Malocclusion and rhinitis in children: an easy-going relationship or a yet to be resolved paradox? A systematic literature revision

Objective: The relation between nasal flow and malocclusion represents a practical concern to pediatricians, otorhinolaryngologists, orthodontists, allergists and speech therapists. If naso-respiratory function may influence craniofacial growth is still debated. Chronic mouth-breathing is reported to be associated also with a characteristic pattern of dental occlusion. On the other hand, also malocclusion may reduce nasal air flows promoting nasal obstruction. Hereby, the aim of this review was to describe the relationship between rhinitis and malocclusion in children. Methods: An electronic search was conducted using online database including Pubmed, Web of Science, Google Scholar and Embase. All studies published through to January 30, 2017 investigating the prevalence of malocclusion in children and adolescents (aged 0-20 years) affected by rhinitis and the prevalence of rhinitis in children with malocclusion were included. The protocol was registered at PROSPERO - International prospective register of systematic reviews under CRD42016053619. Results: Ten studies with 2733 patients were included in the analysis. The prevalence of malocclusion in children with rhinitis was specified in four of the studies ranging from as high as 78.2% to as low as 3%. Two out of the studies reported the prevalence of rhinitis in children with malocclusion with a rate ranging from 59.2 to 76.4%. Conclusion: The results of this review underline the importance of the diagnosis and treatment of the nasal obstruction at an early age to prevent an altered facial growth, but the data currently available on this topic do not allow to establish a possible causal relationship between rhinitis and malocclusion

Respiratory infections in allergic children: the preventive role of a multicomponent nutraceutical

Allergic children with respiratory infections (RI) are a demanding challenge for the paediatrician. Antibiotic prescription represents a critical problem, mainly concerning the growing issue of resistance. To prevent RI would be therefore a goal in clinical practice. In this regard, modulation of immune system may have a critical role. e aim of the present study was to measure the number of respiratory infections and the use of antibiotics in two groups of children su ering from allergic rhinoconjunctivitis. e rst group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). e children were visited at baseline and after 1 year. e number of RI and of antibiotic courses was the primary outcomes. Children in AG reported a signi cant reduced number of RI and of antibiotic course in comparison with CG (p=0.01 and 0.002 respectively). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the number of respiratory infections and consequently the use of antibiotics in children with allergic rhinoconjunctivitis. (www.actabiomedica.it

Upper airway involvement in pediatric COVID-19

The clinical spectrum of SARS-CoV-2 infection is mixed. It ranges from asymptomatic cases, medium-intensity forms with mild to moderate symptoms, to severe ones with bilateral lung involvement and respiratory distress, which can require transfer to ICUs and intubation. In most cases, the clinical picture is characterized by a persistent fever, cough, dyspnoea, expectoration, myalgias, arthralgias, headache, gastrointestinal symptoms, nasal congestion, and pharyngodynia. The spread of COVID-19 in Europe has highlighted an atypical presentation of disease involving upper airways and, above all, dysfunction of olfactory and gustatory senses. There is ample evidence that COVID-19 is significantly less severe in children than in adults. However, due to difficulties in assessing the disorder in children, especially among very young patients, the olfaction and gustatory dysfunctions remain open issues. This article sheds light on the upper airway involvement in pediatric COVID-19 subjects

COVID-19-related anosmia: the olfactory pathway hypothesis and early intervention

Anosmia is a well-described symptom of Corona Virus Disease 2019 (COVID-19). Several respiratory viruses are able to cause post-viral olfactory dysfunction, suggesting a sensorineural damage. Since the olfactory bulb is considered an immunological organ contributing to prevent the invasion of viruses, it could have a role in host defense. The inflammatory products locally released in COVID-19, leading to a local damage and causing olfactory loss, simultaneously may interfere with the viral spread into the central nervous system. In this context, olfactory receptors could play a role as an alternative way of SARS-CoV-2 entry into cells locally, in the central nervous system, and systemically. Differences in olfactory bulb due to sex and age may contribute to clarify the different susceptibility to infection and understand the role of age in transmission and disease severity. Finally, evaluation of the degree of functional impairment (grading), central/peripheral anosmia (localization), and the temporal course (evolution) may be useful tools to counteract COVID-19

Identification of Novel 3-Hydroxy-pyran-4-One Derivatives as Potent HIV-1 Integrase Inhibitors Using in silico Structure-Based Combinatorial Library Design Approach

