Genetic diversity and its impact on disease severity in respiratory syncytial virus subtype-A and -B bronchiolitis before and after pandemic restrictions in Rome.

OBJECTIVES: To scrutinize whether the high circulation of respiratory syncytial virus (RSV) observed in 2021-2022 and 2022-2023 was due to viral diversity, we characterized RSV-A and -B strains causing bronchiolitis in Rome, before and after the COVID-19 pandemic. METHODS: RSV-positive samples, prospectively collected from infants hospitalized for bronchiolitis from 2017-2018 to 2022-2023, were sequenced in the G gene; phylogenetic results and amino acid substitutions were analyzed. Subtype-specific data were compared among seasons. RESULTS: Predominance of RSV-A and -B alternated in the pre-pandemic seasons; RSV-A dominated in 2021-2022 whereas RSV-B was predominant in 2022-2023. RSV-A sequences were ON1 genotype but quite distant from the ancestor; two divergent clades included sequences from pre- and post-pandemic seasons. Nearly all RSV-B were BA10 genotype; a divergent clade included only strains from 2021-2022 to 2022-2023. RSV-A cases had lower need of O2 therapy and of intensive care during 2021-2022 with respect to all other seasons. RSV-B infected infants were more frequently admitted to intensive care units and needed O2 in 2022-2023. CONCLUSIONS: The intense RSV peak in 2021-2022, driven by RSV-A phylogenetically related to pre-pandemic strains is attributable to the immune debt created by pandemic restrictions. The RSV-B genetic divergence observed in post-pandemic strains may have increased the RSV-B specific immune debt, being a possible contributor to bronchiolitis severity in 2022-2023.

Pediatric bronchoscopy: recent advances and clinical challenges.

Introduction: During the last 40 years equipment has been improved with smaller instruments and sufficient size working channels. This has ensured that bronchoscopy offers therapeutic and interventional options.Areas covered: We provide a review of recent advances and clinical challenges in pediatric bronchoscopy. This includes single-use bronchoscopes, endobronchial ultrasound, and cryoprobe. Bronchoscopy in persistent preschool wheezing and asthma is included. The indications for interventional bronchoscopy have amplified and included balloon dilatation, endoscopic intubation, the use of airway stents, whole lung lavage, closing of fistulas and air leak, as well as an update on removal of foreign bodies. Others include the use of laser and microdebrider in airway surgery. Experience with bronchoscope during the COVID-19 pandemic has been included in this review. PubMed was searched for articles on pediatric bronchoscopy, including rigid bronchoscopy as well as interventional bronchoscopy with a focus on reviewing literature in the past 5 years.Expert opinion: As the proficiency of pediatric interventional pulmonologists continues to grow more interventions are being performed. There is a scarcity of published evidence in this field. Courses for pediatric interventional bronchoscopy need to be developed. The COVID-19 experience resulted in safer bronchoscopy practice for all involved.

Vernal Keratoconjunctivitis: an update focused on clinical grading system.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a severe disease with a prevalence of < 1 case out of 10,000 in Europe, which occurs mainly in pediatric age and is characterized by a severe and often bilateral chronic inflammation of the ocular surface. The diagnosis is generally confirmed by the finding at the ocular examination of conjunctival hyperemia, papillary hypertrophy in the tarsal conjunctiva, giant papillae, papillae in the limbus region. OBJECTIVE: Aim of this review is to provide an updated overview on the disease focused on clinical grading system, searching papers published in the last decade on VKC in scientific databases. RESULTS: Currently there are no standardized criteria for diagnosis of VKC and there is no uniformity to define disease severity, which makes difficult to diagnose and treat the disease. CONCLUSIONS: Given the wide overlap of the symptoms of VKC with the allergic conjunctivitis, criteria of probable, possible or improbable diagnosis are needed, providing pediatricians with parameters useful for deciding whether to drive the patient to the ophthalmologist for diagnostic confirmation.

Use of a short-term whole blood intracellular staining assay to study the T-cell response in respiratory syncytial virus-infected pediatric patients.

The aim of the present study was the development of a reliable method to evaluate the pattern of the ongoing T-cell response in young infants affected by respiratory infection. To this purpose, we enrolled 44 infants hospitalized with a diagnosis of respiratory syncytial virus bronchiolitis. After a short-term stimulation of whole blood samples, intracellular IFN-g and IL-4 cytokines were measured in CD4+ and CD8+ T-cell subsets by flow cytometry. A stringent staining and gating strategy was used in order to maximize the reduction of background noise and to exclude false positives. The frequencies of cytokine-producing T-cell subsets, albeit low, were easily quantifiable. Cytokine responses were higher in infants sampled > 7 days from the onset of symptoms. The use of a rigorous strategy for cell staining and gating, coupled with a short-term stimulation of whole blood and a careful evaluation of time elapsed from the onset of symptoms constitutes a convincing approach for future clinical studies.

