The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis.

The human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, possibly due to the properties of the immature neonatal pulmonary immune system. Using the newborn lamb, a classical model of human lung development and a translational model of RSV infection, we aimed to explore the role of cell-mediated immunity in RSV disease during early life. Remarkably, in healthy conditions, the developing T cell compartment of the neonatal lung showed major differences to that seen in the mature adult lung. The most striking observation being a high baseline frequency of bronchoalveolar IL-4-producing CD4+ and CD8+ T cells, which declined progressively over developmental age. RSV infection exacerbated this pro-type 2 environment in the bronchoalveolar space, rather than inducing a type 2 response per se. Moreover, regulatory T cell suppressive functions occurred very early to dampen this pro-type 2 environment, rather than shutting them down afterwards, while γδ T cells dropped and failed to produce IL-17. Importantly, RSV disease severity was related to the magnitude of those unconventional bronchoalveolar T cell responses. These findings provide novel insights in the mechanisms of RSV immunopathogenesis in early life, and constitute a major step for the understanding of RSV disease severity.

Are late preterm infants as susceptible to RSV infection as full term infants?

Preterm infants are at increased risk of being rehospitalised during the first few months of life with severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) that usually manifests as apnea and hypoxemia. This occurs more commonly in preterm infants < 33 weeks gestational age (GA), but recent studies demonstrate that late preterm infants (those born between 34 weeks and 0 days to 36 weeks and 6 days GA) are equally susceptible to RSV LRTI as those with lower GA. Factors associated with severe LRTI include immaturity of both the humoral and cell-mediated immune system and interrupted lung development prior to 36 weeks GA which results in lower functional residual capacity, reduced compliance, diminished forced expiratory air flow and impaired gas exchange. Morbidity and mortality are significantly increased in late preterms compared to their term counterparts. Prophylaxis with palivizumab against RSV infection seems to be crucial. Due to the large number of infants in this age group, additional risk factors have been identified in order to tailor palivizumab prophylaxis effectively to those at highest risk for severe RSV LRTI.

Special populations: do we need evidence from randomized controlled trials to support the need for respiratory syncytial virus prophylaxis?

Congenital abnormalities and impaired mechanisms that govern the normal coordinated physiology of breathing, sucking, swallowing and airway clearance, place infants with underlying medical disorders at high risk for respiratory morbidity following respiratory syncytial virus (RSV) lower respiratory tract infection. The use of RSV prophylaxis in premature infants' ≤ 35 weeks gestational age, infants with chronic lung and hemodynamically significant heart disease is firmly established through randomized controlled clinical trials (RCT's). RSV prophylaxis in infants with serious medical illnesses must be justified based on emerging scientific literature and the overriding concept of achieving a balance between benefit and harm with treatment. This article will explore the current evidence for palivizumab prophylaxis in a variety of disorders and examine existing differences between pediatric advisory body recommendations and real world practice.

Respiratory outcomes, utilization and costs 12 months following a respiratory syncytial virus diagnosis among commercially insured late-preterm infants.

OBJECTIVES: To determine, among a commercially-insured population of late-preterm infants, utilization of healthcare resources and costs during the 1 year following a diagnosis of respiratory syncytial virus lower respiratory infection (RSV LRI). METHODS: Administrative claims for non-capitated, commercially-insured infants <1 year old were used to identify infants diagnosed with RSV LRI and unspecified bronchiolitis/pneumonia (UBP). Infants were stratified by the setting of diagnosis. Infants without evidence of RSV LRI or UBP were selected as a comparison group. Economic and clinical outcomes were analyzed descriptively using propensity score weighting and logged ordinary least squares models were used to examine the relationship between RSV and costs (adjusted to 2006 USD) incurred within 1 year of RSV LRI. RESULTS: The majority of infants were 3 months or older at the time of RSV LRI or UBP diagnosis. The rate of wheezing was significantly greater for infants in the RSV LRI and UBP cohorts relative to the comparison group (p < 0.001). Infantile asthma rates were 6-9 times higher among RSV LRI and UBP infants than the comparison group. RSV LRI and UBP infants also had significantly more emergency department visits and outpatient visits than the comparison group. The marginal healthcare costs were significantly higher for RSV LRI inpatients ($24,027) and outpatients ($2703) infants than for the comparison group (all p < 0.001). CONCLUSION: Commercially insured late-preterm infants with RSV infection are at high risk for recurrent wheezing and infantile asthma during the 1-year period after the initial episode and impose a significant economic burden to the healthcare system.

