Role of genetic investigation in the diagnosis of short stature in a cohort of Italian children.

BACKGROUND: Short stature (SS) is defined as height more than 2 standard deviations below the mean for age and sex. Hypothyroidism, celiac disease, growth hormone deficiency, hormonal abnormalities, and genetic conditions are among its causes. A wide range of conditions often due to largely unknown genetic variants can elude conventional diagnostic workup. AIM: We used next-generation sequencing (NGS) to better understand the etiology of SS in a cohort of Italian children. PATIENTS AND METHODS: The study sample was 125 children with SS of unknown origin referred to our Institute between 2015 and 2021. All had undergone complete auxological and hormonal investigations to exclude common causes of SS. Genetic analysis was performed using a NGS panel of 104 genes. Clinical data were reviewed to clarify the pathogenicity of the variants detected. RESULTS: In this cohort, 43 potentially causing variants were identified in 38 children. A syndromic genetic condition was diagnosed in 7: Noonan syndrome in 3, Leri-Weill syndrome in 3, and hypochondroplasia in 1. Moreover, 8 benign variants and other 37 like benign variants were found. In 88 children, 179 variants of uncertain significance (VUS) were identified. No variant was found in 16 children. CONCLUSION: Genetic analysis is a useful tool in the diagnostic workup of patients with SS, in adapting management and treatment, and in identifying syndromes with mild atypical clinical features. The role of VUS should not be underestimated, particularly when multiple VUS with possible mutual worsening effects are present in the same child.

Retrospective definition of reaction risk in Italian children with peanut, hazelnut and walnut allergy through component-resolved diagnosis.

BACKGROUND: Serum IgE evaluation of peanut, hazelnut and walnut allergens through the use of component-resolved diagnosis (CRD) can be more accurate than IgE against whole food to associate with severe or mild reactions. OBJECTIVES: The aim of the study was to retrospectively define the level of reaction risk in children with peanut, hazelnut and walnut sensitization through the use of CRD. METHODS: 34 patients [n=22 males, 65%; median age eight years, interquartile range (IQR) 5.0-11.0 years] with a reported history of reactions to peanut and/or hazelnut and/or walnut had their serum analyzed for specific IgE (s-IgE) by ImmunoCAP® and ISAC® microarray technique. RESULTS: In children with previous reactions to peanut, the positivity of Arah1 and Arah2 s-IgE was associated with a history of anaphylaxis to such food, while the positivity of Arah8 s-IgE were associated with mild reactions. Regarding hazelnut, the presence of positive Cora9 and, particularly, Cora14 s-IgE was associated with a history of anaphylaxis, while positive Cora1.0401 s-IgE were associated with mild reactions. Concerning walnut, the presence of positive Jug r 1, Jug r 2, Jug r 3 s-IgE was associated with a history of anaphylaxis to such food. ImmmunoCAP® proved to be more useful in retrospectively defining the risk of hazelnut anaphylaxis, because of the possibility of measuring Cor a14 s-IgE. CONCLUSIONS: Our data show that the use of CRD in patients with allergy to peanut, hazelnut and walnut could allow for greater accuracy in retrospectively defining the risk of anaphylactic reaction to such foods.

Awareness of allergic enterocolitis among primary-care paediatricians: A web-based pilot survey.

BACKGROUND: Allergic enterocolitis, also known as food protein-induced enterocolitis syndrome (FPIES), is an increasingly reported and potentially severe non-IgE mediated food allergy of the first years of life, which is often misdiagnosed due to its non-specific presenting symptoms and lack of diagnostic guidelines. OBJECTIVE: We sought to determine the knowledge of clinical, diagnostic and therapeutic features of FPIES among Italian primary-care paediatricians. METHODS: A 16-question anonymous web-based survey was sent via email to randomly selected primary care paediatricians working in the north of Italy. RESULTS: There were 194 completed surveys (48.5% response rate). Among respondents, 12.4% declared full understanding of FPIES, 49% limited knowledge, 31.4% had simply heard about FPIES and 7.2% had never heard about it. When presented with clinical anecdotes, 54.1% recognised acute FPIES and 12.9% recognised all chronic FPIES, whereas 10.3% misdiagnosed FPIES as allergic proctocolitis or infantile colic. To diagnose FPIES 55.7% declared to need negative skin prick test or specific-IgE to the trigger food, whereas 56.7% considered necessary a confirmatory oral challenge. Epinephrine was considered the mainstay in treating acute FPIES by 25.8% of respondents. Only 59.8% referred out to an allergist for the long-term reintroduction of the culprit food. Overall, 20.1% reported to care children with FPIES in their practice, with cow's milk formula and fish being the most common triggers; the diagnosis was self-made by the participant in 38.5% of these cases and by an allergist in 48.7%. CONCLUSION: There is a need for promoting awareness of FPIES to minimise delay in diagnosis and unnecessary diagnostic and therapeutic interventions.

