Addition of a nutraceutical to montelukast or inhaled steroid in the treatment of wheezing during COVID-19 pandemic: a multicenter, open-label, randomized controlled trial.

Background and aim Recurrent wheezing is often triggered by viral respiratory infections. The aims of our study were: i) to evaluate whether the addition of a nutraceutical (Leucodif®), could improve the efficacy of montelukast or inhaled steroids (ICS) compared to the single treatment; ii) to verify whether a treatment is more effective than another. Our study was biased by the COVID-19 pandemic, which resulted in a lockdown of almost two months in Italy. Methods The multicenter, open-label study enrolled 84 children aged 2-6 years diagnosed with recurrent wheezing and randomized them into four treatment arms for three months: ICS treatment; ii) montelukast; iii) montelukast + Leucodif; iv) ICS + Leucodif. Children were assessed at baseline and after one, two, and three months of treatment using the TRACK score for both the caregiver and the physician. Results Out of the 84 patients, 18 patients received ICS therapy, 22 patients ICS + Leucodif, 24 patients montelukast, and 20 patients montelukast + Leucodif. All four treatments resulted in a significant reduction in symptoms with no differences among the various groups. Conclusions Our study demonstrates that montelukast therapy appears to be equally effective as ICS therapy and that the addition of the nutraceutical Leucodif does not appear to improve the treatment outcome. However, in our opinion our study was strongly influenced and biased by the lockdown due to the COVID-19 pandemic, which inherently resulted in reduced exposure to the viruses that commonly cause respiratory infections in children.

IL-17 serum level in patients with chronic mucocutaneous candidiasis disease.

BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is defined by recurrent or persistent superficial infections involving nails, skin, and/or oral and genital mucosae. IL-17 promotes the recruitment, chemotaxis, and expansion of neutrophils and acts directly on keratinocytes and epithelial cells, driving the production of antimicrobial peptides, essential for the immune response against Candida. AIM: To evaluate the serum level of IL-17 in a family affected by CMC restricted to the nails of the hands and feet. METHODS: Serum IL-17 was assayed on 16 patients (aged 21 ± 3.1 years) suffering from persistent onychomycosis caused by Candida and 18 healthy controls (aged 19 ± 2.7 years). Comparisons between groups were performed by Student's unpaired t-test. The level of significance was set at 0.05. RESULTS: The mean serum IL-17 level in patients was 74 ± 1.42 pg/ml, whereas the control group showed a significantly lower level of 25.6 ± 6.7 pg/ml (p < 0.05). CONCLUSIONS: We showed a potential defect in the IL-17 signaling pathway in a family affected by CMC restricted to the nails of the hands and feet. Further research is needed to clarify the immunological mechanisms and the genetic etiology at the basis of the unusual clinical presentation in this family.

Respiratory syncytial virus seropositivity at birth is associated with adverse neonatal respiratory outcomes.

BACKGROUND: More than 60 years since the discovery of the respiratory syncytial virus (RSV), the effects of prenatal exposure to this virus remain largely unknown. In this investigation, we sought to find evidence of RSV seroconversion in cord blood and explore its clinical implications for the newborn. METHODS: Offspring from 22 pregnant women with a history of viral respiratory infection during the third trimester of pregnancy (respiratory viral illness [RVI] group) and 40 controls were enrolled in this study between 1 September 2016 and 31 March 2019. Cord blood sera were tested for anti-RSV antibodies by indirect fluorescent antibody assay. RSV seropositivity was defined as the presence of anti-RSV immunoglobulin M (IgM) or immunoglobulin A (IgA), in addition to IgG in cord blood serum at ≥1:20 dilution. RESULTS: Anti-RSV IgG was present in all cord blood serum samples from infants born to RVI mothers (95% confidence interval [CI] = 82%-100%), with 16 samples also having elevated titers for either anti-RSV IgA or IgM (73%; 95% CI = 52%-87%). No controls had evidence of anti-RSV antibodies. Eight (50%) seropositive newborns developed at least one respiratory tract finding, including respiratory distress syndrome (N = 8), respiratory failure (N = 3), and pneumonia (N = 1). RSV seropositive newborns also required more days on oxygen, had leukocytosis and elevated C-reactive protein (P = .025, P = .047, and P < .001, respectively). CONCLUSION: This study provides evidence of acute seropositivity against RSV in cord blood of newborns delivered from mothers with a history of upper respiratory tract illness in the third trimester. Cord blood seropositivity for anti-RSV IgA or IgM was associated with adverse clinical and laboratory outcomes in newborns.

