Diagnosis of Primary Ciliary Dyskinesia by a Targeted Next-Generation Sequencing Panel: Molecular and Clinical Findings in Italian Patients.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder that alters mucociliary clearance, with consequent chronic disease of upper and lower airways. Diagnosis of PCD is challenging, and genetic testing is hampered by the high heterogeneity of the disease, because autosomal recessive causative mutations were found in 34 different genes. In this study, we clinically and molecularly characterized a cohort of 51 Italian patients with clinical signs of PCD. A custom next-generation sequencing panel that enables the affordable and simultaneous screening of 24 PCD genes was developed for genetic analysis. After variant filtering and prioritization, the molecular diagnosis of PCD was achieved in 43% of the patients. Overall, 5 homozygous and 27 compound heterozygous mutations, 21 of which were never reported before, were identified in 11 PCD genes. The DNAH5 and DNAH11 genes were the most common cause of PCD in Italy, but some population specificities were identified. In addition, the number of unsolved cases and the identification of only a single mutation in six patients suggest further genetic heterogeneity and invoke the need of novel strategies to detect unconventional pathogenic DNA variants. Finally, despite the availability of mutation databases and in silico prediction tools helping the interpretation of variants in next-generation sequencing screenings, a comprehensive segregation analysis is required to establish the in trans inheritance and support the pathogenic role of mutations.

Serum-specific IgE and allergen immunotherapy in allergic children.

AIM: Allergen immunotherapy (AIT) is indicated in IgE-mediated respiratory allergy. Recently, it has been reported that serum-specific IgE (sIgE) levels >10 kU/l may predict AIT efficacy in adults with allergic rhinitis. The aim of the present preliminary study was to investigate whether this cut-off could also be associated with perception of effective AIT in children with allergic asthma and/or rhinitis due to house dust mites (HDM). METHODS: A total of 31 allergic children (17 males; mean age of 12.5 years) with levels of serum sIgE to HDM >10 kU/l were evaluated. Eight allergic children (five males; mean age of 13.4 years) with levels of serum sIgE to HDM <10 kU/l were considered as control. All patients were treated with sublingual immunotherapy for 3 years with HDM allergen extract. Children's perception of AIT efficacy was assessed by visual analog scale (VAS), considering both symptom severity and drug use. Responder patients were defined with >6 VAS. Severity of nasal symptoms was assessed by nasal VAS, and asthma control was evaluated by asthma control test; both were considered before and after AIT. RESULTS: All children (but one) with sIgE >10 kU/l perceived AIT efficacy, whereas only one child with sIgE <10 kU/l perceived AIT benefit (p < 0.001). There was a strong relationship between perception of AIT efficacy by VAS and serum sIgE levels (r = 0.615; p < 0.001). Also, nasal VAS and asthma control tests significantly improved only in children with sIgE >10 kU/l (p < 0.001 for both). CONCLUSION: Allergen-sIgE assessment before AIT prescription might represent a useful tool to individuate potential responders.

May T1 diabetes mellitus protect from asthma?

BACKGROUND: Type 1 diabetes mellitus (T1DM) may be associated with allergy. It was previously reported that >20% of children with T1DM had allergic rhinitis (AR), but none was asthmatic. This finding was surprising as allergic rhinitis is frequently associated with asthma and asthma prevalence is about 10% of the general paediatric population. Thus, it was hypothesized that T1DM could protect from asthma. OBJECTIVES: The aim of this preliminary study was to evaluate the pulmonary function and the response to bronchodilation testing in children, suffering from T1DM with associated AR, comparing them with a control group of children with AR alone. METHODS: Twenty children with T1DM and AR were compared with 59 children with AR alone; spirometry and bronchodilation testing were performed in all patients. RESULTS: There were no statistically significant differences in both "at baseline" and after bronchodilation testing about FVC, FEV1, and FEF25-75 values. However, changes in "post-bronchodilator" values of FEF25-75 (ΔFEF25-75) were significantly higher in children with AR alone than in children with T1DM and AR (p=0.04). CONCLUSIONS: This preliminary study could sustain the hypothesis that T1DM in children suffering also from AR might exert a protective effect of preventing the possible evolution in asthma.

Perception of bronchodilation assessed by Visual Analogue Scale in children with asthma.

BACKGROUND: Visual Analogue Scale (VAS) has been proposed as a useful tool for assessing the perception of asthma symptoms, a cornerstone in disease management. While airway flow limitation and its reversibility are thought to be a useful marker of disease severity, there are very few studies that evaluated the response to bronchodilation (BD) testing perception by VAS. To investigate whether VAS assessment of breathlessness perception could provide a useful tool to assess the response to BD testing in asthmatic children. METHODS: This cross-sectional study included a total of 150 children (96 males, mean age 11.05 years) with asthma, 50 had bronchial obstruction (i.e. FEV1 <80% of predicted). Perception of breathlessness was assessed by VAS; lung function was measured by spirometry. BD testing was performed in all children. RESULTS: In children with bronchial obstruction, VAS at baseline was 4.7 and significantly increased to 6.9 (p<0.001) after BD. In children without bronchial obstruction, VAS at baseline was 7.4, but further significantly increased to 8.4 after BD testing (p<0.01). There was a significant difference in Δ VAS between children with bronchial reversibility and children without it (p<0.0001). CONCLUSIONS: The present study demonstrates that VAS might be considered an initial tool to assess the BD response in children with asthma, mainly with overt bronchial obstruction.