IgE to cyclophilins in pollen-allergic children: Epidemiologic, clinical, and diagnostic relevance of a neglected panallergen.

BACKGROUND: Cyclophilins are ubiquitous panallergens whose epidemiologic, diagnostic, and clinical relevance is largely unknown and whose sensitization is rarely examined in routine allergy practice. OBJECTIVE: We investigated the epidemiologic, diagnostic, and clinical relevance of cyclophilins in seasonal allergic rhinitis and its comorbidities. METHODS: We examined a random sample of 253 (25%) of 1263 Italian children with seasonal allergic rhinitis from the Panallergens in Pediatrics (PAN-PED) cohort with characterized disease phenotypes. Nested studies of sensitization prevalence, correlation, and allergen extract inhibition were performed in patients sensitized to birch pollen extract but lacking IgE to Bet v 1/2/4 (74/1263) or with highest serum level of IgE to Bet v 1 (26/1263); and in patients with sensitization to various extracts (ragweed, mugwort, pellitory, Plantago, and plane tree), but not to their respective major allergenic molecule, profilins, and polcalcins. IgE to cyclophilin was detected with recombinant Bet v 7, and extract inhibition tests were performed with the same rBet v 7. RESULTS: IgE to rBet v 7 was detected in 43 (17%) of 253 patients. It was associated with asthma (P < .028) and oral allergy syndrome (P < .017) in univariate but not multivariate analysis adjusted for IgE to profilins (Phl p 12), PR-10s (Bet v 1), and lipid transfer proteins (Pru p 3). IgE to rBet v 7 was also highly prevalent (47/74, 63%) among patients with unexplained sensitization to birch pollen extract. In patients with unexplained sensitization to ragweed, mugwort, pellitory, Plantago and plane tree pollen, the levels of IgE to those extracts correlated with the levels of IgE to rBet v 7, and they were also significantly inhibited by rBet v 7 (inhibition range 45%-74%). CONCLUSIONS: IgE sensitization to cyclophilin is frequent in pollen-allergic patients living in temperate areas and can produce "false" positive outcomes in skin prick and IgE tests to pollen extracts. Molecular diagnostic guidelines should include this panallergen family.

IgE to cross-reactive carbohydrate determinants (CCD) in childhood: Prevalence, risk factors, putative origins.

BACKGROUND: IgE antibodies to cross-reactive carbohydrate determinants (CCD) are usually clinically irrelevant but they can be a cause of false positive outcomes of allergen-specific IgE tests in vitro. Their prevalence and levels have been so far cross-sectionally examined among adult allergic patients and much less is known about their origins and relevance in childhood. METHODS: We examined CCD with a cross-sectional approach in 1263 Italian pollen allergic children (Panallergen in Paediatrics, PAN-PED), as well as with a longitudinal approach in 612 German children (Multicenter Allergy Study, MAS), whose cutaneous and IgE sensitization profile to a broad panel of allergen extracts and molecules was already known. The presence and levels of IgE to CCD were examined in the sera of both cohorts using bromelain (MUXF3) as reagent and a novel chemiluminescence detection system, operating in a solid phase of fluorescently labelled and streptavidin-coated paramagnetic microparticles (NOVEOS, HYCOR, USA). RESULTS: IgE to CCD was found in 22% of the Italian pollen allergic children, mainly in association with an IgE response to grass pollen. Children with IgE to CCD had higher total IgE levels and were sensitized to more allergenic molecules of Phleum pratense than those with no IgE to CCD. Among participants of the German MAS birth cohort study, IgE to CCD emerged early in life (even at pre-school age), with IgE sensitization to group 1 and 4 allergen molecules of grasses, and almost invariably persisted over the full observation period. CONCLUSIONS: Our results contribute to dissect the immunological origins, onset, evolution and risk factors of CCD-sIgE response in childhood, and raise the hypothesis that group 1 and/or 4 allergen molecules of grass pollen are major inducers of these antibodies through an antigen-specific, T-B cell cognate interaction.

Dietary Intervention during Weaning and Development of Food Allergy: What Is the State of the Art?

