BACKGROUND:Asthma is a heterogeneous disease with different outcomes. For children with asthma at the age of 7 years, 67-75% are symptom-free as adults. Data on the important link between childhood and adult asthma are sparse. OBJECTIVE:We aimed to investigate factors associated with persistence of childhood asthma over three years of follow-up by linking data between Korea childhood Asthma Study (KAS) and their matched claims data from Health Insurance Review and Assessment Service (HIRA). METHODS:We analyzed data from 450 preadolescent children aged 7 to 10 years and classified them into remission or persistence groups. Baseline clinical characteristics and exposure to air pollution materials including PM2.5 and PM10 during three years of follow-up were compared. The main outcome was asthma persistence which was defined as the presence of asthma episodes with healthcare utilization and prescription of asthma medications within three years after KAS enrollment. RESULTS:At the third year of follow-up, after stepwise regression analysis, lower age at enrollment (adjusted odds ratio (aOR): 0.79; 95% confidence interval (CI): 0.64-0.96), male sex (aOR: 1.66; 95%CI: 1.05-2.63), proximity from an air-polluting facility (aOR: 2.4; 95%CI: 1.34-4.29), higher level outdoor PM2.5 (aOR: 1.1; 95%CI: 1.02-1.20), and higher rate of doctor-diagnosed food allergy (FA) (aOR: 2.33; 95%CI: 1.06-5.12) were significantly associated with persistence. CONCLUSION:We discovered various independent risk factors for the persistence of childhood asthma. By linking HIRA claims data, we could clarify risk factors for persistence in a well-defined study population.

The data that support the findings of this study are available from the HIRA. Restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available due to personal information protection. Data are available at https://opendata.hira.or.kr/home.do. Appendix S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age‐related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children.

Background It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children. Purpose This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children. Methods We performed a population-based cross-sectional study in 916 preschool children aged 4–6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma. Results The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed. Conclusion The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

High-flow nasal cannula (HFNC) is a relatively safe and effective noninvasive ventilation method that was recently accepted as a treatment option for acute respiratory support before endotracheal intubation or invasive ventilation. The action mechanism of HFNC includes a decrease in nasopharyngeal resistance, washout of dead space, reduction in inflow of ambient air, and an increase in airway pressure. In preterm infants, HFNC can be used to prevent reintubation and initial noninvasive respiratory support after birth. In children, flow level adjustments are crucial considering their maximal efficacy and complications. Randomized controlled studies suggest that HFNC can be used in cases of moderate to severe bronchiolitis upon initial low-flow oxygen failure. HFNC can also reduce intubation and mechanical ventilation in children with respiratory failure. Several observational studies have shown that HFNC can be beneficial in acute asthma and other respiratory distress. Multicenter randomized studies are warranted to determine the feasibility and adherence of HFNC and continuous positive airway pressure in pediatric intensive care units. The development of clinical guidelines for HFNC, including flow settings, indications, and contraindications, device management, efficacy identification, and safety issues are needed, particularly in children.

Background: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. Methods: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. Results: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged <18 years. In children and adolescents, foods (84.8%) were the most common cause of anaphylaxis, followed by drugs (7.2%); in adults, drugs (58.3%) were the most common cause, followed by foods (28.3%) and insect venom (8.1%). The onset time was ≤10 min in 37.6% of patients. Among the 351 cases registered via the emergency department (ED) of participating hospitals, epinephrine was administered to 63.8% of patients. Among those receiving epinephrine in the ED, 13.8% required 2 or more epinephrine shots. Severe anaphylaxis accounted for 23.5% cases (38.1% in adults; 13.7% in children); patients with drug and insect venom-induced anaphylaxis had higher rates of severe anaphylaxis. Conclusion: This multicenter registry provides data on anaphylaxis for all age groups for the first time in Asia. The major causes and severity of anaphylaxis were remarkably different according to age group, and the acute treatment features of anaphylaxis in the EDs were examined in detail.

