RESUMEN
BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear. METHODS: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed. RESULTS: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]). CONCLUSIONS: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.).
Asunto(s)
Anticuerpos Monoclonales Humanizados , Antivirales , Bronquiolitis Viral , Infecciones por Virus Sincitial Respiratorio , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Bronquiolitis Viral/tratamiento farmacológico , Bronquiolitis Viral/etiología , Bronquiolitis Viral/terapia , Bronquiolitis Viral/virología , Estudios de Casos y Controles , Hospitalización/estadística & datos numéricos , Modelos Logísticos , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/terapia , Virus Sincitial Respiratorio Humano , Respiración ArtificialRESUMEN
In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.
Asunto(s)
Hospitalización , Unidades de Cuidado Intensivo Pediátrico , Infecciones por Virus Sincitial Respiratorio , Humanos , Francia/epidemiología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Lactante , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Estudios de Casos y Controles , Masculino , Femenino , Hospitalización/estadística & datos numéricos , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , Bronquiolitis/tratamiento farmacológico , Bronquiolitis/virología , Bronquiolitis Viral/tratamiento farmacológico , Bronquiolitis Viral/virología , Resultado del TratamientoRESUMEN
Viral load measurement of Respiratory syncytial virus (RSV) in acute bronchiolitis depends on specimen collection, viral load quantification, and transport media. The aim of this study was to investigate viral load in three-way-comparative analyses; nasal swab versus nasal wash, quantitative real-time polymerase chain reaction (RT-PCR) versus cell tissue culture, and various transport media. A prospective cohort study of infants aged < 12 months, admitted to the Soroka Medical Center, due to acute bronchiolitis, was conducted. Two nasal swabs and two nasal wash samples (in UTM and VCM) were collected from each infant upon admission and after 48 h. Samples were immediately stored at -80 °C and tested at Viroclinics DDL (Rotterdam, Netherlands). Quantitative RT-PCR and quantitative virus culture were performed using tissue culture infective dose (TCID50). Spearman's correlation coefficient test assessed the correlation between the different methods, viral load, and clinical severity score. One hundred samples were collected from 13 infants (mean age 5.7 ± 3.8 months, 46% males). Twelve patients were RSV-A positive, and one was RSV-B positive. A high correlation was found between transport media- UTM and VCM (0.92, P < 0.001) and between nasal swabs and nasal wash samples (0.62, P = 0.02). RSV signals were higher in nasal wash than in swabs. PCR signals were lower in the second collection compared to the first. No correlation was found between viral load and clinical severity. Conclusion: RSV viral load is comparable across nasal wash, nasal swabs, and various transport media. However, it did not correlate with clinical severity, probably due to the limited sample size. Broader analyses are warranted. What is Known: ⢠Viral load measurement in Respiratory Syncytial Virus (RSV) bronchiolitis depends on specimen collection, viral load quantification, and transport media. ⢠The COVID-19 pandemic underscored the paramount significance of proper specimen collection, notably through nasal swabs. What is New: ⢠RSV viral load was investigated in three-way-comparative analyses. ⢠RSV viral load correlated well across PCR and tissue culture, nasal wash and swabs, and various transport media. RSV viral load did not correlate with clinical severity.
