Understanding of lipid transfer protein sensitization patterns and its clinical significance in children.

Background: Lipid transfer proteins (LTP) are the most common food allergens in the Mediterranean region. Objective: The study aimed to investigate co-sensitization patterns and cluster relationships between LTP allergen molecules across a broad range of allergen-specific sensitization patterns, and clinical outcomes in eastern Mediterranean children. Methods: Among 496 children evaluated for multiple sensitizations with multiplex testing, 105 children (21%) with 16 different LTP sensitizations were analyzed. Clinical reactivity was examined based on clear-cut history of immunoglobulin E mediated symptoms (oral allergy syndrome [OAS], systemic reactions, and anaphylaxis). Results: All children included were sensitive to food LTPs, but 56% were sensitive to pollen LTPs. The number of children with OAS and clinical reactivity was 12 and 59, respectively, and no cofactors were reported. The most common sensitizations were Pru p 3 (74%) and Cor a 8 (66%). Significant correlations were observed in the heatmap between the LTP molecules other than Par j 2 and Tri a 14. Overall, clinical reactivity was associated with increased age and number of LTP molecule positivity. Conclusion: In the eastern Mediterranean region, 21% of children with multiple food and/or pollen sensitizations were found to have LTP sensitization; however, almost half reported clinical reactivity. The hierarchical pathway highlights that distinct LTP allergen molecules can act as primary sensitizers. Clinical reactivity is linked to increasing numbers of LTP molecule positivity and increasing age.

Recognition of nuts and seeds in children with/without food allergies and their mothers: A reflection of culinary culture.

BACKGROUND: Nuts and seeds are among the leading causes of food allergy. Effective food allergy management hinges on the ability to identify and avoid relevant foods. AIM: To evaluate the nut/seed recognition ability in both children and mothers. METHODS: Primary caregivers (mothers) and their children (6-18 years old) with/without food allergies were shown photographs of nuts/seeds, and their products with visible/hidden allergens to assess their ability to recognize accurately. RESULTS: A total of 196 children and 184 mothers participated. The median ages of the children and mothers were 7.6 (6.8-10) and 37.8 (33.1-41.5) years, respectively. Over 75% of the children/adolescents and over 90% of the mothers accurately identified the kernel forms of nuts/seeds, except pine nuts. Walnuts, hazelnuts, almonds, and cashews were the most accurately recognized kernel forms by both populations. Generally, the kernel forms were recognized 5-20% more accurately than their in-shell forms, followed by products with visible and hidden forms, respectively. Some Turkish culinary-specific products with visible/hidden allergens were recognized as frequently as the kernel/in-shell forms by both study groups. Although there was a similar recognition pattern between study groups and subgroups (nut/seed allergy, other food allergy, controls), higher rates of recognition were found in mothers than in their children and adolescents than in schoolchildren. CONCLUSION: In Eastern Mediterranean region, nuts and sesame seeds are highly recognized by both mothers and their children. Accurate identification of these foods is likely a culinary feature, but not the result of increased awareness. More information is needed on whether this ability reduces the risk of exposure.

Mite allergen sensitization patterns in Turkish children: Age-related changes and molecular correlations.

BACKGROUND: Mites are ubiquitous aeroallergens found worldwide. Elucidating individual mite allergen sensitization patterns provides critical insights for managing allergic diseases. This study aimed to investigate molecular allergen (MA) sensitization patterns across different age groups and explore cluster relationships among mite-sensitized children. METHODS: We analyzed 76 children who exhibited sensitization to at least one of the 17 distinct mite MAs through microarray testing. RESULTS: Dermatophagoides farinae exhibited a slightly higher prevalence of sensitization compared with Dermatophagoides pteronyssinus. Der p 1/2 and Der f 1/2 demonstrated an almost 40% sensitization rate, while Der p 10/Blo t 10, Der p 20, Der p 23, and Gly d 2/Lep d 2 displayed an approximately 20% sensitization rate. Sensitization levels and ratios increased significantly with age for Der p 23 but showed numerical rises for other MAs, except for Der p 10/Blo t 10. The presence of various types of atopic diseases had only a minimal impact on sensitization profiles. Strong correlations emerged between Der f 2 and Der p 2, Der p 10 and Blo t 10, Der p 21 and Blo t 5, as well as Gly d 2 and Lep d 2. Hierarchical cluster analysis substantiated these relationships. Der p 10 and its homolog Blo t 10-sensitive patients (15/76) were mostly seen as mono sensitization(12/15). Ten patients exhibited monosensitization to Der p 20, suggesting a possible association with scabies infection. CONCLUSION: In children, mite sensitization diversity and levels increased with age. The presence of significant correlations/cluster relationships among these sensitizations underscores homologies among specific MAs.

