Type 2 inflammation in cystic fibrosis: New insights.

Recently, type 2 inflammation has been recognized as one of the most critical factors participating in the pathogenesis of cystic fibrosis (CF). On the one hand, type 2 inflammation restores tissue homeostasis and contributes to the resolution of inflammation following an injury. On the other hand, type 2 response-activated immune cells may become dysregulated or chronically activated, causing tissue fibrosis. Among the type 2 cytokine-driven inflammatory pathways, the transforming growth factor ß (TGFß), interleukin (IL)-17, IL-33, and IL-13 have been identified as essential mediators in patients suffering from CF. Given their critical role, we firmly believe that an adequate comprehension of the type 2-mediated pathways can identify attractive targets to decrease pharmacologically the inflammation and fibrosis occurring in the pulmonary tissue of patients suffering from CF.

Clinical course and risk factors for severe COVID-19 among Italian patients with cystic fibrosis: a study within the Italian Cystic Fibrosis Society.

PURPOSE: To describe the clinical course of COVID-19 in patients with cystic fibrosis (CF) and to identify risk factors for severe COVID-19. METHODS: We conducted a prospective study within the Italian CF Society. CF centers collected baseline and follow-up data of patients with virologically confirmed SARS-CoV-2 infection between March 2020 and June 2021. Odds ratios (ORs) for severe SARS-CoV-2 (as defined by hospital admission) were estimated by logistic regression models. RESULTS: The study included 236 patients with positive molecular test for SARS-CoV-2. Six patients died, 43 patients were admitted to hospital, 4 admitted to intensive care unit. Pancreatic insufficiency was associated with increased risk of severe COVID-19 (OR 4.04, 95% CI 1.52; 10.8). After adjusting for age and pancreatic insufficiency, forced expiratory volume in one second (FEVp) < 40% (OR 4.54, 95% CI 1.56; 13.2), oxygen therapy (OR 12.3, 95% CI 2.91-51.7), underweight (OR 2.92, 95% CI 1.12; 7.57), organ transplantation (OR 7.31, 95% CI 2.59; 20.7), diabetes (OR 2.67, 95% CI 1.23; 5.80) and liver disease (OR 3.67, 95% CI 1.77; 7.59) were associated with increased risk of severe COVID-19, while use of dornase alfa was associated with a reduced risk (OR 0.34, 95% CI 0.13-0.88). No significant changes were observed in FEVp from baseline to a median follow-up of 2 months (median difference: 0, interquartile range: - 4; 5, P = 0.62). CONCLUSION: Clinical features indicative of severe form of CF are associated with increased risk of COVID-19 hospitalization. SARS-CoV-2 infected patients do not experience a deterioration of respiratory function.

Cystic Fibrosis and Oxidative Stress: The Role of CFTR.

There is substantial evidence in the literature that patients with cystic fibrosis (CF) have higher oxidative stress than patients with other diseases or healthy subjects. This results in an increase in reactive oxygen species (ROS) and in a deficit of antioxidant molecules and plays a fundamental role in the progression of chronic lung damage. Although it is known that recurrent infection-inflammation cycles in CF patients generate a highly oxidative environment, numerous clinical and preclinical studies suggest that the airways of a patient with CF present an inherently abnormal proinflammatory milieu due to elevated oxidative stress and abnormal lipid metabolism even before they become infected. This could be directly related to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency, which appears to produce a redox imbalance in epithelial cells and extracellular fluids. This review aims to summarize the main mechanism by which CFTR deficiency is intrinsically responsible for the proinflammatory environment that characterizes the lung of a patient with CF.

Metal-Oxide Based Nanomaterials: Synthesis, Characterization and Their Applications in Electrical and Electrochemical Sensors.

Pure, mixed and doped metal oxides (MOX) have attracted great interest for the development of electrical and electrochemical sensors since they are cheaper, faster, easier to operate and capable of online analysis and real-time identification. This review focuses on highly sensitive chemoresistive type sensors based on doped-SnO2, RhO, ZnO-Ca, Smx-CoFe2-xO4 semiconductors used to detect toxic gases (H2, CO, NO2) and volatile organic compounds (VOCs) (e.g., acetone, ethanol) in monitoring of gaseous markers in the breath of patients with specific pathologies and for environmental pollution control. Interesting results about the monitoring of biochemical substances as dopamine, epinephrine, serotonin and glucose have been also reported using electrochemical sensors based on hybrid MOX nanocomposite modified glassy carbon and screen-printed carbon electrodes. The fundamental sensing mechanisms and commercial limitations of the MOX-based electrical and electrochemical sensors are discussed providing research directions to bridge the existing gap between new sensing concepts and real-world analytical applications.

