Rhinoviruses as critical agents in severe bronchiolitis in infants

ObjectivesTo detect RSV or other thirteen respiratory viruses as possible causer agent of bronchiolitis in infants.MethodThis is an epidemiological analytical study, conducted using a nasopharyngeal aspirate of 173 hospitalized children younger than two years old with severe bronchiolitis in three hospitals in the Campinas Metropolitan Region (CMR) during 2013-14. The data was statically evaluated by Pearson's chi-squared test with statistical significance of 0.05 and 95% confidence level.ResultsAs expected, the most prevalent viruses detected were RSV A and B in 47% and 16% of the samples, respectively. However, almost a third of severe bronchiolitis cases there were no detection of RSV, and the viruses more commonly detected were rhinoviruses, which were identified in almost a quarter of all positive samples for at least a viral agent.ConclusionsAlthough nothing could be concluded from the disease severity and clinical-epidemiological data, the present study's results indicate that severe bronchiolitis is not always related to RSV infections in children younger than two years old, and the rhinoviruses were more prevalent in these cases. These findings reinforce the need to carry out a viral diagnosis in the hospital emergency would be very appropriate for all cases of respiratory infections in children, even for diseases in which the primary etiological agent seems to be well known.     

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??Viral bronchiolitis is one of the most common health problems in children worldwide. The most common pathogen is respiratory syncytial virus??RSV????and other pathogens include rhinovirus??human metapneumovirus??bocavirus and so on. Infant hospitalized for viral bronchiolitis will have recurrent wheezing or asthma later??disease severity??virus type??atopy and genetic polymorphisms will increase the risk of asthma. The definition of viral bronchiolitis is not uniform??and the difficulty of defining wheezing and its frequency is a great obstacle to study the relationship between them. Future studies should give full consideration to the heterogeneity of bronchiolitis??and observe and compare the risk of asthma in different phenotypes of bronchiolitis.     

Risk factors for respiratory syncytial virus associated apnoea

Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Children's Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO₂, pCO₂ and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO₂ and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8 – 6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3 – 12.9) in children with recurrent episodes of apnoea. Conclusions Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea. Received: 12 May 1997 / Accepted in revised form: 22 August 1997     

Acute viral bronchiolitis and its sequelae in developing countries

Acute viral bronchiolitis (AVB) is a common disease found throughout the world. Various aspects of it are being studied: its epidemiology, diagnosis, prognosis and treatment. Most of these studies are being conducted in developed countries, with only a few taking place in developing countries. Risk factors such as poor nutrition, an adverse environment and early weaning should be studied where these features are common. Treatment aspects such as cost-effectiveness in low income settings need further study. Use of ribavirin and respiratory syncytial virus (RSV)-immunoglobulin are good examples. Post-bronchiolitic sequelae also need to be studied in low income countries. There is evidence that bronchiolitis obliterans is unusually frequent in some Latin-American countries such as Argentina and Brazil. It will be helpful to undertake combined studies in countries with the same socio-economics, investigating the preventive and management aspects of AVB and its sequelae to reduce the morbidity and mortality.     

Surfactant protein D gene polymorphism associated with severe respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is the major respiratory tract pathogen in infancy. Host-related differences in susceptibility to severe RSV infection suggest that genetic factors may play a role. In this study, a candidate-gene approach was used to study whether the surfactant protein D (SP-D) gene polymorphism associates with severe RSV infection. DNA samples from 84 infants hospitalized for the treatment of RSV bronchiolitis and 93 healthy controls were analyzed. The controls were matched with the cases on the basis of sex, hospital district, date of birth (+/-2 wk) and gestational age at birth (+/-2 wk). Three biallelic SP-D gene polymorphisms were genotyped. Significant differences were observed in the SP-D allele frequencies for amino acid 11 between the RSV infants and their matched controls. The frequency of the allele coding for Met 11 (p = 0.033) was increased in the severe RSV group. The frequency of the homozygous genotype Met/Met for amino acid 11 was increased in the RSV group relative to the controls, whereas the heterozygous genotype tended to be less frequent among the RSV cases than in the matched controls. Conditional logistic regression analysis was used to study whether the confounders, i.e. smoking and number of children in the family, influence the association between the homozygous SP-D genotype for methionine 11 and the risk of RSV bronchiolitis. The results further confirmed this association (p = 0.028). To our knowledge, the present report provides the first evidence of a specific gene associated with susceptibility to severe RSV infection.     

