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Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Respiratory health in children is essential for general wellbeing and healthy development in the short and long term. It is well known that many respiratory diseases in adulthood have their origins in early life, and therefore research on prevention of respiratory diseases and management of children with respiratory diseases will benefit patients during the full life course. Scientific and clinical advances in the field of respiratory health are moving at a fast pace. This article summarises some of the highlights in paediatric respiratory medicine presented at the hybrid European Respiratory Society (ERS) International Congress 2023 which took place in Milan (Italy). Selected sessions are summarised by Early Career Members of the Paediatrics Assembly (Assembly 7) under the supervision of senior ERS officers, and cover a wide range of research areas in children, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis, respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology and bronchology.

Abstract Background Malaria caused by Plasmodium falciparum is one of the leading causes of human morbidity and mortality from infectious diseases, predominantly in tropical and sub-tropical countries. As genetic variations in the toll-like receptors (TLRs)-signalling pathway have been associated with either susceptibility or resistance to several infectious and inflammatory diseases, the supposition is that single nucleotide polymorphisms (SNPs) of TLR2, TLR4, TLR9, Toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A could modulate malaria susceptibility and severity. Methods This study was planned to make a further contribution to solving the problem of the real role of the most common polymorphisms of TLR4, TLR9, TIRAP and FCGR2A genes in modulating the risk of malaria and disease severity in children from Burundi, Central Africa. All the paediatric patients aged six months to 10 years admitted to the hospital of Kiremba, Burundi, between February 2011 and September 2011, for fever and suspicion of acute malaria were screened for malaria parasitaemia by light microscopy of thick and thin blood smears. In children with malaria and in uninfected controls enrolled during the study period in the same hospital, blood samples were obtained on filter paper and TLR4 Asp299Gly rs4986790, TLR9 G1174A rs352139, T-1486 C rs187084 TLR9 T-1237 C rs5743836, TIRAP Ser180Leu rs8177374 and the FCGR2A His131Arg rs1801274 polymorphisms were studied using an ABI PRISM 7900 HT Fast Real-time instrument. Results A total of 602 patients and 337 controls were enrolled. Among the malaria cases, 553 (91.9 %) were considered as suffering from uncomplicated and 49 (8.1 %) from severe malaria. TLR9 T1237C rs5743836CC was associated with an increased risk of developing malaria (p = 0.03), although it was found with the same frequency in uncomplicated and severe malaria cases. No other differences were found in all alleles studied and in genotype frequencies between malaria cases and uninfected controls as well as between uncomplicated and severe malaria cases. Conclusions TLR9 T1237C seems to condition susceptibility to malaria in Burundian children but not its severity, whereas none of the assessed SNPs of TLR4, TIRAP and FCGR2A seem to influence susceptibility to malaria and disease severity in this population.

Since the beginning of the pandemic, while progressive movements have mainly focused on social inequalities exacerbated by the sanitary emergency, a number of protests emerged and quickly became visible that initially targeted the policies taken to reduce contagion and subsequently focused on the vaccine and vaccination. In the attempt to account for the rapid development of these protests, social scientists have mostly turned to classical approaches used in the analysis of far-right organizations and sects, looking at broad transformations in society or at fear and a sense of insecurity at the individual level. In this article, we build upon a social movement approach to look at the main characteristics of the protests against anti-contagion measures. From a theoretical point of view, we point to the importance of disentangling the specific waves happening within broader protest cycles. Empirically, focusing on the Italian case, we present a novel development in protest event analysis looking at the specific forms of action, the actors involved, and their claims in two waves of contention during the pandemic in Italy, between 2020 and 2021.

A new methodology to improve the sensitivity to new physics contributions to the Standard Model processes at LHC is presented. A Variational AutoEncoder trained on Standard Model processes is used to identify Effective Field Theory contributions as anomalies. While the output of the model is supposed to be very similar to the inputs for Standard Model events, it is expected to deviate significantly for events generated through new physics processes. The reconstruction loss can then be used to select a signal enriched region which is by construction independent of the nature of the chosen new physics process. In order to improve further the discrimination power, an adversarial layer is introduced with a cross entropy term added to the loss function, optimizing at the same time the reconstruction of the input variables of the Standard Model and classification of new physics processes. This procedure ensures that the model is optimized for discrimination, with a small price in terms of model dependency to physics process. In this work I will discuss in detail the above-mentioned method using generator level Vector Boson Scattering events produced at LHC assuming an integrated luminosity of 350/fb.