Asunto(s)
Bronquiolitis Viral , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Carga Viral , Humanos , Lactante , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/virología , Masculino , Estudios Prospectivos , Femenino , Bronquiolitis Viral/virología , Bronquiolitis Viral/diagnóstico , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Manejo de Especímenes/métodos , HospitalizaciónRESUMEN
Bronchiolitis in children is associated with significant rates of morbidity and mortality. Many studies have been performed using samples from hospitalized bronchiolitis patients, but little is known about the immunological responses from infants suffering from mild/moderate bronchiolitis that do not require hospitalization. We have studied a collection of nasal lavage fluid (NLF) samples from outpatient bronchiolitis children as a novel strategy to unravel local humoral and cellular responses, which are not fully characterized. The children were age-stratified in three groups, two of them (GI under 2-months, GII between 2-4 months) presenting a first episode of bronchiolitis, and GIII (between 4 months and 2 years) with recurrent respiratory infections. Here we show that elevated levels of pro-inflammatory cytokines (IL1ß, IL6, TNFα, IL18, IL23), regulatory cytokines (IL10, IL17A) and IFNγ were found in the three bronchiolitis cohorts. However, little or no change was observed for IL33 and MCP1, at difference to previous results from bronchiolitis hospitalized patients. Furthermore, our results show a tendency to IL1ß, IL6, IL18 and TNFα increased levels in children with mild pattern of symptom severity and in those in which non RSV respiratory virus were detected compared to RSV+ samples. By contrast, no such differences were found based on gender distribution. Bronchiolitis NLFs contained more IgM, IgG1, IgG3 IgG4 and IgA than NLF from their age-matched healthy controls. NLF from bronchiolitis children predominantly contained neutrophils, and also low frequency of monocytes and few CD4+ and CD8+ T cells. NLF from infants older than 4-months contained more intermediate monocytes and B cell subsets, including naïve and memory cells. BCR repertoire analysis of NLF samples showed a biased VH1 usage in IgM repertoires, with low levels of somatic hypermutation. Strikingly, algorithmic studies of the mutation profiles, denoted antigenic selection on IgA-NLF repertoires. Our results support the use of NLF samples to analyze immune responses and may have therapeutic implications.
Asunto(s)
Bronquiolitis Viral , Niño , Humanos , Lactante , Bronquiolitis Viral/inmunología , Bronquiolitis Viral/virología , Linfocitos T CD8-positivos , Citocinas/metabolismo , Inmunidad , Inmunoglobulina A/análisis , Inmunoglobulina M/análisis , Factor de Necrosis Tumoral alfa , Virus/aislamiento & purificaciónRESUMEN
Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6-week- to 12-month-old infants presenting at the emergency department with moderate to severe acute bronchiolitis. Viral testing was performed, and we found that 98% of samples were positive, including 90% for respiratory syncytial virus, 34% for human rhino virus, and 55% for viral co-detections, with a predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) exist. The role of virus detection and the burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.
Asunto(s)
Bronquiolitis Viral/virología , Coinfección/virología , Bronquiolitis Viral/epidemiología , Coinfección/epidemiología , Servicio de Urgencia en Hospital , Francia/epidemiología , Humanos , Lactante , Reacción en Cadena de la Polimerasa Multiplex , Nasofaringe/virología , Virus Sincitial Respiratorio Humano/clasificación , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Virus/clasificación , Virus/genética , Virus/aislamiento & purificaciónRESUMEN
Respiratory syncytial virus (RSV) bronchiolitis is not only the leading cause of hospitalization in U.S. infants, but also a major risk factor for asthma development. While emerging evidence suggests clinical heterogeneity within RSV bronchiolitis, little is known about its biologically-distinct endotypes. Here, we integrated clinical, virus, airway microbiome (species-level), transcriptome, and metabolome data of 221 infants hospitalized with RSV bronchiolitis in a multicentre prospective cohort study. We identified four biologically- and clinically-meaningful endotypes: A) clinicalclassicmicrobiomeM. nonliquefaciensinflammationIFN-intermediate, B) clinicalatopicmicrobiomeS. pneumoniae/M. catarrhalisinflammationIFN-high, C) clinicalseveremicrobiomemixedinflammationIFN-low, and D) clinicalnon-atopicmicrobiomeM.catarrhalisinflammationIL-6. Particularly, compared with endotype A infants, endotype B infants-who are characterized by a high proportion of IgE sensitization and rhinovirus coinfection, S. pneumoniae/M. catarrhalis codominance, and high IFN-α and -γ response-had a significantly higher risk for developing asthma (9% vs. 38%; OR, 6.00: 95%CI, 2.08-21.9; P = 0.002). Our findings provide an evidence base for the early identification of high-risk children during a critical period of airway development.
