A Case Report of Postinfectious Bronchiolitis Obliterans After Coronavirus Disease 2019 in a 10-YearOld 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 (FEV 1 % pred ), 63%; FEV 1 /FVC, 0.81; and forced expiratory flow 25-75 % 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.

Serum IgE specific to egg white and its components and open baked eggoral food challenge tests in children younger than 6 years

Purpose@#Sixty to eighty percent of children with egg allergy are able to tolerate eggs in baked form. The purpose of this study was to evaluate the clinical usefulness and diagnostic value of measurements of IgE specific to egg white, ovalbumin, and ovomucoid for reactivity to baked egg in children with sensitivity to egg. @*Methods@#Two hundred seventeen children with suspected egg allergy underwent open food challenges with baked egg (in the form of muffins). The outcomes of the challenges were compared to the serum concentrations of IgE specific to egg white, ovalbumin, and ovomucoid by using ImmunoCAP. @*Results@#There were no statistically significant differences in levels of IgE specific to egg white, ovalbumin, and ovomucoid between the baked egg challenge positive and negative groups younger than 2 years (n = 163). However, significant differences were observed between the challenge positive and negative groups in 54 subjects aged 2 to 5 years (all P < 0.05). The optimal cutoff points of egg white, ovalbumin, and ovomucoid specific IgE levels among children aged 2 to 5 years were 12.40 kU A/L (sensitivity 79%, specificity 66%), 4.07 kU A/L (sensitivity 88%, specificity 58%), and 3.65 kU A/L (sensitivity 77%, specificity 62%), respectively. @*Conclusion@#The level of IgE specific to egg white and its components can predict the reactivity to baked egg in children aged 2 to 5years.

Clinical characteristics and associated factors of Mycoplasma pneumoniaepneumonia with atelectasis in children

Purpose@#Patients with Mycoplasma pneumoniae pneumonia (MPP) can develop atelectasis, and some cases of atelectasis may persist for over 4 weeks. However, the risk factors for the development and persistence of atelectasis ( > 4 weeks) in children with MPP and their clinical characteristics remain understudied. We aimed to investigate the clinical characteristics and associated factors of MPP with atelectasis in children. @*Methods@#We retrospectively analyzed the medical records of 477 children with MPP treated at Pusan National University Yangsan Hospital from November 2014 to March 2020. Demographics, clinical information, laboratory data, and radiological findings were collected from all patients. The patients were divided into 2 groups according to the presence of atelectasis with MPP. The group with atelectasis was further divided into 2 groups according to whether atelectasis was improved. @*Results@#Among 477 children with MPP, 105 developed atelectasis, and 34 showed persistent atelectasis. Children with atelectasis had longer lengths of hospitalization than children without atelectasis. High lactate dehydrogenase (LDH) levels and whole lobar consolidation were independently associated factors for presenting with atelectasis, and long macrolide therapy duration before admission ( > 3 days) was related to persistent atelectasis ( > 4 weeks). @*Conclusion@#High LDH levels and whole lobar consolidation were independent associated factors for presenting with atelectasis, and a long macrolide therapy duration before admission was associated with persistent atelectasis. Careful observation and management of children with these associated factors for atelectasis will improve the prognosis of children with MPP.

Innate Type 2 Response to Aspergillus fumigatus in a Murine Model of Atopic Dermatitis–like Skin Inflammation

Background@#Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). @*Methods@#We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. @*Results@#The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. @*Conclusions@#Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

Innate Type 2 Response to Aspergillus fumigatus in a Murine Model of Atopic Dermatitis–like Skin Inflammation

Background@#Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mediated by T helper type 2 (Th2) cells in acute phase. Group 2 innate lymphoid cells (ILCs) play a role in the initiation of the Th2 response. Although mold exposure is associated with the development of AD, studies on the underlying mechanisms are lacking. This study investigated whether group 2 ILCs are involved in inflammation in AD-like skin induced by Aspergillus fumigatus (Af). @*Methods@#We investigated changes of group 2 ILCs population in Af-induced AD-like skin lesions. To induce AD-like skin lesions, Af extracts were applied to the dorsal skin of BALB/c and Rag1−/− mice five times per week, with repeat exposures at 2-week intervals. @*Results@#The clinical parameters were higher in the Af-treated group than in the control group. Histologic findings revealed epiderrmal and dermal thickening as well as eosinophil and mast cell infiltration into the skin of Af-treated mice. Populations of group 2 ILCs in the skin were also significantly higher in the Af-treated group. In addition, interleukin-33 mRNA expression was significantly higher in the skin lesions of the Af-treated mice. In the Rag1−/− mice lacking mature lymphocytes, AD-like skin lesions were still induced by Af and ILCs depletion using an anti-CD90.2 mAb lowered the Af-induced inflammatory response. @*Conclusions@#Group 2 ILCs may play a role in a murine model of Af-induced AD-like skin lesions.

