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On March 11, 2020, the World Health Organization (WHO) declared the pandemic because of a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). In January 2020, the first transmission to healthcare workers (HCWs) was described. SARS‐CoV‐2 is transmitted between people because of contact, droplets, and airborne. Airborne transmission is caused by aerosols that remain infectious when suspended in air over long distances and time. In the clinical setting, airborne transmission may occur during aerosol generating procedures like flexible bronchoscopy. To date, although the role of children in the transmission of SARS‐CoV‐2 is not clear the execution of bronchoscopy is associated with a considerably increased risk of SARS‐CoV‐2 transmission to HCWs. The aim of this overview is to summarize available recommendations and to apply them to pediatric bronchoscopy. We performed systematic literature searches using the MEDLINE (accessed via PubMed) and Scopus databases. We reviewed major recommendations and position statements published at the moment by the American Association for Bronchology and Interventional Pulmonology, WHO, European Center for Disease Prevention and Control and expert groups on the management of patients with COVID‐19 to limit transmission among HCWs. To date there is a lack of recommendations for safe bronchoscopy during the pandemic period. The main indications concern adults and little has been said about children. We have summarized available recommendations and we have applied them to pediatric bronchoscopy.

BACKGROUND Community-acquired pneumonia (CAP) represents one of the most common infectious diseases among children. Diagnosis of CAP is mainly clinical. Chest X-ray (CXR) remains the gold standard for the diagnosis in severe or controversial conditions. Recently, some authors have focused on the application of ultrasound in lung diseases but the role of lung ultrasound (LUS) in the diagnosis of CAP is still debated. We aimed to study the concordance between LUS and CXR in evaluating specific signs of CAP. As a secondary aim, we sought to determine the sensitivity and specificity of LUS in CAP diagnosis compared with CXR. Finally, we evaluated the role of LUS during the follow up. METHODS We enrolled 68 children (

Severe Acute Respiratory Syndrome – Coronavirus – 2 (SARS-CoV-2) and its related Coronavirus Disease – 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.

In recent decades, scientific studies of chemical processes involving metabolites have been steadily increasing, indicating that we are well into the metabolomics era. This has resulted in numerous studies that explore the field of biomarkers. One of the medical areas most concerned with these innovations is certainly that of childhood respiratory disorders, including asthma and cystic fibrosis. This current study is a review of the literature about biomarkers used or studied in the field of pediatric pulmonology, including asthma and cystic fibrosis.

The COL2A1 gene consists of 54 exons spanning over 31.5 kb and encodes for type II collagen. Type II collagen is the main component of hyaline cartilage extracellular matrix, nucleus pulposus of intervertebral discus, vitreous humor of the eye and inner ear structure. Molecular defects in COL2A1 gene cause a wide variety of rare autosomal-dominant conditions known as type II collagenopathies. A clear genotype-phenotype relationship is not yet known. However, some correlations are described. Spondyloephyseal dysplasia congenita was suggested for a short-trunk dwarfing condition affecting primarily the vertebrae and the proximal epiphyses of the long bones.

In the last twenty years, despite high vaccination coverage, epidemics of pertussis are occurring in both developing and developed countries. Many reasons could explain the pertussis resurgence: the increasing awareness of the disease, the availability of new diagnostic tests with higher sensitivity, the emergence of new Bordetella pertussis (B. pertussis) strains different from those contained in the current vaccines, the asymptomatic transmission of B. pertussis in adolescents and adults and the shorter duration of protection given by the acellular pertussis (aP) vaccine. New preventive strategies have already been implemented, such as booster doses of aP vaccine in adolescents and adults, maternal immunisation during pregnancy and the "cocooning" strategy, but more are still needed. Knowing what is new about this old disease is necessary to reduce its incidence and to protect infants too young to be vaccinated, which have the highest risk of complications and death.

Lung ultrasound has become increasingly used in both adult and pediatric populations, allowing the rapid evaluation of many lung and pleura diseases. This popularity is due to several advantages of the method such as the low cost, rapidity, lack of ionizing radiation, availability of bedside and repeatability of the method. These features are even more important after the outbreak of the SARS-CoV-2 pandemic, given the possibility of recognizing through ultrasound the signs of interstitial lung syndrome typical of pneumonia caused by the virus. The purpose of this paper is to review the available evidence of lung ultrasound (LUS) in children and its main applications in pediatric diseases.