Asunto(s)
Asma/complicaciones , Asma/virología , Bronquiolitis Viral/complicaciones , Bronquiolitis Viral/virología , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/virología , Asma/epidemiología , Femenino , Expresión Génica , Predisposición Genética a la Enfermedad , Hospitalización , Humanos , Lactante , Masculino , Metaboloma , Microbiota , Estudios Prospectivos , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/genética , Sistema Respiratorio , Rhinovirus , Factores de Riesgo , Transcriptoma , Estados Unidos/epidemiologíaRESUMEN
Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient's biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.
Asunto(s)
Bronquiolitis Viral/virología , Antígenos de Histocompatibilidad Menor/farmacología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Transcriptoma/efectos de los fármacos , Bronquiolitis Viral/sangre , Humanos , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/efectos de los fármacos , Virus Sincitial Respiratorio Humano/patogenicidad , Índice de Severidad de la Enfermedad , Transcriptoma/inmunología , Virosis/tratamiento farmacológico , Virosis/virologíaRESUMEN
Although there is increasing evidence showing that infants with viral bronchiolitis exhibit a high degree of heterogeneity, a core uncertainty shared by many clinicians is with regard to understanding which patients are most likely to benefit from bronchodilators such as albuterol. Based on our review, we concluded that older infants with rhinovirus (RV) bronchiolitis, especially those with a nasopharyngeal microbiome dominated by Haemophilus influenzae; those affected during nonpeak months or during non-respiratory syncytial virus (RSV) predominant months; those with wheezing at presentation; those with clinical characteristics such as atopic dermatitis or a family history of asthma in a first-degree relative; and those infants infected with RSV genotypes ON1 and BA, have the greatest likelihood of benefiting from albuterol. Presently, this patient profile could serve as the basis for rational albuterol administration in patients with viral bronchiolitis, at least on a therapeutic trial basis, and it could also be the starting point for future targeted randomized clinical trials (RCTs) on the use of albuterol among a subset of infants with bronchiolitis.
Asunto(s)
Albuterol/uso terapéutico , Bronquiolitis Viral/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Bronquiolitis Viral/diagnóstico , Bronquiolitis Viral/virología , Humanos , Lactante , Nasofaringe/microbiología , Fenotipo , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/patogenicidad , Rhinovirus/patogenicidad , Estaciones del AñoRESUMEN
Bronchiolitis is a common viral illness that affects the lower respiratory tract of infants and young children. The disease is characterized by wheezing and increased mucus production and can range from mild to severe in terms of respiratory distress. This article reviews the epidemiology, clinical presentation, and treatment of bronchiolitis.
Asunto(s)
Bronquiolitis Viral/terapia , Bronquiolitis Viral/virología , Infecciones por Virus Sincitial Respiratorio , Administración por Inhalación , Corticoesteroides/administración & dosificación , Factores de Edad , Albuterol/administración & dosificación , Bronquiolitis Viral/diagnóstico , Bronquiolitis Viral/epidemiología , Femenino , Humanos , Lactante , Masculino , Nebulizadores y Vaporizadores , Ruidos Respiratorios , Virus Sincitiales Respiratorios/patogenicidad , Factores de Riesgo , Solución Salina Hipertónica/administración & dosificación , Índice de Severidad de la Enfermedad , Procedimientos Innecesarios , VacunaciónRESUMEN
Human respiratory syncytial virus (HRSV) is the leading cause of severe respiratory tract disease in infants. Most HRSV infections remain restricted to the upper respiratory tract (URT), but in a small percentage of patients the infection spreads to the lower respiratory tract, resulting in bronchiolitis or pneumonia. We have a limited understanding of HRSV pathogenesis and what factors determine disease severity, partly due to the widespread use of tissue-culture-adapted viruses. Here, we studied early viral dissemination and tropism of HRSV in cotton rats, BALB/cJ mice and C57BL/6 mice. We used a novel recombinant (r) strain based on a subgroup A clinical isolate (A11) expressing EGFP [rHRSVA11EGFP(5)]. A recombinant laboratory-adapted HRSV strain [rHRSVA2EGFP(5)] was used as a direct comparison. Our results show that rHRSVA11EGFP(5) replicated to higher viral titres than laboratory-adapted rHRSVA2EGFP(5) in the URT of cotton rats and mice. HRSV-infected cells were detected as early as 2 days post-inoculation in both species in the nasal septa and lungs. Infection was predominantly present in ciliated epithelial cells in cotton rats and in the olfactory mucosa of mice. In our opinion, this study highlights that the choice of virus strain is important when studying HRSV pathogenesis in vivo and demonstrates that A11 is a representative clinical-based virus. Additionally, we show critical differences in tropism and inflammation when comparing HRSV infection of cotton rats and mice.