The many faces of pediatric urticaria.

Urticaria is a common disease that can affect individuals of all age groups, with approximately one-quarter of the population experiencing it at least once in their lifetime. Lesions characterized by erythema and itchy hives can appear anywhere on the body. These can vary in size ranging from millimeters to centimeters, and typically clear within 24 h. About 40% of patients with urticaria have accompanying angioedema, which involves localized deep tissue swelling. Urticaria usually occurs spontaneously and is classified into acute and chronic forms, with the latter referring to a condition that lasts for more than 6 weeks. The prevalence of chronic urticaria in the general population ranges from 0.5% to 5%, and it can either be inducible or spontaneous. The most common form of pediatric urticaria is acute and is usually self-limiting. However, a broad differential diagnosis should be considered in children with urticaria, particularly if they also have accompanying systemic complaints. Differential diagnoses of pediatric urticaria include chronic spontaneous urticaria, chronic inducible urticaria, serum sickness-like reaction, urticarial vasculitis, and mast cell disorders. Conditions that can mimic urticaria, including but not limited to cryopyrinopathies, hyper IgD syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA), Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPs), and Schnitzler syndrome should also be considered. The many faces of pediatric urticaria can be both easy and confusing. A pragmatic approach relies on clinical foresight and understanding the various forms of urticaria and their potential mimickers. This approach can pave the way for an accurate and optimized diagnostic approach in children with urticaria.

Nutritional risks in children with food allergy.

BACKGROUND: Food allergies (FA) are a growing problem in the pediatric population and clinical features differ according to the underlying immunological mechanisms. While the primary management strategy is to eliminate the culprit food from the diet, assessment of the potential nutritional risks of elimination is also an integral part of management. In cases that do not improve over time; if you have basic food allergies and multiple food allergies, this can also lead to negative nutritional consequences. The contribution of basic nutrients, economical and easily accessible foods to the diet, is critical and has an important place in meeting the daily adequate intake of many nutrients. In the presence of food allergy, it is necessary to meet the vitamins and minerals that cannot be obtained from allergic foods, with alternative sources or supplements. For example, insufficient calcium intake in cow's milk allergy (CMA), the most common FA in early childhood, is very likely if an alternative supplement has not been introduced. In the management of CMA, choosing the appropriate formula and/or supplement for the clinical characteristics of children, when necessary, has an important place. In conclusion, nutritional risk assessment of children with FA requires a comprehensive, detailed, and multidisciplinary approach.

Can early life interventions prevent food allergies?

BACKGROUND: The incidence of food allergies is increasing all over the world. Prevention strategies intend to reduce food sensitization risk and subsequent allergies. In this review, we will discuss the recent data concerning different geographic regions for the prevention of food allergies in children. METHODS: This review provides recommendations for the prevention of food allergies based on the recent data available in the PUBMED database in English (up to December 2022). RESULTS: The best strategy to prevent food allergies is regarded as the early introduction of allergenic foods to an infant`s diet. A healthy and diverse diet is recommended for infants and their mothers, in accordance with the family`s eating habits and regional food culture, rather than avoiding certain foods or using supplements. Avoiding common food allergens in the maternal diet during pregnancy and/or breastfeeding is not recommended. Exclusive breastfeeding is generally recommended for all mothers for at least 6 months. There is no specific association between exclusive breastfeeding and the primary prevention of any specific food allergy. Where a breastmilk substitute is needed, the best alternative should be chosen according to the infant`s nutritional needs. There is no substantial evidence to support the use of hydrolyzed or soy formula in infancy against food allergies or sensitization. CONCLUSIONS: Feeding patterns in infancy play an important role in the risk of developing food allergies. Existing strategies to prevent allergies are relatively ineffective and further research is needed to figure out strategies for food allergy prevention, particularly in high-risk infants.

