Tugba Arikoglu

The association of vitamin D, cathelicidin, and vitamin D binding protein with acute asthma attacks in children.

BACKGROUND Recent evidence about the various effects of vitamin D (vit D) on innate and adaptive immunity has led to a search for the role of vit D in asthma. It is postulated that a decrease in cathelicidin, a multifunctional host defense molecule, production due to low vit D status may predispose to infectious complications in children with asthma. OBJECTIVE The aim of this study was to determine the association of vit D, vit D-binding protein (VDBP) and cathelicidin with acute asthma attacks among children with allergic asthma. METHODS This prospective study included 35 patients with acute asthma attack and 32 children with controlled asthma, and all were matched by sampling season, sensitization to mites, and previous severity of asthma. A comprehensive questionnaire about risk factors, blood sampling for 25-hydroxyvitamin D vit D, VDBP, and cathelicidin levels; spirometric indices were used. Factors that influence serum vit D and cathelicidin levels and the development of asthma attacks were evaluated with multivariate analysis. RESULTS The mean serum vit D levels of the attack group was significantly lower than that of the controlled asthma group (p < 0.001). The mean cathelicidin level was significantly higher in the acute asthma group than with the controlled subjects with asthma (p = 0.002). There was no difference between the acute and controlled asthma groups in terms of markers of allergy and serum VDBP levels. Risk factors that may influence vit D levels revealed that body mass index (BMI) (p = 0.038), duration of sun exposure (p < 0.001), and amount of dietary vit D (p < 0.001) independently affected serum vit D levels. Risk factors that may result in acute asthma showed that low serum levels of vit D were significantly related to the risk of asthma attacks (p < 0.001, adjusted odds ratio 16.11). Cathelicidin levels showed a significant positive association with asthma attacks and BMI. CONCLUSIONS Vit D deficiency showed a significant relationship to the development of asthma attacks independent of cathelicidin deficiency and other factors associated with the severity of chronic asthma.

A new hemostatic agent--Ankaferd blood stopper: management of gastrointestinal bleeding in an infant and other experiences in children.

Ankaferd blood stopper (ABS) is a standardized medicinal plant extract that stimulates the formation of an encapsulated protein network that provides focal points for erythrocyte aggregation. It has a therapeutic potential to be used for the management of external hemorrhage. Here, the authors report an infant bleeding from peptic ulcer was stopped successfully by gastroscopic application of ABS and other cases that used topical ABS for mucosal bleedings are also presented.

Impulse oscillometry in acute and stable asthmatic children: a comparison with spirometry

Abstract Objective: Lung function tests have attracted interest for the diagnosis and follow-up of childhood asthma in recent years. For patients who cannot perform forced expiratory maneuvers, impulse oscillometry (IOS), performed during spontaneous breathing, may be an alternative tool. Methods: Thirty-five acute, 107 stable asthmatic and 103 healthy children who presented to our clinic performed IOS followed by spirometry before and after salbutamol inhalation. The mean baseline and reversibility of IOS and spirometry parameters were compared between the groups. Correlation analyses were undertaken within the asthmatics, and the healthy controls separately. To distinguish the three groups, the sensitivity and specificity of baseline and reversibility values of IOS and spirometry were computed. When spirometry was taken as the gold standard, the discriminating performance of IOS to detect the airway obstruction and reversibility was investigated. Results: The mean absolute values of Zrs, R5, R5−R20, X5, X10, X15, Fres, AX, and all spirometric parameters, and the mean reversibility values of R5, R10, Fres, AX and forced expiratory volume in one second were different between the groups and the highest area under curve values to discriminate the groups was obtained from area of reactance (AX) and ΔAX. Zrs, all resistance (including R5−R20) and reactance parameters, Fres and AX were correlated with at least one spirometric parameter. Spirometric reversibility was detected by ≤−22.34 and ≤−39.05 cut-off values of ΔR5 and ΔAX, respectively. Conclusions: IOS has shown a highly significant association with spirometric indices and reversibility testing. It may be a substitute for spirometry in children who fail to perform forced expiratory maneuvers.

A NOVEL L218P MUTATION IN NADH-CYTOCHROME B5 REDUCTASE ASSOCIATED WITH TYPE I RECESSIVE CONGENITAL METHEMOGLOBINEMIA

The presence of central cyanosis that is unrelated to cardiopulmonary causes alerts clinicians to a possible diagnosis of methemoglobinemia. Congenital methemoglobinemia due to deficiency of nicotinamide-adenine dinucleotide (NADH)-cytochrome b5 reductase (cb5r) is an autosomal recessive disorder characterized by life long cyanosis. Here we report a six-year old boy who presented with central cyanosis and upon examination revealed a methemoglobin level of 19.0%. Sequencing the CYB5R3 gene identified a homozygous T→C transition at base c.653, which changed codon 218 from leucine to proline (L218P) in cb5r protein. Treatment with ascorbic acid relieved the cyanosis and returned methemoglobin levels to normal.

