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OBJECTIVE The literature provides some evidence of peripheral airways key role in the pathogenesis of asthma. However, the extent to which lung periphery including acinar zone contribute to asthma activity and control in pediatric population is unclear. Therefore, the aim of the study was to estimate peripheral airways involvement in children with asthma exacerbation and stable asthma simultaneously via different pulmonary function tests. METHODS Children with asthma exacerbation (n = 20) and stable asthma (n = 22) performed spirometry, body plethysmography, exhaled nitric oxide, impulse oscillometry (IOS), and multiple-breath washout (MBW). RESULTS Peripheral airway's function indexes were increased in children with asthma, particularly in group with asthma exacerbation when compared with stable asthma group. The prevalence of abnormal results was significantly higher in asthma exacerbation. All children with asthma exacerbation had conductive ventilation inhomogeneity; 76% had acinar ventilation inhomogeneity. According to IOS measurements, resistance and reactance were within normal range, but other IOS parameters were significantly higher in children with asthma exacerbation compared with stable asthma group. The 36% of children with acute asthma had air trapping. CONCLUSION Significant involvement of peripheral airways was observed in children with asthma, particularly in asthma exacerbation, which determine lung periphery as important additional target for therapy and provide new insights into pathophysiological process of pediatric asthma.

Lung ultrasound (LUS) has been increasingly used in diagnosing and monitoring of various pulmonary diseases in children. The aim of the current study was to evaluate its usefulness in children with persistent tachypnea of infancy (PTI). This was a controlled, prospective, cross-sectional study that included children with PTI and healthy subjects. In patients with PTI, LUS was performed at baseline and then after 6 and 12 months of follow-up. Baseline results of LUS were compared to (a) baseline high-resolution computed tomography (HRCT) images, (b) LUS examinations in control group, and (c) follow-up LUS examinations. Twenty children with PTI were enrolled. B-lines were found in all children with PTI and in 11 (55%) control subjects (P < .001). The total number of B-lines, the maximal number of B lines in any intercostal space, the distance between B-lines, and pleural thickness were significantly increased in children with PTI compared to controls. An irregularity of the pleural line was found in all patients with PTI and in none of the healthy children. There were no significant changes in LUS findings in patients with PTI during the study period. The comparison of HRCT indices and LUS findings revealed significant correlations between the mean lung attenuation, skewness, kurtosis and fraction of interstitial pulmonary involvement, and the number of B-lines as well as the pleural line thickness. LUS seems to be a promising diagnostic tool in children with PTI. Its inclusion in the diagnostic work-up may enable to reduce the number of costly, hazardous, and ionizing radiation-based imaging procedures.

In about 3% of children, viral infections of the airways that develop in early childhood lead to narrowing of the laryngeal lumen in the subglottic region resulting in symptoms such as hoarseness, abarking cough, stridor, and dyspnea. These infections may eventually cause respiratory failure. The disease is often called acute subglottic laryngitis (ASL). Terms such as pseudocroup, croup syndrome, acute obstructive laryngitis and spasmodic croup are used interchangeably when referencing this disease. Although the differential diagnosis should include other rare diseases such as epiglottitis, diphtheria, fibrinous laryngitis and bacterial tracheobronchitis, the diagnosis of ASL should always be made on the basis of clinical criteria.

Periostin is considered to be a marker of eosinophilic inflammation in patients with asthma. However, there are no literature data on exhaled breath condensate (EBC) periostin level in pediatric patients with asthma. The aim of this study was to analyze EBC periostin concentration in children with mild asthma and to evaluate the potential usefulness of EBC periostin level as a biomarker for the disease.EBC and serum periostin concentrations were measured by enzyme-linked immunosorbent assay in 23 children with asthma and 23 healthy controls.EBC periostin concentration was 250- to 780-fold lower than that found in serum. No significant differences between serum nor EBC periostin concentration in asthmatics and the control group were showed. The comparison between children with Th2 and non-Th2 type of asthma did not show significant differences in periostin concentration, both in serum and EBC. Serum periostin concentration inversely correlated with BMI and age not only in asthma patients but also in controls.In children with mild asthma, periostin may be measured not only in serum but also in EBC. The low periostin level in patients with mild asthma and lack of difference between asthmatic subjects and controls indicate that EBC periostin may not be useful as an asthma biomarker in this group.

The prevalence of allergic diseases has reached epidemic proportions in the Western world. Although farm-living has been associated with a lower prevalence of asthma and atopy, a marked increase in atopy among rural populations after accession to the European Union has been recently reported in Poland. Here, we aimed to investigate the effect of living environment on the prevalence of atopy and allergic diseases in Polish children.400 schoolchildren aged 10-14 years from the capital city (223) and from traditional rural part of the country (177) were recruited from June to November 2011. Data on allergic diseases and symptoms were collected by means of questionnaire and physical examination. Atopy was assessed based on skin prick tests (SPTs) reactivity to inhalant allergens in 350 children.A high discrepancy between the prevalence of allergic symptoms (46.7%) and doctor-diagnosed allergic diseases (25%) was demonstrated (p0.0001). Urban children had a higher overall prevalence of allergic diseases and atopy than children living in rural areas, 29.3% versus 17.1% (p = 0.007) and 33.5% versus 20% (p = 0.0045), respectively. However, no significant differences in the rates of particular allergic diseases were noted (p0.05). There was higher SPT positivity to trees, grass, corn, weeds, animal dander, and molds in urban children (p0.05).Our data support the protective effect of farm-living on the prevalence of atopy and overall allergic diseases, albeit not on particular allergic diseases, in children in Poland. The underlying mechanisms are not identified, but current socioeconomic changes may be responsible.