Characteristics of tree nut, peanut, and seed consumption in the eastern Mediterranean region.

BACKGROUND: Nuts and seeds are among the most common causes of food allergy (FA), and consumption differences across cultures and geographic regions are thought to account for the diversity of these allergies. METHODS: Caregivers of infants (age 12-24 months) with or without FA were questioned in face-to-face interviews to identify the nut and seed consumption practices in the household, during pregnancy, breastfeeding, and early childhood. RESULTS: Of the 171 infants (median age: 17.3 months) included in the study, 75 were healthy and 96 had FA. More than two-thirds of the infants in the whole group started to be fed with walnuts, sesame/tahini, hazelnuts, almonds, and sunflower seeds. The percentages of healthy infants who were not fed with tree nuts, seeds, and peanuts were 4%, 4%, and 49.3%, respectively, for the healthy infants, and 11.8%, 11.8%, and 67.8% for those with FA. In the FA group, sesame and peanut consumption was initiated at a younger age, and walnut, hazelnut, and almond consumption at an older age compared to the healthy infants (p < 0.05 for each). Walnuts and sesame/tahini were the most consumed nuts at home, and peanuts and pumpkin seeds were the least consumed. Mothers reported that they increased tree nut consumption during pregnancy due to their positive effect on health and sesame/tahini consumption during breastfeeding to increase breast milk, respectively. CONCLUSION: The uniqueness of Turkish culinary culture is characterized by the frequent consumption of tree nuts and seeds, with further increases during pregnancy/lactation and early introduction to the diet of infants.

Eosinophilia in children: characteristics, etiology and diagnostic algorithm.

Eosinophilia is common in children and may be caused by various disorders. Large-cohort studies, including mild cases, are limited in children. This study aimed to reveal underlying etiologies of childhood eosinophilia and to create a diagnostic algorithm. Children (< 18 years) with absolute eosinophil counts (AECs) ≥ 0.5 × 109/L were reviewed from medical files. Clinical characteristics and laboratory values were recorded. Patients were grouped based on the severity of eosinophilia as mild (0.5-1.5 × 109/L), moderate (≥ 1.5 × 109/L) and severe (≥ 5.0 × 109/L). An algorithm was formed to evaluate these patients. We included 1178 children with mild (80.8%), moderate (17.8%) and severe eosinophilia (1.4%). The most common reasons of eosinophilia were allergic diseases (80%), primary immunodeficiency (PID) (8.5%), infectious diseases (5.8%), malignancies (0.8%) and rheumatic diseases (0.7%). Only 0.3% of children presented with idiopatic hypereosinophilic syndrome. Allergic diseases and PIDs were the most common etiologies in mild/moderate and severe groups, respectively. The median duration of eosinophilia was 7.0 (3.0-17.0) months in the study population and was the shortest in severe cases (2.0 (2.0-5.0) months). Multiple logistic regression analysis demonstrated food allergy [OR:1.866, 95%CI:1.225-2.842, p = 0.004] and PIDs [OR:2.200, 95%CI:1.213-3.992, p = 0.009] as independent factors for childhood eosinophilia. A diagnostic algorithm including mild form was presented for childhood eosinophilia.    Conclusion: Eosinophilia was frequently determined due to secondary causes; allergic diseases in mild/moderate eosinophilia, PIDs in severe group. Etiology of eosinophilia was diverse, and an algorithm concerning the severity of eosinophilia would be practical and rational. What is Known: • In children, eosinophilia is common, and mild eosinophilia occurs frequently. • Malignancies presents frequently with severe eosinophilia. What is New: • Primary immunodeficiencies were not a rare cause of eosinophilia, especially in countries such as the Middle East and eastern Mediterranean countries, where the countries consanguineous marriages are common, and should be investigated in children with eosinophilia who do not have allergic or infectious diseases. • In literature, there are many algorithms about childhood hypereosinophilia. However, mild eosinophilia is extremely important in children. Because all patients with malignancy and most of the patients with rheumatic diseases presented with mild eosinophilia. Therefore, we proposed an algorithm for childhood eosinophilia that includes mild eosinophilia besides moderate and severe cases.

