ARIA-ITALY multidisciplinary consensus on nasal polyposis and biological treatments.

In the recent years, it was recognized that type-2 inflammation links many forms of nasal polyposis with severe asthma. Thus, some biological drugs developed for severe asthma appeared to exert an effect on nasal polyposis. So far, there are several trials supporting this concept; therefore, some monoclonal antibodies for severe asthma were assessed also in polyposis, with promising results. Since different specialists are involved in the management of nasal polyposis (eg, pulmonologists, ENT, allergists), it was felt that an educational and informative document was needed to better identify the indications of biologicals in nasal polyposis. We collected the main Italian Scientific Societies, and prepared (under the Allergic Rhinitis and its Impact on Asthma, ARIA) a document endorsed by all Societies, to provide a provisional statement for the future use of monoclonal antibodies as a medical treatment for polyposis. It is the first nationwide endorsed document on this aspect. The current pathogenic knowledge and the experimental evidence are herein reviewed, and some suggestions for a correct prescription and follow-up are provided.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Inter-society consensus for the use of inhaled corticosteroids in infants, children and adolescents with airway diseases.

BACKGROUND: In 2019, a multidisciplinary panel of experts from eight Italian scientific paediatric societies developed a consensus document for the use of inhaled corticosteroids in the management and prevention of the most common paediatric airways disorders. The aim is to provide healthcare providers with a multidisciplinary document including indications useful in the clinical practice. The consensus document was intended to be addressed to paediatricians who work in the Paediatric Divisions, the Primary Care Services and the Emergency Departments, as well as to Residents or PhD students, paediatric nurses and specialists or consultants in paediatric pulmonology, allergy, infectious diseases, and ear, nose, and throat medicine. METHODS: Clinical questions identifying Population, Intervention(s), Comparison and Outcome(s) were addressed by methodologists and a general agreement on the topics and the strength of the recommendations (according to the GRADE system) was obtained following the Delphi method. The literature selection included secondary sources such as evidence-based guidelines and systematic reviews and was integrated with primary studies subsequently published. RESULTS: The expert panel provided a number of recommendations on the use of inhaled corticosteroids in preschool wheezing, bronchial asthma, allergic and non-allergic rhinitis, acute and chronic rhinosinusitis, adenoid hypertrophy, laryngitis and laryngospasm. CONCLUSIONS: We provided a multidisciplinary update on the current recommendations for the management and prevention of the most common paediatric airways disorders requiring inhaled corticosteroids, in order to share useful indications, identify gaps in knowledge and drive future research.

Inhaled corticosteroids use in childhood respiratory diseases: an italian survey on pediatricians' prescription habits.

BACKGROUND: A national consensus document on inhaled corticosteroids (ICS) use in childhood, produced by the main Italian pediatric scientific societies, has been recently released. The aim of this study was to gather information on the current pediatricians' ICS prescription habits in Italy for the management of the most common pediatric respiratory diseases, namely allergic rhinitis (AR), asthma, preschool wheezing and laryngitis. METHODS: From the 1st October 2018 to the 31st January 2019 a link to an online questionnaire was sent monthly through a newsletter to the members of the Italian Society of Pediatrics. The questionnaire included 18 items on ICS use in the most common pediatric respiratory diseases. Data collection and reporting was based on STROBE Statement Checklist for cross-sectional studies. RESULTS: One thousand-two questionnaires were returned from primary care pediatricians (39.1%), hospital pediatricians (38.7%), private practicers (16.4%), university pediatricians (3.1%) and Pediatrics residents (2.7%). We found a good adherence to the international guidelines on AR, with prevalent use of oral antihistamine (60.6%) in the secretive phenotype and nasal ICS in the obstructive phenotype (64.8%). In asthma exacerbations ICS are not used in 53.4% of cases, but they are used at high dose in 27.9% and at low dose in 18.7% of cases. In intermittent asthma, ICS are not chosen as a daily controller therapy in 54.1% of cases, while they are chosen as a low dose daily therapy in 44.5% of cases (high dose in 1.4%). In children with persistent asthma, ICS are chosen as a daily low dose therapy in 67.4% of cases and as a daily high dose therapy in 31%. In the management of preschool wheezing, when a long-term treatment is needed, ICS are chosen both alone and in association with antileukotrienes in 71.4% of cases. Children affected by recurrent asthma exacerbations and wheezing are closely followed up, in particular by their primary care pediatricians. The preference for certain molecules in the treatment of different respiratory diseases also emerged. CONCLUSIONS: Pediatricians' ICS prescription habits in Italy should be improved, especially in the management of asthma. Future surveys on a more numerous sample will be useful to analyze differences in prescription habits on the basis of pediatricians' work settings and geographical distribution.

