Can serum periostin, YKL-40, and osteopontin levels in pre-school children with recurrent wheezing predict later development of asthma?

BACKGROUND: Currently, there are no reliable clinical tools available for predicting asthma in pre-school-aged children with recurrent wheezing. The aim of this study was to evaluate the usefulness of serum periostin, YKL-40, and osteopontin biomarkers in wheezy pre-school-aged children for predicting the development of asthma in school ages. METHODS: The study was prospectively conducted between 2011 and 2017. The clinical features of the pre-school-aged children with recurrent wheezing and the levels of serum periostin, YKL-40, and osteopontin were measured. The same participants were reevaluated in school-age period, and participants with asthma were identified. Relative risk (RR) for the development of asthma was analyzed. RESULTS: Of the 197 pre-school-aged children with recurrent wheezing who were reevaluated in school-age years, 32% of them had asthma. Serum periostin, YKL-40, and osteopontin levels at admission could not predict participants who would have asthma symptoms in school-age years. The RR for continuing of asthma symptoms was higher in participants who had their first wheezing episode before 1 year of age, preterm birth, cesarean section delivery, prenatal smoking exposure, multi-trigger wheezing, parental asthma, modified asthma predictive index positivity, prophylactic vitamin D intake ≤ 12 months, breastfeeding time ≤ 12 month, and aeroallergen sensitivity [RR (95% CI) and P value: 2.813 (1.299-6.091), 0.002; 1.972 (1.274-3.052), 0.009; 1.929 (1.195-3.114), 0.004; 2.232 (1.463-3.406), <0.001; 3.152 (1.949-5.097), <0.001; 1.730 (1.144-2.615), 0.016; 2.427 (1.559-3.777), <0.001; 2.955 (1.558-5.604), <0.001; 1.767 (1.084-2.881), 0.016; 0.765 (0.556-1.053), 0.016; respectively]. CONCLUSION: Results have shown that clinical features were more valuable than biomarkers in predicting having asthma in school-age years in participants who had recurrent wheezing in pre-school-age period.

Risk Factors Influencing Tolerance and Clinical Features of Food Protein-induced Allergic Proctocolitis.

OBJECTIVE: Continued progress in our understanding of the food protein-induced allergic proctocolitis (FPIAP) will provide the development of diagnostic tests and treatments. We aimed to identify precisely the clinical features and natural course of the disease in a large group of patients. Also, we investigated the predicting risk factors for persistent course since influencing parameters has not yet been established. METHODS: Infants who were admitted with rectal bleeding and had a diagnosis of food protein-induced allergic proctocolitis in 5 different allergy or gastroenterology outpatient clinics were enrolled. Clinical features, laboratory tests, and prognosis were evaluated. Risk factors for persistent course were determined by logistic regression analyses. RESULTS: Among the 257 infants, 50.2% (n = 129) were girls and cow's milk (99.2%) was the most common trigger. Twenty-four percent of the patients had multiple food allergies and had more common antibiotic use (41.9% vs 11.8%), atopic dermatitis (21% vs 10.2%), wheezing (11.3% vs 1.5%), colic (33.8% vs 11.2%), and IgE sensitization (50% vs 13.5%) compared to the single-food allergic group (P < 0.001, P = 0.025, P = 0.003, P < 0.001, respectively). In multivariate logistic regression analysis, presence of colic (odds ratio [OR]: 5.128, 95% confidence interval [CI]: 1.926-13.655, P = 0.001), IgE sensitization (OR: 3.964, 95% CI: 1.424-11.034, P = 0.008), and having allergy to multiple foods (OR: 3.679, 95% CI: 1.278-10.593, P = 0.001] were found to be risk factors for continuing disease after 1 year of age. CONCLUSION: Although most children achieve tolerance at 1 year of age, IgE sensitization, allergy to multiple foods, and presence of colic were risk factors for persistent course and late tolerance. In this context, these children may require more close and extended follow-up.

Allergy-specific Phenome-Wide Association Study for Immunogenes in Turkish Children.

