KAAACI Allergic Rhinitis Guidelines: Part 1. Update in pharmacotherapy

The prevalence of allergic rhinitis (AR) and the socioeconomic burden associated with the medical cost and quality of life of AR have progressively increased. Therefore, practical guidelines for the appropriate management of AR need to be developed based on scientific evidence considering the real-world environment, values, and preferences of patients and physicians. The Korean Academy of Asthma, Allergy and Clinical Immunology revised clinical guidelines for AR to address key clinical questions of the management of AR. Part 1 of the revised guideline covers the pharmacological management of patients with AR in Korea. Through a meta-analysis and a systematic review, we made 4 recommendations for AR pharmacotherapy, including intranasal corticosteroid (INCS)/intranasal antihistamine combination therapy, oral antihistamine/INCS combination therapy, leukotriene receptor antagonist treatment in AR patients with asthma, and prophylactic treatment for patients with pollen-induced AR. However, all recommendations are conditional because of the low or very low evidence of certainty. Well-designed and strictly executed randomized controlled trials are needed to measure and report appropriate outcomes.

KAAACI Allergic Rhinitis Guidelines: Part 2. Update in nonpharmacotherapy

Allergic rhinitis is the most common chronic disease worldwide. Various upper airway symptoms lower quality of life, and due to the recurrent symptoms, multiple treatments are usually attempted rather than one definitive treatment. There are alternatives to medical (medication-based) and nonmedical treatments. A guideline is needed to understand allergic rhinitis and develop an appropriate treatment plan. We have developed guidelines for medical treatment based on previous reports. The current guidelines herein are associated with the “KAAACI Evidence-Based Guidelines for Allergic Rhinitis in Korea, Part 1: Update in pharmacotherapy” in which we aimed to provide evidence-based recommendations for the medical treatment of allergic rhinitis. Part 2 focuses on nonpharmacological management, including allergen-specific immunotherapy, subcutaneous or sublingual immunotherapy, nasal saline irrigation, environmental management strategies, companion animal management, and nasal turbinate surgery. The evidence to support the treatment efficacy, safety, and selection has been systematically reviewed. However, larger controlled studies are needed to elevate the level of evidence to select rational non-medical therapeutic options for patients with allergic rhinitis.

A case of vocal cord dysfunction diagnosed in a 10-year-old girl with recurrent wheezing and dyspnea

Vocal cord dysfunction is one of the causes of dyspnea and is characterized by paradoxical closure of the vocal cords. The paradoxical movement of the vocal cords produces the limitation of airflow, resulting dyspnea, chest tightening, hoarseness, stridor, or wheezing. These findings are similar to those of other upper airway obstruction diseases or asthma; therefore, a high index of suspicion and clear differential diagnosis are required. Here, we discuss a case of vocal cord dysfunction aged 10 years that presented recurrent wheezing and dyspnea. The abnormal movement of the vocal cords was observed by fiberoptic laryngotracheobronchoscopy, which was correlated with stridor during respiration. Repeated episodic symptoms were controlled by the multidisciplinary team approach; however, surgical treatment was needed to stabilize the symptom.

Current practice of antibiotics skin test in pediatric inpatients:A single-center experience

Background@#Routine practice of antibiotic skin test (AST) before administering antibiotics is with little scientific basis. However, AST is frequently performed in real-world practice. We aimed to explore the current practice status of AST. @*Methods@#All admission cases in Severance Hospital between January 2019 and December 2020 of patients at less than 19 years of age were collected retrospectively. AST results for 4 penicillins (ampicillin, ampicillin-sulbactam, amoxicillin-clavulanate, and piperacillin-tazobactam) and 6 cephalosporins (cefazolin, cefotaxime, cefotiam, cefpiramide, ceftriaxone, and flomoxef) as well as adverse drug reaction (ADR) reports were collected. @*Results@#Among 36,381 hospitalization cases, 7,589 and 16,468 were administered penicillins and cephalosporins, respectively. Penicillins were administered without AST in 2,622 cases (35%), 2 (0.08%) of which showed ADR. Of the remaining 4,967 cases who received AST, 57 (1.1%) showed a positive reaction. For cephalosporins, 15,473 cases (94%) received antibiotics without AST. Among them, 17 cases (0.1%) showed ADRs. For 995 cases that rceived AST, 22 (2.2%) revealed a positive reaction. Among 79 cases who were AST positive, 10 took the original medication. @*Conclusion@#The current practice of AST reveals heterogeneous and inconsistent patterns. This brings the need for a standardized guideline for the safe and effective use of antibiotics.