Impacto clínico de la implantación de la ventilación por alto flujo de oxígeno en el tratamiento de la bronquiolitis en una planta de hospitalización pediátrica

ObjectiveTo analyse the safety and efficacy of high-flow oxygen therapy for treatment of moderate to severe bronchiolitis in children admitted to the paediatric hospital wards.MethodsA prospective observational study was conducted on children < 18 months of age with bronchiolitis admitted to the paediatric ward of a tertiary-care teaching hospital during the 2011-12 respiratory season. Children were treated with a high-flow ventilation system (Fisher & Paykel). Clinical and cardio-respiratory parameters were evaluated every hour for the duration of therapy.ResultsA total of 25 patients, with a median age of 2 months (range: 0.6-11 months) were included. Respiratory syncytial virus (RSV) was positive in 75% of cases. Indications for high-flow therapy included: progressive respiratory distress (Wood-Downes ≥ 8) (88%), apnoea (8%) and desaturation (4%). Median duration of therapy was 4 days (range: 3-7 days), with a median of 9 days in hospital (range: 8-12 days). High flow therapy was associated with a significant decrease in cardio-respiratory parameters, heart rate, respiratory rate, which resulted in a significant improvement of the Wood-Downes Score (from 10±1.21 to 3±0.77, P=.001). No adverse effects were observed. Five patients (20%) were admitted to the Paediatric Intensive Care Unit (PICU), which represents an 80% reduction of PICU admissions compared with historic data of previous years.ConclusionsHigh-flow ventilation therapy achieved a significant improvement in heart rate, respiratory rate, and scale of severity in patients with bronchiolitis. This novel therapeutic strategy allows safe management of bronchiolitis patients in the regular ward, reducing admissions to the PICU.     

Respiratory syncytial virus infection in high risk infants and the potential impact of prophylaxis in a United Kingdom cohort

BACKGROUND—Bronchiolitis caused by respiratory syncytial virus (RSV) is an important cause of morbidity in ex-premature infants. In a randomised placebo controlled trial monoclonal antibody prophylaxis showed a 55% reduction in relative risk of hospital admission for these high risk infants, against a background incidence of 10.6 admissions per 100 high risk infants.
AIMS—To follow a cohort of high risk infants in order to assess hospitalisation rate from RSV and the potential impact of prophylaxis for these patients in a UK local health authority.
METHODS—A cohort of high risk infants from a local health authority were followed over the 1998/99 and 1999/2000 RSV seasons. The high risk population was defined as infants who, at the beginning of the seasons studied, were: (1) under 6 months old and born prior to 36 weeks gestation with no domiciliary oxygen requirement; or (2) under 24 months of age and discharged home in supplemental oxygen. All admissions with bronchiolitis during the season were identified.
RESULTS—A total of 370 high risk infants were identified for the 1998/99 season and 286 for the following year. Over the two years there were 68 admissions. Significantly more admissions occurred from group 2 infants. RSV was identified in 27 cases (four admissions per hundred high risk infants). Prophylaxis may have saved up to £195 134 in hospital costs over the two years, but would have cost £1.1 million in drug acquisition costs.
CONCLUSIONS—Careful consideration of risk factors is needed when selecting infants for RSV prophylaxis.

     

Virologic testing in bronchiolitis: does it change management decisions and predict outcomes?

The aim of this study was to evaluate the clinical, therapeutic, laboratory, and radiological differences between respiratory syncytial virus (RSV) and non-RSV bronchiolitis in order to assess if the prior knowledge of viral etiology changed management decisions and would be able to predict outcomes. Medical charts of children <1 year admitted to the emergency department with bronchiolitis during two RSV seasons (2010–2012) were reviewed. We analyzed 221 episodes of bronchiolitis. The percentage of exams performed (95 % confidence interval (CI) 0.74–2.52), abnormal laboratory and radiological findings (95 % CI 0.53–16.89) did not differ between groups. RSV bronchiolitis had a more severe clinical course. However, virologic testing for RSV had low specificity in identifying at-risk patients for hospitalization, longer hospital length of stay, and need of oxygen therapy and nasogastric tube (44, 40, 42, and 35 %, respectively), and while statistically significant, the positive likelihood ratios were only slightly greater than 1. Conclusion: Although RSV bronchiolitis has a more severe clinical course, virologic testing does not help in management decisions, and at an individual level, as a performance test, it seems insufficient to precisely predict outcomes.     