Enforcing surveillance of antimicrobial resistance and antibiotic use to drive stewardship: experience in a paediatric setting.

BACKGROUND: Antibiotic stewardship (AS) interventions in paediatrics are still not standardized regarding methodology, metrics, and outcomes. We report the results of an AS intervention in the paediatric area based on education and guideline provision via an electronic App. MATERIALS AND METHODS: The AS intervention was conducted in 2021 through observation, education, audit and feedback and provision of an electronic App (Firstline.org) to support antibiotic prescription based on local susceptibility data. The primary outcome was the antibiotic consumption in the 12 months following the intervention (year 2022) compared with a historical 12-month control (year 2019) via an interrupted time series analysis. Secondary outcomes were appropriateness of therapy, length of stay, 30-day readmission, transfers to the paediatric intensive care unit, in-hospital mortality, and prevalence of antimicrobial resistance (AMR). RESULTS: During the post-intervention phase, 29 cross-sectional audits and feedback were conducted including 467 patients. Prescriptions were appropriate according to the guidelines in 85.7% of cases, with a stable trend over time. A significant decrease in antibiotic consumption was measured in terms of defined daily doses per 1000 patient days (-222.13; P<0.001) and days of therapy per 1000 patient days (-452.49; P<0.001) in the post-intervention period with a clear inversion of the Access to Watch ratio (from 0.7 to 1.7). Length of stay, in-hospital mortality, intensive care unit transfers, and incidence of AMR infections remained stable, while 30-day readmission decreased from 4.9 per 100 admissions to 2.8 per 100 admissions (P<0.001). CONCLUSIONS: The intervention was associated with a significant reduction in antimicrobial consumption and an increase in the appropriateness of prescriptions. Electronic tools can be of value in promoting adherence to guidelines and ensuring the sustainability of results.

Interdisciplinary management of orofacial lesions in early childhood: paediatric alert system at University of Verona.

BACKGROUND: Orofacial trauma (OFT) occurs frequently in children and requires thorough evaluation not only by paediatric dentists but also by all specialists involved in emergency services, particularly in cases involving children under 3 years of age, given their inability to directly participate in clinical-anamnestic evaluations. Addressing early childhood orofacial trauma resulting from maltreatment, this study explores the key role played by various healthcare professionals, including paediatric dentists, general dentists, maxillofacial surgeons, dental hygienists, and paediatricians, in the optimal management of these cases. In the event of trauma due to suspected or confirmed mistreatment, it is essential that all healthcare workers involved have precise knowledge of the appropriate course of action from both a clinical and legal point of view, guaranteeing maximum protection for the young patient. This is particularly significant as cases of mistreatment with apparently minor consequences can degenerate into situations of irreparable severity. The latest guidelines from the International Association of Dental Traumatology (IADT) in 2020 continue to emphasise the potential correlation between OFT and cases of abuse or violence. Recent recommendations in the literature highlight the importance of facilitating mandatory reporting of incidents to relevant authorities and improving information sharing between dental healthcare professionals and child welfare services. A new flow diagram, called Paediatric Orofacial Trauma Alert (P.O.T.A.), has been proposed at the University of Verona. This tool is specifically designed to assist specialists dealing with early childhood orofacial trauma cases by assisting them in identifying potential cases of maltreatment. In this innovative approach, the collaborative efforts of general dentists, paediatric dentists, maxillofacial surgeons, dental hygienists and paediatricians play a vital role in cases of abuse. In addition to restoring the oral health of young patients, these professionals can activate a vast network of contacts, ensuring not only optimal oral health care but also providing comprehensive support to victims. The objective is to safeguard not only the physical but also the psychological well-being of these vulnerable subjects.

Ambroxol inhibits neutrophil respiratory burst activated by alpha chain integrin adhesion.

