data. Low, moderate, and high RSV hospitalization (RSVH) rates as well as average hospital length of stay, intensive care unit (ICU) admissions and mechanical ventilation (MV) frequencies were derived from published observational studies. Palivizumab efficacy was derived from two randomized clinical trials. RSV events that would be attributable to the 2014 guidance change were calculated for preterm infants 29–31 and 32–34 wGA.
Results
Annual number of infants 29–34 wGA surviving the neonatal period was estimated at 123,687. Of these, an estimated 44,712 (37%) would receive palivizumab based on the 2012 guidance. The annual number of RSVH among infants 29–34 wGA would increase from 3580 under the 2012 guidance to 6166 under the 2014 guidance based on moderate rates. This would result in an additional 24,440 hospitalization days, 1162 ICU admissions, and 584 MV events among this population.
Conclusions
Based on published historical and contemporary data on RSVH rates in preterm infants 29–34 wGA, the 2014 AAP guidance is expected to result in additional burden to the healthcare system and families of preterm infants. The impact of the new guidance will be difficult to detect among the overall infant population, particularly in settings without routine testing for RSV, but the impact will be substantial for the small high-risk population affected by the changes.
Funding
AstraZeneca.
Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab prophylaxis against respiratory syncytial virus (RSV) was first published in a policy statement in 1998. Guidance initially was based on the result from a single randomized, placebo-controlled clinical trial conducted in 1996-1997 describing an overall reduction in RSV hospitalization rate from 10.6% among placebo recipients to 4.8% among children who received prophylaxis. The results of a second randomized, placebo-controlled trial of children with hemodynamically significant heart disease were published in 2003 and revealed a reduction in RSV hospitalization rate from 9.7% in control subjects to 5.3% among prophylaxis recipients. Because no additional controlled trials regarding efficacy were published, AAP guidance has been updated periodically to reflect the most recent literature regarding children at greatest risk of severe disease. Since the last update in 2012, new data have become available regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effects of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, and the effect of prophylaxis on wheezing and palivizumab-resistant RSV isolates. These data enable further refinement of AAP guidance to most clearly focus on those children at greatest risk.
Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed.
We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists.
From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval [CI], 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%).
The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).
Significance
Rhinovirus is the most frequent cause of the common cold, as well as one of the most important causes of asthma exacerbations. Most rhinovirus strains replicate better at the cooler temperatures found in the nasal cavity than at lung temperature, but the underlying mechanisms are not known. Using a mouse-adapted virus, we found that airway epithelial cells supporting rhinovirus replication initiate a more robust antiviral defense response through RIG-I–like receptor (RLR)–dependent interferon secretion and enhanced interferon responsiveness at lung temperature vs. nasal cavity temperature. Airway cells with genetic deficiencies in RLR or type I interferon receptor signaling supported much higher levels of viral replication at 37 °C. Thus, cooler temperatures can enable replication of the common cold virus, at least in part, by diminishing antiviral immune responses.
Background:
We investigated whether children with a higher respiratory syncytial virus (RSV) genomic load are at a higher risk of more-severe bronchiolitis.
Methods:
Two multicenter prospective cohort studies in the United States and Finland used the same protocol to enroll children aged <2 years hospitalized for bronchiolitis and collect nasopharyngeal aspirates. By using real-time polymerase chain reaction analysis, patients were classified into 3 genomic load status groups: low, intermediate, and high. Outcome measures were a length of hospital stay (LOS) of ≥3 days and intensive care use, defined as admission to the intensive care unit or use of mechanical ventilation.
Results:
Of 2615 enrolled children, 1764 (67%) had RSV bronchiolitis. Children with a low genomic load had a higher unadjusted risk of having a length of stay of ≥3 days (52%), compared with children with intermediate and those with high genomic loads (42% and 51%, respectively). In a multivariable model, the risk of having a length of stay of ≥3 days remained significantly higher in the groups with intermediate (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.20-1.69) and high (OR, 1.58; 95% CI, 1.29-1.94) genomic loads. Similarly, children with a high genomic load had a higher risk of intensive care use (20%, compared with 15% and 16% in the groups with low and intermediate genomic loads, respectively). In a multivariable model, the risk remained significantly higher in the group with a high genomic load (OR, 1.43; 95% CI, 1.03-1.99).
Conclusion:
Children with a higher RSV genomic load had a higher risk for more-severe bronchiolitis.
This guideline is a revision of the clinical practice guideline, "Diagnosis and Management of Bronchiolitis," published by the American Academy of Pediatrics in 2006. The guideline applies to children from 1 through 23 months of age. Other exclusions are noted. Each key action statement indicates level of evidence, benefit-harm relationship, and level of recommendation. Key action statements are as follows:
Background:
Pneumonia is the leading cause of childhood mortality globally. Respiratory syncytial virus (RSV) is the most important viral cause of pneumonia. Maternal serum antibody protects infants from RSV disease. The objective of our study was to characterize RSV antibody levels in mother-infant pairs.
Methods:
Serial serum samples were collected from mother-infant pairs in Bangladesh from the third trimester of pregnancy to 72 weeks postpartum and tested using an RSV antibody microneutralization assay. Serologic infection was defined as a 4-fold increase in antibody titer. Maternal antibody half-life was calculated using infant antibody titers from birth to 20 weeks.
