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Bronchopulmonary dysplasia (BPD) is one of the most common pulmonary sequelae of extreme preterm birth, with long-lasting respiratory symptoms and reduced lung function. A reliable predictive tool of BPD development is urgent and its search remains one of the major challenges for neonatologists approaching the upcoming arrival of possible new preventive therapies. Biomarkers, identifying an ongoing pathogenetic pathway, could allow both the selection of preterm infants with an evolving disease and potentially the therapeutic targets of the indicted pathogenesis. The "omic" sciences represent well-known promising tools for this objective. In this review, we resume the current laboratoristic, metabolomic, proteomic, and microbiomic evidence in the prediction of BPD. KEY POINTS: · The early prediction of BPD development would allow the targeted implementation of new preventive therapies.. · BPD is a multifactorial disease consequently it is unlikely to find a single disease biomarker.. · "Omic" sciences offer a promising insight in BPD pathogenesis and its development's fingerprints.., Competing Interests: None declared., (Thieme. All rights reserved.)

Bronchopulmonary dysplasia (BPD) despite numerous efforts of neonatologists remains one of the most frequent and long-lasting chronic respiratory diseases consequent to extreme preterm birth. New clinical trials are exploring the possible use of mesenchymal stem cells (MSCs) and especially their products, extracellular vesicles (EVs), that overcome some of the possible issues related to the use of live cells. MSCs already reached clinical implementation; MSC-EVs, on the contrary, showed extremely promising results in the preclinical setting but are still waiting their first in human results that are likely to happen soon. KEY POINTS: · BPD is one of the most frequent complications of preterm birth, and its prevention lacks an effective tool.. · EVs have shown encouraging results in preclinical animal models.. · Technical and biological advancements are needed before routine clinical use.., Competing Interests: B.D.V. is a consultant for clinical and regulatory development EXO Biologics SA. M.M. is part of the scientific board of Exo Biologics. E.B. reports consulting fees from Astra-Zeneca, Sanofi, and Exo Biologics outside the submitted work., (Thieme. All rights reserved.)

This article aims to assess the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-associated hospitalization (RSVH) rates in otherwise healthy moderate/late preterm infants and discuss the role of palivizumab in preventing acute and long-term outcomes. We identified studies in the PubMed and Embase databases that reported patient-level data on (1) exposure to palivizumab in preterm infants born between 29 and 35 weeks of gestational age (or subsets within this range) ≤ 2 years of chronological age, and (2) the outcome of RSVH. Six studies assessed RSVH in infants this gestational age who had been exposed or not to palivizumab and reported patient-level data. Exposure was associated with a reduction in RSVH rates that was comparable to the reduction seen in controlled clinical trials (weighed mean 4.0-fold reduction). RSV immunoprophylaxis in preterm infants within 29 to 35 weeks of gestational age is associated with a considerably lower burden of RSVH. KEY POINTS: · RSV is the leading cause of lower respiratory tract infection hospitalization in infants.. · Palivizumab prevents RSVH in a real-world scenario.. · Immunoprophylaxis should be used in high-risk infants.., Competing Interests: E.B. lectures for AstraZeneca, Chiesi, and Sanofi, and is a member of RESVINET. P.M. has participated in speakers bureau for Abbvie, AstraZeneca, and Janssen Pharmaceuticals, and advisory board for Abbvie, Janssen Pharmaceuticals, Medimmune, Sanofi-Pasteur, and is a member of RESVINET. M.S.L. has performed speaker and advisor activities for AstraZeneca and Sanofi. C.T. has been a speaker for AstraZeneca and Sanofi., (Thieme. All rights reserved.)

