Clinical characteristics of pediatric patients infected with SARS-CoV-2 versus common human coronaviruses: a national multicenter study.

BACKGROUND: Human coronaviruses (HCoV) cause mild upper respiratory infections; however, in 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged, causing an acute respiratory disease pandemic. Coronaviruses exhibit marked epidemiological and clinical differences. PURPOSE: This study compared the clinical, laboratory, and radiographic findings of children infected with SARS-CoV-2 versus HCoV. METHODS: SARS-CoV-2 data were obtained from the Korea Disease Control and Prevention Agency (KDCA) registry and 4 dedicated coronavirus disease 2019 (COVID-19) hospitals. Medical records of children admitted with a single HCoV infection from January 2015 to March 2020 were collected from 10 secondary/tertiary hospitals. Clinical data included age, sex, underlying disease, symptoms, test results, imaging findings, treatment, and length of hospital stay. RESULTS: We compared the clinical characteristics of children infected with HCoV (n=475) to those of children infected with SARS-CoV-2 (272 from KDCA, 218 from COVID-19 hospitals). HCoV patients were younger than KDCA patients (older than 9 years:3.6% vs. 75.7%; P<0.001) and patients at COVID-19 hospitals (2.0±2.9 vs 11.3±5.3; P<0.001). Patients with SARS-CoV-2 infection had a lower rate of fever (26.6% vs. 66.7%; P<0.001) and fewer respiratory symptoms than those with HCoV infection. Clinical severity, as determined by oxygen therapy and medication usage, was worse in children with HCoV infection. Children and adolescents with SARS-CoV-2 had less severe symptoms. CONCLUSION: Children and adolescents with COVID-19 had a milder clinical course and less severe disease than those with HCoV in terms of symptoms at admission, examination findings, and laboratory and radiology results.

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.

Analysis of national surveillance of respiratory pathogens for community-acquired pneumonia in children and adolescents.

BACKGROUND: Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP. METHODS: The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020. RESULTS: A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports. CONCLUSIONS: This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.

Prediction of COVID-19-related Mortality and 30-Day and 60-Day Survival Probabilities Using a Nomogram.

BACKGROUND: Prediction of mortality in patients with coronavirus disease 2019 (COVID-19) is a key to improving the clinical outcomes, considering that the COVID-19 pandemic has led to the collapse of healthcare systems in many regions worldwide. This study aimed to identify the factors associated with COVID-19 mortality and to develop a nomogram for predicting mortality using clinical parameters and underlying diseases. METHODS: This study was performed in 5,626 patients with confirmed COVID-19 between February 1 and April 30, 2020 in South Korea. A Cox proportional hazards model and logistic regression model were used to construct a nomogram for predicting 30-day and 60-day survival probabilities and overall mortality, respectively in the train set. Calibration and discrimination were performed to validate the nomograms in the test set. RESULTS: Age ≥ 70 years, male, presence of fever and dyspnea at the time of COVID-19 diagnosis, and diabetes mellitus, cancer, or dementia as underling diseases were significantly related to 30-day and 60-day survival and mortality in COVID-19 patients. The nomogram showed good calibration for survival probabilities and mortality. In the train set, the areas under the curve (AUCs) for 30-day and 60-day survival was 0.914 and 0.954, respectively; the AUC for mortality of 0.959. In the test set, AUCs for 30-day and 60-day survival was 0.876 and 0.660, respectively, and that for mortality was 0.926. The online calculators can be found at https://koreastat.shinyapps.io/RiskofCOVID19/. CONCLUSION: The prediction model could accurately predict COVID-19-related mortality; thus, it would be helpful for identifying the risk of mortality and establishing medical policies during the pandemic to improve the clinical outcomes.

The association of obstructive sleep apnea with dyslipidemia in Korean children and adolescents: a single-center, cross-sectional study.

