Mirjana Turkalj

Validation of a multi-sensor activity monitor for assessing sleep in children and adolescents

OBJECTIVE To assess the validity of a multi-sensor activity monitor in estimating sleep and wake compared to polysomnography in children and adolescents. METHODS A total of 43 children and adolescents (29 boys, 14 girls), aged 7-17years (mean age [SD] = 11.0 [2.4] years) participated in the study. Participants wore the SenseWear Pro(3) Armband™ (SWA) body monitor (BodyMedia Inc) during an overnight polysomnographic assessment in a paediatric sleep laboratory. Sleep measures included sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE). RESULTS No systematic bias of the SWA was noted for any of the sleep measures assessed, but limits of agreement were wide and amounted to -76 to +58min for SOL, -75 to 102min for WASO, -109 to +99min for TST and -22 to +20% for SE. In addition, no effect of gender, age group (children versus adolescents) or overweight on the accuracy of the SWA was found. CONCLUSIONS The SenseWear Armband™ showed good agreement with polysomnography at the group level, while at the individual level rather, poor agreement between the two methods was observed. Consequently, at this point the use of the SWA in the clinical evaluation of sleep cannot be advocated.

Effects of allergic diseases and age on the composition of serum IgG glycome in children

It is speculated that immunoglobulin G (IgG) plays a regulatory role in allergic reactions. The glycans on the Fc region are known to affect IgG effector functions, thereby possibly having a role in IgG modulation of allergic response. This is the first study investigating patients’ IgG glycosylation profile in allergic diseases. Subclass specific IgG glycosylation profile was analyzed in two cohorts of allergen sensitized and non-sensitized 3- to 11-year-old children (conducted at University of Aberdeen, UK and Children’s Hospital Srebrnjak, Zagreb, Croatia) with 893 subjects in total. IgG was isolated from serum/plasma by affinity chromatography on Protein G. IgG tryptic glycopeptides were analyzed by liquid chromatography electrospray ionization mass spectrometry. In the Zagreb cohort IgG glycome composition changed with age across all IgG subclasses. In both cohorts, IgG glycome composition did not differ in allergen sensitized subjects, nor children sensitized to individual allergens, single allergen mean wheal diameter or positive wheal sum values. In the Zagreb study the results were also replicated for high total serum IgE and in children with self-reported manifest allergic disease. In conclusion, our findings demonstrate no association between serum IgG glycome composition and allergic diseases in children.

Urates in exhaled breath condensate as a biomarker of control in childhood asthma

Abstract Objective: The aim of this study was to (1) investigate the possibility to use urates in exhaled breath condensate (EBC) as a biomarker of airway inflammation and control in childhood asthma and (2) explore their association with other biomarkers of airway inflammation and clinical indices of asthma control (Asthma Control Test [ACT], quality of life [PAQLQ], lung function, prn beta-agonist use, time from last exacerbation [TLE]. Methods: This cross-sectional study comprised 103 consecutive patients (age 6–18 years) divided in groups of uncontrolled ([NC], n = 53) and controlled asthma ([C], n = 50). Measured lung function and biomarkers included: spirometry, eosinophilic cationic protein (ECP), high-sensitivity C-reactive protein (hs-CRP), exhaled NO (FENO), pH and urates in EBC and exhaled breath temperature (EBT). Results: Statistically significant differences were found between groups for EBC urates, EBC pH and EBT (NC versus C: EBC urates, median [IQR], µmol/L; 10 [6] versus 45 [29], p < 0.001; EBC pH, mean [SD], 7.2 [0.17] versus 7.33 [0.16], p = 0.002; EBT mean [SD], °C; 34.26 [0.83], versus 33.90 [0.60], p = 0.014). EBC urates showed significant association with TLE and FENO (r = 0.518, p < 0.001; r = 0.369, p = 0.007, respectively) in NC, and EBC pH (r = 0.351, p < 0.001), FEV1 (r = 0.222, p = 0.024), ACT (r = 0.654, p < 0.001), PAQLQ (r = 0.686, p < 0.001) and prn salbutamol use (r = −0.527, p < 0.001) in all asthmatics. Conclusion: In our study, EBC urates were found to be the best single predictor of asthma control and underlying airway inflammation. Our results provide evidence supporting the potential utility to use EBC urates as an additional non-invasive biomarker of control in childhood asthma.