The purpose of the present study was to investigate the possible anti-oxidant effect(s) of Ambroxol on neutrophils activated by ligand-binding of the drug with membrane-associated adhesion integrin CD11a and to estimate dose-response changes in oxygen free radical production. The amount of free radical production by anti-CD11a- and anti-CD4-coated neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (FMLP) and challenged with increasing concentration of Ambroxol, was evaluated within a time frame of 90 minutes. A significant dose-dependent effect response of Ambroxol on O2‾ production by cells coated with anti-CD11a antibody was observed. This preliminary study opens a new perspective on the therapeutic role of Ambroxol as an antioxidant drug and for its potential use in controlling oxidative stress, particularly in leukocyte-dependent inflammation.

Timing of introduction of solid food and risk of allergic disease development: understanding the evidence.

Strategies to prevent or reduce the risk of allergic diseases are needed. The time of exclusive breastfeeding and introduction of solid foods is a key factor that may influence the development of allergy. For this reason, the aim of this review was to examine the association between exposure to solid foods in the infant's diet and the development of allergic diseases in children. Classical prophylactic feeding guidelines recommended a delayed introduction of solids for the prevention of atopic diseases. Is it really true that a delayed introduction of solids (after the 4th or 6th month) is protective against the development of eczema, asthma, allergic rhinitis and food or inhalant sensitisation? In recent years, many authors have found that there is no statistically significant association between delayed introduction of solids and protection for the development of allergic diseases. Furthermore, late introduction of solid foods could be associated with increased risk of allergic sensitisation to foods, inhalant allergens and celiac disease in children. Tolerance may be driven by the contact of the mucosal immune system with the allergen at the right time of life; the protective effects seem to be enhanced by the practice of the breastfeeding at the same time when weaning is started. Therefore, recent guidelines propose a "window" approach for weaning practice starting at the 17th week and introducing almost all foods within the 27th week of life to reduce the risk of chronic diseases such as allergic ones and the celiac disease. Guidelines emphasize the role of breastfeeding during the weaning practice.

Unusual shift from IgE-mediated milk allergy to food protein-induced enterocolitis syndrome.

Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe non-IgE-mediated food allergy usually caused by cow's milk or soy, and more rarely by solid foods such as rice, oats, barley, chicken, turkey, egg white, green peas and peanuts. In children with FPIES, the presence of specific IgE antibodies to the causative food, either at presentation or during follow-up, defines an "atypical form" of FPIES characterized by a lesser probability of developing tolerance and a potential progression to typical IgE-mediated hypersensitivity. Although it is uncommon, the shift from non-IgE-mediated milk-protein induced enterocolitis syndrome to IgE-mediated milk allergy has recently been described. We report the first case, to our knowledge, of a shift from IgE-mediated cow's milk allergy to pure non-IgE-mediated FPIES, in a 4-month-old male infant.

Bronchial and alveolar nitric oxide in exercise-induced bronchoconstriction in asthmatic children.

BACKGROUND: Epidemiological studies have shown an association between the severity of exercise-induced bronchoconstriction (EIB) and fractional exhaled nitric oxide at the flow of 50 mL/s (FeNO(50)). However, no study has assessed the correlation between alveolar production (C(alv)) and bronchial flux (J(NO)) of nitric oxide (NO) and EIB in asthmatic children. OBJECTIVE: To identify the relationship between severity of EIB and bronchial or alveolar nitric oxide. METHODS: Our group included 36 allergic children with intermittent asthma. The EIB was determined by a standard exercise challenge and the severity was expressed as the maximum change in percentage from the baseline value of lung function (ΔFEV(1)%, ΔFEF(25-75)%) after exercising. A chemiluminescence analyser at multiple flows was used to calculate FeNO(50), J(NO) and C(alv,) which reflect large airways, J(NO) and alveolar concentration of NO respectively. RESULTS: Sixteen (44.4%) children presented a ∆FEV(1) ≥ 10%, eight (22.2%) had ∆FEV(1) ≥ 15% and nine (25%) children had a ∆FEF(25-75) ≥ 26%. A significant correlation was observed between severity of EIB and FeNO(50) , J(NO) and C(alv.) EIB was significantly more severe in children sensitive to indoor allergens compared with outdoor allergens only (P = 0.014); those children showed also higher levels of C(alv) (P = 0.003) and of J(NO) (P = 0.044). CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that inflammation is present in the central and peripheral airways and that it is associated with the severity of EIB. Clinicaltrials.gov NCT00952835.

Vaccine allergy evaluation and management at the specialized Green Channel Consultation Clinic.