Radiologic Assessment of Lung Edema Score as a Predictor of Clinical Outcome in Children with Acute Respiratory Distress Syndrome

Purpose@#The radiographic assessment of lung edema (RALE) score enables objective quantification of lung edema and is a valuable prognostic marker of adult acute respiratory distress syndrome (ARDS). We aimed to evaluate the validity of RALE score in children with ARDS. @*Materials and Methods@#The RALE score was measured for its reliability and correlation to other ARDS severity indices. ARDSspecific mortality was defined as death from severe pulmonary dysfunction or the need for extracorporeal membrane oxygenation therapy. The C-index of the RALE score and other ARDS severity indices were compared via survival analyses. @*Results@#Among 296 children with ARDS, 88 did not survive, and there were 70 ARDS-specific non-survivors. The RALE score showed good reliability with an intraclass correlation coefficient of 0.809 [95% confidence interval (CI), 0.760–0.848]. In univariable analysis, the RALE score had a hazard ratio (HR) of 1.19 (95% CI, 1.18–3.11), and the significance was maintained in multivariable analysis adjusting with age, ARDS etiology, and comorbidity, with an HR of 1.77 (95% CI, 1.05–2.91). The RALE score was a good predictor of ARDS-specific mortality, with a C-index of 0.607 (95% CI, 0.519–0.695). @*Conclusion@#The RALE score is a reliable measure for ARDS severity and a useful prognostic marker of mortality in children, especially for ARDS-specific mortality. This score provides information that clinicians can use to decide the proper time of aggressive therapy targeting severe lung injury and to appropriately manage the fluid balance of children with ARDS.

Allergen sensitization trajectories in children with respiratory and allergic diseases

Purpose@#There is a lack of a report about the trajectories of allergen sensitization, although it is important to understand the change of allergen sensitization to manage allergic disease. This study aimed to analyze the change and trajectories of allergen sensitization in children with respiratory and allergic diseases. @*Methods@#From 2006 to 2020, children with respiratory and allergic diseases or screened for allergic sensitization were evaluated. We visualized the alterations and the trajectories of allergen sensitization using stacked area graphs, box plots, and Sankey diagrams. @*Results@#A total of 2,804 subjects were included, and allergic rhino-conjunctivitis was diagnosed in 1,931 children (68.9%). The mean age for the first test was 4.1 years, and that for the second test was 6.5 years. Children sensitized to class 1 food allergen before age 5 showed sensitizations more for other allergens and at a younger age after age 5 than children who were not. The atopic tendency continued once it had been obtained before the early school age in the persistence or the new development of sensitization. @*Conclusion@#Allergen sensitization has changed over time and has shown different patterns according to age. Its trajectory has taken a wide variety of courses in children with respiratory and allergic diseases until the early school age. These changes reflect the allergic diseases and socio-environmental characteristics of children and adolescents.

Associations between pollen and allergic rhinitis in children and adolescents

Allergic rhinitis (AR) is a type of rhinitis accompanied by sensitization to allergens. One of the most clinically important allergens is pollen. Recently, due to climate change and CO 2 air pollution, the flowering period starts earlier and persists longer. In addition, antigenicity due to environmental pollution is also being strengthened. As a result, the sensitization rate to pollen antigens is on the rise. It is known that the prevalence of AR especially caused by pollen is rapidly escalating. Although the causal relationship between pollen exposure and the severity of rhinitis is not precisely established, an association of rhinitis symptoms with the time of pollen scattering exists. In addition, the mixed effect of environmental pollution and pollen may play a role in the development of rhinitis symptoms. Therefore, in order to avoid pollen, it is necessary to constantly improve pollen forecast and minimize the contact with pollen indoors and outdoors. Treatment of AR should be performed according to guidelines. Also, continuous efforts to solve the environmental problems affecting the ecology of pollen are needed.

