Cystic fibrosis is a progressive disease affecting various organs of the human body, including the respiratory system. While the effect of bacterial infection on cystic fibrosis outcome has been comprehensively described, little is known about the impact of viruses. We collected 49 nasopharyngeal swabs derived from cystic fibrosis paediatric patients during pulmonary exacerbation and tested them for the presence of respiratory viruses to elucidate the influence of the viral infection on their clinical outcome. We found that patients infected with a virus, compared to those in whom molecular testing for viruses was negative, are characterised by a better clinical outcome, as measured by the Shwachman–Kulczycki score (p = 0.006) and have better chest radiographs, as indicated by the Brasfield score (p = 0.002). Moreover, these patients have lower C-reactive protein levels (p = 0.002). We assume this unexpected association of better clinical outcomes during viral infection should be studied further.

The updated and enhanced guidelines for the diagnosis and treatment of asthma in children and adults were developed by expert physicians from four Polish medical societies, using the GRADE methodology. The guidelines provide a concise and clear overview of the principles of asthma diagnosis and treatment, designed for physicians of all medical specialties, with a particular focus on primary care physicians. They can also be used in coordinated care processes.

BACKGROUND Childhood asthma, especially in the youngest children, is difficult to diagnose and is often based on the patient's symptoms. This study compared metabolite concentrations in serum samples between 13 children with asthma and IgE-dependent allergy and 10 without asthma and IgE-dependent allergy, aged between 6 months and 5 years. MATERIAL AND METHODS The study included a total of 23 children. The targeted metabolomic analysis was performed using an AbsoluteIDQ p180 kit and analyzed using a triple quadrupole tandem mass spectrometer coupled with a high-performance liquid chromatograph. Statistical analyses included univariate tests and univariate and multivariate receiver operating characteristic (ROC) curves. RESULTS Of the 188 metabolites, 131 were determined in the samples. Additionally, 48 sums and ratios of metabolites were calculated. Significant differences (P<0.05) were found for the 6 metabolites of sphingolipids and glycerophospholipids and ratio serotonin synthesis. Multivariate ROC curve analysis was performed for phosphatidylcholine 40: 4 and serotonin synthesis ratio, which were selected based on the univariate ROC curve analysis results. This combined indicator's area under the curve (AUC) demonstrated greater sensitivity and specificity than the individual variables. CONCLUSIONS Our study sheds new light on differences in serum metabolite concentrations between patients under 5 years of age with asthma and IgE-dependent allergy and patients without asthma or IgE-dependent allergy. A multiclassifier integrating PC 40: 4 and serotonin synthesis ratio is a promising biomarker for diagnosing childhood asthma with IgE-dependent allergy, facilitating faster, more precise, and personalized diagnosis and treatment of pediatric patients.

The aim of our review is to summarize the available literature where metabolomics was used in studies on childhood asthma, and to find metabolites that are diagnostic biomarker candidates in childhood asthma. Moreover, the review also describes studies related to metabo-endotypes and heterogeneity of childhood asthma, severity of the disease, and response to drug treatment. Metabolomics has opened up new perspectives in childhood asthma investigation. Based on the available literature, we found nine metabolites that demonstrated the highest diagnostic potential for differentiation between children with asthma and healthy controls: adenine, adenosine, benzoic acid, hypoxanthine, p-cresol, taurocholate, threonine, tyrosine, and 1-methyl nicotinamide. Many of the identified metabolites are closely associated with inflammatory processes responsible for asthma. Metabolomic analysis also contributed to characterizing new asthma endotypes highlighting the heterogeneity of pediatric asthma. Metabolomics can bring about valuable insights, which, when integrated with other omic disciplines, can facilitate the diagnosis and management of childhood asthma and the search for new biomarkers of the disease. Improvements in the detection of asthma in preschool children, including asthma endotypes, will ease application of proper treatment and enable elimination of unnecessary test treatment of corticosteroids in young patients.