To dissect the role of immunogenetics in allergy and asthma, we performed a phenome-wide association study in 974 Turkish children selected from a cross-sectional study conducted using ISAAC (International Study of Asthma and Allergies in Children) Phase II tools. We investigated 9 loci involved in different immune functions (ADAM33, ADRB2, CD14, IL13, IL4, IL4R, MS4A2, SERPINE1, and TNF) with respect to 116 traits assessed through blood tests, hypertonic saline challenge tests, questionnaires, and skin prick tests. Multiple associations were observed for ADAM33: rs2280090 was associated with reduced MEF240% (i.e., the ratio of Mean Expiratory Flow after 240s of hypertonic saline inhalation with respect to the age- and ancestry-matched reference value) and with an increased risk of allergic bronchitis (p = 1.77*10(-4) and p = 7.94*10(-4), respectively); rs3918396 was associated with wheezing and eczema comorbidity (p = 3.41*10(-4)). IL4 rs2243250 was associated with increased FEV240 (Forced Expiratory Flow Volume after 240s of hypertonic saline inhalation; p = 4.81*10(-4)) and CD14 rs2569190 was associated with asthma diagnosis (p = 1.36*10(-3)). ADAM33 and IL4 appeared to play a role in the processes linked to allergic airway inflammation and lung function. Due to its association with wheezing and eczema comorbidity, ADAM33 may also be involved in the atopic march.

Direct oral provocation tests in non-immediate mild cutaneous reactions related to beta-lactam antibiotics.

BACKGROUND: Skin testing has a limited role in the diagnosis of non-immediate beta-lactam hypersensitivity in children. The aim of this study was to report the results of oral provocation tests performed without skin tests in children with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. METHODS: Oral provocation tests with suspected antibiotics were performed to patients with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. Skin tests were not performed before provocation tests. A total of five doses were administered with half-an-hour intervals in increasing doses. Provocation was continued for 5 days. RESULTS: A total of 119 patients with a median age of 4.3 (IQR: 2-7.5) years, of whom 58% were males, were included in the study. Amoxicillin-clavulanic acid was the most frequently responsible agent in 87 (73.1%) patients, and most common type of rash was maculopapular in 74 (62.2%) patients. Four patients (3.4%) had an urticarial reaction during the provocation test. CONCLUSION: We did not experience any severe reactions during oral provocation test without previous skin tests performed to children with non-immediate mild cutaneous reactions without systemic symptoms. Omitting skin tests before oral provocation test in this group of children can help decreasing the burden of allergy clinics and alleviating the discomfort of children.

Nonsteroidal anti-inflammatory drug hypersensitivity among children.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) are the second-most frequent drugs that cause hypersensitivity reactions among children. Studies related to NSAIDs hypersensitivity in children are limited. In this study, we aimed to evaluate children admitted with suspicion of NSAIDs reaction. METHOD: Between January 1, 2011, and November 30, 2014, we included patients with suspicion of NSAIDs hypersensitivity in our clinic. For evaluation, skin tests and oral provocation tests with the drug (suspected or alternative) were proposed. Reactions were classified and defined according to the latest European Academy of Allergy and Clinical Immunology position paper on NSAID hypersensitivity. RESULTS: During the study period, 123 patients (with 136 drug reactions) were admitted to our clinic with suspected NSAID hypersensitivity. The mean (standard deviation) age of the patients, 67 female (55%), was 83.10 ± 56.05 months. Thirteen patients described reactions to more than one chemically unrelated NSAID, and 110 patients described reactions with chemically similar drugs. Eight patients were not included because they did not have provocation tests. Thus, 115 patients were evaluated. A hundred and thirty provocations were performed. Twenty patients (17.4%) were diagnosed with NSAID hypersensitivity (13 patients diagnosed by provocation tests and 7 patients diagnosed according to their history). The most frequently encountered agent was ibuprofen (50% [10/20]). Eighty percent (16 patients) of the reactions were considered "non-cross-reactive type." Fifteen patients (75%) were classified as having single-NSAID-induced urticaria and/or angioedema, three patients were classified as having NSAID-induced urticaria and/or angioedema, one patient was classified as having NSAID-exacerbated respiratory disease, and the other patients were classified as having single-NSAID-induced delayed hypersensitivity reactions. CONCLUSION: Detailed history and drug provocation tests are important to verify NSAID hypersensitivity. The most common type is the non-cross-reactive type, and, in our study, the most common responsible drug was ibuprofen.

Characteristics and Prognosis of Allergic Proctocolitis in Infants.