Objectives To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN-ɣ) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB antigens) in the QuantiFERON-TB Gold in-Tube test (QFT-GIT), (Cellestis Ltd., Australia). Working hypothesis Is TB-antigen-induced IFN-ɣ response in children ≤5 years sufficient to consider QFT-GIT a possible tool for TB diagnostics? Study design, patient-subject selection, and methods: We recruited children 0-17 years old suspected of TB infection to this cross-sectional study, in whom QFT-GIT and TST were performed. We analyzed the median IFN-ɣ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN-ɣ level in both tubes and age. Results A total of 153 children were enrolled, age median was 7.8 (IQR:8), 45 (29.4%) aged ≤5 years (median 3.4, IQR:1.7), 108 > 5 years (median 10.55, IQR:5.93). In the mitogen tubes, the median IFN-ɣ level was higher in children >5 years (median 17.87, IQR:2.1 vs 16.77, IQR:7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR:0.21vs 0.06, IQR:0.09, P = 0.04). We proved a positive correlation between IFN-ɣ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = -0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = -0.39, P = 0.01). Conclusions The youngest children release sufficient amount of IFN-ɣ in response to TB antigens thus QFT-GIT might be a useful tool for TB diagnostics in this age group.

This is a retrospective study whose main objective was to analyze the influence of the Polish Guidelines for the Management of Respiratory Tract Infections of 2010 (PGMRTI) on in-hospital treatment of children with community-acquired pneumonia (CAP). Files from four Warsaw hospitals were reviewed to identify children with uncomplicated CAP, treated before (2008-2009) (pre-PGMRTI) and after (2011-2012) (post-PGMRTI) publication of the guidelines. Predefined data on the management were compared. A cohort of 2,359 children (1,081 pre-PGMRTI and 1,278 post-PGMRTI) was included. We found that co-amoxiclav was the most common first-line therapy in children3 months of age (34.6% and 40.4% pre- and post-PGMRTI, respectively), followed by cefuroxime (31.8% and 20.9% pre- and post-PGMRTI, respectively; p 0.0001) and macrolides (17.4% and 24.5% pre- and post-PGMRTI, respectively; p 0.0001). Amoxicillin was rarely used (5.4% and 4.9%, pre- and post-PGMRTI, respectively). The study revealed an overuse of inhaled bronchodilators, corticosteroids, and mucoactive drugs. Blood diagnostic tests were applied to a significant percentage of patients: blood cultures (41.2% and 44.5% pre-and post-PGMRTI, respectively) and serology for atypical pathogens (27.9% and 44.9% pre-and post-PGMRTI, respectively; p 0.0001). The number of follow-up chest X-rays increased (30.5% and 53.8% pre- and post-PGMRTI, respectively; p 0.0001). In conclusion, the study demonstrates an unsatisfactory influence of the guidelines on in-hospital management of CAP in children. Despite an explicit recommendation for the use of amoxicillin, it was still underused. Other methods of education and guideline dissemination are needed to optimize the prescribing of antibiotics.

In our previous paper [M. Rępalska et al., Rev. Sci. Instrum. 90, 024103 (2019)], a new method for measuring the growth of children based on the measurement of the lower leg length during foot movement was described. This current paper presents more measurements being conducted to ensure the effectiveness of the proposed arrangement. The study was carried out at weekly intervals with a research group amounting to 20 participants. The presented results show that the method allows for the identification of even a weekly increase in the lower leg length at different velocities of growth. In addition, the method enables the estimation of the trend characterizing each individual and can distinguish the periods of time during which perturbative factors in the process of growth may arise. A metrological analysis was also conducted, allowing a qualitative evaluation of the results, which are presented together with the measurement uncertainties.

Background An increasing incidence of parapneumonic effusion and pleural empyema (PPE/PE) has been reported in recent studies. As only few data on etiology of PPE/PE in Central Europe have been reported, we undertook a study on the etiology of PPE/PE in children, using both standard culture and molecular techniques. Methods This prospective study was conducted between June 2011 and December 2013. Consecutive children with PPE/PE complicating community acquired pneumonia, who required diagnostic/therapeutic thoracentesis were included. Blood and pleural fluid samples for microbiological cultures were collected. Molecular methods were applied to identify Streptococcus pneumonia, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and respiratory viruses in pleural fluid. Results The study group included 64 children, median age 4 (1–15). Seven of 64 (10.9%) blood cultures and 11 of 64 (17.2%) pleural fluid cultures revealed bacterial growth. The most common bacteria detected was S. pneumoniae (13 blood and pleural fluid samples from 11/64 (17.2%) children). DNA sequences of typical bacteria were found in 29/64 (45.3%) pleural fluid samples. S. pneumoniae was identified in 90% of these samples. The most common serotypes were: serotype 6B in 9/26 (36.6%), 19A in 6/26 (23%), serotype 3 in 3/26 (11.5%), 6A and 23F (both in 2/26 i.e. 7.7%) patients. Molecular methods identified atypical bacteria in 8/58 (13.8%) and respiratory viruses in 12/58 (20.7%) pleural fluid samples. Conclusions S. pneumoniae, in particular serotype 6B and 19A, is the most common etiologic agent of PPE/PE in Polish children. The use of PCR significantly improves pathogen identification in pleural fluid., Highlights • Pleural empyema is challenging complication of childhood community acquired pneumonia. • S. pneumoniae is the most common pathogen responsible for pleural empyema in children. • Serotypes 6B and 19A were most commonly identified as causative pathogens. • The use of PCR improves the efficacy of pathogen identification in pleural fluid. • Molecular methods can help to detect atypical bacteria and viruses in pleural fluid.