Results:
The ratio of infant cord blood to maternal serum RSV antibody titers in 149 mother-infant pairs was 1.01 (95% confidence interval [CI], .99-1.03). Maternal RSV antibody titers in the third trimester and at birth were strongly correlated (R = 0.68). Antibody half-life was 38 days (95% CI, 36-42 days). Higher cord blood RSV antibody titers were associated with a lower risk of serologic infection (P = .01) and maintenance of antibody titer above a potentially protective threshold (P < .001).
Conclusions:
Efficient transplacental transfer of RSV-specific antibody from mother to the fetus was documented in mother-infant pairs in Asia. Higher cord blood antibody titers were associated with protection from serologic infection.
Respiratory syncytial virus (RSV) can induce severe lower respiratory tract infections in infants and is the leading cause of bronchiolitis in children worldwide. RSV-induced inflammation is believed to contribute substantially to the severity of disease. T helper (Th)2-, Th9-, and Th17-related cytokines are all observed in infants hospitalized following a severe RSV infection. These cytokines cause an influx of inflammatory cells, resulting in mucus production and reduced lung function. Consistent with the data from RSV-infected infants, CD4 T cell production of Interleukin (IL)-9, IL-13, and IL-17 has all been shown to contribute to RSV-induced disease in a murine model of RSV infection. Conversely, murine studies indicate that the combined actions of regulatory factors such as CD4 regulatory T cells and IL-10 inhibit the inflammatory cytokine response and limit RSV-induced disease. In support of this, IL-10 polymorphisms are associated with susceptibility to severe disease in infants. Insufficient regulation and excess inflammation not only impact disease following primary RSV infection it can also have a major impact following vaccination. Prior immunization with a formalin-inactivated (FI-RSV) vaccine resulted in enhanced disease in infants following a natural RSV infection. A Th2 CD4 T cell response has been implicated to be a major contributor in mediating vaccine-enhanced disease. Thus, future RSV vaccines must induce a balanced CD4 T cell response in order to facilitate viral clearance while inducing proper regulation of the immune response.
Respiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants.
In the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis.
Palivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group [1.8%] vs. 2309 of 51,726 days [4.5%] in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01).
In otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.).
Provider-dependent practice variation in children hospitalized with bronchiolitis is not uncommon. Clinical practice guidelines (CPGs) can streamline practice and reduce utilization however, CPG implementation is complex.
A multidisciplinary team developed and implemented CPGs for management of bronchiolitis for children <2 years old. Children with comorbidities, ICU admissions, and outside hospital transfers were excluded. Implementation involved teamwork and collaboration, provider education, online access to CPGs, order sets, data sharing, and monthly team meetings. Resource utilization was defined as use of chest x-rays (CXRs), antibiotics, steroids, and more than 2 doses of inhaled bronchodilator use. Outcome metrics included length of stay (LOS) and readmission rate. Bronchiolitis season was defined as September to April. Data were collected for 2 seasons post implementation.
The number CPG-eligible patients in the pre- and 2 postimplementation periods were similar (1244, preimplementation; 1159, postimplementation season 1; 1283 postimplementation season 2). CXRs decreased from 59.7% to 45.1% (P < .0001) in season 1 to 39% (P < .0001) in season 2. Bronchodilator use decreased from 27% to 20% (P < .01) in season 1 to 14% (P < .002) in season 2. Steroid use significantly reduced from 19% to 11% (P < .01). Antibiotic use did not change significantly (P = .16). LOS decreased from 2.3 to 1.8 days (P < .0001) in season 1 and 1.9 days (P < .05) in season 2. All-cause 7-day readmission rate did not change (P = .45).
Bronchiolitis CPG implementation resulted in reduced use of CXRs, bronchodilators, steroids, and LOS without affecting 7-day all-cause readmissions.
Background:
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children globally, with the highest burden in low- and middle-income countries where the association between RSV activity and climate remains unclear.
Methods:
Monthly laboratory-confirmed RSV cases and associations with climate data were assessed for respiratory surveillance sites in tropical and subtropical areas (Bangladesh, China, Egypt, Guatemala, Kenya, South Africa, and Thailand) during 2004-2012. Average monthly minimum and maximum temperatures, relative humidity, and precipitation were calculated using daily local weather data from the US National Climatic Data Center.
Results:
RSV circulated with 1-2 epidemic periods each year in site areas. RSV seasonal timing and duration were generally consistent within country from year to year. Associations between RSV and weather varied across years and geographic locations. RSV usually peaked in climates with high annual precipitation (Bangladesh, Guatemala, and Thailand) during wet months, whereas RSV peaked during cooler months in moderately hot (China) and arid (Egypt) regions. In South Africa, RSV peaked in autumn, whereas no associations with seasonal weather trends were observed in Kenya.
Conclusions:
Further understanding of RSV seasonality in developing countries and various climate regions will be important to better understand the epidemiology of RSV and for timing the use of future RSV vaccines and immunoprophylaxis in low- and middle-income countries.
Objective:
To identify risk factors for inpatient apnea among children hospitalized with bronchiolitis.
Methods:
We enrolled 2207 children, aged <2 years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to 2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real-time polymerase chain reaction was used to test NPA samples for 16 viruses. Inpatient apnea was ascertained by daily chart review, with outcome data in 2156 children (98%). Age was corrected for birth <37 weeks. Multivariable logistic regression was performed to identify independent risk factors for inpatient apnea.
Results:
Inpatient apnea was identified in 108 children (5%, 95% confidence interval [CI] 4%-6%). Statistically significant, independent predictors of inpatient apnea included: corrected ages of <2 weeks (odds ratio [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age ≥ 6 months; birth weight <2.3 kg (5 pounds; OR 2.15), compared with ≥ 3.2 kg (7 pounds); caretaker report of previous apnea during this bronchiolitis episode (OR 3.63); preadmission respiratory rates of <30 (OR 4.05), 30 to 39 (OR 2.35) and >70 (OR 2.26), compared with 40 to 49; and having a preadmission room air oxygen saturation <90% (OR 1.60). Apnea risk was similar across the major viral pathogens.
