MicroRNA Levels in Exhaled Breath Condensate of Patients with Esophageal Atresia.

MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the regulation of inflammation and have not been evaluated in exhaled breath condensates (EBC) of patients with esophageal atresia and tracheoesophageal fistula (EA-TEF). It is aimed to evaluate the levels of miRNA-21 and miRNA-24 in EBC of patients with EA-TEF. Patients who received surgery for EA-TEF (EA) were assessed for age, sex, types of anomaly, surgical treatments, and respiratory problems. A 500-1000 mL of EBC was obtained from each participant with EcoScreen. The levels of miRNA-21 and miRNA-24 in the EBC were analyzed by real-time polymerase chain reaction and compared between the EA group and the control group consisting of healthy children with no history of respiratory problems (n = 17). The levels of miRNAs in relation to respiratory problems and gastroesophageal reflux (GER) were also assessed. A total of 19 patients were enrolled in the EA group with a mean age of 7.8 ± 3.2 years and a male-to-female ratio of 10:9 EA cases had significantly lower levels of miRNA-21 (P < 0.05) compared to that in control group. The miRNA-24 levels did not differ between groups (P > 0.05). EA patients with positive pH testing for GER (n = 6) and fundoplication (n = 6) had higher levels of miRNA-21 than those with normal pH testing and without fundoplication, respectively (n = 13, P < 0.05). The levels of miRNA-21 and miRNA-24 did not differ between patients with and without proton pump inhibitor treatment (P > 0.05). The lower levels of miRNA-21 in the EBC of EA patients suggest a hyperreactive airway problem, which may be associated with GER and its surgical treatment.

Omalizumab treatment in adolescents with chronic spontaneous urticaria: Efficacy and safety.

BACKGROUND: Omalizumab is useful as an add-on treatment in patients unresponsive to high doses of second-generation antihistamines. This study aimed to evaluate the efficacy and safety of omalizumab treatment in adolescents with refractory chronic spontaneous urticaria (CSU). METHODS: CSU patients aged 12-18 years old with the diagnosis of symptomatic CSU and unresponsive to classical treatment were included in the study. All patients had an urticaria-activity-score (UAS7) of ≥16 or and were treated with 300mg omalizumab every four weeks. The degree of response was classified into complete, partial and non-responders due to UAS7. RESULTS: A total of 29 patients were evaluated. The median age and symptom onset age of the patients was 15.2 (IQR, 12.8-16.5) years and 14.0 (IQR, 11.8-15.9) years, respectively. The median duration of urticaria was eight (IQR, 4-24) months at admission. Eleven (37.9%) patients had angioedema and ten (34.5%) patients had concomitant allergic diseases. The median age at the beginning of treatment with omalizumab was 15.4 (IQR, 12.9-16.9) years. The median symptom duration was 12 (IQR, 6.5-27.5) months before the omalizumab treatment. Twenty-eight (96.5%) of the patients (89.6% complete, 6.9% partial) achieved response; however, one patient was a non-responder (3.5%). The adverse effect was observed in one (3.4%) patient as angioedema after the third dose. Twenty-three patients were followed up for a median of 18 (IQR, 13-27) months. Relapse was observed in three (13%) patients. CONCLUSIONS: Omalizumab is considered as an effective and safe treatment for CSU in adolescents. Relapses mostly occur within the first year after the cessation of treatment.

Physicians prescribe adrenaline autoinjectors, do parents use them when needed?

