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.

Secuestro pulmonar intralobar / Intralobar pulmonary sequestration

El secuestro pulmonar es una malformación congénita del tracto respiratorio inferior, rara e importante. En niños y adultos suele presentarse con infecciones pulmonares a repetición o crónicas severas. Se describió un caso de una paciente de 19 años de edad que tuvo un cuadro de sepsis respiratoria bajas a repetición. En los estudios de imágenes de tórax se evidenció opacidad homogénea en hemitórax derecho. Fue intervenida quirúrgicamente; se le realizó una lobectomía inferior derecha la cual fue diagnóstica para secuestro pulmonar, con evolución satisfactoria(AU)

Pulmonary sequestration is a rare and important congenital malformation of the lower respiratory tract. In children and adults, it usually presents with severe chronic or repeated lung infections. A case of a female 19-year-old patient who had recurrent lower respiratory sepsis is reported. Homogeneous opacity was evident in the chest imaging studies in the right hemithorax. She underwent surgery. A lower right lobectomy was performed, which was diagnostic for pulmonary sequestration, with satisfactory evolution(AU)

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.

The multicenter Italian birth cohort study on incidence and determinants of lower respiratory tract infection hospitalization in infants at 33 weeks GA or more: preliminary results.

BACKGROUND: Respiratory syncytial virus (RSV) causes respiratory infections during the first year of life. Very premature infants have more severe diseases and also 'late preterm infants' may be more susceptible to the infection. AIM OF THE STUDY: To evaluate in an Italian cohort the incidence and risk factors of severe hospitalized lower respiratory tract infection (LRTI) induced or not by RSV during the first year of life. METHODS: A cohort of 33(+0d)-34(+6d) wGA newborns paired with two sex- and age-matched 35(+0d)-37(+6d) wGA and ≥ 38(+0d) wGA newborns were enrolled. Hospitalization for LRTI induced or not by RSV during the first year of life was assessed through phone interview at the end of the RSV season (November-March) and at the completion of the first year of life. The parents were asked to report hospitalization for any reason. RESULTS: 1064 neonates were enrolled (November 2009-October 2010), 697 had at least one phone follow-up by September 2010. Babies of 33(+0d)-34(+6d) wGA were more frequently conceived through assisted fertilization technologies, born from cesarean delivery had more frequently acute perinatal risk factors and were more frequently twins. After a mean 6 month-follow-up, we registered 29 hospitalizations for LRTI induced or not by RSV. Hospitalizations were slightly and non-significantly more frequent in 33(+0d)-37(+6d) wGA infants. The risk of hospitalization was significantly 60% reduced in breastfed babies and four folds significantly increased during the RSV season. CONCLUSION: The very preliminary data of this ongoing study suggest that in 'late-preterm' infants some individual/environmental characteristics of the infants play a relevant role in determining the risk of severe RSV infection.

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.

Surgical treatment of congenital bronchopulmonary disease in children.

From 1987 to 1992, 22 children (age 0 days-14 years) were operated for congenital bronchopulmonary disease. One patient had a hamartoma. Four children had a bronchogenic cyst, in 1 patient combined with an esophageal duplication. Intrapulmonary sequestration was diagnosed in 3 children; one of whom had an esophageal duplication as well. Four children had localized emphysema. In 1 patient histology showed rhabdomyosarcoma. A lobectomy was performed following chemotherapy but recurrence was not resectable at a third thoracotomy. Ten patients had cystic adenomatoid malformation, 6 were dependent on artificial ventilation before surgery. Three patients with cystic adenomatoid malformation died in hospital: 2 after pneumonectomy who were shown to have bilateral disease and 1 died after bilobectomy and was shown to have a hypoplastic contralateral lung. Hospital morbidity involved 1 patient with recurrent pneumothorax, 2 with atelectasis of the operated lung and 3 with prolonged artificial ventilation. Late mortality involved 1 patient due to pulmonary rhabdomyosarcoma. After 1-26 months of follow-up there were no late complications. Adequate multidisciplinary treatment allows acceptable mortality and low morbidity in surgery for congenital bronchopulmonary disease in children.

Serological evidence of Ureaplasma urealyticum infection in neonatal respiratory disease.

Since up to 80 percent of pregnant women and 30 percent of neonates may be colonized with genital mycoplasmas, it is difficult to determine whether true infection occurs. The antibody responses to eight serotypes of U. urealyticum were assessed in mothers and infants in 21 cases of neonatal respiratory disease (RD) and 24 normal cases. Among the normal population of mothers and infants, a titer of greater than or equal to 1:32 occurred in 0.25 percent (1/394). In mother-infant paired titers, a fourfold difference occurred in 2.6 percent (5/192). Among 54 RD neonates, 55.6 percent had a titer of greater than or equal to 1:32 compared to only 4.2 percent of normal neonates (p less than .001). Fourfold elevations in antibody titers of greater than 1:32 were observed in the neonate in 52.4 percent of RD cases compared to 0 percent of 24 normal pairs (p less than .001) and in 28.6 percent of mothers of RD neonates compared to 0 percent in normal cases (p = .013). We observed that 43.3 percent of RD neonates with titers greater than or equal to 1:32 died compared to 16.6 percent of RD neonates exhibiting no elevation of antibody response over the maternal level. Among the six who died, 66.7 percent of neonates and 16.7 percent of their mothers had elevated titers, compared to 33.3 percent of 15 surviving infants and 40.0 percent of their mothers. These elevated antibody responses strongly support the concept that U. urealyticum causes infection in the perinatal period in association with neonatal respiratory disease. Since the elevation in titers was detected close to delivery in many cases, the infection may occur in utero.