Food allergy (FA) affects approximately 6-8% of children worldwide causing a significant impact on the quality of life of children and their families. In past years, the possible role of weaning in the development of FA has been studied. According to recent studies, this is still controversial and influenced by several factors, such as the type of food, the age at food introduction and family history. In this narrative review, we aimed to collect the most recent evidence about weaning and its role in FA development, organizing the gathered data based on both the type of study and the food. As shown in most of the studies included in this review, early food introduction did not show a potential protective role against FA development, and we conclude that further evidence is needed from future clinical trials.

Molecular Mechanism and Clinical Effects of Probiotics in the Management of Cow's Milk Protein Allergy.

Cow's milk protein allergy (CMPA) is the most common food allergy (FA) in infancy, affecting approximately 2% of children under 4 years of age. According to recent studies, the increasing prevalence of FAs can be associated with changes in composition and function of gut microbiota or "dysbiosis". Gut microbiota regulation, mediated by probiotics, may modulate the systemic inflammatory and immune responses, influencing the development of allergies, with possible clinical benefits. This narrative review collects the actual evidence of probiotics' efficacy in the management of pediatric CMPA, with a specific focus on the molecular mechanisms of action. Most studies included in this review have shown a beneficial effect of probiotics in CMPA patients, especially in terms of achieving tolerance and improving symptoms.

COVID-19, anosmia, and ageusia in atopic children.

More than a year and a half after the beginning of the coronavirus disease 2019 (COVID-19) pandemic, symptoms, such as loss of smell and taste (anosmia and ageusia, respectively), remain difficult to characterize and quantify, especially in children, since no validated tests to assess these disorders are available. However, these symptoms can also be seen in children, although less frequently than observed in the adult population. In this article, we present the results of a national survey that collected the responses of 267 Italian pediatricians on the presence of anosmia and ageusia in children affected by COVID-19. These data were then compared with existing literature.

Allergic rhinitis, microbiota and passive smoke in children: A pilot study.

BACKGROUND: Allergic rhinitis (AR) is one of the most common allergic diseases affecting children. Objective assessment of nasal obstruction is possible through active anterior rhinomanometry (AAR). Several factors, such as passive smoke exposure (PSE), are triggers for worsening nasal obstruction and chronic inflammation. PSE affects bacterial eubiosis in the upper respiratory tract. This study evaluates the influence of PSE and cotinine levels on both nasal obstruction and local microbiome composition in children with AR. METHODS: Fifty patients (aged between 6 and 16 years) with AR monosensitized grass pollen were enrolled. They underwent skin prick tests, a nasal swab to evaluate the microbial composition of the anterior nostrils, a basal AAR, a post-decongestion AAR, and spirometry. Serum cotinine levels were assessed to evaluate PSE. RESULTS: A significantly lower percentage of mean nasal flow (mNF%) was observed before and after hydrazine administration in subjects exposed to passive smoke (Exp group) compared with the non-exposed group. In contrast, higher cotinine levels were observed in the Exp group than in the controls. PSE has been associated with a decrease in biodiversity and a change in the nasal microbiome composition; instead, although to a different extent, the abundance of specific taxa resulted in being correlated to cotinine levels and nasal flow. CONCLUSION: Children with AR exposed to passive smoke with positive serum cotinine could represent a risk factor for developing nasal obstruction and microbial dysbiosis, suggesting their possible role in pathophysiological processes.

Probiotics Function in Preventing Atopic Dermatitis in Children.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by relapsing eczematous injuries and severe pruritus. In the last few years, the AD prevalence has been increasing, reaching 20% in children and 10% in adults in high-income countries. Recently, the potential role of probiotics in AD prevention has generated considerable interest. As many clinical studies show, the gut microbiota is able to modulate systemic inflammatory and immune responses influencing the development of sensitization and allergy. Probiotics are used increasingly against AD. However, the molecular mechanisms underlying the probiotics mediated anti-allergic effect remain unclear and there is controversy about their efficacy. In this narrative review, we examine the actual evidence on the effect of probiotic supplementation for AD prevention in the pediatric population, discussing also the potential biological mechanisms of action in this regard.

Selective IgA Deficiency and Allergy: A Fresh Look to an Old Story.

