Usefulness of ultrasonography in diagnosis of intestinal obstruction by a water bead

Water beads are dangerous foreign bodies causing intestinal obstruction in young children because the beads absorb water and are radiolucent. Although the features lead to progressive intestinal obstruction, it is difficult to diagnose ingestion of the beads by imaging studies. For the diagnosis, ultrasonography is safe, fast, and accurate. The imaging modality can show intestinal water beads as spherical, anechoic, smoothly demarcated cysts. This characteristic finding may be more useful in rapid and accurate diagnosis than computed tomography scan. We report a case of an 8-month-old boy who obtained a timely sonographic diagnosis of water bead-induced small bowel obstruction in the emergency department.

Successful Treatment of Severe Hemolytic Disease of the Newborn Caused by Anti-Jk b / 임상소아혈액종양

Hemolytic disease of the newborn (HDN) is a condition in which maternal antibodies cross the placenta and cause hemolytic reactions. Anti-RhD was the most common cause, but with the introduction of immunoglobulin, the frequency has decreased sig nificantly, making hemolytic disease caused by other minor blood g roups more important. Kidd antigen is also known to cause hemolytic transfusion reactions. Only 13 cases have been reported so far, because Kidd antig en dose not usually cause HDN. Most cases have a good outcome, and only two fatal cases have been reported.A four-day-old male patient was hospitalized for jaundice, and hemolysis was confirmed by blood test. The mother’s blood was Jkb antibody positive. The patient did not improve with phototherapy, so an exchange transfusion was performed. Additional hemolysis occurred, so we undertook transfusion of red blood cells, resulting in cessation of hemolysis. We report HDN caused by Jkb antibody that responded to exchange blood transfusion.

Successful Treatment of Severe Hemolytic Disease of the Newborn Caused by Anti-Jk b / 임상소아혈액종양

Hemolytic disease of the newborn (HDN) is a condition in which maternal antibodies cross the placenta and cause hemolytic reactions. Anti-RhD was the most common cause, but with the introduction of immunoglobulin, the frequency has decreased sig nificantly, making hemolytic disease caused by other minor blood g roups more important. Kidd antigen is also known to cause hemolytic transfusion reactions. Only 13 cases have been reported so far, because Kidd antig en dose not usually cause HDN. Most cases have a good outcome, and only two fatal cases have been reported.A four-day-old male patient was hospitalized for jaundice, and hemolysis was confirmed by blood test. The mother’s blood was Jkb antibody positive. The patient did not improve with phototherapy, so an exchange transfusion was performed. Additional hemolysis occurred, so we undertook transfusion of red blood cells, resulting in cessation of hemolysis. We report HDN caused by Jkb antibody that responded to exchange blood transfusion.

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.

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.

Severe Obstructive Sleep Apnea in a 7-Year-Boy with Achondroplasia :A Case Report / 수면정신생리

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder in which narrowing and obstruction of the upper airway lead to frequent arousal and decreased arterial oxygenation during sleep. OSA is more common in children with genetic disorders like achondroplasia compared to children without genetic disorders. Achondroplasia is genetic disorder characterized by hypoplasia of the facial bone and skull base with foramen magnum stenosis, resulting in exceedingly high frequency of OSA. The authors present a case of a patient with achondroplasia diagnosed with severe OSA through polysomnography after adenectomy showed little therapeutic effect and who was treated with continuous positive airway pressure.

Severe Obstructive Sleep Apnea in a 7-Year-Boy with Achondroplasia :A Case Report / 수면정신생리

Obstructive sleep apnea (OSA) is a sleep-related breathing disorder in which narrowing and obstruction of the upper airway lead to frequent arousal and decreased arterial oxygenation during sleep. OSA is more common in children with genetic disorders like achondroplasia compared to children without genetic disorders. Achondroplasia is genetic disorder characterized by hypoplasia of the facial bone and skull base with foramen magnum stenosis, resulting in exceedingly high frequency of OSA. The authors present a case of a patient with achondroplasia diagnosed with severe OSA through polysomnography after adenectomy showed little therapeutic effect and who was treated with continuous positive airway pressure.

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.

