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Changes of diurnal variation of peak expiratory flow rate (%PEF variation) and their relationship with bronchial hyperresponsiveness (BHR) to methacholine (PC20) were evaluated in 12 children with mild-to-moderate asthma and house-dust mite allergy, during successive periods of stay in a mite-free environment at high altitude (1756 m) and at their home at sea level. The children remained at the high altitude from October until the end of December; then they spent a 3-week period at home and returned to high altitude residence in January. PEF was measured daily, in the morning and in the evening, during the 3 months' stay at high altitude and them for 10 days after the return in January. PC20 was assessed in 8/12 children, once a month from October to December, and at the return in January. Mean absolute PEF values did not change significantly throughout the study. From October to December, patients showed a significant decrease of mean %PEF variation (P = 0.04), while PC20 showed an increase (P = 0.05). After the 3 weeks at home, both %PEF variation (P = 0.03) and PC20 (P = 0.05) significantly worsened. The correlation between PC20 values and mean %PEF variation in the 2 days before and after each methacholine test was r = -0.63 (P = 0.001). Our data suggest that there is a beneficial effect of a prolonged stay in a mite-free environment, on both PEF variability and BHR, also in asthmatic children with good pulmonary function. PEF variability and bronchial responsiveness to methacholine were significantly correlated also for small changes of the two variables. [ABSTRACT FROM AUTHOR]

The article presents information on the effects of allergen exposure-avoidance on inflammation in asthmatic children. Allergen exposure-avoidance is associated with changes in serums and nasal-specific IgE, allergen-induced histamine release from basophils as well as with changes in eosinophil percent count in the sputum and in serum markers of eosinophil activation. Allergen avoidance is associated with a decrease, not only in BHR but also in specific bronchial hyper-responsiveness, after a long period of allergen avoidance, asthmatic children undergoing specific bronchial challenge, develop fewer late reactions and the enhancement of BHR by late reaction to allergen is far less marked.

Fifteen healthy volunteers took part in a study to investigate the effect of food on the bioavailability of a slow-release formulation of theophylline. Serum theophylline levels were measured every two hours for ten hours after a single oral dose of 500 mg of theophylline. Serum levels were significantly higher after the dose was taken on an empty stomach; however, serum levels were significantly higher 10 hours later when the dose was taken after a standard meal. Despite these differences, eating had no overall effect on theophylline bioavailability. Two analytic methods for measuring serum levels of theophylline were compared, and it was found that fluorometry could measure lower levels and was therefore more precise than an enzyme immunoassay method, which is probably due to the complete automation and reduced interference of bilirubin and hemoglobin. [ABSTRACT FROM AUTHOR]

A girl presented in the neonatal period with hydrocephalus, bronchiectasis, and ciliary aplasia. A common defect both in respiratory tract cilia and in ventricular ependyma cilia may explain the association of the two diseases. [ABSTRACT FROM AUTHOR]

Background: Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease.Case Presentation: A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation.Conclusions: Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD. [ABSTRACT FROM AUTHOR]

In treating acute bronchiolitis in infants, the decision to use continuous positive airway pressure (CPAP) often involves infant referral from the pediatric ward to the pediatric intensive care unit (PICU). We present our experience of CPAP use in a general pediatric ward, aiming to reduce the pressure on the PICU in recent outbreaks of bronchiolitis. Clinical data of patients less than 12 months of age and admitted for bronchiolitis from 1 October 2021 to 31 March 2023 were retrospectively collected. Of 82 infants admitted for bronchiolitis, 16 (19%) were treated with nasal CPAP (nCPAP group); of the remaining 66, 21 (26%) were treated with a low-flow nasal cannula (LFNC) only, 1 (1%) was also treated a with high-flow nasal cannula (HFNC), 12 (15%) were treated with an HFNC only, and 41 (50%) were treated without oxygen support (no-nCPAP group). Overall, coinfection with RSV and SARS-CoV-2 was observed in three patients and SARS-CoV-2 infection was observed in two patients. None of them required any type of oxygen support. Only 3/16 (19%) infants in the nCPAP group were referred to the PICU due to worsening clinical conditions despite nCPAP support. In our experience of treating epidemic bronchiolitis, nCPAP can be safely managed in a general pediatric ward, thus reducing the burden of admissions to the PICU. Training and regular updating of the pediatric staff, careful monitoring of the patient, and close cooperation with the PICU were instrumental for our team.