Selective IgA deficiency (SIgAD) is the most common human primary immune deficiency (PID). It is classified as a humoral PID characterized by isolated deficiency of IgA (less than 7 mg/dL but normal serum IgG and IgM) in subjects greater than 4 years of age. Intrinsic defects in the maturation of B cells and a perturbation of Th cells and/or cytokine signals have been hypothesized to contribute to SIgAD pathogenesis. The genetic basis of IgA deficiency remains to be clarified. Patients with SIgAD can be either asymptomatic or symptomatic with clinical manifestations including allergy, autoimmunity and recurrent infections mainly of the respiratory and gastrointestinal tract. Studies analyzing allergy on SIgAD patients showed prevalence up to 84%, supporting in most cases the relationship between sIgAD and allergic disease. However, the prevalence of allergic disorders may be influenced by various factors. Thus, the question of whether allergy is more common in SIgAD patients compared to healthy subjects remains to be defined. Different hypotheses support an increased susceptibility to allergy in subjects with SIgAD. Recurrent infections due to loss of secretory IgA might have a role in the pathogenesis of allergy, and vice versa. Perturbation of microbiota also plays a role. The aim of this review is to examine the association between SIgAD and atopic disease and to update readers on advances over time at this important interface between allergy and SIgAD.

Update on rhinitis and rhinosinusitis.

Rhinitis is a common, under-diagnosed condition in childhood and adolescence. Pathogenic classification of rhinitis includes allergic rhinitis (AR) and non-allergic rhinitis (NAR); the latter is characterized by non-infectious and infectious subtypes; non-infectious subtype is by far the most prevalent in infancy. Endotyping may help to predict chronic rhinosinusitis (CRS) risk factors, as well as disease progression and response to different treatments. The validation of pediatric algorithms and the implementation of novel biotherapeutics in the endotype-driven integrated pathways of CRS will lead in the next future to more successful disease management.

Is oxidative stress involved in vernal keratoconjunctivitis? Results from a pilot study in children.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a rare chronic conjunctivitis characterized by a predominantly eosinophil-mediated inflammatory disorder that could develop critical complications such as blindness. Oxidative stress plays a pivotal role in the pathogenesis of several allergic diseases. The role of oxidative stress has been hypothesized in VKC, but no study explored this issue. Furthermore, cyclosporine A (CsA) exerts an anti-inflammatory and antioxidant action on the conjunctiva. This study aimed to assess the oxidative stress in VKC patients and controls and to study the effect of CsA on oxidative stress in these subjects. METHODS: Thirty-six consecutive children, including 12 VKC (nine males, 75%; mean age 10.17; SD ± 2.48) patients without treatment, 12 VKC patients treated with CsA (nine males, 75%; mean age 9.08; SD ± 2.75), and 12 controls (CT) (seven males, 58%; mean age 8.58; SD ± 1.78), were recruited. A cross-sectional study was performed to compare H2 O2 in the serum with that in the tears of these children. RESULTS: Compared with CT and VKC children treated with CsA, VKC untreated children had significantly higher values of hydrogen peroxide (H2 O2 ) in the serum and the tears. No significant differences were observed between CT and VKC treated with CsA. A significant correlation was found at the linear regression analysis between serum and tear H2 O2 levels. CONCLUSION: This study provides the first report attesting that patients with VKC have high oxidative stress; furthermore, it suggests that CsA could have an anti-inflammatory and antioxidant action that could be useful to prevent the poor VKC outcome.

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.

Assessing repeatability and reproducibility of Anterior Active Rhinomanometry (AAR) in children.

BACKGROUND: Repeatability and reproducibility are essential for clinicians for several purposes. Although discouraged, use of the Coefficient of Variation (CV) for assessing repeatability and reproducibility, rather than the Intraclass Correlation Coefficient (ICC), is still widespread. The aim of the present study was to highlight how using inappropriate indices may lead to misleading results, and this is done by simulation study and using real data on Anterior Active Rhinomanometry (AAR) in both healthy children and ones with rhinitis. METHODS: A simulation study was carried out to highlight how using inappropriate indices could be misleading. Then a comparison was made between CV and ICC to assess repeatability and reproducibility of AAR, for which previous studies have given underestimated results. AAR is recommended as the gold standard tool for measuring nasal resistance in clinical practice. RESULTS: A simulation study showed that the ICCs estimated from data generated assuming a true CV yielded results in agreement with estimated CVs; by contrast, if data were generated assuming a true ICC, CVs yielded conflicting results. For AAR, ICCs showed good repeatability, whereas CVs showed unacceptable repeatability. AUC and 95% CI for AAR showed good performance in predicting current symptoms of rhinitis in the overall study population. CONCLUSIONS: The present study focused on the importance of the choice of appropriate indices of repeatability and reproducibility, demonstrating the repeatability of AAR in both healthy children and ones with rhinitis. TRIAL REGISTRATION: ClinicalTrials.gov (ID: NCT03286049; Registration Date: September 15, 2017; Actual Study Start Date: January 10, 2018).