Management of bronchiolitis

Bronchiolitis is the commonest cause of hospital admission in infancy. Severity varies from mild and self-limiting through to respiratory failure requiring intensive care and ventilation. Many viruses cause bronchiolitis, the commonest being respiratory syncytial virus (RSV). Supportive care is the mainstay of treatment, with emphasis on fluid replacement and oxygen therapy. Agents with evidence of no benefit in acute bronchiolitis include β₂ agonists, ipratropium, montelukast, corticosteroids, antiviral agents such as ribavirin or RSV immunoglobulin, physiotherapy, nebulized deoxyribonuclease or antibiotics. It is possible that nebulized epinephrine has a small short-term effect, and that nebulized 3% hypertonic saline administered with a bronchodilator may decrease length of stay in hospital. Preventative strategies such as RSV immunoglobulin or the anti-RSV monoclonal antibody palivizumab can decrease disease severity.     

Teenage asthma after severe infantile bronchiolitis or pneumonia

OBJECTIVE: The purpose of the study was to evaluate asthma at >13 y of age in children with infantile bronchiolitis or pneumonia. METHODS: In 1981-1982, 127 children at <2 y of age were hospitalized for bronchiolitis (n = 81) or pneumonia (n = 46). Respiratory syncytial virus (RSV) infection, eosinophilia and markers of atopy were assessed and recorded on admission. At a median age of 14.9 y, atopic and asthmatic symptoms were screened by a written questionnaire in 98/127 (77%) study subjects. RESULTS: Asthma was present, according to two definitions, in 14% to 23% in the original bronchiolitis and in 12% to 15% in the original pneumonia group. The figures were 8% to 17% in the RSV infection and 16% to 23% in the non-RSV infection group. Early asthma-predictive factors were repeated wheezing, atopic dermatitis and elevated blood eosinophils. All but one of the teenage asthmatics had allergic rhinitis. CONCLUSION: An increased risk for asthma persists until the teenage period after bronchiolitis and pneumonia in infancy. Both early and later atopy were significant risk factors. The present study was unable to demonstrate the association between early RSV infection and teenage asthma.     

Systematic literature review assessing tobacco smoke exposure as a risk factor for serious respiratory syncytial virus disease among infants and young children

Background

The role of environmental tobacco smoke (ETS) exposure as a risk factor for serious respiratory syncytial virus (RSV) disease among infants and young children has not been clearly established. This systematic review was conducted to explore the association between ETS exposure and serious RSV disease in children younger than 5?years, including infants and young children with elevated risk for serious RSV disease.

Methods

A systematic review of English-language studies using the PubMed and EMBASE databases (1990?C2009) was performed to retrieve studies that evaluated ETS as a potential risk factor for serious RSV illness. Studies assessing risk factors associated with hospitalization, emergency department visit, or physician visit due to RSV (based on laboratory confirmation of RSV or clinical diagnosis of RSV) in children under the age of 5?years were included.

Results

The literature search identified 30 relevant articles, categorized by laboratory confirmation of RSV infection (n?=?14), clinical diagnosis of RSV disease (n?=?8), and assessment of RSV disease severity (n?=?8). Across these three categories of studies, at least 1 type of ETS exposure was associated with statistically significant increases in risk in multivariate or bivariate analysis, as follows: 12 of 14 studies on risk of hospitalization or ED visit for laboratory-confirmed RSV infection; 6 of 8 studies of RSV disease based on clinical diagnosis; and 5 of the 8 studies assessing severity of RSV as shown by hospitalization rates or degree of hypoxia. Also, 7 of the 30 studies focused on populations of premature infants, and the majority (5 studies) found a significant association between ETS exposure and RSV risk in the multivariate or bivariate analyses.

Conclusion

We found ample evidence that ETS exposure places infants and young children at increased risk of hospitalization for RSV-attributable lower respiratory tract infection and increases the severity of illness among hospitalized children. Additional evidence is needed regarding the association of ETS exposure and outpatient RSV lower respiratory tract illness. Challenges and potential pitfalls of assessing ETS exposure in children are discussed.     

