The impact of the recent AAP changes in palivizumab authorization on RSV-induced bronchiolitis severity and incidence.
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ABSTRACT:
SUBMITTER: Capizzi A
PROVIDER: S-EPMC5557508 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:The trends in hospitalization rates and risk factors for severe bronchiolitis have not been recently described, especially after the routine implementation of prophylaxis for respiratory syncytial virus (RSV) infections.To define the burden of hospitalizations related to RSV and non-RSV bronchiolitis in a tertiary-care children's hospital from 2002 to 2007 and to identify the risk factors associated with severe disease.Medical records of patients hospitalized for bronchiolitis were reviewed for demographic, clinical, microbiologic, and radiologic characteristics as well as the presence of underlying medical conditions. Differences were evaluated between children with RSV and non-RSV bronchiolitis, and multivariable logistic regression analyses were performed to identify independent risk factors for severe disease.Bronchiolitis hospitalizations in children younger than 2 years old (n = 4800) significantly increased from 536 (3.3%) in 2002 to 1241 (5.5%) in 2007, mainly because of RSV infections. Patients with RSV bronchiolitis (n = 2840 [66%]) were younger at hospitalization and had a lower percentage of underlying medical conditions than children hospitalized with non-RSV bronchiolitis (27 vs 37.5%; P < .001). However, disease severity defined by length of hospitalization and requirement of supplemental oxygen, intensive care, and mechanical ventilation was significantly worse in children with RSV bronchiolitis. RSV infection and prematurity, regardless of the etiology, were identified as independent risk factors for severe bronchiolitis.There was a significant increase in hospitalizations for RSV bronchiolitis from 2002 to 2007. A majority of the children with RSV bronchiolitis were previously healthy, but their disease severity was worse compared with those hospitalized with non-RSV bronchiolitis.
| S-EPMC3761792 | biostudies-literature
Project description:Acute viral bronchiolitis causes significant mortality in the developing world, is the number one cause of infant hospitalisation in the developed world, and is associated with the later development of chronic lung diseases such as asthma. A vaccine against respiratory syncytial virus (RSV), the leading cause of viral bronchiolitis in infancy, remains elusive, and hence new therapeutic modalities are needed to limit disease severity. However, much remains unknown about the underlying pathogenic mechanisms. Neutrophilic inflammation is the predominant phenotype observed in infants with both mild and severe disease, however, a clear understanding of the beneficial and deleterious effects of neutrophils is lacking. In this review, we describe the multifaceted roles of neutrophils in host defence and antiviral immunity, consider their contribution to bronchiolitis pathogenesis, and discuss whether new approaches that target neutrophil effector functions will be suitable for treating severe RSV bronchiolitis.
| S-EPMC7472258 | biostudies-literature
Project description:AimWe sought to determine the proportion of bronchiolitis episodes attributable to respiratory syncytial virus (RSV) among ICD-9 coded infant bronchiolitis episodes which were tested for RSV.MethodsBronchiolitis healthcare encounters were extracted from Kaiser Permanente Northern California databases for years 2006 to 2009. We used ICD-9 codes for bronchiolitis to capture bronchiolitis-related healthcare encounters including hospital admissions (Hospitalization), emergency department visits (EDV), and outpatient visits (OPV). We reported the monthly proportion of RSV-positive bronchiolitis episodes among tested bronchiolitis episodes. We used logistic regression to assess association between bronchiolitis episodes and patient demographic and health care characteristics. We also used logistic regression to assess association between decision to test and patient demographics and health care characteristics.ResultsAmong 10,411 ICD-9 coded infant bronchiolitis episodes, 29% were RSV tested. Fifty one percent of those tested were RSV positive. Between December and February, and in infants ≤6 months, the proportion of bronchiolitis episodes that were attributable to RSV was 77.2% among hospitalized episodes, 78.3% among EDV episodes, and 60.9% among OPV episodes, respectively. The proportion of RSV-positive bronchiolitis episodes varied based upon infant age at diagnosis, level of health care service used, and time of the year of the episode.ConclusionEstimation of the proportion of ICD-9 coded bronchiolitis episodes attributable to RSV is more specific when restricting to bronchiolitis episodes during peak months, younger infant age, and those requiring higher level of healthcare.
| S-EPMC6295609 | biostudies-literature
Project description:While 30%-70% of RSV-infected infants develop bronchiolitis, 2% require hospitalization. It is not clear why disease severity differs among healthy, full-term infants; however, virus titers, inflammation, and Th2 bias are proposed explanations. While TLR4 is associated with these disease phenotypes, the role of this receptor in respiratory syncytial virus (RSV) pathogenesis is controversial. Here, we evaluated the interaction between TLR4 and environmental factors in RSV disease and defined the immune mediators associated with severe illness. Two independent populations of infants with RSV bronchiolitis revealed that the severity of RSV infection is determined by the TLR4 genotype of the individual and by environmental exposure to LPS. RSV-infected infants with severe disease exhibited a high GATA3/T-bet ratio, which manifested as a high IL-4/IFN-? ratio in respiratory secretions. The IL-4/IFN-? ratio present in infants with severe RSV is indicative of Th2 polarization. Murine models of RSV infection confirmed that LPS exposure, Tlr4 genotype, and Th2 polarization influence disease phenotypes. Together, the results of this study identify environmental and genetic factors that influence RSV pathogenesis and reveal that a high IL-4/IFN-? ratio is associated with severe disease. Moreover, these molecules should be explored as potential targets for therapeutic intervention.