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.

Nasal reactivity evaluation in children with allergic rhinitis receiving grass pollen sublingual immunotherapy.

Background: The European Academy of Allergy and Clinical Immunology guidelines, strongly recommended allergen immunotherapy (AIT) as an effective treatment to achieve long-term clinical benefits and to modify the natural history of allergic diseases. Sublingual immunotherapy (SLIT) offers the possibility of home administration, which improves patient comfort and compliance. Objective: The primary outcome of this study was to assess the change in nasal reactivity after grass-pollen AIT treatment. Methods: This was a monocentric, prospective, observational study conducted in Rome from September 2016 to June 2018, in the Pediatric Department of Policlinico Umberto I. We enrolled children, ages between 6 and 12 years, with persistent allergic rhinitis (AR), sensitized to grass pollen. At the first visit (V0, September 2016), one group received the first dose of oral immunotherapy for grass-pollen spray buccal and the other group continued only standard therapy. All the patients had nasal specific immunoglobulin I (IgE) assay (Phl p1, Phl p5), active anterior rhinomanometry with a nasal provocation test (NPT), and spirometry. The patients attended two follow-up visits, in May 2017 (V1) and May 2018 (V2), with the same examinations as at V0. Results: During the treatment, we observed, in the treated group, a significant increase in the mean nasal flow compared with untreated children (p < 0.001). In the AIT group, we found an improvement of nasal function and only 21.05% of all the children in the active group with a positive NPT result at V2. In the control group, we found, at V2, a worsening of nasal function, with 89.47% of the children with a positive NPT result. Furthermore, we found a significant reduction of nasal specific IgE levels at the end of the observation period in the treated group. Conclusion: Analysis of our data provided evidence for a clinical effect of SLIT in inducing clinical changes and allergen tolerance in children with AR.

Adherence to Prescribed E-Diary Recording by Patients With Seasonal Allergic Rhinitis: Observational Study.

BACKGROUND: Complete diagnosis and therapy of seasonal allergic rhinoconjunctivitis require evidence that exposure to the sensitizing pollen triggers allergic symptoms. Electronic clinical diaries, by recording disease severity scores and pollen exposure, can demonstrate this association. However, patients who spontaneously download an e-diary app show very low adherence to their recording. OBJECTIVE: The objective of our study was to assess adherence of patients with seasonal allergic rhinitis to symptom recording via e-diary explicitly prescribed by an allergist within a blended care approach. METHODS: The @IT-2020 project is investigating the diagnostic synergy of mobile health and molecular allergology in patients with seasonal allergic rhinitis. In the pilot phase of the study, we recruited Italian children (Rome, Italy) and adults (Pordenone, Italy) with seasonal allergic rhinitis and instructed them to record their symptoms, medication intake, and general conditions daily through a mobile app (Allergy.Monitor) during the relevant pollen season. RESULTS: Overall, we recruited 101 Italian children (Rome) and 93 adults (Pordenone) with seasonal allergic rhinitis. Adherence to device use slowly declined during monitoring in 3 phases: phase A: first week, ≥1267/1358, 90%; phase B: second to sixth week, 4992/5884, 80% to 90%; and phase C: seventh week onward, 2063/2606, 70% to 80%. At the individual level, the adherence assessed in the second and third weeks of recording predicted with enough confidence (Rome: Spearman ρ=0.75; P<.001; Pordenone: ρ=0.81; P<.001) the overall patient adherence to recording and was inversely related to postponed reporting (ρ=-0.55; P<.001; in both centers). Recording adherence was significantly higher during the peak grass pollen season in Rome, but not in Pordenone. CONCLUSIONS: Adherence to daily recording in an e-diary, prescribed and motivated by an allergist in a blended care setting, was very high. This observation supports the use of e-diaries in addition to face-to-face visits for diagnosis and treatment of seasonal allergic rhinitis and deserves further investigation in real-life contexts.