There is growing evidence in medical literature to support an association between early-life respiratory syncytial virus lower respiratory tract-lower respiratory tract infection (RSV-LRTI) and recurrent wheezing/asthma-like symptoms. It has been estimated that children with a history of RSV-LRTI have a 2- to 12-fold higher risk of developing asthma. The connection between RSV infection and a developmental trajectory of reduced lung function remains throughout adolescence and early adulthood, suggesting a possible role for RSV even in the inception of chronic obstructive pulmonary disease. That is why the postnatal period appears to offer a specific window of opportunity for early intervention to prevent chronic obstructive lung diseases. The mechanisms by which RSV contributes to the onset of wheezing/asthma and lung function impairment are not fully understood but appear to relate to injury caused directly by the virus and/or to pre-existing predisposing factors. While awaiting a deeper understanding of the association between RSV and chronic lung diseases, the crucial role of pediatricians and physicians is to develop strategies to prevent RSV infections to try and protect children's lifelong respiratory health. KEY POINTS: · Several evidence suggest a link between RSV infection in early life and wheezing/asthma development.. · RSV infection appears to have long term respiratory effects.. · The prevention of RSV infections could reduce the incidence of chronic obstructive respiratory diseases.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Premature infants have the highest risk of being hospitalized with respiratory syncytial virus (RSV) infections. Palivizumab is the only licensed agent for RSVhospitalization (RSVH) prophylaxis in infants born at < 35 weeks of gestational age (wGA). In 2016, the Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) has restricted the eligibility for reimbursement to infants at high risk of RSVH, ruling out palivizumab administration for infants born at > 29 wGA. The aim of the present study was to compare the incidence of RSVH in two consecutive epidemic seasons (2015-2016 vs. 2016-2017), that is, before and after the new AIFA recommendations on palivizumab eligibility., Study Design: This was a noninterventional retrospective cohort study conducted at three neonatal intensive care units (NICUs) in northern Italy. Infants born at 29 and 35 wGA between March 15, 2015 and March 14, 2017 were enrolled for this study. Electronic medical charts were reviewed and parents were interviewed by telephone. Data were collected on neonatal course during NICU stay, palivizumab administration, and hospitalizations related to respiratory infections during the 1st year of life, comparing the infants born in season 1 with season 2., Results: Of 632 eligible infants, data were available for 536 (262 in season 1 and 274 in season 2). Overall, RSVH occurred 1.9 and 5.1% in infants in seasons 1 and 2, respectively (odds ratio [OR] = 2.77; 95% confidence interval [CI]: 0.98-7.8, p  = 0.045). When the analysis was limited to patients not exposed to palivizumab, RSVHs were recorded for 1.8 and 5.9% infants in seasons 1 and 2, respectively (OR = 3.42; 95% CI: 0.96-12.20, p  = 0.045). It is noteworthy that the incidence of hospital admissions for respiratory viruses other than RSV did not differ between the two seasons., Conclusion: Restricting eligibility for palivizumab reimbursement led to a significant increase in RSVH but had no impact on hospitalizations for other respiratory viruses. Future decisions on palivizumab prescription and coverage rules should be driven by a careful assessment of the cost-benefit ratio., Competing Interests: P.M. received speaker fees from Abbvie, Janssen; advisory board fees from Abbvie, Sanofi-Pasteur, Janssen, Medimmune; he is founding member of Respiratory Syncytial Virus Network (ReSViNET) Foundation. E.B. received speaker fees from Abbvie, GSK, Janssen; he is founding member of Respiratory Syncytial Virus Network (ReSViNET) Foundation. All the other authors have nothing to disclose related to this article., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Despite notable advances in the survival and management of preterm infants in recent decades, chronic lung disease remains a common complication. Approximately one in three infants born preterm (< 32 weeks of gestation) are hospitalized with respiratory problems (mainly due to infections) in their first 2 years of life, and the risk of childhood wheezing is three times higher in this population. By comparison with infants born at term, there seems to be a higher incidence of respiratory morbidity in those born preterm, even in the absence of bronchopulmonary dysplasia (BPD) and in late-preterm babies. Although long-term follow-up data are still not collected systematically, there is evidence of preterm infants' respiratory symptoms, lung function impairments, and radiological abnormalities, tending to persist throughout childhood and into early adulthood. Respiratory conditions associated with preterm birth are often diagnosed and treated as asthma, but the pathophysiological patterns of BPD and asthma are very different. Future research should focus on characterizing preterm infants' pathological pulmonary features by gestational age at birth, and presence or absence of BPD. Improving our current knowledge of the respiratory disorder associated with prematurity might hopefully prompt targeted follow-up protocols, and novel prevention strategies and treatment approaches., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Heated, humidified high-flow delivered by nasal cannulae (HHHFNC) is increasingly used for noninvasive respiratory support in preterm infants and critically ill children due to its perceived effectiveness and ease of use. Evidence from randomized controlled trials suggests that HHHFNC and continuous positive airway pressure (CPAP) are equally effective as postextubation support in preterm infants. HHHFNC is also used for weaning preterm infants from CPAP. Data on HHHFNC used as the primary support for treating respiratory distress syndrome are conflicting. HHHFNC use in preterm infants is associated with reduced nasal trauma. Inability to measure the pressure generated by HHHFNC systems is a concern because overexpansion can lead to an air leak and lung injury. Great caution is warranted when HHHFNC is used in extremely low-birth-weight infants (who were rarely included in these randomized controlled trials) because a recent retrospective study found its use is associated with a higher likelihood of bronchopulmonary dysplasia or death in this population. HHHFNC has also become popular in pediatric intensive care units and pediatric wards as a method for delivering oxygen and noninvasive respiratory support. Most published studies were conducted on infants and young children with bronchiolitis. The results of a few observational studies and two randomized trials suggest that HHHFNC therapy is effective in the treatment of bronchiolitis. This review discusses the proposed mechanisms of action behind HHHFNC, the results of observational studies, and the evidence emerging from clinical trials on the use of HHHFNC in preterm infants and children critically ill with bronchiolitis., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)