Inhaled corticosteroids used for the control of asthma in a “real-life” setting do not affect linear growth velocity in prepubertal children

Summary Background Recent guidelines recommend inhaled corticosteroids as the first-line treatment for persistent asthma. However, long-term corticosteroid treatment in children has raised concerns about potential growth rate deceleration. We aimed to assess the association of growth velocity with the use of inhaled corticosteroids in prepubertal children with asthma in a “real-life” setting. Material/Methods This study included 844 children aged 4–9.5 years coming to the hospital for regular check-ups between October 2006 and February 2009 for asthma with/without allergic rhinitis and no other known constraints of growth. Out of the 844 children, 790 had all data needed for analysis – 245 children were not treated with ICS, 545 children received ICS (fluticasone, budesonide) with/without INCS (fluticasone, mometasone or budesonide). During the study period, 48 children with/without ICS received short SCS courses. Results Mean (SE) height at the first check-up was 123.1 (0.31) cm; range (100.0–147.8 cm). Mean (SE) linear growth velocity (LGV) of the included children was 0.185 (0.0035) mm/day between 2 check-ups. No significant difference was found in LGV between the group not treated with ICS (0.180 mm/day±0.0055) and the group treated with ICS (0.187±0.0044 mm/day). Also, there was no statistical difference between subgroups according to additional therapy with INCS and SCS. No significant correlation was found for LGV and daily dose of ICS (r=0.086, p>0.05). Conclusions In our retrospective study using electronic hospital database, ICS and combined use of corticosteroids did not show any association with LGV in prepubertal asthmatic children in a “real-life” setting.

Normal Variation of Bronchial Reactivity in Nonasthmatics is Associated with the Level of Mite-Specific IgE

Objective. To investigate association between non-specific bronchial reactivity (NBR) and level of mite specific IgE amongst mite-sensitized non-asthmatic subjects. Methods. Subjects attending occupational check-up were assessed for: respiratory symptoms, atopic status (skin prick testing [SPT], total and specific IgE), spirometry and NBR. Individuals without history of respiratory disease (N = 234) were included into analysis. Results. All subjects had normal spirometry and 99% had normal NBR while 41.8% had detectable specific IgE to mites. Lung function parameters and NBR were significantly lower in mite sensitized subjects. Multiple regression analysis controlling for age, gender, smoking, family history, SPT, IgE, and lung function showed that NBR was significantly associated only with mite specific IgE level (ß = 0.26; 95% CI, 0.05–0.47; p = 0.018). Conclusion. Even in subjects without allergic symptoms, IgE-mediated sensitization does not appear to be all or nothing phenomenon influencing the normal variability of underlying airway reactivity.

Allergen-Specific IgE Measurement: Intermethod Comparison of Two Assay Systems in Diagnosing Clinical Allergy

Our aim was to examine the performance of IMMULITE 2000 assay for specific IgE (sIgE) by comparing it with ImmunoCAP technology in light of a clinical background.

Diagnostic value of a pattern of exhaled breath condensate biomarkers in asthmatic children

BACKGROUND Diagnosing asthma in children is a challenge and using a single biomarker from exhaled breath condensate (EBC) showed the lack of improvement in it. OBJECTIVE The aim of this study was to assess the diagnostic potential of a pattern of simple chemical biomarkers from EBC in diagnosing asthma in children in a real-life setting, its association with lung function and gastroesophageal reflux disease (GERD). METHODS In 75 consecutive children aged 5-7 years with asthma-like symptoms the following tests were performed: skin prick tests, spirometry, impulse oscillometry (IOS), exhaled NO (FENO), 24-hour oesophageal pH monitoring and EBC collection with subsequent analysis of pH, carbon dioxide tension, oxygen tension, and concentrations of magnesium, calcium, iron and urates. RESULTS No significant differences were found for individual EBC biomarkers between asthmatics and non-asthmatics (p>0.05 for all). A pattern of six EBC biomarkers showed a statistically significant (p=0.046) predictive model for asthma (AUC=0.698, PPV=84.2%, NPV=38.9%). None to moderate association (R2 up to 0.43) between EBC biomarkers and lung function measures and FENO was found, with IOS parameters showing the best association with EBC biomarkers. A significantly higher EBC Fe was found in children with asthma and GERD compared to asthmatics without GERD (p=0.049). CONCLUSIONS An approach that involves a pattern of EBC biomarkers had a better diagnostic accuracy for asthma in children in real-life settings compared to a single one. Poor to moderate association of EBC biomarkers with lung function suggests a complementary value of EBC analysis for asthma diagnosis in children.

