Incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in South Korea.

INTRODUCTION: Children's rare lung diseases are a heterogeneous group of rare lung diseases with significant morbidity and mortality. There is very limited information on the incidence and prevalence of children's rare lung diseases in Asia. We investigated the nationwide incidence, prevalence, and pattern of medical service utilization of children's rare lung diseases in Korea. METHODS: We studied patients who were diagnosed with rare lung diseases coded per International Statistical Classification of Diseases and Related Health Problems, 10th Edition and registered in the national rare diseases database of confirmed patients. Data was extracted from the Korean National Health Insurance Service Claims database over 2019-2021. RESULTS: Average incidence rate was 12.9 new cases per million children per year, and average prevalence rate was 60.2 cases per million children during the study period of 2019-2021. We found that more than 65% of new cases were diagnosed before 2 years of age. ChILD, primary ciliary dyskinesia, and cystic fibrosis were usually diagnosed after 6 years of age. Congenital airway and lung anomalies were often diagnosed before 2 years of age. Busan and Gyeongsangnam-do residents tended to visit hospitals near their place of residence, while residents of other areas tended to visit hospitals in Seoul regardless of their area of residence. CONCLUSIONS: We examined the epidemiology of rare lung diseases in children in South Korea. Our estimation of the incidence and prevalence could be used for sustainable health care and equitable distribution of health care resources.

Allergic rhinitis phenotypes with distinct transcriptome profiles in children: A birth cohort.

BACKGROUND: Allergic rhinitis (AR) phenotypes in childhood are unclear. OBJECTIVES: This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic characteristics. METHODS: Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype. RESULTS: Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late-onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection-related defense response, whereas late-onset AR was associated with T cell-related immune response. CONCLUSIONS: Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late- and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.

Evidence-based management guidelines for noncystic fibrosis bronchiectasis in children and adolescents.

Noncystic fibrosis bronchiectasis is a chronic respiratory disease that carries high socioeconomic and medical burdens and is caused by diverse respiratory illnesses. To improve clinical outcomes, early recognition, active treatment of exacerbations, and prevention of further exacerbations are essential. However, evidence for the treatment and prevention of acute exacerbation of noncystic fibrosis bronchiectasis, especially in children, is lacking. Therefore, the evidence- and consensus-based guidelines for medical and nonmedical treatment strategies for noncystic fibrosis bronchiectasis in children and adolescents were developed by the Korean Academy of Pediatric Allergy and Respiratory Disease using the methods recommended by the Grading of Recommendations Assessment, Development, and Evaluation working group with evidence published through July 2, 2020. This guideline encompasses evidence-based treatment recommendations as well as expert opinions, addressing crucial aspects of the treatment and management of noncystic fibrosis bronchiectasis in children. This includes considerations for antibiotics and airway clearance strategies, particularly in areas where evidence may be limited. Large, well-designed, and controlled studies are required to accumulate further evidence of management strategies for noncystic fibrosis bronchiectasis in children and adolescents.

Clinical Manifestations and Genotype of Primary Ciliary Dyskinesia Diagnosed in Korea: Multicenter Study.

PURPOSE: Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder that leads to secondary ciliary dysfunction. PCD is a rare disease, and data on it are limited in Korea. This study systematically evaluated the clinical symptoms, diagnostic characteristics, and treatment modalities of pediatric PCD in Korea. METHODS: This Korean nationwide, multicenter study, conducted between January 2000 and August 2022, reviewed the medical records of pediatric patients diagnosed with PCD. Prospective studies have been added to determine whether additional genetic testing is warranted in some patients. RESULTS: Overall, 41 patients were diagnosed with PCD in 15 medical institutions. The mean age at diagnosis was 11.8 ± 5.4 years (range: 0.5 months-18.9 years). Most patients (40/41) were born full term, 15 (36.6%) had neonatal respiratory symptoms, and 12 (29.3%) had a history of admission to the neonatal intensive care unit. The most common complaint (58.5%) was chronic nasal symptoms. Thirty-three patients were diagnosed with transmission electron microscopy (TEM) and 12 patients by genetic studies. TEM mostly identified outer dynein arm defects (alone or combined with inner dynein arm defects, n = 17). The genes with the highest mutation rates were DNAH5 (3 cases) and DNAAF1 (3 cases). Rare genotypes (RPGR, HYDIN, NME5) were found as well. Chest computed tomography revealed bronchiectasis in 33 out of 41 patients. Among them, 15 patients had a PrImary CiliAry DyskinesiA Rule score of over 5 points. CONCLUSIONS: To our knowledge, this is the first multicenter study to report the clinical characteristics, diagnostic methods, and genotypes of PCD in Korea. These results can be used as basic data for further PCD research.