Background We aimed to investigate the treatment response and associated factors for loss of control in children with chronic spontaneous urticaria (CSU). Methods A total of 240 CSU patients (aged 0-17 years) were enrolled in a single-center study in Korea from May 2014 to May 2019. We retrospectively reviewed the medical records and compared the duration of treatment and step of medications using the urticaria control test (UCT, range 0-16 points). Serum total immunoglobulin levels, eosinophil count, allergic sensitization, autologous serum skin test, antinuclear antibody, thyroid function test, erythrocyte sedimentation rate, and C-reactive protein were measured. The patients were divided into well-controlled (sustained UCT >= 12), partly controlled (fluctuating UCT around 12), and poorly controlled (sustained UCT <12) groups. Results Of the 240 children, 150 (62.5%) achieved well-controlled status; 74 (30.8%), partly controlled; and 16 (6.7%), poorly controlled. Longer duration (adjusted odds ratio: 1.09, 95% confidence interval: 1.05-1.13,P < .001) and higher treatment steps (5.61, 2.82-11.14,P < .001) for reaching the initial 12 points or more of UCT score, initial urticaria activity score (UAS) score (1.06, 1.03-1.09,P < .001), and food sensitization (1.88, 1.03-3.46,P = .041) were associated with inadequate treatment response. The mean duration to symptom free for 1 month without medication was 14.6 months in the well-controlled group and 22.1 months in the partly controlled group (P = .002). Conclusion Children with CSU have a good treatment response. Longer duration and higher treatment step until the initial disease control, higher initial UAS7 score, and food sensitization can predict inadequate treatment response.

Pierre Robin sequence (PRS), also called Robin sequence, is a congenital anomaly characterized by a triad of micrognathia, glossoptosis, and upper airway obstruction. Infants with PRS can present with varying degrees of respiratory difficulty secondary to upper airway obstruction. There has been no consensus for the treatment of upper airway obstruction in infants with PRS, but recent studies recommend attempting non-surgical interventions before surgical treatment. In this case report, we present 3 cases of infants diagnosed with PRS who showed persistent respiratory difficulties after birth. Before considering surgical intervention, insertion of a nasopharyngeal airway was attempted in these infants. Following this procedure, symptoms of upper airway obstruction were relieved, and all infants were discharged without surgical interventions; the nasopharyngeal airway was removed 1 to 2 months later. To date, no infant has shown signs of upper airway obstruction. Nasopharyngeal airway insertion is a highly effective and less invasive treatment option for infants with PRS. However, it is not widely known and used in Korea. Nasopharyngeal airway insertion can be preferentially considered before surgical intervention for upper airway obstruction in such infants.

BackgroundAsthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma.MethodsWe designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects' baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation.DiscussionBased on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects' personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Sensitization plays important roles in the development of asthma and AR in children. We elucidated the association between sensitization patterns and allergic diseases. A cohort of 548 children was enrolled from the Panel Study of Korean Children (PSKC) study. Skin prick tests for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to evaluate the presence of allergic diseases. The sensitization rate was 46.4%. Sensitization to indoor allergens (Der f, Dermatophagoides pteronyssinus [Der p], cat epithelium, dog dander, cockroach) showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23) and allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06) in the preceding 12 months. In contrast, sensitization to outdoor allergens (grass mixture, alder, birch, oak, Japanese hop, Mugwort, ragweed, hazel) was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and with symptoms in the preceding 12 months of AR and asthma, but not with BHR. A higher degree of sensitization to indoor and outdoor allergens was associated with symptoms in the preceding 12 months of asthma and AR. The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization patterns and asthma/AR and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

BACKGROUNDSensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases.METHODSA cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used.RESULTSThe sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR.CONCLUSIONThe sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Background: Asthma and allergic diseases account for school absenteeism and may limit academic and social opportunities for a substantial number of students, because they are common chronic disorders affecting school-aged children. We evaluated the prevalence of asthma and allergic diseases in Korean children, as well as associated school absenteeism. Methods: We administered a questionnaire-based survey to 148 asthma-friendly schools from 14 counties or cities in Gyeonggi province in South Korea. The questionnaire was modified from the ISAAC questionnaire, which consists of 13 questions regarding prevalence of asthma, allergic rhinitis, and atopic dermatitis, and the impact of these conditions on school attendance. Results: A total of 41,062 subjects (aged 7-12 years) were enrolled in this study. The overall lifetime prevalence of asthma, allergic rhinitis, and atopic dermatitis was 5.3%, 38.4%, and 25.0%, respectively. Among subjects who had ever been diagnosed with asthma, 9.1% missed school due to asthmatic complaints. Many subjects with allergic rhinitis (3.2%) or atopic dermatitis (1.8%) also responded that they had missed school because of their diseases. Subjects with current symptoms or having undergone a recent treatment for allergic rhinitis or atopic dermatitis had a significantly increased risk of missing school due to asthma. Conclusion: Asthma and allergic diseases present a substantial health and socioeconomic burden, as demonstrated by the prevalence and related school absenteeism among school-aged children in Korea. Coexisting symptomatic allergic rhinitis and atopic dermatitis are associated with increased risk of school absenteeism due to asthma.