Phenotypes of persistent hen`s egg allergy in children and adolescents.

BACKGROUND: Optimum management of food allergy (FA) includes consideration of co-allergies and multimorbidities and tolerance assessment. Documentation of FA practices may pave the way for better practice. METHODS: Patients aged 3-18 years, with persistent IgE-mediated hen`s egg allergy were reviewed. RESULTS: A total of 102 children with a median age of 59 months (IQR= 40-84) (72.2% males) were included. All were diagnosed during infancy and the initial symptoms were atopic dermatitis (65.6%), urticaria (18.6%), and anaphylaxis (5.9%). Of the total population, 21 (20.6%) experienced anaphylaxis with hen`s eggs, and 79.4%, 89.2%, and 30.4% had multiple FAs (≥2 food categories), ever atopic dermatitis, and asthma, respectively. The most common co-allergies were tree nuts, cow`s milk, and seeds, respectively. From 52 heated egg yolk and 47 baked egg oral food challenges, 48 (92.3%) and 41 (87.2%) were found as tolerant, respectively. The baked egg nontolerant group had a greater egg white skin prick test diameter [9 mm (IQR: 6-11.5) vs. 6 mm (IQR: 4.5-9); (p=0.009)] and specific IgE [12.6 kU/L (IQR: 4.11-45.4) vs. 6.2 kU/L (IQR: 1.9-12.4) (p=0.009)], respectively. In the multivariate analysis, baked egg tolerance was more likely in those with egg yolk-tolerant subgroup (OR: 6.480, 95% CI: 2.524-16.638; p < 0.001) and heated egg tolerance in those with baked egg tolerance (OR: 6.943, 95% CI: 1.554-31.017; p=0.011). CONCLUSIONS: Persistent hen`s egg allergy is characterized by multiple food allergies and age-related multimorbidities. Baked egg and heated egg yolk tolerance were more likely to be considered in a subgroup with a high expectation for finding a way to eliminate their allergy.

In Chronic Spontaneous Urticaria, Complete Response to Antihistamine Treatment Is Linked to Low Disease Activity.

INTRODUCTION: The use of predictors of response to a specific treatment in patients with chronic spontaneous urticaria (CSU) can improve disease management, help prevent unnecessary healthcare costs, and save time. In this study, we aimed to identify predictors of complete response to standard-dosed and higher than standard-dosed antihistamine treatments in patients with CSU. METHODS: Medical records of 475 CSU patients, 120 of them <18 years old, from 3 different centers were analyzed. We used 15 machine learning (ML) models as well as traditional statistical methods to predict complete response to standard-dosed and higher than standard-dosed antihistamine treatment based on 17 clinical parameters. RESULTS: CSU disease activity, which was assessed by urticaria activity score (UAS), was the only clinical parameter that predicted complete response to standard-dosed and higher than standard-dosed antihistamine treatment, with ML models and traditional statistics, for all age groups. Based on ROC analyses, optimal cut-off values of disease activity to predict complete response were UAS <3 and UAS <4 for standard-dosed (area under the ROC curve [AUC] = 0.69; p = 0.001) and higher than standard-dosed (AUC = 0.79; p = 0.001) antihistamine treatments, respectively. Also, ML models identified lower total IgE (<150 IU/mL) as a predictor of complete response to a standard-dosed antihistamine and lower CRP (<3.4 mg/mL) as a predictor of complete response to higher than standard-dose antihistamine treatment. DISCUSSION: In this study, we showed that patients with UAS <3 are highly likely to have complete response to standard-dosed AH and those with a UAS <4 are highly likely to have complete response to higher than standard-dosed AH treatment. Low CSU disease activity is the only universal predictor of complete response to AH treatment with both ML models and traditional statistics for all age groups.

A case-control study of the effects of Aspergillus clinical phenotypes on pulmonary functions in patients with cystic fibrosis.