A Novel Approach to Investigate the Superheating Grain Refinement Process of Aluminum-Bearing Magnesium Alloys Using Rapid Solidification Process.

The superheating process is a unique grain refining method found only in aluminum-containing magnesium alloys. It is a relatively simple method of controlling the temperature of the melt without adding a nucleating agent or refining agent for grain refinement. Although previous studies have been conducted on this process, the precise mechanism underlying this phenomenon has yet to be elucidated. In this study, a new approach was used to investigate the grain refinement mechanism of aluminum-containing magnesium alloys by the melting superheating process. AZ91 alloy, a representative Mg-Al alloy, was used in the study, and a rapid solidification process was designed to enable precise temperature control. Temperature control was successfully conducted in a unique way by measuring the temperature of the ceramic tube during the rapid solidification process. The presence of Al8Mn5 and Al10Mn3 particles in non-superheated and superheated AZ91 ribbon samples, respectively, manufactured by the rapid solidification process, was revealed. The role of these Al-Mn particles as nucleants in non-superheated and superheated samples was examined by employing STEM equipment. The crystallographic coherence between Al8Mn5 particles and magnesium was very poor, while Al10Mn3 particles showed better coherence than Al8Mn5. We speculated that Al10Mn3 particles generated by the superheating process may act as nucleants for α-Mg grains; this was the main cause of the superheating grain refinement of the AZ91 alloy.

Combined effect of hygienic and polygenic risk scores in children with allergic rhinitis.

BACKGROUND: Although the development of allergic rhinitis (AR) is associated with multiple genetic and hygienic environmental factors, previous studies have focused mostly on the effect of a single factor on the development of AR. OBJECTIVE: This study aimed to investigate the combined effect of multiple genetic and hygienic environmental risk factors on AR development in school children. METHODS: We conducted a cross-sectional study, comprising 1,797 children aged 9-12 years. Weighted environmental risk score (ERS) was calculated by using four hygienic environmental factors, including antibiotic use during infancy, cesarean section delivery, breast milk feeding, and having older siblings. Weighted polygenic risk score (PRS) was calculated by using four single nucleotide polymorphisms (SNPs), including interleukin-13 (rs20541), cluster of differentiation 14 (rs2569190), toll-like receptor 4 (rs1927911), and glutathione S-transferase P1 (rs1695). Multivariable logistic regression analysis was used. RESULTS: More than three courses of antibiotic use during infancy increased the risk of current AR (adjusted odd ratio [aOR], 2.058; 95% confidence interval [CI]: 1.290-3.284). Having older siblings, especially > 2 (aOR, 0.526; 95%Cl: 0.303-0.913) had a protective effect. High ERS ( > median; aOR, 2.079; 95%Cl: 1.466-2.947) and PRS ( > median; aOR, 1.627; 95%Cl: 1.117-2.370) increased the risk of current AR independently. Furthermore, children who had both high ERS and PRS showed a higher risk of current AR (aOR, 3.176; 95%Cl: 1.787-5.645). CONCLUSIONS: Exposure to multiple hygienic risk factors during infancy increases the risk of AR in genetically susceptible children.

Fetal growth rather than prematurity determines lung function in children with asthma.

BACKGROUND AND OBJECTIVE: Preterm birth or fetal growth has been associated with reduced lung function and asthma during childhood in the general population. We aimed to elucidate whether prematurity or fetal growth has a significant influence on lung function or symptoms in children with stable asthma. METHODS: We included children with stable asthma who participated in the Korean childhood Asthma Study cohort. Asthma symptoms were determined by asthma control test (ACT). Percent predicted values of pre- and post-bronchodilator (BD) lung function including forced expiratory volume in 1 second (FEV1 ), forced vital capacity (FVC), and forced expiratory flow at 25%-75% of FVC (FEF25%-75% ) were measured. Lung function and symptoms were compared according to the history of preterm birth and birth weight (BW) for gestational age (GA). RESULTS: The study population consisted of 566 children (age range: 5-18 years). There were no significant differences in lung function and ACT between preterm and term subjects. We observed no significant difference in ACT but significant differences were observed in pre- and post-BD FEV1 , pre- and post-BD FVC, and post-BD FEF25%-75% according to BW for GA in total subjects. Two-way ANOVA revealed that BW for GA rather than prematurity was a significant determining factor for pre- and post-BD lung function. After regression analysis, BW for GA was still a significant determining factor of pre- and post-BD FEV1 and pre- and post-BD FEF25%-75% . CONCLUSION: Fetal growth rather than prematurity appears to have a significant effect on lung function in children with stable asthma.

