BACKGROUND:Dupilumab is a new biological drug approved for the treatment of type 2 inflammatory diseases, such as asthma. Dupilumab is a fully humanized monoclonal antibody that acts against both interleukin-4 and interleukin-13 receptors. This study evaluated the time--dependent effect of dupilumab on asthma exacerbations and quality of life in adolescents with uncontrolled severe asthma.MATERIALS AND METHODS:Five adolescents suffering from uncontrolled severe asthma and treated with dupilumab were recruited. All subjects were evaluated for 4, 12, and 24 weeks after the first dose of dupilumab. Outcome measures included lung function, fractional exhaled nitric oxide, asthma control and quality of life assessed by validated questionnaires (Asthma Control Test and Asthma Control Questionnaire).RESULTS:The quality of life improved quickly after 4 weeks of treatment and 80% of adolescents halved the dose of inhaled corticosteroids necessary to control asthma symptoms. These results were still maintained for 24 weeks after start of the therapy. None of the patients had any asthma exacerbation during the study period.CONCLUSION:Results of this study demonstrated that dupilumab was quickly effective to reduce asthma exacerbation and ameliorate quality of life in severe asthmatic adolescents.

OBJECTIVE:Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens.DESIGN:In-vitro model of adipogenesis.METHODS:We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARɣ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment.RESULTS:Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF.CONCLUSION:Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.

The prevalence of allergic rhinitis is rising, and it is impacting children’s growth and quality of life. To uncover unconventional treatment modalities, research was carried out to clarify the significance of novel components in the pathophysiology of allergic rhinitis. One of these elements was gut microbiota, which plays a crucial role in the development and evolution of allergic disorders. Specifically, dysbiosis, defined as impaired microbiota composition, characterizes allergic disorders. In light of this concept, probiotics (beneficial bacteria) may restore gut dysbiosis, rebalance the immune response, and indirectly influence the clinical course of allergic diseases. In this article, we discussed the role of the gut–lung axis in children and reported on new findings. We also reviewed the most relevant studies about probiotics in patients with allergic rhinitis.

Background: The concept of atopic march was introduced about 15 years ago to define the temporal progression of different allergic conditions, from atopic dermatitis and food allergies in earliest childhood to the development of asthma and allergic rhinitis in older children. Case Presentation: The authors describe a case report of a young girl who went through the stages of atopic march. The child first showed atopic dermatitis and food allergy in infancy, and, after-wards, she manifested allergic rhinitis and asthma in childhood. Discussion: This timeline reflects the atopic march's spatial evolution, beginning with the skin and gastrointestinal tract and progressing to the upper and lower airways. Conclusion: In accord with the most recent evidence, rather than being defined in terms of chrono-logical progression, atopic diseases should be investigated as a spectrum of atopic disorders that might take various developmental paths. According to this theory, the use of Component Resolved Diagnosis in atopic children can be beneficial for highlighting and predicting the atopic profile du-ring the earliest years of life before symptoms arise, helping to stratify the clinical risk and preven-ting the onset of the atopic march and severe responses.

Background: Long COVID affects 8 to 10 % of children. Currently, the COVID-19 fo-llow-up protocols in children include chest auscultation, collection of growth parameters, including weight, height and body mass index, execution of the six-minute walking test, basal spirometry, and afterwards, bronchodilation test and lung ultrasound. Case Presentation: In this paper, the authors describe a case series of long COVID followed up for 9 months at the Department of Pediatrics of the University Luigi Vanvitelli. The review of the lite-rature was performed on PubMed using the keywords COVID-19, follow-up, children, and lung ul-trasound. The aim of this article was to highlight the need to create custom follow-up programs for long Covid in children through the description of a case followed up at our Pediatric Department and a review of the current literature Discussion: The reversal of pathological lung ultrasound signs occurred in six or nine months des-pite the early improvement of respiratory symptoms and pulmonary function. There are limited stu-dies on the ultrasonography follow-up of kids with COVID-19 in the literature, and there are still no follow-up COVID-19 guidelines for paediatric population. Conclusion: Pathological lung ultrasound in children recovered from COVID-19, may take time to resolve; therefore, evaluating patients with lung ultrasound in the following months could be a ra-diation-saving approach useful for children who have fully recovered and have no warning signs.

