Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP).

Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.

Correction to: Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.

In the published article [1], an error has been noticed in the author group section.

Case report: acute clinical presentation and neonatal management of primary hyperparathyroidism due to a novel CaSR mutation.

BACKGROUND: Neonatal severe primary hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis, characterized by striking hyperparathyroidism, marked hypercalcemia and hyperparathyroid bone disease. We report the case of a newborn with a novel homozygous mutation of the CaSR, treated by successful subtotal parathyroidectomy, who had an acute presentation of the disease, i.e. out-of hospital cardiorespiratory arrest. . CASE PRESENTATION: A 8-day-old female newborn was admitted to the NICU of University of Bari "Aldo Moro" (Italy) after a cardiorespiratory arrest occurred at home. Severe hypercalcemia was found and different drug therapies were employed (Furosemide, Cinacalcet and bisphosphonate), as well as hyperhydration, until subtotal parathyroidectomy, was performed at day 32. Our patient's mutation was never described before so that a strict and individualized long-term follow-up was started. CONCLUSIONS: This case of NSHPT suggests that a near-miss event, labelled as a possible case of SIDS, could also be due to severe hypercalcemia and evidentiates the difficulties of the neonatal management of NSHPT. Furthermore, the identification of the specific CaSR mutation provides the substrate for prenatal diagnosis.

Correlation between vitamin D serum levels and passive smoking exposure in children with asthma.

OBJECTIVE: To establish the relationship between vitamin D serum levels, pulmonary function, asthma control, and passive smoking exposure in children with asthma. METHODS: We studied the relationship between 25-hydroxy cholecalciferol (25[OH]D) concentrations and baseline spirometry and levels of asthma control, and the effect of parental tobacco smoke exposure in 152 white children (84 boys [55.3%]) with a mean age ± standard deviation of 9.9 ± 2.0 years (range 5-15 years) in a cross-sectional study carried out during the winter and early spring. RESULTS: Only 9.9% of our children had a sufficient serum 25(OH)D level (at least 30-40 ng/mL). A significant positive correlation was found between the force vital capacity % predicted, forced expiratory volume in the first second of expiration % predicted, and serum 25(OH)D level (r = 0.36, p < 0.001 for both). The subjects with controlled asthma had higher serum levels of 25(OH)D than children with partially controlled or noncontrolled asthma, both according to Global Initiative for Asthma parameters and the Test for the control of asthma in childhood (p = 0.011). Children with both nonsmoking parents presented significantly higher serum levels of 25(OH)D than children with both smoking parents (median, 20.5 ng/mL [interquartile range {IQR}, 16.6-24.0 ng/mL] versus median, 14.5 ng/mL [IQR, 11.1-19.1 ng/mL], respectively; p < 0.001), with intermediate values for children exposed to single maternal (median, 20.3 ng/mL [IQR, 13.0-23.2 ng/mL]) or to paternal smoking (median, 17.8 ng/mL [IQR, 14.7-22.1 ng/mL]). CONCLUSION: Our results indicated that hypovitaminosis D was frequent in children with asthma who lived in a Mediterranean country. In these children, lower levels of vitamin D were associated with reduced asthma control and passive smoking exposure.

Effect of montelukast on markers of airway remodeling in children with asthma.

BACKGROUND: Asthma is a pathology characterized by chronic inflammation and remodeling of the airways. OBJECTIVES: To evaluate the effect of montelukast treatment on markers of airway inflammation and remodeling in children with mild asthma and to evaluate if the administration of montelukast to children with mild asthma could inhibit the release of matrix metallopeptidase 9, matrix metallopeptidase 12, tissue inhibitor of metalloproteinase 1, transforming growth factor beta 1, C-peptide terminal procollagen type (PICP), and eosinophils count, which are markers of inflammation and remodeling in induced sputum. METHODS: Thirty children with mild asthma were recruited. They were randomized into two groups: group A received montelukast and as needed beta-2-agonist for 8 weeks (T0-T1), whereas group B received placebo and as needed beta-2-agonist for 8 weeks. After 2 weeks of washout (T1-T2), they were reallocated for treatment according a crossover design (T2-T3). Tests for lung function, oral exhaled nitric oxide, and hypertonic saline solution-induced sputum level were performed at T0-T1-T2-T3. RESULTS: In the placebo group, the PICP mean (standard deviation [SD]) value at baseline was 2279.42 ± 2530.77 pg/mL and 1916.00 ± 2178.75 pg/mL after treatment. Patients treated with montelukast, in contrast, showed a baseline mean (SD) value of 2439.29 ± 2834.51 pg/mL and 1406.72 ± 1508.65 pg/mL after treatment. The difference between the mean pre- and posttreatment decrease of PICP in the two groups was statistically significant (delta -690.21 pg/mL [95% confidence interval, -1220.83 to -159.5844 pg/mL]; p = 0.011). The mean (SD) percentage of the eosinophil count in the placebo group was 3.11 ± 4.03% at baseline and 4.86 ± 5.83% after treatment. Patients treated with montelukast, in contrast, showed a percentage mean (SD) value at baseline of 4.51 ± 5.48% and, after treatment, of 3.06 ± 3.29%. The difference between the mean pre- and posttreatment decrease of the percentage eosinophil count in the two groups was statistically significant (delta -2.76% [95% confidence interval, -4.65 to -0.87%]; p = 0.004). CONCLUSION: This study investigated in vivo effects of montelukast on remodeling markers. The reduction of PICP levels and eosinophil count supported the hypothesis that montelukast can modulate collagen deposition in airways and reduce eosinophilic airway inflammation. Clinical Trials database clinicaltrials.gov (NCT00875082).