The diffusion of the SARS‐CoV‐2 virus and the implementation of restrictive measures led to a drastic reduction of respiratory syncytial virus (RSV) diffusion. Few RSV cases have been detected worldwide, even after the removal of the restrictions. We review the current literature and present possible explanations on why there has been a significant reduction of RSV detection during the COVID‐19 pandemic. We also hypothesize what may happen when RSV begins to circulate again. The increase of an immunologically naïve population, with infants born from mothers who have not reinforced their immunity to RSV, could lead to greater RSV epidemics in the coming seasons. It is crucial to prepare the scientific community and to keep RSV surveillance active to avoid dramatic consequences.

To the editor: [...]

Background: Community-acquired pneumonia (CAP) is an acute bacterial or viral inflammation of the lung parenchyma. Worldwide it is one of the most common infectious diseases among children. Diagnosis of CAP is clinical, but chestX-ray (CXR) is used in special clinical situation or severe cases. The role of lung ultrasound (LUS) to diagnose and manage CAP is still debated. Aim: 1) To evaluate concordance between LUS and CXR in evaluating specific signs of CAP (Cohen’s Test). 2) To determine sensitivity and specificity of LUS in the diagnosis of CAP compared to CXR. 3) To evaluate the role of LUS during the follow-up of patients hospitalized for CAP. Methods: We enrolled 68 patients younger than 16 years: 41 cases with clinical and radiological diagnosis of CAP and 27 controls with no respiratory diseases who performed a LUS during hospitalization. Nine-teen cases were re-evaluated 30 days after discharge with both LUS and CXR. Results: LUS confirmed CAP diagnosis in 40/41 cases, showing the presence of single or multiple consolidations. Concordance (K) between LUS and CXR was 0.88 in the right hemithorax and 0.70 in the left hemithorax. Moreover, LUS showed 97% of sensitivity and 96% of specificity in the diagnosis of CAP compared to CXR. During the follow-up, LUS sensitivity and specificity were 100% and 94%, respectively. Conclusion: Our study showed the potential benefit of LUS in the diagnosis and follow-up of children with CAP, possibly avoiding the need to take CXR.

Introduction Acute bronchiolitis is the most common respiratory illness and the main cause of respiratory failure in infant. Effective therapy is not available. A relatively new, safe and promising method of non-invasive respiratory support is oxygen delivery by high-flow nasal cannula (HFNC), but several questions concerning HFNC clinical practice remain unanswered. Aim The main aim of our study is to analyse the clinical course of infants hospitalized for bronchiolitis who underwent HFNC in order to identify clinical, laboratory or radiological findings that can have an impact on HFNC failure, which is defined as requirement for mechanical ventilation (MV). Methods We conducted a retrospective data analysis of case records of 130 patients less than 12 months hospitalized for bronchiolitis who underwent HFNC and clinical epidemiological laboratory and radiological data were collected. Results Only 11 (8.5%) out 130 infants required invasive mechanical ventilation for clinical deterioration. Patients who needed to switch from HFNC to MV because of a progressive respiratory failure showed more frequently a complete upper lobe consolidation on CXR (90.9%) than infants exclusively supported by HFNC (14.9%). They were younger with a lower admission weight and they had a lower lymphocyte count than patients who underwent HFNC only. Discussion Our study suggests that a complete upper lobe consolidation in young infants is a significant risk factor for HFNC failure. Further studies are needed to understand if an early identification of consolidation following by an adequate follow-up and proper therapeutic strategies may reduce the number of children who require mechanical ventilation.

Pneumonia is an important cause of morbidity and mortality in children. We described viral aetiologies, with particular interest in detecting SARS-CoV-2, in hospitalized pneumonia children. Human rhinovirus was the most frequently detected agent. No children tested positive for SARS-CoV-2. Our findings suggest that SARS-CoV-2 infection is rare in children and it was not circulating in Rome before COVID-19 outbreak.

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.