Bacteriotherapy with Streptococcus salivarius 24SMB and Streptococcus oralis 89a nasal spray for treatment of upper respiratory tract infections in children: a pilot study on short-term efficacy.

BACKGROUND: Recurrent respiratory infections (RRIs) are defined by the presence of at least one of the following criteria: (i) > 6 annual respiratory infections (RIs); (ii) > 1 monthly RIs involving the upper airways from September to April; (iii) > 3 annual RIs involving the lower airways represent a very common health problem in the first years of life. We conducted a multi-centre, prospective, single-open study to assess the efficacy and the safety of Streptococcus salivarius 24SMBc and Streptococcus oralis 89a in the prevention of upper respiratory tract infections (URTIs) in children. METHODS: Ninety-one children (M:F = 47:44, mean age 7.4 ± 2.3 years) with RRIs were enrolled in the study between September and November 2018. At baseline, children received Streptococcus salivarius 24SMBc and Streptococcus oralis 89a as 2 puffs for nostril twice/day for 7 days/months. The treatment lasted for 3 consecutive months. Efficacy was expressed in terms of absence or presence of fever, cough, bronchospasm, rhinorrhea and otalgia, at 1 month (T1), and 3 (T3) months. Safety and tolerability of the probiotic were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment. RESULTS: Children treated with Streptococcus salivarius 24SMBc and Streptococcus oralis 89a showed a significant decrease of symptoms including episodes of fever, cough, bronchospasm, rhinorrhea, and otalgia (p < 0.001) compared to baseline. The treatment significantly reduced the number of episodes of fever, cough, bronchospasm, rhinorrhea, otalgia, and cough also in patients with positive familial history for atopy and in atopic children (p < 0.05). No significant differences in symptoms among children with negative familial history for atopy and children with positive familial history for atopy subgroups, not atopic and atopic children subgroups, and smoke-exposed and not smoke-exposed subgroups were observed (p > 0.05). Conducting a subgroup analysis according to the age, it has been reported that children aged 1-3 years old showed an improvement in all symptoms, however, they become statistically significant only at the end of the 3 months of treatment (p < 0.05). Conversely, in children aged 3-6 and 6-12 years old, the therapeutic efficacy was progressive and significant already from the first month of therapy (p < 0.05). None of the children were withdrawn from the study because of AEs, although 9 children experienced burning nose leading to interruption of therapy. CONCLUSIONS: Our findings suggest that Streptococcus salivarius 24SMBc and Streptococcus oralis 89a treatment is safe and seems to be effective on short-term in the treatment of RRIs. Studies involving a longer observation period are necessary to establish the real efficacy of the product for the treatment of pediatric patients affected by RRIs.

Cetirizine use in childhood: an update of a friendly 30-year drug.

Cetirizine is a second-generation antihistamine, derived from the metabolism of hydroxyzine, highly specific for the H1 receptors, and with marked antiallergic properties. Although its history began more than 30 years ago, it remains one of the most used drugs in children with a leading role in the medical care of children with allergic diseases. Cetirizine use is licensed for paediatric patients for the treatment of allergic rhinitis, and chronic spontaneous urticaria, in Europe in children older than 2 years old and in the USA in children older than 6 months old. This review provides a practical update on the use of cetirizine in children and adolescents.

Recurrent respiratory infections between immunity and atopy.

Recurrent respiratory infections (RRIs) are frequent in children and are characterized by more than 6 airway infections in 1 year or more than 1 upper airway infection per month in the period between September and April or more than 3 lower airway infections in 1 year. Often pediatric RRIs are related to predisposing factors, such as reduced airway size, poor tussive reflex, and immaturity of the immune system. RRIs due to immature immune system are a transient condition, with spontaneous resolution in the school age. However, some RRIs are expression of more complex diseases. Red flags are the onset of symptoms in the first year of life, the involvement of other systems, unusual pathogens, slowing of growth, severe infections of the lower airways, and recurrence of the infection site. To help the pediatrician in the RRI differential diagnosis, we have created a roadmap based on scientific literature data and clinical practice that identifies 6 macro areas: immunodeficiencies, simple minimal genetic immunodeficiency, atopy, obesity, nutritional deficiencies, autoinflammatory diseases, and complex diseases.

Antihistamines: ABC for the pediatricians.