BACKGROUND: Anaphylaxis is a sudden, severe, and potentially life-threatening allergic reaction, affecting a portion of allergic patients. Adrenaline is the first-line medication for anaphylaxis and available in many parts of the world as adrenaline autoinjectors (AAIs). OBJECTIVE: Aim of this study was to determine attitudes and knowledge levels of patients/parents regarding the use of AAIs, frequency, and rate of appropriate AAI use and to give a standardized and better education by improving on mistakes during administration. METHOD: 190 patients aged 1-18 years who were prescribed AAIs for any reason between 2012 and 2017 in Hacettepe University Pediatric Allergy Unit. Demographic data were collected during face-to-face interview or by telephone. Parents completed a mini-survey regarding use, carriage, and storage of AAI. RESULTS: Some 190 patients (64.7% male) aged 7.83 (4.99-12.08) years, median (inter-quartile), were included in the study. The indications for AAI prescription were food allergy (78.9%); venom allergy (14.2%); idiopathic anaphylaxis (3.7%); mastocytosis (2.1%); and drug allergy (1.0%). One-fourth of AAI-prescribed patients experienced anaphylaxis requiring the use of AAI within the past five years. However, only 30% of the patients dared to use AAI; only three-quarters of whom had managed to use it correctly. CONCLUSION: After prescription of AAI and initial training, patients and parents' concerns and fears should be taken into consideration and necessary support should be provided. At every opportunity and each clinical visit, not only should training sessions be repeated but also the patients and parents should be psychologically supported.

Actual drug allergy during childhood: Five years' experience at a tertiary referral centre.

BACKGROUND: Drug hypersensitivity reactions (DHR) are common in the paediatric population, representing a public health problem. Recent studies have confirmed that the frequency of drug allergy is overestimated by both parents and physicians. The aim of this study is to determine the prevalence and risk factors of actual drug allergies in children admitted to a tertiary referral allergy centre. METHODS: Medical records covering the period of 2005-2010 of children with a history of DHR were reviewed. Demographic features of the patients and results of skin and drug provocation tests were noted. The European Network for Drug Allergy (ENDA) questionnaire was filled by using medical records and making phone calls with parents. RESULTS: Ninety-six patients with 140 DHRs were evaluated. Seventeen children had confirmed drug allergy by positive skin tests (n=11) and drug provocation tests (n=5). One patient underwent severe anaphylaxis and subsequent cardiac arrest during infusion of the drug, and therefore diagnostic tests were not performed. Actual drug allergy was more frequent in children with chronic diseases (58.8% vs. 26.5%, p=0.018) and histories of anaphylaxis during DHR (58.8% vs. 24%, p=0.001). The patients' history of anaphylaxis [OR: 5.789, 95%CI: 1.880-17.554, p=0.002], sweating [OR: 7.8, 95%CI: 1.041-58.443, p=0.046] and dyspnoea [OR: 5.230, 95%CI: 1.836-14.894, p=0.002] during suspicious DHRs increased the risk for actual drug allergy. CONCLUSION: Actual drug allergy was determined in 17.7% of the patients with a suspicious DHR. Having a history of anaphylaxis during suspected drug reactions as well as symptoms of sweating and dyspnoea increased the risk for actual drug allergy.

Baseline management of asthma control

Asthma is a complex, chronic inflammatory disease of the lower airways affecting people of all ages. Approximately 300 million individuals are currently suffering from asthma worldwide. The prevalence of asthma is estimated to range from 3% to 38% in children and from 2% to 12% in adults. The disease causes lost school and work days, limitations in daily activities, and sleep disturbances. Lung function impairment also occurs, resulting in decreased quality of life unless disease control is achieved and a high annual financial burden is incurred. Achievement and maintenance of control through assessment of clinical manifestations and future risk has become the aim of treatment over the years. Unfortunately, the desired level of asthma control has not been achieved in a considerable number of regions throughout the world, and the level of control is overestimated by both patients and their parents. This review examines the mortality and morbidity rates for asthma, emphasizes the challenges inherent to control management, and provides data on the tools used to measure control level

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Baseline management of asthma control.

Asthma is a complex, chronic inflammatory disease of the lower airways affecting people of all ages. Approximately 300 million individuals are currently suffering from asthma worldwide. The prevalence of asthma is estimated to range from 3% to 38% in children and from 2% to 12% in adults. The disease causes lost school and work days, limitations in daily activities, and sleep disturbances. Lung function impairment also occurs, resulting in decreased quality of life unless disease control is achieved and a high annual financial burden is incurred. Achievement and maintenance of control through assessment of clinical manifestations and future risk has become the aim of treatment over the years. Unfortunately, the desired level of asthma control has not been achieved in a considerable number of regions throughout the world, and the level of control is overestimated by both patients and their parents. This review examines the mortality and morbidity rates for asthma, emphasizes the challenges inherent to control management, and provides data on the tools used to measure control level.