In recent years, questionnaires were published in English to assess the quality of life of patients with PCD (Primary Ciliary Diskinesia) for adults, adolescents aged 13–17 years, and children aged 6–12 years and their caregivers. This study aimed to prepare Polish versions of the questionnaires and validate them in specific age groups with the participation of Polish patients with PCD. The individual questionnaires were translated and discussed with the involvement of the creator of the original questionnaire in English. Patients completed the questionnaires according to their affiliation with one of the groups. Validation was based on internal consistency analysis (Cronbach’s alpha coefficient and split-half reliability) and test–retest reliability (intraclass correlation coefficient—ICC). The internal consistency of all questionnaires was from moderate to very good (Cronbach’s alpha 0.67–0.91, split-half reliability 0.53–0.95). The consistency of the measurements showed excellent repeatability (ICC 0.67–0.91). The surveyed Polish PCD patients rated their quality of life quite well (63–77%). QOL questionnaires for patients with PCD can be used routinely during each medical check-up as a simple tool to provide the doctor with an indication of the effectiveness of treatment and the impact of the disease on the patient’s quality of life.

An IgE-mediated food allergy (FA) in atopic dermatitis (AD) children should be easily differentiated from other immune-mediated adverse effects related to food. Specific IgEs for particular protein components has provided additional diagnostic value. However, component-resolved diagnostics (CRD) has not solved all diagnostic problems either. We analysed the serum profile of 42 amino acids (AAs) in 76 AD children aged 2-60 months with an IgE-mediated FA (n = 36), with a non-IgE-mediated FA (n = 15) and without an FA (n = 25) using high-performance liquid chromatography coupled with mass spectrometry (LC-MS/MS) and an aTRAQ kit. We identified homocitrulline (Hcit), sarcosine (Sar) and L-tyrosine (Tyr) as features that differentiated the studied groups (one-way ANOVA with least significant difference post hoc test). The Hcit concentrations in the non-IgE-mediated FA group were significantly decreased compared with the IgE-mediated FA group (p = 0.018) and the control group (p = 0.008). In AD children with a non-IgE-mediated FA, the Tyr levels were also significantly reduced compared with the controls (p = 0.009). The mean concentration of Sar was the highest in the non-IgE-mediated FA group and the lowest in the IgE-mediated FA group (p = 0.047). Future studies should elucidate the involvement of these AAs in the molecular pathway of IgE- and non-IgE-mediated allergic responses.

Aim: Recently, the most commonly used for multiple breath washout device, the Exhalyzer D, has been shown to overestimate lung clearance index (LCI) results due to a software error. Our study aimed to compare the predictive values of LCI in the CF pulmonary exacerbations (PE) calculated with the updated (3.3.1) and the previous (3.2.1) version of the Spiroware software. Materials and Methods: The measurements were performed during 259 visits in CF pediatric patients. We used 39ΔPE pairs (PE preceded by stable visit) and 138ΔS pairs (stable visit preceded by stable visit) to compare the LCI changes during PE. The areas under the receiver operating curves (AUCROC) and odds ratios were calculated based on the differences between ΔPEs and ΔSs. The exacerbation risk was estimated using a logistic regression model with generalized estimating equations (GEE). Results: There were statistically significant differences in LCI 2.5% median values measured using the two versions of the software in the stable condition but not during PE. The AUCROC for changes between the two consecutive visits for LCI did not change significantly using the updated Spiroware software. Conclusions: Despite the lower median values, using the recalculated LCI values does not influence the diagnostic accuracy of this parameter in CF PE.

Next to cow’s milk and eggs, plant foods, i.e., legumes, tree nuts and cereal grains, most often sensitise atopic children. Storage proteins constitutes the most relevant protein fraction of plant foods, causing primary sensitisation. They exhibit strong allergenic properties and immunogenicity. Our goal was to analyse sensitisation to 26 plant storage proteins in a group of 76 children aged 0–5 years with chronic symptoms of atopic dermatitis using Allergy Explorer ALEX2 and to discover changes in serum protein–peptide patterns in allergic patients with the use of MALDI-TOF-MS. We reported that 25% of children were allergic to 2S albumins, 19.7% to 7S globulins, 13.2% to 11S globulins and 1.3% to cereal prolamins. The most common allergenic molecules were Ara h 1 (18.4%), Ara h 2 (17.1%), Ara h 6 (15.8%) and Ara h 3 (11.8%) from peanuts, and the mean serum sIgE concentrations in allergic patients were 10.93 kUA/L, 15.353 kUA/L, 15.359 kUA/L and 9.038 kUA/L, respectively. In children allergic to storage proteins compared to the other patients (both allergic and non-allergic), the cell cycle control protein 50A, testis-expressed sequence 13B, DENN domain-containing protein 5A and SKI family transcriptional corepressor 2 were altered. Our results indicate that the IgE-mediated allergy to storage proteins is a huge problem in a group of young, atopic children, and show the potential of proteomic analysis in the prediction of primary sensitisation to plant foods. It is the next crucial step for understanding the molecular consequences of allergy to storage proteins.