Frequency of exacerbation and degree of required asthma medication can characterize childhood longitudinal asthma trajectories.

BACKGROUND: To the best of our knowledge, there have been no investigations of longitudinal asthma trajectories based on asthma exacerbation frequency and medications required for asthma control in children. OBJECTIVE: To investigate longitudinal asthma trajectories based on the exacerbation frequency throughout childhood and asthma medication ranks. METHODS: A total of 531 children aged 7 to 10 years were enrolled from the Korean childhood Asthma Study. Required asthma medications for control of asthma from 6 to 12 years of age and asthma exacerbation frequency from birth to 12 years of age were obtained from the Korean National Health Insurance System database. Longitudinal asthma trajectories were identified on the basis of asthma exacerbation frequency and asthma medication ranks. RESULTS: Four asthma clusters were identified: lesser exacerbation with low-step treatment (8.1%), lesser exacerbations with middle-step treatment (30.7%), highly frequent exacerbations in early childhood with small-airway dysfunction (5.7%), and frequent exacerbations with high-step treatment (55.6%). The frequent exacerbations with high-step treatment cluster were characterized by a high prevalence of male sex, increased blood eosinophil (counts) with fractional exhaled nitric oxide, and high prevalence of comorbidities. The highly frequent exacerbation in early childhood with small-airway dysfunction cluster was characterized by recurrent wheeze in preschool age, with high prevalence of acute bronchiolitis in infancy and a greater number of family members with small-airway dysfunction at school age. CONCLUSION: The present study identified 4 longitudinal asthma trajectories on the basis of the frequency of asthma exacerbation and asthma medication ranks. These results would help clarify the heterogeneities and pathophysiologies of childhood asthma.

Degree of Impurity and Carbon Contents in the Grain Size of Mg-Al Magnesium Alloys.

In this study, the tendency of having different grain structures depending on the impurity levels in AZ91 alloys was investigated. Two types of AZ91 alloys were analyzed: commercial-purity AZ91 and high-purity AZ91. The average grain size of the commercial-purity AZ91 alloy and high-purity AZ91 is 320 µm and 90 µm, respectively. Thermal analysis revealed negligible undercooling in the high-purity AZ91 alloy, while undercooling of 1.3 °C was observed in the commercial-purity AZ91 alloy. A CS analyzer was employed to precisely analyze the carbon composition of both alloys. The carbon content of the high-purity AZ91 alloy was found to be 197 ppm, while the commercial-purity AZ91 alloy contained 104 ppm, indicating a difference of approximately 2 times. The higher carbon content in the high-purity AZ91 alloy is believed to be due to the use of high-purity pure Mg in its production (the carbon content of high-purity pure Mg is 251 ppm). To simulate the vacuum distillation process commonly used in the production of high-purity Mg ingots, experiments were conducted to investigate the reaction of carbon with oxygen to produce CO and CO2. XPS analysis and simulation results for activities confirmed the formation of CO and CO2 during the vacuum distillation process. It could be speculated that the carbon sources in the high-purity Mg ingot provide Al-C particles, which act as nucleants for Mg grains in the high-purity AZ91 alloy. Thus, it can be considered the main reason that high-purity AZ91 alloys have a finer grain structure than that of commercial-purity AZ91 alloys.

The association between MTHFR polymorphism, dietary methyl donors, and childhood asthma and atopy.