RANTES启动子-28C/G基因多态性与呼吸道合胞病毒致细支气管炎易感性的关联

目的 探讨正常T淋巴细胞表达和分泌的活性调节蛋白RANTES的启动子-28C/G基因多态性与呼吸道合胞病毒(RSV)致细支气管炎(既往称毛细支气管炎)易感的关联性.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测238例RSV细支气管炎患儿及288例正常对照者的RANTES-28C/G多态性,ELISA法检测血清总IgE浓度,全自动血细胞计数仪计数嗜酸性粒细胞,并搜集受检者的特应性体质史、特应性家族史及临床相关资料.结果 RANTES-28C/G基因型分布在RSV细支气管炎组和对照组均符合Hardy-Weinberg平衡.与对照组比较,RANTES-28C/G基因型及等位基因频率在RSV细支气管炎组中的分布差异均有统计学意义(G=10.22,P＜0.01;x2=9.708,P＜0.01);与CC基因型个体相比,携带G等位基因的个体发生RSV细支气管炎的风险增加了2.09倍(OR:2.09,95% CI=1.32～3.30,P＜0.01).在RSV细支气管炎组,携带G等位基因个体具有特应性体质和特应性家族史的风险分别比CC基因型个体增加了1.85倍(OR=1.85,95% CI=1.01～3.38,P＜0.05)和1.91倍(OR=1.91,95% CI=1.03～3.54,P＜0.05),其嗜酸性粒细胞计数亦显著升高(Z=-2.303,P＜0.05).结论 RANTES启动子-28C/G基因多态性与RSV细支气管炎易感性相关联,并且-28G等位基因与RSV细支气管炎患儿的特应性体质及特应性家族史相关联.     

Natural infection of infants with respiratory syncytial virus subgroups A and B: a study of frequency, disease severity, and viral load

Heterogeneity in respiratory syncytial virus (RSV) disease severity likely is due to a combination of host and viral factors. Infection with RSV subgroup A is thought to produce more severe disease than RSV-B. Higher RSV loads correlate with greater disease severity in hospitalized infants. Whether subgroup-specific variations in disease severity result from differences in RSV load has not been studied. A total of 102 RSV-hospitalized infants <2 y of age were studied. Nasal washes were collected in a standardized manner and were cultured in <3 h in parallel with an RSV quantitative standard in a HEp-2 plaque assay. RSV-A (72%) was more frequent than RSV-B. Disease severity risk factors were similar between subgroups. RSV loads were similar between A and B subgroups (4.77 versus 4.68 log PFU/mL). Measures of disease severity were also similar between subgroups.     

Bronchiolitis caused by respiratory syncytial virus in very young infants and transmitted maternal antibodies

The study with an Enzyme Linked Immunosorbent Assay of the sera of 57 infants aged less than 9 weeks and developing a bronchiolitis, argues for the absence of a protective role for the maternally transmitted anti-respiratory syncytial virus (RSV) IgG and for the existence of a positive relationship between these antibodies levels - which are not neutralizing - and the severity of RSV bronchiolitis.     

Laboratory diagnosis of COVID-19

ObjectivesThis was a non-systematic review of the literature on the laboratory diagnosis of COVID-19.Data sourcesSearches in PubMed and Google Scholar for articles made available in 2020, using the terms “diagnosis” OR “diagnostic” OR “diagnostic tests” OR “tests” AND “COVID-19” OR “SARS-CoV-2” in the title.Summary of findingsTests for the etiological agent identify genetic material of SARS-CoV-2 or humoral responses to it. The gold standard for diagnosis is the identification of viral genome targets by real-time polymerase chain reaction (RT-PCR) in respiratory tract materials during the first week of symptoms. Serological tests should be indicated from the second week of symptoms onwards. A wide range of different tests is available, with variable sensitivity and specificity, most of which require validation. Laboratory tests such as complete blood count, C-reactive protein (CRP), D-dimer, clotting tests, lactic dehydrogenase (LDH), ferritin, and procalcitonin identify risk of disease with greater severity, thromboembolic complications, myocardial damage, and/or worse prognosis. Imaging tests may be useful for diagnosis, especially when there is a compatible clinical picture, and other tests presented negative results or were unavailable.ConclusionsThe identification of genetic material of the virus by RT-PCR is the gold standard test, but its sensitivity is not satisfactory. The diagnosis of COVID-19 should be based on clinical data, epidemiological history, tests for etiological diagnosis, and tests to support the diagnosis of the disease and/or its complications. New diagnostic methods with higher sensitivity and specificity, as well as faster results, are necessary.     

毛细支气管炎的病原学及临床流行病学特征

毛细支气管炎是婴幼儿常见的急性下呼吸道感染性疾病。毛细支气管炎主要由病毒感染引起,其中呼吸道合胞病毒（RSV）最常见,肺炎支原体、 肺炎衣原体、沙眼衣原体等感染也可引起毛细支气管炎。毛细支气管炎主要发生于 2 岁以下婴幼儿,发病高峰年龄为 2～6 月龄。毛细支气管炎是导致婴儿住院的最常见原因,6月龄以下的婴儿入院率最高。由于毛细支气管炎主要是 RSV 感染所致,所以其季节特征与当地RSV的流行特征相似。毛细支气管炎是一种发病率高但病死率低的疾病。年龄＜3月龄、早产儿、先天性心脏病等是重症毛细支气管炎的危险因素。     