Background Positive serology for cytomegalovirus (CMV) has been associated with all-cause mortality risk but its role in COPD mortality is unknown. The objective of the present study was to assess the relationship between CMV serology and COPD mortality. Methods We analysed data from 806 participants in the Tucson Epidemiological Study of Airway Obstructive Disease who, at enrolment, were aged 28–70 years and had completed lung function tests. We tested CMV serology in sera from enrolment and defined “high CMV serology” as being in the highest tertile. Vital status, date and cause of death were assessed through death certificates and/or linkage with the National Death Index up to January 2017. The association of CMV serology with all-cause and cause-specific mortality risk was tested in Cox models adjusted for age, sex, level of education, body mass index, smoking status and pack-years. Results High CMV serology was marginally associated with all-cause mortality (p=0.071) but the effect was inversely dependent on age, with the association being much stronger among participants, Using a 45-year longitudinal population-based cohort, it was demonstrated for the first time that high CMV serology predicts COPD mortality risk, particularly in younger subjects, identifying a novel and early risk factor for COPD mortality http://bit.ly/32odP0Q

Aim To test the hypothesis that the balance of type-1/type-2 immune response differs between infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis during the peak months and those during the nonpeak months. Methods We prospectively enrolled 90 unrelated full-term previously healthy infants hospitalized during the first year of life for RSV sole bronchiolitis over 2 epidemics (November 2016 to April 2017 and October 2017 to April 2018). We stratified infants as follows: hospitalized during the peak months (n: 71) and during the nonpeak months (n: 19). The frequencies of CD4+ producing interferon (IFN)-γ and interleukin (IL)-4 and of CD8+ producing IFN-γ T cells were measured by flow cytometry from infant peripheral whole blood. The T-helper cell (Th2) polarization index was calculated as the ratio between CD4+ T cells producing IL-4 and CD4+ T cells producing IFN-γ. Results Infants hospitalized during nonpeak months were significantly less frequently breast-fed, had a higher eosinophils count, a significantly higher percentage of CD4+ T cells producing IL-4 and higher Th2 polarization index than infants hospitalized during the peak months. Conclusions We elucidated the presence of different endotypes in infants with RSV sole bronchiolitis. Previously healthy full-term infants hospitalized during the nonpeak months seem to be more likely those with a possible predisposition to atopy.

BACKGROUND Bronchiolitis is the most common acute viral infection of the lower respiratory tract in infants. Clinical severity is associated with different risk factors; however, no clinical, laboratory, or radiological findings are able to predict the course of the disease in full-term infants. Lung ultrasound (LUS) is a valid technique for the diagnosis and evaluation of pediatric respiratory diseases. AIMS The aim of our study was to correlate an LUS score with a clinical score, to describe lung ultrasound findings in cases and controls, and to compare LUS findings with chest X-ray (CXR) in infants hospitalized with bronchiolitis. METHODS We conducted a single-center, longitudinal, prospective study on 92 infants. Sixty-three out of 92 infants were hospitalized for acute bronchiolitis (cases) and twenty-nine out of 92 for diseases not involving the respiratory system (controls). All patients with bronchiolitis underwent a clinical evaluation with the assignment of a clinical severity score and performed lung ultrasound with the assignment of an LUS score. Twenty-three out of 63 infants with bronchiolitis underwent also a CXR for clinical indications. Control infants performed only LUS. RESULTS In infants with bronchiolitis LUS score showed a positive correlation with the clinical score (r = .62, p

Background A study of respiratory syncytial virus-A (RSV A) genotype ON1 genetic variability and clinical severity in infants hospitalized with bronchiolitis over 6 epidemic seasons (2012–2013 to 2017–2018) was carried out. Methods From prospectively enrolled term infants hospitalized for bronchiolitis, samples positive for RSV A ON1 (N = 139) were sequenced in the second half of the G gene. Patients’ clinical data were obtained from medical files and each infant was assigned a clinical severity score. ANOVA comparison and adjusted multinomial logistic regression were used to evaluate clinical severity score and clinical parameters. Results The phylogenetic analysis of 54 strains showed 3 distinct clades; sequences in the last 2 seasons differed from previous seasons. The most divergent and numerous cluster of 2017–2018 strains was characterized by a novel pattern of amino acid changes, some in antigenic sites. Several amino acid changes altered predicted glycosylation sites, with acquisition of around 10 new O-glycosylation sites. Clinical severity of bronchiolitis increased in 2016–2017 and 2017–2018 and changed according to the epidemic seasons only. Conclusions Amino acid changes in the hypervariable part of G protein may have altered functions and/or changed its immunogenicity, leading to an impact on disease severity.

