Impatto del microbioma (polmonare e intestinale) sull’asma

L’asma è una delle patologie croniche più diffuse e rappresenta la malattia respiratoria cronica più frequente nell’età pediatrica. Sono sempre più numerosi gli studi volti a individuare delle strategie preventive per ridurne l’incidenza: negli ultimi decenni è stato dimostrato che esiste una “finestra” temporale che si apre già durante la vita intrauterina e nella quale vari fattori ambientali possono interagire con il substrato genetico per favorire l’insorgenza dell’asma e, più in generale, delle malattie allergiche. Negli ultimi anni è stato ampiamente studiato il ruolo del microbioma intestinale dimostrandone la capacità di modulare la risposta immunitaria. Una disbiosi intestinale in epoca precoce, con sbilanciamento della composizione del microbioma a favore di Escherichia coli e Clostridium difficile e a discapito dei Bifidobacteria, può predisporre allo sviluppo delle allergopatie. Più recentemente è stato dimostrato che esiste un microbioma anche a livello delle vie aeree inferiori, la cui composizione può essere influenzata dalle infezioni virali e che, nei soggetti asmatici, è caratterizzata dalla prevalenza del phylum Proteobacteria. Non è stato ancora dimostrato se sia possibile ridurre l’insorgenza dell’asma agendo sul microbioma, mentre è necessario tenere a mente la necessità di ridurre l’impiego degli antibiotici per limitare le interferenze sul microbioma, soprattutto nei neonati e nei lattanti

Il link asma-obesità: aspetti patogenetici, clinico-funzionali e diagnostico-terapeutici

L’asma e l’obesità sono considerate un problema primario di salute pubblica dell’età infantile, che sta assumendo proporzioni globalmente “epidemiche”. Diversi studi epidemiologici hanno chiaramente evidenziato la presenza di un’associazione tra le due patologie. Tale complessa interazione patogenetica vede coinvolti fattori genetici, di sviluppo, di funzione polmonare, immunologici e comportamentali; alcuni di essi sono ad oggi ancora poco studiati e conosciuti. Per tale motivo, non è possibile identificare un meccanismo prevalente sugli altri che sia alla base della relazione causale tra le due patologie. Il crescente interesse scientifico nei confronti dell’associazione tra asma e obesità ha contribuito a delineare diversi fenotipi di patologia presenti nelle varie epoche della vita. La caratterizzazione clinica dei soggetti asmatici obesi è presupposto fondamentale per identificare terapie mirate a raggiungere il controllo dell’asma e contemporaneamente a ridurre il peso del soggetto prevenendo le complicanze legate all’obesità

I farmaci biologici nell’asma del bambino

I farmaci biologici hanno recentemente rivoluzionato l’approccio terapeutico al paziente con asma grave. Attraverso l’inibizione di precisi target molecolari implicati nella patogenesi della malattia asmatica, questi farmaci trovano un’innovativa applicazione nell’ambito della medicina moderna che, sempre più spesso, si indirizza verso un trattamento personalizzato sulla base delle specifiche caratteristiche infiammatorie (endotipi con relativi biomarcatori) che la patologia presenta nel singolo paziente. Tra i farmaci biologici disponibili per l’età pediatrica, ad oggi omalizumab è il farmaco di scelta per la terapia aggiuntiva dell’asma grave, con significative evidenze di efficacia e sicurezza e con maggiore esperienza clinica in “real life”. Le nuove molecole, come mepolizumab, reslizumab e dupilumab, sono attualmente in fase di sperimentazione clinica per l’età pediatrica, sulla base dei risultati positivi ottenuti negli studi sulla popolazione adulta

Correlation between serum 25 (OH)-vitamin D levels and severity of atopic dermatitis in children

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

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 assessedthe 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 lungfunction (\u394FEV(1)%, \u394FEF(25-75)%) after exercising. A chemiluminescence analyser at multiple flows was used to calculate FeNO(50), J(NO) and C(alv,) which reflectlarge airways, J(NO) and alveolar concentration of NO respectively.RESULTS: Sixteen (44.4%) children presented a 06FEV(1) 65 10%, eight (22.2%) had 06FEV(1) 65 15% and nine (25%) children had a 06FEF(25-75) 65 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

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 assessedthe 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 lungfunction (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 reflectlarge 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

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 \ub1 2530.77 pg/mL and 1916.00 \ub1 2178.75 pg/mL after treatment. Patients treated with montelukast, in contrast, showed a baseline mean (SD) value of 2439.29 \ub1 2834.51 pg/mL and 1406.72 \ub1 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 \ub1 4.03% at baseline and 4.86 \ub1 5.83% after treatment. Patients treated with montelukast, in contrast, showed a percentage mean (SD) value at baseline of 4.51 \ub1 5.48% and, after treatment, of 3.06 \ub1 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

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

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

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

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.