Risk-Scoring Tool for respiratory syncytial virus prophylaxis in premature infants born at 33-35 completed weeks' gestational age in Canada.

OBJECTIVE: To study the impact of the Risk-Scoring Tool (RST) as a strategy for targeting prophylaxis effectively in 33-35-week gestational age (GA) Canadian infants who range from low to high risk by evaluating the subsequent incidence of respiratory syncytial virus (RSV) infections resulting in emergency room (ER) visits and hospitalization. DESIGN: Prospective, descriptive study. SETTING: McMaster Children's Hospital and St Joseph's Healthcare in Hamilton, Ontario. PARTICIPANTS: Premature infants between 33 and 35 weeks' completed gestation who were less than 6 months' chronological age at the start of, or during, the local 2005-2008 RSV winter seasons. METHODS: A validated, Canadian RST was used to calculate a total risk score based on seven risk factors. Only infants at moderate (RST score 49-64) and high risk (RST score 65-100) received palivizumab at monthly intervals from November to April and were followed during the respective RSV seasons. All parents received information on RSV prevention at hospital discharge. Parents of all recruited infants were contacted by telephone in May at the end of each season, and medical records were checked to determine ER visits for RSV-related respiratory tract infections and RSV hospitalization. Means, standard deviations, ranges, and percents were used to describe the variables for patients enrolled in the study. RESULTS: Over 3 years, 430 infants were recruited. Of these, 346 (81%), 57 (13%), and 27 (6%) were in the low-, moderate- and high-risk categories, respectively, based on their risk scores. A total of 78 (18.1%) infants received full courses of palivizumab. Six out of 57 (10.5%) infants in the moderate-risk group did not receive prophylaxis, while all 27 high-risk group infants received palivizumab. Seven (1.6%) infants were RSV-positive and five (low-risk) infants were hospitalized. One high-risk, RSV-positive infant, was seen in the ER, and discharged home. There were no statistical differences in the number of infants with RSV-related ER visits and hospitalizations within the risk category groups (p = 0.43). The limitations of this study include the observational design and the relatively small sample size. CONCLUSIONS: The RST is a practical, easy-to-use instrument to guide judicious RSV prophylaxis for moderate-high-risk, 33-35-week GA infants. It is cost-effective, reducing hospitalization in infants who are most 'at-risk', while avoiding prophylaxis in a large segment (81.9%) of this GA cohort who are considered low risk for RSV infection.

[Prevalence of Chlamydia trachomatis in newborn infants with respiratory problems]. / Prevalencia de Chlamydia trachomatis en recién nacidos con dificultad respiratoria.

The prevalence of C. trachomatis in neonates with respiratory distress was studied after 24 h of birth, nine patients were positive for C. trachomatis culture (12.9%). The chest radiographs showed six with hyaline membrane disease and two with pneumonia. One patient with treatment of ventilation mechanics developed bronchopulmonary dysplasia and was C. trachomatis positive in a second cell culture. Of the nine patients with C. trachomatis, eight were neonates preterm with low weight to the birth and with leukocytosis. Six patients were delivered by cesarean section. These results suggest that C. trachomatis can participate in an important way in the development of the distress respiratory in infants preterm.

[Central nervous system lesions in fetuses and newborns in intrauterine infection caused by respiratory viruses]. / Porazheniia tsentral'noi nervnoi sistemy plodov i novorozhdennykh pri vnutriutrobnoi infektsii, vyzvannoi respiratornymi virusami.

Congenital respiratory viral infection is followed in the CNS of fetuses and newborns by grave dyscirculatory disturbances with glia proliferation and nervous tissue edema. The process is mainly localized in the periventricular regions of the brain ventricles. Neurologic and morphologic consequences of these damages in the CNS of fetuses and newborns need further studies.