Respiratory Syncytial Virus (RSV) is the leading cause of bronchiolitis, and the severity may be influenced by the bacterial ecosystem. Our aim was to analyze the nasal microbiota from 48 infants affected by bronchiolitis from RSV virus and 28 infants with bronchiolitis but negative for the virus. Results showed a significantly lower biodiversity in the RSV-positive group with respect to the RSV-negative group, a specific microbial profile associated with the RSV-positive group different from that observed in the negative group, and significant modifications in the relative abundance of taxa in the RSV-positive group, as well as in the RSV-A group, with respect to the negative group. Furthermore, microbial network analyses evidenced, in all studied groups, the presence of two predominant sub-networks characterized by peculiar inter- and intra-group correlation patterns as well as a general loss of connectivity among microbes in the RSV-positive group, particularly in the RSV-A group. Our results indicated that infants with more severe bronchiolitis disease, caused by RSV-A infection, present significant perturbations of both the nasal microbiota structure and the microbial relationships. Patients with a milder bronchiolitis course (RSV-B-infected and patients who have cleared the virus) presented less severe alterations.

Background We aimed to study respiratory syncytial virus (RSV) genotype distribution, clinical presentation, and disease severity in infants with bronchiolitis from RSV subtypes and new RSV genotypes. Methods We prospectively enrolled previously healthy term infants less than 1 year old hospitalized for bronchiolitis in an Italian university hospital over 12 epidemic seasons. In 312 nasopharyngeal washings positive for RSV, we sequenced the viral genotype and analyzed this according to patient data. Strain-specific RSV loads were quantified for 273 specimens. Results From 2005-2006 to 2011-2012, the RSV-A genotype NA1 predominated, and was replaced in 2012 by the novel ON1. All infants infected with RSV subtype B were genotype BA. Stratifying data according to genotypes NA1, ON1, and BA showed that NA1-infected infants were the youngest and had the most severe clinical course. Conversely, BA-infected infants had less severe symptoms and more frequently had eosinophilia and a family history of asthma. Infants with the ON1 genotype had a milder clinical course than those with NA1 and more risk factors for asthma, despite having the highest viral loads. Conclusion The disease course in infants hospitalized for acute RSV bronchiolitis may depend on the RSV genotype.

The heterogeneous nature of asthma requires personalised treatments. Monoclonal antibody treatments showed good efficacy, and should be considered when symptoms are poorly controlled despite good inhaler technique, compliance and controlled comorbidities. http://ow.ly/UWpg30hImQh.

Spirometry plays a pivotal role in the diagnosis and management of COPD and other respiratory diseases. Since lung function varies with age, height, sex and ethnicity, accurate interpretation is dependent upon using appropriate reference ranges. In this article, we will present two landmark papers: one on changes in forced expiratory volume in 1 s (FEV1) over time in COPD [1] and the other focussing on spirometry reference ranges produced by the Global Lung Function Initiative (GLI) [2]., A discussion of two landmark papers highlighting the use of spirometry as a sensitive measure of the rate of decline in FEV1 in COPD, and the importance of using the Global Lung Function Initiative reference data http://bit.ly/2C0Nhqa

Bronchiolitis is the first lower respiratory tract viral infection manifesting in infants younger than 12 months of age. Our aim was to evaluate clinical and serological differences in infants with bronchiolitis from a single or from multiple viruses. Our secondary aim was to investigate differences in recurrent wheezing episodes after 12‐24‐36 months of follow‐up. We reviewed the clinical records for 486 full‐term infants hospitalized for bronchiolitis with at least one virus detected in the nasopharyngeal aspirate. In 431 (88.7%) patients one virus was detected and in 55 (11.3%) infants more than one virus was found. No differences were observed in the length of hospitalization, clinical severity score, O2 supplementation or admission to the intensive care unit. Single virus was associated with higher serum C‐reactive protein (C‐RP) than infants with multiple viruses and higher blood neutrophil counts. Respiratory syncytial virus (RSV) was the most frequently detected virus. RSV alone was associated with higher C‐RP (P = 0.007), compared to RSV coinfection. Infants with human rhinovirus (hRV) alone had higher white blood cell counts, higher blood neutrophils, and higher serum C‐RP levels than hRV co‐infection (P = 0.029, P = 0.008, P = 0.008). RSV + hRV, the most frequent co‐infection, was associated with lower neutrophil count and lower C‐RP levels (P = 0.008, P = 0.016) and less fever (P = 0.012), when comparing RSV versus hRV versus RSV + hRV. No differences were found in the frequency of recurrent wheezing between single versus multiple viruses after bronchiolitis. Our findings suggest that in infants with bronchiolitis multiple viral co‐infections can occur, without influence in the clinical severity of the disease. Infants with co‐infection seems to mount a lower inflammatory response.