Asunto(s)
Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/fisiología , Virus Sincitial Respiratorio Humano/patogenicidad , Infecciones del Sistema Respiratorio/virología , Animales , Bronquiolitis Viral/virología , Modelos Animales de Enfermedad , Humanos , Pulmón/virología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nariz/virología , Mucosa Olfatoria/virología , Mucosa Respiratoria/virología , Virus Sincitial Respiratorio Humano/genética , Sistema Respiratorio/virología , Rinitis/virología , Sigmodontinae , Carga Viral , Tropismo Viral , Replicación ViralRESUMEN
BACKGROUND: Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS: As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS: The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS: HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.
Asunto(s)
Bronquiolitis Viral/epidemiología , Infecciones por Coronavirus/epidemiología , Hospitalización , Neumonía Viral/epidemiología , Adolescente , Distribución por Edad , Betacoronavirus , Bronquiolitis Viral/fisiopatología , Bronquiolitis Viral/virología , COVID-19 , Niño , Preescolar , Infecciones por Coronavirus/fisiopatología , Infecciones por Coronavirus/virología , Coronavirus Humano NL63 , Coronavirus Humano OC43 , Femenino , Fiebre/fisiopatología , Humanos , Hipoxia/fisiopatología , Lactante , Recién Nacido , Gripe Humana/epidemiología , Gripe Humana/fisiopatología , Gripe Humana/virología , Masculino , Coronavirus del Síndrome Respiratorio de Oriente Medio , Pandemias , Infecciones por Picornaviridae/epidemiología , Infecciones por Picornaviridae/fisiopatología , Infecciones por Picornaviridae/virología , Neumonía Viral/fisiopatología , Neumonía Viral/virología , Estudios Prospectivos , Ruidos Respiratorios/fisiopatología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/fisiopatología , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/fisiopatología , Infecciones del Sistema Respiratorio/virología , Rhinovirus , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , SARS-CoV-2 , Estaciones del Año , Síndrome Respiratorio Agudo Grave , Índice de Severidad de la Enfermedad , España/epidemiologíaRESUMEN
INTRODUCTION AND OBJECTIVES: Despite the recommendation against routine use of inhaled bronchodilators in infants with viral bronchiolitis given in the main clinical practice guidelines (CPGs) on viral bronchiolitis, albuterol is widely prescribed to patients with this disease. The aim of this study was to identify predictors of prescription of albuterol in a population of infants hospitalized for viral bronchiolitis. MATERIAL AND METHODS: An analytical cross-sectional study performed during the period from March 2014 to August 2015, in a random sample of patients <2 years old hospitalized in the Fundacion Hospital La Misericordia, a hospital located in Bogota, Colombia. After reviewing the electronic medical records, we collected demographic, clinical, and disease-related information, including prescription of albuterol at any time during the course of hospitalization as the outcome variable. RESULTS: For a total of 1365 study participants, 1042 (76.3%) were prescribed with albuterol therapy. After controlling for potential confounders, it was found that age (OR 1.11; CI 95% 1.08-1.15; p<0.001), and a prolonged length of stay (LOS) (OR 1.93; CI 95% 1.44-2.60; p<0.001) were independent predictors of prescription of albuterol in our sample of patients. By contrast, albuterol prescription was less likely in the post-guideline assessment period (OR 0.41; CI 95% 0.31-0.54; p<0.001), and in infants with RSV isolation (OR 0.71; CI 95% 0.52-0.97; p=0.035). CONCLUSIONS: Albuterol was highly prescribed in our population of inpatients with the disease. The independent predictors of prescription of albuterol in our sample of patients were age, implementation of a CPG on viral bronchiolitis, RSV isolation, and LOS.