Nutraceuticals in the Prevention of Viral Infections, including COVID-19, among the Pediatric Population: A Review of the Literature.

In recent years, there has been a growth in scientific interest in nutraceuticals, which are those nutrients in foods that have beneficial effects on health. Nutraceuticals can be extracted, used for food supplements, or added to foods. There has long been interest in the antiviral properties of nutraceuticals, which are especially topical in the context of the ongoing COVID-19 pandemic. Therefore, the purpose of this review is to evaluate the main nutraceuticals to which antiviral roles have been attributed (either by direct action on viruses or by modulating the immune system), with a focus on the pediatric population. Furthermore, the possible applications of these substances against SARS-CoV-2 will be considered.

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.

Allergic bronchopulmonary aspergillosis in children.

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by Aspergillus induced hypersensitivity that occurs in immunocompetent but susceptible patients with asthma and/or cystic fibrosis (CF). In children, ABPA remains mostly undiagnosed resulting in one of the most common causes of poorly controlled asthma and highly significant morbidity in children with CF. Currently, no specific diagnostic criteria of ABPA for children are available. Corticosteroids and itraconazole are the mainstays of therapy although there is a lack of randomized clinical trials regarding their usefulness for ABPA in children. Several monoclonal antibodies, such as omalizumab and mepolizumab, may be potential therapies for refractory ABPA in pediatric patients; however, further data are required to clarify the optimal dose and duration of therapy as a routine treatment approach.

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.

Pidotimod in allergic diseases.

The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active substances, commonly known as immunostimulants, have been introduced for the prevention and treatment of allergic diseases in pediatric population. Among the heterogeneous group of biologically active molecules to date available, pidotimod (Axil, Valeas S.p.A, Milan) is proved to be able to ameliorate both innate and adaptive immunity and enhances the immune system properties often impaired in patients with allergic disorders.

Monitoring of Chemical Risk Factors for Sudden Infant Death Syndrome (SIDS) by Hydroxyapatite-Graphene-MWCNT Composite-Based Sensors.

Sensing properties of chemical sensors based on ternary hydroxyapatite-graphene-multiwalled carbon nanotube (HA-GN-MWCNT) nanocomposite in the detection of chemical substances representing risk factors for sudden infant death syndrome (SIDS), have been evaluated. Characterization data of the synthesized composite have shown that the graphene-MWCNT network serves as a matrix to uniformly disperse the hydroxyapatite nanoparticles and provide suitable electrical properties required for developing novel electrochemical and conductometric sensors. A HA-GN-MWCNT composite-modified glassy carbon electrode (HA-GN-MWCNT/GCE) has been fabricated and tested for the simultaneous monitoring of nicotine and caffeine by cyclic voltammetry (CV) and square wave voltammetry (SWV), whereas a HA-GN-MWCNT conductive gas sensor has been tested for the detection of CO2 in ambient air. Reported results suggest that the synergic combination of the chemical properties of HA and electrical/electrochemical characteristics of the mixed graphene-MWCNT network play a prominent role in enhancing the electrochemical and gas sensing behavior of the ternary HA-GN-MWCNT hybrid nanostructure. The high performances of the developed sensors make them suitable for monitoring unhealthy actions (e. g. smoking, drinking coffee) in breastfeeding women and environmental factors (bad air quality), which are associated with an enhanced risk for SIDS.

Measurement of nitric oxide and assessment of airway diseases in children: an update.

INTRODUCTION: Nitric oxide (NO) is a gas synthesized by the inducible NO synthase enzyme in airway cells and it is thought to make important functions in the airway inflammation of several respiratory diseases. EVIDENCE ACQUISITION: This current study is a review of the literature from 1990 to present about NO and its use in clinical practice. The databases used were PubMed, Scopus, and Cochrane Library. EVIDENCE SYNTHESIS: At the respiratory level there are three different measurements sites of NO: nNO (nasal nitric oxide), FeNO (exhaled fraction of nitric oxide), CaNO (alveolar nitric oxide). Each of them is produced at different levels of the respiratory tract and is involved in various diseases. nNO finds its use, principally, in the allergic rhinitis in fact it can be used as a measure of therapeutic efficacy, but not for the evaluation of the severity; also in primary ciliary dyskinesia (PCD), where high levels exclude the disease, and in chronic rhinosinusitis, but it is not currently used as a diagnostic or prognostic marker. FeNO has a greatest use in bronchial asthma, particularly, it is considered a non-invasive biomarker to identify and to monitor airway inflammation but currently, there is not a consensus on the use of the FeNO in the management of asthma treatment. Finally, CaNO is the least used in clinical practice, because lack of standardization of measurement techniques. CONCLUSIONS: Nitric oxide is a sensitive indicator of the presence of airway inflammation and ciliary dysfunction, although some studies have shown varying or conflicting results.