This review has been prepared by the Early Career Members and Chairs of the European Respiratory Society (ERS) Assembly 7: Paediatrics. We here summarise the highlights of the advances in paediatric respiratory research presented at the ERS International Congress 2022. The eight scientific groups of this Assembly cover a wide range of research areas, including respiratory physiology and sleep, asthma and allergy, cystic fibrosis (CF), respiratory infection and immunology, neonatology and intensive care, respiratory epidemiology, bronchology, and lung and airway developmental biology. Specifically, we report on abstracts presented at the congress on the effect of high altitude on sleep, sleep disorders, the hypoxic challenge test, and measurements of ventilation inhomogeneity. We discuss prevention of preschool wheeze and asthma, and new asthma medications. In children with CF, we describe how to monitor the effect of CF transmembrane conductance regulator modulator therapy. We present respiratory manifestations and chronic lung disease associated with common variable immunodeficiency. Furthermore, we discuss how to monitor respiratory function in neonatal and paediatric intensive care units. In respiratory epidemiology, we present the latest news from population-based and clinical cohort studies. We also focus on innovative and interventional procedures for the paediatric airway, such as cryotherapy. Finally, we stress the importance of better understanding the molecular mechanisms underlying normal and abnormal lung development.

Objective: Monitoring infants’ breathing activity is crucial in research and clinical applications but remains a challenge. This study aims to develop a contactless method to monitor breathing patterns and thoracoabdominal asynchronies in infants inside the incubator, using depth cameras. Methods: We proposed an algorithm to extract the 3D displacements of the ribcage and abdomen from the analysis of depth images. We evaluated the accuracy of the system in-vitro vs. a reference motion capture analyzer. We also conducted a feasibility study on 12 patients receiving non-invasive respiratory support to estimate the mean and the variability of the chest wall displacements in preterm infants and evaluate the suitability of the proposed system in the clinical setting. Results: In-vitro, the mean (95% CI) error in the measurement of amplitude, frequency and phase shift between compartmental displacements was −0.14 (−0.57, 0.28) mm, 0.02 (−0.99, 1.03) bpm, and −0.40 (−1.76, 0.95)°, respectively. In-vivo, the mean (95% CI) amplitude of the ribcage and abdomen displacements were 0.99 (0.34, 2.67) mm and 1.20 (0.40, 2.15) mm, respectively. Conclusions: The developed system proved accurate in-vitro and was suitable for the clinical environment. Clinical Impact: The proposed method has value for evaluating infants’ breathing patterns in research applications and, after further development, may represent a simple monitoring tool for infants’ respiratory activity inside the incubator.

Abstract Background Current criteria for surfactant administration assume that hypoxia is a direct marker of lung-volume de-recruitment. We first introduced an early, non-invasive assessment of lung mechanics by the Forced Oscillation Technique (FOT) and evaluated its role in predicting the need for surfactant therapy. Objectives To evaluate whether lung reactance (Xrs) assessment by FOT within 2 h of birth identifies infants who would need surfactant within 24 h; to eventually determine Xrs performance and a cut-off value for early detection of infants requiring surfactant. Methods We conducted a prospective, observational, non-randomized study in our tertiary NICU in Milan. Eligible infants were born between 27+0 and 34+6 weeks’ gestation, presenting respiratory distress after birth. Exclusion criteria: endotracheal intubation at birth, major malformations participation in other interventional trials, parental consent denied. We assessed Xrs during nasal CPAP at 5 cmH2O at 10 Hz within 2 h of life, recording flow and pressure tracing through a Fabian Ventilator for off-line analysis. Clinicians were blinded to FOT results. Results We enrolled 61 infants, with a median [IQR] gestational age of 31.9 [30.3; 32.9] weeks and birth weight 1490 [1230; 1816] g; 2 infants were excluded from the analysis for set-up malfunctioning. 14/59 infants received surfactant within 24 h. Xrs predicted surfactant need with a cut-off − 33.4 cmH2O*s/L and AUC-ROC = 0.86 (0.76–0.96), with sensitivity 0.85 and specificity 0.83. An Xrs cut-off value of − 23.3 cmH2O*s/L identified infants needing surfactant or respiratory support > 28 days with AUC-ROC = 0.89 (0.81–0.97), sensitivity 0.86 and specificity 0.77. Interestingly, 12 infants with Xrs

High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of Poractant alfa). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.

