Clinical implication of exhaled breath temperature measurement in pediatric asthma

PURPOSE: Exhaled breath temperature (EBT) has been suggested as a noninvasive marker of airway inflammation in asthma. The aim of this study was to determine its clinical implication in children with asthma. METHODS: A total of 233 children were enrolled in this study. Among them, 116 were asthmatic children and 117 were healthy children. Spirometry, bronchodilator response (BDR) test, methacholine challenge test, and skin prick test were performed. EBT, fractional exhaled nitric oxide (FeNO), blood eosinophils, and total IgE levels were measured. EBT was measured by using X-halo. RESULTS: EBT was significantly higher in the asthma group than in the control group (median [interquartile range], 32.1℃ [30.0℃–33.9℃] vs. 29.7℃ [29.0℃–31.3℃], P<0.001). EBT was significantly higher in poorly or partly controlled asthmatic children than well-controlled asthmatic children (33.5℃ [31.0℃–34.4℃] vs. 30.3℃ [29.3℃–32.9℃], P<0.0001). Among total subjects, EBT was significantly higher in the atopic group than in the nonatopic group (32.4℃ [30.3℃–34.0℃] vs. 29.8℃ [29.0℃–30.3℃], P<0.001). There were neither significant associations between EBT and BDR (r=0.109, P=0.241) nor between EBT and PC20 (provocation concentration causing a 20% fall in FEV1) in total subjects (r=0.127, P=0.316). EBT did not show any association with FeNO (r=0.353, P=0.071). CONCLUSION: Our study suggests that EBT might play a role as an ancillary marker for allergic airway inflammation and the degree of control in pediatric asthma patients. Additional studies are required to explore the value of EBT in detail.

ERRATUM: Acknowledgments. Diagnostic utility of skin prick test to cooked egg in children with egg allergy

In this paper, acknowledgments section for grant support was omitted unintentionally.

Utility of tools for the assessment of asthma control in childhood asthma

PURPOSE: The goal of asthma control is to maintain well-controlled state. In this study, we investigated whether childhood asthma control test (C-ACT) may reflect lung function and whether fractional exhaled nitric oxide (FeNO) can be used to improve the accuracy of C-ACT in reflecting the asthma control level. METHODS: We reviewed the medical records of 155 patients with asthma underwent lung function tests and C-ACT upon visiting our outpatient clinic. We compared lung function test results according to the C-ACT score stratified by atopy and also examined FeNO according to C-ACT and the Global Initiative for Asthma (GINA) guidelines. The diagnostic accuracy of well-controlled asthma by C-ACT, FeNO, and C-ACT+FeNO was examined. We also calculated the cutoff value of FeNO and C-ACT for well-controlled asthma. RESULTS: Peak expiratory flow (PEF) showed a significant correlation with the C-ACT score. Stratified by atopy, PEF, and forced expiration in one second (FEV1) showed significant correlations with the C-ACT score in the atopic asthma group. There was no difference in FeNO between subjects with C-ACT> or =20 and <20, but FeNO was significantly higher in the uncontrolled asthma according to the GINA guidelines. The diagnostic accuracy of well-controlled asthma was higher when FeNO was combined with the C-ACT score than C-ACT or FeNO. Our study showed that the cutoff values of C-ACT and FeNO 19 and 18.3 ppb (parts per billion), respectively, for well-controlled asthma. CONCLUSION: C-ACT showed a significant correlation with PEF, and atopic asthma group showed significant correlations with PEF and FEV1. A combination of C-ACT with FeNO might reflect asthma control status more accurately.

