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.

Awareness of anaphylaxis among community and emergency responders in Korea

Purpose@#Anaphylaxis is life-threatening, so early recognition and proper response are critical. This study evaluated the awareness of anaphylaxis in Korean community including teachers, 119 rescue team, and doctors in public service. @*Methods@#A questionnaire of anonymously structured 9 items about anaphylaxis was administered to the teachers working in kindergartens or elementary schools, 119 rescue team, and public health physicians in Gangwon province in 2017. Additional questionnaire about knowledge on anaphylaxis management was administered to the physicians. @*Results@#A total of 415 people participated in the survey. About 4% of child care and health teachers experienced anaphylaxis within 1 year, but the overall awareness of anaphylaxis was very low, regardless of the educational level of anaphylaxis. 119 rescue teams experienced more anaphylactic patients, but they lacked knowledge of epinephrine administration and epinephrine autoinjector (EAI), independent of the educational level of anaphylaxis. Public health physicians had good knowledge of early treatment for anaphylaxis, but there was a lack of knowledge for epinephrine injection sites, observation plan, and EAI. @*Conclusion@#The awareness of anaphylaxis among community and emergency responders seems likely to be inadequate. Systematic and continuous education by anaphylaxis specialists is necessary for community health care providers.

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.

Erratum: Pollen-Food Allergy Syndrome in Korean Pollinosis Patients: A Nationwide Survey

This erratum is being published to correct the error on page 650 of the article. The number of participating research institution should be corrected.

Clinical Manifestations and Risk Factors of Anaphylaxis in Pollen-Food Allergy Syndrome

PURPOSE: Many studies have reported that pollen-food allergy syndrome (PFAS) can cause anaphylaxis. No comprehensive investigations into anaphylaxis in PFAS have been conducted, however. In this study, we investigated the clinical manifestations and risk factors for anaphylaxis in PFAS in Korean patients with pollinosis. MATERIALS AND METHODS: Data were obtained from a nationwide cross-sectional study that previously reported on PFAS in Korean patients with pollinosis. Data from 273 patients with PFAS were collected, including demographics, list of culprit fruits and vegetables, and clinical manifestations of food allergy. We analyzed 27 anaphylaxis patients and compared them with patients with PFAS with oropharyngeal symptoms only (n=130). RESULTS: The most common cause of anaphylaxis in PFAS was peanut (33.3%), apple (22.2%), walnut (22.2%), pine nut (18.5%), peach (14.8%), and ginseng (14.8%). Anaphylaxis was significantly associated with the strength of sensitization to alder, hazel, willow, poplar, timothy, and ragweed (p<0.05, respectively). Multivariable analysis revealed that the presence of atopic dermatitis [odds ratio (OR), 3.58; 95% confidence interval (CI), 1.25–10.23; p=0.017]; sensitization to hazel (OR, 5.27; 95% CI, 1.79–15.53; p=0.003), timothy (OR, 11.8; 95% CI, 2.70–51.64; p=0.001), or ragweed (OR, 3.18; 95% CI, 1.03–9.87; p=0.045); and the number of culprit foods (OR, 1.25; 95% CI, 1.15–1.37; p<0.001) were related to the development of anaphylaxis in PFAS. CONCLUSION: The most common culprit foods causing anaphylaxis in PFAS were peanut and apple. The presence of atopic dermatitis; sensitization to hazel, timothy, or ragweed; and a greater number of culprit foods were risk factors for anaphylaxis in PFAS.