Conclusions:
In this prospective, multicenter study of children hospitalized with bronchiolitis, inpatient apnea was associated with younger corrected age, lower birth weight, history of apnea, and preadmission clinical factors including low or high respiratory rates and low room air oxygen saturation. Several bronchiolitis pathogens were associated with apnea, with similar apnea risk across the major viral pathogens.
Objective:
To examine temporal trend in the national incidence of bronchiolitis hospitalizations, use of mechanical ventilation, and hospital charges between 2000 and 2009.
Methods:
We performed a serial, cross-sectional analysis of a nationally representative sample of children hospitalized with bronchiolitis. The Kids Inpatient Database was used to identify children <2 years of age with bronchiolitis by International Classification of Diseases, Ninth Revision, Clinical Modification code 466.1. Primary outcome measures were incidence of bronchiolitis hospitalizations, mechanical ventilation (noninvasive or invasive) use, and hospital charges. Temporal trends were evaluated accounting for sampling weights.
Results:
The 4 separated years (2000, 2003, 2006, and 2009) of national discharge data included 544 828 weighted discharges with bronchiolitis. Between 2000 and 2009, the incidence of bronchiolitis hospitalization decreased from 17.9 to 14.9 per 1000 person-years among all US children aged <2 years (17% decrease; P(trend) < .001). By contrast, there was an increase in children with high-risk medical conditions (5.9%-7.9%; 34% increase; P(trend) < .001) and use of mechanical ventilation (1.9%-2.3%; 21% increase; P(trend) = .008). Nationwide hospital charges increased from 1.73 billion (30% increase; P(trend) < .001); this increase was driven by a rise in the geometric mean of hospital charges per case from 8530 (34% increase; P(trend) < .001).
Conclusions:
Between 2000 and 2009, we found a significant decline in bronchiolitis hospitalizations among US children. By contrast, use of mechanical ventilation and hospital charges for bronchiolitis significantly increased over this same period.
Few US studies have assessed racial disparities in viral respiratory hospitalizations among children. This study enrolled black and white children under 5 years of age who were hospitalized for acute respiratory illness (ARI) in 3 US counties during October-May 2002-2009. Population-based rates of hospitalization were calculated by race for ARI and laboratory-confirmed influenza and respiratory syncytial virus (RSV), using US Census denominators. Relative rates of hospitalization between racial groups were estimated. Of 1,415 hospitalized black children and 1,824 hospitalized white children with ARI enrolled in the study, 108 (8%) black children and 111 (6%) white children had influenza and 230 (19%) black children and 441 (29%) white children had RSV. Hospitalization rates were higher among black children than among white children for ARI (relative rate (RR) = 1.7, 95% confidence interval (CI): 1.6, 1.8) and influenza (RR = 2.1, 95% CI: 1.6, 2.9). For RSV, rates were similar among black and white children under age 12 months but higher for black children aged 12 months or more (for ages 12-23 months, RR = 1.7, 95% CI: 1.1, 2.5; for ages 24-59 months, RR = 2.2, 95% CI: 1.3, 3.6). Black children versus white children were significantly more likely to have public insurance or no insurance (85% vs. 43%) and a history of asthma/wheezing (28% vs. 18%) but not more severe illness. The observed racial disparities require further study.
Human respiratory syncytial virus (hRSV) is the most important viral agent of pediatric respiratory infections worldwide. The only specific treatment available today is a humanized monoclonal antibody (Palivizumab) directed against the F glycoprotein, administered prophylactically to children at very high risk of severe hRSV infections. Palivizumab, as most anti-F antibodies so far described, recognizes an epitope that is shared by the two conformations in which hRSV_F can fold, the metastable prefusion form and the highly stable postfusion conformation. We now describe a unique class of antibodies specific for the prefusion form of this protein that account for most of the neutralizing activity of either a rabbit serum raised against a vaccinia virus recombinant expressing hRSV_F or a human Ig preparation (Respigam), which was used for prophylaxis before Palivizumab. These antibodies therefore offer unique possibilities for immune intervention against hRSV, and their production should be assessed in trials of hRSV vaccines.
Respiratory syncytial virus (RSV) disease severity was thought to be a result of host immunopathology but alternatively may be driven by high-level viral replication. The relationships between RSV load, viral clearance dynamics, and disease severity have not been carefully evaluated.
Previously healthy RSV-infected children <2 years old were recruited. RSV load was measured in respiratory secretions by fresh quantitative culture over 3 hospital days. Measures of disease severity were hospital admission, duration of hospitalization, requirement for intensive care, and respiratory failure.
Multivariate logistic regression models revealed independent predictors of increased duration of hospitalization: male sex, lower weight, and higher viral load on any day. Viral loads at day 3 were more significantly associated with requirement for intensive care and respiratory failure than were viral loads at earlier time points. Faster RSV clearance was independently associated with shorter hospitalization.
These observations challenge the immunopathology-based pathogenesis paradigm. They also have major therapeutic implications, suggesting that application of antiviral agents early in the disease course, even at a time when viral replication is at its highest, might improve subsequent morbidity by significantly lowering viral load and direct viral cytopathic effects, and aborting the potential downstream immunopathology.