Prompt and stable control of hyperthyroidism is fundamental to avoid the detrimental effects of thyroid hormone excess, and antithyroid drugs, mainly methimazole (MMI), represent the first-line treatment for Graves’ disease (GD) hyperthyroidism. Decreased serum concentrations of selenium (Se) and calcifediol (25(OH)D, VitD) have been reported in newly diagnosed GD patients in observational studies. Low Se levels might exacerbate oxidative stress by compromising the antioxidant machinery’s response to reactive oxygen species, and low VitD levels might hamper the anti-inflammatory immune response. We performed a randomized controlled clinical trial (EudraCT 2017-00505011) to investigate whether Se and cholecalciferol (VitD) addition to MMI is associated with a prompter control of hyperthyroidism. Forty-two consecutive patients with newly-onset GD and marginal/insufficient Se and VitD levels were randomly assigned to treatment with either MMI monotherapy or MMI combined with Se and VitD. Se treatment was withdrawn after 180 days, while the other treatments were continued. Combination therapy resulted in a significantly greater reduction in serum FT4 concentration at 45 days (-37.9 pg/ml, CI 95%, -43.7 to -32.2 pg/ml) and 180 days (-36.5 pg/ml, CI 95%, -42 to -30.9 pg/ml) compared to MMI monotherapy (respectively: -25.7 pg/ml, CI 95%, -31.6 to -19.7 pg/ml and -22.9 pg/ml, CI 95%, -28 to -17.3 pg/ml, p 0.002). Data at 270 days confirmed this trend (-37.8 pg/ml, CI 95%, -43.6 to -32.1 pg/ml vs -24.4 pg/ml, CI 95%, -30.3 to -18.4 pg/ml). The quality of life (QoL) score was investigated by the validated “Thyroid-related Patient-Reported Outcome” questionnaire (ThyPRO). ThyPRO composite score showed a greater improvement in the intervention group at 45 days (-14.6, CI 95%, -18.8 to -10.4), 180 (-9, CI 95%, -13.9 to -4.2) and 270 days (-14.3, CI 95%, -19.5 to -9.1) compared to MMI group (respectively, -5.2, CI 95%, -9.5 to -1; -5.4, CI 95%, -10.6 to -0.2 and -3.5, CI 95%, -9 to -2.1, p 0-6 months and 6-9 months

Respiratory management during extracorporeal membrane oxygenation (ECMO) is complex. Assessment of lung mechanics might support a patient-tailored ventilatory strategy. We report, for the first time, the use of the forced oscillation technique (FOT) to evaluate lung function during neonatal ECMO to improve the individualization of respiratory support. The patient was a formerly preterm infant at a corrected age of 40 weeks (gestational age 32 weeks) undergoing veno-arterial ECMO for refractory respiratory failure secondary to influenza A (H1N1) pneumonia. We used the FOT as a bedside non-invasive tool for daily monitoring of lung mechanics, from ECMO day 6 (E6) until decannulation. A small-amplitude, 5-Hz oscillatory pressure was overimposed on the ventilation waveform at the airway opening during positive end-expiratory pressure (PEEP) trials. From E6 to E9, lung mechanics changes with PEEP indicated a largely de-recruited and easily over-distendable lung that was not recruitable by applying lung-protective PEEP values. After surfactant and steroid administration, oscillatory reactance (Xrs) values began improving, suggesting a more recruited and pressure-recruitable lung. On E11, despite the lack of improvement in the radiographic appearance of the thorax, the FOT measurements showed a more recruited lung. Weaning from ECMO was started, and the patient was extubated within 48 h. The decannulation was successful, and the patient was extubated within 48 h after ECMO weaning. First-year respiratory and neurodevelopmental follow-up evaluation was unremarkable. This report suggests the potential usefulness of the FOT for monitoring the lung mechanics of ventilated newborns during ECMO to achieve individualized respiratory management. Such tailoring might improve neonatal outcomes and support clinicians with the establishment of a timely and safer weaning approach. These findings need to be verified on a larger population.

Despite of improved survival of premature infants, the incidence of long term pulmonary complications, mostly associated with ventilation-induced lung injury, remains high. Non invasive ventilation (NIV) is able to reduce the adverse effects of mechanical ventilation. Although nasal continuous positive airway pressure (NCPAP) is an effective mode of NIV, traumatic nasal complications and intolerance of the nasal interface are common. Recently high flow nasal cannula (HFNC) is emerging as a better tolerated form of NIV, allowing better access to the baby’s face, which may improve nursing, feeding and bonding. HFNC may be effective in the treatment of some neonatal respiratory conditions while being more user-friendly for care-givers than conventional NCPAP. Limited evidence is available to support the specific role, efficacy and safety of HFNC in newborns and to demonstrate efficacy compared with NCPAP; some studies suggest a potential role for HFNC in respiratory care of the neonate as a distinct non invasive ventilatory support. We present the preliminary data of a randomized clinical trial; the aim of this study was to assess efficacy and safety of HFNC compared to NCPAP in preterm newborns with mild to moderate respiratory distress syndrome (RDS).