Pollen-Food Allergy Syndrome in Korean Pollinosis Patients: A Nationwide Survey

PURPOSE: Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergy in pollinosis patients caused by raw fruits and vegetables and is the most common food allergy in adults. However, there has been no nationwide study on PFAS in Korea. In this study, we investigated the prevalence and clinical characteristics of PFAS in Korea. METHODS: Twenty-two investigators participated in this study, in which patients with allergic rhinoconjunctivitis and/or bronchial asthma with pollen allergy were enrolled. The questionnaires included demographic characteristics, a list of fruits and vegetables, and clinical manifestations of food allergy. Pollen allergy was diagnosed by skin prick test and/or measurement of the serum level of specific IgE. RESULTS: A total of 648 pollinosis patients were enrolled. The prevalence of PFAS was 41.7% (n = 270). PFAS patients exhibited cutaneous (43.0%), respiratory (20.0%), cardiovascular (3.7%) or neurologic symptoms (4.8%) in addition to oropharyngeal symptoms. Anaphylaxis was noted in 8.9% of the PFAS patients. Seventy types of foods were linked to PFAS; e.g., peach (48.5%), apple (46.7%), kiwi (30.4%), peanut (17.4%), plum (16.3%), chestnut (14.8%), pineapple (13.7%), walnut (14.1%), Korean melon (12.6%), tomato (11.9%), melon (11.5%) and apricot (10.7%). Korean foods such as taro/taro stem (8.9%), ginseong (8.2%), perilla leaf (4.4%), bellflower root (4.4%), crown daisy (3.0%), deodeok (3.3%), kudzu root (3.0%) and lotus root (2.6%) were also linked to PFAS. CONCLUSIONS: This was the first nationwide study of PFAS in Korea. The prevalence of PFAS was 41.7%, and 8.9% of the PFAS patients had anaphylaxis. These results will provide clinically useful information to physicians.

Clinical diagnostic guidelines for allergic rhinitis: diagnosis

As the prevalence and socioeconomic burden of allergic rhinitis is steadily increasing every year, it is essential that clinical practitioners diagnose and manage allergic rhinitis in an evidence-based manner. Therefore, the Korean Academy of Asthma, Allergy and Clinical Immunology developed new clinical guidelines for Korean patients and practitioners. We first performed a questionnaire survey to address the core questions, about which clinical practitioners are the most curious. A large group of physicians (allergists), pediatricians, and otorhinolaryngologists developed answers for those questions by performing a systematic literature review and determining the appropriate levels of recommendation. In this article, we propose 11 answers for core questions regarding the diagnosis and differential diagnosis of allergic rhinitis.

Clinical diagnostic guidelines for allergic rhinitis: diagnosis

As the prevalence and socioeconomic burden of allergic rhinitis is steadily increasing every year, it is essential that clinical practitioners diagnose and manage allergic rhinitis in an evidence-based manner. Therefore, the Korean Academy of Asthma, Allergy and Clinical Immunology developed new clinical guidelines for Korean patients and practitioners. We first performed a questionnaire survey to address the core questions, about which clinical practitioners are the most curious. A large group of physicians (allergists), pediatricians, and otorhinolaryngologists developed answers for those questions by performing a systematic literature review and determining the appropriate levels of recommendation. In this article, we propose 11 answers for core questions regarding the diagnosis and differential diagnosis of allergic rhinitis.

Unmet Primary Physicians' Needs for Allergic Rhinitis Care in Korea

Allergic rhinitis (AR) is one of the most common chronic allergic respiratory diseases worldwide. Various practical guidelines for AR have been developed and updated to improve the care of AR patients; however, up to 40% patients remain symptomatic. The unmet need for AR care is one of the greatest public health problems in the world. The gaps between guideline and real-world practice, and differences according to the region, culture, and medical environments may be the causes of unmet needs for AR care. Because there is no evidence-based AR practical guideline reflecting the Korean particularity, various needs are increasing. The purpose of the study was to evaluate whether existing guidelines are sufficient for AR patient management in real practice and whether development of regional guidelines to reflect regional differences is needed in Korea. A total of 99 primary physicians comprising internists, pediatricians, and otolaryngologists (n=33 for each) were surveyed by a questionnaire relating to unmet needs for AR care between June 2 and June 16 of 2014. Among 39 question items, participants strongly agreed on 15 items that existing guidelines were highly insufficient and needed new guidelines. However, there was some disagreement according to specialties for another 24 items. In conclusion, the survey results demonstrated that many physicians did not agree with the current AR guideline, and a new guideline reflecting Korean particularity was needed.