Background: Urinary tract infection (UTI) represents one of the most common infectious diseases and a major cause of antibiotic prescription in children. To prevent recurrent infections and long-term complications, low-dose continuous antibiotic prophylaxis (CAP) has been used. However, the efficacy of CAP is controversial. The aim of this document was to develop updated guidelines on the efficacy and safety of CAP to prevent pediatric UTIs. Methods: A panel of experts on pediatric infectious diseases, pediatric nephrology, pediatric urology, and primary care was asked clinical questions concerning the role of CAP in preventing UTIs in children. Overall, 15 clinical questions were addressed, and the search strategy included accessing electronic databases and a manual search of gray literature published in the last 25 years. After data extraction and narrative synthesis of results, recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Results: The use of CAP is not recommended in children with a previous UTI, with recurrent UTIs, with vesicoureteral reflux (VUR) of any grade, with isolated hydronephrosis, and with neurogenic bladder. CAP is suggested in children with significant obstructive uropathies until surgical correction. Close surveillance based on early diagnosis of UTI episodes and prompt antibiotic therapy is proposed for conditions in which CAP is not recommended. Conclusions: Our systematic review shows that CAP plays a limited role in preventing recurrences of UTI in children and has no effect on its complications. On the other hand, the emergence of new antimicrobial resistances is a proven risk.

Metal-derived platinum complexes are widely used to treat solid tumors. However, systemic toxicity and tumor resistance to these drugs encourage further research into similarly effective compounds. Among others, organotin compounds have been shown to inhibit cell growth and induce cell death and autophagy. Nevertheless, the impact of the ligand structure and mechanisms involved in the toxicity of organotin compounds have not been clarified. In the present study, the biological activities of commercially available bis(tributyltin) oxide and tributyltin chloride, in comparison to those of specially synthesized tributyltin trifluoroacetate (TBT-OCOCF 3 ) and of cisplatin, were assessed using cells with different levels of tumorigenicity. The results show that tributyltins were more cytotoxic than cisplatin in all the tested cell lines. NMR revealed that this was not related to the interaction with DNA but to the inhibition of glucose uptake into the cells. Moreover, highly tumorigenic cells were less susceptible than nontumorigenic cells to the nonunique pattern of death induced by TBT-OCOCF 3 . Nevertheless, tumorigenic cells became sensitive when cotreated with wortmannin and TBT-OCOCF 3 , although no concomitant induction of autophagy by the compound was detected. Thus, TBT-OCOCF 3 might be the prototype of a family of potential anticancer agents.

Antibiotics account for over 10% of the overall drug expense of the National Health System in Italy in 2021. Their use in children is of particular interest on one side, because acute infections are very common in children, while they build their immunologic library of competence; on the other side, although many acute infections are expected and turn out to be of viral origin, caregivers will often ask the family doctor or primary care attending to reassure them by prescribing antibiotic treatment, although it may often be unnecessary. The inappropriate prescription of antibiotics in children may likely be a source not only of undue economic burden for the public health system but also of increasing development of antimicrobial resistance (AMR). Based on those issues, the inappropriate use of antibiotics in children should be avoided to reduce the risks of unnecessary toxicity, increase in health costs, lifelong effects, and selection of resistant organisms causing undue deaths. Antimicrobial stewardship (AMS) describes a coherent set of actions that ensure an optimal use of antimicrobials to improve patient outcomes while limiting the risk of adverse events including AMR. The aim of this paper is to spread some concept of good use of antibiotics for pediatricians or every other physician involved in the choice to prescribe, or not, antibiotics in children. Several actions could be of help in this process, including the following: (1) identify patients with high probability of bacterial infection; (2) collect samples for culture study before starting antibiotic treatment if invasive bacterial infection is suspected; (3) select the appropriate antibiotic molecule based on local resistance and narrow spectrum for the suspected pathogen(s); avoid multi-antibiotic association; prescribe correct dosage; (4) choose the best route of administration (oral vs. parenteral) and the best schedule of administration for every prescription (i.e., multiple administration for beta lactam); (5) schedule clinical and laboratory re-evaluation with the aim to consider therapeutic de-escalation; (6) stop antibiotic administration as soon as possible, avoiding the application of "antibiotic course".