OBJECTIVES: The dietary protein proctocolitis, also known as allergic proctocolitis (AP), is characterized by the presence of mucoid, frothy, and bloody stools in an otherwise healthy infant. The aim of this study was to describe a group of children with AP, diagnosed according to the criterion-standard method, food challenge to provide clinicians with more information on typical presentation, and an overview on nutritional management strategies and prognosis. METHODS: We collected data on infants with AP in our allergy and gastroenterology outpatient clinics. Any other conditions that may cause bloody diarrhea were ruled out. Skin prick tests and atopy patch tests were performed for diagnosis, and patients were studied for resolution. To the patients whose rectal bleeding did not recover with oligoantigenic maternal diet in addition to amino acid-based formula, endoscopic evaluation was performed to confirm the diagnosis and to exclude other reasons of rectal bleeding. RESULTS: Sixty patients were diagnosed as having AP. The age of onset was 1.7 ±â€Š1.32 months. All of the patients were triggered by milk, 6.6% with milk and egg, 3.3% with milk and chicken, 1.7% with milk and wheat, 1.7% with milk and potato, and 3.3% had multiple food allergy. 53.3% (n = 32) acquired tolerance by age 1, 25.0% (n = 15) by 2 years, 5% (n = 3) by 3, and 1.7% (n = 1) by 4 years. CONCLUSIONS: Milk was a triggering factor for all of the patients. Resolution of AP is usually within 1 year but symptoms of some patients may continue even longer. An extension of the follow-up period is required according to our study.

Negative predictive value of drug provocation tests in children.

BACKGROUND: The negative predictive value of the drug provocation test is important for both the patient and the physician. However, in children, this predictive value is unresolved. METHODS: The study included patients who had drug provocation test with a suspected drug and was diagnosed as 'not allergic to the drug'. Three months after allergy workup, the patients were contacted and asked for reexposure to the tested drug. Patients who have reported reactions during reexposure were reevaluated with skin tests and drug provocation. RESULTS: During the study period, 217 provocations were performed to 203 patients. Of these, 163 patients (80.3%) with 175 negative drug provocation tests could be contacted. Ninety-one (52%) of the 175 cases reported to use the tested drug again, and 11 (12%) of these cases declared that they had a new reaction. Two of the eleven cases refused reevaluation. Nine cases were evaluated by drug allergy workup. Two of the nine cases were classified as allergic after retests. Collectively, the negative predictive value was 95.6% (87 of 91 cases) for all drug challenges. CONCLUSIONS: The negative predictive value of the drug provocation test is abundant in children; however, negative drug provocation tests do not necessarily predict tolerance for the drug.

Viral etiology in infants hospitalized for acute bronchiolitis.

Acute bronchiolitis is predominantly a viral disease. Respiratory syncytial virus is the most common agent, but other newly identified viruses have also been considered as causes. The aim of the present study is to determine the respiratory viruses causing acute bronchiolitis in hospitalized infants. Infants younger than 2 years of age who were hospitalized for acute viral bronchiolitis in a children's hospital between November 2011 and May 2012 were evaluated for the presence of viruses as etiologic agents using a realtime polymerase chain reaction method.A total of 55 infants were included in this study. The mean age of the children was 6.98±5.53 months, and 63.6% were male. In the 55 children, 63 viruses were detected. A single viral pathogen was detected in 47 (85.5%) patients, and two viruses were co-detected in 8 (14.6%) patients. Respiratory syncytial virus was the most common virus identified, accounting for 25 (45.5%) cases, followed by rhinovirus (n=9, 16.4%), and human metapneumovirus (n = 8, 14.5%).Although respiratory syncytial virus remains the major viral pathogen in infants hospitalized for acute broncholitis, more than half of bronchiolitis cases are associated with other respiratory viruses.

Prevalence of confirmed IgE-mediated food allergy among adolescents in Turkey.

BACKGROUND: Although food allergy is an important health problem in Western countries, the prevalence varies among geographic regions. There is limited data on the prevalence of food allergy especially for adolescent age group, and the data from Turkey and Mediterranean region are even scarce. METHODS: The study is a cross-sectional survey including a questionnaire followed by phone survey with families that have reported food allergy and clinical evaluation of children having a history compatible with food allergy after phone survey. The sample number of students has been calculated 9096 of a total of 210.000 students at the second stage (6th, 7th, and 8th grades) of state elementary schools in the metropolitan counties of Ankara province with the assumption of food allergy prevalence (P) = 1% and a δ value = 0.2 (α < 0.05, ß = 0.8). RESULTS: Of 11,233 questionnaires distributed at 34 schools, 10,096 (89.4%) have been returned. The number of reported food allergy was 1139 (11.2%), and it was reduced to 133 (1.3%) after phone survey. After clinical evaluation by skin test, specific IgE and double-blind placebo-controlled food challenge (DBPCFC), proven IgE-mediated food allergy was determined in 15 (0.15%) children. The foods most commonly resulting food allergy were peanut 0.05% and treenuts 0.05%. CONCLUSION: The prevalence of food allergy among adolescent age group has been confirmed to be comparatively low in Turkey. Peanuts and treenuts were determined to be the most common causes of IgE-mediated food allergy.