Diagnostic utility of skin prick test to cooked egg in children with egg allergy

PURPOSE: Reliable predictors of tolerance to cooked egg in an egg allergic population are not established. We investigated the usefulness of the skin prick test to cooked egg in children with egg allergy. METHODS: We studied 36 children with egg allergy. Skin prick tests (SPTs) for the uncooked or cooked form of egg white and egg yolk, whole egg, ovomucoid (OVM), and ovalbumin (OVA) were performed at diagnosis. The reagents of cooked egg for SPT were prepared by baking for 25 minutes in 200 degree oven. We also examined specific IgE levels to whole egg, egg white, egg yolk, OVM, and OVA. RESULTS: Patients with history of allergic reaction to extensively heated egg showed significantly increased wheal size for cooked egg white (median [interquartile range]), 10.5 [7.0-14.6] vs. 4.2 [0.0-5.6], P<0.001) and OVM (9.6 [7.3-13.8] vs. 5.6 [0.0-7.8], P=0.001) than those without the history. The strongest positive correlation was found between wheal size for cooked egg white and OVM (r=0.788, P<0.001). SPT wheal size for cooked egg white were positively correlated with serum OVM-specific IgE levels (r=0.691, P<0.001). Cutoff value was 7.0 mm in SPT wheal size for cooked egg white, the sensitivity was 73.1% and specificity was 99.0%. SPT for cooked egg white showed significantly higher area under curve than serum egg white specific IgE. CONCLUSION: Our results suggest that SPT to cooked egg white may be useful predictor of allergic reaction to cooked egg. Further investigations will be needed.

Heterogeneity of asthma according to systemic inflammatory pattern in children

PURPOSE: Asthma is a chronic airway inflammation. We evaluated whether systemic inflammatory patterns could reflect the nature of airway inflammation. We assessed characteristics of asthma according to systemic inflammatory patterns. METHODS: A total of 413 children with asthma were enrolled in the study. Four systemic inflammatory patterns were classified according to eosinophil and neutrophil counts in peripheral blood. Children with neutrophil count> or =5,000/microL were defined as the NEU(hi) group, those with neutrophil count or =650/microL were defined as the EOS(hi) group, those with eosinophil count<240/microL as the EOS(lo) group. The remaining patients were excluded from the study. The characteristics of asthma include pulmonary function test results, bronchodilator response, airway hyperresponsiveness, and atopy. RESULTS: The EOS(hi) group had a lower PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second [FEV1]), a lower FEV1, and a higher immunoglobulin E level rather than the EOS(lo) groups, although there were no significant differences between the NEU(hi) and NEU(lo) groups. The eosinophil percentages of the induced sputum samples were higher in the EOS(hi) group than the EOS(lo) group and correlated with blood eosinophil counts. CONCLUSION: Eosinophilic inflammation was related to characteristics of asthma and sputum eosinophils. However, neutrophilic inflammation reflected neither asthma features, sputum neutrophils, nor eosinophilic inflammation. Further studies on blood neutrophils involving asthma phenotypes in terms of more specific characteristics of asthma should be needed in children.

Fractional Exhaled Nitric Oxide and Impulse Oscillometry in Children With Allergic Rhinitis

PURPOSE: Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response (BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a risk factor for asthma development, we evaluated these 3 characteristics in AR using measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test (MCT), and impulse oscillometry (IOS). METHODS: This study included 112 children with asthma (asthma group), 196 children with AR (AR group), and 32 control subjects (control group). We compared pulmonary function parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2 categories: the AR group with BHR and the AR group without, and again pulmonary function and FeNO levels were compared between the 2 subgroups. RESULTS: FeNO levels were more increased in the AR and asthma groups than in the control group; within the AR group, FeNO was higher in the AR group with BHR than in the AR group without. The BDR was more increased in the AR group than in the control group when percent changes in reactance at 5 Hz (Delta X5) and reactance area (Delta AX) were compared. In the AR group, however, there was no difference in Delta X5 and Delta AX between the AR group with BHR and the AR group without. CONCLUSIONS: Reversible airway obstruction on IOS and elevated FeNO levels were observed in children with AR. Because elevated FeNO levels can indicate airway inflammation and because chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS can be a useful tool for detecting lower airway involvement of AR independent of BHR assessed in the MCT.