Introduction: Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. Material and methods: There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. Results: FEV1, FEV1/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs. 9 (11%). 24-months observation didn’t reveal progression in lung function impairment. Conclusions: Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

Lung ultrasound (LUS) is as an easily accessible, radiation-free imaging technique that might be used as a diagnostic tool in community-acquired pneumonia (CAP). The aim of the study was to evaluate the usefulness and accuracy of LUS in the diagnosis and monitoring of childhood CAP. One hundred six consecutive children aged between 1 and 213 (median 52.5) months referred to the hospital with suspicion of CAP were enrolled. All patients underwent LUS on the day of admission, followed by chest radiograph (CXR). Lung ultrasound was also performed in 25 children between 5th-7th and 31 children between 10th-14th day after admission. Radiographic signs of pneumonia were demonstrated in 76 children, while lung ultrasound revealed pulmonary abnormalities consistent with pneumonia in 71 children. LUS gave false negative results in 5 patients with parahilar pulmonary infiltrates demonstrated by CXR. Almost perfect overall agreement between LUS and CXR was found in terms of pneumonia diagnosis (Cohen kappa coefficient of 0.89). The diagnostic performance of LUS in demonstration of lung involvement was as follows: sensitivity of 93.4%, specificity of 100%, positive predictive value of 100%, negative predictive value of 85.7% and accuracy of 95.3%. Our study showed that LUS is a sensitive and highly specific diagnostic method in children with CAP. Therefore, LUS may be considered as the first imaging test in children with suspicion of CAP. A diagnostic algorithm of CAP which includes LUS should be validated in prospective studies. Lung ultrasound can also be used to follow-up resolution of pneumonic lesions.

Decreased level of L-arginine may lead to airway hyperresponsiveness, inflammation, and airway remodeling. Changes in L-arginine metabolism were observed earlier in adult asthmatic patients. Studies on L-arginine metabolism in children with bronchial asthma are limited. Because biosynthesis of L-arginine is insufficient in growing children, its potential metabolic alterations may have important clinical implications. This study was designed to evaluate L-arginine metabolism in children with well-controlled asthma. The studies were conducted on blood serum of 30 asthmatic and 20 healthy children (control group). Levels of L-arginine and its metabolic products, L-citrulline and L-ornithine, were measured by HPLC. Arginase activity was determined spectrophotometrically. Disease severity was evaluated by the asthma control test (ACT) and the level of nitric oxide (NO) in exhaled air. In asthmatic children L-arginine concentration was significantly lowered, whereas arginase activity was unchanged when compared with the healthy group. However, L-ornithine and L-citrulline levels were significantly increased. There was no correlation between arginase activity, amino acids levels, ACT scores, and exhaled NO. In children with chronic, well-controlled asthma L-arginine metabolism is altered. Given that L-arginine is absolutely essential for children, our findings may be of particular importance for the management of children with non-exacerbated asthma. They may also help to develop new therapeutic strategies targeted at L-arginine metabolism in the future.

Alpha-1 antitrypsin (AAT) deficiency is the most common genetic disorder in the adult popu-lation of European descent [...]

Background Detection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. Objective The aim of this study was to assess the potential of this technique for the diagnosis of pediatric cow milk allergy. Material and methods The quantification of total and specific IgE and basophil activation test were performed to evaluate cow milk allergic (n = 9), and non-allergic children (n = 15). Results Allergen-induced basophil activation was detected as a CD203c up-regulation. The expression of CD203c antigen on basophils was measured with flow cytometry. The antigen CD203c was detected on 15.4 ± 10.2% basophils from allergic children after incubation with specific allergens in concentration 1:10, whereas in the control group there were 3.0 ± 1.5% of basophils positive for this molecule (P < 0.05). Stimulation with allergen diluted 1:500 resulted in activation of 15.3 ± 11.2% of basophils in allergic children and 3.8 ± 2.3% of cells in the control group (P < 0.05). Positive results of an allergenicity test (above the cut- off level of 10%) were obtained in 7 out of the 9 allergic children. In 5 cases, the cutoff level was reached with both dilution of allergens (1:10 and 1:500). In 1 patient, positive stimulation was observed after stimulation with allergen diluted 1:10 and in another case only 1:500 resulted in stimulation of more then 10% of basophils. In no child of the control group, stimulation above 10% was noted. Conclusions This study demonstrates that the analysis of allergen-induced CD203c up-regulation with flow cytometry is a reliable tool for the diagnosis of cow milk allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity.