A novel G6PC3 gene mutation in severe congenital neutropenia: pancytopenia and variable bone marrow phenotype can also be part of this syndrome

Glucose‐6‐phosphatase catalytic subunit 3 (G6PC3) deficiency is a newly described syndrome characterized by severe congenital neutropenia associated with multiple organ abnormalities including cardiac and urogenital malformations. The underlying pathophysiology of increased apoptosis of myeloid cells and of neutrophil dysfunction in G6PC3 deficiency involves disturbed glucose metabolism, increased endoplasmic reticulum stress and deficient protein folding. Here, we report a new case of G6PC3 deficiency caused by a novel homozygous G6PC3 gene mutation p.Trp59Arg. The patient showed pancytopenia and a variable bone marrow phenotype with maturation arrest and vacuolization in myeloid lineage cells and a normocellular marrow, respectively. She also showed persistent lymphopenia with low CD4 T‐ and CD19 B‐cell counts. Lymphopenia and even pancytopenia as well as a variable bone marrow phenotype can be part of this syndrome. These clinical findings in a patient with chronic neutropenia should alert the clinician to consider a diagnosis of G6PC3 deficiency.

Seasonal variation of asthma control, lung function tests and allergic inflammation in relation to vitamin D levels: a prospective annual study

Introduction There are scarce data about the role of vitamin D (vitD) in asthma control related to seasons and other confounders. Aim To investigate the seasonal relationship between vitD levels and asthma control, lung function tests (LFTs) and cytokines during a 1-year period, among 7–17-year-old asthmatic children. Material and methods Thirty patients with asthma with house dust mite monosensitization were evaluated 3 monthly about the previous month’s health and vitD related lifestyle factors and asthma control test (ACT), spirometry and bronchial provocation test for a year. Serum vitD, vitD binding protein (VDBP), total IgE levels, absolute eosinophil and Treg counts and cytokine levels were simultaneously measured. The seasonal changes of vitD and other parameters and the relationship between 120 pooled data sets of vitD and major outcomes were evaluated. Results Mean vitD levels, forced expiratory volume in 1 s (FEV1%) and ACT score were lowest in winter and highest in summer. Pooled vitD levels were positively correlated with pooled ACT scores, Treg counts, FEV1% values and VDBP levels and negatively with total immunoglobulin E (IgE) and interleukin-4 (IL-4) levels and bronchodilator response. VitD levels were positively associated with ACT score, and FEV1% value and negatively with serum IgE level and bronchodilator response after adjusting for confounders. Conclusions This study revealed that asthma control measures, LFTs and IgE levels were significantly related to serum vitD levels, independent from age, body mass index, inhaled corticosteroid use, sun exposure and season among asthmatic children. Vitamin D levels showed a positive correlation with Treg counts and a negative correlation with Th2 type cytokines.

The Effect of Vitamin D Pathway Genes on Asthma Susceptibility, Asthma Control and Vitamin D Levels in Turkish Asthmatic Children

ABSTRACT The aim of this study was to investigate the associations between the vitamin D (vitD) pathway genes and asthma susceptibility, asthma control and serum vitD levels. Thirty asthmatic children and 30 non-asthmatic (controls) children were genotyped for 9 single nucleotide polymorphisms (SNPs) of vitD pathway genes. These genes were VitD receptor (VDR), 25-hydroxylase (CYP2R1 and CYP27A1), 1-alpha hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and VDBP (GC). Genotype and allele frequencies were compared between the groups and their associations with asthma control test (ACT) score and VitD level were investigated. The F allele of VDR1 (FokI) SNP carriers were 2.97 times more likely to develop asthma than those carrying the f allele. Ff genotype of VDR FokI SNP was associated with low ACT score compared to the FF genotype after adjustment. No association between the genotypes and alleles and the level of vitD was found. In conclusion, VDR fokI polymorphism was found to be associated with asthma susceptibility and asthma control in Turkish children.

Prevalence and risk factors for wheezing and allergic diseases in preschool children: A perspective from the Mediterranean coast of Turkey