Asunto(s)
Albuterol/administración & dosificación , Bronquiolitis Viral/tratamiento farmacológico , Broncodilatadores/administración & dosificación , Prescripciones de Medicamentos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Administración por Inhalación , Factores de Edad , Albuterol/normas , Bronquiolitis Viral/diagnóstico , Bronquiolitis Viral/inmunología , Bronquiolitis Viral/virología , Broncodilatadores/normas , Colombia , Estudios Transversales , Prescripciones de Medicamentos/normas , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Adhesión a Directriz/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Masculino , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Virus Sincitiales Respiratorios/aislamiento & purificación , Medición de Riesgo/estadística & datos numéricos , Factores de RiesgoRESUMEN
Aim Determine the seasonal incidence of hospital Respiratory Syncytial Virus (RSV) bronchiolitis and explore the variables associated with admission to ward versus the Paediatric Intensive Care Unit (PICU). Method Retrospective case-control study. Children, aged ≤2 years, between November and March, over a 3 year period with a positive RSV nasopharyngeal aspirate test. Results A total of 557 children were included; 19% (n=106) required PICU admission. Children admitted to the PICU were younger in age, median (IQR) 6.93 (3.96, 11.89) weeks compared to children who remained on the wards 11.00 (5.86, 24.14) weeks. Being underweight at the point of admission (adjusted odds ratio 3.15, 95% 1.46, 6.70, p=0.003) was associated with a PICU admission. Conclusion Number of RSV bronchiolitis hospitalisations are increasing each year. Age, weight and the use of HFNC were independent predictors for PICU admission.
Asunto(s)
Bronquiolitis Viral/etiología , Bronquiolitis Viral/virología , Hospitalización/estadística & datos numéricos , Virus Sincitiales Respiratorios , Factores de Edad , Peso Corporal , Bronquiolitis Viral/epidemiología , Estudios de Casos y Controles , Niño , Humanos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: It is unclear whether multiple respiratory viral infections are associated with more severe bronchiolitis requiring pediatric intensive care unit (PICU) admission. We aimed to identify the association between multiple respiratory viral infections and PICU admission among infants with bronchiolitis. METHODS: We performed a 1:1 case-control study enrolling previously healthy full-term infants (≤12 months) with bronchiolitis admitted to the PICU as cases and those to the general pediatric ward as controls from 2015 to 2017. Multiplex polymerase chain reaction (PCR) was used for detection of the respiratory viruses. We summarized the characteristics of infants admitted to the PICU and the general pediatric unit. Multivariable logistic regression analysis was used to fit the association between multiple respiratory viral infections (≥2 strains) and PICU admission. RESULTS: A total of 135 infants admitted to the PICU were compared with 135 randomly selected control infants admitted to the general pediatric unit. The PICU patients were younger (median: 2.2 months, interquartile range: 1.3-4.2) than the general ward patients (median: 3.2 months, interquartile range: 1.6-6.4). Respiratory syncytial virus (74.1%), rhinovirus (28.9%), and coronavirus (5.9%) were the most common viruses for bronchiolitis requiring PICU admission. Patients with bronchiolitis admitted to the PICU tended to have multiple viral infections compared with patients on the general ward (23.0% vs. 10.4%, P<0.001). In the multivariable logistic regression analysis, bronchiolitis with multiple viral infections was associated with higher odds of PICU admission (adjusted odds ratio: 2.56, 95% confidence interval: 1.17-5.57, P=0.02). CONCLUSION: Infants with multiviral bronchiolitis have higher odds of PICU admission compared with those with a single or nondetectable viral infection.