Many children with asthma continue to experience symptoms despite available therapies.This study evaluated the efficacy and safety of omalizumab, a humanized anti-IgE mAb, in children with moderate-to-severe persistent allergic (IgE-mediated) asthma that was inadequately controlled despite treatment with medium-dose or high-dose inhaled corticosteroids (ICSs) with or without other controller medications.A randomized, double-blind, placebo-controlled trial enrolled children age 6 to12 years with perennial allergen sensitivity and history of exacerbations and asthma symptoms despite at least medium-dose ICSs. Patients were randomized 2:1 to receive omalizumab (75-375 mg sc, q2 or q4 wk) or placebo over a period of 52 weeks (24-week fixed-steroid phase followed by a 28-week adjustable-steroid phase).A total of 627 patients (omalizumab, n = 421; placebo, n = 206) were randomized, with efficacy analyzed in 576 (omalizumab, n = 384; placebo, n = 192). Over the 24-week fixed-steroid phase, omalizumab reduced the rate of clinically significant asthma exacerbations (worsening symptoms requiring doubling of baseline ICS dose and/or systemic steroids) by 31% versus placebo (0.45 vs 0.64; rate ratio, 0.69; P = .007). Over a period of 52 weeks, the exacerbation rate was reduced by 43% versus placebo (P.001). Omalizumab significantly reduced severe exacerbations. Over a period of 52 weeks, omalizumab had an acceptable safety profile, with no difference in overall incidence of adverse events compared with placebo.Add-on omalizumab is effective and well tolerated as maintenance therapy in children (6 to12 years) with moderate-to-severe persistent allergic (IgE-mediated) asthma whose symptoms are inadequately controlled despite medium to high doses of ICSs.

Aim The aim of this study was to evaluate the factors that could predict the development of local complications (parapneumonic effusion/pleural empyema, necrotizing pneumonia, and lung abscess) in children with community-acquired pneumonia (CAP). Methods Demographic, clinical, and laboratory data were prospectively collected and compared in children with noncomplicated and complicated CAP. Results Two-hundred and three patients aged from 2 months to 17 years were enrolled. There were 141 and 62 children with noncomplicated and complicated CAP, respectively. Significantly longer duration of fever and a higher level of acute phase reactants were demonstrated in complicated when noncomplicated to complicated CAP. Asymmetric chest pain as well as prehospital treatment with ibuprofen and acetaminophen were significantly more common in patients with complicated CAP (P

Background An increasing incidence of parapneumonic effusion and pleural empyema (PPE/PE) in children has been found in several studies published in the last decades. The aim of the study was to evaluate the incidence, etiology, clinical features, treatment strategies and outcomes of PPE/PE in children treated in a referral pulmonary center in central Poland. Material and methods We performed a retrospective analysis of clinical, radiological and laboratory data of all children aged between 1 month and 18 years with PPE/PE due to community acquired pneumonia (CAP) between January 2002 and December 2013. Results One thousand nine hundred and thirty three children with CAP were hospitalized between 2002 and 2013. Parapneumonic effusion or PE was diagnosed in 323 children (16.7%). The proportion of children with CAP related PPE/PE increased from 5.4% in 2002 to 18.8% in 2013. Streptococcus pneumoniae was the most common causative microorganism, responsible for 66.7% cases of known etiology. All children were treated with antibiotics and in 22.6%, and 74.3% of the patients therapeutic thoracentesis, pleural drainage with or without intrapleural fibrinolysis was performed, respectively. Approximately 3% of patients required surgical intervention. Conclusions A significant increase in the incidence of PPE/PE in children with CAP treated in our institution in the last twelve years was found. S. pneumoniae was the most common causative microorganism. Antibiotic therapy with chest drain insertion ± intrapleural fibrinolysis is an effective treatment of PPE/PE and surgical intervention is seldom necessary. With proper management, the overall prognosis in children with CAP related PPE/PE is good.

Matrix metalloproteinase (MMP)-9 is involved in pathophysiology of asthma, mainly asthma-associated airway remodeling. Exhaled breath condensates (EBC) of asthmatics contain increased amounts of MMP-9 with activity higher, than in healthy controls. The increased activity of MMP-9 may originate from its excessive production and activation, but may also result from variations in MMP-9 structure, which are determined by single nucleotide polymorphisms (SNPs). In this pilot study we aimed to assess the possible influence of two functional MMP-9 polymorphisms, Q279R and R668Q, on enzymatic activity of MMP-9, measured in EBC of asthmatic children. The concentration and activity of MMP-9 were analyzed in EBC of 20 children with allergic asthma using specific standard ELISA and novel immunoenzymatic activity assay. The SNPs of MMP-9 were assessed using real-time PCR-based genotyping test. We have found that MMP-9 concentration in breath condensates of children with stable asthma was slightly higher in ELISA, than in the activity assay. Moreover, these results and activity-to-amount ratio have revealed some relationship with a presence of specific 279R and/or 668Q MMP-9 gene variants. Our observation suggests that at least in some patients MMP-9 hyperactivity may result from genetic predisposition, determined by polymorphic variants of MMP-9 gene. Moreover, it supports previous reports postulating significance of MMP-9 in pathogenesis of asthma. However, this issue still requires further studies.