Gastroesophageal reflux and respiratory diseases: does a real link exist?

INTRODUCTION: Gastro-esophageal reflux disease (GERD) indicates a gastroesophageal reflux that causes symptoms such as pain, and needs medical therapy, and may result in complications such as erosive esophagitis, aspiration pneumonia. Here, we review if it exists a real link between clinical presentation of some respiratory diseases such as asthma, chronic cough, cystic fibrosis and laryngopharyngitis and GERD. EVIDENCE ACQUISITION: This review was conducted employing 2 databases: PubMed and Science Direct. EVIDENCE SYNTHESIS: Asthma may lead to reflux, and reflux could exacerbate asthma or cause asthma-like symptoms. Prevalence of GERD in children with asthma ranged from as low 32% to as high 80%. There are several studies where the use of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists lead to inconclusive results. The relation of chronic unexplained cough to GERD remains controversial in children and pediatric guidelines do not currently recommend empirical GERD treatment trials for pediatric chronic cough. Gastroesophageal reflux is more frequent in patients with cystic fibrosis (CF) than general population. Although PPIs are regularly prescribed in approximately half of the patients with CF, there are no specific guidelines for treatment of reflux in CF and it was shown that chronic treatment with PPIs was correlated to possible increased risk of exacerbations. CONCLUSIONS: The pathogenesis of GER-related respiratory symptoms is multifactorial. The causal relationship between these two conditions may be difficult to prove also with the aid of supporting tests. Multichannel intraluminal impedance associated with pH-metry (pH/MII) detect all gastroesophageal reflux episodes accompanied with a bolus movement and classify GER episodes according to their content (liquid, gas and mixed), pH value and proximal extension. There are no consistent evidences confirming the validity of medical therapy in reflux with respiratory symptoms.

Food Allergies: Current and Future Treatments.

Food allergies are an increasingly public health problem, affecting up to 10% of children and causing a significant burden on affected patients, resulting in dietary restrictions, fear of accidental ingestion and related risk of severe reactions, as well as a reduced quality of life. Currently, there is no specific cure for a food allergy, so the only available management is limited to strict dietary avoidance, education on prompt recognition of symptoms, and emergency treatment of adverse reactions. Several allergen specific- and nonspecific-therapies, aiming to acquire a persistent food tolerance, are under investigation as potential treatments; however, to date, only immunotherapy has been identified as the most promising therapeutic approach for food allergy treatment. The aim of this review is to provide an updated overview on changes in the treatment landscape for food allergies.

Acute bronchiolitis: Influence of viral co-infection in infants hospitalized over 12 consecutive epidemic seasons.

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.

CO2 sensing properties of electro-spun Ca-doped ZnO fibres.

The availability of low-cost, high-performing sensors for carbon dioxide detection in the environment may play a crucial role for reducing CO2 emissions and limiting global warming. In this study, calcium-doped zinc oxide nanofibres with different Ca to Zn loading ratios (1:40 or 1:20) are synthesised via electro-spinning, thoroughly characterised and, for the first time, tested as an active material for the detection of carbon dioxide. The results of their characterisation show that the highly porous fibres consist of interconnected grains of oxide with the hexagonal wurtzite structure of zincite. Depending on the Ca:Zn loading ratio, calcium fully or partly segregates to form calcite on the fibre surface. The high response of the sensor based on the fibres with the highest Ca-doping level can be attributed to the synergy between the fibre morphology and the basicity of Ca-ion sites, which favour the diffusion of the gas molecules within the sensing layer and the CO2 adsorption, respectively.

Photo-Electrochemical Sensing of Dopamine by a Novel Porous TiO2 Array-Modified Screen-Printed Ti Electrode.