Highly sensitive techniques, such as PCR, have greatly improved the detection of respiratory viruses. However, the sensitivity of PCR tests also complicates clinical interpretation, as the presence of small amounts of viral targets may not necessarily have clinical relevance. We performed a prospective case-control study in asymptomatic and symptomatic young children. PCR detection of 14 respiratory viruses was performed in nasal washes, and results were quantified in copies per milliliter. A total of 141 cases and 157 controls were included. In 72% of the cases and 28% of the controls, at least one virus was identified. When stratified for age, at least one virus was identified in 47% of the controls younger than 1 year old. Rhinovirus (RV) was frequently detected in both symptomatic and asymptomatic individuals. Receiver operating characteristic analysis for quantitative rhinovirus detection showed that cutoff values for clinical relevance are feasible for RV. In contrast to rhinovirus, respiratory syncytial virus (RSV) was rarely detected in controls, suggesting that a positive RSV test result is almost always of clinical relevance, independent of viral quantity. In conclusion, our study shows that asymptomatic carriage of a respiratory virus occurs frequently in young children. However, significant differences in the amount of virus present were observed between cases and controls. This suggests that defining cutoff levels should be feasible and represents the next necessary step for diagnosing viral respiratory infections using molecular tests.
Prematurely born infants who develop respiratory syncytial virus (RSV) lower respiratory tract infections (LRTIs) have lung function abnormalities at follow-up. The aim of this study was to determine whether prematurely born infants who developed symptomatic RSV, or other viral LRTI(s), had poorer premorbid lung function than infants who did not develop LRTIs during the RSV season.
Lung function (functional residual capacity (FRC), compliance (Crs) and resistance (Rrs) of the respiratory system) was measured at 36 weeks postmenstrual age. After neonatal unit discharge, nasopharyngeal aspirates were obtained whenever the infants had an LRTI, regardless of whether this was in the community or in hospital. Nasopharyngeal aspirates were examined for RSV A and B, rhinovirus, influenza A and B, parainfluenza 1, 2 and 3, human metapneumovirus and adenovirus.
159 infants with a median gestational age of 34 (range 23-36) weeks were prospectively followed. 73 infants developed LRTIs: 27 had at least one RSV LRTI and 31 had at least one other viral LRTI, but not an RSV LRTI. Overall, there were no significant differences in the FRC (p=0.54), Crs (p=0.11) or Rrs (p=0.12) results between those who developed an RSV or other viral LRTI and those who did not develop an LRTI. Infants with RSV or other viral LRTIs who were admitted to hospital compared with those who were not had higher Rrs results (p=0.033 and p=0.039, respectively).
Diminished premorbid lung function may predispose prematurely born infants to severe viral LRTIs in infancy.
An increased prevalence of asthma/recurrent wheeze (RW), clinical allergy and allergic sensitisation up to age 13 years has previously been reported in subjects hospitalised with respiratory syncytial virus (RSV) bronchiolitis in their first year of life compared with matched controls. A study was undertaken to examine whether these features persist into early adulthood, to report longitudinal wheeze and allergy patterns, and to see how large and small airway function relates to RSV infection and asthma.
Follow-up at age 18 years was performed in 46 of 47 subjects with RSV and 92 of 93 controls. Assessments included questionnaire, clinical examination, skin prick tests, serum IgE antibodies to inhaled allergens, blood eosinophils, fraction of exhaled nitric oxide (FeNO), spirometry, multiple breath washout (lung clearance index, LCI) and dry air hyperventilation challenge.
Increased prevalence of asthma/RW (39% vs 9%), clinical allergy (43% vs 17%) and sensitisation to perennial allergens (41% vs 14%) were present at age 18 in the RSV cohort compared with controls. Persistent/relapsing wheeze associated with early allergic sensitisation predominated in the RSV cohort compared with controls (30% vs 1%). Spirometric function was reduced in subjects with RSV with or without current asthma, but not in asthmatic controls. LCI was linked only to current asthma, airway hyperresponsiveness and FeNO.
Severe early RSV bronchiolitis is associated with an increased prevalence of allergic asthma persisting into early adulthood. Small airway dysfunction (LCI) is related to current asthma and airway inflammation but not to RSV bronchiolitis. Reduced spirometry after RSV may reflect airway remodelling.
Quantitation of respiratory viruses by PCR could potentially aid in clinical interpretation of PCR results. We conducted a study in children admitted with acute respiratory tract infections to study correlations between the clinical course of illness and semiquantitative detection of 14 respiratory viruses. Clinical improvement was associated with reduction of viral quantity after 3 days of hospitalization.
To explore the epidemiologic and clinical features of, and interactions among, multipathogen infections in hospitalized children with acute respiratory tract infection (ARTI). A prospective study of children admitted with ARTI was conducted. Peripheral blood samples were analyzed by indirect immunofluorescence to detect respiratory agents including respiratory syncytial virus; adenovirus; influenza virus (Flu) types A and B; parainfluenza virus (PIV) types 1, 2, and 3; chlamydia pneumonia; and mycoplasma pneumonia. A medical history of each child was taken.
Respiratory agents were detected in 164 (51.9%) of 316 children with ARTI. A single agent was identified in 50 (15.8%) children, and multiple agents in 114 (36.1%). Flu A was the most frequently detected agent, followed by Flu B. Coinfection occurred predominantly in August and was more frequent in children between 3 and 6 years of age. A significantly higher proportion of Flu A, Flu B, and PIV 1 was detected in samples with two or more pathogens per sample than in samples with a single pathogen.