Asthma Severity and the Controller Prescription in Children at 12 Tertiary Hospitals

PURPOSE: Guidelines need to be tailored to where they are applied. We aimed to describe the distinctive asthma severity profile and the pattern of controller prescription in Korean children. METHODS: Twelve pediatric allergists from tertiary medical centers reviewed medical records of all asthmatic children who visited their clinics between September 1 and November 30 of 2013. Controller prescriptions were re-classified into 4 categories, then the prevalence of each asthma severity category and the controller prescription patterns according to asthma severity assessed by a Western (Global Initiative for Asthma, GINA) and an Asia-Pacific (Japanese Pediatric GuideLine, JPGL) guideline were evaluated. RESULTS: A total of 840 cases were reviewed. Both GINA and JPGL revealed that 328 (39.0%) and 249 (29.6%) subjects had intermittent asthma whereas 24 (2.9%) and 21 (2.5%) subjects had severe persistent asthma, respectively. Although higher category controllers tended to be prescribed to those who had more severe asthma, there was much overlap in categories of prescribed controllers between groups with regard to asthma severities. Leukotriene receptor antagonists (LTRA) was the most frequently prescribed as a single controller (40%) or as an add-on medication (19%) in the group of asthmatic children <6 years. CONCLUSIONS: Korean children have distinctive patterns of asthma severity and management strategies with a lower prevalence of severe asthma and a preference toward LTRA rather than low dose inhaled corticosteroids (ICS) alone or add-on long-acting beta-agonist (LABA) in the group of <6 year-old asthmatics that has not been predicted in Western countries. Thus, strategies tailored to regional situations need to be developed and recommended.

Clinical diagnostic guidelines of allergic rhinitis: comprehensive treatment and consideration of special circumstances

In order to prevent sensitization to a new allergen and the development of asthma, practitioners may consider allergen-specific immunotherapy in patients with allergic rhinitis. Additionally, in patients with severe allergic rhinitis refractory to medication, practitioners can also consider surgical management for improving the patients' nasal symptoms. However, there are still no practical guidelines regarding the indications for immunotherapy, the appropriate selection of the allergen, and the optimal duration of therapy. Moreover, no clear indications exist for surgical treatment. Pregnant or lactating women frequently complain of symptoms of rhinitis. However, due to the fear of potential complications to their babies, they avoid medical treatment despite significant discomfort. Therefore, we present 14 answers to core questions about immunotherapy, surgical treatment, and considerations for special circumstances, such as pregnancy and lactation.

Crinical diagnostic guidelines for allergic rhinitis: medical treatment

The social and economic burden of allergic rhinitis (AR) is increasing, with significant effects on the quality of life of patients suffering from AR. Therefore, physicians require evidence-based guidelines regarding the diagnosis, differential diagnosis and proper management management of patients with AR. The Korean Academy of Asthma, Allergy and Clinical Immunology developed new clinical guidelines for the appropriate management of AR, especially in Korean patients. For the core questions (i.e. questions that most practitioners were curious about), several experts in the field of allergology, pediatrics, and otorhinolaryngology developed a set of practical guidelines based on a systematic review of the literature. Furthermore, we determined the level of evidence associated with the recommendations for each answer. In this article, we suggest 15 answers for core questions about the medical treatment of AR.

