ERS International Congress 2023: highlights from the Paediatrics Assembly.

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.

ERS International Congress 2022: highlights from the Paediatrics Assembly.

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.

E-cigarettes and youth: an unresolved Public Health concern.

The use of electronic cigarettes (e-cigarette) and vaping devices started as a potential aid for cessation and reducing the harmful consequences of cigarette smoking, mainly in the adult population. Today e-cigarette use is highly increasing in vulnerable populations, especially young and pregnant women, due to the misconception of its harmless use.Despite the growing acknowledgment in e-cigarette as a potential harmful device, and due to mixed information found concerning its beneficial aid for smokers, along with an insufficient clinical study done in human models, it is important to further evaluate the possible benefits and risks of non-combusting, vaping nicotine or non-nicotine delivery devices.In this review we tried to summarize the latest updated information found in the literature, concentrating mainly in the variety of adverse effects of e-cigarette use and its contribution for recent and future health concerns.

The Key Role of Lung Ultrasound in the Diagnosis of a Mature Cystic Teratoma in a Child with Suspected Difficult to Treat Pneumonia: A Case Report.

To date, the diagnosis of mediastinal teratoma and mediastinal masses relies on the use of chest X-ray and CT. Lung and thoracic ultrasound is becoming increasingly used in the diagnosis and follow-up of many lung and thoracic diseases. Here, we report the case of a mature cystic teratoma in which the performance of lung ultrasound allowed to speed up the diagnostic workup and to provide the indication for the execution of CT of the thorax allowing the diagnosis.

Modifiable environmental factors predispose term infants to bronchiolitis but bronchiolitis itself predisposes to respiratory sequelae.

INTRODUCTION: Viral bronchiolitis is a common lower respiratory tract infection in infants. Environmental and genetic factors can favor respiratory tract infections. AIM: The aim of this study is to analyze risk factors for bronchiolitis and to investigate the predisposing factors for developing transient wheezing and asthma through a 6-year follow-up after hospitalization for bronchiolitis compared with a group of healthy controls that belonged to Piccolipiù cohort, who never had bronchiolitis. METHODS: We enrolled 645 infants hospitalized with bronchiolitis. A structured questionnaire was used to obtain demographic and clinical data. At 6 years of age, 370 cases and 183 controls were investigated for the presence of asthma by the structured questionnaire, for prick test and for spirometry, and were classified to asthmatic, transient wheezing, and no wheezing/no asthma. RESULTS: Breastfeeding was an independent protective factor (odds ratio [OR]: 0.3, 95% confidence interval [95% CI]: 0.2-0.4, p < 0.001) and tobacco smoke was a risk factor for the development of bronchiolitis (OR: 2.1, 95% CI: 1.4-3.1, p < 0.001). Analyzing follow-up, bronchiolitis increased the risk of developing transient wheezing by 12.9 (95% CI: 6.3-26.1, p < 0.001) and of developing asthma by 4.6 (95% CI: 1.9-10.7, p < 0.001). A positive family history of atopy increased the risk of developing asthma by 3.1 (95% CI: 1.4-6.7, p = 0.005). Asthmatic patients had a lower % FEV1, a lower % flow-volume curve (FVC), and a lower FEV1/FVC value, and they had more frequently positive skin prick test. CONCLUSION: Bronchiolitis is influenced by environmental factors: tobacco smoke increases its risk and breastfeeding is a protective factor. At the end of 6 years of follow-up, bronchiolitis is a significant risk factor to have pre-school wheezing and asthma.

ACE2 expression is related to the interferon response in airway epithelial cells but is that functional for SARS-CoV-2 entry?

In vitro interferon (IFN)α treatment of primary human upper airway basal cells has been shown to drive ACE2 expression, the receptor of SARS-CoV-2. The protease furin is also involved in mediating SARS-CoV-2 and other viral infections, although its association with early IFN response has not been evaluated yet. In order to assess the in vivo relationship between ACE2 and furin expression and the IFN response in nasopharyngeal cells, we first examined ACE2 and furin levels and their correlation with the well-known marker of IFNs' activation, ISG15, in children (n = 59) and adults (n = 48), during respiratory diseases not caused by SARS-CoV-2. A strong positive correlation was found between ACE2 expression, but not of furin, and ISG15 in all patients analyzed. In addition, type I and III IFN stimulation experiments were performed to examine the IFN-mediated activation of ACE2 isoforms (full-length and truncated) and furin in epithelial cell lines. Following all the IFNs treatments, only the truncated ACE2 levels, were upregulated significantly in the A549 and Calu3 cells, in particular by type I IFNs. If confirmed in vivo following IFNs' activation, the induction of the truncated ACE2 isoform only would not enhance the risk of SARS-CoV-2 infection in the respiratory tract.