Our study suggests that there is a high occurrence of multipathogen infections in children admitted with ARTI and that coinfection is associated with certain pathogens.
Severe respiratory syncytial virus (RSV) infection is associated with asthma but the nature of this association is imperfectly understood.
To examine the nature of the association between severe RSV infection and asthma in a population-based sample of twins.
Data on hospitalization due to RSV infection was gathered for all twins born in Denmark between 1994 and 2000 (8,280 pairs) and linked to information on asthma obtained from hospital discharge registries and parent-completed questionnaires. Genetic variance components models and direction of causation models were fitted to the observed data.
RSV hospitalization and asthma were positively associated (r = 0.43), and genetic determinants for the two disorders overlapped completely. Modeling the direction of causation between RSV hospitalization and asthma showed that a model in which asthma "causes" RSV hospitalization fitted the data significantly better (P = 0.39 for deterioration in model fit) than a model in which RSV hospitalization "causes" asthma (P < 0.001 for deterioration in model fit), even when sex, birth weight, and maternal smoking during pregnancy were accounted for.
RSV infection that is severe enough to warrant hospitalization does not cause asthma but is an indicator of the genetic predisposition to asthma.
Background: The clinical impact of polymicrobial respiratory infections remains uncertain. Previous reports are contradictory regarding an association with severe disease. Methods: Three hundred forty-six specimens from children with acute respiratory illness identified at the University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory were evaluated by direct immunofluorescent assay and/or viral culture by Clinical Microbiology Laboratory and later by molecular study for the presence of influenza, parainfluenza, respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus and human bocavirus. Demographic and clinical data were abstracted from medical records. Results: Multiple viruses were detected in 46 (21.7%) of 212 virus-positive specimens with the most frequent virus-virus combinations being HRV-res-piratory syncytial virus (n = 12), HRV-human bocavirus (n = 6) and HRV-parainfluenza virus 3 (n = 4). Risk factors for coinfection included male gender (OR [odds ratio]: 1.70, 95% confidence interval [CI]: 0.83-3.46), 6 months to 1 year age (OR: 2.15, 95% CI: 0.75-6.19) and history of immunosuppression (OR: 2.05, 95% CI: 0.99-4.23). Children with viral coinfections were less likely than children with single virus infections to be admitted to an intensive care unit (OR: 0.32, 95% CI: 0.08-1.27); however, this may be explained by undetected viral-bacterial coinfections. Conclusions: HRY respiratory syncytial virus, human bocavirus, and polymicrobial infections were prevalent in this study. Although the cross-sectional design could not easily examine polymicrobial infection and disease severity, prospective, population-based research regarding the clinical impact of such infections is warranted.
The Food and Drug Administration recently approved the use of palivizumab (pale-vizhumab), an intramuscularly administered monoclonal antibody preparation. Recommendations for its use are based on a large, randomized study demonstrating a 55% reduction in the risk of hospitalization attributable to respiratory syncytial virus (RSV) infections in high-risk pediatric patients. Infants and children with chronic lung disease (CLD), formerly designated bronchopulmonary dysplasia, as well as prematurely born infants without CLD experienced a reduced number of hospitalizations while receiving palivizumab compared with a placebo. Both palivizumab and respiratory syncytial virus immune globulin intravenous (RSV-IGIV) are available for protecting high-risk children against serious complications from RSV infections. Palivizumab is preferred for most high-risk children because of ease of administration (intramuscular), lack of interference with measles-mumps-rubella vaccine and varicella vaccine, and lack of complications associated with intravenous administration of human immune globulin products. RSV-IGIV, however, provides additional protection against other respiratory vital illnesses and may be preferred for selected high- risk children including those receiving replacement intravenous immune globulin because of underlying immune deficiency or human immunodeficiency virus infection. For premature infants about to be discharged from hospitals during the RSV season, physicians could consider administering RSV-IGIV for the first month of prophylaxis. Most of the guidelines from the American Academy of Pediatrics for the selection of infants and children to receive RSV-prophylaxis remain unchanged. Palivizumab has been shown to provide benefit for infants who were 32 to 35 weeks of gestation at birth. RSV-IGIV is contraindicated and palivizumab is not recommended for children with cyanotic congenital heart disease. The number of patients with adverse events judged to be related to palivizumab was similar to that of the placebo group (11% vs 10%, respectively); discontinuation of injections for adverse events related to palivizumab was rare.
Background:
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children. We aimed to assess the safety and efficacy of an anti-RSV monoclonal antibody (motavizumab) in healthy term (≥36 weeks' gestational age) infants for the prevention of medically attended RSV acute lower respiratory tract infections.
Methods:
This phase 3, double-blind, placebo-controlled, randomised trial enrolled healthy Native American infants aged 6 months or younger who were born at 36 weeks' gestational age in southwestern USA, on the Navajo Nation, the White Mountain Apache reservation, and the San Carlos Apache Indian reservation. Participants were randomly assigned (2:1) to receive either five monthly intramuscular doses of motavizumab (15 mg/kg) or placebo. They were followed up for 150 days after the first dose, and the primary endpoints were respiratory admission to hospital with a positive result for RSV by RT-PCR and death caused by RSV. Participants were followed up for medically attended wheezing until they reached age 3 years. Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00121108.