NOTCH1 Pathway is Involved in Polyhexamethylene Guanidine-Induced Humidifier Disinfectant Lung Injuries

0.2 and p<0.05. NOTCH1 was identified as a candidate network hub gene in cases. NOTCH1 transcripts significantly increased in lung tissues from HDLI cases compared to unexposed controls (p=0.05). NOTCH1 may play an important role in pulmonary fibrosis of HDLI.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

Indoor pet ownership in infancy is a risk factor for the development of sensitization to pets and asthma in childhood

PURPOSE: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. METHODS: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. RESULTS: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29–13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65–18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physicians) (aOR, 6.36; 95% CI, 1.54–26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. CONCLUSION: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Association of Genetic Polymorphisms with Atopic Dermatitis, Clinical Severity and Total IgE: A Replication and Extended Study

PURPOSE: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease affecting up to 20% of children and 3% of adults worldwide. Although previous reports including genome-wide association study (GWAS) approaches have identified several risk factors that appear to be associated with AD development, replication studies are lacking. In our current study, we replicated the associations between candidate susceptibility loci and AD. METHODS: A total of 885 Korean subjects (425 AD patients and 460 unaffected controls) were genotyped for 17 single nucleotide polymorphisms (SNPs) from previous GWASs and meta-analyses of AD and from immune-related genes. RESULTS: Several SNPs showed significant associations with AD in the case-control analysis (minimum P=0.005 at rs17389644), suggesting that these polymorphisms may be related to this disease. In addition, several SNPs showed significant signals (minimum P=0.004 at rs6473227) in severe AD compared to unaffected controls. In additional linear regression analysis, a few genotypes appeared to have potential effects on the SCORing AD (SCORAD) values (minimum P=0.003 at rs13361382 on TMEM232) and immunoglobulin E (IgE) levels (minimum P < 0.0001 at rs4713555 near HLA-DRB1 and HLA-DQA1) in AD patients. CONCLUSIONS: Our replication and extended study provide additional supporting information on the genetic associations (especially, variants in TMEM232 and nearby to IL21 and HLA-DRB1/HLA-DQA1) related to AD, its clinical severity and IgE involvement.

Two Cases of Chloromethylisothiazolinone and Methylisothiazolinone-associated Toxic Lung Injury

Previous animal studies have not conclusively determined the association between exposure to humidifier disinfectants (HDs) containing 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT) and/or 2-methyl-4-isothiazolin-3-one (MIT) and development of HD-associated lung injuries. Nonetheless, patients exposed to HDs containing only CMIT and/or MIT showed clinically similar lung injuries to those exposed to HDs containing polyhexamethylene guanidine (PHMG) or oligo (2-[2-ethoxy]ethoxyethyl) guanidinium chloride (PGH). Here, we report twin sisters with lung injuries associated with exposure to CMIT/MIT-containing HDs. At 6 months of age, a younger twin sister presented with the 3-day history of cough, sputum, and respiratory difficulty. Chest radiography revealed multiple patchy consolidation and ground-glass opacities with pneumothorax and pneumomediastinum. Thoracostomy was performed due to pneumothorax at admission and she was discharged at 11 days of hospitalization. At 5 years of age, multiple tiny nodules and faint centrilobular ground-glass opacities were observed with the small pneumatocele. The elder sister visited a tertiary hospital due to dyspnea at 12 months of age. Chest radiography showed consolidation, pneumomediastinum, and pulmonary interstitial emphysema. There was no response to the administration of immunosuppressant drugs and antifibrotic agents. At 5 years of age, chest CT revealed ground-glass opacity and multiple tiny centrilobular ground-glass opacities nodules in both lungs with exercise intolerance.

The First Successful Lung Transplantation in a Korean Child with Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive inherited multisystem disorder caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Respiratory failure remains the most frequent cause of morbidity and mortality. Lung transplantation is the only option to treat end-stage lung disease. Very few cases of CF occur in Koreans. We report the case of a 12-year-old girl with respiratory failure due to CF who underwent lung transplantation. She had been diagnosed with CF 8 years previously after being treated for recurrent Pseudomonas aeruginosa pneumonia and malnutrition based on sweat chloride concentrations and the CFTR protein gene mutation test. Progression to end-stage lung disease and respiratory failure led to registration with the Korean Network for Organ Sharing. She underwent successful double lung transplantation in 2014. Although she has diabetes mellitus and chronic kidney disease, she has a better quality of life and a prolonged life expectancy.