A new molecular multiplex IgE assay for the diagnosis of pollen allergy in Mediterranean countries: A validation study.

BACKGROUND: The identification of the primary sensitizing pollen is difficult in Southern European patients with Seasonal Allergic Rhinitis (SAR) if sensitized to various pollen sources with overlapping seasonality. A more precise diagnosis is obtained by IgE assays to allergen molecules, currently available as singleplex or microarrays. OBJECTIVES: To test the analytical performance of a multi-parameter immunoblot molecular "Pollen Test" specifically designed to test IgE antibodies to pollen extracts and molecules clinically relevant in Southern Europe. METHODS: Sera were obtained from 101 children and 98 adults with SAR and tested with a customized multiplex immunoblot assay (EUROLINE Southern European Pollen Profile [ESEP]; EUROIMMUN AG, Luebeck, Germany) containing a comprehensive panel of allergen extracts and molecules. ESEP's outcomes were then compared in selected sera (ESEP positive to negative = 2:1) with those of singleplex IgE assays (ImmunoCAP; ThermoFisher Scientific, Uppsala, Sweden). For each of the examined reagents, qualitative (sensitivity, specificity, accuracy), semi-quantitative (classes) and quantitative (Spearman's rank correlation, Bland-Altmann plots) comparisons were performed. RESULTS: Compared to ImmunoCAP, cumulative ESEP's sensitivity and specificity were 87% (95% CI 84%-90%) and 88% (83%-93%) for extracts and 99% (98%-100%) and 87% (83%-91%) for molecules. Cohen's kappa coefficients (κC ) ranged for extracts from 0.18 (Pellitory) to 0.50 (Cypress) and for molecules from 0.21 (Ole e 1) to 0.68 (Phl p 7). The quantitative outcomes of the two diagnostic tests were highly correlated, with Spearman's rank correlation coefficients always exceeding 0.80. Bland-Altmann plots showed a tendency of ESEP to overestimate serum specific IgE levels, when compared to ImmunoCAP. CONCLUSIONS AND CLINICAL RELEVANCE: Sensitivity and specificity of ESEP in testing serum IgE antibodies against pollen allergen extracts and molecules, in Italian patients with SAR, both exceeded 85%. The advantages and limitations of a multiplex customized immunoblot assay, in the routine clinical use of molecular diagnostics in Southern European pollen allergic patients, deserve to be tested.

Early molecular biomarkers predicting the evolution of allergic rhinitis and its comorbidities: A longitudinal multicenter study of a patient cohort.

BACKGROUND: Pollen-related seasonal allergic rhinoconjunctivitis (SAR) is a very frequent pediatric disease in Westernized countries. Risk factors and disease phenotypes have been thoroughly examined in several cross-sectional studies. By contrast, only a few studies have examined disease evolution in patient cohorts. We investigated predictive biomarkers of disease evolution in a large cohort of children with SAR. METHODS: During 2015-2017 (follow-up), we re-examined 401 patients from those enrolled in 2009-2011 (baseline) by the "Panallergens in Pediatrics" study, a large multicenter survey of Italian children with SAR. Information on clinical history (standard questionnaire, AllergyCARD®; TPS, Italy) and skin prick tests for inhalant and foods extracts (ALK-Abelló, Hørsholm, Denmark) was acquired as at baseline visit. Evolution in clinical and sensitization data of patients was analyzed over time, as well as their association with the main baseline characteristics and atopy risk factors. RESULTS: The average age of participants was 10.4 ± 3.4 years at baseline and 16.2 ± 3.6 years at follow-up. SAR persisted in 93.3% of patients at follow-up and became more frequently associated with asthma (from 36.7% at baseline to 48.6% at follow-up) and oral allergy syndrome (OAS, from 23.4% to 37.7%). Compared to baseline, the prevalence of skin sensitization to some pollens (Phleum pratense, Corylus avellana, Platanus acerifolia, Artemisia vulgaris) and vegetables (hazelnut, wheat, and apple) significantly decreased at follow-up. Earlier onset of SAR and polysensitization at baseline were associated with incident asthma at follow-up. The presence at baseline of serum IgE to the following allergen molecules was identified as biomarkers of clinical evolution: (a) Phl p 1, for persistence of SAR; (b) Phl p 5, for persistence of both rhinitis and asthma; (c) Pru p 3, for new onset of asthma; (d) Bet v 1, for persistence of OAS. CONCLUSIONS: Seasonal allergic rhinoconjunctivitis is clinically heterogeneous in its evolution from childhood to adolescence. The detection of serum IgE to specific molecules (Phl p 1, Phl p 5, Bet v 1, Pru p 3) may be useful as biomarkers to predict SAR persistence and future onset of comorbidities, such as asthma and/or OAS.