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 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.

We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At birth, he experienced severe respiratory distress necessitating tracheotomy. Endoscopy done because mechanical ventilation failed to resolve desaturations disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting guaranteed a suitable respiratory status and allowed a child who was expected to die at birth, to reach 13.5 years old in good conditions.

Background: Respiratory Syncytial Virus (RSV) is the leading cause of bronchiolitis. The local bacterial ecosystem may influence RSV disease severity and the immune response. Aim: To evaluate the association between RSV infection, nasal microbiota composition (NMC) and patients’ immune response in infants with bronchiolitis. Materials and Methods: We characterized the NMC of 47 hospitalized infants Results: NMC differed among RSV and non RSV groups. In RSV-positive nasal samples alfa-diversity was reduced and NMC differed between RSV-A and RSV-B. Discriminant bacterial species were Clostridium indolis for RSV-A group and Hemophilus haemolyticus for RSV-B. In infants with RSV, there was a significant cross-correlation among NMC (evaluated as β diversity) and white blood cells level, expression of Lambda3 and Beta IFN genes and Th1/Th2 response. Conclusions: This preliminary study showed differences in the NMC in relation to the aetiological cause of bronchiolitis and the type of immune response, that are worthy of further examination in larger groups.

Background: Risk factors for bronchiolitis and for long term respiratory sequelae remain unclear. Aim: To study the occurrences of asthma and allergic sensitization after bronchiolitis. Materials: 622 children hospitalized for bronchiolitis (cases) during 9 consecutive seasons and 65 healthy children enrolled in “Piccolipiu” cohort with negative history for bronchiolitis (controls) were followed for 6 years. A structured questionnaire was used to obtain demographic information from all children. Parents were interviewed 5 years after hospitalization to check whether their children experienced recurrent wheezing. At 6 years of age 253 cases and all controls performed prick test. Results: Cases had lower gestational age (p=0.001), lower birth weight (p=0.016), higher smoking exposure during their first year of life (p Conclusions: Environmental factors seems to have an important role in bronchiolitis. Bronchiolitis is a risk factor or asthma but not for allergic sensitization.

Rationale: We aimed to study wheezing recurrence after bronchiolitis from different RSV genotypes: RSVA NA1 and ON1, and RSVB BA. Methods: We prospectively enrolled term infants Results: 125 infants had NA1, 49 ON1, and 41 BA bronchiolitis. At 3 years, we registered wheezing in 65.6% NA1, 77.6% ON1 and 75.6% BA bronchiolitis children. Patients with wheezing had a higher RSV load when hospitalized with bronchiolitis (6.3±1.6 vs 5.6±1.5; p=0.015 copies/ml), particularly in ON1 infants (7.3±1.1vs 6.3±1.3; p=0.026). Among NA1 infants, wheezing was more frequent in children who had a severe bronchiolitis comparing to those children who had a mild bronchiolitis (75.9% vs 56.7%; p=0.025). The logistic regression analysis adjusted for sex, family history of asthma, passive smoking exposure, RSV genotype and eosinophils count, found severe bronchiolitis (OR: 2.9; 95% CI: 1.3, 6.6; p=0.01) and high viral load (OR:1.3; 95% CI: 1.0, 1.6; p=0.04) as risk factors for wheezing at 3 years. Conclusion: Viral factors (genotype specific-viral load) and clinical factors (severity score) contribute to the occurrence of respiratory sequelae after hospitalization for RSV sole bronchiolitis.