We describe herein the development and experimental validation of a computational protocol for optimizing a series of 3-hydroxy-pyran-4-one derivatives as HIV integrase inhibitors (HIV INIs). Starting from a previously developed micromolar inhibitors of HIV integrase (HIV IN), we performed an in-depth investigation based on an in silico structure-based combinatorial library designing approach. This method allowed us to combine a combinatorial library design and side chain hopping with Quantum Polarized Ligand Docking (QPLD) studies and Molecular Dynamics (MD) simulation. The combinatorial library design allowed the identification of the best decorations for our promising scaffold. The resulting compounds were assessed by the mentioned QPLD methodology using a homology model of full-length binary HIV IN/DNA for retrieving the best performing compounds acting as HIV INIs. Along with the prediction of physico-chemical properties, we were able to select a limited number of drug-like compounds potentially displaying potent HIV IN inhibition. From this final set, based on the synthetic accessibility, we further shortlisted three representative compounds for the synthesis. The compounds were experimentally assessed in vitro for evaluating overall HIV-1 IN inhibition, HIV-1 IN strand transfer activity inhibition, HIV-1 activity inhibition and cellular toxicity. Gratifyingly, all of them showed relevant inhibitory activity in the in vitro tests along with no toxicity. Among them HPCAR-28 represents the most promising compound as potential anti-HIV agent, showing inhibitory activity against HIV IN in the low nanomolar range, comparable to that found for Raltegravir, and relevant potency in inhibiting HIV-1 replication and HIV-1 IN strand transfer activity. In summary, our results outline HPCAR-28 as a useful optimized hit for the potential treatment of HIV-1 infection by targeting HIV IN

Updates on Children with Allergic Rhinitis and Asthma during the COVID‐19 Outbreak

Background: During the lockdown period caused by the SARS‐CoV‐2 pandemic, we monitored via online survey the trend of allergic symptoms and the therapeutic compliance in pa‐ tients followed at our center. Material and methods: In June 2020, we selected children followed at the Allergy and Immunology Service of Umberto I Hospital, aged between 6 and 16 years old, di‐ agnosed with asthma and/or rhinitis and sensitized to grass pollen or dust mite. We sent an email with 12 multiple‐choice questions investigating several areas: type of disease and sensitization, recurrence of symptoms, medication use during lockdown compared to the same period of the previous year. Results: The results of 82 questionnaires showed that 17.8% of patients suffered from asthma, 24.4% from rhinitis, and 57.8% from both. Within the group of asthmatic children, most of them presented an improvement of their symptoms. Likewise, with regard to allergic rhi‐ nitis, most of them reported better clinical conditions. Regarding treatment, we observed a global decrease in the use of on‐demand therapies (salbutamol, nasal corticosteroid, and antihistamine) for both pathologies. In addition, there was a reduction in the use of basal therapy for asthma and rhinitis from 2019 (23.3%) to 2020 (15.5%). Conclusions: Our data show a general trend of clinical improvement and a reduction in the use of on‐demand and basal therapy in allergic children during the lockdown

Cross-sectional survey on impact of paediatric COVID-19 among Italian paediatricians: report from the SIAIP rhino- sinusitis and conjunctivitis committee

Background: There is ample evidence that COVID-19 is significantly less severe in children than in adults and asthma and allergy, the most common chronic disorders in children, are not included in the top 10 comorbidities related to COVID-19 fatalities. Nevertheless, concerns about asthma and allergy are still high.. In order to evaluate the impact of paediatric COVID-19 among Italian paediatricians, we sent a 20-questions anonymous internet-based survey to 250 Italian paediatricians with particular address to allergic symptoms and those affecting the upper airways. Methods: The questionnaire was conceived and pretested in April 2020, by a working group of experts of the Italian Paediatric Society for Allergy and Immunology (SIAIP), and structured into different sections of 20 categorized and multiple choice questions. The first part included questions about epidemiological data follows by a second part assessing the way to manage a suspected COVID-19 infection and personal experiences about that. The third part concerned questions about patients’ clinical characteristics and clinical manifestations. The survey was emailed once between April and mid-May 2020. Results: A total 99 participants had participated in our survey and provided responses to our electronic questionnaire. The distribution of patients reported per month varies significantly according to the geographical area (P = 0.02). Data confirmed that in the North part of Italy the rate of patients referred is higher than in the rest of Italy. Almost all respondents (98%) reported caring for up to a maximum of 10 infected children and the last 2% more than twenty. Among these patients, according to the 75% of responders, a maximum rate of 20% were affected by allergic rhino-conjunctivitis and in particular in the North of Italy while in the Centre and in the South there was a higher incidence (P = 0.09). Almost the same applies for asthma, 83% of responders declared that up to a maximum of 20% of affected children were asthmatic, from 20 to 40% for the 13,5% of responders and from 40 to 60% for the last 3,5%. As for the allergic conjunctivitis also for asthma, we found a higher incidence in the Centre and in South than in the North (P = 0.03). Conclusions: This study is the first to provide a comprehensive review of COVID-19 knowledge and impact among paediatricians in Italy about allergic asthma and upper airway involvement. From our point of view, it provides important information clearly useful for improving a good practice