Asthma in children and adolescents: the ControL'Asma project.

The control of asthma is the objective of asthma management. However, it is difficult to obtain in clinical practice. The Italian Society of Allergy and Clinical Immunology promoted the nationwide project "ControL'Asma" to investigate the real situation in a group of children and adolescents with asthma. The preliminary outcomes demonstrated that many asthmatic subjects do not achieve adequate asthma control. Moreover, asthma in Italian children and adolescents was usually more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled and partly controlled asthma affected about the half of subjects. However, this project suggested that the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.

Indoor Air Quality Levels in Schools: Role of Student Activities and No Activities.

This work describes a methodology for the definition of indoor air quality monitoring plans in schools and above all to improve the knowledge and evaluation of the indoor concentration levels of some chemical pollutants. The aim is to guide interventions to improve the health of students and exposed staff connected with the activities carried out there. The proposed methodology is based on the simultaneous study of chemical (indoor/outdoor PM2.5, NO2, CO2) and physical (temperature, humidity) parameters by means of automatic analyzers coupled with gaseous compounds (benzene, toluene, ethylbenzene, xylenes, formaldehyde and NO2) sampled by denuders. The important novelty is that all the data were collected daily in two different situations, i.e., during school activities and no-school activities, allowing us to evaluate the exposure of each student or person. The different behaviors of all the measured pollutants during the two different situations are reported and commented on. Finally, a statistical approach will show how the investigated compounds are distributed around the two components of combustion processes and photochemical reactions.

Overrating Classifier Performance in ROC Analysis in the Absence of a Test Set: Evidence from Simulation and Italian CARATkids Validation.

BACKGROUND: The use of receiver operating characteristic curves, or "ROC analysis," has become quite common in biomedical research to support decisions. However, sensitivity, specificity, and misclassification rates are still often estimated using the training sample, overlooking the risk of overrating the test performance. METHODS: A simulation study was performed to highlight the inferential implications of splitting (or not) the dataset into training and test set. The normality assumption was made for the classifier given the disease status, and the Youden's criterion considered for the detection of the optimal cutoff. Then, an ROC analysis with sample split was applied to assess the discriminant validity of the Italian version of the Control of Allergic Rhinitis and Asthma Test (CARATkids) questionnaire for children with asthma and rhinitis, for which recent studies may have reported liberal performance estimates. RESULTS: The simulation study showed that both single split and cross-validation (CV) provided unbiased estimators of sensitivity, specificity, and misclassification rate, therefore allowing computation of confidence intervals. For the Italian CARATkids questionnaire, the misclassification rate estimated by fivefold CV was 0.22, with 95% confidence interval 0.14 to 0.30, indicating an acceptable discriminant validity. CONCLUSIONS: Splitting into training and test set avoids overrating the test performance in ROC analysis. Validated through this method, the Italian CARATkids is valid for assessing disease control in children with asthma and rhinitis.

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.

Guideline on management of the acute asthma attack in children by Italian Society of Pediatrics.

BACKGROUND: Acute asthma attack is a frequent condition in children. It is one of the most common reasons for emergency department (ED) visit and hospitalization. Appropriate care is fundamental, considering both the high prevalence of asthma in children, and its life-threatening risks. Italian Society of Pediatrics recently issued a guideline on the management of acute asthma attack in children over age 2, in ambulatory and emergency department settings. METHODS: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was adopted. A literature search was performed using the Cochrane Library and Medline/PubMed databases, retrieving studies in English or Italian and including children over age 2 year. RESULTS: Inhaled ß2 agonists are the first line drugs for acute asthma attack in children. Ipratropium bromide should be added in moderate/severe attacks. Early use of systemic steroids is associated with reduced risk of ED visits and hospitalization. High doses of inhaled steroids should not replace systemic steroids. Aminophylline use should be avoided in mild/moderate attacks. Weak evidence supports its use in life-threatening attacks. Epinephrine should not be used in the treatment of acute asthma for its lower cost / benefit ratio, compared to ß2 agonists. Intravenous magnesium solphate could be used in children with severe attacks and/or forced expiratory volume1 (FEV1) lower than 60% predicted, unresponsive to initial inhaled therapy. Heliox could be administered in life-threatening attacks. Leukotriene receptor antagonists are not recommended. CONCLUSIONS: This Guideline is expected to be a useful resource in managing acute asthma attacks in children over age 2.