Importance of serum basal tryptase levels in children with insect venom allergy.

BACKGROUND: The importance of serum basal tryptase (sBT) levels on patients with venom allergy is highlighted in recent adulthood studies. The aim of this study was to evaluate the sBT levels of venom-allergic children with varying severity of clinical reactions. We also aimed to document the association between sBT levels and severe systemic reactions (SR). METHODS: Serum basal tryptase levels were estimated by UniCAP (Pharmacia & Upjohn, Uppsala, Sweden). Children who suffered from large local reaction (LLR) or SR after insect stings were included along with healthy control subjects without a history of any local or SR after insect stings. RESULTS: A total of 128 children (55 with SR, 18 with LLR, and 55 age and sex-matched control subjects) with a median age of 8.9 years (range 3.2-17.4) were enrolled. Severe SR was encountered in 24 (44%) patients with SRs. The median level of sBT in children with SRs (median, interquartile range) [4.2 µg/l (3.6-4.9)] was significantly higher than in children with LLRs [3.1 µg/l (2.5-4.0)] and healthy control subjects [2.9 µg/l (2.3-3.4)] (P < 0.001). Logistic regression analysis revealed sBT ≥ 4.8 µg/l as a significant risk factor for severe SR (5.7 [1.5-21.4]; P = 0.01) in children with venom allergy. CONCLUSIONS: Our results indicate that sBT levels are associated with a higher risk of severe SR in children with insect venom hypersensitivity. Determination of sBT levels may help clinicians to identify patients under risk of severe SRs and optimal and timely use of therapeutic interventions in children with venom allergy.

Similar prevalence, different spectrum: IgE-mediated food allergy among Turkish adolescents.

BACKGROUND: Scarcity of reliable data on food allergy prevalence exists in Turkey. We aimed to assess reported and confirmed IgE-mediated food allergy prevalence, and define the spectrum of allergenic food. METHODS: We prospectively evaluated the ISAAC Phase II study population for food allergy. Participants that reported experiencing food allergy symptom in the last year and/or were skin prick test positive for a predefined list of food allergens, were interviewed via telephone, and those considered as having food allergy were invited to undergo clinical investigation, including challenge tests. RESULTS: A total of 6963 questionnaires were available. Parental reported food allergy prevalence and skin prick sensitisation rate were 20.2 ± 0.9% and 5.9 ± 0.6%. According to the above-defined criteria, 1162 children (symptom positive n=909, skin prick test positive n=301, both positive n=48) were selected and 813 (70.0%) were interviewed via telephone. Out of 152 adolescents reporting a current complaint, 87 accepted clinical investigation. There were 12 food allergies diagnosed in nine adolescents, with food allergy prevalence of 0.16 ± 0.11%. The most common foods involved in allergic reactions were walnut (n=3) and beef meat (n=2), followed by hen's egg (n=1), peanut (n=1), spinach (n=1), kiwi (n=1), cheese (n=1), hazelnut (n=1) and peach (n=1). CONCLUSIONS: While parental reported food allergy prevalence was within the range reported previously, confirmed IgE-mediated food allergy prevalence among adolescents was at least 0.16%, and the spectrum of foods involved in allergy differed from Western countries, implying environmental factors may play a role.

The reliability and validity of Turkish version of Childhood Asthma Control Test.