Clinical Characteristics of Atopic Dermatitis in Korean School-Aged Children and Adolescents According to Onset Age and Severity

Background@#Atopic dermatitis (AD) is a heterogeneous disease with different age of onset, disease course, clinical symptoms, severity, and risk of comorbidity. The characteristics of children with AD also vary by age or country. However, little is known about the clinical characteristics of AD in Korean school-aged children and adolescents. Furthermore, there are few studies on phenotypic differences according to onset age. This study aimed to explore the clinical characteristics and phenotypes according to onset age and severity of AD in children and adolescents in Korea. @*Methods@#AD patients aged 6–18 years who presented to 18 hospitals nationwide were surveyed.The patients were examined for disease severity by pediatric allergy specialists, and data on history of other allergic diseases, familial allergy history, onset age, trigger factors, lesion sites,treatment history and quality of life were collected. The results of the patient’s allergy test were also analyzed. The patients were classified into infancy-onset (< 2 years of age), preschoolonset (2–5 years of age), and childhood-onset (≥ 6 years of age) groups. Study population was analyzed for clinical features according to onset-age groups and severity groups. @*Results@#A total of 258 patients with a mean age of 10.62 ± 3.18 years were included in the study. Infancy-onset group accounted for about 60% of all patients and presented significantly more other allergic diseases, such as allergic rhinitis and asthma (P = 0.002 and P = 0.001, respectively). Food allergy symptoms and diagnoses were highly relevant to both earlier onset and more severe group. Inhalant allergen sensitization was significantly associated with both infancy-onset group and severe group (P = 0.012 and P = 0.024, respectively). A family history of food allergies was significantly associated with infancyonset group (P = 0.036). Severe group was significantly associated with a family history of AD, especially a paternal history of AD (P = 0.048 and P = 0.004, respectively). Facial (periorbital, ear, and cheek) lesions, periauricular fissures, hand/foot eczema, and xerosis were associated with infancy-onset group. The earlier the onset of AD, the poorer the quality of life (P = 0.038). Systemic immunosuppressants were used in only 9.6% of the patients in the severe group. @*Conclusion@#This study analyzed the clinical features of AD in Korean children and adolescents through a multicenter nationwide study and demonstrated the phenotypic differences according to onset age and severity. Considering the findings that the early-onset group is more severe and accompanied by more systemic allergic diseases, early management should be emphasized in young children and infants.

Adverse reactions to coronavirus disease 2019 vaccines in children and adolescents

The incidence of coronavirus diseases 2019 (COVID-19), including severe cases, has been increasing in both children and adolescents with the spread of the delta variant. COVID-19 vaccines have been identified to be effective in the prevention of COVID-19transmission in children and adolescents and keeping schools open. However, adverse reactions associated with COVID-19 vaccination in children and adolescents contribute to parents’ hesitation to proceed with vaccination, especially due to serious, albeit rare, reactions. The results from COVID-19 vaccine clinical trials on the safety and efficacy of COVID-19 vaccines in children and adolescents are promising in terms of their effects on COVID-19 infection prevention. In the present study, we summarize the adverse reactions of COVID-19 vaccines in children and adolescents, based on the clinical trials, mainly including Pfizer-BioNTech and Moderna COVID-19 vaccines. In the Pfizer-BioNTech COVID-19 clinical trials, the most common local adverse reaction was pain at the injection site in 74.1%–86%, depending on age, and the most common systemic adverse reaction was fatigue, followed by headache, myalgia, diarrhea, and fever with differences in the distribution according to age. There was no severe adverse reaction related to any COVID-19 vaccine in children and adolescents during the study period. In the mass vaccination program of COVID-19 in children and adolescent, myocarditis has rarely been diagnosed after COVID-19 vaccination, which most commonly occurred in boys after the second dose. Currently, Pfizer-BioNTech COVID-19 vaccines can be safely recommended in children and adolescents for the prevention of COVID-19 infection and the reduction in COVID-19 severity.

Effects of outdoor air pollution on children with allergic rhinitis

The global worsening of air pollution has decreased the quality of life. Air pollutants can induce oxidative stress, epigenetic changes, and alterations to microRNA expression in the airway and skin, leading to immune dysregulation. Previous epidemiological studies suggest a strong association between outdoor environmental pollution and childhood allergic disease, especially allergic rhinitis (AR). Moreover, traffic-related air pollution has increased the severity and incidence of AR, and heavy traffic has been associated with an increased prevalence of AR. Thus, this review aimed to define outdoor environmental pollution and clarify the mechanisms by which air pollutants aggravate AR. In addition, we performed a systematic review and meta-analysis to summarize the findings of several domestic and international epidemiological and clinical studies about the effects of air pollution on AR in children.