Findings:
During the autumn seasons (October to December) between 2004 and 2007, 2127 infants of the 2596 infants enrolled were randomly assigned to receive either motavizumab (1417) or placebo (710). After ITT analysis, motavizumab resulted in an 87% relative reduction (relative risk [RR] 0·13, 95% CI 0·08-0·21) in the proportion of infants admitted to hospital with RSV (21 [2%] of 1417 participants who received motavizumab; 80 [11%] of 710 participants who received placebo, p<0·0001). Serious adverse events were less common in particpants taking motavizumab (212 [15%]) than particpants on placebo (148 [21%]). Six deaths occurred in study participants (motavizumab, n=4 [0·3%]; placebo, n=2 [0·3%]); none were deemed to be related to the study product. Hypersensitivity events were more common in patients given motavizumab (208 [14·7%]) than in placebo recipients (87 [12·3%]; p=0·14). There was no effect on rates of medically attended wheezing in children aged 1-3 years (190 [14·9%] of participants randomly assigned to receive motavizumab vs 90 [14·0%] participants randomly assigned to receive placebo).
Interpretation:
To our knowledge, this is the only trial of an anti-RSV antibody to prevent serious RSV disease in healthy term infants. Motavizumab significantly reduced the RSV-associated inpatient and outpatient burden and set a benchmark for the efficacy of RSV prevention strategies. The findings do not support a direct, generalisable, causal association between RSV lower respiratory tract infection and subsequent long-term wheezing in term infants.
Funding:
MedImmune.
Objective
To determine the safety and efficacy of prophylaxis with palivizumab in reducing the incidence of hospitalization because of respiratory syncytial virus (RSV) infection in high-risk infants.
Methods
A randomized, double-blind, placebo-controlled trial was conducted at 139 centers in the United States, the United Kingdom, and Canada. During the 1996 to 1997 RSV season, 1502 children with prematurity (≤35 weeks) or bronchopulmonary dysplasia (BPD) were randomized to receive 5 injections of either palivizumab (15 mg/kg) or an equivalent volume of placebo by intramuscular injection every 30 days. The primary endpoint was hospitalization with confirmed RSV infection. Children were followed for 150 days (30 days from the last injection). Those with hospitalization as a result of RSV infection were evaluated for total number of days in the hospital, total days with increased supplemental oxygen, total days with moderate or severe lower respiratory tract illness, and incidence and total days of intensive care and mechanical ventilation. The incidence of hospitalization for respiratory illness not caused by RSV and the incidence of otitis media were also evaluated. The placebo and palivizumab groups were balanced at entry for demographics and RSV risk factors. Ninety-nine percent of children in both groups completed the protocol and ∼93% received all five scheduled injections.
Results
Palivizumab prophylaxis resulted in a 55% reduction in hospitalization as a result of RSV (10.6% placebo vs 4.8% palivizumab). Children with prematurity but without BPD had a 78% reduction in RSV hospitalization (8.1% vs 1.8%); children with BPD had a 39% reduction (12.8% vs 7.9%). When gender, entry age, entry weight, BPD, and gestational age were included in a logistic regression model, the effect of prophylaxis with palivizumab remained statistically significant. The palivizumab group had proportionally fewer total RSV hospital days, fewer RSV hospital days with increased oxygen, fewer RSV hospital days with a moderate/severe lower respiratory tract illness, and a lower incidence of intensive care unit admission. Palivizumab was safe and well tolerated. No significant differences were observed in reported adverse events between the two groups. Few children discontinued injections for related adverse events (0.3%). Reactions at the site of injection were uncommon (1.8% placebo vs 2.7% palivizumab); the most frequent reaction was mild and transient erythema. Mild or moderate elevations of aspartate aminotransferase occurred in 1.6% of placebo recipients and 3.6% of palivizumab recipients; for alanine aminotransferase these percentages were 2.0% and 2.3%, respectively. Hepatic and renal adverse events related to the study drug were similar in the two groups.
Conclusions
Monthly intramuscular administration of palivizumab is safe and effective for prevention of serious RSV illness in premature children and those with BPD.
Diminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations persist up to adulthood has not been established.
As part of the prospective Tucson Children's Respiratory Study, LRIs during the first 3 years of life were ascertained by pediatricians. Spirometry was performed at ages 11, 16, 22, and 26 years. The occurrence of asthma/wheeze during the previous year was ascertained at ages 11, 13, 16, 18, 22, 24, 26, and 29 years. Longitudinal random effects models and generalized estimating equations were used to assess the relation of LRIs to lung function and asthma.
Compared with participants without early-life LRIs, those with pneumonia had the most severe subsequent lung function impairment, with mean ± SE deficits of -3.9% ± 0.9% (P < .001) and -2.5% ± 0.8% (P = .001) for pre- and post-bronchodilator FEV1:FVC ratio from age 11 to 26 years, respectively. Pneumonia was associated with increased risk for asthma (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.11-3.44) and wheeze (OR: 1.94; 95% CI: 1.28-2.95) over the same age range. Early non-pneumonia LRIs were associated with mildly impaired pre-bronchodilator FEV1 (-62.8 ± 27.9mL, P = .024) and FEV1:FVC ratio (-1.1 ± 0.5%, P = .018), and wheeze (OR: 1.37; 95% CI: 1.09-1.72).
Early pneumonia is associated with asthma and impaired airway function, which is partially reversible with bronchodilators and persists into adulthood. Early pneumonia may be a major risk factor for adult chronic obstructive pulmonary disease.
Copyright © 2015 by the American Academy of Pediatrics.
Respiratory syncytial virus (RSV) is a common cause of pediatric hospitalization, but the mortality rate and estimated annual deaths are based on decades-old data. Our objective was to describe contemporary RSV-associated mortality in hospitalized infants and children aged <2 years.