Background Bronchial hyperresponsiveness (BHR) is a fundamental pathophysiological characteristic of asthma. Although several factors such as airway caliber can affect BHR, no study has established age-dependent cutoff values of BHR to methacholine for the diagnosis of asthma in children. We investigated the cutoff values of the methacholine challenge test (MCT) in the diagnosis of asthma according to age. Methods A total of 2383 individuals aged from 6 to 15 years old were included in this study. MCTs using the five-breath technique were performed in 350 children with suspected asthma based on symptoms by pediatric allergists and in 2033 healthy children from a general population-based cohort. We determined the provocative concentration of methacholine producing a 20% decrease in forced expiratory volume in 1 second from baseline (PC 20 ). A modified Korean version of the International Study of Asthma and Allergies in Childhood questionnaire was used to distinguish asthmatics and healthy subjects. Receiver-operator characteristic curve analysis was used to assess the cutoff value of PC 20 for the diagnosis of asthma. Results Cutoff values of methacholine PC 20 , which provided the best combination of diagnostic sensitivity and specificity, showed an increasing pattern with age: 5.8, 9.1, 11.8, 12.6, 14.9, 21.7, 23.3, 21.1, 21.1, and 24.6 mg/mL at ages 6, 7, 8, 9, 10, 11, 12, 13, 14, and 15 years, respectively. Conclusion The application of different cutoff values of methacholine PC 20 depending on age might be a practical modification for the diagnosis of asthma in children and adolescents with asthmatic symptoms.

Background Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood. Objective To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases. Methods We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis. Results Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria, and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively). Conclusion Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases.

Although second-hand smoke (SHS) exposure is associated with asthma, its effect on eczema is unclear. Especially, the effect of maternal passive smoking on childhood eczema has rarely been studied. Polymorphisms in tumor necrosis factor-α (TNF-α), toll-like receptor 4 (TLR4), and glutathione S-transferase P1 (GSTP1) genes interact with air pollutants and modify allergic disease development. This study aimed to investigate the effect of gene–environment interactions between SHS exposure and TNF-α/TLR4/GSTP1 polymorphisms on childhood eczema. From 2005 to 2006, 3,639 children aged 7 or 8 years were enrolled and followed up 2 years later. Details of SHS exposure and eczema were collected by questionnaires. TNF-α (rs1800629), TLR4 (rs1927911), and GSTP1 (rs1695) genotypes were determined. Maternal passive smoking during pregnancy was associated with increased prevalence of eczema diagnosis ever (adjusted odds ratio [aOR] 1.50, 95% confidence intervals [CI] 1.25–1.79), and eczema symptoms in the past 12 months...

Purpose: There are many reports that the prevalence of food allergy (FA) is globally increasing. We investigated the change in FA prevalence since the last 20 years in elementary school children, in Seoul, Korea.Methods: A modified International Study of Asthma and Allergies in Childhood questionnaire survey was done to elementary school children in Seoul, Korea in 1995, 2000, 2005, 2008, and 2012. The numbers of subjects included in the analysis were 7,963, 7,971, 7,131, 3,975, and 3,307, respectively. Blood and skin prick tests were done in 2008 and 2012.Results: The prevalence rates of FA diagnosis ever were 4.6% (95% confidence interval [CI], 4.1-5.1), 5.2% (95% CI, 4.7-5.7), 6.4% (95% CI, 5.9-7.0), 5.5% (95% CI, 4.8-6.3), and 6.6% (95% CI, 5.8-7.6) in 1995, 2000, 2005, 2008, and 2012, respectively (P-value for trend <0.001). Asthma (adjusted odds ratio [aOR], 2.209; 95% CI, 1.589-3.072), allergic rhinitis (aOR, 1.874; 95% CI, 1.473-2.384), and atopic dermatitis (aOR, 4.288; 95% CI, 3.340-5.506) were associated with FA diagnosis. Parental allergic disease history (aOR, 2.191; 95% CI, 1.666-2.881), antibiotics use in infancy (aOR, 1.484; 95% CI, 1.170-1.883), and house mold exposure in infancy (aOR, 1.540; 95% CI, 1.172-2.024) were risk factors for FA diagnosis. Sensitization to inhalant allergens (aOR, 1.867; 95% CI, 1.091-3.194) and increased serum total IgE (aOR, 2.014; 95% CI, 1.081-3.752) were associated with FA diagnosis.Conclusion: The prevalence of FA diagnosis is likely to be increasing since the last 20 years in Seoul. Antibiotics use in infancy and house mold exposure in infancy were risk factors for FA diagnosis. (Allergy Asthma Respir Dis 2016:4:276-283)