In this paper, the development of a nanoporous TiO2 array-modified Ti electrode for photo-electrochemical (PEC) sensing of dopamine (DA) is reported. A porous TiO2 array-modified electrode was fabricated from the controlled anodic oxidation of a Ti working electrode of commercial screen-printed electrodes (SPE). The anodization process and the related morphological and microstructural transformation of the bare Ti electrode into a TiO2/Ti electrode was followed by scanning electron microscopy (SEM) and UV-visible reflectance spectroscopy (DR-UV-Vis). The modified electrode was irradiated with a low-power (120 mW) UV-Vis LED lamp (λ = 400 nm) and showed good performance for the detection of DA with a large linear response range, a sensitivity of 462 nA mM-1 cm-2, and a limit of detection of 20 µM. Moreover, it showed higher photocurrents in the presence of DA in comparison to some foreign species such as ascorbic acid, uric acid, glucose, K⁺, Na⁺, and Cl-. Thus, this proposed low-cost photo-electrochemical sensor, with the advantage of very simple fabrication, demonstrates potential applications for the determination of dopamine in real samples.

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.

A systematic review of food protein-induced enterocolitis syndrome from the last 40 years.

OBJECTIVE: To provide a complete, exhaustive summary of current literature relevant to food protein-induced enterocolitis syndrome (FPIES). DATA SOURCES: Data have been extracted from PubMed and Science Direct databases. STUDY SELECTIONS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, a literature search for peer-reviewed journal articles in English through January 1975 with updates through October 2016 was conducted. Relevant publications were reviewed that included pediatric and adult populations. Information on the study design, sample, intervention, comparators, outcome, timeframe, and risk of bias were abstracted for each article. RESULTS: Of 135 reviewed reports, 52 were included in this systematic review. In accordance with the age at onset, clinical features, and offending foods, it is possible to distiguish different types of FPIES. An immune systemic involvement can occur in patients with FPIES. In addition to the most common causative foods (cow's milk, soy, and rice), any food can potentially cause FPIES. Although specific diagnostic tests are not available, open food challenge remains the gold standard for FPIES diagnosis. Moreover, because of the lack of randomized clinical trials and of use of different adopted methods, confounding factors might mask critical findings, leading to poor knowledge of this pleiotropic clinical entity. CONCLUSION: Multicenter studies are needed to better develop an evidence-based approach to pathophysiology, prevalence, diagnosis, and natural history of the disease.

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.

High mobility group box 1: Biomarker of inhaled corticosteroid treatment response in children with moderate-severe asthma.

BACKGROUND: High mobility group box 1 (HMGB1) is abnormally expressed in serum and sputum of patients with allergic asthma. OBJECTIVE: The aim of this study was to investigate the role of HMGB1 as guidance for treatment management of children with asthma. METHODS: Thirty children with asthma and 44 healthy children were enrolled. The patients were classified according to Global Initiative for Asthma Guideline disease severity criteria. Sputum HMGB1 levels and lung function index (percentage forced expiratory volume in 1 second [FEV1%]) were recorded in the cohort study at baseline (T0) and after 3 (T3) and 6 (T6) months of inhaled corticosteroids (ICS) treatment. RESULTS: Sputum HMGB1 levels were significantly higher in all the patients with asthma (p < 0.001). An inverse correlation between sputum HMGB1 levels and pulmonary function parameters was observed only in the children with moderate asthma (T0: FEV1%, r = -0.9891, p < 0.001; T3: FEV1%, r = -0.6763, p < 0.001; T6: FEV1%, r = -0.5419, p < 0.05) and in the children with severe asthma (T0: FEV1%, r = -0.8696, p < 0.001; T3: FEV1%, r = -0.6477, p < 0.05; T6: FEV1%, r = -0.8627, p < 0.001). After ICS treatment, a significant decrease of sputum HMGB1 levels was noted in moderate (T0 [93.44 ± 20.65 ng/mL] versus T3 [77.96 ± 1.81 ng/mL] versus T6 [67.75 ± 3.01 ng/mL]; p < 0.0001) and in the children with severe asthma (T0 [130.3 ± 7.48 ng/mL] versus T3 [156.9 ± 1.09 ng/mL] versus T6 [116.08 ± 4.77 ng/mL]; p < 0.0001) data are mean ± standard deviation, respectively. The area under the receiver operating characteristic curve, performed to define the diagnostic profile of sputum HMGB1 levels in identifying the children with asthma, was 0.713. CONCLUSION: In addition to the findings that HMGB1 is a sensitive biomarker of allergic asthma in children, our data demonstrated a significant correlation between the decrease of HMGB1 levels and a successful treatment response.