Infants hospitalized for Bordetella pertussis infection commonly have respiratory viral coinfections.

BACKGROUND: Whether viral coinfections cause more severe disease than Bordetella pertussis (B. pertussis) alone remains unclear. We compared clinical disease severity and sought clinical and demographic differences between infants with B. pertussis infection alone and those with respiratory viral coinfections. We also analyzed how respiratory infections were distributed during the 2 years study. METHODS: We enrolled 53 infants with pertussis younger than 180 days (median age 58 days, range 17­109 days, 64. 1% boys), hospitalized in the Pediatric Departments at "Sapienza" University Rome and Bambino Gesù Children's Hospital from August 2012 to November 2014. We tested in naso-pharyngeal washings B. pertussis and 14 respiratory viruses with real-time reverse-transcriptase-polymerase chain reaction. Clinical data were obtained from hospital records and demographic characteristics collected using a structured questionnaire. RESULTS: 28/53 infants had B. pertussis alone and 25 viral coinfection: 10 human rhinovirus (9 alone and 1 in coinfection with parainfluenza virus), 3 human coronavirus, 2 respiratory syncytial virus. No differences were observed in clinical disease severity between infants with B. pertussis infection alone and those with coinfections. Infants with B. pertussis alone were younger than infants with coinfections, and less often breastfeed at admission. CONCLUSIONS: In this descriptive study, no associations between clinical severity and pertussis with or without co-infections were found. TRIAL REGISTRATION: Policlinico Umberto I: protocol 213/14, 3085/13.02.2014, retrospectively registered. Bambino Gesù Children's Hospital: protocol n. RF-2010-2317709.

Difficult diagnosis of atypical kawasaki disease in an infant younger than six months: a case report.

BACKGROUND: Kawasaki disease (KD) is an acute inflammatory vasculitis of unknown origin. CASE PRESENTATION: We report the case of a 5-month-old child with an atypical form of KD, characterized by undulating symptoms, who developed an aneurysm of the right coronary artery and an ectasia of the left anterior descending coronary artery. CONCLUSION: This case report underlines the difficulties in recognizing incomplete forms of the illness in young infants, who are at higher risk of cardiac complications.

European Respiratory Society guidelines for the diagnosis of primary ciliary dyskinesia

The diagnosis of primary ciliary dyskinesia is often confirmed with standard, albeit complex and expensive, tests. In many cases, however, the diagnosis remains difficult despite the array of sophisticated diagnostic tests. There is no "gold standard" reference test. Hence, a Task Force supported by the European Respiratory Society has developed this guideline to provide evidence-based recommendations on diagnostic testing, especially in light of new developments in such tests, and the need for robust diagnoses of patients who might enter randomised controlled trials of treatments. The guideline is based on pre-defined questions relevant for clinical care, a systematic review of the literature, and assessment of the evidence using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. It focuses on clinical presentation, nasal nitric oxide, analysis of ciliary beat frequency and pattern by high-speed video-microscopy analysis, transmission electron microscopy, genotyping and immunofluorescence. It then used a modified Delphi survey to develop an algorithm for the use of diagnostic tests to definitively confirm and exclude the diagnosis of primary ciliary dyskinesia; and to provide advice when the diagnosis was not conclusive. Finally, this guideline proposes a set of quality criteria for future research on the validity of diagnostic methods for primary ciliary dyskinesia

Draft Genome Sequence of a Bordetella pertussis Strain with the Virulence-Associated Allelic Variant ptxP3, Isolated in Italy.

Despite a universal immunization program, pertussis has persisted and resurged, and is of particular concern for infants in terms of morbidity and mortality. Here, we report the genome sequence of a Bordetella pertussis strain with the virulence-associated allelic variant ptxP3, isolated from a 45-day-old infant.

Rapid spread of the novel respiratory syncytial virus A ON1 genotype, central Italy, 2011 to 2013.