Asunto(s)
Bronquiolitis Viral/virología , Coinfección/virología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Admisión del Paciente/estadística & datos numéricos , Bronquiolitis Viral/diagnóstico , Bronquiolitis Viral/terapia , Estudios de Casos y Controles , Coinfección/diagnóstico , Coinfección/terapia , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Although recent guidelines recommend a minimalist approach to bronchiolitis, there are several issues with this posture. First, there are concerns about the definition of the disease, the quality of the guidelines, the method of administration of bronchodilators, and the availability of tools to evaluate the response to therapies. Second, for decades it has been assumed that all cases of viral bronchiolitis are the same, but recent evidence has shown that this is not the case. Distinct bronchiolitis phenotypes have been described, with heterogeneity in clinical presentation, molecular immune signatures and clinically relevant outcomes such as respiratory failure and recurrent wheezing. New research is critically needed to refine viral bronchiolitis phenotyping at the molecular and clinical levels as well as to define phenotype-specific responses to different therapeutic options.
Asunto(s)
Bronquiolitis Viral/tratamiento farmacológico , Bronquiolitis Viral/fisiopatología , Broncodilatadores/uso terapéutico , Ruidos Respiratorios/fisiopatología , Péptidos Catiónicos Antimicrobianos/inmunología , Bronquiolitis Viral/inmunología , Bronquiolitis Viral/virología , Dermatitis Atópica/inmunología , Eosinofilia/sangre , Adhesión a Directriz , Hospitalización , Humanos , Microbiota/inmunología , Fenotipo , Infecciones por Picornaviridae/tratamiento farmacológico , Infecciones por Picornaviridae/inmunología , Infecciones por Picornaviridae/fisiopatología , Guías de Práctica Clínica como Asunto , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/fisiopatología , Virus Sincitial Respiratorio Humano , Rhinovirus , Células Th2/inmunología , CatelicidinasRESUMEN
Respiratory syncytial virus (RSV) is worldwide a very important virus leading to infection of the respiratory system. In particular preterm babies, infants and elderly adults are prone to developing severe diseases such as bronchiolitis or pneumonia, which require intensive care and cause increased mortality. Although RSV is rapidly detected, preventive and therapeutic measures are limited. New antivirals are already in clinical trials.
Asunto(s)
Antivirales/administración & dosificación , Bronquiolitis/diagnóstico , Bronquiolitis/prevención & control , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Infecciones por Virus Sincitial Respiratorio/prevención & control , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Adulto , Anciano , Antivirales/uso terapéutico , Bronquiolitis/tratamiento farmacológico , Bronquiolitis/virología , Bronquiolitis Viral/diagnóstico , Bronquiolitis Viral/virología , Humanos , Lactante , Recién Nacido , Neumonía/diagnóstico , Neumonía/virología , Infecciones por Virus Sincitial Respiratorio/tratamiento farmacológico , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/inmunología , Factores de RiesgoAsunto(s)
Asma/virología , Proteínas Sanguíneas/análisis , Bronquiolitis Viral/virología , Resfriado Común/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/fisiología , Rhinovirus/fisiología , Asma/inmunología , Bronquiolitis Viral/inmunología , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Metabolismo de los Lípidos , Masculino , Metaboloma , Estudios Prospectivos , Riesgo , Índice de Severidad de la EnfermedadRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Lactante , Infecciones por Virus Sincitial Respiratorio/complicaciones , Enfermedades del Sistema Nervioso/etiología , Bronquiolitis Viral/complicaciones , Bronquiolitis Viral/virologíaRESUMEN
INTRODUCTION: Passive transplacental immunity against respiratory syncytial virus (RSV) appears to mediate in the protection of the infant for the first 6 months of life. Lower environmental exposure in pregnant women to RSV epidemic may influence the susceptibility of these infants to infection by lowering the levels of antibodies that are transferred to the fetus. OBJECTIVES: To contrast the risk of severe disease progression in infants with acute bronchiolitis by RSV, according to the mother's level of exposure to epidemic. METHOD: Retrospective cohort study of previously healthy infants with RSV-acute bronchiolitis during 5 epidemics was made. We compared the severity of the infection in those born during the period of risk (when is less likely the mother's exposure to epidemic and the transfer of antibodies to the fetus: October 15th-December 15 th in our latitude) with the rest of acute bronchiolitis. Bivariate analysis was performed regarding birth in period of risk and the rest of variables, using the Chi-square test. Multivariate logistic regression analysis was performed to study possible classical confounding factors. RESULTS: 695 infants were included in the study. 