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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.

Pulmonary surfactant is a heterogeneous combination of lipids and proteins, which prevents alveolar collapse at the end of expiration cycle by decreasing the alveolar surface tension at the air-liquid interface. At birth, the expression of surfactant is very important for normal lung function and it is strictly correlated to gestational age. The best known genetic mutations associated with the onset of respiratory distress in preterm and full-term newborns and with interstitial lung disease later in childhood are those involving the phospholipid transporter (ABCA3) or surfactant proteins C and B (SP-C and SP-B) genes. In particular, mutations in the SP-B gene induce respiratory distress in neonatal period, while alterations on gene encoding for SP-C are commonly associated with diffuse lung disease in children or in adults. Both clinical phenotypes are present, if genetic mutations interest even the phospholipid transporter ABCA3 ambiguity in the sentence. Interstitial lung disease in children (chILD) is defined as a mixed category of mainly chronic and rare respiratory disorders with increased mortality and morbidity. Although genetic alterations are mainly responsible for the onset of these diseases, however, there are also other pathogenic factors that contribute to increase the severity of clinical presentation. In this review, we analyze all clinical features of these rare pulmonary diseases in neonatal and in pediatric age.

The recently discovered truncated, non-functional, ACE2 transcript (dACE2), but not the full-length ACE2 (f-lACE2), is induced by IFNs in differentiated airway cells. We measured expression of both ACE2 isoforms in SARS-CoV-2 positive and negative subjects, in relation to Interferon-stimulated genes. A significant activation of dACE2 transcript was found, in SARS-CoV-2 positive adults either hospitalized or not, showing a positive correlation with ISG15; f-lACE2 expression was weakly activated and not ISG-related. We confirmed a specific activation of dACE2 transcript in nasopharyngeal cells, related to the mucosal IFN response.

Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients.We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV140%), group 2 (FEV1 40-70%), group 3 (FEV170%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods.Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight (Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually.

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.

In the era of data-driven decision-making, unacceptable haziness, and inconsistency surrounds the yearlong scientific and public debate on the school closure policy in the coronavirus disease-2019 (COVID-19) pandemic mitigation efforts.The present literature review stems out of the need for a clear scaffold collecting in one place all current evidence, as well as helping to organize incoming future evidence, concerning both the role of schools in driving the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) community spread and the cost-effectiveness of school closure in containing such spread.References for this review were initially identified through searches of PubMed, Scopus, and Cochrane Library for articles published from March 2020 to March 2021 by the use of key terms "Schools," "COVID-19," "pandemic," "clusters," "outbreak," and "seroprevalence," selecting all articles from 2020 to 2021 with full-text availability. A further search was undertaken by screening citations of articles found in the original search and through Google Scholar and ResearchGate.Overall, evidence shows that opening schools and keeping them open in the context of the SARS-CoV-2 pandemic is possible, although behaviorally challenging and unfeasible if educational facilities or testing services are inadequate. Contrary to other respiratory viruses, children are not chief targets of SARS-CoV-2 infection, transmission, and disease. It also appears that the second wave of the SARS-CoV-2 virus spread in the WHO European region has been unrelated to school re-opening.A fact-based understanding of what is currently known on such a consequential policy is required to provide a basis of evidence for advocacy of either school closure or school opening at times of high-intensity community transmission of SARS-CoV-2.

Background: We previously demonstrated an 81% reduction in pediatric Emergency Rooms (ER) admissions in Italy during lockdown, from March 9 to May 3, 2020 (doi: 10.3390/ijerph17238753.). Since May 2020 lockdown measures were mitigated allowing the reopening of schools in September 2020. Aim: To evaluate pediatric ER admissions during schools reopening in Italy. Methods: We performed a retrospective multicenter study involving 11 Italian pediatric ERs. We compared total ER admissions from September 24, 2020 to November 6, 2020 with those during the corresponding timeframe in 2019. We evaluated 16 ER specific diagnoses grouped in Air communicable and Non-air communicable. Finally, we recognized four different triage categories: white, green, yellow and red. Results: In 2020 total ER admissions reduced by 51% compared to 2019 (8744 vs 17080, respectively). The decrease in Air communicable diseases was significantly higher compared to Non-air communicable diseases (-60% vs -41%, respectively). ER admissions in each triage category decreased in 2020 compared to 2019 but, in percentage, yellow codes increased and green codes decreased. Conclusions: We can speculate that social distancing and simple hygiene measures drastically reduced the circulation of air communicable diseases even during the reopening of schools. The increase in yellow codes during the lockdown period may be related to a lack of primary care and, consequently, a delay in ER admissions.

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 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.

To the editor: [...]

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.

Highlights • Combined expression of ACE2 isoforms was higher in virus-infected children than in adults. • In patients ACE2 expression level was consistently associated with that of ISG15. • The furin level was not correlated with patient’s age nor with ISG15. • Cell lines’ stimulation by type I/III Interferons induced only the truncated ACE2 isoform., 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 concentration, 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.

To the editor: [...]