Exposure to environmental tobacco smoke (ETS) has been shown to increase symptoms of allergic bronchial asthma, but direct effects on the expression of inflammatory markers have not been demonstrated thus far.The aim of this study was to assess the correlation of ETS exposure with the expression of proinflammatory mediators in airway secretions, including IFN-gamma and IL-12, as well as IL-5 and IL-13, in allergic asthmatic schoolchildren and healthy control subjects.By using the nasopharyngeal aspiration technique, airway secretions were collected from 24 atopic children with asthma (age, 6-16 years) and 26 healthy control subjects, and the concentration of cytokines was measured with immunoenzymatic methods.IL-13 levels were highly increased in patients with asthma (P.005), and parental tobacco smoke resulted in a significant increase in airway IL-13 secretion in these children compared with that seen in nonexposed children and healthy control subjects (median, 860 pg/mL vs 242 pg/mL and 125 pg/mL, respectively). Furthermore, a positive correlation between IL-13 levels and serum IgE concentrations (r(s) = 0.55) was found in children with allergic asthma.These results indicate that ETS augments the expression and secretion of IL-13 in allergic asthma and that nasopharyngeal aspiration is a suitable method to assess cytokine measurements in airways in children. Measurements of IL-13 in secretions might be taken into account as a noninvasive marker of airway inflammation and to assess the detrimental effects of ETS.

Necrotizing pneumonia (NP) is an emerging complication of community acquired pneumonia (CAP) in children. This study aimed at the evaluation of etiology, clinical features, treatment, and prognosis of NP. The institutional database of children with CAP treated between April 2008 and July 2013 was searched to identify children with NP. Then, data on the NP characteristics were retrospectively reviewed and analyzed. We found that NP constituted 32/882 (3.7%) of all CAPs. The median age of children with NP was 4 (range 1-10) years. The causative pathogens were identified in 12/32 children (37.5%) with Streptococcus pneumoniae being the most common (6/32). All but one patient developed complications: parapneumonic effusion (PPE), pleural empyema or bronchopleural fistula (BPF), which required prompt local treatment. The median duration of hospital stay and antibiotic treatment was 26 (IQR 21-30) and 28 (IQR 22.5-32.5) days, respectively. Despite severe course of the disease no deaths occurred. A follow-up visit after 6 months revealed that none of the patients presented with any signs and symptoms which could be related to earlier pneumonia. Chest radiographs showed complete or almost complete resolution of pulmonary and pleural lesions in all patients. We conclude that necrotizing pneumonia is a relatively rare but severe form of CAP that is almost always complicated by PPE/empyema and/or BPF. It can be successfully treated with antibiotics and pleural drainage without major surgical intervention.

Interpretation of spirometry strongly depends on the applied predicted values. New Global Lung Initiative (GLI) reference values have recently been published but their influence on spirometry interpretation in children has not been widely evaluated. The aim of the study was to compare the interpretation of spirometry using GLI-2012 vs. Polish-1998 reference values. Spirometry results of 315 Caucasian children aged 4-18 were analyzed. Airway obstruction was defined as FEV1/FVCLLN (lower limit of normal: 5th percentile, -1,64 standard deviation), while restrictive ventilatory pattern as FVCLLN and FEV1/FVCLLN. The findings were that FEV1 and FVC expressed as GLI-2012 or Polish-1998 z-scores differed significantly (p0.05). The mean FEV1 z-score was -0.68±1.25 vs. -0.13±1.70 and the mean FVC was -0.34±1.08 vs. 0.30±1.15 for GLI-2012 and Polish-1998, respectively. There was no difference for FEV1/FVC z-scores. Obstructive and restrictive ventilatory patterns were diagnosed in 20.3% and 7.6% children using GLI-2012 values compared with 17.5% and 3.8% when using Polish-1998 reference values, respectively. In conclusion, the use of GLI-2012 reference values in the population of Polish children increases the number of detected lung function abnormalities compared with Polish-1998 reference values.

Aim: To evaluate nitric oxide and interleukin (IL)-6, IL-8 and IL-13 in the exhaled breath of children with allergic rhinitis (AR), before and after intranasal allergen exposure. Methods: A total of 49 children with AR – comprising 20 who also had episodic asthma (AR+A) and 29 without asthma (AR) – were compared with 34 healthy controls. Nitric oxide concentrations in exhaled air (eNO) and IL-6, IL-8 and IL-13 in exhaled breath condensates (EBC) were measured in winter, outside the natural allergen exposure season, before and after an intranasal allergen challenge. Results: The mean concentrations of eNO, IL-6 and IL-13 were significantly higher in the two AR groups. The concentration of IL-8 was below the assay detection limit in all EBC samples. The intranasal allergen challenge increased IL-13/EBC levels in both AR groups, but did not influence mean concentrations of eNO, IL-6 or IL-8. No challenge-related changes in IL-13/EBC were observed in the allergen-exposed controls or placebo-exposed children. Conclusion: Despite local application, the intranasal allergen challenge increased IL-13/ EBC concentration in the AR children. As EBC reflects the status of lower airway segments, our observation may support the ‘united airways’ hypothesis, suggesting a functional link between the upper and lower airways.