Abstract Purpose: Respiratory syncytial virus (RSV) is responsible for most cases of acute bronchiolitis in infants that require hospitalization. The infection is modulated by the local inflammatory response of the immune system via the production of pro-inflammatory cytokines. This study sought to determine the differences in the local immune response between children with RSV-positive and RSV-negative bronchiolitis. We also analyzed correlations between clinical parameters and molecular markers to define useful biomarkers of RSV infection.Methods: Children hospitalized due to acute bronchiolitis were recruited during three consecutive epidemiological seasons and divided into RSV-positive (n=42) and RSV-negative (n=81) groups. Clinical and demographic data were collected. RNA was isolated from nasopharyngeal aspirates and transcribed into cDNA. Gene expression of selected cytokines (IL-1β, IL-4, IL-8, IL-10, IL-12, IFN-γ and TNF-α) was analyzed via quantitative real-time PCR. Statistical analysis was performed in Statistica v.13.Results: RSV-positive patients were longer hospitalized (P=0.005) and required longer supplemental oxygen therapy (P<0.0001). Moreover, they had lower admission weight (P=0.017), lower partial pressure of oxygen (P=0.02) and higher CRP levels (P=0.02). Significantly higher rates of cesarean delivery (P=0.04) and familial atopy (P=0.006) were also observed in patients with an RSV infection. Comparison analysis revealed that IL-10, IL-12 and IFN-γ gene expression was significantly lower in patients with RSV than in patients without RSV (P=0.020, P=0.039 and P =0.003, respectively). In contrast, the expression of other cytokines did not differ significantly between the studied groups. Logistic regression analysis indicated that the expression of Th1 and Th2 cytokines, combined with clinical risk factors, significantly improved discrimination accuracy between RSV-positive and RSV-negative patients. Conclusions: Our results show that the expression of several cytokines significantly differs between children with RSV-positive and RSV-negative bronchiolitis, suggesting their involvement in the pathomechanism of RSV infection. The gene expression of IL-10, IL-12 and IFN-γ cytokines, lower admission weight, cesarean delivery and familial atopy could become clinical and diagnostic markers that facilitate the discrimination between RSV and non-RSV aetiology of bronchiolitis.

The main risk factor for the development of food allergies (FAs) in children is atopic dermatitis (AD). AD is usually recognized as the Th1/Th2 paradigm of allergic disease. Recently, the Th1/Th2 paradigm in allergy and autoimmunity has been revised, including the role of the Th17 cell population and related cytokines. However, there are only a few studies that have found Th17 cytokine involvement in the allergic inflammatory response, especially with food allergens. This research aimed to analyze the serum profile of cytokines involved in the T-helper cell type 17 immune response pathway in young, atopic children with an IgE-mediated and delayed-type FA. The study involved 76 children (0–5 years old) with chronic AD. We used the Bio-Plex system to simultaneously determine the concentrations of 15 different cytokines in one experiment. In accordance with complete dermatological and allergological examination, including OFC testing and ALEX2 assays, participants were divided into 3 groups: IgE-mediated FA, delayed-type FA, and the control group. Data were analyzed using univariate statistical tests. In the IgE-mediated FA group, the circulating levels of tested cytokines had increased compared with those of other patients; however, a statistically significant difference was only obtained for IL-1beta (p < 0.05). According to the ROC curves, IL-1beta may be considered an effective predictor of IgE-mediated FA in AD children (p < 0.05; AUC = 0.67). In the delayed-type FA group, the concentration of most cytokines had slightly decreased compared to the control group. The obtained results suggest that FA influences the Th17-related cytokine profile in the serum of AD children. More advanced studies are needed to confirm the involvement of Th17 cytokines in the allergic inflammatory response and to prove their usefulness in clinical practice.