Background: Children with mild or asymptomatic COVID-19 represent the majority of paediatric cases. Hospitalisation and critical care are required only in a small proportion of SARS-CoV-2 positive children who present severe symptoms, like interstitial lung disease. A quarter of children experience persistent symptoms some months later after being hospitalised, and they need to be properly followed up. Case Presentation: The authors describe a case report of long-COVID in a 5 years old child, who was previously hospitalized for a severe case of COVID-19 (an interstitial lung disease requiring oxygen), followed up in 3 months in our Pediatric Department. Results: After 3 months post-hospitalisation, despite his clinic history, the clinical examination was normal, during the six-minute walking test he did not desaturate, the spirometry was in the norm and the lung ultrasound did not show any pathological findings. Conclusion: We reported a case of a child previously hospitalised for interstitial lung disease with long-COVID, who has been followed up 3 months after the hospitalisation by our Department of Pediatrics of the University ‘Luigi Vanvitelli’. Based on our experience, even in children who have experienced a severe form of COVID-19 disease and who continue to exhibit symptoms, a proper follow-up can demonstrate a full recovery in a few months.

Background. Food allergy is common in the Mediterranean, especially concerning lipid transfer proteins (LTPs) allergy. LTPs are widespread plant food allergens in fruits, vegetables, nuts, pollen, and latex. Also, LTPs are prevalent food allergens in the Mediterranean area. They can sensitize via the gastrointestinal tract and cause a wide range of conditions: from mild reactions, such as oral allergy syndrome, to severe reactions, such as anaphylaxis. LTP allergy in the adult population is well described in the literature, concerning both the prevalence and clinical characteristics. However, there is poor knowledge about its prevalence and clinical manifestation in children living in the Mediterranean. Materials and Methods. This study, including 800 children aged from 1 to 18 years, investigated the prevalence of 8 different molecules of nonspecific LTP over time in an Italian pediatric population visited over the last 11 years. Results. About 52% of the test population was sensitized to at least one LTP molecule. For all the LTPs analyzed, sensitization increased over time. In particular, using the years 2010 through 2020 as a comparison, the major increases were observed for the LTPs of the English walnut Jug r 3, the peanut Ara h 9, and the plane tree Pla a 3 (about 50%); the increase of the LTP of the Hazelnut Cor a 8 was about 36%, and that of the LTP of the artemisia Art v 3 was approximately 30%. Conclusions. The latest evidence in the literature indicates an increase in food allergy prevalence in the general population, including children. Therefore, the present survey represents an interesting perspective about the pediatric population of the Mediterranean area, exploring the trend of LTP allergy.

OBJECTIVE Seasonal allergic rhinitis (SAR) is a common disease of childhood and is characterized by type 2 inflammation, bothersome symptoms, and impaired quality of life (QoL). Intranasal corticosteroids are effective medications in managing SAR. In addition, mometasone furoate nasal spray (MFNS) is a well-known therapeutic option. However, the literature provided no data about the effects of MFNS in European children with SAR. Thus, this study addressed this unmet requirement. METHODS MFNS was compared to isotonic saline. Both treatments were prescribed: one drop of spray per nostril, twice a day, for 3 weeks. Nasal cytology, total symptom score (TSS), visual analogic scale concerning the parental perception of severity of symptoms, and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) were assessed at baseline, after 7 and 21 days, and 1 month after discontinuation. RESULTS MFNS significantly reduced eosinophil and mast cell counts, improved QoL, and relieved symptoms, as assessed by doctors and perceived by parents. These effects persisted over time, even after discontinuation. Both treatments were safe and well-tolerated. CONCLUSIONS The present study documented that a 3-week MFNS treatment was able to significantly dampen type 2 inflammation, improve QoL, and reduce severity of symptoms in Italian children with SAR, and was safe.