Exhaled breath condensate (EBC) contains various mediators of inflammation. Since their concentrations correlate with severity of inflammatory response, EBC assessment allows non-invasive detection of various respiratory tract diseases and enables monitoring of their progression or treatment effectiveness. In this study, authors evaluate the usefulness of cysteinyl leukotrienes (cysLT) measurement in EBC, as non-invasive diagnostic markers of allergic rhinitis in children. It has been found that the assessment of cysLT in EBC, when performed out of the natural allergen exposure, can discriminate between healthy and allergic rhinitis individuals, with sensitivity 87.8 % and specificity 76.4 %, at the threshold level 39.05 pg/ml. The change of peak nasal inspiratory flow (ΔPNIF), measured before and after intranasal allergen challenge allowed recognition of healthy/allergic rhinitis-suffering individuals with sensitivity 76.8 % and specificity 78.6 %, at the threshold level of −3.2 l/min. When ΔPNIF assessment was combined with the measurement of cysLT in EBC, the sensitivity of such diagnostic approach reached 100 % and its specificity increased up to 84.6 %. The proposed algorithm was found to sufficiently discriminate between allergic rhinitis-suffering and healthy children, however, its clinical usefulness especially in young children requires further studies.

Atopic allergy is among the immune tolerance-related disorders resulting from a failure of the regulatory network. Regulatory T cells (Tregs) play a leading role in the development of homeostasis in the immune system. The aim of this study was to determine the role of Tregs in the pathogenesis of atopic diseases in children by exploring the relationship between Treg frequency, activation markers and the clinical manifestations of the disease.Twenty allergic and 50 healthy children were enrolled to the study. Peripheral blood mononuclear cells were stained with monoclonal antibodies (anti-CD25-CD4-CD127-FoxP3-CD69-CD71) and evaluated using flow cytometry. Tregs were identified as CD4+CD25(+/high)FoxP3+CD127- T cells.The percentage of Tregs in allergic patients (2.3%) was significantly decreased in comparison to healthy controls (4.6%, p = 0.003). The frequency of Tregs in patients with symptoms of atopic dermatitis and/or food allergy (1.7%) was significantly lower than in patients without these symptoms (2.9%, p = 0.04). A significant correlation between the percentage of Tregs and the sIgE serum concentration was observed (p = 0.037). Relative fluorescence intensities of FoxP3 expression in allergic patients were higher than in healthy controls (p = 0.00004). The frequency of CD4+CD25(high)CD127-CD71+ cells did not differ between the groups.Tregs display substantial deficiencies in atopic children, especially in children with multiorgan involvement, compared to patients with single organ manifestations. Additionally, there is an association between Tregs and the sIgE serum concentration. Better identification and characterization of Tregs in allergy is needed as they limit responses to foreign antigens, thereby minimizing T cell-mediated immunopathology in allergic diseases.

Hymenoptera venom allergy, although rare in children, by its potential fatalities, leads to many psychosocial consequences, influencing quality of life of children and their parents. Aim of this paper is the estimation of health-related quality of life of venom allergic children treated with specific immunotherapy, and their parents. Assessment of factors influencing health-related quality of life levels was also performed.Sample under study consisted of 73 children: mean age 10.6, SD 2, 4, treated because of Hymenoptera venom allergy in 5 clinical allergy centers in Poland. Data was collected using VQLQ questionnaire adapted for children and their parents. Determinants of quality of life were assessed with multivariate linear and logistic regression models. Analysis were done with SPSS 15 for Windows package.Girls reported higher level of anxiety than boys (B = 0.47; 95% CI = (0.01; 0.94)). Level of caution in children increased along with increase of their anxiety against re-sting (B = 0.49; 95% CI = (0.27; 0.71)). Level of anxiety of children who were under treatment from 6 months to 2 years was lower than level of anxiety of parents of children treated shorter than 6 months (B = -1.21; 95% CI = (-2.16; -0.25)). The lowest level of caution was reported by parents of children aged 10 year or less (B = -0.86; 95% CI = (-1.67; -0.05)), while the highest was reported by parents of children aged 11 years (B = 0.86; 95% CI = (0.20; 1.53)) in comparison to parents of children aged 12 years or more. Parents' caution increased along with increase of their anxiety (B = 0.61; 95% CI = (0.40; 0.83)). Higher level of limitations was imposed by parents of children treated with rush or ultra rush method, in comparison to parents of children treated with conventional method (B = 1.27; 95% CI = (0.21; 2.33)). Levels of quality of life in children and their parents were strongly dependent in the same dimensions.1. Levels of quality of life in particular dimension in children is related to level of the same dimension in parents. 2. Age of children influenced level of caution of their parents. 3. Treatment duration influenced level of anxiety of parents. 4. Safety feeling acquired by parents at the beginning of treatment improves their quality of life in all dimensions.