Childhood asthma is a chronic airway disease, which pathogenesis is markedly heterogeneous–with multiple phenotypes defining visible characteristics and endotypes defining molecular mechanisms. Cytokines and chemokines released during inflammatory responses are key immune mediators. The cytokine response can largely determine the susceptibility to childhood asthma and its severity. The purpose of this study was to characterize the immune profile of childhood asthma. The study involved 26 children (3–18 years old), who were divided into 2 groups: study–with childhood asthma; control–without asthma. The innovative Bio-Plex method was used to determine the serum concentration of 37 inflammatory proteins in one experiment. The results were analyzed using univariate statistical tests. In the study group, the level of the 10 tested markers increased, while the level of the remaining 9 decreased compared to the control; a statistically significant reduction in concentration was obtained only for the MMP-1(p<0.05). According to the ROC curve, MMP-1 can be considered an effective discriminator of childhood asthma (p<0.05; AUC=0.752). Cytokines/chemokines may be useful in the diagnosis of childhood asthma and may also become a prognostic target in determining the phenotype/endotype of this condition. This study should be a prelude to and an incentive for more complex proteomic analyzes.

Hymenoptera venom allergy significantly affects the quality of life. Due to the divergences in the results of the available test and clinical symptoms of patients, the current widely applied diagnostic methods are often insufficient to classify patients for venom immunotherapy (VIT). Therefore it is still needed to search for new, more precise, and accurate diagnostic methods. Hence, this research aimed to discover new biomarkers of Hymenoptera venom allergy in a group of inflammation factors using set of multi-marker Bioplex panel. The adoption of a novel methodology based on Luminex/xMAP enabled simultaneous determination of serum levels of 37 different inflammatory proteins in one experiment. The study involved 21 patients allergic to wasp and/or honey bee venom and 42 healthy participants. According to univariate and multivariate statistics, soluble CD30/tumor necrosis factor receptor superfamily, member 8 (sCD30/TNFRSF8), and the soluble tumor necrosis factor receptor 1 (sTNF-R1) may be considered as effective prognostic factors, their circulating levels were significantly decreased in the allergy group (p-value < 0.05; the Area Under the Curve (AUC) ~0.7; Variable Importance in Projection (VIP) scores >1.2). The obtained results shed new light on the allergic inflammatory response and may contribute to modification and improvement of the diagnostic and monitoring methods. Further, large-scale studies are still needed to explain mechanisms of action of studied compounds and to definitively prove their usefulness in clinical practice.

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA TÄ polska-Jóźwiak K, Szczawińska-Popłonyk A, Bręborowicz A. Interstitial lung disease and bronchiectasis in children with primary immunodeficiencies: a single-centre experience. Pediatria Polska - Polish Journal of Paediatrics. 2021;96(1):16-22. doi:10.5114/polp.2021.104824. APA TÄ polska-Jóźwiak, K., Szczawińska-Popłonyk, A., & Bręborowicz, A. (2021). Interstitial lung disease and bronchiectasis in children with primary immunodeficiencies: a single-centre experience. Pediatria Polska - Polish Journal of Paediatrics, 96(1), 16-22. https://doi.org/10.5114/polp.2021.104824 Chicago TÄ polska-Jóźwiak, Katarzyna, Aleksandra Szczawińska-Popłonyk, and Anna Bręborowicz. 2021. "Interstitial lung disease and bronchiectasis in children with primary immunodeficiencies: a single-centre experience". Pediatria Polska - Polish Journal of Paediatrics 96 (1): 16-22. doi:10.5114/polp.2021.104824. Harvard TÄ polska-Jóźwiak, K., Szczawińska-Popłonyk, A., and Bręborowicz, A. (2021). Interstitial lung disease and bronchiectasis in children with primary immunodeficiencies: a single-centre experience. Pediatria Polska - Polish Journal of Paediatrics, 96(1), pp.16-22. https://doi.org/10.5114/polp.2021.104824 MLA TÄ polska-Jóźwiak, Katarzyna et al. "Interstitial lung disease and bronchiectasis in children with primary immunodeficiencies: a single-centre experience." Pediatria Polska - Polish Journal of Paediatrics, vol. 96, no. 1, 2021, pp. 16-22. doi:10.5114/polp.2021.104824. Vancouver TÄ polska-Jóźwiak K, Szczawińska-Popłonyk A, Bręborowicz A. Interstitial lung disease and bronchiectasis in children with primary immunodeficiencies: a single-centre experience. Pediatria Polska - Polish Journal of Paediatrics. 2021;96(1):16-22. doi:10.5114/polp.2021.104824.