We queried the Healthcare Cost and Utilization Project Kids' Inpatient Database (KID) for 2000, 2003, 2006, and 2009 and the Pediatric Health Information System (PHIS) administrative data from 2000 to 2011 for hospitalizations with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for RSV infection and mortality.
The KID data sets identified 607 937 RSV-associated admissions and 550 deaths (9.0 deaths/10 000 admissions). The PHIS data set identified 264 721 RSV-associated admissions and 671 deaths (25.4 deaths/10 000 admissions) (P < .001 compared with the KID data set). The 2009 KID data set estimated 42.0 annual deaths (3.0 deaths/10 000 admissions) for those with a primary diagnosis of RSV. The PHIS data set identified 259 deaths with a primary diagnosis of RSV, with mortality rates peaking at 14.0/10 000 admissions in 2002 and 2003 and decreasing to 4.0/10 000 patients by 2011 (odds ratio: 0.27 [95% confidence interval: 0.14-0.52]). The majority of deaths in both the KID and PHIS data sets occurred in infants with complex chronic conditions and in those with other acute conditions such as sepsis that could have contributed to their deaths.
Deaths associated with RSV are uncommon in the 21st century. Children with complex chronic conditions account for the majority of deaths, and the relative contribution of RSV infection to their deaths is unclear.
Copyright © 2015 by the American Academy of Pediatrics.
It is unclear whether the infectious etiology of severe bronchiolitis affects short-term outcomes, such as post-hospitalization relapse. We tested the hypothesis that children hospitalized with rhinovirus (RV) bronchiolitis, either as a sole pathogen or in combination with respiratory syncytial virus (RSV), are at increased risk of relapse.
We performed a 16-center, prospective cohort study of hospitalized children age <2 years with bronchiolitis. During the winters of 2007 to 2010, researchers collected clinical data and nasopharyngeal aspirates from study participants; the aspirates were tested using real-time polymerase chain reaction. The primary outcome was bronchiolitis relapse (urgent bronchiolitis visit or scheduled visit at which additions to the bronchiolitis medications were made) during the 2 weeks after hospital discharge.
Among 1836 enrolled children with 2-week follow-up data, the median age was 4 months and 60% were male. Overall, 48% had sole RSV infection, 8% had sole RV infection, and 13% had RSV/RV co-infection. Compared with children with sole RSV infection, and adjusting for 10 demographic and clinical characteristics and clustering of patients within hospitals, children with sole RV infection did not differ in their likelihood of relapse (OR, 0.99; 95%CI, 0.52-1.90; P=0.98), whereas those with RSV/RV co-infection were more likely to have relapse (OR, 1.54; 95%CI, 1.03-2.30; P=0.03).
In this prospective, multicenter, multiyear study of children hospitalized with bronchiolitis, we found that RSV/RV co-infection was independently associated with a higher likelihood of bronchiolitis relapse. Present data support the concept that the infectious etiology of severe bronchiolitis affects short-term outcomes.
BACKGROUND
Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization among infants. However, estimates of the RSV hospitalization burden have varied, and precision has been limited by the use of age strata grouped in blocks of 6 to ≥12 months.METHODS:We analyzed data from a 5-year, prospective, population-based surveillance for young children who were hospitalized with laboratory-confirmed (reverse-transcriptase polymerase chain reaction) RSV acute respiratory illness (ARI) during October through March 2000-2005. The total population at risk was stratified by month of age by birth certificate information to yield hospitalization rates.RESULTS:There were 559 (26%) RSV-infected children among the 2149 enrolled children hospitalized with ARI (85% of all eligible children with ARI). The average RSV hospitalization rate was 5.2 per 1000 children <24 months old. The highest age-specific rate was in infants 1 month old (25.9 per 1000 children). Infants ≤2 months of age, who comprised 44% of RSV-hospitalized children, had a hospitalization rate of 17.9 per 1000 children. Most children (79%) were previously healthy. Very preterm infants (<30 weeks' gestation) accounted for only 3% of RSV cases but had RSV hospitalization rates 3 times that of term infants.CONCLUSIONS:Young infants, especially those who were 1 month old, were at greatest risk of RSV hospitalization. Four-fifths of RSV-hospitalized infants were previously healthy. To substantially reduce the burden of RSV hospitalizations, effective general preventive strategies will be required for all young infants, not just those with risk factors.
Background:
Both genetic variation at the 17q21 locus and virus-induced respiratory wheezing illnesses are associated with the development of asthma. Our aim was to determine the effects of these two factors on the risk of asthma in the Childhood Origins of Asthma (COAST) and the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) birth cohorts.
Methods:
We tested genotypes at the 17q21 locus for associations with asthma and with human rhinovirus (HRV) and respiratory syncytial virus (RSV) wheezing illnesses and tested for interactions between 17q21 genotypes and HRV and RSV wheezing illnesses with respect to the risk of asthma. Finally, we examined genotype-specific expression of 17q21 genes in unstimulated and HRV-stimulated peripheral-blood mononuclear cells (PBMCs).
Results:
The 17q21 variants were associated with HRV wheezing illnesses in early life, but not with RSV wheezing illnesses. The associations of 17q21 variants with asthma were restricted to children who had had HRV wheezing illnesses, resulting in a significant interaction effect with respect to the risk of asthma. Moreover, the expression levels of ORMDL3 and of GSDMB were significantly increased in HRV-stimulated PBMCs, as compared with unstimulated PBMCs. The expression of these genes was associated with 17q21 variants in both conditions, although the increase with exposure to HRV was not genotype-specific.