Bronchiolitis causes a remarkable number of hospitalizations; its epidemiology follows that of respiratory syncytial virus (RSV), its main pathogen. The aim of this study was to evaluate the presenting features, treatment approach, and impact of medical therapy in four pediatric hospitals in Italy. Data on infants < 24 months of age hospitalized with bronchiolitis in the 2021-2022 season were collected. Between October 2021 and February 2022, 214 children were admitted. Median hospital stay was 5 days; none of the patients died. The distribution of the presenting features is largely comparable in the 33 (15.8%) RSV-negative versus the 176 (84.2%) RSV-positive children; also, no difference was observed in medical therapy provided: duration of oxygen therapy, administration of steroid, and duration of hospital stay. Systemic steroids, inhalation, or antibiotic therapy were given to 34.6%, 79.4%, and 49.1% of children respectively. Of the 214 patients with bronchiolitis, only 19 (8.8%) were admitted to ICU.   Conclusion: Our data suggest that, irrespective of treatments provided, RSV-positive and RSV-negative children had a similar clinical course. The results of our retrospective study further underline the need to improve adherence to existing guidelines on bronchiolitis treatment. What is Known: • Bronchiolitis is a common diseases with seasonal peak. The outcome is usually favorable but hospitalization and even ICU admission is not exceptional. What is New: • Children with RSV associated bronchiolitis do not have a different course and outcome. The analysis of the 2021-2022 cohort, following COVID pandemic peaking, did not show a different course and outcome. • Adherence to literature recommendation, i.e. to focus on oxygen and hydration therapy while avoiding unnecessary systemic therapy with steroid and antibiotics, should be improved., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Asthma is the most prevalent pediatric chronic disease. Bronchodilator drug response (BDR) and fractional exhaled nitric oxide (FeNO) are clinical biomarkers of asthma. Although DNA methylation (DNAm) contributes to asthma pathogenesis, the influence of DNAm on BDR and FeNO is scarcely investigated. This study aims to identify DNAm markers in whole blood associated either with BDR or FeNO in pediatric asthma. We analyzed 121 samples from children with moderate-to-severe asthma. The association of genome-wide DNAm with BDR and FeNO has been assessed using regression models, adjusting for age, sex, ancestry, and tissue heterogeneity. Cross-tissue validation was assessed in 50 nasal samples. Differentially methylated regions (DMRs) and enrichment in traits and biological pathways were assessed. A false discovery rate (FDR) < 0.1 and a genome-wide significance threshold of p < 9 × 10 -8 were used to control for false-positive results. The CpG cg12835256 ( PLA2G12A ) was genome-wide associated with FeNO in blood samples (coefficient= -0.015, p = 2.53 × 10 -9 ) and nominally associated in nasal samples (coefficient = -0.015, p = 0.045). Additionally, three CpGs were suggestively associated with BDR (FDR < 0.1). We identified 12 and four DMRs associated with FeNO and BDR (FDR < 0.05), respectively. An enrichment in allergic and inflammatory processes, smoking, and aging was observed. We reported novel associations of DNAm markers associated with BDR and FeNO enriched in asthma-related processes.

Objectives: Kawasaki disease (KD) is the most frequent cause of acquired heart disease in children in high-income countries because of coronary artery involvement. Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors., Methods: Multicenter retrospective and prospective study including 372 consecutive children (58% boys; mean age 34.3 ± 30.3 months, Caucasian 85%) was diagnosed with KD. We divided the cohort into 2 groups according to the presence of coronary anomalies (CAA) and aneurysms. We compared the groups and studied the risk factors for CAA and for aneurysms, the most severe lesions., Results: Children with CAA were 91/372 (24.46%, aneurysms 20/372, 5.37%). Children with CAA were more likely to have a longer duration of fever (p < 0.001), later day of treatment (p < 0.001), to be IVIG non-responders and late treated (p < 0.001), while age, clinical presentation, and seasonality were not different. They also had significantly higher WBC and neutrophils, lower lymphocytes, Hb and Na during the acute stage, and slower resolution of inflammation. Age, IVIG unresponsiveness, and presence of non-coronary cardiac findings were independent risk factors for CAA and for aneurysms, while neutrophils just for CAA. Age under 6 months was a risk factor for the aneurysm. Aneurysms occurred more frequently in the first quartile of the age of KD onset (under 14 months)., Conclusion: Very young children with non-coronary cardiac findings are at increased risk for a more severe form of KD with aneurysms. These children could benefit from adjunctive therapy beside IVIG, especially if they have higher markers of inflammation, particularly neutrophils. Key points • Risk factors for coronary lesions can vary in consideration of different genetic background and environmental factors. • Risk factors for coronary involvement have been extensively studied in the Asian population, and others have been validated in cohorts with mixed ethnicities. • In our predominantly Caucasian population, non-coronary cardiac findings, age younger than 6 months, and IVIG unresponsiveness are independent risk factors for a more severe form of KD with aneurysms.