Hypersensitivity reaction to aspirin accompanied by severe eosinophilia in a child with history of Kawasaki disease

Drug hypersensitivity is one of drug adverse reactions that develop in susceptible patients following exposure to certain drugs and cannot be predicted from the known pharmacology of a drug. Severe hypersensitivity is associated with high morbidity and mortality. Although the issue of hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) has been largely investigated in adults, data related to NSAIDs hypersensitivity is insufficient in childhood. And in spite of the recommendation to avoid use of aspirin due to Reye syndrome in children, aspirin is one of major treatment along with intravenous immunoglobulin in Kawasaki disease. We report a case of a 10-month-old boy who underwent intravenous immunoglobulin and aspirin treatment for Kawasaki disease, and subsequently revealed severe leukocytosis and eosinophilia. To our knowledge, there have been no previous reports of aspirin-induced eosinophilia in Korea.

Increased inflammatory mediator in exhaled breath condensate from asthmatic children

PURPOSE: There has recently been increasing interest in the use of exhaled breath condensate (EBC) as a simple noninvasive means for understanding the physiology of asthma. The aim of this study was to evaluate the levels of leukotriene B4 (LTB4) and eosinophil cationic protein (ECP) in the EBC of asthmatic children. METHODS: We measured LTB4 and ECP levels in EBC from children aged 6-14 years, including healthy children (n=25) and asthmatic children (n=25). We also measured serum LTB4 and serum ECP. Pulmonary function tests and methacholine challenge tests were performed on all subjects. RESULTS: Exhaled LTB4 levels were increased significantly in patients with asthma compared to normal subjects (7.1+/-3.7 pg/mL vs. 2.2+/-1.7 pg/mL, P<0.05). Serum LTB4 levels were not significantly different in patients with asthma compared to normal subjects (674.7+/-484.1 pg/mL vs. 487.1+/-272.0 pg/mL, P=0.156,) and no significant correlations were found between exhaled and serum LTB4 concentrations in children with asthma (r=0.052, P=0.758). Exhaled ECP levels were not significantly different in patients with asthma compared to normal subjects (P=0.419). Serum ECP levels were significantly increased in patients with asthma compared to normal subjects (44.37+/-32.14 microg/L vs. 16.40+/-13.23 microg/L, P=0.001). CONCLUSION: We found significantly elevated LTB4 levels in the EBC of asthmatic children. Our results suggest that EBC may be one of the supportive tools to measure airway inflammation in children with asthma.

Usefulness of Thrombocytopenia and Changes in Platelet Counts as Prognostic Markers in Pediatric Intensive Care Units / 대한구급학회지

BACKGROUND: Thrombocytopenia has been shown to be a useful predictor of mortality in adult intensive care units (ICUs). The aim of this study is to assess whether the level of platelet count at ICU admission and the changes in platelet counts can predict mortality in the pediatric ICU (PICU). METHODS: Platelet counts were checked daily for at least 4 days in a total of 303 children who were admitted to the ICU. We compared the initial platelet counts and changes in platelet counts between survivors and non-survivors. A multivariable logistic regression model, a receiver operating characteristic curve and a linear mixed model were used. RESULTS: The initial platelet count was significantly lower in non-survivors when compared to survivors. Multivariate analysis demonstrated that platelet count <120 x 10(9)/L (Odds ratio, 4.913; 95% confidence interval 2.451-9.851; p < 0.0001) was an independent predictor of mortality. In the case of children with thrombocytopenia (<120 x 10(9)/L) at admission to the ICU, the platelet counts increased serially in survivors, whereas non-survivors maintained their decreased platelet counts. In the case of children without thrombocytopenia, the platelet counts decreased most on day 3 in non-survivors. CONCLUSIONS: At admission to the ICU, thrombocytopenia defined as a platelet count <120 x 10(9)/L can be a useful predictor of mortality in children. In children who had initial thrombocytopenia, the serial increase of platelet counts can be related to increased survival, whereas in children who did not have initial thrombocytopenia, more than a 10% decrease of platelet counts on day 3 can be related to mortality.

