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.

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.

A case of airway hemangioma in a 1-month-old infant with dyspnea

Infantile hemangiomas are the most common benign tumors of infancy. However, hemangiomas located in the respiratory tract are rare and could cause life-threatening events due to airway obstruction. To date, the best recommended treatment for infantile hemangioma is oral propranolol because it demonstrates faster effects and fewer adverse effects than systemic corticosteroid therapy. Here, we report a case of a 1-month-old girl who presented with respiratory symptoms and hemangioma on the scalp. The hemangioma extended from the right base of the skull to thoracic inlet, causing inspiratory stridor and dyspnea. Treatment with oral propranolol was initiated and her symptoms regressed. Imaging showed regression of the hemangioma. This is a rare case of skin hemangioma found on the scalp, in which the hemangioma extended from the base of the skull to the subglottis, precipitating respiratory symptoms from airway obstruction. Based on this encounter, the presentation of skin hemangioma on the head, coupled with respiratory symptoms, necessitates the use of imaging studies, such as computed tomography, ultrasound, and magnetic resonance imaging to ascertain the extent of hemangioma.

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.

Clinical characteristics of children who visited the emergency department with extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infection and its risk factors

Purpose@#To identify the differences in features between children with urinary tract infection (UTI) caused by extended-spectrum beta-lactamases (ESBL)-positive and -negative Escherichia coli, and analyze risk factors for the former infection. @*Methods@#We reviewed medical records of children younger than 36 months with E. coli UTI who visited the emergency department from January 2012 through January 2019. Differences in variables regarding clinical, laboratory, and microbiologic (i.e., ESBL-positive E. coli on urine culture) features, and outcomes between the ESBL-positive and -negative groups were identified. Factors associated with ESBL-positive E. coli infection were analyzed by logistic regression. @*Results@#The children were classified into the ESBL-positive (n = 151) and -negative (n = 40) groups. The former group showed higher frequency of prior UTI (P = 0.038) without other differences between the groups. The median counts of white blood cells, absolute neutrophils, and absolute lymphocytes were higher in the ESBL-positive group than in the other group (P = 0.009, 0.022, and 0.027, respectively). The former group showed longer median hospital length of stay (11.0 days [interquartile range, 8.9-12.0] vs. 6.0 [5.0-7.0]; P < 0.001), and more frequent recurrence per child (3.0 [2.5-3.0] vs. 1.0 [1.0-1.75]; P = 0.047) and presence of vesicoureteral reflux (27.5% vs. 13.2%; P = 0.001). Logistic regression showed leukocytosis (odds ratio, 12.85; 95% confidence interval, 1.04-157.69) and vesicoureteral reflux (4.00; 1.19-13.43) as the factors for ESBL-positive E. coli infection. @*Conclusion@#The ESBL-positive group showed significantly higher leukocyte count and rate of vesicoureteral reflux than the ESBL-negative group. For children with these features, empirical antibiotics should be chosen in consideration of the resistant bacteria.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Clinical characteristics of children who visited the emergency department with extended-spectrum beta-lactamase-producing Escherichia coli urinary tract infection and its risk factors

