Prolonged Treatment with Inhaled Corticosteroids does not Normalize High Activity of Matrix Metalloproteinase-9 in Exhaled Breath Condensates of Children with Asthma.

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.

Fluticasone or montelukast in preschool wheeze: a randomized controlled trial.

INTRODUCTION: Approximately 30% of children younger than 3 years experience at least 1 episode of wheezing. Antiasthmatic medication is routinely prescribed, but its effectiveness remains unclear. Our study was aimed to evaluate the effect of anti-inflammatory treatment on frequency and severity of preschool wheeze episodes (PWEs). METHODS: Children aged 6 to 36 months with the first up to the third PWE were randomly assigned to receive montelukast, fluticasone, or no treatment for 12 weeks. The outcome measures were the number of PWEs, the number of hospitalizations due to PWE, and the severity of respiratory symptoms. results: There were no significant differences in outcome measures between the groups. However, tobacco-exposed children treated with fluticasone had significantly fewer PWEs (P = .01). CONCLUSION: Neither montelukast nor fluticasone has proven effective in the prevention of PWE recurrence. Children of smoking parents may benefit from fluticasone treatment after PWE. This observation requires confirmation in larger studies.

Environmental tobacco smoke exposure and risk of allergic sensitisation in children: a systematic review and meta-analysis.

BACKGROUND: Environmental tobacco smoke (ETS) exposure in children is linked with the development of allergic asthma. However, its influence on allergic sensitisation in children has not been conclusively determined. OBJECTIVE: To systematically review existing evidence of ETS exposure's impact on markers of allergic sensitisation in children. METHODS: CENTRAL, MEDLINE and EMBASE databases were searched. Included studies assessed following markers of atopic sensitisation: total immunoglobulin E (tIgE) concentrations, at least one specific IgE (sIgE+), and positive skin-prick tests (SPTs+) in ETS-exposed and non-exposed children. RESULTS: 8 studies on the influence of ETS on tIgE concentration (2603 patients), 6 studies on ETS and sIgE+ (9230 participants) and 14 papers on ETS and SPT (14 150 patients) met our inclusion criteria. ETS was shown to raise tIgE concentrations by 27.7 IU/mL (95% CI 7.8 to 47.7; I(2)=58%; results based on 3 studies) and to increase the risk of atopic sensitisation, as assessed by sIgE+ (OR=1.12, 95%CI 1.00 to 1.25; I(2)=54%; results based on 4 studies) and SPT+ (OR=1.15; 95% CI 1.04 to 1.28; I(2)=0%; results based on 10 studies). In a subgroup analysis, this effect was most pronounced in children <7 years (preschoolers) by OR=1.20; (95% CI 1.05 to 1.38) and OR=1.30 (95% CI 1.05 to 1.61), (for sIgE+ and SPT+, respectively). CONCLUSIONS: Current analysis supports an association between ETS exposure in early childhood and the increased risk of allergic sensitisation. Subgroup meta-analyses demonstrate that younger children suffer the most from detrimental immunomodulating effects of ETS exposure. This study underscores ETS as an important but avoidable risk factor for the development of allergic disease in children.

[Coexistence of pulmonary sequestration and congenital cystic adenomatoid malformation. Case report and review of literature]. / Wspólistnienie sekwestracji pluca i wrodzonej torbielowatosci gruczolakowatej pluc. Prezentacja przypadku klinicznego i przeglad pismiennictwa.

This paper presents a case report of an infant, with a prenatally diagnosed congenital lung malformation, which proved to be pulmonary sequestration and congenital cystic adenomatoid malformation. The authors discuss current knowledge on diagnosis, clinical course and suggestions of ante- and postnatal management of patients with pulmonary sequestration or/and congenital cystic lung malformation.

Nitric oxide, IL-6 and IL-13 are increased in the exhaled breath condensates of children with allergic rhinitis.

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.

Increased cys-leukotrienes in exhaled breath condensate and decrease of PNIF after intranasal allergen challenge support the recognition of allergic rhinitis in children.

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.

Low prevalence of pulmonary involvement in children with inflammatory bowel disease.

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.

Local treatment of empyema in children: a systematic review of randomized controlled trials.

UNLABELLED: 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. CONCLUSION: 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.

Parental tobacco smoking is associated with augmented IL-13 secretion in children with allergic asthma.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Fatal course of pulmonary Absidia sp. infection in a 4-year-old girl undergoing treatment for acute lymphoblastic leukemia.

Absidia sp. is a rare etiologic agent responsible for infectious complications in immunosuppressed patients. The authors describe a 4-year-old girl with acute lymphoblastic leukemia complicated with pleuropneumonia caused by an Absidia infection during the induction of remission. A review of the published reports in current literature is included for comparison. To the authors' knowledge only six cases of primary pulmonary absidiomycosis have been published. Despite its uncommon pulmonary presentation, mucormycosis should be considered in patients with an immunosuppressing illness and positive risk factors and when a pulmonary lesion is not responding to appropriate antibiotic therapy.

Impaired apoptosis of lymphocytes derived from patient with decreased expression of caspase-8 results in Alps-like phenotype.

Human autoimmune lymphoproliferative syndrome has been described as a result of various mutations concerning genes encoding receptor CD95 and/or its ligand - CD178. However, recently, several cases with identical clinical manifestation, despite a normal structure of CD95 or CD178 have also been reported. In this study we analyzed PBMC obtained from patient with clinically overt lymphoproliferative disorder. Using in vitro assays as well as molecular methods we tested expression and biological activity of CD95 and CD178 molecules. We found that analyzed patient's lymphocytes displayed normal cytotoxic activity against CD95-bearing targets. However, CD95-dependent induction of apoptosis in analyzed lymphocytes was diminished, as compared to healthy control. Surprisingly, the molecular studies did not reveal any abnormalities in structure of patient-derived CD95 receptor molecule. Therefore, expression of other factors involved in CD95-mediated signaling pathway was estimated using RNase protection assay. The expression of FADD was comparable to that of healthy control. However, it has been found that patient-derived lymphocytes expressed reduced amount of caspase-8 mRNA, as compared to control subject cells. This report confirms previous observations that lymphoproliferative disorder could be associated not only with CD95 and/or CD178 mutations, but also with dysfunction of other components of apoptosis induction pathway. However, the detailed molecular mechanism of observed abnormalities in caspase-8 expression remains to be elucidated.