Treatment of IgE-mediated food allergy involves avoiding the food causing the allergic reaction. In association, an action plan for allergic reactions is indicated, sometimes including self-injectable adrenaline. In addition to these dietary and medical implications, there are two equally important ones: nutritional and psychosocial. From a nutritional point of view, it is known that children suffering from food allergy have a growth delay in height and weight compared to their non-allergic peers. Specifically, this condition is directly related to the specific food excluded from the diet, the number of foods excluded and the duration of the elimination diet. From a psychosocial point of view, the child often cannot eat the foods other guests eat. Children with food allergy may perceive an aura of parental anxiety around their mealtime and may be afraid that what they eat could have harmful consequences for their health. Furthermore, children’s and their parents’ quality of life appears to be affected. The need to manage the allergy and the nutritional and psychosocial problems positions the pediatric nutritionist and the child neuropsychiatrist as support figures for the pediatric allergist in managing the child with food allergy.

Allergen-specific immunotherapy (AIT) was born in 1911 and great progress has been made over the last 110 years, from the invention of subcutaneous and sublingual administration to new strategies. It can be applied in respiratory allergies, such as rhinoconjunctivitis and asthma, with even long-term effects in the use of drugs, symptoms, hospitalizations and prognosis. Many protocols are described in venom allergy, but it is not yet established which is the best and further studies are needed to guide personalized treatment. The use in food allergies is growing, it determines immunological changes in a long-term process, with results that are different between adulthood and pediatric age. Sensitization to allergenic molecules is a gradual process that starts from one or a few molecules, often asymptomatic, to a polymolecular sensitization through a “molecular spreading”. New strategies in AIT have been proposed in recent years, such as the use of adjuvants and modifications of allergens, while biomarkers that allow optimization of treatment with AIT are continually being studied.

BACKGROUND:Primary ciliary dyskinesia (PCD) represents a group of rare hereditary disorders characterised by deficient ciliary airway clearance that can be associated with laterality defects. We aimed to describe the underlying gene defects, geographical differences in genotypes and their relationship to diagnostic findings and clinical phenotypes. METHODS:Genetic variants and clinical findings (age, sex, body mass index, laterality defects, forced expiratory volume in 1 s (FEV1)) were collected from 19 countries using the European Reference Network's ERN-LUNG international PCD Registry. Genetic data were evaluated according to American College of Medical Genetics and Genomics guidelines. We assessed regional distribution of implicated genes and genetic variants as well as genotype correlations with laterality defects and FEV1. RESULTS:The study included 1236 individuals carrying 908 distinct pathogenic DNA variants in 46 PCD genes. We found considerable variation in the distribution of PCD genotypes across countries due to the presence of distinct founder variants. The prevalence of PCD genotypes associated with pathognomonic ultrastructural defects (mean 72%, range 47-100%) and laterality defects (mean 42%, range 28-69%) varied widely among countries. The prevalence of laterality defects was significantly lower in PCD individuals without pathognomonic ciliary ultrastructure defects (18%). The PCD cohort had a reduced median FEV1 z-score (-1.66). Median FEV1 z-scores were significantly lower in CCNO (-3.26), CCDC39 (-2.49) and CCDC40 (-2.96) variant groups, while the FEV1 z-score reductions were significantly milder in DNAH11 (-0.83) and ODAD1 (-0.85) variant groups compared to the whole PCD cohort. CONCLUSION:This unprecedented multinational dataset of DNA variants and information on their distribution across countries facilitates interpretation of the genetic epidemiology of PCD and indicates that the genetic variant can predict diagnostic and phenotypic features such as the course of lung function.

The Hyper IgE Syndromes are rare primary immunodeficiencies characterized by eczema, recurrent skin and respiratory infections and elevated serum IgE levels. Nowadays a geneticmolecular characterization is possible and allows the distinction in various monogenic pathologies, which share some clinical characteristics but also important differences. In addition to long-known STAT3 and DOCK8 gene mutations, in fact, also ZNF341, CARD11, ERBB2IP, IL6R and IL6ST genes mutations can cause the disease. The main clinical manifestations are represented by newborn rash, eczema similar to atopic dermatitis, bacterial and viral skin infections, cold abscesses, respiratory infections with possible pulmonary complications, allergies, gastrointestinal manifestations, malignancies and connective tissue abnormalities. Diagnosis is still a challenge because, especially in the early stages of life, it is difficult to distinguish from other pathologies characterized by eczema and high IgE, such as atopic dermatitis. Several scores and diagnostic pathways have been developed, but it is essential to seek a genetic diagnosis. Treatment is based on prevention and early treatment of infections, meticulous skincare, intravenous immunoglobulins and HSCT, which, in some HIES subtypes, can modify the prognosis. Prognosis is related to the affected gene, but also to early diagnosis, timely treatment of infections and early HSCT.