Antihistamines are currently one of the most commonly administered drugs in children. They are used to treat symptoms that depend on histamine release, namely allergic diseases, such as rhinitis, asthma, urticaria, and anaphylaxis. It is possible to distinguish first- and second-generation antihistamines. Pharmacological effects and therapeutic indications are similar, but second-generation antihistamines have fewer adverse effects because they are more selective for peripheral H1 receptors. Although they have been on the market for several years, there are still many adverse effects linked to the antihistamine safety profile, especially in the first years of life. Thus, many antihistamines are prescribed off-label, especially in children younger than 2 years of age, which is the age-group where most of the data on drug safety are lacking and many antihistamines are not recommended. This article aims to provide a practical update on the use of antihistamines in children.

Cetirizine modifies quality of life and symptoms in children with seasonal allergic rhinitis: a pilot study.

Background and aim Seasonal allergic rhinitis (SAR) is a common disease in childhood that is characterized by bothersome symptoms and impaired quality of life (QoL). As histamine is the pivotal pathogenic mediator in SAR, antihistamines are the first-line option in the treatment. Cetirizine is a well-known effective antihistamine. This real-life pilot study aimed to investigate the effectiveness of a 4-week continuous cetirizine treatment in a group of Italian children with SAR. Methods Total symptom score (TSS) and the Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) were assessed at baseline and the end of the treatment. Results Cetirizine significantly improved QoL (in all domains) and symptom severity (p<0.001 for both). Conclusions The present preliminary study showed that a 4-week cetirizine treatment was able to improve QoL significantly. Cetirizine treatment also significantly reduced symptom severity in Italian children with SAR and was safe.

Focus on the cetirizine use in clinical practice: a reappraisal 30 years later.

Antihistamines are currently one of the most commonly administered categories of drugs. They are used to treat symptoms that are secondary to histamine release, which is typical of certain allergic conditions, including rhinitis, conjunctivitis, asthma, urticaria, and anaphylaxis. Cetirizine belongs to the second-generation family, so, it is very selective for peripheral H1 receptors, is potent and quickly relieves symptoms, exerts additional anti-allergic/anti-inflammatory effects, and is usually well-tolerated. It has been marketed 30 years ago. In these years, a remarkable body of evidence has been built. The current review provides a practical update on the use of cetirizine in clinical practice.

Novel therapeutic targets for allergic airway disease in children.

The aim of precision medicine is setting up targeted therapies for selected patients that would ideally have high effectiveness and few side effects. This is made possible by targeted therapy drugs that selectively act on a specific pathway. Precision medicine is spreading to many medical specialties, and there is increasing interest in the context of allergic airway diseases, such as allergic rhinitis, chronic rhinosinusitis, and asthma. This review is an update of new targets in the treatment of childhood allergic upper airway diseases and asthma, including the most recent biologic drugs that have already been licensed or are in the pipeline to be tested with children.

Targeted Therapy for Severe Asthma in Children and Adolescents: Current and Future Perspectives.

Severe asthma in children remains a significant issue. It places a heavy burden on affected individuals and society as a whole in terms of high morbidity, mortality, consumption of healthcare resources, and side effects from high-dose corticosteroid therapy. New, targeted biologic therapies for asthma have emerged as effective add-on options, complementing our expanding understanding of asthma phenotypes/endotypes and the underlying immunopathology of the disease spectrum. They include omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab. Omalizumab represents the first available therapeutic option for allergic asthma in patients as young as 6 years of age. Its efficacy and safety have been established by several randomized controlled trials specifically conducted in pediatric patients, leading to its final registration > 10 years ago. Three new interleukin (IL)-5 targeted agents, mepolizumab, reslizumab, and benralizumab, have been approved for the treatment of severe eosinophilic asthma starting from 6 years of age, and varying by country. More recently, dupilumab, a targeted agent against the IL-4 receptor α-chain, was approved for patients ≥12 years of age in the United States after pivotal trials were completed. The late-stage clinical testing of these targeted agents has mostly involved patients aged 12 years and up, and the application of those data to younger children can be inappropriate and carry risk. The efficacy and safety of these newer biologics in children should be supported by adequate research within this targeted age group. In this review, we will present the most recent evidence on these five biological therapies for severe asthma and will discuss dosage and administration, their efficacy, safety, and future prospects, with a focus on the pediatric age group, defined as age < 18 years.

High mobility group box 1 and markers of oxidative stress in human cord blood.