INTRODUCTION: There are no precise data about the effect of Aspergillus infection on lung function other than allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis (pwCF). Here, we aimed to determine clinical phenotypes caused by Aspergillus spp. using laboratory and immunologic parameters and to compare Aspergillus phenotypes in terms of pulmonary function tests (PFT) prospectively. METHODS: Twenty-three pwCF who had Aspergillus isolation from respiratory cultures in the last year (case group) and 20 pwCF without Aspergillus isolation in sputum (control group) were included. Aspergillus immunoglobulin (Ig)-G, Aspergillus IgE, Aspergillus polymerase chain reaction (PCR), galactomannan, total IgE from blood samples, and Aspergillus PCR and galactomannan from sputum, and skin prick test reactivity to Aspergillus antigen were used to distinguish different Aspergillus phenotypes. Pulmonary functions and frequency of pulmonary exacerbations were evaluated during a 1-year follow-up. RESULTS: Of 23 pwCF, 11 (47.8%) had Aspergillus colonization, nine (39.1%) had Aspergillus bronchitis, and three (13%) had ABPA. Aspergillus infection was not associated with worse z-scores of forced expiratory volume in the first second (FEV1) (p = 0.612), forced vital capacity  (p = 0.939), and the median FEV 1% decline (0.0%/year vs. -4.7%/year, p = 0.626). The frequency of pulmonary exacerbations in the Aspergillus infected and noninfected groups was similar. CONCLUSION: Although Aspergillus spp. Isolation in pwCF was not associated with decreased lung function, a further decline was seen in the ABPA subgroup, and frequent pulmonary exacerbations during the 1-year follow-up.

Hypersensitivity reactions to biologics in children.

INTRODUCTION: Hypersensitivity reactions (HSRs) have been observed with the use of biologics in children. The management of HSRs in children is mainly based on experiences from the adult population. Recently, data from different centers experienced in managing these reactions, including desensitization in children, have been published, allowing clinicians to have an appropriate global overview and compare results. AREAS COVERED: This review highlights the published data on hypersensitivity reactions to biologics in children and drug desensitization protocols adapted to the pediatric population. EXPERT OPINION: With regard to HSRs to biologics in children, few data are available. Compared with the adult population, there is a lack of knowledge in the endophenotypes, management and the standardization of protocols including premedication regimens in children. An international consensus is needed to provide clinicians with new insight on how to apply personalized management and to perform tailored desensitization protocols in pediatric populations. Various specialists including allergists, pediatricians, oncologists, hematologists, rheumatologists, and pharmacists, should build a multidisciplinary management team to keep pediatric patients on their best treatment options in the safest manner.

Presence of fetal DNA in maternal exhaled breath condensate.

OBJECTIVES: Cell-free DNA has been found in all body fluids, but DNAs emerging from locations that are not in direct contact with breath in exhaled breath condensate (EBC) are yet to be found. The potential of EBC for prenatal and cancer screening prompted us to investigate whether fetal DNA is present in maternal EBC. METHOD: A total of 20 pregnant women's EBC and blood samples were collected. Four Y chromosome-specific assays were tested on all EBC and plasma samples by quantitative PCR (qPCR). The best-performing assay was used for digital droplet PCR (ddPCR) on all EBC and the six plasma samples. RESULTS: The sex of the fetuses was accurately determined from plasma samples. DNA sequences could not be properly amplified in EBC samples by the qPCR. By ddPCR, the Y chromosome sequence was amplified in two of the 11 EBC samples, from women carrying male fetuses (2/11), and the Y chromosome sequence was not amplified in the EBC of women carrying female fetuses (9/9). Exhaled breath condensate ddPCR result's specificity was 100%, the detection rate of Y chromosome was 18.18% (2/11), and the corrected accuracy was 59.09%. CONCLUSION: Our finding of "the presence of fetal DNA in maternal EBC", despite the low detection rate, might have a major impact on prenatal diagnosis and cancer screening.

Exploring the Heterogeneity of IgE-Mediated Food Allergy through Latent Class Analysis.