Respiratory diseases are a major cause of morbidity in neonates, especially preterm infants; a long term complication of prematurity such as bronchopulmonary dysplasia (BPD) is particularly relevant today. The exact role of the Pulmonary Function Test (PFT) in this area is not yet well defined; the PFT in newborns and infants - in contrast to what happens in uncooperative children and adults - are routinely used only in a few centers. The assessment of pulmonary function in newborns and infants, however, is nowadays possible with the same reliability that in cooperative patients with the possibility to extend the assessment of polmonary function from bench to bed. The assessment of pulmonary function must be carried out with non invasive and safe methods, at the bedside, with the possibility of continuous monitoring and providing adequate calculation and management of data. The ability to assess lung function helps to define the mechanisms of respiratory failure, improving the treatment and its effects and is therefore a useful tool in the follow-up of newborn and infant with pulmonary disease.

Outbreaks of nosocomial pathogens are one of the most relevant problems in Neonatal Intensive Care Unit (NICU). Many factors contribute to the onset of an epidemic, including virulence of the pathogen and vulnerability of the infants hospitalized in NICU. Outbreaks are often caused by multidrug-resistant organisms (MDROs). MDROs are defined as microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents. MDROs, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and certain gram-negative bacilli (GNB), have important infection control implications. Once MDROs are introduced into a healthcare setting, transmission and persistence of the resistant strain is determined by the availability of vulnerable patients, selective pressure exerted by antimicrobial use, increased potential for transmission from larger numbers of infected or colonized patients (“colonization pressure”), and the impact of adherence to prevention efforts. Often, routine infection control measures are not enough to contain outbreaks, and additional control measures are needed, including implementation of hand hygiene, cohorting of infected/colonized infants, neonatal surveillance cultures, screening of healthcare workers and decolonization of neonates and/or healthcare workers in selected cases. In this review, we report the practices we developed in our NICU to contain an epidemic. These recommendations reflect the experience of the group, as well as the findings of the current literature.

Respiratory diseases are a major cause of morbidity in neonates, especially preterm infants; a long term complication of prematurity such as bronchopulmonary dysplasia (BPD) is particularly relevant today. The exact role of the Pulmonary Function Test (PFT) in this area is not yet well defined; the PFT in newborns and infants - in contrast to what happens in uncooperative children and adults - are routinely used only in a few centers. The assessment of pulmonary function in newborns and infants, however, is nowadays possible with the same reliability that in cooperative patients with the possibility to extend the assessment of polmonary function from bench to bed. The assessment of pulmonary function must be carried out with non invasive and safe methods, at the bedside, with the possibility of continuous monitoring and providing adequate calculation and management of data. The ability to assess lung function helps to define the mechanisms of respiratory failure, improving the treatment and its effects and is therefore a useful tool in the follow-up of newborn and infant with pulmonary disease.

Despite of improved survival of premature infants, the incidence of long term pulmonary complications, mostly associated with ventilation-induced lung injury, remains high. Non invasive ventilation (NIV) is able to reduce the adverse effects of mechanical ventilation. Although nasal continuous positive airway pressure (NCPAP) is an effective mode of NIV, traumatic nasal complications and intolerance of the nasal interface are common. Recently high flow nasal cannula (HFNC) is emerging as an efficient, better tolerated form of NIV, allowing better access to the baby’s face, which may improve nursing, feeding and bonding. The aim of this review is to discuss the available evidence of effectiveness and safety of HFNC in preterm newborns with respiratory distress syndrome (RDS). It is known that distending pressure generated by HFNC increases with increasing flow rate and decreasing infant size and varies according to the amount of leaks by nose and mouth. The effects of HFNC on lung mechanics, its clinical efficacy and safety are still insufficiently investigated. In conclusion, there is a growing evidence of the feasibility of HFNC as an alternative mode of NIV. However, further larger randomized trials are required, before being able to recommend HFNC in the treatment of moderate respiratory distress of preterm infants.