Respiratory infections positive for human respiratory syncytial virus (RSV) subtype A were characterised in children admitted to hospitals in Rome and Ancona (Italy) over the last three epidemic seasons. Different strains of the novel RSV-A genotype ON1, first identified in Ontario (Canada) in December 2010, were detected for the first time in Italy in the following 2011/12 epidemic season. They bear an insertion of 24 amino acids in the G glycoprotein as well as amino acid changes likely to change antigenicity. By early 2013, ON1 strains had spread so efficiently that they had nearly replaced other RSV-A strains. Notably, the RSV peak in the 2012/13 epidemic season occurred earlier and, compared with the previous two seasons, influenza-like illnesses diagnoses were more frequent in younger children; bronchiolitis cases had a less severe clinical course. Nonetheless, the ON1-associated intensive care unit admission rate was similar, if not greater, than that attributable to other RSV-A strains. Improving RSV surveillance would allow timely understanding of the epidemiological and clinicopathological features of the novel RSV-A genotype.

Surfactant therapy for acute respiratory distress in children.

In children with acute lung injury the endogenous surfactant system is altered via a variety of different mechanisms, including inflammation, vascular dysfunction, oxidant injury, cellular injury and oedema. This article examines the pathophysiology of acute lung injury and surfactant use for treatment of acute respiratory failure in infants and children.

Viral bronchiolitis in children: a common condition with few therapeutic options.

Even though bronchiolitis is a disease that has been recognized for many years, there are still few therapeutic strategies beyond supportive therapies. Bronchiolitis is the most frequent cause of hospital admission in children less than 1 year of age. The incidence is estimated to be about 150° million cases a year worldwide, and 2-3% of these cases require hospitalization. It is acknowledged that viruses cause bronchiolitis, but most of the studies focus on RSV. The RSV causes a more severe form of bronchiolitis in children with risk factors including prematurity, cardiovascular disease and immunodeficiency. Other viruses involved in causing bronchiolitis include RV, hMPV, hBoV and co-infections. The RV seems to be associated with a less severe acute disease, but there is a correlation between the early infection and subsequent wheezing bronchitis and asthma in later childhood and adulthood. The supportive therapies used are intravenous fluids and oxygen supplement administered by nasal cannula or CPAP in most complicated patients. Additional pharmacological therapies include epinephrine, 3% hypertonic saline and corticosteroids. The Epinephrine seems to have the greatest short-term benefits and reduces the need of hospital admission, whereas hypertonic saline and corticosteroids seem to reduce the length of hospital stay. As bronchiolitis is such a prevalent disease in children and RV seems to play an important role, perhaps more studies should center around the RV's contribution to the initial disease and following pathology.

Outcomes after tongue-lip adhesion or mandibular distraction osteogenesis in infants with Pierre Robin sequence and severe airway obstruction.

The objective was to review and compare outcomes after tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002-2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44±24 vs 217±134, P<0.003). The length of hospital stay was longer for infants treated with MDO than for those treated with TLA. The rate of complications was similar. Infants with severe airway obstruction related to PRS can benefit safely from either TLA or MDO. Although MDO lengthens the time to discharge, this option stabilizes airway patency of infants with PRS more efficiently and achieves full oral feeding more rapidly than TLA.

Sevoflurane inhalation for severe bronchial obstruction in infants with bronchiolitis.

Bronchiolitis is a lower respiratory tract viral infection which may result in severe bronchial obstruction and respiratory failure despite treatment with beta-adrenergic agonists and glucocorticoids. Here we describe two otherwise healthy infants with severe bronchiolitis whose clinical course was complicated by marked bronchial obstruction and respiratory acidosis refractory to conventional medications (ß-stimulants, anticholinergics and corticosteroids) and non-invasive positive pressure ventilation. Sevoflurane inhalation allowed both infants to attain a sustained, clinical improvement in ventilation and one patient to avoid mechanical ventilation. We suggest that sevoflurane inhalation may be a therapeutic option in the treatment of young infants with severe bronchiolitis who respond poorly to conventional therapy.

Antenatal and postnatal management of congenital cystic adenomatoid malformation.

Congenital thoracic malformations (CTMs) are a heterogeneous group of rare disorders that may involve the airways or lung parenchyma. The authors have focused on the condition that causes the most controversy, namely, congenital cystic adenomatoid malformation (CCAM). The reported incidence is 3.5 and 0.94 per 10,000 live births for CTMs and CCAMs respectively. Ultrasound is the antenatal imaging modality of choice for screening for CCAMs whilst magnetic resonance imaging is complimentary for morphological and volumetric evaluation of the foetal lung. Most CCAMs are detected antenatally with only a small proportion presenting postnatally. Only a few CCAMs cause foetal problems, with foetal hydrops being the best predictor of death. Although many CCAMs regress during pregnancy, most remain detectable postnatally by CT scans. Surgical excision of symptomatic lesions is relatively straightforward, but management of asymptomatic lesions is controversial. Some surgeons adopt a "wait and see" approach operating only on those patients who develop symptoms, but others operate on asymptomatic patients usually within the first year of life. Due to the potential of malignant transformation, children should have long term follow up. There is an urgent need to delineate the natural history of antenatally detected CCAMs to guide future management.