INTRODUCTION: The reliability and validity of Turkish version of Childhood Asthma Control Test (C-ACT). PURPOSE: The management of asthma is an important as well as difficult issue of physician's daily practice particularly in busy clinical settings. C-ACT was created to identify asthma control levels in children aged 4-11 years. Our aim was to evaluate the reliability, validity and responsiveness of C-ACT in a Turkish sample of children with asthma. METHOD: In this multicenter study, 368 children were enrolled. C-ACT was completed every month by parents and patients who were evaluated in 3 visits within 2 month intervals. At each visit, physicians interpret the control level and decided for the treatment step as established in GINA guidelines. RESULTS: The internal consistency reliability of the Turkish version of C-ACT (C-ACT1 to C-ACT5) was found to be 0.82, 0.83, 0.82, 0.82 and 0.80, respectively (reliability statistics, Cronbach's alpha). Test-retest reliability was 0.71. There was significant correlation between C-ACT and physician's assessment of asthma control at visit 1 (r = 0.65, P < 0.001). CONCLUSIONS: Turkish version of C-ACT is an accurate and reliable tool to evaluate asthma control in children aged 4-11 years. Its widespread use may facilitate appropriate assessment of asthma control and may lead to decrease the number of uncontrolled patients.

Asthma programmes in diverse regions of the world: challenges, successes and lessons learnt.

International surveys have demonstrated that asthma is still underdiagnosed and undertreated in many parts of the world. Despite improvements in the standard of asthma care delivered in many areas, as evidenced by improved global asthma mortality data, much information on projects and programmes undertaken in resource-limited regions of the world is not in the public domain. The aim of this report is to review projects and programmes in diverse regions around the world so that health care providers, planners and consumers may draw on the successes, failures and lessons learnt. Such real world experiences may contribute to achieving Global Initiative for Asthma goals of asthma control. Asthma projects and programmes in Argentina, Australia, Brazil, China, Japan, Mexico, Philippines, Russia, South Africa and Turkey were discussed by a group of experts in asthma care, the Advancing Asthma Care Network, from their respective countries, over a course of three satellite meetings in 2010. Collective analyses consistently identified low rates of dissemination and implementation of national and international treatment guidelines, low levels of continuing medical education and training of primary health care professionals and access and distribution of inhaled corticosteroids to be major barriers that are critical to the overall success of a national asthma management programme. In the less developed asthma programmes, under-recognition and undertreatment further limited the success of the programmes. Evidence from well-established national asthma management programmes suggests that establishment of a successful programme entails a logical progression through specific developmental stages, starting with political/stakeholder endorsement and commitment, followed by epidemiological evaluation, evaluation of disease burden, evaluation of access to care and best therapy, and finally optimisation and maintenance therapy for individual patients.

Prevalence, burden, and risk factors of atopic eczema in schoolchildren aged 10-11 years: a national multicenter study.

BACKGROUND: Little is known about the epidemiology of atopic eczema (AE), and studies from the Mediterranean region and the Middle East are limited. OBJECTIVE: We investigated the frequency, burden, and risk factors of AE in a developing country. METHODS: The International Study of Asthma and Allergies in Childhood Phase II questionnaire was used to survey a representative sample of 10 to 11-year-old children in Turkey. Children were examined by allergists, and parents completed standardized questionnaires. RESULTS: Among 6755 children, the prevalence of having eczema during one's lifetime or currently was 17.1% and 8.1%, respectively. The prevalence of visits to the doctor, nocturnal awakening, school absenteeism, and drug usage was 36.3%, 56%, 9.7%, and 28.7%, respectively. Associated factors were current rhinoconjunctivitis (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.99-3.21), current wheezing (OR, 2.10; 95% CI, 1.58-2.79), family history of allergic disease (OR, 1.62; 95% CI, 1.21-2.18), low birth weight (OR, 1.79; 95% CI, 1.08-2.94), and exposure to animals in the first year of life (OR, 1.47; 95% CI, 1.06-2.03). CONCLUSIONS: In a developing Mediterranean country, the prevalence of AE is comparable to that of developed countries in the same region and lower than that observed in developed countries elsewhere. The course of the disease and risk factors of AE probably differ in developing countries.

Extent and burden of allergic diseases in elementary schoolchildren: a national multicenter study.