Purpose@#To identify the differences in features between children with urinary tract infection (UTI) caused by extended-spectrum beta-lactamases (ESBL)-positive and -negative Escherichia coli, and analyze risk factors for the former infection. @*Methods@#We reviewed medical records of children younger than 36 months with E. coli UTI who visited the emergency department from January 2012 through January 2019. Differences in variables regarding clinical, laboratory, and microbiologic (i.e., ESBL-positive E. coli on urine culture) features, and outcomes between the ESBL-positive and -negative groups were identified. Factors associated with ESBL-positive E. coli infection were analyzed by logistic regression. @*Results@#The children were classified into the ESBL-positive (n = 151) and -negative (n = 40) groups. The former group showed higher frequency of prior UTI (P = 0.038) without other differences between the groups. The median counts of white blood cells, absolute neutrophils, and absolute lymphocytes were higher in the ESBL-positive group than in the other group (P = 0.009, 0.022, and 0.027, respectively). The former group showed longer median hospital length of stay (11.0 days [interquartile range, 8.9-12.0] vs. 6.0 [5.0-7.0]; P < 0.001), and more frequent recurrence per child (3.0 [2.5-3.0] vs. 1.0 [1.0-1.75]; P = 0.047) and presence of vesicoureteral reflux (27.5% vs. 13.2%; P = 0.001). Logistic regression showed leukocytosis (odds ratio, 12.85; 95% confidence interval, 1.04-157.69) and vesicoureteral reflux (4.00; 1.19-13.43) as the factors for ESBL-positive E. coli infection. @*Conclusion@#The ESBL-positive group showed significantly higher leukocyte count and rate of vesicoureteral reflux than the ESBL-negative group. For children with these features, empirical antibiotics should be chosen in consideration of the resistant bacteria.

Imbalance of Gut Streptococcus, Clostridium, and Akkermansia Determines the Natural Course of Atopic Dermatitis in Infant

PURPOSE: The roles of gut microbiota on the natural course of atopic dermatitis (AD) are not yet fully understood. We investigated whether the composition and function of gut microbiota and short-chain fatty acids (SCFAs) at 6 months of age could affect the natural course of AD up to 24 months in early childhood.METHODS: Fecal samples from 132 infants were analyzed using pyrosequencing, including 84 healthy controls, 22 transient AD and 26 persistent AD subjects from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort. The functional profile of the gut microbiome was analyzed by whole-metagenome sequencing. SCFAs were measured using gas chromatography-mass spectrometry.RESULTS: Low levels of Streptococcus and high amounts of Akkermansia were evident in transient AD cases, and low Clostridium, Akkermansia and high Streptococcus were found in children with persistent AD. The relative abundance of Streptococcus positively correlated with scoring of AD (SCORAD) score, whereas that of Clostridium negatively correlated with SCORAD score. The persistent AD group showed decreased gut microbial functional genes related to oxidative phosphorylation compared with healthy controls. Butyrate and valerate levels were lower in transient AD infants compared with healthy and persistent AD infants.CONCLUSIONS: Compositions, functions and metabolites of the early gut microbiome are related to natural courses of AD in infants.

The KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children: Part 1. Definition, Methodology and First-line Management

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Risk factors for the development of asthma symptoms in children with allergic rhinitis

Purpose@#Both allergic rhinitis and asthma are considered one airway disease, which interacts with each other in disease onset and symptom worsening. We evaluated factors developing new or persistent asthma symptoms in elementary school children with allergic rhinitis. @*Methods@#We selected 343 children aged 6 to 7 years who had rhinitis symptoms within 12 months and allergic sensitization on skin prick tests among 2,491 elementary school children. The questionnaires on symptoms, medical history and environments, blood eosinophils, serum total IgE, pulmonary function test, and bronchial provocation tests were obtained. Using multiple regression analysis, we evaluated factors for later asthma symptoms during a follow-up period of 4 years. @*Results@#The independent risk factors for later asthma symptoms among children with allergic rhinitis were higher body mass index (adjusted odds ratio [aOR], 1.29; 95% confidence interval [CI], 1.06–1.56; P= 0.012), a parental diagnosis of asthma (aOR, 6.19; 95% CI, 1.59–24.06; P= 0.008), residence in the rural area (aOR, 5.37; 95% CI, 1.34–21.42; P= 0.017), and a history of bronchiolitis in the first 2 years (aOR, 5.82; 95% CI, 1.42–23.80; P= 0.014). However, pulmonary functions, the levels of bronchial hyper-responsiveness, and the patterns of sensitization showed not significant factors. Children whose allergic rhinitis was treated in the follow-up period were less likely to have asthma symptoms later (aOR, 0.30; 95% CI, 0.10–0.93; P= 0.036). @*Conclusion@#In the school-aged children with allergic rhinitis, body mass index and asthma-related risk factors are crucial for developing asthma symptoms. The appropriate treatment of rhinitis may decrease asthma symptoms.