BACKGROUND: Studies investigating the genetic association of the C677T methylenetetrahydrofolate reductase (MTHFR) genotype and dietary methyl donors with asthma and atopy are limited, and have variable results. OBJECTIVE: To investigate the effect of dietary methyl donor intake on the risk of childhood asthma and atopy, based on the C677T polymorphism in the MTHFR gene. METHODS: This cross-sectional study included 2,333 elementary school children aged 6-8 years across Korea during 2005 and 2006, as part of the first Children's Health and Environmental Research survey. Genotyping for the MTHFR (rs1801133) polymorphism was performed using the TaqMan assay. Multivariable-adjusted logistic regression analysis was performed to determine a descriptive association between the dietary methyl donor intake, MTHFR polymorphism, and childhood asthma and atopy. RESULTS: Intake of dietary methyl donors like folates was significantly associated with a decreased risk of the wheezing symptom, in the past 12 months, and "ever asthma" diagnosis, respectively. Vitamin B6 intake was also associated with a decreased atopy risk. The T allele of the MTHFR (rs1801133) gene was significantly associated with a decreased risk of atopy. Increased intakes of folate, vitamin B2, and vitamin B6 were protective factors against atopy, especially in children with the T allele on the MTHFR gene, compared to those with lower intakes and the CC genotype. CONCLUSIONS: High intakes of dietary methyl donors were associated with reduced risk of atopy and asthma symptoms. These may have additive effects related to the susceptibility alleles of the MTHFR gene. The clinical implications require evaluation.

Particulate matter exposure during pregnancy increases risk of childhood asthma: modified by gender and NRF2 genotype.

BACKGROUND: Exposure to particulate matter (PM) has been known to develop asthma in children and the oxidative stress-related mechanisms are suggested. For the development of asthma, not only the exposure dose but also the critical window and the risk modifying factors should be evaluated. OBJECTIVE: We investigated whether prenatal exposure to PM10 increases the risk of childhood asthma and evaluated the modifying factors, such as gender and reactive oxidative stress-related gene. METHODS: A general population-based birth cohort, the Panel Study of Korean Children (PSKC), including 1572 mother-baby dyads was analyzed. Children were defined to have asthma at age 7 when a parent reported physician-diagnosed asthma. Exposure to PM10 during pregnancy was estimated by land-use regression models based on national monitoring system. TaqMan method was used for genotyping nuclear factor, erythroid 2-related factor, NRF2 (rs6726395). A logistic Bayesian distributed lag interaction model (BDLIM) was used to evaluate the associations between prenatal PM10 exposure and childhood asthma by gender and NRF2. RESULTS: Exposure to PM10 during pregnancy was associated with the development of asthma (aOR 1.03, 95% CI 1.001.06). Stratifying by gender and NRF2 genotype, exposure to PM10 during 26-28 weeks gestation increased the risk of childhood asthma, especially in boys with NRF2 GG genotype. CONCLUSIONS: A critical window for PM10 exposure on the development of childhood asthma was during 26-28 weeks of gestation, and this was modified by gender and NRF2 genotype.

Phenotype of Atopic Dermatitis With Food Allergy Predicts Development of Childhood Asthma via Gut Wnt Signaling.

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by a wide spectrum of clinical phenotype. However, specific description of phenotypes of AD depending on the comorbidities in early childhood is lacking. This study aimed to investigate whether the AD phenotype in early childhood is related to childhood asthma and to elucidate the mechanisms involved. METHODS: Data on the first 3 years of life were collected prospectively from 1,699 children in the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). We applied an unsupervised latent class analysis to the following five factors: food sensitization, inhalant sensitization, food allergy (FA), AD, and recurrent wheezing. The risks of developing FA, AD, allergic rhinitis (AR), and asthma in children aged 5-7 years were evaluated. Colonocyte transcriptome and ingenuity pathway analysis were performed. RESULTS: Four phenotypes were identified; no allergic diseases (78.4%), AD without sensitization (16.4%), FA with AD (2.9%), and AD with sensitization (7.8%). The FA with AD had the highest risk for FA, AR, and asthma and the highest cord blood immunoglobulin E (IgE) levels. In AD without sensitization and with sensitization, scoring of AD (SCORAD) in early childhood was higher than in FA with AD. Canonical pathway analysis with the colonocyte transcriptome revealed that the key pathway in FA with AD was 'Wnt/ß-catenin Signaling.' The relative abundance of Wnt6 mRNA was positively correlated with food-specific IgE levels at 1 and 3 years. CONCLUSIONS: When FA is present in various phenotypes of AD at early life, regardless of severity of eczema, it may be associated with gut Wnt signaling and later development of asthma.

Influence of Age on Effort Required to Complete Spirometry in Children and Adolescents.