Forced expiratory flow between 25% and 75% of vital capacity as a predictor for bronchial hyperresponsiveness in children with allergic rhinitis

PURPOSE: Allergic rhinitis (AR) is regarded as a risk factor for asthma and bronchial hyperresponsiveness (BHR) is frequently observed in patients with AR. The purpose of this study is to analyze the characteristics of AR patients with BHR and identify factors that contribute to the incidence of BHR. METHODS: The medical records of a total of 176 children with AR were analyzed retrospectively. All patients were evaluated by performing spirometry and a methacholine challenge test. RESULTS: One hundred and fifty-five patients (88%) were classified as the BHR-negative group and 21 patients (12%) were classified as the BHR-positive group. Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75 %predicted) was reduced, and total eosinphil counts, total immunoglobulin E (IgE) level, and serum specific IgE levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae were higher in the BHR-positive group compared to the BHR-negative group. However, FEF25-75 was the only statistically significant predictor for the presence of BHR on multivariate logistic regression analysis. The cutoff value to distinguish BHR-positive subjects obtained from a receiver operating characteristics curve of FEF25-75 was 88.4%. A higher frequency of BHR was found in the group with a FEF25-75 less than 88.4%, and the sensitivity, specificity, positive predictive value and negative predictive value were 57.1%, 80.6%, 28.6%, and 93.3%, respectively. CONCLUSION: Reduced FEF25-75 values in children with AR can be helpful in predicting BHR. Children with low FEF25-75 in spirometric tests should be followed closely for apparent onset of clinical symptoms of asthma.

Prognostic Usefulness of Eosinopenia in the Pediatric Intensive Care Unit

Eosinopenia, a biomarker for infection, has recently been shown to be a predictor of adult mortality in the intensive care unit (ICU). Our study assessed the usefulness of eosinopenia as a mortality and an infection biomarker in the pediatric ICU (PICU). We compared the PICU mortality scores, eosinophil count and percentage at ICU admission between children who survived and those who did not survive and between children with infection and those without infection. A total of 150 patients were evaluated. The initial eosinophil count and percentage were significantly lower in the group that did not survive when compared to those that did survive (P < 0.001; P < 0.001). However, there was no significant difference in the eosinophil count and percentage seen in patients with and without infection. Eosinopenia, defined as an eosinophil count < 15 cells/microL and an eosinophil percentage < 0.25%, (hazard ratio [HR]: 2.96; P = 0.008) along with a Pediatric Index of Mortality (PIM) 2 (HR: 1.03; P = 0.004) were both determined to be independent predictors of mortality in the PICU. The presence of eosinopenia at the ICU admission can be a useful biomarker for mortality in children, but is not useful as a biomarker for infection.

The safety of influenza vaccination in children with egg allergy

PURPOSE: Although influenza vaccine contains some residual egg protein (ovalbumin), recent studies have been reported that the influenza vaccine is even safe for patients with egg allergy. The object of this study was to assess the safety of influenza vaccination and estimate the risk factors of allergic reactions to influenza vaccination in children with egg allergy. METHODS: The medical records of 108 children were reviewed retrospectively, those were diagnosed as egg allergy at Department of Pediatrics in Severance Children's Hospital between January 2006 and December 2011. All of them were vaccinated with very low ovalbumin concentration (< or =0.12 microg/mL). Patients were vaccinated in graded doses by the international guideline. Subjects without allergic reactions to influenza vaccine among egg allergy patients were recruited as control subjects. RESULTS: Only 12 subjects of patients had adverse reactions to influenza vaccination. There were no significant relationships between adverse reactions to influenza vaccine and their own history of other allergy, history of breast feeding or graded vaccination. The egg allergy symptoms or egg-specific IgE levels were not associated with adverse reactions to influenza vaccination. CONCLUSION: These results show that patients with egg allergy may have adverse reactions with influenza vaccine, but severe adverse reactions are rare as general population. Therefore, the patients with egg allergy can be safe vaccinated with influenza vaccine, regardless of severity of allergic reaction after egg ingestion or methods of vaccination.