Background: Respiratory syncytial virus (RSV)-A genotype ON1 caused a less severe bronchiolitis course than the previously circulating RSV-A genotype (Midulla, F et al JID 2018;219:526-534). However, ON1 continued to circulate worldwide and to differentiate in new strains. Aim: to study the variability of the viral glycoprotein G in relation to clinical severity in bronchiolitis cases. Methods: From prospectively enrolled previously healthy term infants hospitalized for bronchiolitis in 2012-13 to 2017-18 epidemic seasons, cases positive to RSV-A ON1 only were selected. After sequencing the second half of the G gene of about 70 samples, a phylogenetic analysis was performed. Demographic and clinical data were compared among divergent ON1 clades. Results: The phylogenetic analysis of the G gene identified genomic variants appearing since 2012; some of them were not maintained in the following seasons. All sequences did not present polymorphisms in the conserved tract of the G protein that binds the cellular receptor and in the heparin-binding domain. Nonetheless, most strains sequenced in the 2017-18 season set well apart from those of the previous epidemic seasons, in two distant branches of the phylogenetic tree. The two more divergent branches were characterized by patterns of aminoacid changes never reported before, some of which located in antigenic sites. Moreover, substitutions may have altered N- and O-glycosilation sites. Patients infected with divergent strains presented higher severity scores. Conclusions: The aminoacid changes detected in the hypervariable part of the G protein may have altered functions and/or changed its immunogenicity determining an impact on disease severity.

Background: Positive serology for cytomegalovirus (CMV) has been associated with all-cause mortality risk in previous studies. Aims: We sought to determine the relation of CMV serology to COPD mortality. Methods: We analyzed data from 806 participants in the TESAOD cohort who at enrollment in 1972 were aged 28–70 yrs and completed lung function tests. CMV serology in serum samples from enrollment was categorized as low, medium, and high tertiles. Date and cause of death were assessed through death certificates and linkage to the National Death Index up to January 2017. The association of CMV serology to all-cause and cause-specific mortality was tested in Cox models adjusted for age, sex, level of education, BMI, smoking status, and pack-years. Results: CMV serology was associated with subsequent all-cause mortality, but the effect was strongly dependent on age at enrollment. Among subjects Conclusions: High CMV serology is a novel and potentially modifiable risk factor for COPD mortality.

Introduction: Respiratory syncytial virus (RSV) A ON1, firstly detected in 2010, has progressively replaced the previous circulating subtype RSV A NA1. Aims and Objectives: The aim of our study was to compare the clinical severity of RSV A ON1 bronchiolitis in hospitalised children over six epidemic seasons. Methods: We enrolled 497 patients younger than 12 months, hospitalised for RSV bronchiolitis, through the epidemic seasons 2005/2006-2017/2018. We analyzed the genotype in 391 samples and selected the RSV A ON1 positive patients. For each patient, demographic and clinical data were collected from clinical records. A severity score (range 0-8) was calculated based on respiratory rate, peripheral oxygen saturation, presence of withdrawals and feeding difficulty. Furthermore, we retrospectively collected the number of bronchiolitis visiting the Emergency Department and the number of hospitalised bronchiolitis through the epidemic seasons 2012/2013-2017/2018. Results: From the epidemic season 2012/2013, when RSV A ON1 was first detected, the rate of bronchiolitis hospitalised per bronchiolitis visited in the Emergency Department progressively increased (from 51.3% in 2012/2013 to 66.9% in 2017/2018). The severity score showed the same trend: β coefficient 0.52 (95% confidential interval: 0.38-0.66), p-value Conclusions: During the last six seasons (from 2012/2013) the severity of RSV A ON1 bronchiolitis has progressively increased. This phenomenon could be explained by the variability of the virus or by the host immune response.

Tracheomalacia and tracheobronchomalacia may be primary abnormalities of the large airways or associated with a wide variety of congenital and acquired conditions. The evidence on diagnosis, classification and management is scant. There is no universally accepted classification of severity. Clinical presentation includes early-onset stridor or fixed wheeze, recurrent infections, brassy cough and even near-death attacks, depending on the site and severity of the lesion. Diagnosis is usually made by flexible bronchoscopy in a free-breathing child but may also be shown by other dynamic imaging techniques such as low-contrast volume bronchography, computed tomography or magnetic resonance imaging. Lung function testing can provide supportive evidence but is not diagnostic. Management may be medical or surgical, depending on the nature and severity of the lesions, but the evidence base for any therapy is limited. While medical options that include bronchodilators, anti-muscarinic agents, mucolytics and antibiotics (as well as treatment of comorbidities and associated conditions) are used, there is currently little evidence for benefit. Chest physiotherapy is commonly prescribed, but the evidence base is poor. When symptoms are severe, surgical options include aortopexy or posterior tracheopexy, tracheal resection of short affected segments, internal stents and external airway splinting. If respiratory support is needed, continuous positive airway pressure is the most commonly used modality eitherviaa face mask or tracheostomy. Parents of children with tracheobronchomalacia report diagnostic delays and anxieties about how to manage their child's condition, and want more information. There is a need for more research to establish an evidence base for malacia. This European Respiratory Society statement provides a review of the current literature to inform future study.