Pollen-induced allergic rhinitis in 1360 Italian children: comorbidities and determinants of severity.

BACKGROUND: Pollen-induced allergic rhinoconjunctivitis (AR) is highly prevalent and rapidly evolving during childhood. General practitioners may not be fully aware of the nature and severity of symptoms experienced by patients and might underestimate the prevalence of moderate or severe disease. Thus, the relevance of early diagnosis and intervention may be overlooked. OBJECTIVES: To investigate the severity of pollen-induced AR and its determinants in Italian children referred to allergy specialists and who had never received specific immunotherapy (SIT). METHODS: Children (age 4-18 yr) affected by pollen-induced AR who had never undergone SIT were recruited between May 2009 and June 2011 in 16 pediatric outpatient clinics in 14 Italian cities. Recruited children's parents answered standardized questionnaires on atopic diseases (International Study of Allergy and Asthma in Childhood, Allergic Rhinitis and its Impact on Asthma, Global Initiative for Asthma). The children underwent skin-prick test (SPT) with several airborne allergens and six food allergens. Information on socio-demographic factors, parental history of allergic diseases, education, perinatal events, breastfeeding, nutrition and environmental exposure in early life was collected through an informatics platform shared by the whole network of clinical centers (AllergyCARD™). RESULTS: Among the 1360 recruited patients (68% males, age 10.5 ± 3.4 yr), 695 (51%) had moderate-to-severe AR, 533 (39%) asthma, and 325 (23.9%) oral allergy syndrome (OAS). Reported onset of pollen-induced AR was on average at 5.3 ± 2.8 yr, and its mean duration from onset was 5.2 ± 3.3 yr. Only 6.2% of the patients were pollen-monosensitized, and 84.9% were sensitized to ≥3 pollens. A longer AR duration was significantly associated with moderate-to-severe AR symptoms (p 0.004), asthma (p 0.030), and OAS comorbidities (p < 0.001). CONCLUSIONS: This nationwide study may raise awareness of the severity of pollen-induced AR among Italian children who have never received pollen SIT. The strong association between pollen-induced AR duration and several markers of disease severity needs replication in longitudinal studies, while suggesting that countrywide initiatives for earlier diagnosis and intervention should be planned.

Respiratory epithelial imbalances in asthma pathophysiology.

The pathophysiology of asthma is complex and involves a number of factors including atopy and bronchial hyperreactivity. A strong body of evidence suggests that structural and functional respiratory epithelial alterations play a crucial role in both development and persistence of this condition. From the onset of symptoms the airways epithelium of asthmatic patients seems to be altered and unable to repair. The interactions between the epithelium and the underlying mesenchyma, which are jointly referred to as the epithelial-mesenchymal trophic unit (EMTU), are thought to result in a self-sustaining damage of the airways and, ultimately, in a chronic inflammatory scenario. A better understanding of the relationship occurring across EMTU, environmental noxae, and factors of susceptibility to epithelial damage is likely to pave the way to future new preventive and therapeutic strategies for this condition.

Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis.

Diagnosis of primary ciliary dyskinesia (PCD) sometimes requires repeated nasal brushing to exclude secondary ciliary alterations. Our aim was to evaluate whether the use of a new method of nasal epithelial cell culture can speed PCD diagnosis in doubtful cases and to identify which are the most informative parameters by means of a multilayer artificial neural network (ANN). A cross-sectional study was performed in patients with suspected PCD. All patients underwent nasal brushing for ciliary motion analysis, ultrastructural assessment and evaluation of ciliary function after ciliogenesis in culture by ANN. 151 subjects were studied. A diagnostic suspension cell culture was obtained in 117 nasal brushings. A diagnosis of PCD was made in 36 subjects (29 of whom were children). In nine out of the 36 patients the diagnosis was made only after a second brushing, because of equivocal results of both tests at first examination. In each of these subjects diagnosis of PCD was confirmed by cell culture results. Cell culture in suspension evaluated by means of ANN allows the separation of PCD from secondary ciliary dyskinesia patients after only 5 days of culture and allows diagnosis to be reached in doubtful cases, thus avoiding the necessity of a second sample.