Age Limit in Bronchiolitis Diagnosis: 6 or 12 Months?

Aim: The most frequent cause of lower respiratory tract infection in infants is bronchiolitis. Up to now there is no agreement on the upper limit age of bronchiolitis. Our aim was to identify if there are clinical differences in infants hospitalized for bronchiolitis between 0-6 months and 6-12 months of age. A secondary aim was to establish whether there was differences in terms of recurrent wheezing at 12, 24, and 36 months of follow-up. Methods: We retrospectively analyzed clinical and virological records of 824 infants hospitalized for bronchiolitis during 11 consecutive epidemic seasons. From each infant at admission to the hospital nasopharyngeal washing was collected, clinical severity was assessed and clinical data were extracted from a structured questionnaire. At 12-24-36 months after discharge, parents were interviewed seeking information on recurrent wheezing. Results: A total of 773 infants (Group1) were ≤6 months of age, while 51 were >6 months (Group 2). No differences between family history for atopy and passive smoking exposure were observed between the two groups. Respiratory syncyzial virus was detected more frequently in Group 1 and human bocavirus in Group 2. The clinical severity score (p = 0.011) and the use of intravenous fluids (p = 0.0001) were higher in Group 1 with respect to Group 2 infants. At 36 months follow-up 163/106 (39.4%) Group 1 and 9/9 Group 2 infants experienced recurrent wheezing (p = 0.149). Conclusion: We demonstrated that 0-6 months old infants bronchiolitis differs from > 6 months bronchiolitis.

Human bocavirus in children hospitalized for acute respiratory tract infection in Rome.

BACKGROUND: The role of human bocavirus (HBoV) as a respiratory pathogen has not been fulfilled yet. We aimed to describe clinical and serological characteristics of children with HBoV hospitalized for acute respiratory tract infection and to evaluate whether differences occur between HBoV alone and in co-infection. METHODS: We retrospectively reviewed data from 60 children (median age of 6.2 months, range 0.6-70.9) hospitalized for acute respiratory symptoms, with HBoV detected from a respiratory sample, using a reverse transcriptase-PCR for 14 respiratory viruses (including respiratory syncytial virus (RSV), influenza virus A and B, human coronavirus OC43, 229E, NL-63 and HUK1, adenovirus, rhinovirus, parainfluenza virus1-3, and human metapneumovirus). RESULTS: HBoV was detected alone in 29 (48.3%) patients, while in co-infection with other viruses in 31 patients (51.7%), with a peak between December and January. Among the 60 patients, 34 were bronchiolitis, 19 wheezing, 3 pneumonia, 2 upper respiratory tract infection, and 2 whooping cough. Seven children (11.6%) required admission to the paediatric intensive care unit (PICU) for respiratory failure. No differences was observed in age, family history for atopy and/or asthma, clinical presentations, chest X-ray, or laboratory findings in children with HBoV alone vs. multiple viral detection. RSV was the most frequently co-detected virus (61.3%). When compared with HBoV detection alone, the co-detection of RSV and HBoV was associated with male sex (P = 0.013), younger age (P = 0.01), and lower blood neutrophil count (P = 0.032). CONCLUSIONS: HBoV can be detected alone and in co-infection respiratory samples of children with an acute respiratory tract infection. A cause-effect relationship between HBoV and respiratory infection is not clear, so further studies are needed to clarify this point.

Modifiable risk factors associated with bronchiolitis.