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. 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). 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). 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.

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.

Background The clinical picture of celiac disease is changing with the emergence of subclinical forms and growing evidence reporting associated neurological disorders. Aims To establish the prevalence of celiac disease in children suffering from recurrent headache. Methods In our retrospective study we collected charts from 1131 children attending our tertiary care Centre for Paediatric Headache over the period 2001–2012. They were screened for celiac disease and positive patients were referred to our Operative Unit for Coeliac disease and confirmed positive children underwent upper endoscopy with multiple duodenal biopsies. Celiac children started a gluten-free diet. Results 883 children (481 females; median age, 9.8 years, range 3–19) performed celiac disease screening, and among them, 11 children (7 females; median age, 8.2 years, range: 4.8–13.9) were diagnosed with celiac disease. Seven children (5 females, median age, 11.9 years, range: 10.3–13.9) had been diagnosed as celiac prior to the neurological evaluation. The prevalence of celiac disease in our sample is 2.04% vs. 1.2% of the general population (p = 0.034). Conclusions Our study demonstrates, on a large series, that celiac disease prevalence is doubled in patients with chronic headache. Screening for celiac disease could be advised as part of the diagnostic work-up in these paediatric patients, particularly among pharmacological non-responders.

Bronchiolitis is the most common acute lower respiratory tract infection in infants and the first cause of hospitalization in this age group. Despite it has been studied for over 70 years, its management remains controversial and nowadays the treatment is only supportive. Pediatricians should be well acquainted with the clinical course of the disease. In particular, they should know that the severity of respiratory symptoms peaks between days 3-7 of the disease and dehydration is a key sign to consider for the management. In this review, we will discuss the most controversial points in the management of bronchiolitis according to six evidence-based guidelines, six clinical practice guidelines and five consensus-based reviews.

Background As the expression of type III IFN receptor is restricted to the mucosal surfaces, its evaluation could be crucial to characterize the role of IFNλs during bronchiolitis. Objectives This study was designed to investigate airway type III IFN receptor (IFNLR1/IL10RB) expression during respiratory syncytial virus (RSV) or human rhinovirus (HRV) bronchiolitis. Study design Seventy-one 1–6 month old infants hospitalized with their first episode of acute RSV or HRV bronchiolitis were selected for this study. Expression of IFNLR1, IL10RB and IFN-stimulated genes (ISGs) MxA and ISG56 in cells of nasopharyngeal washings taken within the first 48 h of admission were determined by a real-time hydrolysis probe RT-PCR assay. The ability of types I and III IFNs to induce the expression of both IFNLR1 and IL10RB in vitro was also evaluated. Results Airway IFNLR1 transcript levels were significantly higher in HRV bronchiolitis infants compared to those with RSV bronchiolitis. No differences were recorded for IL10RB-mRNA between RSV or HRV infection. IFNLR1 mRNA levels increased significantly in infants infected with the C species of HRV and in those with a higher clinical score index and with an eosinophil count >3%. There were no correlations in vivo between type III IFN receptors and those of ISGs and neither IFNLR1 nor IL10RB were induced in vitro by IFNs. Conclusions These results suggest that IFNLR1 are increased in HRV-infected infants with more severe bronchiolitis and blood eosinophilia and in those infected with the HRVC species.