| S-EPMC4319428 | biostudies-literature
Project description:ObjectivesAcute bronchiolitis commonly causes respiratory failure in children ≤2 years, and is particularly severe in those with Down syndrome (DS). Obstructive sleep apnea (OSA), common in DS, is also associated with respiratory complications. However, it is unknown whether OSA is associated with worse outcomes in children with and without DS, hospitalized with bronchiolitis. We hypothesized that in children with bronchiolitis, OSA is associated with worse outcomes in those with DS, independent of DS-related comorbidities.MethodsHospital discharge records of children with bronchiolitis aged ≤2 years were obtained for 1997-2012 from the Kid's Inpatient Database. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were non-invasive mechanical ventilation (NIMV), length of hospital stay, and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for DS-associated comorbidities.ResultsThere were 928,961 hospitalizations for bronchiolitis. The DS group with bronchiolitis (n = 8697) was more likely to have OSA [241 (2.77%) vs 1293 (0.14%), p < 0.001] compared to the non-DS group (n = 920,264). Multivariable logistic regression showed that OSA was associated with IMV (adjusted odds ratio [OR], 3.32 [95% CI 2.54-4.35], p < 0.0001) in all children with bronchiolitis; and in those with DS, it was associated with IMV (adjusted OR, 2.34 [95% CI 1.38-3.97], p = 0.002), NIMV (adjusted OR, 8.21 [95% CI 4.48-15.04], p < 0.0001) and IACH (adjusted β, 0.18 [95% CI 0.02-0.34], p = 0.031).ConclusionsOSA is independently associated with assisted ventilation in all children hospitalized with bronchiolitis, regardless of DS-associated comorbidities in those with DS. The severity of bronchiolitis in children with DS may be driven by the high prevalence of OSA.
| S-EPMC8205980 | biostudies-literature
Project description:BackgroundSince the 1980s, Spain experienced two decades of sharply increasing breast cancer incidence. Declines in breast cancer incidence have recently been reported in many developed countries. We examined whether a similar downturn might have taken place in Spain in recent years.MethodsCases of invasive female breast cancer were drawn from all population-based Spanish cancer registries that had at least 10 years of uninterrupted registration over the period 1980-2004. Overall and age-specific changes in incidence rates were evaluated using change-point Poisson models, which allow for accurate detection and estimation of trend changes. All statistical tests were two-sided.ResultsA total of 80,453 incident cases of invasive breast cancer were identified. Overall age- and registry-adjusted incidence rates rose by 2.9% (95% confidence interval [CI] = 2.7% to 3.1%) annually during the 1980s and 1990s; there was a statistically significant change in this trend in 2001 (95% CI = 1998 to 2004; P value for the existence of a change point <.001), after which incidence declined annually by 3.0% (95% CI = 1.8% to 4.1%). This trend differed by age group: There was a steady increase in incidence for women younger than 45 years, an abrupt downturn in 2001 for women aged 45-64 years, and a gradual leveling off in 1995 for women aged 65 years or older. Separate analyses for registries that had at least 15 years of uninterrupted registration detected a statistically significant interruption of the previous upward trend in breast cancer incidence in provinces that had aggressive breast cancer screening programs and high screening participation rates, including Navarra (change point = 1991, P < .001), Granada (change point = 2002, P = .003), Bizkaia (change point = 1998, P < .001), Gipuzkoa (change point = 1998, P = .001), and Araba (change point = 1997, P = .002).ConclusionsThe recent downturn in breast cancer incidence among Spanish women older than 45 years is best explained by a period effect linked to screening saturation.
| S-EPMC2778670 | biostudies-literature
Project description:Between 75 000 and 125 000 U.S. infants are hospitalized for respiratory syncytial virus (RSV) bronchiolitis every year. Up to half will be diagnosed with asthma in later childhood. Vitamin D deficiency has been associated with susceptibility to asthma and respiratory infections. Measured vitamin D is largely bound to vitamin D-binding protein (VDBP); VDBP levels are influenced by its gene (GC) haplotype.We assessed the relationship between polymorphisms rs7041 and rs4588, which define haplotypes GC1s, GC1f, and GC2, and RSV bronchiolitis susceptibility and subsequent asthma.We retrospectively recruited 198 otherwise healthy children (93% White) hospitalized for severe RSV bronchiolitis in Boston and 333 parents into a follow-up study to assess asthma diagnosis. Data were analysed using family-based genetic association tests. We independently validated our results in 465 White children hospitalized with RSV bronchiolitis and 930 White population controls from the Netherlands.The rs7041_C allele (denoting haplotype GC1s) was overtransmitted (P = 0.02, additive model) in the entire Boston cohort, in Whites (P = 0.03), and especially in children subsequently diagnosed with asthma (P = 0.006). The GC1f haplotype was undertransmitted in the asthma subgroups (all races and White, both P < 0.05). The rs7041_C allele was also more frequent in the RSV bronchiolitis group compared with controls (OR 1.12, 95% CI 1.02, 1.4, P = 0.03) in the Netherlands, especially in mechanically ventilated patients (P = 0.009).GC1s haplotype carriage may increase the risk of RSV bronchiolitis in infancy and subsequent asthma development. The GC1s haplotype is associated with higher VDBP levels, resulting in less freely available vitamin D.Vitamin D-binding protein (VDBP) haplotypes influence free vitamin D levels. We report an association between a VDBP haplotype and hospitalization for RSV bronchiolitis in infancy in two independent cohorts.