Effects of inhaled hypertonic (7%) saline on lung function test in preschool children with cystic fibrosis: results of a crossover, randomized clinical trial.

BACKGROUND: This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. METHODS: Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0.9% sodium chloride) twice a day. After a 16 weeks period, therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments. Monitoring visits, spirometry (COSMED Quark PFT4 ergo) and Rint were scheduled at 0,4,16,20,32 weeks. At T0, spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy. Salbutamol (400 mcg) was administered before the drug at each visit. RESULTS: After a 16-weeks treatment with HS an improvement of FVC (p = 0.02) and a favorable trend of FEV1 were registered. A worsening of FEV1 (p < 0.0001) and of FEF25-75 (p = 0.019) were found in NS group. No differences were found in expiratory and inspiratory Rint in both groups. No serious adverse events occurred. CONCLUSIONS: Seven percent hypertonic saline therapy proved to be a useful and safe treatment in young CF children with clinically stable conditions. TRIAL REGISTRATION: ISRCTN12345678 .

Clinical practice recommendations for allergen-specific immunotherapy in children: the Italian consensus report.

Allergen-specific immunotherapy (AIT) is currently recognized as a clinically effective treatment for allergic diseases, with a unique disease-modifying effect. AIT was introduced in clinical practice one century ago, and performed in the early years with allergenic extracts of poor quality and definition. After the mechanism of allergic reaction were recognized, the practice of AIT was refined, leading to remarkable improvement in the efficacy and safety profile of the treatment. Currently AIT is accepted and routinely prescribed worldwide for respiratory allergies and hymenoptera venom allergy. Both the subcutaneous (SCIT) and sublingual (SLIT) routes of administration are used in the pediatric population.AIT is recommended in allergic rhinitis/conjunctivitis with/without allergic asthma, with an evidence of specific IgE-sensitization towards clinically relevant inhalant allergens. Long-term studies provided evidence that AIT can also prevent the onset of asthma and of new sensitizations. The favorable response to AIT is strictly linked to adherence to treatment, that lasts 3-5 years. Therefore, several factors should be carefully evaluated before starting this intervention, including the severity of symptoms, pharmacotherapy requirements and children and caregivers' preference and compliance.In recent years, there have been increasing interest in the role of AIT for the treatment of IgE-associated food allergy and extrinsic atopic dermatitis. A growing body of evidence shows that oral immunotherapy represents a promising treatment option for IgE-associated food allergy. On the contrary, there are still controversies on the effectiveness of AIT for patients with atopic dermatitis.This consensus document was promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP) to provide evidence-based recommendations on AIT in order to implement and optimize current prescription practices of this treatment for allergic children.

Management of acute respiratory diseases in the pediatric population: the role of oral corticosteroids.

Respiratory diseases account for about 25% of all pediatric consultations, and 10% of these are for asthma. The other main pediatric respiratory diseases, in terms of incidence, are bronchiolitis, acute bronchitis and respiratory infections. Oral corticosteroids, in particular prednisolone, are often used to treat acute respiratory diseases given their anti-inflammatory effects. However, the efficacy of treatment with oral corticosteroids differs among the various types of pediatric respiratory diseases. Notably, also the adverse effects of corticosteroid treatment can differ depending on dosage, duration of treatment and type of corticosteroid administered - a case in point being growth retardation in long-course treatment. A large body of data has accumulated on this topic. In this article, we have reviewed the data and guidelines related to the role of oral corticosteroids in the treatment and management of pediatric bronchiolitis, wheezing, asthma and croup in the attempt to provide guidance for physicians. Also included is a section on the management of acute respiratory failure in children.