When asthma and rhinitis coexist, could rhinitis reduce asthma control in children?

Background: Bronchial asthma and rhinitis are among the most common diseases in children and frequently coexist in the patient. The primary aim of anti-asthmatic therapy is disease control. Several questionnaires can be used in pediatrics to assess asthma control and the Children Asthma Control Test (C-ACT) is one of the most used. Objective: To evaluate the percentage of asthma control in our cohort of patients with asthma and correlate C-ACT with bronchial and nasal function tests. Methods: We enrolled all children ages between 5 and 11 years with persistent bronchial asthma, sensitized to dust mite, and who presented to our center during an 8-month period. All the children had skin-prick tests, spirometry, measurement of fractional exhaled nitric oxide levels, active anterior rhinomanometry, measurement of nasal nitric oxide level, and C-ACT. Results: Sixty patients were enrolled; 80% of these children had rhinitis. According to C-ACT, 31% of our patients had uncontrolled asthma. Nasal flow values were significantly lower in patients with uncontrolled asthma, who also had higher nasal inflammation. Conclusion: The disease is not controlled in a significant percentage of children with asthma. In patients with uncontrolled asthma, worse nasal flow was detected. These results supported the relationship between upper and lower airways, and highlighted the importance of performing nasal function tests in all patients with asthma, which could be useful to determine whether better control of asthma symptoms can be reached through an appropriate treatment of rhinitis.

Role of NADPH oxidase-2 and oxidative stress in children exposed to passive smoking.

This study explored oxidative stress, nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) activity and endothelial function in children exposed or not to passive smoking. Compared with controls (n=57), Nox2 activity and isoprostanes were higher in children exposed to passive smoking (n=57); conversely, nitric oxide (NO) bioavailability and flow-mediated dilation were lower in children exposed to passive smoking. A bivariate analysis showed that Nox2 activity correlated with flow-mediated dilation, NO bioavailability and isoprostanes. A multivariate analysis showed that Nox2 activity was significantly associated with serum isoprostanes and cotinine levels; flow-mediated dilation was associated with isoprostanes and carotid intima-media thickness.In children exposed to passive smoking, Nox2-derived oxidative stress is upregulated and inversely associated with impaired artery dilation.

Passive Smoking Exacerbates Nicotinamide-Adenine Dinucleotide Phosphate Oxidase Isoform 2-Induced Oxidative Stress and Arterial Dysfunction in Children with Persistent Allergic Rhinitis.

OBJECTIVE: To characterize nicotinamide-adenine dinucleotide phosphate oxidase isoform 2 (NOX2), oxidative stress, and endothelial function in children with and without allergic rhinitis and to ascertain the effect of passive smoke exposure on these factors, because there is an established association between allergic rhinitis and increased cardiovascular risk in adults. METHODS: We recruited 130 children-65 with persistent allergic rhinitis and 65 healthy controls. A cross-sectional study was performed to compare endothelial function by flow-mediated dilation, blood levels of isoprostanes, serum activity of soluble NOX2-dp (sNOX2-dp), and nitric oxide bioavailability, in these 2 groups of children. Serum cotinine levels were assessed to measure exposure to passive smoking. RESULTS: Compared with healthy controls, children with persistent allergic rhinitis had significantly higher sNOX2-dp and isoprostanes levels, lower flow-mediated dilation, and reduced nitric oxide bioavailability. Multivariable linear regression analysis showed that flow-mediated dilation, isoprostanes, and cotinine were independently associated with sNOX2-dp levels. Of note, sNOX2-dp serum levels were significantly higher in children with allergic rhinitis exposed to smoke, as compared with unexposed children with allergic rhinitis. CONCLUSION: NOX2 is activated in children with persistent allergic rhinitis and passive smoke exposure exacerbates this effect. We further demonstrate an association between higher sNOX2-dp and oxidative stress and endothelial dysfunction.