From March 9 to May 3, 2020, lockdown was declared in Italy due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Our aim was to evaluate how the SARS-CoV-2 pandemic and related preventive strategies affected pediatric emergency rooms (ERs) during this period. We performed a retrospective cohort multicenter study, comparing the lockdown period to the corresponding period in 2019. We examined 15 Italian pediatric ERs in terms of visit rates, specific diagnoses (grouped as air communicable diseases and non-air communicable diseases), and triage categories. During the lockdown period, ER admissions decreased by 81% compared to 2019 (52,364 vs. 10,112). All ER specific diagnoses decreased in 2020 and this reduction was significantly higher for air communicable diseases (25,462 vs. 2934, p &lt, 0.001). Considering the triage category, red codes remained similar (1% vs. 1%), yellow codes increased (11.2% vs. 22.3%), and green codes decreased (80.3% vs. 69.5%). We can speculate that social distancing and simple hygiene measures drastically reduced the spread of air communicable diseases. The increase in yellow codes may have been related to a delay in primary care and, consequently, in ER admissions.

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 ERS International Congress 2018 represented the theatre, for researchers with an interest in respiratory medicine, to feature their work to the researchers’ community. In this article, we provide the insight from the paediatric assembly, summarizing the results of the highest quoted abstracts presented at the meeting. We grouped the reviewed abstract in different categories as follows.

These fellowships are focused on young scientists and clinicians in the early stages of their research career in respiratory medicine. They provide a unique opportunity to visit a host institution in a country other than the candidate’s own for 1–3 months, with the aim of learning a research technique not available in the home institution. The call for applications will be open in the summer and will close on October 1, 2018., An overview of @ERStalk fellowship opportunities with testimonials from previous fellows, and 12 tips for getting involved in #ERSCongress from @EarlyCareerERS http://ow.ly/XUaI30jjpPc

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.

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.

As the English dramatist Thomas Dekker wrote, “Sleep is that golden chain that ties health and our bodies together”. One of the most frequently sleep-related disorders (SRD) is obstructive sleep apnoea syndrome (OSAS). OSAS is a relatively “young” disease and at the same time, one of the most important respiratory conditions discovered in the last 50 years due to its incidence, prevalence, health-related impact on the patient’s life and economic burden [1]., Have we reached the point where respiratory polygraphy can replace polysomnography in the assessment of OSAS? http://ow.ly/UxCU30bNopq

Today, the term “study” is very frequently used in quite a broad sense: survey, clinical trial, analysis, research and other terms with deeply different meanings are often generally indicated as “studies”. A “study” can be generally defined as a process composed of several actions aimed to verify one or more hypotheses (objectives), with the ultimate goal of sharing the answers (results) with a target audience, in the form of a scientific paper, presentation or poster., The key for the success of a study lies in the careful design of all its different phases, from the statement of the objectives to the dissemination of the results http://ow.ly/5NbG30kHEnQ

Noninvasive ventilation (NIV) is now an established evidence-based treatment for acute hypercapnic respiratory failure (AHRF), predominantly for defined patients admitted with exacerbations of chronic obstructive pulmonary disease (COPD), but also a range of other conditions including obesity-related respiratory failure and chest wall deformities requiring an acute hospital admission. Over the past two decades, there has been a significant shift towards greater use of NIV in place of invasive mechanical ventilation (IMV) in this group of patients. Here we set out to discuss a landmark paper in this respect: the report of the YONIV trial (Yorkshire Noninvasive Ventilation Trial), published in June 2000, which addressed the key practical questions around the early use of ward-based NIV at the time [1]. A recent narrative review on the epidemiology of NIV for acute respiratory failure in COPD patients concluded that this dramatic increase in NIV use is probably due to the increased experience of the medical teams, treating sicker patients with comorbidities and utilising NIV outside the intensive care unit (ICU), further confirming the pivotal role of the original trial enabling the early use of acute NIV on medical wards [2]., The landmark YONIV trial addressed key practical questions surrounding the early use of ward-based noninvasive ventilation, which is now an established evidence-based treatment for acute hypercapnic respiratory failure http://ow.ly/BDC530iWhne

Travel and stay at high altitude for recreational purposes or work is challenging, because the demand for acute acclimatisation to hypobaric hypoxia triggers distinct respiratory, cardiovascular, neurohumoral and psychological shift. The respiratory response, such as increase in respiratory rate, hypoxic vasoconstriction and other mechanisms, may be most pronounced. Acute mountain sickness (AMS) is likely to develop in unacclimatised subjects who rapidly ascend to high altitude, with clearly growing prevalence with increasing altitude [1]. Because AMS is diagnosed when other potential reasons are ruled out, the diagnosis is to a great extent subjective, because the leading symptom of this condition is headache. This article aims to provide more information on AMS, a prevalent condition at high altitude, as well as on emerging novel methods of diagnosis, and to discuss the feasibility of their use at high altitude., An electronic nose does not simply detect the concentrations of selected VOCs in the exhaled air, but verifies the cumulative signature, reflecting the overall VOC concentration. This technology is novel but promising. http://ow.ly/IPCt30mbIBV

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.