Bronchial hyperresponsiveness (BHR) is a key feature of asthma, but the natural course is heterogenous. Total 1,245 elementary school children were included from the CHEER study. ISSAC questionnaire, total IgE, blood eosinophil (%), skin prick test, pulmonary function test, and methacholine challenge test were done at age 6-8 years for baseline and follow up at age 10-12 years. We divided the BHR changing pattern into 4 pheynotypes. Multinomial logistic regression analysis was done to evaluate the risk factors for each phenotype. 4 phenotypes of BHR were composed of BHR never (897), BHR remission (197), BHR new (81), and BHR persistent (70) respectively. BHR persistent showed high eosinophil, high logIgE, and low lung function than other groups. Atopic sensitization (aOR=4.329, 95% CI 2.056-9.115), especially Dp and Df sensitization (aOR=2.986, 95% CI 1.475-6.044, aOR=3.284, 95% CI 1.627-6.627) were the risk factors for BHR persistent at age 6-8 years. Newly sensitization of Dp and Df at 10-12 years were associated with BHR new later (aOR=2.258, 95% CI 1.206-4.225, aOR=2.657, 95% CI 1.394-5.065). The mean Dp and Df wheal size of BHR persistent were bigger than other groups (P value < 0.05), but later at 10-12 years, there were no differences between BHR persisten and BHR new. Eosinophil (%) and logIgE of BHR persistent were higher than other groups at all age. Atopic sensitization with Dp and Df was the most important risk factor for BHR persistent and was associated with later development of BHR. These findings suggest that high and new allergen sensitization is linked to persistent BHR and new development of BHR.

Objectives25-hydroxyvitamin D (25[OH]D) deficiency and genetic variants at the 17q12-21 locus are independent risk factors for respiratory tract infections (RTIs). We aimed to investigate whether the effect of 25(OH)D at birth and 1 year of age and the polymorphism at the 17q12-21 locus, or interactions between these two factors, increase susceptibility to RTIs in the first year of life.MethodsWe tested cord-blood (CB) 25(OH)D at birth and 1 year of age and genotypes of a variant at the 17q12-21 locus for associations with RTIs, particularly lower respiratory tract infections (LRTIs), and determined whether there exist interactions between 25(OH)D and 17q12-21 genotypes in a birth cohort of 473 infants.ResultsThe levels of CB 25(OH)D inversely associate with development of RTIs and LRTIs during the first year of life. There exists an inverse association of 25(OH)D at birth, but not at 1 year, with the risk of acquiring LRTIs in early infancy (adjusted odds ratio [aOR], 2.37; 95% confidence interval [CI]: 1.23-4.60; P=0.010 and aOR, 0.50; 95%CI: 0.23-1.12; P=0.094). We have also found a significant interaction between CB 25(OH)D and a variant at the 17q12-21 locus with respect to the development of early LRTIs, such that associations between a variant at the 17q12-21 locus and LRTIs are restricted to infants with low CB 25(OH)D concentrations (P for interaction=0.013). In addition, when infants with a variant at the 17q12-21 locus had been exposed to chronic 25(OH)D deficiency over the first year, their risk of LRTIs was increased.ConclusionCB 25(OH)D deficiency during fetal life contribute to the development of LRTIs in genetically susceptible infants. Pediatr Pulmonol. 2016; 51:958-967. (c) 2016 Wiley Periodicals, Inc.

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(Nn2) (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 Fills (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 (aOH=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 GO (aOR=7.37) genotypes increased the combined LRTIs-promoting effects of prenatal exposure to the 2 indoor pollutants. Such effects of prenatal indoor PM(2.)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.

Asthma is characterized by airway inflammation, and bronchial airways are particularly susceptible to oxidant-induced tissue damage.