Risk factors and protective factors in pediatric patients with allergic rhinitis

Among allergic diseases of the Korean pediatric population, allergic rhinitis shows the most rapidly increasing prevalence. Its economic burden is substantial in many Asian countries including South Korea. This investigation of its risk factors aims to reduce the socioeconomic burden by blocking exposure of susceptible individuals to identified causes. However, the risk factors of allergic rhinitis varied considerably depending on the seasons, geographical locations, and populations involved. This review article primarily deals with studies on the risk factors for allergic rhinitis in Korean children that were published during the last 10 years and additionally investigates associated large scale international studies. Our investigation identified several single-nucleotide polymorphisms, inhalant allergens, pollution, tobacco smoke, chemicals, and family affluence as risk factors for allergic rhinitis. In contrast, breastfeeding, older sibling, and microbial diversity were protective factors against allergic rhinitis. This suggests that various genetic and environmental factors might affect the manifestation and presentation of allergic rhinitis complexly. These findings are beneficial as they can provide insights into modifiable risk factors that may hinder the development of allergic rhinitis.

Main epidemiological characteristics and natural history of pediatric allergic rhinitis

Allergic rhinitis (AR) is one of the most common allergic diseases characterized by stuffy nose, rhinorrhea, sneezing, and itching. Researchers have indicated an increase in the prevalence of AR and younger-age onset during the last few decades. The increasing burden of AR has caused many researchers to investigate time trends of the prevalence of AR and to identify its risk factors. The most commonly used epidemiological studies are cross-sectional ones such as the International Study of Asthma and Allergies in Childhood study and big data from National Health Insurance Service or National Health and Nutrition Examination Survey. However, these studies have many limitations including recall bias, selection bias, and deficit of objective evaluation. Furthermore, crosssectional studies cannot reflect new risk factors associated with the development of AR. New epidemiological studies will be needed to cover genetic factors, environmental changes, microbiomes, and lifestyles that are known to be risk factors for AR. Further studies will be needed to determine the prevalence, natural history, and risk factors of AR in order to advance our understanding of the pathophysiology, prevention, and management of comorbidities of AR.

Changes in allergen sensitization in children with allergic diseases in the 1980 to 2019

Purpose@#Allergen sensitization is constantly changing, and understanding these changes can help manage and prevent allergic diseases. This research analyzed and compared the changes in allergen sensitization in children diagnosed with allergic diseases using the skin test and the multiple allergen simultaneous test. @*Methods@#We retrospectively analyzed the data on children who were diagnosed with allergic diseases and received immunotherapy at Yonsei Medical Center from 1980 to 1998 and they were screened for allergen sensitization at Severance Hospital from 2005 to 2019. @*Results@#Between 1980 and 1998, and between 2005 and 2019, data on 3,205 (male, 70.3%; mean age, 7.2 ± 2.9 years) and 15,318 children (male, 62.8%; mean age, 8.8 ± 4.5 years) were analyzed. The sensitized allergens that appeared in the 1980–1998 included Dermatophagoides farinae (91.0%), Dermatophagoides pteronyssinus (76.3%), cockroach (13.5%), and Alternaria (11.5%), in order of frequency; further, the sensitized allergens that appeared in the 2005–2019 included D. farinae (45.0%), D. pteronyssinus (39.6%), cat dander (12.2%), and dog dander (9.1%), in order of frequency. D. farinae and D. pteronyssinus demonstrated the highest sensitization rates, although the rates decreased gradually. The sensitization to cat dander and dog dander showed a growing trend, and sensitization to Humulus japonicus, Candida, and cockroach decreased after 2005. @*Conclusion@#Over the past 40 years, the allergen sensitization in Korean children with allergic diseases has increased. These changes reflect lifestyle and environmental changes and influence allergic disease management approaches. Thus, changes in allergic sensitization should be monitored continuously.