INTRODUCTION: Food allergy (FA) is a heterogeneous disease with multiple morbidities and a huge burden for patients and healthcare systems. Variable manifestations, comorbidities (atopic dermatitis [AD], asthma, and/or allergic rhinitis [AR]), severity (anaphylaxis), and outcomes suggest the existence of different endotypes that cluster analyses may reveal. In this study, we aimed to investigate distinct subgroups among patients with FAs using data from 524 children/adolescents. METHODS: 524 patients with IgE-mediated FA (353 male [67%]; median age 4.4 years [IQR:3.0-6.8]), 354 (68%) had multiple FA. The history of AD, asthma, AR, and anaphylaxis was recorded in 59.4%, 35.5%, 24.2%, and 51.2% of the patients, respectively. Latent class analysis was carried out to distinguish clinical FA phenotypes using five potential markers of allergy severity (single/multiple FA, never/inactive/current asthma and AD, AR, and anaphylaxis). RESULTS: Three distinct phenotypes were identified: (1) multiple FA with eczema and respiratory multimorbidity (42%), (2) multiple FA with persistent eczema (34%), and (3) single FA with respiratory multimorbidity without eczema (24%). Compared with the single FA cluster, the prevalence of AD was significantly higher in multiple FA groups. Cluster 1 had the highest frequency of AR and allergic asthma, and the lowest rate of total tolerance of FA. DISCUSSION: We put forward the hypothesis of underlying pathogenesis according to the clinical phenotypes. While skin barrier defect may play a dominant role in the pathogenesis in Cluster 2, immune dysregulation may be dominant in Cluster 3. In Cluster 1, the most severe group, a combination of both skin barrier defects and immune dysregulation may be responsible for the clinical features.

A Potentially Fatal Outcome of Oral Contraceptive Therapy: Estrogen-Triggered Hereditary Angioedema in an Adolescent

Hereditary angioedema (HAE) is characterized by recurrent angioedema attacks with no urticaria. This disease has a high mortality due to asphyxia. Level of complement component 4 (C4), C1 esterase inhibitor (C1-INH) level and function, and genetic mutations determine different endotypes of HAE. Clinical presentation and the triggers of vasogenic edema may change according to the endotypes. An adolescent girl with oligomenorrhea, obesity, hirsutism, and acanthosis nigricans was diagnosed with polycystic ovary syndrome and prescribed ethinyl estradiol and cyproterone acetate containing oral contraceptive (OC). On the sixteenth day of treatment, she developed angioedema of the face, neck, and chest leading to dyspnea. Adrenaline, antihistamine, and corticosteroid treatments were ineffective. In the family history, the patient's mother and two cousins had a history of angioedema. C1-INH concentrate was administered with a diagnosis of HAE. C4 and C1-INH level and activity were normal. Genetic analysis identified a mutation in the factor 12 (F12) gene, and the diagnosis of F12-related HAE was made. OC treatment was discontinued. She has had no additional angioedema attacks in the follow-up period of two years. OC containing estrogen may induce the life-threatening first attack of F12-related HAE even in children. Recurring angioedema attacks in the family should be asked before prescribing estrogen-containing OC pills.

Systemic treatments in atopic dermatitis in children.

Atopic dermatitis (AD) is a very common skin disease caused by inflammatory reactions, in which the main symptoms of severe itching and recurrent eczema diminish quality of life. As epidermal barrier function and the immune system play a critical role in atopic dermatitis, promoting IgE-mediated sensitization can be the main targets of AD treatment. The goal of AD treatment should be to eliminate the symptoms and obtain longterm eczema control with a multi-step approach adapted to the severity of the disease. Basic management for all patients comprises the use of moisturisers and avoiding triggers. While topical therapy is effective for most children diagnosed with AD, there may also be children who require systemic therapy. The aim of this paper was to present an extensive review of the systemic agents commonly used in childhood atopic dermatitis which mainly target cutaneous inflammation.

Hypersensitivity to Biological Treatments in Juvenile Idiopathic Arthritis: How Should It Be Managed?

Juvenile idiopathic arthritis (JIA) is one of the most frequent diseases in the practice of pediatric rheumatology. JIA treatments have been modified and improved with the use of biological drugs along with technological innovations. However, different types of hypersensitivity reactions to biological drugs have also been reported. Anaphylaxis and infusion reactions occurring during the intravenous infusion require a critical approach in the acute period. On the other hand, the detection of drug-related late-type reactions and the development of antibodies to the agent highlight the need for an understanding of the drug-induced etiology to prevent the patient from continuing the treatment with the culprit drug. The chronic disease process, concomitant immune dysregulation, and multiple drug use may result in these hypersensitivity reactions. In this review, the hypersensitivity reactions to the biological treatments used in patients with juvenile idiopathic arthritis and the management of these conditions are discussed.