BACKGROUND: Scarcity of standardized, comparable data on allergic diseases in schoolchildren in Turkey requires further multicenter studies based on the use of objective tools in addition to parent-completed questionnaires to improve the validity and reliability of results. METHODS: Using International Study of Asthma and Allergies in Children (ISAAC) Phase II tools, elementary schoolchildren aged 9 to 11 years were surveyed in 5 city centers in different regions of Turkey. RESULTS: We surveyed 6963 children from 70 schools and found that 35% had had at least 1 symptom of allergic diseases in the past year. Based on parental reports, the overall prevalence rates for wheezing, rhinoconjunctivitis, and eczema in the past year were 15.8%, 23.5%, and 8.1%, respectively. The overall frequencies of atopy, flexural dermatitis, and bronchial hyperreactivity were 18.9%, 3.6%, and 24.2%, respectively. There were large variations in the prevalence of both symptoms and objective signs between study centers. Absence from school for at least 1 day was reported for 34.2% of children with a diagnosis of asthma or allergic rhinitis. CONCLUSIONS: Approximately one third of elementary schoolchildren reported symptoms compatible with allergic diseases in the past year. The interregional differences in both symptoms and objective test results are possibly due to differences in environmental conditions. Unfortunately, serious problems are still encountered in the timely and proper diagnosis and treatment of allergic diseases.

A multicenter survey of childhood asthma in Turkey. II: Utilization of asthma drugs, control levels and their determinants.

Many surveys worldwide have consistently demonstrated a low level of asthma control and under-utilization of preventive asthma drugs. However, these studies have been frequently criticized for using population-based samples, which include many patients with no or irregular follow-ups. Our aim, in this study, was to define the extent of asthma drug utilization, control levels, and their determinants among children with asthma attending to pediatric asthma centers in Turkey. Asthmatic children (age range: 6-18 yr) with at least 1-yr follow-up seen at 12 asthma outpatient clinics during a 1-month period with scheduled or unscheduled visits were included and were surveyed with a questionnaire-guided interview. Files from the previous year were evaluated retrospectively to document control levels and their determinants. From 618 children allocated, most were mild asthmatics (85.6%). Almost 30% and 15% of children reported current use of emergency service and hospitalization, respectively; and 51.4% and 53.1% of children with persistent and intermittent disease, respectively, were on daily preventive therapy, including inhaled corticosteroids. Disease severity [odds ratio: 12.6 (95% confidence intervals: 5.3-29.8)], hospitalization within the last year [3.4 (1.4-8.2)], no use of inhaled steroids [2.9 (1.1- 7.3)], and female gender [2.3 (1.1-5.4)] were major predictors of poor asthma control as defined by their physicians. In this national pediatric asthma study, we found a low level of disease control and discrepancies between preventive drug usage and disease severity, which shows that the expectations of guidelines have not been met even in facilitated centers, thus indicating the need to revise the severity-based approach of asthma guidelines. Efforts to implement the control-based approach of new guidelines (Global Initiative for Asthma 2006) would be worthwhile.

Lower airways inflammation in allergic rhinitics: a comparison with asthmatics and normal controls.