Evaluation of pulmonary disease using static lung volumes in primary ciliary dyskinesia.

BACKGROUND: In primary ciliary dyskinesia (PCD) lung damage is usually evaluated by high-resolution CT (HRCT). OBJECTIVE: To evaluate whether HRCT abnormalities and Pseudomonas aeruginosa infection were better predicted by spirometry or plethysmography. METHODS: A cross-sectional study performed in consecutive patients with PCD who underwent sputum culture, spirometry, plethysmography and HRCT within 48 h. Principal component analysis and soft computing were used for data evaluation. RESULTS: Fifty patients (26 children) were studied. P aeruginosa infection was found in 40% of the patients and bronchiectasis in 88%. There was a correlation between infection with P aeruginosa and extent of bronchiectasis (p=0.009; r =0.367) and air-trapping (p=0.03; r =0.315). Moreover, there was an association between infection with P aeruginosa and residual volume (RV) values >150% (p=0.04) and RV/total lung capacity (TLC) ratio >140% (p=0.001), but not between infection with P aeruginosa and forced expiratory volume in 1 s (FEV(1))<80%, or forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%))<70% or FEV(1)/FVC<70% (<80% in children). Severity of the total lung impairment on chest HRCT directly correlated with RV when expressed as per cent predicted (p=0.003; r =0.423), and RV/TLC (p<0.001; r =0.513) or when expressed as z scores (p=0.002, r =0.451 and p<0.001, r =0.536 respectively). Principal component analysis on plethysmographic but not on spirometry data allowed recognition of different severities of focal air trapping, atelectasis and extent of bronchiectasis. CONCLUSIONS: Plethysmography better predicts HRCT abnormalities than spirometry. Whether it might be a useful test to define populations of patients with PCD who should or should not have HRCT scans requires further longitudinal studies.

Nasal mucosa temperature as a marker of disease in children with allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the nasal mucosa. This study was designed to investigate the role of nasal mucosa temperature in AR. METHODS: We investigated the relationship between eosinophilic infiltration, nasal obstruction, and nasal mucosa temperature in 35 children with rhinitis aged 6-12 years. RESULTS: A significant relationship was shown between nasal temperature values and eosinophil infiltration at nasal cytology (p < 0.01). Nasal temperature was also significantly associated with nasal obstruction, assessed in terms of nasal volume (Vol [2-5 cm]; p < 0.05) and minimum cross-sectional area (p < 0.01). No significant correlation emerged between the degree of nasal obstruction and presence of eosinophils at nasal cytology (p > 0.05). CONCLUSION: These results suggest a relationship between nasal temperature and nasal mucosa inflammation and obstruction.

Exhaled breath temperature and exercise-induced bronchoconstriction in asthmatic children.

It has been hypothesized that exhaled breath temperature (EBT) is related to the degree of airway inflammation/remodeling in asthma. The purpose of this study was to evaluate the relationship between the level of airway response to exercise and EBT in a group of controlled or partly controlled asthmatic children. Fifty asthmatic children underwent measurements of EBT before and after a standardized exercise test. EBT was 32.92 ± 1.13 and 33.35 ± 0.95°C before and after exercise, respectively (P < 0.001). The % decrease in FEV(1) was significantly correlated with the increase in EBT (r = 0.44, P = 0.0013), being r = 0.49 (P < 0.005) in the children who were not receiving regular inhaled corticosteroids (ICS) and 0.37 (n.s.) in those who were. This study further supports the hypothesis that EBT can be considered a potential composite tool for monitoring asthma.

Evaluation of association between exercise-induced bronchoconstriction and childhood asthma control test questionnaire scores in children.

OBJECTIVE: Asthma control represents a major challenge in the management of asthmatic children; however, correct perception of control is poor. The aim of the study was to evaluate the association between subjective answers given to the Childhood Asthma Control Test (C-ACT) and objective evaluation of exercise-induced bronchonstriction (EIB) by standardized treadmill exercise challenge. METHODS: EIB was evaluated by standardized treadmill exercise challenge and related to C-ACT scores in 92 asthmatic children. RESULTS: Of the 92 studied children only six children had a concordance between a positive challenge test (ΔFEV1 ≥ 13%) and a positive response to the exercise-related issue of the C-ACT questionnaire (C-ACT total score ≤ 19). There was no significant association between the degree of EIB and the scores relative to the single question on exercise-related problems while a significant association was found when considering the whole questionnaire with C-ACT total score > 19 (r = -0.40, P < 0.001). The two single questions showing a significant association were those focusing on nocturnal asthma. The areas under the ROC curve (AUC) for the sum of the scores of these questions in relationship to a positive response to the exercise test was 0.74. The AUC of the C-ACT total score was 0.76 and 0.55 for the specific question on EIB related problems. CONCLUSION: The discrimination power of the C-ACT total score in relationship to EIB was moderately good, and C-ACT questionnaire was capable of correctly predicting the absence of EIB in children reporting a global score > 19. However, direct questions on EIB are associated with a high number of false positive and negative responses; better associations are found questioning on the presence on nocturnal symptoms.