Legumes are an inexpensive and essential protein source worldwide. The most consumed legumes include peanuts, soybeans, lentils, lupines, peas, common bean and chickpeas. In addition, the food industry is growing interested in expanding the use of legumes to partially replace or substitute cereals. Legumes were described to cause IgE-mediated allergies, and their growing use may also increase the incidence of allergy. The epidemiology of legume allergy varies by region; peanuts and soybeans are the legumes most involved in food allergies in Western countries, whereas lentils, peas, and chickpeas are reported as culprit allergens mainly in the Mediterranean area and India. This review, edited by the Italian Society of Pediatric Allergology and Immunology, summarizes the scientific literature on legume allergy in children and proposes a diagnostic workup and therapeutic approach.

BACKGROUND:International guidelines disagree on how best to diagnose primary ciliary dyskinesia (PCD), not least because many tests rely on pattern recognition. We hypothesized that quantitative distribution of ciliary ultrastructural and motion abnormalities would detect most frequent PCD-causing groups of genes by soft computing analysis.METHODS:Archived data on transmission electron microscopy and high-speed video analysis from 212 PCD patients were re-examined to quantitate distribution of ultrastructural (10 parameters) and functional ciliary features (4 beat pattern and 2 frequency parameters). The correlation between ultrastructural and motion features was evaluated by blinded clustering analysis of the first two principal components, obtained from ultrastructural variables for each patient. Soft computing was applied to ultrastructure to predict ciliary beat frequency (CBF) and motion patterns by a regression model. Another model classified the patients into the five most frequent PCD-causing gene groups, from their ultrastructure, CBF and beat patterns.RESULTS:The patients were subdivided into six clusters with similar values to homologous ultrastructural phenotype, motion patterns, and CBF, except for clusters 1 and 4, attributable to normal ultrastructure. The regression model confirmed the ability to predict functional ciliary features from ultrastructural parameters. The genetic classification model identified most of the different groups of genes, starting from all quantitative parameters.CONCLUSIONS:Applying soft computing methodologies to PCD diagnostic tests optimizes their value by moving from pattern recognition to quantification. The approach may also be useful to evaluate atypical PCD, and novel genetic abnormalities of unclear disease-producing potential in the future.

The Hyper IgE Syndromes are rare primary immunodeficiencies characterized by eczema, recurrent skin and respiratory infections and elevated serum IgE levels. Nowadays a genetic-molecular characterization is possible and allows the distinction in various monogenic pathologies, which share some clinical characteristics but also important differences. In addition to long-known STAT3 and DOCK8 gene mutations, in fact, also ZNF341, CARD11, ERBB2IP, IL6R and IL6ST genes mutations can cause the disease. The main clinical manifestations are represented by newborn rash, eczema similar to atopic dermatitis, bacterial and viral skin infections, cold abscesses, respiratory infections with possible pulmonary complications, allergies, gastrointestinal manifestations, malignancies and connective tissue abnormalities. Diagnosis is still a challenge because, especially in the early stages of life, it is difficult to distinguish from other pathologies characterized by eczema and high IgE, such as atopic dermatitis. Several scores and diagnostic pathways have been developed, but it is essential to seek a genetic diagnosis. Treatment is based on prevention and early treatment of infections, meticulous skincare, intravenous immunoglobulins and HSCT, which, in some HIES subtypes, can modify the prognosis. Prognosis is related to the affected gene, but also to early diagnosis, timely treatment of infections and early HSCT.

Fish is one of the “big nine” foods triggering allergic reactions. For this reason, fish allergens must be accurately specified on food labels. Fish allergy affects less than 1% of the world population, but a higher prevalence is observed in pediatric cohorts, up to 7%. Parvalbumin is the main fish allergen found in the muscles. In childhood, sensitization to fish allergens occurs most frequently through the ingestion of fish, rarely transcutaneously or by inhalation. Fish allergy symptoms usually appear within two hours of the allergen contact. The diagnosis begins with the collection of the history. If it is suggestive of fish allergy, prick tests or the measurement of serum-specific IgE should be performed to confirm the suspicion. The oral food challenge is the gold standard for the diagnosis. It is not recommended in case of a severe allergic reaction. It is important to make a differential diagnosis with anisakiasis or scombroid poisoning, which have overlapping clinical features but differ in pathogenesis. Traditionally, managing fish allergy involves avoiding the triggering species (sometimes all bony fish species) and requires an action plan for accidental exposures. The present review will analyze IgE- and non-IgE-mediated fish allergy in children from epidemiology, pathogenesis to clinical features. Moreover, clinical management will be addressed with a particular focus on potential nutritional deficiencies.