Consistency of GINA criteria and childhood asthma control test on the determination of asthma control.

BACKGROUND: Reliable assessment of asthma control is essential for effective treatment. Although several methods are used to assess asthma control, it is still suboptimal all over the world. Childhood asthma control test (C-ACT) is a widely used complementary test in determining the level of asthma control in conjunction with GINA guidelines. OBJECTIVE: To evaluate the consistency between the childhood asthma control test (C-ACT) and the Global Initiative for Asthma (GINA) guideline-based asthma control measure in children with asthma and, if present, to investigate the reasons for any discrepancy. METHODS: Patients and their caregivers filled a C-ACT and a socioeconomic status survey before the physician visit. Asthma control level was also assessed according to GINA criteria by a pediatric allergist who was blinded to C-ACT scores. RESULTS: The mean age of the total 314 patients was 9.0 ± 1.9 yr, ranging between 4.3 and 11.8 yr, of whom 56.1% (n = 176) were men. Regarding the study group, 54.8% of patients were controlled according to GINA, and 51.0% of patients were controlled according to C-ACT (score ≥20). There was inconsistency between GINA and C-ACT in 26.7% (84/314) of the study group when the patients were evaluated individually (κ = 0.464). There was not any significant variable that could predict the consistency and inconsistency between these methods. CONCLUSION: Consistency between GINA and C-ACT is not as to be expected. Using only one method for determining the control level of asthma does not seem to be reliable and accurate.

Demonstration of an aberrant mast-cell population with clonal markers in a subset of patients with "idiopathic" anaphylaxis.

Idiopathic anaphylaxis remains a perplexing disorder in which existing prophylactic therapy is inadequate. In this prospective study, we sought to determine whether patients with idiopathic anaphylaxis might have evidence for a clonal disorder of mast cells related to mastocytosis and for which novel targeted therapies might be considered. We report 12 patients with "idiopathic" anaphylaxis who did not exhibit either urticaria pigmentosa or the characteristic bone marrow biopsy finding of multifocal mast-cell aggregates observed in systemic mastocytosis. Of these 12 patients, 5 had evidence of 1 or more minor criteria for mastocytosis. C-KIT mutational analysis was positive for the 816D>V activating mutation in 3 of 3 patients in CD25(+) bone marrow cells where the analysis was performed. These results demonstrate the presence of an aberrant mast-cell population carrying clonal markers in a subset of patients diagnosed with "idiopathic" anaphylaxis, who may respond to inhibitors targeting mutated C-KIT. This intramural clinical trial was conducted in 2003 and 2004 and was registered at (http://clinicalcenter.nih.gov) with a study number 03-I-0010. Since the study is now closed, it is no longer available online.

Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature.

BACKGROUND: Mast cells and basophils share similar morphologic and functional properties; however, it is not known whether they are derived from a bilineage (basophil/mast cell)-restricted progenitor. OBJECTIVE: To assess whether basophils and mast cells are derived from common committed progenitors using the c-kit D816V mutation as a biologic signature. METHODS: The D816V c-kit mutation found in mast cells of patients with systemic mastocytosis is used as a trackable genetic marker to assess the lineage relationship between mast cells and basophils. Blood and bone marrow aspirates were collected from 33 consecutive patients with mastocytosis with different disease severity. Peripheral blood basophils, monocytes and neutrophils were sorted by immunomagnetic beads. Presence of the D816V c-kit mutation was analyzed by restriction fragment length polymorphism in the genomic DNA and mRNA from sorted cells in all patients and in the genomic DNA of individual basophils of 1 patient. RESULTS: The c-kit D816V mutation was detectable in basophils of 5 patients (15%). All 5 patients had the c-kit mutation also detectable in monocytes and thus had multilineage involvement. Single cell analysis of the genomic DNA in 1 patient showed a similar degree of clonal expansion in basophils, monocytes, and neutrophils. Mutated c-kit was expressed at the mRNA level in all 5 patients. There was no difference in surface Kit expression levels in basophils. CONCLUSION: Basophils carrying the D816V c-kit mutation in mastocytosis were detected only in the context of a multilineage involvement. These results argue against the presence of a bilineage-restricted committed progenitor for mast cells and basophils.