BACKGROUND: Parturition induces considerable oxidative stress and many inflammatory mediators, such as high mobility group box 1 (HMGB1), are involved from the beginning of the pregnancy to birth. The aim of the present study was to evaluate serum cord blood concentration of diacron-reactive oxygen metabolites (d-ROM), biological antioxidant potential (BAP), and HMGB1 to investigate the perinatal oxidative status of neonates and correlation with mode of delivery, as well as the influence of labor. METHODS: The subjects consisted of 214 neonates delivered at University Hospital "G. Martino", Messina, in a 6 months period. Venous blood samples were collected from the umbilical cord after cord separation. RESULTS: Umbilical cord venous blood HMGB1 was significantly higher in the spontaneous vaginal delivery (SVD) group than in the elective or emergency cesarean section (CS) group (P = 0.018). Regarding labor, there was no significant difference in HMGB1 concentration in umbilical vein blood between the spontaneous and induced labor groups (P = 0.250). Furthermore, d-ROM was significantly different between the SVD group and the elective or emergency CS group (P = 0.044). BAP concentration, however, was not significantly different, not even with regard to mode of labor. CONCLUSION: Oxidation is higher in newborns delivered by SVD than in those delivered by CS, and HMGB1 may be involved in the mechanisms of birth, and responsible for decidual modifications that lead to birth.

Antihistamines: Recommended Dosage - Divergence between Clinical Practice and Guideline Recommendations.

The updosing of second-generation antihistamines for chronic urticaria is based on inconsistent findings. Herein, we report data on the treatment of children with chronic spontaneous urticaria (CSU) unresponsive to single doses of second-generation H(1)-antihistamines in whom an increase in antihistamine was performed without improvement and with a high prevalence of adverse events. Thus, it appears that well-controlled, well-designed clinical trials are needed to clarify which nonsedating antihistamines should be used, in what dose, and for how long in patients not responding to the standard treatment, despite the improvement in health care that guidelines help to incorporate. Furthermore, a critical use of such guidelines should be done to improve the knowledge in CSU, especially in the pediatric population.

Omalizumab treatment in a 12 year-old girl with chronic spontaneous urticaria.

Background: Omalizumab is a recombinant humanized IgG monoclonal antibody, which binds the Fc region of free IgE prevent its binding to its high-affinity receptor (FcεR1) on mast cells and basophils. Omalizumab was approved as add-on therapy for moderate-to-severe persistent allergic asthma and for patients with chronic spontaneous urticaria resistant to antihistamine treatment. Patient and results: This article reports effective and safe treatment of a 12 years old girl with add-on omalizumab. On an initial dose of omalizumab of 300 mg once every 4 weeks, the patient experienced resolution of symptoms to a degree that exceeded the effect of previous treatments. Conclusion: Convincing evidence in support of the efficacy and safety of Omalizumab in the treatment of CSU in adolescent has accumulated over the past few years.

Minor pulmonary malformations in a child.

Can you diagnose this child with minor pulmonary malformations and recurrent pulmonary symptoms? http://ow.ly/6zQB30jHZAP.

Induction of high-mobility group Box-1 in vitro and in vivo by respiratory syncytial virus.

BackgroundDespite decades that have passed since its discovery, accurate biomarkers of respiratory syncytial virus (RSV) disease activity and effective therapeutic strategies are still lacking. The high-mobility group box type 1 (HMGB1) protein has been proposed as a possible link between RSV and immune system, but only limited information is currently available to support this hypothesis.MethodsExpression of HMGB1 gene and protein was analyzed by quantitative PCR, enzyme-linked immunosorbent assay (ELISA), western blot, immunocytochemistry, and confocal microscopy in immortalized and primary human bronchial epithelial cells, as well as in rat pup lungs. The role of HMGB1 in RSV infection was explored using glycyrrhizin, a selective HMGB1 inhibitor.ResultsRSV infection strongly induced HMGB1 expression both in vitro and in vivo. Glycyrrhizin dose-dependently inhibited HMGB1 upregulation in both RSV-infected immortalized and primary human bronchial epithelial cells, and this effect was associated with significant reduction of viral replication.ConclusionOur data suggest that HMGB1 expression increases during RSV replication. This seems to have a critical pathogenic role as its selective inhibition virtually modified the infection. These observations provide further insight into the pathophysiology of RSV infection and uncover a potential biomarker and therapeutic target for the most common respiratory infection of infancy.

Illegal immigration: the puzzling role of several risk factors for rhabdomyolysis.