BACKGROUND: Suspected vaccine allergy may be a cause of incomplete or delayed vaccination. Patients at risk of adverse reactions or suspected contraindications need specialized consultation about subsequent vaccinations. OBJECTIVE: To analyse consultancy results for patients at risk of allergic reactions to vaccines as evaluated by the Green Channel University Hospital Immunization Consultancy Clinic. METHODS: A review of cases of allergic reactions to vaccines or contraindications due to underlying diseases or sensitization to vaccine components submitted to the Green Channel was carried out. Analysed data included detailed clinical reaction history, skin and in vitro allergy testing with vaccine components, recommendations for vaccination and outcome of subsequent vaccine administrations. RESULTS: A total of 519 cases, 370 referred for previous local or systemic reactions to vaccines, mostly cutaneous, and 149 sent for suspected contraindications were evaluated. Skin testing was performed on 152 patients, specific IgE determination in 37 subjects and patch testing in 173 cases. After consultation, 442 (85%) subjects were advised to continue vaccination, with personalized precautions (premedication, or alternative brand, or administration in graded doses) for 200 of them. Among the 352 (80%) patients vaccinated as per Green Channel instructions, 33 subjects (9.3%) reported mild allergic or non-specific symptoms and one (0.3%) urticaria with bronchospasm. CONCLUSION AND CLINICAL RELEVANCE: Even though vaccine allergy occurs very rarely, a safe procedure for immunization can be applied, through specialized allergy consultancy, for most subjects with suspected allergy to vaccines, and who could be potentially excluded from vaccination for risk of adverse reactions.

Markers of oxidative stress are increased in exhaled breath condensates of children with atopic dermatitis.

BACKGROUND: Airway inflammation may be present in subjects affected by atopic dermatitis (AD) but still without asthma symptoms. Exhaled breath condensate (EBC) reflects the composition of bronchoalveolar extracellular lining fluid that contains a large number of mediators of airway inflammation and oxidative damage. OBJECTIVES: We assessed inflammatory markers in the EBC of patients with AD. Fifty-six children (34 girls and 22 boys) were enrolled: 33 affected by AD and 23 healthy controls. METHODS: EBC was collected using a condenser device. We measured EBC pH and concentrations of leukotriene B4 (LTB4), 8-isoprostane, H(2) O(2) , malondialdehyde and 4-hydroxynoneal. Respiratory resistance was also evaluated. RESULTS: EBC pH in patients with AD was significantly lower than in healthy children, median (range) being 8·02 (7·94-8·12) in AD vs. 8·11 (8·05-8·16) (P = 0·02). The values of exhaled 8-isoprostane and LTB4 were significantly increased in subjects with AD compared with normal controls (P < 0·01 and P < 0·001, respectively). There was increased 4-hydroxynoneal in patients with AD but this did not reach statistical significance. Evaluating respiratory resistance, no bronchoreversibility was demonstrated in the children with AD. CONCLUSIONS: pH, LTB4 and 8-isoprostane in EBC could be sensitive markers of airway inflammation in children with AD. Prospective studies would be of interest to evaluate if airway inflammation, not yet clinically evident, could predict the development of asthma later in life in children with AD.

Adolescent health care in Italy: a mini-review.

The purpose of this mini-review is to present the National Health System and services available for adolescents in Italy, and to review the most relevant data on morbidity and mortality in Italian teens. Adolescent medicine in Italy is not a separate speciality, but there are some distinct services for adolescents in paediatric departments or gynaecologic wards, mostly in large cities where university hospitals or hospital of national relevance are located. Primary health care in Italy is provided mainly by general practitioners (GPs) and pediatricians, and on-call physicians (Guardia Medica) for after-hours medical care and services. The number of centres providing care for adolescents in Italy is 4097 (50% of these are in the North of Italy, 20% in the Central regions and 20% in the South and Islands). The population of Italy on January 1st 2011 was approximately 60,477,881 and the number of adolescents, aged 10 to 19 years, was 6,214,000. The most frequent causes of death in adolescents are motor vehicle accidents - more than half of which are related to drug or alcohol use - followed by cancer and suicide. In primary care, adolescents present with a large number of issues, particularly upper respiratory infections, musculoskeletal problems, pain syndromes, obesity, eating disorders, dermatological issues, mood and somatoform disorders, school and mental health problems, and chronic fatigue, many of which require a coordinated, multidisciplinary management approach. The estimated population with a chronic illness is 8%. There are no specific protocols for the transition to adult medicine physicians for patients with chronic diseases or special health needs. In order to improve the quality and quantity of education in adolescent health for paediatricians and GPs, the Study Group of Emilia and Romagna Region for Adolescent Health Care (SGA-ER) is going to organize, beginning in 2012, a two year educational intervention course in adolescent health.