Current Status of Patient Education in the Management of Atopic Dermatitis in Korea

Patient education is important for successful management of atopic dermatitis; however, due to limited time and resources, patient education remains insufficient. This study aimed to investigate the current state of education provided by Korean dermatologists, pediatric allergists, and allergists to patients with atopic dermatitis. A questionnaire survey consisting of items regarding educational programs for patients with atopic dermatitis was conducted via e-mail. In total, 153 participants responded to the questionnaires, and 26.8% indicated that they have had separate educational programs. The workforce involved in the educational program included nurses, residents or fellows, dieticians, pharmacists, and clinical psychologists. Most education protocols addressed the characteristics and natural course of atopic dermatitis and environmental management. Overall, 96.7% of the participants replied that an additional charge is needed for education; moreover, additional assistance from an academic society or association, in the form of medical staff, organized data, and advertisement, is required to develop and provide a well-structured educational program. A standardized education protocol will effectively provide appropriate education for patients with atopic dermatitis. Arrangement of education fees, covered by the National Health Insurance Service, will lead to the establishment of a structured educational program and participation of an additional medical workforce.

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.

Clinical analysis of risk factors in refractory mycoplasma pneumonia in children

PURPOSE: Refractory Mycoplasma pneumonia (RMP) has been increasing not only in Korea but worldwide. We investigated the incidence of M. pneumonia resistant to macrolides and risk factors for RMP. METHODS: From October 2015 to May 2016, 62 pediatric patients who were admitted due to pneumonia diagnosed on the basis of chest x-ray with respiratory symptoms and positive for M. pneumoniae in polymerase chain reaction with no evidence of other bacterial or viral infections were included. Sequence analysis of the 23S rRNA gene in M. pneumoniae was performed to identify macrolide resistance. Patients with congenital anomalies, history of pulmonary disease, and unclear information on antibiotic use were excluded. RESULTS: Mutations in the 23S rRNA gene were detected in 50 of 62 patients (80.6%). Risk factors were analyzed in only 45 patients. The RMP group consisted of 26 patients (57.8%) who had fever lasting more than 5 days and deteriorating chest x-ray findings. The lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were significantly higher in the RMP group than in the non-RMP group (LDH: 300±79 U/L vs. 469±206 U/L, CRP: 4.9±4.3 mg/dL vs. 2.5±1.7 mg/dL; P = 0.04 vs. P = 0.026). In univariate analysis, the RMP group was significantly associated with 23S rRNA gene mutation, lobar pneumonia, and pleural effusion (odds ration [OR]: 10.8, 4.1, 5.3; P = 0.004, P = 0.036, P = 0.046). The presence of macrolide resistance was found to be only a significant risk factor in logistic regression (OR; 8.827; 95% confidence interval, 1.376–56.622; P = 0.022). CONCLUSION: Macrolide resistance was a significant risk factor in patients with RMP and identification of macrolide resistance might be helpful in predicting RMP and establishing target therapy for RMP.

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.

Tuberculosis-associated hemophagocytic lymphohistiocytosis in adolescent diagnosed by polymerase chain reaction / 소아과

We present a case of tuberculosis-associated hemophagocytic lymphohistiocytosis in a 14-year-old girl. The patient presented with weight loss, malaise, fatigue, prolonged fever, and generalized lymphadenopathy. Laboratory investigation revealed pancytopenia (white blood cells, 2,020 cells/microL; hemoglobin, 10.2 g/dL; platelets, 52,000 cells/microL), hypertriglyceridemia (229 mg/dL), and hyperferritinemia (1,420 ng/mL). Bone marrow biopsy showed a hypocellular bone marrow with a large numbers of histiocytes and marked hemophagocytosis; based on these findings, she was diagnosed with hemophagocytic lymphohistiocytosis. Polymerase chain reaction (PCR) with both the bone marrow aspiration and sputum samples revealed the presence of Mycobacterium tuberculosis. Antitubercular therapy with immune modulation therapy including dexamethasone and intravenous immunoglobulin was initiated. The results of all laboratory tests including bone marrow biopsy and PCR with both the bone marrow aspiration and sputum samples were normalized after treatment. Thus, early bone marrow biopsy and the use of techniques such as PCR can avoid delays in diagnosis and improve the survival rates of patients with tuberculosis-associated hemophagocytic lymphohistiocytosis.