The prevalence of non-allergic asthma in childhood is low, peaking in late adulthood. It is triggered by factors other than allergens, like cold and dry air, respiratory infections, hormonal changes, smoke and air pollution. In the literature, there are few studies that describe non-allergic asthma in pediatric age. Even though it is a less common disorder in kids, it is crucial to identify the causes in order to keep asthma under control, particularly in patients not responding to conventional treatments. In this review, we discuss non-IgE-mediated forms of asthma, collecting the latest research on etiopathogenesis and treatment.

ABSTRACT Integrase strand transfer inhibitors (INSTI) are a recently available class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report more significant weight gain among persons receiving INSTI-based ART regimens for initial therapy compared to protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens. In our experimental setting, we used the in vitro model of adipogenesis of 3T3-L1 cells to investigate the effects of the NRTIs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with four integrase strand transfer inhibitors: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG) and bictegravir (BIC) on adipose differentiation. In addition, protein expression levels of PPARɣ and C/EBPα, and the intracellular lipid accumulation by Red Oil staining, were used to monitor adipocyte differentiation. Compared to control, RAL, ELV, DTG, and BIC were all able to increase adipogenesis, being in this, RAL and ELV more efficient. On the other hand, TAF and TDF inhibited adipogenesis. Moreover, when used in combination with the other INSTI molecules, TAF and TDF were able to reduce the adipogenic effects of all four drugs. This ability was more evident when TAF was used in combination with DTG and BIC. All these data suggest that TAF and TDF have an inhibitory effect on adipogenesis in vitro and that they could also effectively counteract the increased adipogenesis caused by the treatment with INSTIs. Finally, to evaluate if the 3T3-L1 cell could express fibroblast-like features following INSTIs treatment, we evaluated the immunohistochemical expression of ER-TR7, a well-known fibroblastic marker. This last assay showed that treatment with INSTIs increased the expression of ER-TR7 compared to control and to cells treated with TAF o TDF. In conclusion, our experimental data support the evidence that in vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used, while TAF and TDF have an antagonistic role on this phenomenon.

Exercise-induced bronchoconstriction (EIB) is a transient airflow obstruction, typically 5–15 min after physical activity. The pathophysiology of EIB is related to the thermal and osmotic changes of the bronchial mucosa, which cause the release of mediators and the development of bronchoconstriction in the airways. EIB in children often causes an important limitation to physical activities and sports. However, by taking appropriate precautions and through adequate pharmacological control of the condition, routine exercise is extremely safe in children. This review aims to raise awareness of EIB by proposing an update, based on the latest studies, on pathological mechanisms, diagnosis, and therapeutic approaches in children.

A novel coronavirus (SARS‐CoV‐2) is responsible for a severe acute respiratory syndrome called coronavirus disease 2019 (COVID‐19). It is originated in Wuhan, China, in December 2019. Due to its extreme transmissibility with droplets and human contacts, in a few months, it has become a pandemic. Nowadays, no effective therapy is available, and the scientific community is moving to find a therapeutic choice to fight this silent enemy. Studies are ongoing on several therapeutic options, including antiviral agents, immunomodulant drugs, and immunotherapy. Due to viral features, including the ability to start an inflammatory response that seems to be the fulcrum of COVID‐19 pathogenic action, immunotherapy could represent a promising alternative waiting for the vaccine. High‐dose intravenous immunoglobulin (IVIg), already used in other infectious diseases, could represent an effective help. The aim of this narrative review is to reassemble the clinical experiences on the use of IVIg in COVID‐19 and the rationale of its use.

The placenta, a temporary organ that forms during pregnancy, is the largest fetal organ and the first to develop. It is recognized as an organ that plays a vital role as a metabolic and physical barrier in the fetoplacental unit; throughout fetal development it acts as the lungs, gut, kidneys, and liver of the fetus. When its two components, the fetal and the maternal one, successfully interact, pregnancy proceeds healthily. However, in some cases there may be pregnancy disorders, such as preeclampsia (PE) and gestational diabetes mellitus (GDM), which can lead to a different outcome for the mother and the newborn. In recent years, several studies have been conducted to try to understand how the expression of factors involved in the development of the placenta varies under pathological conditions compared with normal conditions. The purpose of this review is to summarize recent discoveries in this field.