Aim of the study was to assess validity and reliability of adaptations of VQLQ for Polish children with Hymenoptera venom allergy and their parents. Sample under study consisted of 73 children aged up to 14 years, who were treated with specific venom immunotherapy (VIT) in 2008 in centres conducting this procedure in Poland, and their parents. Theoretical validity of the scales was assessed with exploratory factor analysis using principal component analysis method. Reliability of the scales was assessed in terms of internal consistency with Cronbach alpha coefficient. Results of analysis showed that both scales measure 4 dimension of quality of life and reliability of scales measuring particular dimensions is at least acceptable in case of scale for children, and high in case of scale for parents. Both adapted scales are valid and reliable tools measuring quality of life in children with Hymenoptera venom allergy and their parents' quality of life in the face of child's allergy.

The aim of the study is to systematically evaluate data from randomized controlled trials (RCTs) on the efficacy of using intrapleural fibrinolytic agents in the treatment of complicated parapneumonic effusions or empyema in children. The Cochrane Library, MEDLINE and EMBASE databases were searched in July 2009. Four RCTs, involving 194 children, were included. In two RCTs, intrapleural fibrinolytic treatment was compared with normal saline. One of these RCTs showed a significantly reduced hospital stay in those treated with urokinase compared with those treated with normal saline. Otherwise, no fibrinolytic agent had an effect on any other outcome. Two RCTs that compared fibrinolytic treatment with video-assisted thoracoscopic surgery (VATS) revealed no benefit of VATS.There is little evidence that intrapleural fibrinolysis is more effective than normal saline in the local treatment of complicated parapneumonic effusions or empyema in children. There is no evidence that VATS is more effective than fibrinolytic treatment. Only a limited number of trials were available for analysis, so some caution must be exercised in interpreting the strength of the evidence presented.

Many children with severe persistent allergic (IgE-mediated) asthma remain inadequately controlled despite treatment with high-dose inhaled corticosteroids (ICS) plus a long-acting beta(2)-agonist (LABA).This pre-specified analysis of a randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of omalizumab in children (6-12 years) with perennial allergen sensitivity, and history of asthma exacerbations and symptoms despite treatment with ICS (fluticasoneor=500 microg x day(-1) or equivalent) plus a LABA. Patients received omalizumab (75-375 mg once or twice a month by subcutaneous injection, as determined from dosing tables) or placebo over 52 weeks (24-week fixed-steroid then 28-week adjustable-steroid phases).Out of 246 randomized patients (omalizumab, n = 166; placebo, n = 80), efficacy was analysed in 235 (omalizumab, n = 159; placebo, n = 76). Over the 24-week fixed-steroid phase, omalizumab reduced the rate of clinically significant asthma exacerbations (worsening symptoms requiring doubling of baseline ICS dose and/or systemic steroids) by 34% versus placebo (0.42 vs 0.63, rate ratio 0.662; P = 0.047). Over 52 weeks, the exacerbation rate was reduced by 50% (P0.001). Omalizumab had an acceptable safety profile, with no statistically significant (P0.05) differences in adverse events observed between omalizumab and placebo.Add-on omalizumab is well-tolerated and reduces exacerbations in children (6-12 years) with severe persistent allergic asthma, inadequately controlled despite high-dose ICS plus a LABA. It should be noted that the sample size was not based on providing statistical power in the severe subgroup, and no corrections were made for multiple comparisons; however, outcomes consistently favoured omalizumab.

The introduction of inhaled corticosteroids (ICS) has been a milestone in asthma therapy. According to current guidelines ICS are the first line drug in chronic anti-inflammatory therapy. The purpose of first part of this publication is to present updated knowledge on mechanisms of anti-inflammatory action as well as some pharmacokinetics and pharmacodynamics data about commonly used ICS, especially fluticasone propionate (FP) and two others: budesonide (BUD), beclomethasone dipropionate (BDP). Some differences between mentioned drugs have been found concerning systemic activity and safety of therapy. Fluticasone propionate is twice as active as the BUD and BDP. First results of therapy are seen 1-2 week after administration. Fluticasone propionate, more lipophilic than other steroids, has also high glucocorticoid receptor affinity and specificity, high topical anti-inflammatory activity and low systemic bioavailability. Systemic availability of FP depends on absorption from respiratory system. Oral bioavailability can be neglected because of almost total inactivation in liver during first pass. Fluticasone propionate has some features of dissociated steroids which means predominance of transrepression over transactivation--beneficial from safety point of view. Clinical efficacy of FP in chronic asthma therapy in children was confirmed in many studies. It significantly reduces the symptoms and exacerbations of asthma. There is a close correlation between FP use and lung function tests. The therapy with FP decreases bronchial hyperreactivity and the use of systemic steroids and rescue medication. The beneficial action of fluticasone propionate in asthma is due its anti-inflammatory properties within the airways (decreasing levels of direct and indirect markers of airways inflammations are observed).