The miRNA-24, miRNA-21 expressions and matrix metalloproteinase-7 level in exhaled breath condensate of children with primary spontaneous pneumothorax.

Bullous lung diseases may cause primary spontaneous pneumothorax (PSP) in children. The microRNAs (miRNAs) are non-coding RNAs that participate in regulation of inflammation and cancer. We hypothesized that children with bullous lung disease and PSP may have altered miRNA expressions in their exhaled breath condensates (EBCs). Therefore, a prospective study was performed to evaluate the miRNA-24 and 21 expression, and the matrix metalloproteinase-7 (MMP-7) levels in EBC of children with PSP. Children with PSP were evaluated for age, gender, clinical features and results of surgical treatment. EBC samples (500-1000 ml) were collected to evaluate the miRNA-21, 24 expressions, and MMP-7, and tissue-inhibitor-MMP-1 (TIMP-1) levels. miRNA expressions and MMP levels of patients were compared with healthy controls (control group (CG),n= 12). Subjects (n= 16) with a mean age of 15 years (10-19 years), and a male-to-female ratio of 14:2 were enrolled in this study. The most common presenting symptom was sudden chest pain (n= 14). In 62.5% of the cases an underlying bullous lung disease were detected. During an average of 16.6 months (1-60 months) follow up period, four subjects relapsed. The mean MMP-7 (1.74-1.57 ng ml-1), and TIMP-1 (1.92-1.84 ng ml-1) levels were similar between both groups (p> 0.05). miRNA-24 expression was significantly decreased in the PSP group, when compared to the CG (0.16-1 2-ΔΔCT,p< 0.05). In addition, the miRNA-21 expression was not different between the two groups (p> 0.05). In conclusion, the miRNA-24 levels were significantly decreased in children with PSP. Taken together, children with PSP, especially those with bullous disease, should be closely monitored in the long-term period.

Comparison of miRNA expression in patients with seasonal and perennial allergic rhinitis and non-atopic asthma.

BACKGROUND: MicroRNAs (miRNA) are small non-coding molecules that play a significant regulatory role in several allergic diseases. However, their role in allergic rhinitis is still not clearly understood. The aim of this study was to identify the candidate miRNAs that can discriminate between different forms of allergic rhinitis and also differ in and out of the allergen season. METHODS: The study included 20 healthy children, 20 patients with seasonal allergic rhinitis (SAR), 20 non-atopic asthmatics (NA-A), and 12 patients with perennial allergic rhinitis (PAR). Patients with SAR were evaluated comparatively in and outside the allergen season. The changes in the expressions of selected miRNAs (miR- 125b, miR-126, miR-133b, miR-181a, and miR-206) that were found related to the allergic diseases according to the literature were determined using quantitative polymerase chain reaction. RESULTS: In the SAR group, expression levels of miR-125b (p=0.040) and miR181a (p=0.014) were lower than in the controls outside of the allergen season. Expression levels of miR-181a were different between patients with SAR and NA-A (p=0.003), also between the SAR and PAR (p=0.001) groups in multiple comparisons. In contrast, the expression of miR-206 was found to be decreased in patients with NA-A and PAR compared with the controls (p=0.005 and p=0.024, respectively). In correlation analysis, expression levels of miR-125b and peak expiratory flow (PEF) values were found to be negatively correlated in the SAR (p=0.013) and PAR (p=0.029) groups. The expression level of miR-206 was positively correlated with total IgE levels in PAR (p=0.007). Receiver operating characteristic analysis revealed that miR-125b and miR-181a predicted the risk of SAR (p=0.040 and p=0.014, respectively), and miR-206 for NA-A and PAR (p=0.005 and p=0.024, respectively). CONCLUSIONS: Our study showed that expression levels of miRNAs were different according to the type of allergic diseases and the presence of allergens. miR-181a and miR-125b can be candidate biomarkers for SAR, and miR-206 for NA-A and PAR.