The SGA-ER educational intervention in adolescent health care for Italian physicians: goals, content and instructional design.

Adolescent medicine is a field dedicated to helping young people grow and thrive, in relation to their particular stage of development. In Italy, adolescent medicine is not a distinct speciality, but it is practised in some services for adolescents in paediatric departments. Increasing educational opportunities in adolescent health may help to accelerate the development and dissemination of new and improved therapeutic approaches for serving youth and also attract a larger cadre of physicians. Other pediatric subspecialties, e.g. oncology, rheumatology and adolescent psychiatry, have developed successfully and may represent excellent models for adolescent medicine specialists to emulate. The Adolescent Health Study Group of the Emilia and Romagna Region (SGA-ER) was established in 2010 in an effort to generate strategies and possible solutions to improve the quality and quantity of knowledge in adolescent health care for pediatricians and GPs. Several methods and approaches have been implemented to improve physicians' skills in adolescent health care. The authors report the goals, content and instructional design of an educational course in adolescent medicine. Alliances with other adolescent health groups may provide an additional opportunity for networking, interaction and exchange of ideas amongst professionals.

Pharmacological treatment of severe, therapy-resistant asthma in children: what can we learn from where?

There is a lack of high-quality evidence on what treatment should be used in children with properly characterised severe, therapy-resistant asthma. Data have to be largely extrapolated from trials in children with mild asthma, and adults with severe asthma. Therapeutic options can be divided into medications used in lower doses for children with less severe asthma, and those used in other paediatric diseases but not for asthma (for example, methotrexate). In the first category are high-dose inhaled corticosteroids (ICS) (≤ 2,000 µg · day(-1) fluticasone equivalent), oral prednisolone, the anti-immunoglobulin (Ig)E antibody omalizumab, high-dose long-acting ß(2)-agonists, low-dose oral theophylline and intramuscular triamcinolone. If peripheral airway inflammation is thought to be a problem, the use of fine-particle ICS or low-dose oral corticosteroids may be considered. More experimental therapies include oral macrolides, cyclosporin, cytotoxic drugs such as methotrexate and azathioprine, gold salts, intravenous infusions of Ig, subcutaneous ß(2)-agonist treatment and, in those sensitised to fungi, oral antifungal therapy with itraconazole or voriconazole. Those with recurrent severe exacerbations, particularly in the context of good baseline asthma control, are particularly difficult to treat; baseline control and lung function must be optimised with the lowest possible dose of ICS, and allergen triggers and exposures minimised. The use of high-dose ICS, leukotriene receptor antagonists or both at the time of exacerbations can be considered. There is no evidence regarding which therapeutic option to recommend. Better evidence is required for all these treatment options, underscoring the need for the international and co-ordinated approach which we have previously advocated.

Serum vitamin D levels and exercise-induced bronchoconstriction in children with asthma.

Epidemiological studies have established a relationship between low levels of serum vitamin D and reduced lung function in healthy adults, and asthma onset and severity in children. However, no study has examined the relationship between vitamin D levels and exercise-induced bronchoconstriction in asthmatic children. We evaluated the relationship between 25-hydroxyvitamin D concentrations and baseline forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and change in FEV1 (ΔFEV1) after a standardised exercise challenge in 45 children with intermittent asthma. Only 11% of the children had desirable serum vitamin D levels (at least 30-40 ng·mL(-1)). A positive correlation was found between serum 25-hydroxyvitamin D and both FVC (r=0.34; p=0.037) and FEV1 (r=0.32; p=0.037). Subjects with a positive response to the exercise challenge (ΔFEV1≥10%) presented lower serum levels of 25-hydroxyvitamin D than children with a negative challenge (mean±sd 16.2±5.2 versus 23.4±7.0 ng·mL(-1), respectively; p=0.001). Our results indicate that hypovitaminosis D is frequent in asthmatic children who live in a Mediterranean country. In those children, lower levels of vitamin D are associated with reduced lung function and increased reactivity to exercise.

Assessment of problematic severe asthma in children.