Beyond the "Choosing wisely": a possible attempt.

Since the fundamental principles of the medical profession were clearly defined in a physician charter in 2002, special considerations have been expressed about the adequate distribution of health care resources taking in account the individual patient needs to optimize the health care service. The correct application of procedures represents a key point in order to reach the appropriateness of care, that means to avoid unnecessary or inappropriate procedures as well as the underutilization of the necessary procedures. In this context, the Choosing wisely campaign have been widely used and disclosed and even the Italian Society of Pediatric Allergology and Immunology - SIAIP has been working to make recommendations in order to ensure the appropriateness of care in the field of allergy and optimize the use of health care resources.

Prevalence and risk factors for atopic disease in a population of preschool children in Rome: Challenges to early intervention.

BACKGROUND: Allergic diseases are complex identities determined by an interplay of genetic and environmental factors, resulting in the clinical manifestation of the disease. So far in Italy, updated data about the prevalence and risk factors of respiratory and allergic diseases in preschool children are not available. METHODS: Children aged 3-5 years, attending four different nursery schools in an urban district of the city of Rome. A standardized questionnaire developed under the SIDRIA-2 protocol was administered to the parents of the children for the assessment of the potential risk factors and the outcomes. RESULTS: A total of 494 children were enrolled in the study; 289 of them (60.3%) performed a skin prick test (SPT). In the 12 months preceding the interviews, 15% of children experienced at least one episode of wheezing, 5.5% of allergic rhinitis, 11% of children had a doctor diagnosis of asthma, 12% of children who underwent the SPT were positive to at least one of the tested allergens, being diagnosed as atopic. The univariate analysis for the health outcomes of the study shows that asthma was positively associated with daycare attendance, mother's history of atopy, siblings' history of atopy, recurrent siblings' bronchitis, and dermatitis. Atopy was positively associated with mother's history of atopy and dermatitis, whereas there is a borderline protective association with recurrent siblings' bronchitis. CONCLUSIONS: This study represents a first comprehensive epidemiological evaluation of prevalence of respiratory and allergic diseases in children aged 3-5 years in the city of Rome and an updating of the evolution of allergic diseases.

Primary school children often underestimate their nasal obstruction.

BACKGROUND: No consensus has ever been reached about the correlation between nasal resistance and the subjective sensation of nasal patency. The aim of the present study was to better de ne whether primary school and secondary school aged children correctly estimate their nasal obstruction. MATERIALS AND METHODS: Two hundred eighty four children (168 males and 116 female) aged between 6 and 14 years (9.5+2.9 years) affected by Pediatric Allergic Rhinitis underwent Rhinomanometry and they were considered as correctly estimating their nasal obstruction when the grade of nasal patency corresponded to the severity of the NOSE score, overestimating when the grade of nasal patency was <1 when compared to the severity of the score, underestimating when the grade of nasal patency was >1 when compared to the severity of the score. RESULTS: Correlation between NOSE score and nasal patency was statistically significant (r -0.74; p<0.001). Children between 6 and 9 years of age underestimate (43.7%) and children >12 overestimate (34.7%) their symptoms more frequently than children among other age ranges (p<0.001). CONCLUSION: Although NOSE score approximately allow to quantify nasal obstruction, in children, especially between 6 and 9 years of age, an objective measurement of nasal patency should be performed to better define the therapeutic approach.

Sublingual immunotherapy in children and its potential beneficial collateral effect on respiratory tract infections.

Although directed to the control of allergic symptoms, a possible effect of sublingual immunotherapy (SLIT) on susceptibility to infections has been hypothesized. Two hundred sixty-five children aged between 3 and 4 years of age affected by allergic rhinitis completed a 6 year prospective case-control study. One hundred forty-three children after 2 years of SLIT reported a lower prevalence of respiratory tract infections when compared to children not undergoing SLIT.

Intranasal budesonide in children affected by persistent allergic rhinitis and its effect on nasal patency and Nasal Obstruction Symptom Evaluation (NOSE) score.