Among preterm infants, the risk of developing asthma is a matter of debate. This review discusses the state of the art of poorly understood prematurity-associated asthma. Impaired pulmonary function is common in children born prematurely. Preterm infants are prone to developing viral respiratory tract infections, bronchiolitis in the first year of life, and recurrent viral wheezing in preschool age. All of these conditions may precede asthma development. We also discuss the role of both atopic sensitization and intestinal microbiome and, consequently, immune maturation. Diet and pollution have been considered to better understand how prematurity could be associated with asthma. Understanding the effect of factors involved in asthma onset may pave the way to improve the prediction of this asthma phenotype.

Few data are currently available on the effects of aeroallergens in triggering respiratory symptoms in children. To evaluate the potential effects of daily outdoor aeroallergens loads on childhood admissions, in this case-crossover study, we analyzed data from 85 children hospitalized at the University Hospital of Pisa, Italy, for asthma or asthma-like symptoms without respiratory infection, between 2010 and 2019. Data were linked to outdoor allergens, temperature, nitrogen dioxide, and relative humidity observed during the same period. A 10-grains/m3 increase in the total aeroallergen concentration was associated with an increased risk of admission at lag 0 (OR = 1.054, 95% CI: 1.011–1.098), with a smaller effect at lag 1 (OR = 1.037, 95% CI: 1.008–1.067) and lag 2 (OR = 1.021, 95% CI: 1.003–1.039). Trends to larger effects were observed in children with sensitization to one or more aeroallergens (OR = 1.085, 95% CI: 1.004–1.173 at lag 0), in males (OR = 1.069, 95% CI: 1.009–1.132 at lag 0) and in older children (OR = 1.065, 95% CI: 1.007–1.127 at lag 0). Our study shows an association between increased outdoor allergens loads and asthma or asthma-like symptoms in children up to at least two days prior to hospitalization, suggesting that tracking aeroallergen counts may be useful to improve the management of respiratory allergic diseases.

BACKGROUND: We hypothesized that differences in nasal nitric oxide (nNO) and fractional exhaled nitric oxide (FENO) relate to prognosis in primary ciliary dyskinesia (PCD). RESEARCH QUESTION: What is the relationship between baseline values and longitudinal evolution of nNO and FENO and ultrastructure, genotype, and respiratory infections in PCD? STUDY DESIGN AND METHODS: Prospective, longitudinal, single-center study in adults and children evaluated biannually for up to 10 years. We compared cross-sectional and longi-tudinal values of nNO and FENO in ultrastructural (inner dynein arm [IDA] and microtubular disorganization [MTD]) and genetic (CCDC39 and CCDC40) groups known to have worse pulmonary function with patients within the ultrastructural and genetic groups with a better prognosis. Linear mixed-effects models were used to evaluate longitudinal associations. RESULTS: One hundred forty-one patients with PCD underwent 1,014 visits. At enrollment, no differences were found in children in nNO or FENO between the IDA and MTD group and the other ultrastructural groups. In adults, nNO (P = .038) and FENO (P = .032) were significantly lower in the IDA and MTD group than in all other combined ultrastructural groups. FENO values were significantly lower in the CCDC39 and CCDC40 group than in the DNAH5 and DNAH11 combined genotype group (P = .033) and in all other genotypes (P = .032). The IDA and MTD group showed a significant decline in nNO with age (P < .01) compared with other ultrastructural groups who showed stable levels. The CCDC39 and CCDC40 group showed the steepest decline in nNO over time (P < .01) compared with all other genotypes. A higher nNO was associated with lower likelihood of any positive bacterial isolate from the lower respiratory tract (P = .008). Changes in FENO over time did not differ between structural groups or genotypes.