There are many factors contributing to the development of gastrointestinal diseases, grouped into genetic, environmental, and lifestyle factors. In recent years attention has fallen on pathogens; in particular, Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli (E. coli) and Helicobacter pylori have been studied. Several points remain to be clarified, and above all, as regards the adherent‐invasive E. coli strains of E. coli, one wonders if they are a cause or a consequence of the disease. In this review, we have tried to clarify some points by examining a series of recent publications regarding the involvement of the bacterium in the pathology, even if other studies are necessary.

There are many factors contributing to the development of gastrointestinal diseases, grouped into genetic, environmental, and lifestyle factors. In recent years attention has fallen on pathogens; in particular, Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli (E. coli) and Helicobacter pylori have been studied. Several points remain to be clarified, and above all, as regards the adherent-invasive E. coli strains of E. coli, one wonders if they are a cause or a consequence of the disease. In this review, we have tried to clarify some points by examining a series of recent publications regarding the involvement of the bacterium in the pathology, even if other studies are necessary.

Previous studies have demonstrated that different curcumin extracts are able to influence cell metabolic activity vitality in human papillary thyroid carcinoma TPC-1 cells. We continued the study using the most effective extract and adding other nutraceuticals such as piperine and vitamin E, in order to define the possible role of these in modulating the genetic expression of cell markers and to understand the effectiveness in modulating the regression of cancer phenotype. Cells were treated with one extract of curcumin (Naturex® Ultimate Botanical Benefits), with Piperine (Piper Longum, A.C.E.F.) and Vitamin E (Dry Vitamin E-Acetate 50% DC, BASF) alone and in combination, dissolved in the culture medium, for 48 h. Treatment with the different nutraceuticals is able to influence cell cycle regulators (cyclin D1, β-catenin, p21, p53) and activators or inhibitors of apoptosis (BAX, pro-caspase3, Bcl-2). They are able to influence cell cycle distribution and metabolic activity vitality. The inhibitory effect of curcumin, piperine and vitamin E on cell proliferation involves different markers, and in particular inhibits β-catenin, cyclinD1 and p53, making them candidates for a possible use in alternative therapies although further studies are needed.

A nutraceutical product can be defined as a substance that has a physiological benefit or provides protection against chronic diseases. The term nutraceutical is a hybrid term derived from the union of “nutrition” and “pharmaceutical”. The list of studied nutraceuticals is constantly changing and reflects ongoing market developments, research and consumer interest. Spices, in addition to giving color and taste to foods, are also important nutraceutical. Spices have been an integral part of human diets and commerce for millennia but recently, the recognition of the link between health and nutrition has strengthened their importance in the food sector and sparked the interest of researchers who increasingly engage in trying to determine the mechanisms of action of spices and the countless beneficial properties attributed to them. Among the many existing spices, turmeric is one of the most studied for its antioxidant, anti-inflammatory, antibacterial and anticancer properties. The purpose of this review is to briefly summarize the fundamental characteristics of turmeric and give an overview of the use of this spice in several diseases.

After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated fol- lowing several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis. Drawing from these background we decided to evalu- ate the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while the expression of p53 was reduced. Treatment with Maraviroc was also able to block the accumulation of fibrillar collagens and extracellular matrix proteins (ECM), as demonstrated by the decrease of specific markers as Collagen type I, α-SMA and TGF-β1. In addition we observed a down regulation of both met- alloproteins (MMP-2, MMP-9), used for the degradation of the extracellular matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound that may modulate the dynamic of liver fibrosis could be crucial in all chronic liver diseases. Maraviroc could play an important role because, in addition to its own anti-HIV activity, it could reduce the release of pro-inflam- matory citokynes implicated in liver fibrogenesis.