| S-EPMC5062603 | biostudies-literature
Project description:Lung and airway neutrophils are a hallmark of severe disease in infants with respiratory syncytial virus (RSV)-induced lower respiratory tract infections. Despite their abundance in the lungs during RSV infection of both mice and man, the role of neutrophils in viral control and in immune pathology is not clear. Here, antibody mediated neutrophil depletion was used to investigate the degree to which neutrophils impact the lung immune environment, the control of viral replication and the peak severity of disease after RSV infection of mice. Neutrophil depletion did not substantially affect the levels of inflammatory mediators such as type I interferons, IL-6, TNF-α or IL-1β in response to RSV. In addition, the lack of neutrophils did not change the viral load during RSV infection. Neither neutrophil depletion nor the enhancement of lung neutrophils by administration of the chemoattractant CXCL1 during RSV infection affected disease severity as measured by weight loss. Therefore, in this model of RSV infection, lung neutrophils do not offer obvious benefits to the host in terms of increasing anti-viral inflammatory responses or restricting viral replication and neutrophils do not contribute to disease severity.
| S-EPMC6981203 | biostudies-literature
Project description:Little is known about the relationship between the specific airway microbiota composition and severity of bronchiolitis. We aimed to identify nasopharyngeal microbiota profiles and link these profiles to acute severity in infants hospitalised for bronchiolitis.We conducted a multicentre prospective cohort study of 1005 infants (age <1?year) hospitalised for bronchiolitis over three winters, 2011-2014. By applying a 16S rRNA gene sequence and clustering approach to the nasopharyngeal aspirates collected within 24?h of hospitalisation, we determined nasopharyngeal microbiota profiles and their association with bronchiolitis severity. The primary outcome was intensive care use, i.e. admission to an intensive care unit or use of mechanical ventilation.We identified four nasopharyngeal microbiota profiles: three profiles were dominated by one of Haemophilus, Moraxella or Streptococcus, while the fourth profile had the highest bacterial richness. The rate of intensive care use was highest in infants with a Haemophilus-dominant profile and lowest in those with a Moraxella-dominant profile (20.2% versus 12.3%; unadjusted OR 1.81, 95% CI 1.07-3.11, p=0.03). After adjusting for 11 patient-level confounders, the rate remained significantly higher in infants with Haemophilus-dominant profiles (OR 1.98, 95% CI 1.08-3.62, p=0.03). These findings were externally validated in a separate cohort of 307 children hospitalised for bronchiolitis.
| S-EPMC5459592 | biostudies-literature
Project description:BACKGROUND:The pathophysiological basis of severe respiratory syncytial virus (RSV) bronchiolitis in infancy is poorly understood and has hindered vaccine development. Studies implicate the cell-mediated immune response in the pathogenesis of the disease. A recent twin study estimated a heritable contribution of 22% to RSV bronchiolitis. Genetic epidemiology provides a new approach to identifying important immune determinants of disease severity. METHODS:A comprehensive high-density gene-region association study for severe RSV bronchiolitis in infancy at 5q31 across 11 genes including the Th2-cytokine cluster was performed. A haplotype tagging approach was used to analyse genetic variation at 113 single nucleotide polymorphisms (SNPs) in 780 independent cases and 1045 controls. The study had sufficient power to detect small effects, perform extensive haplotype analysis and analyse both a principal phenotype and a refined age-limited phenotype enriched for first-exposure RSV infection. RESULTS:SNP associations were found at IL4 and a highly significant risk haplotype was identified across IL13 CNS-1 and IL4 (odds ratio 1.69, p<0.0001), present in both case-control and family-based analyses. All associations were strongest for a phenotype limited to <6 months of age, implicating this locus in primary RSV disease. The same risk haplotype has previously been shown to be associated with increased IL13 expression. CONCLUSIONS:A haplotype at IL13-1L4, which is associated with increased IL13 production, confers an increased risk of severe primary RSV bronchiolitis in early infancy. This study, together with previous studies implicating the same locus in atopic sensitisation, suggests that primary RSV bronchiolitis and atopy share a genetic contribution at the IL13-IL4 locus.
| S-EPMC3015100 | biostudies-literature