Although effort required to complete spirometry is known to differ by age, no studies have addressed this issue. The present study aimed to identify the difference in the effort required to complete spirometry by age in children and adolescents. Data from 707 children (mean age, 10.2 years; range, 4-25 years) from 6 medical centers were analyzed. In addition to demographics, we obtained information on the time required for as well as the number of demonstrations and spirometry demonstrations and trials from the patients' electronic medical records. A total of 398 (56.3%) male participants were included, and 300 (42.4%) participants had no prior experience receiving spirometry. The mean time required for spirometry demonstration was 2.7 minutes (standard deviation [SD], 2.1 minutes), whereas that for spirometry trial was 5.9 minutes (SD, 5.1 minutes). The total mean time required for spirometry was 8.6 minutes (SD, 6.5 minutes). Significant negative associations were observed between age and effort required to complete spirometry with respect to the time and number of demonstrations and trials. The results of the present study suggest that age may affect the degree of effort required to complete spirometry, with a pattern of increasing effort with decreasing age. This finding provides important evidence for the establishment of health care policies especially regarding lung diseases that can benefit from spirometry.

Assessment of variables associated with prolonged admission duration in children with Mycoplasma pneumoniae pneumonia.

INTRODUCTION: Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide-sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children. METHODS: A prospective multicenter study was conducted in 1063 children <18 years old in July 2018-June 2020. The 454 had a positive M. pneumoniae polymerase chain reaction assay. RESULTS: Most subjects had MRMP (78.4%), and all mutated strains had the A2063G transition. We defined MRMP* (n = 285) as MRMP pneumonia requiring admission and MSMP* (n = 72) as MSMP pneumonia requiring admission. Patients with MRMP pneumonia were older, more likely to have segmental/lobar pneumonia, and had more febrile days than those with MSMP pneumonia. C-reactive protein (CRP), lactate dehydrogenase (LDH), and percentage neutrophils were more strongly associated with MRMP* than MSMP* groups. Percentage neutrophils, CRP, and alanine aminotransferase significantly changed between admission and follow-up measurements in patients with MRMP* (P < 0.05). The duration of admission positively correlated with the number of febrile days after initiation of antibiotic medication and laboratory variables (white blood cell count, CRP, and aspartate aminotransferase [AST]) (P < 0.05). Random forest analysis indicated that the number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission was over five. CONCLUSIONS: This study indicated that children with M. pneumoniae pneumonia with a higher number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission were more likely to have prolonged admission duration.

Atopic Dermatitis With Coexisting Food Allergy in Early Life Is Associated With Childhood Asthma.

PURPOSE: Atopic dermatitis (AD) and food allergy (FA) are associated with respiratory comorbidities, in the concept of 'atopic march.' However, children with AD and a coexisting FA have various disease courses, and the mechanism of atopic march remains unclear. In this study, we investigated whether the phenotype of AD with coexisting FA in early life affected asthma or allergic rhinitis (AR) in school children. METHODS: A total of 1,579 children from the Panel Study on Korean Children (PSKC) cohort were followed-up in 2013. The participants diagnosed with AD in this cohort were classified by the age of AD onset and persistence as well as FA history. We compared the presence of comorbidities-asthma and rhinitis-among different AD phenotypes. RESULTS: Asthma and AR with current symptoms within 12 months at age 6-8 years were associated with early-onset persistent AD phenotype, regardless of coexisting FA. AD with FA conferred a higher risk of recent wheezing at 8 years of age than AD without FA (adjusted odds ratio, 8.09; 95% confidence interval, 2.54-25.76). Children with early-onset persistent AD with FA manifested a distinctive trajectory with a higher prevalence of wheezing and AR at age 5-8 years than those without AD. CONCLUSIONS: AD with FA in early life is strongly associated with asthma and AR in school children, and the early-onset persistent AD with FA had a strong additive effect on the risk of asthma at school age. Classifying AD phenotypes regarding FA in early life will help predict and prevent asthma and AR in school children.

A Case Report of Postinfectious Bronchiolitis Obliterans After Coronavirus Disease 2019 in a 10-Year-Old Child.