Inhaled administration of glucocorticoid doesn't mean lack of systemic effects of drug. Bioavailability of steroid depends on oral absorption and absorption from respiratory system. In case of fluticasone propionate (FP) swallowed dose can be neglected because almost total (99%) inactivation in liver during first pass. In second part of paper the most important safety parameters of therapy with FP are discussed, it means; influence on hypothalamic-pituitary-adrenal axis, growth and bone metabolism. Interpretation of potential side effects should differentiate between abnormal value of laboratory test and clinically important symptoms. Adrenal suppression depends on dose of FP and was found even after low dose (about 200 microg per day), but clinical value of this findings is unknown. Prolonged administration of high doses can suppress hypothalamic-pituitary-adrenal axis; exceptionally, it can induce adrenal insufficiency. Recommended doses of FP given 1 to 2 years doesn't cause growth retardation. Long term studies on influence of drug on final height are needed. FP as other inhaled corticosteroids, may transiently alter bone metabolism. Till now there are no evidences that this drug, when prescribed appropriately in standard doses for asthma control, may decrease the bone mineral density or induce osteoporosis and may increase the risk of bone fractures in asthmatic children. Effective asthma control achieved with FP therapy permits normal activity and development of asthmatic children which prevails over exceptionally noticed side effects.

History Exertional dyspnea for 4 years, medical and family history unremarkable Exertional dyspnea for 2 years, migraine headaches, medical and family history unremarkable Symptoms Central cyanosis, finger clubbing, no abnormalities on heart and lung examination Central cyanosis, finger clubbing, growth retardation (body weight

In the past 16 years, 2004 children with acute lymphoblastic leukemia (ALL) have been treated in the Polish Pediatric Group centers. Eight hundred and eighty-seven (44.3%) of these patients discontinued treatment after the first remission. Acute lymphoblastic leukemia relapse occurred in 180 patients (20.3%). This group was analyzed for the method of treatment and its influence on long-term survival, the time between cessation of treatment and relapse, the character and localization of relapse and later follow-up. It was shown that the patients with the best chance of a second remission are those with late testicular relapse. The most frequent and prognostically poor are bone marrow (BM) relapses which warrant intensive chemotherapy with BM transplantation. Patients with ALL relapse still have the possibility of a second remission and long-term survival.

Summary Background Since extraintestinal sites of inflammation have been demonstrated in patients with Crohn's disease (CD) and ulcerative colitis (UC), both entities are regarded as systemic disorders. There are only scarce data on the prevalence of inflammatory bowel disease (IBD)-associated lung involvement in children. Objectives The aim of our study was to investigate pulmonary involvement in pediatric patients with IBD. Material and methods Fifty children with IBD (25 UC and 25 CD, mean age 14.2 ± 3.2 yrs) and 39 age-matched, healthy, control subjects were included in the study. Pulmonary function testing, methacholine bronchial challenge, fractional exhaled nitric oxide (FeNO) and high resolution computed tomography (HRCT) were used to detect functional and/or structural pulmonary involvement. Results There were no differences in spirometric parameters, lung volumes or lung diffusion capacity for carbon monoxide between IBD patients and control subjects. Highly significant differences were found in FeNO between CD, UC and control patients (mean 9.3 ± 3.3, 27.7 ± 14.8 and 16.6 ± 9.28, respectively; p = 0.000). Bronchial hyperresponsiveness was diagnosed in six IBD cases (14.6%). HRCT (performed in 32 patients from the study group) revealed mild bilateral bronchiectasis in one patient. Conclusions The prevalence of pulmonary involvement in children with IBD is low. Screening for pulmonary involvement in children and young adults with IBD may enable early detection of IBD-related pulmonary diseases which, seems to be notably more common in adult patients. Elevated FeNO could probably be regarded as a marker of airway involvement in non-smoking UC pediatric patients. This requires further studies.

The airway remodeling in asthma is associated with increased amount of matrix metalloproteinase (MMP)-9. High levels of MMP-9 were found in mucosal biopsies, sputum and in exhaled breath condensates (EBC) of asthma patients. However, there are no data concerning real in vivo activity. Inhaled corticosteroids are effective in asthma control, but it is unclear, whether they only attenuate inflammation, or also protect against progressive remodeling of respiratory tract. Therefore, the aim of the study was to assess the amount and activity of MMP-9 in context of pro-inflammatory cytokines (IL-6, IL-8 and tumor necrosis factor, TNF), measured in EBC of asthma-suffering children, treated with inhaled steroids. The study involved 27 children with asthma, continuously treated with inhaled fluticasone propionate, and 22 healthy controls. In addition to routine clinical screening, the selected cytokines in EBC were analyzed using Ultrasensitive ELISA, whereas activity of MMP-9 was assessed using a novel immunozymography method. Despite chronic treatment with inhaled steroids mean MMP-9/EBC activity in asthma group was significantly higher than in healthy controls. Moreover, high MMP-9/EBC in asthma-suffering children significantly correlated with IgE serum levels. The IL-6 and IL-8 concentration was below the detection limit in all EBC samples. TNF/EBC levels were similar in both, asthma and healthy children. We hypothesize that MMP-9 hyperactivity in asthma may be closely related to high IgE serum levels. Our results suggest that inhaled steroids may be ineffective to prevent asthma-associated airway remodeling. Finally, we emphasize the necessity of further research focused on MMP-9 inhibition in asthma treatment.

Pneumonia is still the main cause of initiation antibiotic therapy in children, despite the fact that according to the newest epidemiological data, its incidence seems to be lower. In this paper current data concerning etiology, diagnostics and guidelines are discussed. The empirical antibiotic therapy of childhood pneumonia in different age groups is described. Author showed future trends in research necessary to solve controversies in present guidelines.