Allergic Rhinitis in Preschool Children and the Clinical Utility of FeNO

PURPOSE: The nature of allergic rhinitis (AR) in preschool aged children remains incompletely characterized. This study aimed to investigate the prevalence of AR and its associated risk factors in preschool-aged children and to assess the clinical utility of fractional exhaled nitric oxide (FeNO). METHODS: This general population-based, cross-sectional survey included 933 preschool-aged (3- to 7-year-old) children from Korea. Current AR was defined as having nasal symptoms within the last 12 months and physician-diagnosed AR. RESULTS: The prevalence of current AR in preschool children was 17.0% (156/919). Mold exposure (adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.15-2.43) and the use of antibiotics (aOR, 1.97; 95% CI, 1.33-2.90) during infancy were associated with an increased risk of current AR, whereas having an older sibling (aOR, 0.52; 95% CI, 0.35-0.75) reduced the risk. Children with current atopic AR had significantly higher geometric mean levels of FeNO compared to those with non-atopic rhinitis (12.43; range of 1standard deviation [SD], 7.31-21.14 vs 8.25; range of 1SD, 5.62-12.10, P=0.001) or non-atopic healthy children (8.58; range of 1SD, 5.51-13.38, P<0.001). The FeNO levels were higher in children with current atopic AR compared with atopic healthy children (9.78; range of 1SD, 5.97-16.02, P=0.083). CONCLUSIONS: Mold exposure and use of antibiotics during infancy increases the risk of current AR, whereas having an older sibling reduces it. Children with current atopic AR exhibit higher levels of FeNO compared with non-atopic rhinitis cases, suggesting that FeNO levels may be a useful discriminatory marker for subtypes of AR in preschool children.

Translation and linguistic validation of Korean version of the Test for Respiratory and Asthma Control in Kids instrument

PURPOSE: We aimed to translate the Test for Respiratory and Asthma Control in Kids (TRACK) instrument into Korean, with subsequent linguistic validation. METHODS: The multistep process of forward translation, reconciliation, back-translation, cognitive debriefing, and proofreading of the Korean version of the TRACK was completed. RESULTS: Two bilingual medical personnel independently translated the original English version of the TRACK into Korean one. After moderating the translation into a single reconciled one, 4 other bilingual persons were invited to translate the Korean draft back into an English one. Discrepancies between the original English version and the back-translated one were reviewed, and the need to modify the reconciled Korean draft was discussed. Twenty caregivers of asthmatic children took part in interviews that examine the appropriateness of the Korean version of the TRACK. The feedback from caregivers were then reviewed by a panel of pediatric allergists and reflected in the final Korean version. The document was finally proofread to check the spelling, grammar, layout and formatting. CONCLUSION: Translation and linguistic validation of the Korean version of the TRACK instrument were completed.

ERRATUM: Affiliation Correction. Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

According to the author's request, in this paper, the eighth author's (Bong-Seong Kim) affiliation should be corrected.

Phenotype and endotype in pediatric asthma

Asthma is not a homogeneous disease presenting variable clinical features, but a complex disorder consisting of many different disease entities characterized by variable air-flow limitation. To date, there are little effective preventive-strategies for the development of asthma, and it has been emphasized that early identification and intervention are the best ways to reduce the associated morbidities, quality of life, and socioeconomic burden. Predicting the natural course of asthma is still difficult, although various phenotypic approaches and predictive scores are developed and widely used. The present phenotypes and predictive scores may be reliable in the population, but those appear to be unreliable in each individual in real practice. Either undertreatment or overtreatment in childhood asthma is an important issue, because they are associated with poor compliance, increments of socioeconomic burdens, and poor quality of life. There is no doubt about the clinical efficacy of inhaled corticosteroid (ICS) in childhood asthma, but the negative effect of long-term use of ICS on the height is emerging. Therefore general physicians should consider an individualized management using specific phenotypes and endotypes, and regularly re-evaluate the drug-response, level of control, and adherence/compliance to avoid inadequate treatment.

Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

PURPOSE: There are a number of reports suggesting that widespread propagation of weeds and high concentration of weed pollen have been contributed to climate change. We investigated the interrelationship between allergenic pollen concentration, allergic symptom and meteorological factor. METHODS: We collected data of pollen concentration and meteorological factors in 7 stations nationwide during between 1998 and 2012. We recruited total 297 allergic patients sensitized to weed pollens from each station, conducted a survey about allergic symptom, and calculated symptom index. We surveyed the vegetation area of ragweed and Japanese hop. Based on these data, we performed the long-term trend analysis (X11-ARIMA, autoregressive integrated moving average) on regional pollen concentration, and correlation analysis to investigate the interrelation between weed pollen concentration, allery symptom index and meteorological factor. We have also done regression analysis on vegetation area and maximal pollen concentration. RESULTS: Long-term trend analysis showed the increasing trend of pllen concentration in Seoul. Weed pollen concentration, allergy symptom index and each meteorological factor were not correlated significantly. Regression analysis revealed that increase of weed vegetation area results in increase of weed pollen concentration. Through this regression equation, we estimated the vegetation area that can product pollen concentration triggering allergenic risk. CONCLUSION: Meteorological factors, pollen concentration and allergic symptoms should be consistently assessed and the relationship between each factor should be analyzed, considering climate change. It is necessary to verify the equation for pollen estimation by vegetation area and set up a policy for vegetation control focused on the reduction of allergenic pollen.

Association of SCORAD Index and Aeroallergen Sensitization on Urinary Leukotriene E4 in Children with Atopic Dermatitis / 소아알레르기및호흡기학회지

PURPOSE: Atopic dermatitis (AD) is a genetically determined, chronic relapsing skin disease. The pathogenesis of AD is complex and the course is unpredictable. Atopy is an important risk factor for the development of AD. Cysteinyl leukotrienes (Cys-LTs) were implicated in the pathophysiology of allergic diseases, and are being targeted for their diagnosis and treatments. Early detection of tissue inflammation of target organ is important to enable early prevention and management of allergic diseases. The aim of our study is to evaluate the differences in urinary leukotrienes E4 (LTE4) levels, according to AD symptom score and aeroallergen sensitization in children with AD by using noninvasive techniques. METHODS: We recruited 46 children with AD, using predetermined criteria. Clinical features of AD were evaluated by a physician, using scoring atopic dermatitis (SCORAD) index. Aeroallergen sensitization was measured by using a skin prick test and UniCap. Urine samples were also collected on day of the 1st and 2nd visits, and were analyzed for LTE4 with an enzyme-linked immunoassay kit. RESULTS: SCORAD indeces of children with AD were correlated with urinary LTE4 levels. Total immunoglobulin E (IgE) and eosinophil counts also had significant correlation with urinary LTE4 levels. Especially, aeroallergen sensitization of atopic AD significantly correlated with urinary LTE4 of these patients. CONCLUSION: Urinary LTE4 levels significantly correlated with serum total IgE and number of sensitized aeroallergen in children with AD. Clinical features of AD evaluated with SCORAD index related with urinary LTE4 level. Urinary LTE4 might be a valuable, noninvasive marker for different pathogenesis of AD.

Prevalence of Primary Immunodeficiency in Korea

This study represents the first epidemiological study based on the national registry of primary immunodeficiencies (PID) in Korea. Patient data were collected from 23 major hospitals. A total of 152 patients with PID (under 19 yr of age), who were observed from 2001 to 2005, have been entered in this registry. The period prevalence of PID in Korea in 2005 is 11.25 per million children. The following frequencies were found: antibody deficiencies, 53.3% (n = 81), phagocytic disorders, 28.9% (n = 44); combined immunodeficiencies, 13.2% (n = 20); and T cell deficiencies, 4.6% (n = 7). Congenital agammaglobulinemia (n = 21) and selective IgA deficiency (n = 21) were the most frequently reported antibody deficiency. Other reported deficiencies were common variable immunodeficiencies (n = 16), X-linked agammaglobulinemia (n = 15), IgG subclass deficiency (n = 4). Phagocytic disorder was mostly chronic granulomatous disease. A small number of patients with Wiskott-Aldrich syndrome, hyper-IgE syndrome, and severe combined immunodeficiency were also registered. Overall, the most common first manifestation was pneumonia. This study provides data that permit a more accurate estimation PID patients in Korea.