Dynamics of Gut Microbiota According to the Delivery Mode in Healthy Korean Infants

Microbial colonization of the infant gut is unstable and shows a wide range of diversity between individuals. Gut microbiota play an important role in the development of the immune system, and an imbalance in these organisms can affect health, including an increased risk of allergic diseases. Microbial colonization of young infants is affected by the delivery mode at birth and the consequent alterations of gut microbiota in early life affect the development of allergic diseases. We investigated the effects of the delivery mode on the temporal dynamics of gut microbiota in healthy Korean infants. Fecal samples were collected at 1-3 days, 1 month, and 6 months after birth in six healthy infants. Microbiota were characterized by 16S rRNA shotgun sequencing. At the first and third days of life, infants born by vaginal delivery showed a higher richness and diversity of gut microbiota compared with those born by cesarean section. However, these differences disappeared with age. The Bacteroides genus and Bacteroidetes phylum were abundant in infants born by vaginal delivery, whereas Bacilli and Clostridium g4 were increased in infants born by cesarean section. The Firmicutes phylum and Bacteroides genus showed convergent dynamics with age. This study demonstrated the effect of delivery mode on the dynamics of gut microbiota profiles in healthy Korean infants.

Efficacy of pamidronate in pediatric osteosarcoma patients with low bone mineral density

PURPOSE: Most surviving pediatric osteosarcoma patients experience osteoporosis, bone pain, and pathologic fracture during and after therapy. The aim of this study was to evaluate the efficacy and side effects of pamidronate therapy in these patients. METHODS: Nine osteosarcoma patients (12.8±1.6 years of age; 5 boys and 4 girls) who had a history of nontraumatic fracture or severe pain after completing chemotherapy were included. Intravenous pamidronate (1.5 mg/kg) was given every 6 weeks for 4 to 6 cycles. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry. Clinical outcomes including acute side effects were also evaluated. RESULTS: After pamidronate treatments, all patients experienced decreased pain. Seven of 9 patients could walk without a crutch. The BMD of lumbar spine was increased by 0.108±0.062 mg/cm2 after 8.4±1.0 months (n=8, P=0.017) and the mean z-score improved from -2.14±0.94 to -1.76±0.95 (P=0.161). Six patients (67%) had an acute-phase reaction, and 2 patients had symptomatic hypocalcemia. CONCLUSION: Pamidronate appears to be safe and effective for the treatment of osteosarcoma in children with low BMD and bone pain.

The Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response is Modified by Maternal Atopy

PURPOSE: Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy. METHODS: This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB. RESULTS: Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers. CONCLUSIONS: Maternal atopy modified the effect of prenatal exposure to home renovation on CB serum IgE response as well as the interaction between the exposure and neonatal genes involved in the oxidative stress pathway. These findings suggest that the genetically susceptible offspring of atopic mothers may be more vulnerable to the effect of prenatal exposure to home renovation on the development of allergy.

The First Successful Heart-Lung Transplant in a Korean Child with Humidifier Disinfectant-Associated Interstitial Lung Disease

From 2006 to 2011, an outbreak of a particular type of childhood interstitial lung disease occurred in Korea. The condition was intractable and progressed to severe respiratory failure, with a high mortality rate. Moreover, in several familial cases, the disease affected young women and children simultaneously. Epidemiologic, animal, and post-interventional studies identified the cause as inhalation of humidifier disinfectants. Here, we report a 4-year-old girl who suffered from severe progressive respiratory failure. She could survive by 100 days of extracorporeal membrane oxygenation support and finally, underwent heart-lung transplantation. This is the first successful pediatric heart-lung transplantation carried out in Korea.

Association Between Antibiotic Exposure, Bronchiolitis, and TLR4 (rs1927911) Polymorphisms in Childhood Asthma

PURPOSE: The complex interplay between environmental and genetic factors plays an important role in the development of asthma. Several studies have yielded conflicting results regarding the 2 asthma-related risk factors: antibiotic usage during infancy and/or a history of bronchiolitis during early life and the development of asthma. In addition to these risk factors, we also explored the effects of Toll-like receptor 4 (TLR4) polymorphism on the development of childhood asthma. METHODS: This cross-sectional study involved 7,389 middle school students who were from 8 areas of Seoul, Korea, and completed the International Study of Asthma and Allergies in Childhood questionnaire. The TLR4 polymorphism rs1927911 was genotyped in 1,395 middle school students from two areas using the TaqMan assay. RESULTS: Bronchiolitis in the first 2 years of life, antibiotic exposure during the first year of life, and parental history of asthma were independent risk factors for the development of asthma. When combined, antibiotic use and a history of bronchiolitis increased the risk of asthma (adjusted odds ratio [aOR]: 4.64, 95% confidence interval [CI]: 3.09-6.97, P value for interaction=0.02). In subjects with CC genotype of TLR4, antibiotic exposure and a history of bronchiolitis during infancy, the risk of asthma was increased, compared to subjects without these risk factors (aOR: 5.72, 95% CI: 1.74-18.87). CONCLUSIONS: Early-life antibiotic exposures and a history of bronchiolitis are risk factors for asthma in young adolescents. Polymorphisms of TLR4 modified the influence of these environmental factors. Reducing antibiotic exposure and preventing bronchiolitis during infancy may prevent the development of asthma, especially in genetically susceptible subjects.