A 14-year-old boy presented with low-grade fever, widespread myalgia and difficulty in walking and standing 2 days after the undocumented trip which brought him from western Africa to Italy. His serum creatine phosphokinase was markedly elevated. He was diagnosed with rhabdomyolysis and was volume-restored with normal saline and bicarbonate-containing fluid. Anamnesis revealed illegal, not well-specified, forced consumption in his fatherland, and very bad conditions of the trip (prolonged immobility, dehydration, hypothermia). Workup included a respiratory microbiological panel which was positive for Chlamydia pneumoniae Other microbiological agents were excluded. After 3 weeks, he recovered complete motility. Undocumented immigrants may present several risk factors for rhabdomyolysis that give to this group of individuals a higher risk of developing this disorder.

Caudal Regression and Encephalocele: Rare Manifestations of Expanded Goldenhar Complex.

Oculoauriculovertebral spectrum, or Goldenhar Syndrome, is a condition characterized by variable degrees of uni- or bilateral involvement of craniofacial structures, ocular anomalies, and vertebral defects. Its expressivity is variable; therefore, the term "expanded Goldenhar complex" has been coined. The Goldenhar Syndrome usually involves anomalies in craniofacial structures, but it is known that nervous system anomalies, including encephalocele or caudal regression, may, rarely, occur in this condition. We report two rare cases of infants affected by Goldenhar Syndrome, associated with neural tube defects, specifically caudal regression syndrome and nasal encephaloceles, to underline the extremely complex and heterogeneous clinical features of this oculoauriculovertebral spectrum. These additional particular cases could increase the number of new variable spectrums to be included in the "expanded Goldenhar complex."

Association between Allergies and Hypercholesterolemia: A Systematic Review.

BACKGROUND: There is controversy in the literature regarding the potential relationship between atopic predisposition (AP) and serum cholesterol levels. To this purpose, we reviewed human studies that investigated this possible link. METHODS: Following PRISMA guidelines, a literature search of PubMed and Science Direct for peer-reviewed journal articles in English from January 2003, with updates through to August 2016, was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, time frame, and risk of bias were abstracted for each article. RESULTS: Of 601 reviewed reports, 18 were included in this systematic review. Fifteen studies assessed the relationship between AP and serum cholesterol levels. Due to the lack both of observational and cross-sectional studies from the literature search at this time (only 8 studies also analyzed confounding factors) there is a high possibility of confounding variables (familial and genetic predisposition, age, gender, BMI, comorbidity, and medication status) that could not be ruled out. CONCLUSION: Existing studies are heterogeneous, making it difficult to draw broad conclusions. Future studies and more detailed analyses, considering confounding variables and including a larger and homogeneous population, are needed to strengthen the argument for a link between lipid metabolism and atopy.

Filaggrin mutations and Molluscum contagiosum skin infection in patients with atopic dermatitis.

BACKGROUND: Although mutations in the filaggrin (FLG) gene have been reported to predispose patients with atopic dermatitis (AD) skin infection susceptibility, to date, the data reported in the literature are still controversial. OBJECTIVE: To evaluate the role of FLG polymorphisms expression and risk of developing a concomitant Molluscum contagiosum sustained skin infection in the pediatric population with AD. METHODS: A total of 100 children with AD and 97 healthy children were enrolled. AD was diagnosed and assessed according to the validated European Task Force on Atopic Dermatitis. DNA samples of patients were analyzed for allelic variants in the promoter and coding exon of FLG. Genotyping was performed with polymerase chain reaction amplification and direct sequencing. RESULTS: Sixteen FLG variants have been detected in 29% of patients with AD: 2 synonymous (rs79808464 and rs116222149), 12 missense (rs11584340, rs113136594, rs145828067, rs374910442, rs747005144, rs145627745, rs144209313, rs74129443, rs192455877, rs150957860, rs138055273, rs147472105), 1 stop gained (rs183942200), and 1 frameshift (rs 558269137). In contrast, only 13% of the control group reported FLG mutations (22 heterozygous variants). In addition, the age at disease onset correlated significantly with FLG variants (P < .001). In addition, the AD with FLG gene variants (rs145627745, rs79808464, rs150957860, rs145828067, rs747005144, rs374910442, rs138055273, rs183942200, rs11584340, and rs113136594) reported moderate to severe Scoring Atopic Dermatitis scores. Finally, the AD group and the AD plus M contagiosum skin infection group had a significant association with FLG mutations when compared with the control group (P < .01). CONCLUSION: FLG mutations are associated with early onset of AD, more severe clinical course of disease, and a significantly increased risk of M contagiosum sustained skin infection.