Background: In infants with bronchiolitis the quality and the quantity of the immune response may be related to the viral etiology and the development of respiratory sequelae. The Th1/Th2 pattern of the immune response during bronchiolitis remains unclear. Objective: The aim of our study was to understand the pattern of the immune response in infants with bronchiolitis from RSV or RV. Methods: Nasal washings from infants hospitalized with bronchiolitis were tested for 14 respiratory viruses and RSV and RV cases were enrolled. Demographic and clinical data were taken from the medical files. Peripheral whole blood was obtained immediately after diagnosis and stimulated with Staphilococcus enterotoxin B (SEB). Intracellular production of IFNγ and IL4 by CD4 T cells was analyzed by flow cytometry. Results: 31 RSV (16 boys, median age: 1.9 months, age range: 0.5-12 months) and 10 RV (5 boys, median age: 1.6 months, age range: 0.8-9.2 months) samples were analyzed. Overall, family history of atopy and asthma, demographic and clinical data did not correlate with IFNγ and IL4 production. Basal (p=0.012) and after SEB stimulation (p=0.003) IL4 production was higher in RV than in RSV infants. IL-4/IFNγ ratio indicated a Th2 pattern in infants with bronchiolitis from RV and a Th1 in infants with bronchiolitis from RSV. Conclusion: RSV and RV induce a different immunological pattern in young infants hospitalized for acute bronchiolitis. RV seems to predispose to future atopy, while RSV mainly induces a Th1 oriented immune response. According to our data, anti-inflammatory therapy might play a role in some infants with bronchiolitis.

This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0.9% sodium chloride) twice a day. After a 16 weeks period, therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments. Monitoring visits, spirometry (COSMED Quark PFT4 ergo) and Rint were scheduled at 0,4,16,20,32 weeks. At T0, spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy. Salbutamol (400 mcg) was administered before the drug at each visit. After a 16-weeks treatment with HS an improvement of FVC (p = 0.02) and a favorable trend of FEV1 were registered. A worsening of FEV1 (p

Paediatric airway endoscopy is accepted as a diagnostic and therapeutic procedure, with an expanding number of indications and applications in children. The aim of this European Respiratory Society task force was to produce a statement on interventional bronchoscopy in children, describing the evidence available at present and current clinical practice, and identifying areas deserving further investigation. The multidisciplinary task force panel performed a systematic review of the literature, focusing on whole lung lavage, transbronchial and endobronchial biopsy, transbronchial needle aspiration with endobronchial ultrasound, foreign body extraction, balloon dilation and occlusion, laser-assisted procedures, usage of airway stents, microdebriders, cryotherapy, endoscopic intubation, application of drugs and other liquids, and caregiver perspectives. There is a scarcity of published evidence in this field, and in many cases the task force had to resort to the collective clinical experience of the committee to develop this statement. The highlighted gaps in knowledge underline the need for further research and serve as a call to paediatric bronchoscopists to work together in multicentre collaborations, for the benefit of children with airway disorders.

Background In this study we sought to evaluate the association between viral bronchiolitis, weather conditions, and air pollution in an urban area in Italy. Methods We included infants hospitalized for acute bronchiolitis from 2004 to 2014. All infants underwent a nasal washing for virus detection. A regional agency network collected meteorological data (mean temperature, relative humidity and wind velocity) and the following air pollutants: sulfur dioxide, nitrogen oxide, carbon monoxide, ozone, benzene and suspended particulate matter measuring less than 10 µm (PM10) and less than 2.5 µm (PM2.5) in aerodynamic diameter. We obtained mean weekly concentration data for the day of admission, from the urban background monitoring sites nearest to each child's home address. Overdispersed Poisson regression model was fitted and adjusted for seasonality of the respiratory syncytial virus (RSV) infection, to evaluate the impact of individual characteristics and environmental factors on the probability of a being positive RSV. Results Of the 723 nasal washings from the infants enrolled, 266 (68%) contained RSV, 63 (16.1%) rhinovirus, 26 (6.6%) human bocavirus, 20 (5.1%) human metapneumovirus, and 16 (2.2%) other viruses. The number of RSV-positive infants correlated negatively with temperature (p < 0.001), and positively with relative humidity (p < 0.001). Air pollutant concentrations differed significantly during the peak RSV months and the other months. Benzene concentration was independently associated with RSV incidence (p = 0.0124). Conclusions Seasonal weather conditions and concentration of air pollutants seem to influence RSV-related bronchiolitis epidemics in an Italian urban area., Highlights • Peak RSV activity correlates with cold temperatures and higher relative humidity. • RSV-positive cases correlates positively with BZ, NOx, SO2, PM10 and PM2.5. • The most predictive pollutant for RSV cases (constant temperature and humidity)is BZ.