A case of toxic epidermal necrolysis due to topiramate

Topiramate is an antiepileptic drug effective for multiple types of seizure and is also used to prevent migraine attack. Several side effects have been reported, such as metabolic acidosis, nephrolithiasis, anorexia, weight reduction, drowsiness, glaucoma, hyperthermia, and cognitive dysfunction, whereas skin manifestationis were rarely reported. We report a case of a 12-year-old girl on medication of topiramate for 8 months due to focal epilepsy. She had fever, sore throat, burning sense in the vaginal area, and then flaccid bullae and erythematous patches proceeded to the whole bodyskin and mucosa including the conjunctiva, oral cavity, and genital areas. She was diagnosed with toxic epidermal necrolysis (TEN) and improved after the discontinuation of topiramate and with administration of high-dose intravenous steroid and immunoglobulin. We, herein, report a girl who developed severe side effects on the skin, TEN, due to topiramate.

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.

Comparison of clinical severity between single- and coinfections of respiratory syncytial virus and influenza virus with common respiratory viruses

PURPOSE: Multiple virus infections may affect clinical severity. We investigated the effect of coinfection of respiratory syncytial virus (RSV) and influenza virus with other respiratory viruses on clinical severity. METHODS: Data from 634 samples of a single tertiary hospital between September 2014 and April 2015 were analyzed for clinical characteristics (fever duration and O2 need, steroid use, and ICU care) between single infection and coinfection of RSV (n=290) and influenza virus (n=74) with 16 common respiratory viruses from hospitalized children. RESULTS: The RSV coinfection group (n=109) (3.1±2.7 days) showed significantly longer fever duration than the RSV single infection group (n=181) (2.6±2.6 days) (P=0.04), while there was no difference in O2 need, steroid use or ICU care in the 2 groups. The influenza coinfection group (n=38) showed significantly higher O2 need than the influenza single infection group (n=36) (21.1% vs. 5.6%, P=0.05), while there was no difference in fever duration between the 2 groups. CONCLUSION: The results indicate that RSV and Influenza coinfections can increase clinical severity and that the severity may be influenced by the nature of coinfecting viruses.

The Korean Version of the Test for Respiratory and Asthma Control in Kids (TRACK): Reliability and Validity

BACKGROUND: Test for Respiratory and Asthma Control in Kids (TRACK) questionnaires were developed and validated in various languages to monitor respiratory control in preschool-aged children. We aimed to assess the reliability and validity of the Korean version of the TRACK questionnaire. METHODS: We administered the linguistically validated TRACK questionnaires to caregivers of asthmatic preschool children on two separate visits 4–6 weeks apart. Each physician graded the level of the guideline-based asthma control, assessed the timing of symptoms, and adjusted the therapeutic level at each visit. RESULTS: A total of 137 children were enrolled in the study. Cronbach's alpha was 0.65 for a questionnaire as a whole. The test-retest reliability was 0.72. The median TRACK scores were significantly different between asthma control status categories, with the lowest scores in children classified as poorly controlled and the highest in the well-controlled group (P < 0.001). They were different among groups classified according to the physician adjusted therapeutic levels, with the lowest values in children prescribed step-up therapy (P < 0.001), and according to the recency of respiratory symptoms (P < 0.001). Finally, the changes in TRACK scores between visits were highest in subjects showing improved control, followed by unchanged, and worsened control. When we applied the traditional cut-off of 80 for a well-controlled condition, a sensitivity of 75.6% and a specificity of 70.9% were calculated. CONCLUSION: The Korean translated version of the TRACK questionnaire is valid and reliable to assess respiratory and asthma control in Korean preschool children with asthma symptoms.