The Role of Nasal Nitric Oxide and Anterior Active Rhinomanometry in the Diagnosis of Allergic Rhinitis and Asthma: A Message for Pediatric Clinical Practice

Background: Allergic rhinitis (AR) and asthma are two common atopic diseases, often associated with a common ethiopathogenesis characterized by a Th2 inflammatory response with the release of many biomarkers, such as nitric oxide (NO). Purpose: To evaluate and compare inflammatory (nFeNO and eFeNO) and functional (mNF and FEV1) parameters in AR children with or without asthma in comparison to controls. Secondly, we aimed to identify nFeNO cut-off values and verify their reliability to predict the presence of rhinitis or asthma alone or in combination. Patients and Methods: We enrolled 160 children (6– 12 years of age) with AR and/or asthma divided into four groups: controls, AR, asthma, and AR + asthma. All children underwent the following inflammatory and functional measurements: nFeNO, eFeNO, mNF and FEV1. Results: We observed that levels of nFeNO were extremely higher in children with AR and even more in those with AR + asthma in respect to controls. Notably, all the pathological conditions, especially AR + asthma, showed significantly lower values of mNF compared to healthy children. A negative correlation linked mNF and nFeNO. Then, we found eFeNO values significantly higher in all the pathological groups compared to controls, with major values of this marker in patients affected by asthma and AR + asthma, as well as FEV1 values significantly lower in all the disease groups, especially in children with asthma and AR+ asthma. ROC curve analysis showed that nFeNO was a great predictor for rhinitis alone or with asthma, revealing an accurate cut-off of 662 ppb. Conclusion: nFeNO measurement is non-invasive, easy to perform, economic and a valuable test in case of AR alone or in association with asthma. Thus, it should be used in patients with rhinitis, together with anterior active rhinomanometry (AAR) to diagnose and estimate the degree of nasal obstruction but also in children with asthma to assess their nasal involvement and improve the therapeutic management

Hydrolyzed protein formula for allergy prevention in preterm infants: follow-up analysis of a randomized, triple-blind, placebo-controlled study

Background: Allergic diseases are a major public health burden worldwide. Evidence suggests that early nutrition might play a key role in the future development of allergies and the use of hydrolyzed protein formulas have been proposed to prevent allergic disease, mainly in term infants with risk factors. Aim: To evaluate the preventive effect of a hydrolyzed protein formula vs. an intact protein formula on allergy development in preterm infants with or without risk factors. Methods: We performed a 3-year follow-up study of a previous triple-blind, placebo-controlled randomized trial. Evidence of atopic dermatitis, asthma and IgE-mediated food allergies were evaluated according to a validated parental questionnaire (Comprehensive Early Childhood Allergy Questionnaire). Food sensitization was also investigated by skin prick test at 3 years of chronological age. Results: Of the 30 subjects in the intact protein formula group and 30 in the extensively hydrolyzed formula group, respectively 18 and 16 completed the 3-year follow-up and entered the final analysis. No group differences in the incidence of atopic dermatitis, asthma, IgE-mediated food allergies, and food sensitization were found. Conclusion: Despite the small number of cases, extensively hydrolyzed protein formula seems to be ineffective in allergic diseases prevention in preterm neonates. Further adequately powered, randomized controlled trials evaluating hydrolyzed protein formula administration to prevent allergic diseases in preterm neonates are needed

Oxidative stress and gut-derived lipopolysaccharides in children affected by paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

BACKGROUND: Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) identifies patients with acute onset of obsessive-compulsive and tic disorders. The objective of this study was to evaluate serum NOX2 levels, as well as 8-iso-prostaglandin F2α (8-iso-PGF2α) and lipopolysaccharide (LPS) of PANDAS patients. METHODS: In this study we wanted to compare serum levels of soluble NOX2-dp (sNOX-2-dp), iso-PGF2α and LPS in 60 consecutive subjects, including 30 children affected by PANDAS and 30 controls (CT) matched for age and gender. Serum zonulin was used as intestinal permeability assay. RESULTS: Compared with CT, PANDAS children had increased serum levels of sNOX-2-dp, 8-iso-PGF2α and LPS. Bivariate analysis showed that serum sNOX2-dp was significantly correlated with LPS (Rs = 0.359; p = 0.005), zonulin (Rs = 0.444; p < 0.001) and 8-iso-PGF2α (Rs = 0.704; p < 0.001). Serum LPS significantly correlated with zonulin (Rs = 0.610; p < 0.001), and 8-iso-PGF2α (Rs = 0.591; p = 0.001). Finally, a multiple linear regression analysis showed that serum 8-iso-PGF2α and zonulin were the only independent variables associated with sNOX2-dp (R2 = 68%). CONCLUSION: This study shows that children affected by PANDAS have high circulating levels of sNOX2-dp, isoprostanes and of LPS that could be involved in the process of neuroinflammation