Background and Objectives: In paediatric population, atopic asthma is associated with increased eosinophil counts in patients, that correlate with the airway inflammation measured by the concentration of nitric oxide in exhaled air (FeNO). As the FeNO level is a biomarker of atopic asthma, we assumed that polymorphisms in nitric synthases genes may represent a risk factor for asthma development. The purpose of this study was to analyse the association of NOS genetic variants with childhood asthma in the Polish population. Materials and methods: In study we included 443 children—220 patients diagnosed with atopic asthma and 223 healthy control subjects. We have genotyped 4 single nucleotide polymorphisms (SNP) from 3 genes involved in the nitric oxide synthesis (NOS1, NOS2 and NOS3). All analyses were performed using polymerase chain reaction with restriction fragments length polymorphism (PCR-RFLP). Results: We observed significant differences between cases and controls in SNP rs10459953 in NOS2 gene, considering both genotypes (p = 0.001) and alleles (p = 0.0006). The other analyzed polymorphisms did not show association with disease. Conclusions: According to our results, 5′UTR variant within NOS2 isoform may have an impact of asthma susceptibility in the population of Polish children. Further functional studies are required to understand the role of iNOS polymorphism in NOS2 translation and to consider it as a novel risk factor in childhood asthma. The next step would be to apply this knowledge to improve diagnosis and develop novel personalized asthma therapies.

Introduction. Spontaneous pneumomediastinum is a very rare condition in children. Nevertheless it should be considered in the differential diagnosis in patients who present with chest pain and dyspnoe. Aim. The aim of our study was to describe clinical presentation, management and outcomes of the paediatric patients with spontaneous pneumomediastinum Material and Methods. This was a retrospective analysis of the charts of all the patients who were admitted to the Department of Pneumonology, Paediatric Allergy and Clinical Immunology in a ten year period from 01.01.2011 till 31.12.2020 in whom spontaneous pneumomediastinum was diagnosed. Results. There were 11 children (7 females) with spontaneous pneumomediastinum. The median age of the children was 11 years (range 3 to 17.5 years). Most of the children presented to the hospital with chest pain, three children complained of the neck swelling and four children developed dyspnoe. Three children with the primary spontaneous pneumomediastinum had a history of physical exercise prior to the onset of symptoms. The secondary spontaneous pneumomediastinum occurred in two children with asthma and 4 children with pneumonia. Genetic material of human Bocavirus was identified in 3 cases. In 81.8% of children pneumomediastinum was accompanied by subcutaneous emphysema and in one case, in a child with severe pneumonia and respiratory insufficiency caused by Bocavirus with pneumorrhachis. In 10 children computed tomography was performed, bronchoscopy in 4 and esophagoscopy in two children. There was no evidence of esophageal rupture or bronchial tree rupture in any of our patients. Three children with pneumonia and pneumomediastinum developed respiratory insufficiency, two of these were treated with mechanical ventilation and one with High Flow Nasal Cannula oxygen therapy. All the children received oxygen. In one child surgical procedure was performed and the drain was inserted into mediastinal space in order to decompress it. Outcome was favourable in all children. Mean time to recovery was 10.6 ± 1.2 days. There was no recurrence of symptoms in any of our patients. Conclusions. Spontaneous pneumomediastinum in most cases is a benign condition, sporadically however it may progress rapidly, leading to respiratory insufficiency and warrant invasive management.