Conclusions:
Variants at the 17q21 locus were associated with asthma in children who had had HRV wheezing illnesses and with expression of two genes at this locus. The expression levels of both genes increased in response to HRV stimulation, although the relative increase was not associated with the 17q21 genotypes. (Funded by the National Institutes of Health.).
Background:
The clinical impact of polymicrobial respiratory infections remains uncertain. Previous reports are contradictory regarding an association with severe disease.
Methods:
Three hundred forty-six specimens from children with acute respiratory illness identified at the University of Iowa Hospitals and Clinics Clinical Microbiology Laboratory were evaluated by direct immunofluorescent assay and/or viral culture by Clinical Microbiology Laboratory and later by molecular study for the presence of influenza, parainfluenza, respiratory syncytial virus, adenovirus, human metapneumovirus, rhinovirus and human bocavirus. Demographic and clinical data were abstracted from medical records.
Results:
Multiple viruses were detected in 46 (21.7%) of 212 virus-positive specimens with the most frequent virus-virus combinations being HRV-respiratory syncytial virus (n = 12), HRV-human bocavirus (n = 6) and HRV-parainfluenza virus 3 (n = 4). Risk factors for coinfection included male gender (OR [odds ratio]: 1.70, 95% confidence interval [CI]: 0.83-3.46), 6 months to 1 year age (OR: 2.15, 95% CI: 0.75-6.19) and history of immunosuppression (OR: 2.05, 95% CI: 0.99-4.23). Children with viral coinfections were less likely than children with single virus infections to be admitted to an intensive care unit (OR: 0.32, 95% CI: 0.08-1.27); however, this may be explained by undetected viral-bacterial coinfections.
Conclusions:
HRV, respiratory syncytial virus, human bocavirus, and polymicrobial infections were prevalent in this study. Although the cross-sectional design could not easily examine polymicrobial infection and disease severity, prospective, population-based research regarding the clinical impact of such infections is warranted.
Background:
The identification of multiple viruses during respiratory illness is increasing with advances in rapid molecular testing; however, the epidemiology of respiratory viral coinfections is not well known.
Methods:
In total, 225 childcare attendees were prospectively followed for up to 2 years. Nasal swabs were collected at respiratory illness onset and every 7-10 days until illness resolution. Swabs were tested by polymerase chain reaction for 15 respiratory viruses and subtypes.
Results:
At least 1 virus was detected in 382 (84%) of 455 new-onset illnesses with multiple viruses identified in 212 (46%). The proportion of subject swabs with multiple viruses detected changed as respiratory illnesses progressed from week to week, as did the prevalence of individual viruses. Children with multiple viruses detected at the time of illness onset had less frequent fever (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.35, 0.90), however, these children more often had illness symptoms lasting over 7 days (OR, 1.94; 95% CI, 1.20, 3.14).
Conclusions:
A high proportion of daycare attendees had multiple viruses detected during respiratory illnesses. Delay between onset of illness and viral detection varied by virus, indicating that some viruses may be underrepresented in studies of virus epidemiology that rely on only a single test at symptom onset.
Background:
Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to better understand the systemic host response to acute RSV bronchiolitis in infants and young children.
Methods:
Patients (age ≤ 24 months) who were clinically diagnosed with acute bronchiolitis and who had a positive rapid test for RSV assay were recruited from the Texas Children's Hospital emergency department. Global gene expression of peripheral whole blood cells were analyzed in 21 cases and 37 age-matched healthy controls. Transcripts exhibiting significant upregulation and downregulation as a result of RSV infection were identified and confirmed in a subset of samples using RNA sequencing. The potential pathways affected were analyzed.
Results:
Blood was obtained from patients with acute RSV bronchiolitis (mean age 6 months). Of these, 43% were admitted to the hospital, 52% were given intravenous fluids and 24% received oxygen. Highly significant expression differences were detected in a discovery cohort of White infants (N = 33) and validated in an independent group of African-American infants (N = 19). Individuals with mild disease (N = 15) could not be distinguished from subjects with clinically moderate disease (N = 5). Pathway enrichment analyses of the differentially expressed genes demonstrated extensive activation of the innate immune response, particularly the interferon signaling network. There was a significant downregulation of transcripts corresponding to antigen presentation.
To evaluate the safety, tolerance, and efficacy of palivizumab in children with hemodynamically significant congenital heart disease (CHD).
A randomized, double-blind, placebo-controlled trial included 1287 children with CHD randomly assigned 1:1 to receive 5 monthly intramuscular injections of 15 mg/kg palivizumab or placebo. Children were followed for 150 days. The primary efficacy end point was antigen-confirmed respiratory syncytial virus (RSV) hospitalization.
Palivizumab recipients had a 45% relative reduction in RSV hospitalizations (P=.003), a 56% reduction in total days of RSV hospitalization per 100 children (P=.003), and a 73% reduction in total RSV hospital days with increased supplemental oxygen per 100 children (P=.014). Adverse events were similar in the treatment groups; no child had drug discontinued for a related adverse event. Serious adverse events occurred in 55.4% of palivizumab recipients and 63.1% of placebo recipients (P<.005); none were related to palivizumab. Twenty-one children (3.3%) in the palivizumab group and 27 (4.2%) in the placebo group died; no deaths were attributed to palivizumab. The rates of cardiac surgeries performed earlier than planned were similar in the treatment groups.
Monthly palivizumab (15 mg/kg IM) was safe, well-tolerated, and effective for prophylaxis of serious RSV disease in young children with hemodynamically significant CHD.
Asthma remains an important human disease that is responsible for substantial world