BACKGROUND: We sought to clarify possibly modifiable risk factors related to pollution responsible for acute bronchiolitis in hospitalized infants. METHODS: For this observational study, we recruited 213 consecutive infants with bronchiolitis (cases: median age: 2 months; age range: 0.5-12 months; boys: 55.4%) and 213 children aged <3 years (controls: median age: 12 months; age range: 0.5-36 months; boys: 54.5%) with a negative medical history for lower respiratory tract diseases hospitalized at 'Sapienza' University Rome and IRCCS Bambino Gesù Hospital. Infants' parents completed a standardized 53-item questionnaire seeking information on social-demographic and clinical characteristics, indoor pollution, eating habits and outdoor air pollution. Multivariate logistic regression analyses were run to assess the independent effect of risk factors, accounting for confounders and effect modifiers. RESULTS: In the 213 hospitalized infants the questionnaire identified the following risk factors for acute bronchiolitis: breastfeeding ⩾3 months (OR: 2.1, 95% confidence interval [CI]: 1.2-3.6), presence of older siblings (OR: 2.8, 95% CI: 1.7-4.7), ⩾4 cohabitants (OR: 1.5, 95% CI: 1.1-2.1), and using seed oil for cooking (OR: 1.7, 95% CI: 1.2-2.6). Having renovated their home in the past 12 months and concurrently being exposed daily to smoking, involving more than 11 cigarettes and two or more smoking cohabitants, were more frequent factors in cases than in controls ( p = 0.021 and 0.05), whereas self-estimated proximity to road and traffic was similar in the two groups. CONCLUSIONS: We identified several risk factors for acute bronchiolitis related to indoor and outdoor pollution, including inhaling cooking oil fumes. Having this information would help public health authorities draw up effective preventive measures - for example, teach mothers to avoid handling their child when they have a cold and eliminate exposure to second-hand tobacco smoke.

Risk Factors for Virus-induced Acute Respiratory Tract Infections in Children Younger Than 3 Years and Recurrent Wheezing at 36 Months Follow-Up After Discharge.

BACKGROUND: We sought to know more about how 14 common respiratory viruses manifest clinically, and to identify risk factors for specific virus-induced acute respiratory tract infections (ARTIs) in children younger than 3 years old and for wheezing at 36-month follow-up. METHODS: We retrospectively studied the clinical records for 273 full-term children (median age, 2.9 months; range, 0.26-39; boys, 61.2%) hospitalized for ARTIs, whose nasopharyngeal specimen tested positive for a respiratory virus and 101 children with no history of respiratory diseases (median age, 8 months; range, 0.5-36.5; boys, 58.4%). At 12, 24 and 36 months after children's discharge, all parents were interviewed by telephone with a structured questionnaire on wheezing episodes. RESULTS: The most frequently detected viruses were respiratory syncytial virus in bronchiolitis, human rhinovirus in pneumonia and human bocavirus in wheezing. Multivariate analysis identified, as risk factors for virus-induced ARTIs, the presence of siblings [odds ratio (OR): 3.0 (95% confidence interval [CI]: 1.8-5.2)], smoking cohabitants (OR: 2.3 (95% CI: 2-4.2)] and breastfeeding lasting less than 3 months [OR: 0.5 (95% CI: 0.3-0.9)]. The major risk factor for respiratory syncytial virus-induced ARTIs was exposure to tobacco smoke [OR: 1.8 (95% CI: 1.1-3.2)]. Risk factors for human rhinovirus-induced ARTIs were attending day-care [OR: 5.0 (95% CI: 2.3-10.6)] and high eosinophil blood counts [OR: 2.6 (95% CI: 1.2-5.7)]. The leading risk factor for recurrent wheezing was exposure to tobacco smoke [OR: 2.5 (95% CI: 1.1-15.6)]. CONCLUSIONS: Each respiratory virus leads to a specific clinical manifestation. Avoiding exposing children to tobacco smoke might restrict viral spread from sick parents and siblings to younger children, prevent severe respiratory diseases, and possibly limit sequelae.

Bronchiolitis: Analysis of 10 consecutive epidemic seasons.

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non-peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, "Sapienza" University of Rome over the period 2004-2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co-infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December-January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non-peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330-1335. © 2016 Wiley Periodicals, Inc.

Coeliac disease screening among a large cohort of overweight/obese children.

Coeliac disease (CD) is a chronic, gluten-dependent enteropathy with a prevalence of approximately 1% in Western countries. Up to now, CD has been described only in sporadic cases of obesity. Our study aimed to evaluate retrospectively CD prevalence in a large series of overweight/obese children and adolescents. Among the 1527 overweight/obese children and adolescents consecutively evaluated, 17 (7 boys, 1.11%) were positive for serology and showed villous atrophy. In all of the patients with CD a well-balanced gluten-free diet was started, and a loss of weight rapidly obtained. Our study demonstrates that CD prevalence in overweight/obese children is similar to the general paediatric population in Italy.

Dyspepsia and celiac disease: Prevalence, diagnostic tools and therapy.