Time-effect of montelukast on protection against exercise-induced bronchoconstriction.

INTRODUCTION: Montelukast has been proven to assure a protective effect against exercise-induced bronchoconstriction. AIM: To verify exactly when montelukast begins protection in asthmatic children by evaluating different time intervals between dosing and challenge. METHODS: In a double blind, placebo-controlled, three day doses, crossover study, patients were randomized to receive in sequence treatment with either a placebo or montelukast and assigned to one of seven groups that were tested 1, 2, 3, 4, 5, 6 and 8 h after drug administration, respectively. For each group, the exercise challenge was always performed at the same hour on the first and third days of treatment. RESULTS: Sixty-nine asthmatic children took part in the study. On day 3, the mean FEV(1) % fall from baseline was 25.54 (95% CI = 21.63/29.46) and 14.89 (95% CI = 11.85/17.92) for the placebo and active drug (p < 0.05), respectively. On day 1, the mean fall of FEV(1) was 28.20 (95% CI = 24.46/31.94) and 19.01 (95% CI = 15.71/22.31) for the placebo and montelukast (p < 0.05), respectively. Clinical protection was achieved in 21 (30%) and 33 (48%) subjects by montelukast on the first and third days, respectively. CONCLUSIONS: Montelukast assured protection against exercise-induced bronchoconstriction from the first through the eighth hour from the first day of treatment. However, individual susceptibility to protection was evident since some individuals were not protected at any time. We conclude that in clinical use individual responses to the drug should be carefully evaluated in the follow-up management.

Monitoring asthma control in children with allergies by soft computing of lung function and exhaled nitric oxide.

BACKGROUND: Asthma control is emphasized by new guidelines but remains poor in many children. Evaluation of control relies on subjective patient recall and may be overestimated by health-care professionals. This study assessed the value of spirometry and fractional exhaled nitric oxide (FeNO) measurements, used alone or in combination, in models developed by a machine learning approach in the objective classification of asthma control according to Global Initiative for Asthma guidelines and tested the model in a second group of children with asthma. METHODS: Fifty-three children with persistent atopic asthma underwent two to six evaluations of asthma control, including spirometry and FeNO. Soft computing evaluation was performed by means of artificial neural networks and principal component analysis. The model was then tested in a cross-sectional study in an additional 77 children with allergic asthma. RESULTS: The machine learning method was not able to distinguish different levels of control using either spirometry or FeNO values alone. However, their use in combination modeled by soft computing was able to discriminate levels of asthma control. In particular, the model is able to recognize all children with uncontrolled asthma and correctly identify 99.0% of children with totally controlled asthma. In the cross-sectional study, the model prospectively identified correctly all the uncontrolled children and 79.6% of the controlled children. CONCLUSIONS: Soft computing analysis of spirometry and FeNO allows objective categorization of asthma control status.

Vitamin D serum levels and markers of asthma control in Italian children.

OBJECTIVE: To establish the relationship between vitamin D serum levels, pulmonary function, and asthma control in children. STUDY DESIGN: We studied the relationship between 25-hydroxy cholecalciferol [25(OH)D] concentrations and baseline spirometry and levels of asthma control, assessed according to Global Initiative for Asthma guidelines and the Childhood Asthma Control Test, in 75 children with asthma (age range 5-11 years; 43 males) in a cross-sectional study carried out during the winter and early spring. RESULTS: Only 9.4% of our children had a sufficient serum 25(OH)D (at least 30 to 40 ng/mL). A significant positive correlation was found between forced vital capacity percent predicted and serum 25(OH)D (r = 0.25, P = .040). This was true also for forced expiratory volume in 1 second, even though it was not statistically significant (r = 0.16, P = .157). Subjects with well-controlled asthma had higher serum levels of 25(OH)D than children with partially controlled or non-controlled asthma, with values of (median [Q1; Q3]) 22.2 (16.3; 25.4), 17.8 (11.8; 22.1) and 18.1 (15.0; 18.5), respectively (P = .023). Furthermore, a positive correlation was found between 25(OH)D and the Childhood Asthma Control Test (r = 0.28; P = .011). CONCLUSIONS: Our results indicate that hypovitaminosis D is frequent in children with asthma living in a Mediterranean country. In those children, lower levels of vitamin D are associated with reduced asthma control.