Coronavirus disease 2019 (COVID-19) is usually less severe in children and adolescents than in adults. However, it can cause severe respiratory illness in a small proportion of children with risk factors. Here, we report a rare case of a 10-year-old boy with postinfectious bronchiolitis obliterans that developed after pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This patient was previously healthy apart from a high body mass index (BMI, 30.13; 99.6th percentile for the age bracket), history of preterm birth (35 weeks), and low birth weight (1,850 g). He had persistent exertional dyspnea after recovering from SARS-CoV-2-related pneumonia. Spirometry revealed obstructive lung disease with the following results: predicted forced vital capacity (FVC%pred), 71%; forced expiratory volume in 1 second (FEV1%pred), 63%; FEV1/FVC, 0.81; and forced expiratory flow25-75%pred, 55%. Chest computed tomography showed multifocal areas of parenchymal hyperlucency and mosaic attenuation in both lungs. This case suggests that careful observation of children with obesity and low birth weight is necessary after recovery from SARS-CoV-2-related pneumonia.

Global Trends in the Proportion of Macrolide-Resistant Mycoplasma pneumoniae Infections: A Systematic Review and Meta-analysis.

Importance: The proportion of macrolide-resistant Mycoplasma pneumoniae (MRMP) infections has changed, and it differs according to geographical region. Objective: To analyze the global patterns, including the temporal trends, regional variations, and variant types, in the proportion of MRMP infections in this systematic review and meta-anaysis. Data Sources: PubMed, Cochrane Library, and Embase databases were searched for observational studies from inception to September 10, 2021. Study Selection: Observational studies reporting the proportion of MRMP infections were screened independently by 2 authors. The presence of MRMP infection was defined as any case of M pneumoniae infection positive for any variants associated with macrolide resistance identified using respiratory samples. Data Extraction and Synthesis: Data were extracted independently and in duplicate by 2 reviewers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was used. Random-effects meta-analyses were used to estimate the proportion of MRMP infections. Main Outcomes and Measures: The global patterns in the proportion of MRMP infections were estimated, and the temporal trends and variant types of MRMP infection with regional differences were investigated. Results: This study included 153 studies from 150 articles (27 408 samples in 26 countries) in the meta-analysis. The global patterns in the proportion of MRMP infections showed an increasing trend with regional differences. The proportion of MRMP infections was highest in the Western Pacific regions (53.4%; 95% CI, 47.4%-60.3%), followed by the South East Asian region (9.8%; 95% CI, 0.8%-100%), the region of the Americas (8.4%; 95% CI, 6.1%-11.6%), and the European region (5.1%; 95% CI, 3.3%-8.0%). The most commonly identified variant of MRMP infection was A2063G (96.8%; 95% CI, 95.8%-97.7%), followed by A2064G (4.8%; 95% CI, 3.5%-6.7%). The proportion of MRMP infections was the highest in studies including only children (37.0%; 95% CI, 29.8%-46.1%), followed by those including only adults (15.9%; 95% CI, 6.4%-39.7%) and those including both children and adults (16.7%; 95% CI, 10.1%-27.6%). Conclusions and Relevance: This study provides global trends in the proportion of MRMP infections and suggests that strategies to prevent the spread of MRMP infection and to treat MRMP infections are needed to decrease disease burden.

Sublingual immunotherapy may be effective in reducing house dust mite allergies in children with atopic dermatitis.

AIM: We evaluated the efficacy of sublingual immunotherapy for children aged 5-17 years with atopic dermatitis who were allergic to house dust mites. METHODS: This open-label, controlled, randomised trial from June 2015 to February 2018 comprised 60 subjects from a specialist allergy centre in South Korea. Half received sublingual immunotherapy for 12 months and the other half formed the control group. The subjects were evaluated using specialist scores and specific immunoglobulin and skin prick tests. RESULTS: Sublingual immunotherapy significantly decreased the mean Scoring Atopic Dermatitis measurements in the sublingual group from baseline (30.2 ± 10.7) to 3 months (20.7 ± 8.5) and the effects persisted at 12 months (21.5 ± 12.4). However, the control group only showed a significant difference between baseline (30.4 ± 11.9) and 12 months (24.3 ± 10.2). The levels of Dermatophagoides farina-specific immunoglobulin G4 significantly increased in the treatment group from baseline (0.6 ± 0.5) to 12 months (1.0 ± 0.7), with no significant changes in the control group. New sensitisations to two or more allergens between baseline and 12 months were significantly lower in the sublingual group (21.4%) than controls (54.2%). CONCLUSION: Sublingual immunotherapy improved disease severity and prevented new sensitisations in children with atopic dermatitis who were allergic to dust mites.