The effect of gas standardisation on exhaled breath condensate pH and PCO2

To the Editors: We read with interest the recent article by Kullmann et al. 1 reporting the effect of gas standardisation on exhaled breath condensate (EBC) pH. pH can be determined immediately upon sampling, without gas standardisation 2, or following EBC gas standardisation in case of delayed analysis 3–5. The influence of ambient air and analytical sample preparation pose a major problem for pH and carbon dioxide tension ( P CO2) determination in EBC. In gas standardisation (argon bubbling or CO2-free gas), CO2 is removed from the sample, thus reducing the effect of CO2 on pH determination. Kullmann et al. 1 even proposed CO2 standardisation at a P CO2 of 5.33 kPa, physiological alveolar P CO2. Based on the experience with gas determination in blood, which should not be exposed to ambient air, the aim of our …

A review of clinical efficacy, safety, new developments and adherence to allergen-specific immunotherapy in patients with allergic rhinitis caused by allergy to ragweed pollen ( Ambrosia artemisiifolia )

Allergic rhinitis is a common health problem in both children and adults. The number of patients allergic to ragweed (Ambrosia artemisiifolia) is on the rise throughout Europe, having a significant negative impact on the patients’ and their family’s quality of life. Allergen-specific immunotherapy (AIT) has disease-modifying effects and can induce immune tolerance to allergens. Both subcutaneous immunotherapy and sublingual immunotherapy with ragweed extracts/preparations have clear positive clinical efficacy, especially over pharmacological treatment, even years after the treatment has ended. AIT also has very good safety profiles with extremely rare side effects, and the extracts/preparations used in AIT are commonly well tolerated by patients. However, patient adherence to treatment with AIT seems to be quite low, mostly due to the fact that treatment with AIT is relatively time-demanding and, moreover, due to patients not receiving adequate information and education about the treatment before it starts. AIT is undergoing innovations and improvements in clinical efficacy, safety and patient adherence, especially with new approaches using new adjuvants, recombinant or modified allergens, synthetic peptides, novel routes of administration (epidermal or intralymphatic), and new protocols, which might make AIT more acceptable for a wider range of patients and novel indications. Patient education and support (eg, recall systems) is one of the most important goals for AIT in the future, to further enhance treatment success.

Ataxia-Telangiectasia Presenting as Cerebral Palsy and Recurrent Wheezing: A Case Report

Patient: Male, 8 Final Diagnosis: Ataxia-telangiectasia Symptoms: Ataxia • sinopulmonary infection • telangiectasiae • wheezing Medication: — Clinical Procedure: IVIG supstitution Specialty: Pediatrics and Neonatology Objective: Rare disease Background: Ataxia-telangiectasia (A-T) is an autosomal recessive disease that consists of progressive cerebellar ataxia, variable immunodeficiency, sinopulmonary infections, oculocutaneous telangiectasia, radiosensitivity, early aging, and increased incidence of cancer. Case Report: We report the case of an 8-year-old boy affected by A-T. At 12 months of age, he had a waddling gait, with his upper body leaning forward. Dystonic/dyskinetic cerebral palsy was diagnosed at the age of 3 years. At age 6 he was diagnosed with asthma based on recurrent wheezing episodes. A-T was confirmed at the age 8 years on the basis of clinical signs and laboratory findings (increased alpha fetoprotein - AFP, immunodeficiency, undetectable ataxia-telangiectasia mutated (ATM) protein on immunoblotting, and identification A-T mutation, 5932G>T). Conclusions: The clinical and immunological presentation of ataxia-telangiectasia (A-T) is very heterogeneous and diagnostically challenging, especially at an early age, leading to frequent misdiagnosis.