BACKGROUND: Allergic rhinitis (AR) and asthma represent a continuum of atopic disease. AR is believed to pre-dispose an individual to asthma. Compared with asthmatics and normal controls, the inflammatory response in the lower airways of rhinitics is not fully elucidated. To test the hypothesis that the inflammatory response in the airways of subjects with AR is at a level intermediate between that in normal controls and asthmatics, we have characterized bronchial inflammation and cytokine mRNA levels in non-asthmatic allergic rhinitics and compared it with subjects with allergic asthma and with normal controls. METHODS: Endobronchial mucosal biopsies were obtained at bronchoscopy from 14 allergic rhinitics, 16 asthmatics and 21 normal controls. Biopsies were embedded into glycol methacrylate resin for immunohistochemical analysis of cellular inflammation and snap frozen for semi-quantitative PCR analysis of cytokine mRNA levels. RESULTS: Airway inflammation in rhinitic subjects was characterized by an increase in submucosal eosinophils, mast cells and the mRNA expression of TNF-alpha, at an intermediate level between healthy and asthmatics. In addition, CD3(+) and CD8(+) lymphocytes in the epithelium, the endothelial expression of vascular adhesion molecule-1 and IL-1 beta mRNA were higher in the allergic rhinitics compared with both normal controls and asthmatics, whereas growth-related oncogene alpha-mRNA was decreased in AR compared with both healthy and asthmatics. Airway inflammation in the asthmatic group was characterized by higher numbers of eosinophils and mast cells, together with an increase in TNF-alpha-mRNA compared with both healthy and rhinitics. IFN-gamma mRNA was the highest in normal controls and lowest in the asthmatics. CONCLUSIONS: In individuals with AR the present data suggest an intermediate state of airway inflammation between that observed in normal individuals and subjects with clinical asthma. It is also indicated that IFN-gamma production by CD8(+) T lymphocytes could be protective against the development of airway hyperresponsiveness. Further work is needed to evaluate this hypothesis.

The effect of regular versus on-demand desloratadine treatment in children with allergic rhinitis.

OBJECTIVE: Desloratadine is a potent antihistamine. Whether regular or on-demand use of desloratadine influences its therapeutic efficacy in allergic rhinitis is unknown. The aim of the study was to compare the clinical efficacy and the anti-inflammatory activity of regularly administered desloratadine to its on-demand use in children with allergic rhinitis due to pollen allergy. METHODS: Thirty-seven patients with allergic rhinitis with or without mild intermittent asthma were enrolled in a prospective parallel group study. Patients were treated with desloratadine regularly or on-demand during pollen season. Rescue medications and symptom scores were recorded on a diary card. Nasal flow rate and inflammatory markers were recorded, and methacholine (Mch) challenge test was administered before and within the pollen season. RESULTS: Though symptoms were lower in the evening than in the morning (p<0.001), there was no difference between the two groups. There was no difference between the groups with respect to medication score except that the salbutamol use was lower in the regular treatment group during the fourth week (p=0.032) in the pollen season. Nasal flow rate and inflammatory markers failed to show any difference between the groups. A significant reduction in PC20 values (provocative concentration of Mch causing a 20% fall in FEV(1)) was observed in regular (p=0.016) and on-demand (p=0.005) treatment groups compared to the pre-season measurements. The number of children with a PC20 below 8 mg/ml increased significantly in the on-demand group. CONCLUSION: Our study demonstrates that on-demand use of desloratadine during the pollen season is clinically as effective as regular treatment. However, regular treatment may provide better control of lower airway symptoms and airway reactivity.

Turkish physicians' perception of allergic rhinitis and its impact on asthma.

BACKGROUND: The clinical association of rhinitis and asthma has been recognized for centuries, leading to a current definition of 'one airway, one disease'. Current findings indicate that the optimal treatment of rhinitis might improve coexisting asthma. OBJECTIVES: To evaluate perception of the asthma-rhinitis association and to determine their capability in managing rhinitis. METHODS: Participants of three national asthma meetings, in 2004, were asked to complete a questionnaire which, aside from demographic queries, elicited responses in order to reflect agreement or not with the given statements. RESULTS: Of the 354 attendees, 220 (62%) responded to the questionnaire. Although over 80% reported good perception of the asthma-rhinitis association, only one-third were examining nasal mucosa of asthmatics, and over 70% believed sinus X-ray, blood eosinophil count, and determination of total serum IgE were required to diagnose allergic rhinitis. Between 20% and 40% of the physicians reported misuse of medications for rhinitis. CONCLUSIONS: This survey documented that the asthma-rhinitis association is generally recognized by physicians treating asthma in Turkey. However, there are certain training needs in terms of attitude towards examinations and appropriate use of laboratories and medications for rhinitis. Improved understanding/management of rhinitis may contribute to asthma care as well as patient satisfaction and adherence to treatment.