The prevalence and risk factors of allergic rhinitis from a nationwide study of Korean elementary, middle, and high school students

PURPOSE: We investigated the prevalence and risk factors of allergic rhinitis (AR), nationwide in random children and adolescents of Korea. METHODS: A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire survey was done in 1,820 children from elementary, middle, and high school nationwide in Korea. The subjects were selected by the stratifying sampling method by school grade and five regions. Current AR was defined as having AR symptoms during the last 12 months with a history of physician-diagnosed AR. Skin prick tests for 18 common allergens were performed. RESULTS: The number of males was 945, and that of females was 875. The mean age of the patients was 12.61+/-3.40 years. The prevalence of current AR and atopic current AR were 29.0% and 18.7%, respectively. Risk factors for current AR were male (adjusted odds ratio [aOR], 1.486; 95% confidence interval [CI], 1.189-1.856), family history of paternal AR (aOR, 3.208; 95% CI, 2.460-4.182), family history of maternal AR (aOR, 3.138; 95% CI, 2.446-4.025), antibiotic use in infancy (aOR, 1.547; 95% CI, 1.228-1.949), mold exposure during infancy (aOR, 1.416; 95% CI, 1.103-1.819), mold exposure during the last 12 months (aOR, 1.285; 95% CI, 1.012-1.630), and sensitization on skin prick tests (aOR, 2.596; 95% CI, 2.055-3.279). Risk factors for atopic current AR were the same as those of current AR, whereas breast-milk feeding (aOR, 0.720; 95% CI, 0.530-0.976) was a protective factor. Sensitized allergens as risk factors for current AR were Dermatophagoides pteronyssinus, Dermatophagoides farina, ragweed, mugwort, oak, alder, birch, Japanese hop, cat, and dog. CONCLUSION: The prevalences of current AR and atopic current AR were 29.0% and 18.7%, respectively. Male, sex parental AR, antibiotic use in infancy, mold exposure during the last 12 months, mold exposure during infancy, and atopic sensitization were risk factors for current AR. Breast-milk feeding was a protective factor for atopic current AR. Aeroallergen sensitization was an important risk factor for AR.

Prenatal Particulate Matter/Tobacco Smoke Increases Infants' Respiratory Infections: COCOA Study

PURPOSE: To investigate whether prenatal exposure to indoor fine particulate matter (PM2.5) and environmental tobacco smoke (ETS) affects susceptibility to respiratory tract infections (RTIs) in infancy, to compare their effects between prenatal and postnatal exposure, and to determine whether genetic factors modify these environmental effects. METHODS: The study population consisted of 307 birth cohort infants. A diagnosis of RTIs was based on parental report of a physician's diagnosis. Indoor PM2.5 and ETS levels were measured during pregnancy and infancy. TaqMan was used for genotyping of nuclear factor erythroid 2-related factor (Nrf2) (rs6726395), glutathione-S-transferase-pi (GSTP) 1 (rs1695), and glutathione-S-transferase-mu (GSTM) 1. Microarrays were used for genome-wide methylation analysis. RESULTS: Prenatal exposure to indoor PM2.5 increased the susceptibility of lower RTIs (LRTIs) in infancy (adjusted odds ratio [aOR]=2.11). In terms of combined exposure to both indoor PM2.5 and ETS, prenatal exposure to both pollutants increased susceptibility to LRTIs (aOR=6.56); however, this association was not found for postnatal exposure. The Nrf2 GG (aOR=23.69), GSTM1 null (aOR=8.18), and GSTP1 AG or GG (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM2.5 and ETS exposure were not found for upper RTIs. CONCLUSIONS: Prenatal exposure to both indoor PM2.5 and ETS may increase susceptibility to LRTIs. This effect can be modified by polymorphisms in reactive oxygen species-related genes.