Virological and clinical characterization of respiratory infections in children attending an emergency department during the first autumn-winter circulation of pandemic A (H1N1) 2009 influenza virus.

To characterize respiratory virus infections during the first autumn-winter season of pandemic A (H1N1) 2009 influenza virus (A/H1N1/2009) circulation, a prospective study in children attending a paediatric emergency department at the Sapienza University hospital, Rome, was conducted from November 2009 to March 2010. By means of both nasal washings and pharyngeal swabs, enrolled children were checked for 14 respiratory viruses. The majority of acute respiratory infections resulted from viral pathogens (135/231, 58%). Overall, the most common was respiratory syncytial virus (RSV), in 64% of positive samples; A/H1N1/2009 was the only influenza virus found in 16% and rhinovirus (RV) in 15%. Virus-positive children did not differ significantly from virus-negative children in signs and symptoms at presentation; of the virus groups, RSV-infected children were younger and more frequently admitted to intensive-care units than those infected with A/H1N1/2009 and RV. Of the hospitalized children, stratified by age, both infants and children aged >1 year with RSV were most severely affected, whereas A/H1N1/2009 infections were the mildest overall, although with related pulmonary involvement in older children. Children with RV infections, detected in two flares partially overlapping with the A/H1N1/2009 and RSV peaks, presented with bronchiolitis, wheezing and pneumonia. Leukocytosis occurred more frequently in RV-infected and A/H1N1/2009-infected children, and numbers of blood eosinophils were significantly elevated in RV-infected infants. Given the fact that clinical and epidemiological criteria are not sufficient to identify viral respiratory infections, a timely virological diagnosis could allow different infections to be managed separately.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up.

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0-11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2-4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have significant mortality and long-term morbidity. Only 60-70% survive and usually those in high-volume centres. The current Task Force, therefore, has convened experts to evaluate the current literature and make recommendations on both the antenatal and post-natal management of CDH. The incidence of CDH varies from 1.7 to 5.7 per 10,000 live-born infants depending on the study population. Antenatal ultrasound scanning is routine and increasingly complemented by the use of magnetic resonance imaging. For isolated CDH, antenatal interventions should be considered, but the techniques need vigorous evaluation. After birth, management protocols are often used and have improved outcome in nonrandomised studies, but immediate intubation at birth and gentle ventilation are important. Pulmonary hypertension is common and its optimal management is crucial as its severity predicts the outcome. Usually, surgery is delayed to allow optimal medical stabilisation. The role of minimal invasive post-natal surgery remains to be further defined. There are differences in opinion about whether extracorporeal membrane oxygenation improves outcome. Survivors of CDH can have a high incidence of comorbidities; thus, multidisciplinary follow-up is recommended. Multicentre international trials are necessary to optimise the antenatal and post-natal management of CDH patients.

Paediatrics in Barcelona: highlights from the 2010 ERS Annual Congress.

The aim of this update is to describe the paediatric highlights from the 2010 European Respiratory Society Annual Congress in Barcelona, Spain. Abstracts from the seven groups of the Paediatric Assembly (Respiratory physiology, Asthma and allergy, Cystic fibrosis, Respiratory infection and immunology, Neonatology and paediatric intensive care, Respiratory epidemiology and Bronchology) are presented in the context of the current literature.

An infant with diaphragmatic eventration and respiratory distress.

The authors report a rare case of partial diaphragmatic eventration in a 4-month-old infant with recurrent wheezing and low serum IgA values. Because of persistent respiratory symptoms after therapy with inhaled short-acting beta2 agonists and inhaled nebulized corticosteroids, surgery was undertaken to correct the defect. Despite surgery, the clinical symptoms did not improve. Consequently, gatroesophagel reflux was considered and the diagnosis was confirmed with pH-metry, after which the infant was started on a protonic pump inhibitor therapy (PPI), achieving clinical improvement. Our experience suggests that in infants with congenital diaphragmatic eventration who present with respiratory distress gastro-oesophageal reflux should be suspected, and PPI therapy should be started before planning surgery.