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p < 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p < 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions.

In most children, coronavirus disease 2019 (COVID-19) is a mild or moderate disease. Moreover, in a relevant number of cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains totally asymptomatic. All these findings seem to suggest that otherwise healthy children with suspected COVID-19 might be managed in the community in most cases, thus avoiding hospital admission and closely related medical, social and economic problems, including overwhelming hospitals. Unfortunately, home management of children with suspected COVID-19 rarely occurs, and many children with suspected or laboratory-confirmed SARS-CoV-2 infection are frequently hospitalized irrespective of the severity of disease. To evaluate the role of community health houses (CHHs) in the management of children with COVID-19, 1,009 children with suspected SARS-CoV-2 infection were studied in Emilia-Romagna Region, Italy. Among them, 194 (19.2%) resulted positive for SARS-CoV-2. The majority (583, 58%) were tested at home by CHHs, while 426 (42%) were brought to the hospital for testing. The patients who were managed in the hospital had a significantly lower median age than those who were managed at home (2 vs. 12 years, p < 0.001). Exposure to SARS-CoV-2 cases within the family was significantly more frequent among those who were managed at home (82 vs. 46%, p < 0.05). The clinical findings were similar between the children who were managed at home and those who were managed in the hospital. Only one of the children managed at home (0.7%) required hospitalization; in comparison, 26 (48%) of those whose swab samples were taken at the hospital were hospitalized. Our research shows for the first time the importance of CHHs in the management of COVID-19 in children; because of the high frequency of mild to moderate cases, management by CHHs can reduce the care load in hospitals, providing enormous advantages on the familial, medical, social, and economic levels. These findings could be useful for suggesting a territorial rather than hospital-based strategy in pediatrics in the case of a new wave of the epidemic., (Copyright © 2020 Vergine, Fantini, Marchetti, Stella, Valletta, Biasucci, Lanari, Dodi, Bigi, Magista, Vaienti, Cella, Affanni, Re, Sambri, Esposito and the Regione Emilia-Romagna COVID-19 Pediatric Working Group (RERCOPed).)

Objective: To evaluate the effect of the COVID-19 epidemic on paediatric emergency department (ED) attendance in a region of Northern Italy., Methods: A survey was proposed to six out of nine paediatric EDs in the Emilia Romagna region to evaluate attendance data, distribution by age and gender, triage code score, outcome of clinical course, number of hospitalisations and the distribution of patients by disease. Data were collected during March 2020 and compared with that of March 2019., Results: A drop in paediatric ED attendance of more than 83.8% was observed, with a higher percentage of infants and severe triage scores. The proportion of patients hospitalised was significantly higher in 2020 than in 2019 (p value: <0.001). The effect size for the comparison of proportions of hospitalised patients was 0.379. Looking at the distribution of attendance by type of disease, a significantly different distribution was highlighted (p value: <0.00001, Cramer's V); there was a greater proportion of patients presenting to paediatric EDs with poisonings (effect size=0.07), psychiatric pathologies (effect size=0.110), head injuries (effect size=0.167) and fever (effect size=0.212)., Conclusions: Our survey suggests that in the first month of the COVID-19 epidemic in Italy, there has been an increase in delayed attendance and provision of care of potentially severe diseases in paediatric EDs. Hospital and community paediatricians should be aware of this phenomenon and adopt appropriate strategies to prevent this danger, as it may affect children more seriously than COVID-19 itself., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)