Modifiable prenatal environmental factors for the prevention of childhood asthma

The prevalence of asthma in children is increasing worldwide, yet risk factors for the development of asthma is unclear. Evidence to date indicates that environmental factors are the main reason of the recent increase in the prevalence of asthma. For example, exposure to air pollution and diet as well as microbial alterations are reported as environmental factors. In addition, we should focus on the critical period of the exposure, especially pregnancy period as an important period for human development. Therefore, environmental exposure during pregnancy to tobacco smoke or air pollutants, maternal stress, obesity, and vitamin D may contribute to the development of childhood asthma. Herein, modifiable prenatal exposure, its mechanisms associated with childhood asthma and multiple intervention controlling risk factors needed during pregnancy in order to achieve primary prevention of asthma has been described.

Recent changing pattern of aeroallergen sensitization in children with allergic diseases: A single center study

PURPOSE: Allergic diseases have been increasing worldwide over the past few decades. Allergic sensitization is a pivotal risk factor for the development of allergic diseases. The purpose of this study was to examine changes in allergic sensitization patterns of aeroallergens over the last 10 years in children with respiratory allergic diseases. METHODS: We retrospectively reviewed the medical records of 12,848 children under the age of 18 years who received skin prick tests (n=3,852) or serum specific IgE tests (n=8,996) to evaluate sensitization from 2007 to 2016 in a single center, Seoul, Korea. RESULTS: Sensitization rate to house dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus) reached a plateau in preschool (28.3%–32.8%) and schoolchildren (45.8%–47.2%). Sensitization rate to animal dander (cat and dog) was increasing from 8.4% to 12.5% in preschool children and from 10.3% to 18.6% in schoolchildren (trend P<0.001 each). In preschool children, tree (birch, oak, and alder; from 3.5% to 6.4%), grass (timothy; from 0.8% to 6.5%), weed (ragweed and mugwort; from 2.8% to 6.9%) pollens and mold (Alternaria; from 2.5% to 6.0%) were also in similar increasing pattern (trend P=0.001, P<0.001, P=0.003, and P<0.001, respectively). Additionally, tree (from 9.0% to 15.2%), grass (from 2.6% to 5.2%) pollens were also in increasing pattern in schoolchildren (trend P<0.001 and P=0.024, respectively). CONCLUSION: Over the past 10 years, sensitization patterns of aeroallergen have been changing in Korean children with allergic diseases. We should pay attention to the changing patterns of allergic sensitization to educate and prevent the allergic disease.

Multicenter Adherence Study of Asthma Medication for Children in Korea

PURPOSE: Adherence is a major component of successful medical treatment. However, non-adherence remains a barrier to effective delivery of healthcare worldwide. METHODS: Twenty healthcare facilities (secondary or tertiary hospitals) belonging to the Korean Academy of Pediatric Allergy and Respiratory Diseases (KAPARD) participated. Questionnaires were given to patients currently receiving treatment in the form of inhalant useor oral intake or transdermal patch for mild to moderate asthma. RESULTS: A total of 1,838 patients responded to the questionnaire. Mean age was 5.98 ± 3.79 years (range: 0-18 years). With help from their caregivers, the percentage of patients that answered “taking as prescribed” was 38.04% for inhalant users, 50.09% for oral medication users and 67.42% for transdermal users. Transdermal patch users had significantly greater adherence compared to the other 2 groups (P < 0.001). The 34.15% of inhalant users, 70.33% of oral medication users and 93.00% of transdermal patch users felt that their medication delivery system was “Easy” or “Very easy” to use (P < 0.001). “Method of administration” was deemed to be the most difficult part of the treatment regimen to follow, and 76.7% of patients preferred once-daily administration (i.e., “Frequency of administration”). CONCLUSIONS: Asthma medication adherence in young children was found to be better in the transdermal patch group. This may be due to requiring fewer doses and easy to follow instructions. From an adherence point of view, the transdermal patch seems more useful for long-term asthma control in children compared to oral or inhaled medicine.