The prevalence of dyspepsia is up to 40% in population-based study. Functional dyspepsia is an exclusion diagnosis and it is classified as a chronic abdominal pain-related functional disorder, characterized by the presence of persistent or recurrent pain or discomfort centered in the upper abdomen, neither relief by defecation, nor association with the onset of a change in stool frequency or form. Celiac disease (CD) is a common autoimmune enteropathy, with a prevalence around 1% in the general population. Its diagnosis includes a serological screening and an upper gastrointestinal endoscopy with multiple biopsies. Gluten-free diet is the only effective treatment. CD diagnosis is often delayed in asymptomatic patients or in individuals with less clinical gastrointestinal symptoms. Several studies performed coeliac disease screening in patients with symptoms suggestive of dyspepsia, showing a biopsy-proved prevalence that ranged from 0.5% to 2%. The typical endoscopic markers of villous atrophy are not sufficiently sensitive, so some endoscopic techniques, such as "water immersion" and confocal endomicroscopy were proposed to improve the diagnostic sensitivity and target biopsies. A recent meta-analysis estimated that the prevalence of CD was higher in patients with dyspepsia, but not in a statistically significant way. However this assumption should be confirmed further larger studies.

The celiac iceberg: characterization of the disease in primary schoolchildren.

OBJECTIVE: Celiac disease (CD) has a prevalence of 0.55% to 1% in Italy. Identifying CD in schoolchildren to characterize CD iceberg and evaluate the effect of diagnosis in screening-detected children. METHODS: A total of 7377 5- to 8-year-old children were invited to participate. A total of 5733 salivary samples were collected and tested for anti-transglutaminase antibodies (tTGAb), using a fluid-phase radioimmunoassay. Salivary tTGAb-positive children were analyzed for serum antibodies (anti-endomysium antibodies, radioimmunoassay, and enzyme-linked immunosorbent assay tTGAb). Positive children underwent endoscopy and then started gluten-free diet (GFD) and periodical follow-up. RESULTS: Forty-six subjects were found salivary tTGAb-positive and 16 border-line. Forty-five of 46 and 5 of 15 of them were also serum antibody-positive. Forty-two children showed duodenal villous atrophy and 1 had only type 1 lesions. Three children started GFD without performing endoscopy. CD prevalence (including 23 previously diagnosed children with CD) was 1.2%. Considering all 65 celiacs in our sample, a silent CD was found in 64%, typical in 28%, atypical in 7%, and potential in 1%. All patients showed strict adherence to GFD, weight and stature increase, and well-being improvement. Eighty-five percent and all but 2 screening-detected children with CD had Italian parents. CONCLUSIONS: Our sample size, representative of primary schoolchildren of our region, demonstrated that CD prevalence is growing in Italy, with a modified clinical spectrum and iceberg deepness.

Duodenal bulb in celiac adults: the "whether biopsying" dilemma.

BACKGROUND: Celiac disease (CD)-related lesions were described in duodenal bulb of celiac patients. GOAL: Our aim was to evaluate the morphology of bulb mucosa in adult celiac patients and in controls to evaluate its usefulness for CD diagnosis. STUDY: We studied 43 celiac patients (10 male, median age: 35.2 y) at diagnosis and 43 gastroenterological controls (10 male, median age: 37.8 y), submitted to upper endoscopy for gastroenterological complaints. Histologic lesions were assayed by an experienced pathologist according to the Marsh modified classification. Antiendomysium antibodies and antitransglutaminase antibodies-tTGAb (ELISA and/or RIA) have been tested. In selected patients, DNA was typed for DRB1, DQA1, and DQB1 genes by sequence-specific primer polymerase chain reaction. RESULTS: In all celiac patients lesions were present in the bulb mucosa. One female with thyroiditis, who had a CD daughter, showed lesions only in the duodenal bulb. Patchy villous atrophy was found in another patient. All celiacs were antiendomysium and/or tTGAb positive. DQ2 heterodimer was present in 5 CD patients. The gastroenterological controls showed normal mucosa in the duodenum. CONCLUSIONS: This study demonstrates that CD-related histologic lesions are present in duodenal bulb of adult patients. Moreover, the normal aspect of this mucosa in gastroenterological controls implies the high negative predictive value of this finding. Therefore, we suggest taking at least 1 biopsy on the bulb area and 1 from the distal duodenum for CD diagnosis, in all the patients submitted to upper endoscopy, to avoid missed or delayed diagnosis.