Rationale: Genotype-phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. Objectives: To investigate the evolution of static lung volumes with ultrastructural defects, gene mutations, body mass index, and specific infections in PCD. Methods: Prospective, longitudinal, single-center study in children and adults evaluated twice yearly for up to 10 years. Linear mixed-effects models were used to assess associations between ciliary morphology, genetic mutations, and clinical features. Results: A total of 122 patients had 1,096 visits. At enrollment, almost all spirometric and, especially in adults, plethysmographic parameters were significantly worse in absent inner dynein arms (IDAs), central apparatus (CA) defects, and microtubular disorganization (MTD) (IDA/CA/MTD) compared with patients with normal electron microscopy (EM) results. The mean trend increase with time for residual volume (RV) was significantly higher in IDA/CA/MTD group compared with groups with outer dynein arm defect and normal EM results. The mean trend of RV/total lung capacity in the IDA/CA/MTD group was significantly worse than in all other groups. The steepest rise in lung volumes was in CCDC39 and CCDC40, whereas hyperinflation increased less in DNAH5 and DNAH11 groups. RV/total lung capacity showed a significantly steeper rise in patients with Pseudomonas aeruginosa compared with patients with other infections or patients without infection. Conclusions: Patients with IDA/CA/MTD defects or CCDC39 and CCDC40 mutations had the greatest increase in hyperinflation, whereas those with outer dynein arm defect and normal EM results or DNAH11 and DNAH5 mutations had less severe changes. We have robustly confirmed the worse prognosis for some genetic and ultrastructural defects, which association hitherto rested solely on spirometry.

Pediatric PulmonologyVolume 55, Issue 8 p. 1874-1875 LETTER TO THE EDITOR Cytoplasmic ciliary inclusions can reflect an abnormal ciliogenesis in respiratory epithelium Angela M. Cangiotti MD, PhD, Corresponding Author Angela M. Cangiotti MD, PhD angelamariacangiotti@libero.it Department of Experimental and Clinical Medicine, Biology of Obesity-Electron Microscopy Unit, Center of Obesity, United Hospitals–Marche Polytechnic University, Ancona, Italy Correspondence Angela M. Cangiotti, MD, PhD, Department of Experimental and Clinical Medicine, Biology of Obesity-Electron Microscopy Unit, Marche Polytechnic University, Via Tronto 10/A, 60126, Torrette, Ancona, Italy. Email: angelamariacangiotti@libero.itSearch for more papers by this authorMassimo Pifferi MD, PhD, Massimo Pifferi MD, PhD orcid.org/0000-0002-8266-1923 Department of Paediatrics, University Hospital of Pisa, Pisa, ItalySearch for more papers by this authorRossella Fonnesu Biol Sc, Rossella Fonnesu Biol Sc Department of Paediatrics, University Hospital of Pisa, Pisa, ItalySearch for more papers by this authorSerena Gracci MD, Serena Gracci MD Department of Paediatrics, University Hospital of Pisa, Pisa, ItalySearch for more papers by this authorSaverio Cinti MD, Saverio Cinti MD Department of Experimental and Clinical Medicine, Biology of Obesity-Electron Microscopy Unit, Center of Obesity, United Hospitals–Marche Polytechnic University, Ancona, ItalySearch for more papers by this author Angela M. Cangiotti MD, PhD, Corresponding Author Angela M. Cangiotti MD, PhD angelamariacangiotti@libero.it Department of Experimental and Clinical Medicine, Biology of Obesity-Electron Microscopy Unit, Center of Obesity, United Hospitals–Marche Polytechnic University, Ancona, Italy Correspondence Angela M. Cangiotti, MD, PhD, Department of Experimental and Clinical Medicine, Biology of Obesity-Electron Microscopy Unit, Marche Polytechnic University, Via Tronto 10/A, 60126, Torrette, Ancona, Italy. Email: angelamariacangiotti@libero.itSearch for more papers by this authorMassimo Pifferi MD, PhD, Massimo Pifferi MD, PhD orcid.org/0000-0002-8266-1923 Department of Paediatrics, University Hospital of Pisa, Pisa, ItalySearch for more papers by this authorRossella Fonnesu Biol Sc, Rossella Fonnesu Biol Sc Department of Paediatrics, University Hospital of Pisa, Pisa, ItalySearch for more papers by this authorSerena Gracci MD, Serena Gracci MD Department of Paediatrics, University Hospital of Pisa, Pisa, ItalySearch for more papers by this authorSaverio Cinti MD, Saverio Cinti MD Department of Experimental and Clinical Medicine, Biology of Obesity-Electron Microscopy Unit, Center of Obesity, United Hospitals–Marche Polytechnic University, Ancona, ItalySearch for more papers by this author First published: 26 May 2020 https://doi.org/10.1002/ppul.24859Citations: 1Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume55, Issue8August 2020Pages 1874-1875 RelatedInformation