356 infants were born during the period of risk. Of the 56 patients requiring admission to PICU, 40 of them (71.4%) were born in this period (p = 0.002). In the multivariate analysis, the birth in the period of risk showed a 6.5 OR (95% CI: 2.13-19.7) independently of the rest of variables. CONCLUSIONS: The worst clinical disease progression of the acute bronchiolitis by the RSV in less than 6 months age is related to lower exposure of the pregnant woman to the RSV epidemic
INTRODUCCIÓN: La inmunidad pasiva transplacentaria contra el virus respiratorio sincitial (VRS) parece mediar en la protección del lactante durante los primeros 6 meses de vida. La menor exposición ambiental en embarazadas a la epidemia del VRS puede influir en la susceptibilidad de estos niños a la infección al disminuir los niveles de anticuerpos que se transfieren al feto. OBJETIVOS: Contrastar el riesgo de progresión grave de la enfermedad en los lactantes con bronquiolitis aguda por VRS, de acuerdo con el nivel de exposición de la madre a la epidemia. MÉTODO: Se realizó un estudio de cohortes retrospectivo de recién nacidos previamente sanos con bronquiolitis aguda por VRS durante 5 epidemias. Comparamos la gravedad de la infección en los nacidos durante el período de riesgo (cuando es menos probable la exposición de la madre a la epidemia en nuestra latitud y la transferencia de anticuerpos al feto: del 15 de octubre al 15 de diciembre) con el resto de las bronquiolitis agudas. El análisis bivariante se realizó con respecto al nacimiento en el período de riesgo y el resto de las variables, utilizando la prueba de Chi-cuadrado. Posteriormente un análisis de regresión logística multivariable para estudiar los posibles factores de confusión. RESULTADOS: Seiscientos noventa y cinco bebés fueron incluidos en el estudio. Trescientos cincuenta y seis bebés nacieron durante el período de riesgo. De los 56 pacientes que requieren ingreso en la UCIP, 40 de ellos (71,4%) nacieron en este período (p = 0,002). En el análisis multivariante, el nacimiento en el período de riesgo mostró una OR de 6,5 (IC 95%: 2,13-19,7) independientemente del resto de las variables. CONCLUSIONES: La evolución más grave de la enfermedad clínica de la bronquiolitis aguda por el VRS en menores de 6 meses de edad se relaciona con una menor exposición de la embarazada a la epidemia del VRS
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Bronquiolitis Viral/inmunología , Bronquiolitis Viral/virología , Inmunidad Materno-Adquirida/inmunología , Embarazo/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Enfermedad Aguda , Infecciones por Virus Sincitial Respiratorio/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estudios de CohortesRESUMEN
Human respiratory syncytial virus (HRSV) is the main cause of bronchiolitis during the first year of life, when infections by other viruses, such as rhinovirus, also occur and are clinically indistinguishable from those caused by HRSV. In hospitalized infants with bronchiolitis, the analysis of gene expression profiles from peripheral blood mononuclear cells (PBMC) may be useful for the rapid identification of etiological factors, as well as for developing diagnostic tests, and elucidating pathogenic mechanisms triggered by different viral agents. In this study we conducted a comparative global gene expression analysis of PBMC obtained from two groups of infants with acute viral bronchiolitis who were infected by HRSV (HRSV group) or by HRV (HRV group). We employed a weighted gene co-expression network analysis (WGCNA) which allows the identification of transcriptional modules and their correlations with HRSV or HRV groups. This approach permitted the identification of distinct transcription modules for the HRSV and HRV groups. According to these data, the immune response to HRSV infection-comparatively to HRV infection-was more associated to the activation of the interferon gamma signaling pathways and less related to neutrophil activation mechanisms. Moreover, we also identified host-response molecular markers that could be used for etiopathogenic diagnosis. These results may contribute to the development of new tests for respiratory virus identification. The finding that distinct transcriptional profiles are associated to specific host responses to HRSV or to HRV may also contribute to the elucidation of the pathogenic mechanisms triggered by different respiratory viruses, paving the way for new therapeutic strategies.