The current status and issue of food allergen labeling in Korea

With increasing need to prevent serious food allergy reactions, Korean food allergen labeling regulation has been revised repeatedly. This paper aims to summarize current statuses of food allergen labeling in Korea and foreign countries and to analyze the issue of food allergen labeling regulation. Korean food labeling regulation currently requires 19 items and 22 foods to be reported on labels (eggs, milk, buckwheat, peanut, soybean, wheat, mackerel, crab, shrimp, pork, peach, tomato, sulfite, walnut, chicken, beef, squid, shellfish, and pine nut). However, some common food triggers (for example, almond, cashew nut, and kiwi fruit) are not included in the current labeling regulation. Another issue is that the Korean labeling regulation has not yet been fully implemented for nonprepacked foods; thus, consumers still have difficulty in correctly identifying allergenic ingredients in food. It should be assessed whether warning statements for cross-contamination are reasonable. To prevent the occurrence of serious reactions from accidental ingestion, efforts must be made to solve recently raised issues including the items required to be listed on food labels, the system of standards for labeling and display methods.

Seasonal patterns and etiologies of croup in children during the period 2010–2015: A multicenter retrospective study

PURPOSE: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of parainfluenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to examine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period. METHODS: Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medical records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical information were cross-sectionally reviewed and analyzed. RESULTS: Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a total of 927 who underwent RT-PCR were included in the analysis. Males (61.5%) predominated, and most (63.0%) of them were younger than 2 years of age (median, 19 months; interquartile range, 11–31 months). Peak hospitalization occurred in 2010 and 2012 in even-numbered years, and parainfluenza virus (PIV, 39.7%) was the most common cause of childhood croup requiring hospitalization, followed by respiratory syncytial virus (14.9%), human rhinovirus (12.5%), Mycoplasma pneumonaie (10.6%), and human coronavirus (7.3%). CONCLUSION: It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most common cause of childhood croup; however, croup epidemics could be attributed to other viruses.

Effects of Vacuuming Mattresses on Allergic Rhinitis Symptoms in Children

PURPOSE: To evaluate the effects of daily vacuuming of mattresses on the concentration of house dust mite (HDM) allergens and on allergic rhinitis (AR) symptoms in children sensitized to HDM. METHODS: Forty children between the ages of 6 and 12 years with mild persistent AR and sensitized only to HDM were enrolled and randomly allocated to 2 groups. Caregivers of children in the experimental group cleaned the children's rooms and vacuumed their mattresses daily for 2 weeks. Caregivers of children in the control group cleaned the children's rooms without vacuuming mattresses. Symptoms of AR were checked weekly and dust samples were collected from the mattresses before and after the study. RESULTS: Demographics at the beginning of the study were not significantly different between the 2 groups. In the experimental group, symptoms of AR and dust weight were significantly decreased after 2 weeks (total symptoms of AR, P <0.001; sneezing, P < 0.001; rhinorrhea, P <0.001; nasal obstruction, P < 0.001; itching, P <0.001; and dust weight, P = 0.006). The concentrations of HDM allergens were not changed significantly (Der p1, P = 0.333; Der f1, P = 0.841). In the control group, there were no significant changes in symptoms of AR, dust weight, or the concentration of HDM allergens. CONCLUSIONS: Our findings showed that daily vacuuming of mattresses reduced dust weight and symptoms of AR. However, the concentration of HDM allergens did not significantly decrease.

Analysis of PD-L1 expression in salivary duct carcinoma with its efficacy as a tumor marker / 대한두경부종양학회지

BACKGROUND/OBJECTIVES: Despite multiple approaches of treatments for salivary duct carcinoma, there has been a need for more successful treatment methods because of its poor prognosis. Treatment options like immunotherapy using new technologies have been attempted. Based on recent study results indicating that targeting programmed death receptors are effective in treating various cancers, this study aimed to identify the frequency of PD-L1 expression and its impact on survival rate in salivary duct carcinoma.MATERIALS #SPCHAR_X0026; METHODS: We studied 33 patients with salivary gland cancer who were available for histologic specimens. We examined the expression of PD-L1 in the tissues and analyzed the association with the survival rate and the association with various clinical parameters.RESULTS: According to this study and review of similar studies, we discovered that the expression of PD-L1 in salivary duct carcinoma was lower than other types of cancers. The impact of PD-L1 on survival rate also showed inconsistency in salivary duct carcinoma.CONCLUSION: Immunotherapy by PD-1/PD-L1 checkpoint blockade in salivary duct carcinoma needs further evaluation for clinical application.