BACKGROUND: Intranasal steroids are recognized as an effective treatment for allergic rhinitis (AR) although their effect on nasal patency has never been evaluated with an objective instrument such as anterior rhinomanometry in children. Moreover this effect has been widely assessed with total Nasal Symptom Scores (NSS) including all symptoms of allergic rhinitis and not with scores specifically focused on nasal obstruction such as the Nasal Obstruction Symptom Evaluation score (NOSE). MATERIALS AND METHODS: Sixty children (42 males and 18 female) aged 6-10 years, affected by persistent AR, were randomized and divided in two groups of 30 children to be included in an unblinded trial: one group treated with intranasal budesonide and isotonic nasal saline for 2 weeks and the other group treated only with isotonic nasal saline for 2 weeks. Each child underwent rhinomanometry and completed the NSS and the NOSE scores before and after treatment. RESULTS: At the baseline nasal patency and NSS total score, NOSE total scores were correlated (r=-0.29, p<0.001; r=-60, p<0.001). After 2 weeks of treatment improvements in nasal patency, NSS and NOSE were seen (Δ NSS 4.13 ± 1.38 vs 1.33 ± 1.93, p<0.001; Δ NOSE 34 ± 17.97 vs 9 ± 18.21, p<0.001; Δ nasal patency -26.13 ± 25.25 vs -11.83 ± 11.31, p<0.001). Correlations were found between rhinitis duration and Δ nasal patency and Δ NOSE (r=-0.84, p<0.001; r=0.43, p<0.01). CONCLUSION: Intranasal budesonide is effective in increasing nasal patency in children. Moreover the NOSE score was strongly correlated with nasal flow and, hence, this score should be regarded as a valid and reliable instrument in children.

Nutritional management and follow up of infants and children with food allergy: Italian Society of Pediatric Nutrition/Italian Society of Pediatric Allergy and Immunology Task Force Position Statement.

Although the guidelines on the diagnosis and treatment of food allergy recognize the role of nutrition, there is few literature on the practical issues concerning the nutritional management of children with food allergies. This Consensus Position Statement focuses on the nutritional management and follow-up of infants and children with food allergy.It provides practical advices for the management of children on exclusion diet and it represents an evidence-based consensus on nutritional intervention and follow-up of infants and children with food allergy. Children with food allergies have poor growth compared to non-affected subjects directly proportional to the quantity of foods excluded and the duration of the diet. Nutritional intervention, if properly planned and properly monitored, has proven to be an effective mean to substantiate a recovery in growth. Nutritional intervention depends on the subject's nutritional status at the time of the diagnosis. The assessment of the nutritional status of children with food allergies should follow a diagnostic pathway that involves a series of successive steps, beginning from the collection of a detailed diet-history. It is essential that children following an exclusion diet are followed up regularly. The periodic re-evaluation of the child is needed to assess the nutritional needs, changing with the age, and the compliance to the diet. The follow- up plan should be established on the basis of the age of the child and following the growth pattern.

Duration of a cow-milk exclusion diet worsens parents' perception of quality of life in children with food allergies.

BACKGROUND: In Italy, rigorous studies obtained with specific and validated questionnaires that explore the impact of exclusion diets on health-related quality of life (HRQoL) in children with food allergies are lacking. In this cross-sectional study, we wished to validate the Italian version of a disease-specific quality of life questionnaire, and assess the impact of exclusion diets on the HRQoL in a cohort of Italian children with IgE-mediated food allergies. METHODS: Children on an exclusion diet for ≥1 food were enrolled consecutively, and their parents completed the validated Italian version of the Food Allergy Quality of Life Questionnaire-Parent Form (FAQLQ-PF) and Food Allergy Independent Measure (FAIM). RESULTS: Ninety-six parents of children aged 0-12 years answered the FAQLQ-PF. The validity of the construct of the questionnaire was assessed by correlation between the FAQLQ-PF and FAIM-PF (r = 0.85). The Italian version of the FAQLQ had good internal consistency (Cronbach's α >0.70). Factors that mainly influenced the HRQoL were older age, severity of food allergy, and the duration of the cow milk-exclusion diet. CONCLUSIONS: The FAQLQ-PF, validated in Italian, is a reliable instrument. Worse QoL scores were observed among older children, those with severe systemic reactions, and those with a prolonged cow milk-free diet. It is very important to consider the QoL assessment as an integral part of food-allergy management. These results emphasize the need to administer exclusion diets only for the necessary time and the importance of assessment of the HRQoL in these patients.