Neutrophil-mediated inflammation in respiratory syncytial viral bronchiolitis

BACKGROUND: The involvement of neutrophil-mediated inflammation may play an important role in the pathogenesis of acute respiratory syncytial virus bronchiolitis. However, no measurable marker is sensitive enough to assess neutrophil-mediated inflammation in the airways. Released neutrophil elastase (NE) in intraluminal airways has been reported to induce pulmonary inflammation. The aim of this study was to determine whether the amount of urinary trypsin inhibitor (UTI) in serum, a degenerate induced by NE, reflects the degree of airway inflammation in children with respiratory syncytial viral (RSV) bronchiolitis and whether the severity of inflammation is evaluated. The pre-alpha-/inter-alpha-trypsin inhibitor is assumed to be precursors of the UTI. When NE degrades these inhibitors, UTI is liberated. METHODS: Serum UTI concentrations in infants admitted with RSV bronchiolitis, other viral infections, bacterial pneumonia and control subjects were measured by means of one-step sandwich-type enzyme immunoassay. RESULTS: Serum UTI concentrations in 25 patients on admission were significantly higher than the 15 infantile control values (mean +/- SEM, 22.126 +/- 2.317 and 6.701 +/- 0.719 U/mL, respectively; P < 0.0001). The elevated levels returned to baseline values with improvement in the respiratory symptoms. Higher levels of serum UTI with RSV infection were consistently associated with clinical symptoms and artificial ventilation. Serum NE concentrations of patients were elevated in some patients but not significantly different from controls in the patients who showed only upper respiratory symptoms with RSV infections. CONCLUSION: The findings strongly suggested that neutrophil-mediated events are involved in the pathogenesis of RSV bronchiolitis, and the monitoring of UTI concentrations might be useful for evaluating the neutrophil-mediated airway inflammation.     

Prospective regional study of an epidemic of respiratory syncytial virus (RSV) bronchiolitis]

This prospective study was designed to identify risk factors associated with admission in pediatric intensive care units (PICU) among infants hospitalized for treatment of RSV induced bronchiolitis. This study was population-based and was conducted in Burgundy, a French region with 1,800,000 inhabitants where passive immunoprophylaxis for RSV bronchiolitis was not set up at the time of the study. RESULTS: From December 1st 1999 to April 30th 2000, 484 infants were hospitalized for RSV bronchiolitis in Burgundy: 19.6% were born prematurely (gestational age [GA] below 37 weeks) and at admission, 68.3% had a postnatal age below six months (mean = 5 +/- 5.9 months; median value = 3 months). The duration of hospitalization was 7.3 +/- 12.4 days (median value = 6 days). Among the 484 infants, 31 (6.4%) needed admission in PICU, eight needed mechanical ventilation (1.7%) and one died (0.2%). Univariate analysis identified anamnestic risk factors associated with admission in PICU: prematurity; low birth weight; past history of neonatal respiratory distress syndrome (RDS); mechanical ventilation for RDS treatment; bronchopulmonary dysplasia (BPD) and congenital heart disease. Multivariate analysis identified three independent factors associated with an increased risk for admission in PICU: GA below 32 weeks; RDS and congenital heart disease. CONCLUSION: This study suggests that population at risk for severe RSV bronchiolitis with PICU admission should include all very preterm infants with RDS whatever the outcome of RDS (with or without BPD). These epidemiological data could be helpful to set up indications for passive immunoprophylaxis of RSV induced bronchiolitis.     

The relationship between RSV bronchiolitis and recurrent wheeze: the chicken and the egg

Respiratory syncytial virus bronchiolitis is the most frequent cause of infant hospitalization. RSV bronchiolitis is often followed by recurrent episodes of wheeze. Pathogenesis of RSV bronchiolitis as well as post-bronchiolitis wheeze are incompletely understood. The aim of this review is to provide a brief overview of our current understanding of the complex pathogenesis of RSV bronchiolitis and post-bronchiolitis wheeze. Two non-exclusive hypotheses exist, which are paraphrased for this review as "the chicken and the egg". First, we reviewed the pre-existent genetic, pulmonary and immunological mechanisms of RSV bronchiolitis and post-bronchiolitis wheeze. Second, RSV as the causative virus of long-term airway morbidity is reviewed. Clearly, RSV infection is capable of causing direct damage to the airways and/or inducing long-term inappropriate immune responses to respiratory viruses or aero-allergens. It is concluded that intervention trials aimed at preventing RSV infections are required to establish the relative contribution of both RSV-induced and pre-existent mechanisms to the development of long-term airway disease following RSV bronchiolitis.