A Clinical Approach of Post-Infectious Bronchiolitis Obliterans Using the Results of High Resolution Computed Tomography / 소아알레르기및호흡기학회지

PURPOSE: Bronchiolitis obliterans (BO) is a type of chronic obstructive lung disease. In children, the most common presentation is a post infectious origin. The aim of this study was to determine the clinical features, etiology, and radiologic findings of post infectious BO, which was diagnosed by high resolution computed tomography (HRCT). The results were then compared to those of the control group. METHODS: We diagnosed 52 children with BO by a review of all performed HRCT findings at Severance Children's Hospital between January 2007 and March 2011. A retrospective study was conducted to define the clinical features, etiology, symptoms, and radiologic findings of post infectious BO. Sixty-five children who were diagnosed with lower respiratory infection confirmed by HRCT were defined as the control group for comparison with post infectious BO patients. RESULTS: The mean age of the patients at the time of diagnosis with BO was 41.3+/-5.9 months, and that of the control group was 57.1+/-5.1 months. The initial insult age of BO patients was 14.6+/-2.8 months, and that of the control group was 50.9+/-5.0 months. The frequency of previous admissions due to lower respiratory infection was relatively higher in BO patients than the control group. CONCLUSION: The results suggest that the development of post infectious BO should be early suspected and HRCT should be performed in children with a recurrent admission history of lower respiratory infection, especially in those younger than 2 years of age. Furthermore, continued management of prevent additional infection should be conducted.

A1 Segment Hypoplasia/aplasia Detected by Magnetic Resonance Angiography in Neuropediatric Patients / 대한소아신경학회지

PURPOSE: A variation in the circle of Willis is not so common, but the most frequent type is hypoplasia/aplasia of the precommunicating anterior cerebral arteries (A1 segment). We aimed to examine the incidence and the clinical significance of A1 segment hypoplasia/aplasia in neuropediatric patients. METHODS: We retrospectively studied children with A1 segment hypoplasia/aplasia in brain magnetic resonance angiography (MRA) and compared the clinical and radiological aspects between children with A1 segment hypoplasia/aplasia alone and with other variations in the circle of Willis. RESULTS: Among 301 patients, 34 patients (11.3%) had A1 segment hypoplasia/aplasia. They presented neurological symptoms such as chronic headache, dizziness and visual disturbance. Seven (20.6%) had family history of neurological illness. Twenty seven (79.4%) had A1 segment hypoplasia/aplasia only, and seven (20.6%) had another vascular abnormality. Seven (20.6%) showed abnormal brain magnetic resonance angiography (MRI) results, cerebral atrophy being the most frequent (n=5, 14.7%). The incidence of abnormal brain MRI was 11.1% (n=3) in single vascular abnormality and 57.1% (n=4), significantly higher (p-value 0.02) in combined abnormality group. CONCLUSION: Structural alterations in the cerebral vasculature in children have important pathophysiological and clinical implications. Evaluation of variations in the circle of Willis, especially of A1 segment hypoplasia/aplasia using MRA is recommended.

The Therapeutic Effect of Inhaled Iloprost in Newborn Infants with Severe Persistent Pulmonary Hypertension Refractory to Inhaled Nitric Oxide / 대한주산의학회잡지

Inhaled iloprost, a stable carbacyline derivative of prostacyclin, has been used recently for the treatment of adults with pulmonary hypertension but only few reports are available about its use in neonatal critical care. We report therapeutic trial of inhaled iloprost in newborn infants with persistent pulmonary hypertension of the newborn (PPHN) who did not respond to inhaled nitric oxide (iNO). Inhaled iloprost (Ventavis(R), Bayer Shering Pharma, Germany) was effective in neonates with severe PPHN who showed inadequate response to iNO. We suggest that inhaled iloprost could be considered as an additional therapeutic option in PPHN refractory to iNO.