Introduction: Hymenoptera venom allergy (HVA) is associated with a high risk of anaphylaxis. Effective treatment of HVA patients requires allergologists’ familiarity with the latest HVA recommendations. Aim: Evaluation of current practices in HVA diagnosis in Poland. Material and methods: A survey questionnaire was conducted in 32 HVA centres in Poland. Results: The response rate was 97%. There were 1829 patients evaluated due to HVA in 2015. Sixty six percent (n = 21) of the centres used skin prick tests, out which 90% (n = 19) used 100 µg/ml of the venom extract as the highest concentration. All the centres performed intradermal tests (IDT) and serum specific IgE (sIgE), an initial diagnostic tool in 91% (n = 29). The highest venom concentration in IDT was 1 µg/ml in 75% (n = 24), 0.1 µg/ml in 16% (n = 5), 0.01 µg/ml in 3% (n = 1) and 10 µg/ml in 6% (n = 2). Baseline serum tryptase was assessed in 84% of the centres (n = 27), out of which 53% (n = 17) tested all their patients, whereas 31% (n = 10) checked only those with life-threatening reactions. In case of negative IDT/sIgE, 59% of the centres (n = 19) performed components evaluation, while 19% (n = 6) did the basophil activation test. In case of no identification of the culprit insect and sensitization to both venoms, VIT employed venom with higher sIgE. Conclusions: Most allergology centres in Poland follow HVA guidelines. We identified two inaccuracies in their HVA management including non-adequate venom concentration in IDT and a false belief in correspondence between sIgE concentration and severity of allergic reactions.

Allergic rhinitis (AR) and allergic asthma (AA) exhibit similar inflammatory response in the airways. However, the remodelling is more extensive in the lower airways, suggesting that the inflammation itself is not sufficient for allergic phenotype. We aimed to analyse whether the expression of selected 27 inflammatory and fibrosis-related proteins may be altered in AR and AA in the paediatric population and whether the expression pattern is either similar (due to the inflammation) or disease-specific (due to the remodelling). We analysed 80 paediatric subjects: 39 with AA, 21 with AR and 20 healthy children. The diagnosis of AR and AA was based on clinical manifestation, lung function, positive skin prick tests and increased immunoglobulin E levels. Serum levels of selected inflammatory proteins were measured with custom Magnetic Luminex Assay. Statistical analysis was performed in Statistica v.13. CCL2/MCP1, GM-CSF, gp130 and periostin concentrations were significantly lower, whereas IL-5 levels were higher in AA compared to the control group. CD-40L, CHI3L1/YKL-40, EGF, GM-CSF and periostin levels were significantly decreased in patients with AR than in the control group. Comparison of AA and AR patients revealed significant changes in CHI3L1/YKL-40 ( P = 0.021), IL-5 ( P = 0.036), periostin ( P = 0.013) and VEGFα ( P = 0.046). Significantly altered proteins were good predictors to distinguish between AA and AR ( P < 0.001, OR 46.00, accuracy 88.57%). Our results suggest that the expression of four fibrotic proteins was significantly altered between AA and AR, suggesting possible differences in airway remodelling between upper and lower airways.

Objective: Otitis media with effusion (OME) is a common childhood disease and the main cause of conductive hearing loss in this age group. Many factors predispose to OME but allergy is still widely disputed. The answer may lay in the molecular mechanisms of ear exudate formation and the recent studies showed miRNAs might take part in it. MiRNAs are also potent regulators of allergic response. As miRNAs are present in the middle ear, we hypothesized their expression differs between allergic and non-allergic patients and reflects the difference in pathomechanism of effusion formation between these two groups. Materials and methods: This study aimed to establish the expression of 5 different miRNAs (miR-223-3p, miR-451a, miR-16-5p, miR-320e, miR-25-3p) in ear exudates in children diagnosed with OME. The allergy group consisted of 18 patients whereas the non-allergic group had 36 patients. MicroRNA was isolated from the middle ear fluid collected during myringotomy and transcribed into cDNA. MiRNA expression was measured with TaqManTM MicroRNA Assays and analyzed with DataAssist software. The comparative CT method was used for calculating the relative quantification of gene expression based on the endogenous control gene expression (U6 snRNA-001973). Results: MiR-320e expression was significantly decreased in allergic children with OME. Other studied miRNAs also showed reduced expression in allergic children, but the decrease was not significant. Conclusions: MiRNA expression differs between children with and without allergy in the course of OME, but further studies are needed to explain the exact role of miR-320e and its target genes in OME pathology in allergic patients. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of Oto-Rhino-Laryngological Society of Japan Inc.