Assessment of problematic severe asthma in children should be performed in a step-wise manner to ensure an optimal approach. A four-step assessment scheme is proposed. First, a full diagnostic work-up is performed to exclude other diseases which mimic asthma. Secondly, a multi-disciplinary assessment is performed to identify issues that may need attention, including comorbidities. Thirdly, the pattern of inflammation is assessed, and finally steroid responsiveness is documented. Based upon these four steps an optimal individualised treatment plan is developed. In this article the many gaps in our current knowledge in all these steps are highlighted, and recommendations for current clinical practice and future research are made. The lack of good data and the heterogeneity of problematic severe asthma still limit our ability to optimise the management on an individual basis in this small, but challenging group of patients.

Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children.

BACKGROUND: Vitamin D deficiency could be associated with the prevalence of atopic dermatitis (AD). OBJECTIVES: We carried out a study to see whether deficient/insufficient levels of vitamin D correlate with the severity of atopic skin disease. METHODS: Using the SCORAD index, we evaluated the severity of disease in 37 children (17 girls and 20 boys) aged between 8 months and 12 years with AD, consecutively enrolled in the study. Serum levels of 25-hydroxyvitamin D [25(OH)D] were determined by a chemiluminescent method. Specific IgE (sIgE) to Staphylococcus aureus enterotoxins and sIgE to Malassezia furfur were assayed by the ImmunoCAP system. anova and the Pearson correlation test were used for statistical evaluation. RESULTS: We found severe, moderate and mild AD in nine (24%), 13 (35%) and 15 (41%) children, respectively. Mean ± SD serum levels of 25(OH)D were significantly higher (P < 0·05) in patients with mild disease (36·9 ± 15·7 ng mL(-1)) compared with those with moderate (27·5 ± 8·3 ng mL(-1)) or severe AD (20·5 ± 5·9 ng mL(-1)). The prevalence of patients with sIgE to microbial antigens increased in relation to vitamin D deficiency and AD severity. CONCLUSIONS: These data suggest that vitamin D deficiency may be related to the severity of AD and advocate the need for studies evaluating the use of vitamin D as a potential treatment in patients with this disease.

A comparison between IgE and IgG4 as markers of allergy in children: an experimental trial in a model of natural antigen avoidance.

IgG4 have been hypothesized to act as blocking antibodies capable of preventing IgE-mediated effector cell triggering. This study aims to evaluate the changes in IgG4 in children during a period of natural antigen avoidance. Serum IgE and IgG4 were evaluated in a group of asthmatic children, aged between 7 and 17 years, admitted to the residential house Istituto Pio XII (Misurina, BL, Italy), located at 1,756 m, in a natural model of antigen avoidance. All the patients were skin prick test positive to at least two of the following allergens: Dermatophagoides pteronissynus, Dermatophagoides farinae, cat epithelium, timothy grass pollen and Parietaria pollen. During the 180 days of hospitalization, serum specific IgE and IgG4 were measured six times. A significant decrease (p≤0.05) in serum specific IgE to house dust mite and pollen allergens was observed; by contrast, no significant variations were shown by IgG4 and IgG4/IgE ratio. No significant relationship was found between serum specific IgE, IgG4 and IgG4/IgE ratio variations and the re-exposure to house dust mite allergens during the Christmas holidays. A positive correlation between specific IgE and specific IgG4 was observed at each considered time (T0: r=0.57, p=0.08; T1: r=0.85, p=0.001; T3: r=0.76, p=0.01). The positive correlation between specific IgE and specific IgG4, enduring throughout the entire time of study, suggests a relationship between these classes of immunoglobulins.

Nasal nitric oxide levels in healthy pre-school children.

The evaluation of nasal nitric oxide (nNO) has been proposed as a screening tool in children with clinically suspectable primary ciliary dyskinesia. Nevertheless, normal values have been reported for school-aged children. This study was designed to identify normal nNO levels in pre-school children. nNO was assessed in 300 healthy children aged between 1.5 and 7.2. Two hundred and fifty of them were unable to fulfill the guideline requirements for nNO measurement and were assessed by sampling the nasal air continuously with a constant trans-nasal aspiration flow for 30 s during tidal breathing. For those children who were able to cooperate, the average nNO concentration was calculated according to guidelines. A statistically significant relationship between nNO level and age was demonstrated in this study group of pre-school children (p < 0.001). An increase in nNO of about 100 ppb was observed in children older than 6 yr vs. those aged < 3. This study presents a description of normal nNO values in pre-school children. The effect of the age and the eventual presence of rhinitis and snoring need to be considered whenever nNO is evaluated in the clinical practice, in particular in non-cooperative children.