Estimating Nationwide Prevalence of Live Births with Down Syndrome and Their Medical Expenditures in Korea

BACKGROUND: This study aimed to estimate the nationwide prevalence of live births with Down syndrome (DS) and its trends and compare the observed and model-based predicted prevalence rates. Further, we compared the direct medical expenditures among DS and non-DS patients. METHODS: Using the health administrative data of Health Insurance Review and Assessment in Korea, we selected 2,301 children with DS who were born between 2007 and 2016 to estimate the prevalence of live births with DS, and 12,265 non-DS children who were born between 2010 and 2014 to compare the direct medical expenditures among patients. RESULTS: The prevalence of live births with DS was 5.03 per 10,000 births in 9 years, and 13% of children with DS were medical aid recipients during the study period. The medical expenditure of children with DS was about 10-fold higher than that of non-DS children and their out-of-pocket expenditure was about twice as high. CONCLUSION: The prevalence of live birth with DS is high in the low socioeconomic group and the healthcare costs for the children with DS are significantly higher than those for non-DS children. Therefore, health authorities should help mothers at lower socioeconomic levels to receive adequate antenatal care and consider the cost of medical care for children with DS.

Infantile Anaphylaxis in Korea: a Multicenter Retrospective Case Study

BACKGROUND: Anaphylaxis is increasing in young children. The aim of the present study was to analyze the clinical characteristics of anaphylaxis in Korean infants, with a focus on food triggers. METHODS: The study analyzed the medical records of infants aged 0 to 2 years old who had been diagnosed with anaphylaxis in 23 secondary or tertiary hospitals in Korea. RESULTS: We identified 363 cases of infantile anaphylaxis (66.9% male). Cutaneous symptoms were most prevalent (98.6%), followed by respiratory (83.2%), gastrointestinal (29.8%), and neurologic (11.6%) symptoms. Cardiovascular symptoms were noted in 7.7% of the cases. Most of the cases of anaphylaxis (338; 93.1%) were induced by foods. The most common trigger food was cow's milk and cow's milk products (43.8%), followed by hen's eggs (21.9%), walnuts (8.3%), wheat (7.7%), peanuts (4.8%), other nuts (3.0%), and fish (2.1%). In cow's milk-induced anaphylaxis cases, more than half the cases had cow's milk specific immunoglobulin E (sIgE) levels that were lower than the diagnostic decision points (DDPs), which is 5 kUA/L for those under the age of 1 and 15 kUA/L for those over the age of 1. In anaphylaxis induced by hen's egg, most of the cases (91.8%) had hen's egg sIgE levels that were higher than the DDP, which is 2 kUA/L for those under the age of 2 and 7 kUA/L for those over the age of 2. Of the infantile anaphylaxis cases, 46.8% had been treated with epinephrine, and 25.1% had been prescribed an epinephrine auto-injector. CONCLUSION: Cow's milk is the most frequent trigger food of anaphylaxis in Korean infants. However, we found no significant correlation between the sIgE level and clinical severity. Education is required regarding the importance of epinephrine as the first line therapy for anaphylaxis and on properly prescribing epinephrine for infants with a history of anaphylaxis.

Biomarkers for Recurrent Wheezing and Asthma in Preschool Children

Wheezing is one of the characteristic symptoms of asthma, but all preschool children with wheezing are not diagnosed with asthma. Preschool children are not cooperative enough to participate in spirometry and invasive tests. Thus, there is no conventional method to diagnose asthma in preschool children. We reviewed studies on non-invasive biomarkers for assessing asthma in preschool children. Specimens that can be easily obtained by non-invasive methods are blood, exhaled breath and urine. Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin (EDN) in blood are helpful in evaluating eosinophilic inflammation of the airways. Exhaled breath contains nitric oxide, volatile organic compounds, various cytokines and mediators as analytical components. Fraction of exhaled nitric oxide has been used to assess the degree of eosinophil inflammation and has been standardized in school-age children and adults, but not yet in preschool children. Exhaled breath condensate (EBC) pH and various cytokines/mediators that are detected in EBC seem to be promising biomarkers for assessing asthma, but need more standardization and validation. There are several biomarkers useful for assessing asthma, but none are ideal. Some biomarkers need standardized methods of obtaining samples from uncooperative preschool children for clinical use and require sufficient validation. Recently, another activated eosinophil marker, serum EDN, has shown promising results as a biomarker for recurrent wheezing and asthma in preschool children.