OBJECTIVES The aim of the present study was to determine the prevalence and risk factors of allergic diseases in preschool children from one of the biggest cities in the Mediterranean Region of Turkey. METHODS The study population included 396 preschool children attending to urban daycare centres in Mersin. In the first stage, a comprehensive standardised questionnaire modified from the International Study of Asthma and Allergies in Childhood (ISAAC) was employed. In the second stage, serum food and inhalant specific IgE, and skin tests were performed in 45 children with frequent wheezing and 28 children with no wheezing. RESULTS The prevalence of ever wheezing, current wheezing, physician-diagnosed asthma, allergic rhinitis and eczema were 53% (210), 33.3% (132), 27.3% (108), 13.4% (53) and 8.3% (33), respectively. A family history of atopy (OR=2.5, 95% CI: 1.3-4.7, p=0.004), dampness at home (OR=2.4, 95% CI: 1.2-4.8, p=0.008), a history of intestinal parasites (OR=4.3, 95% CI: 1.7-10.9, p=0.002), previous history of pneumonia (OR=6.9, 95% CI: 1.9-25.9, p=0.004), initiation of complementary foods before the age of three months (OR=6.1, 95%CI: 1.4-26.9, p=0.02) and presence of food allergy (OR=3.1, 95% CI: 1.1-9.2, p=0.03) were found to be significant risk factors for physician-diagnosed asthma. The risk factors for frequent wheezing were maternal smoking during pregnancy (OR=5.2, 95% CI: 0.9-28.7, p=0.05) and high serum IgE levels (OR=2.9, 95% CI: 0.9-9.0, p=0.05) at borderline significance. CONCLUSION Our study was the first epidemiological study in preschool children in the Mediterranean region of Turkey and demonstrated a high prevalence of asthma and allergic diseases, probably related to humid climatic properties in addition to other environmental and genetic factors.

The relation of innate and adaptive immunity with viral-induced acute asthma attacks: Focusing on IP-10 and cathelicidin

Abstract Background Despite growing evidence suggesting potential association between innate and adaptive immunity in viral-induced acute asthma, there is paucity of data in this area. Objective This study aimed to investigate the association of innate and adaptive immunity with acute asthma attacks by analysing the role of IFN-γ-inducible protein 10 (IP-10), TLR2, cathelicidin, vitamin D and cytokines. Material and methods This prospective study included 33 patients with viral-induced acute asthma and 30 children with controlled asthma. Nasopharyngeal swab samples were collected for virus identification and asthma attack scores assessed in acute asthma group. Blood sampling for IP-10, TLR2, cathelicidin, vitamin D levels, and spirometric indices were employed. Results Serum IP-10 and cathelicidin levels of acute asthma group were significantly higher and vitamin D levels were lower than controlled asthma group (IP-10; p =0.006, cathelicidin; p =0.002, vitamin D; p <0.001). Serum IP-10 levels showed a significant negative correlation with age (p =0.009), TLR2 (p =0.05) and spirometric indices (p =0.002) in all asthmatics and a significant positive correlation with parameters of asthma attack severity (p =0.03) in acute asthma group. Higher cathelicidin values showed significant positive relation to IP-10 (beta coefficient: 33, p =0.02). Serum IP-10 levels higher than 38.9pg/ml (sensitivity: 85%, specificity: 47%, p =0.002) were predictive of virus-induced asthma. Serum IP-10 and vitamin D levels were found to be significantly related to viral-asthma attacks (IP-10; aOR: 8.93, p =0.03 and vitamin D; aOR: 0.82, p =0.001). Conclusions Innate immunity biomarkers such as serum IP-10 and cathelicidin can be used to predict viral-induced acute asthma. These biomarkers may provide potential new treatment targets for acute asthma.

Erythrophagocytosis in cold agglutinin disease.

An 8-year-old boy with B precursor acute lymphoblastic leukemia (ALL) presented with a 1-week history of cough and mild fever during the 107th week of St. Jude total XIII high-risk protocol. Physical examination was normal except rales on auscultation. His hemoglobin level was 11.7 g/dL, white blood count was 2.6 10/L (absolute neutrophil count 1560), and platelet count was 208 10/L. Peripheral blood film showed several erythrophagocytosis by monocytes (Fig. 1). Direct Coombs’ test was positive (2+) with complement (C3d). Cold agglutinin titer was 1:64 and 10 days later it was 1:128. Urine analysis and biluribin levels were normal. Although thorax radiography revealed pneumonic infiltration, serologic tests for mycoplasma pneumonia, parainfluenza virus, respiratory synsitial virus and also Epstein–Barr virus, rubella, cytomegalovirus, adenovirus were all negative. At follow-up hemoglobin level decreased to a nadir of 9.2 g/L and cold agglutinins disappeared within 3 months. Cold agglutinin disease (CAD) is an uncommon form of autoimmune hemolytic anemia. The primary form typically affects older adults; however, it is also a secondary disorder in association with a number of different underlying disorders, such as certain infectious diseases (eg, mycoplasma infection and infectious mononucleosis) and lymphoproliferative diseases, especially mature B cell origin such as lymphoma, chronic lymphocytic leukemia, and Waldenström’s macroglobulinemia. Very rarely it was described in patients with ALL. Although infectionassociated CAD is transient, lymphoproliferative disorders produce a more chronic course. Peripheral smear may show agglutination, polychromasia, anisocytosis, poiklocytosis, and occasionally spherocytosis. Cold agglutinin disease should be borne in mind in patients with erythrophagocytosis on peripheral blood smear. REFERENCES