STUDY OBJECTIVES: To evaluate whether obstructive sleep apnea (OSA) and its severity are related to dyslipidemia and alanine transaminase elevation as a marker of nonalcoholic fatty liver disease in children. METHODS: The data collected from polysomnography, laboratory measurements (lipid profile and liver enzyme), and body mass index in children aged 0-18 years who visited the pediatric department between 2012 and 2018 were retrospectively analyzed. RESULTS: There were a total of 273 participants in the study (ages 0-6 years, 7-12 years, and 13-18 years: 61.9%, 26.4%, and 11.7%, respectively). In the ages 7-12 and 13-18 years groups, obesity was strongly associated with OSA severity (Cramer's V = 0.498, P < .001). High-density lipoprotein cholesterol levels were significantly lower in the OSA group than in the non-OSA group, irrespective of the presence of obesity. In addition, high-density lipoprotein cholesterol levels were significantly different between the OSA severity groups after adjusting for body mass index (P = .000). In participants who were obese, moderate and severe OSA were associated with alanine transaminase elevation (P = .023 and P = .045, respectively). CONCLUSIONS: This study suggests that OSA may be an independent risk factor for dyslipidemia and that OSA and obesity have a synergistic effect on alanine transaminase elevation. Early diagnosis and treatment of OSA from childhood, especially in obese children, will reduce metabolic complications. CITATION: Kang EK, Jang MJ, Kim KD, Ahn YM. The association of obstructive sleep apnea with dyslipidemia in Korean children and adolescents: a single-center, cross-sectional study. J Clin Sleep Med. 2021;17(8):1599-1605.

Behavioral insomnia in infants and young children.

In infants and young children, bedtime problems and night waking are common and the main presentations of insomnia. Poor sleep may critically impact the daytime functioning and mood of the child and their caregivers. A comprehensive sleep history, a sleep diary/log, and the BEARS (Bedtime problems, Excessive daytime sleepiness, Awakenings during the night, Regularity and duration of sleep, and Sleep-disordered breathing) sleep screen are useful for diagnosing sleep problems in young children. Behavioral therapies for this type of insomnia include extinction, bedtime fading with positive routines, and scheduled awakening. Previous studies of behavioral interventions for young children showed significant improvements in sleep-onset latency, night waking frequency, and night waking duration. Parent education about their child's sleep, bedtime routines, and sleep hygiene is essential for treatment.

Adherence to Positive Airway Pressure for the Treatment of Obstructive Sleep Apnea in Children With Developmental Disabilities.

STUDY OBJECTIVES: To determine whether adherence to positive airway pressure (PAP) differs in children with developmental disabilities (DD) compared to typically developing (TD) children. METHODS: PAP adherence of 240 children initiated on PAP for obstructive sleep apnea (OSA) was retrospectively analyzed. Adherence between groups, expressed as percentage of nights used and hours of usage on nights used at 3 and 6 months, was compared. Predictive factors of adherence were studied using a median regression model. RESULTS: A total of 103 children with DD (median [interquartile range] age = 7.9 [3.2-13.1] years) and 137 TD (11.0 [5.5-16.1], P = .005) children were included. Percentage of nights used was significantly higher in children with DD at 3 (DD = 86.7 [33.9-97.9], TD = 62.9 [30.8-87.8] P = .01) and 6 months (DD = 90.0 [53.3-100], TD = 70.7 [29.2-90.8], P = .003). Hours of usage on nights used at 3 and 6 months were similar between groups (DD = 5.0 [1.4-7.9], TD = 4.6 [1.9-7.2], P = .715; DD = 6.4 [1.8-8.3], TD = 5.7 [2.5-7.3], P = .345, respectively). This adherence measure improved over time in both groups (DD, P = .007; TD, P = .005). At 6 months, higher median neighborhood income and titration at or before 6 months were significantly predictive for percentage of nights used; higher PAP pressure was significantly predictive for hours of usage in both groups. CONCLUSIONS: Children with DD had better PAP adherence expressed as percentage of nights used than TD children. Hours of usage on nights used at 3 and 6 months were similar between groups and improved over time. Higher income and titration at or before 6 months were predictive of adherence in all children. These findings indicate that children with DD can successfully wear PAP.

The effects of hydrogen peroxide and lipopolysaccharide on rat alveolar L2 cells.

PURPOSE: This study aimed to investigate differential cell responses of alveolar epithelial cells (AECs) after treatments with lipopolysaccharide (LPS) and hydrogen peroxide (H2O2) to mimic the exposure to inflammation and oxidative stress and the mechanisms of a double-hit model of apoptosis. MATERIALS AND METHODS: AECs were cultured and treated with combinations of 1 µg/mL of LPS and 500 µM H2O2 as follows: LPS-only at 0 h, LPS at 0 h with H2O2 at 6 h (LPS + H2O2), H2O2-only at 0 h, H2O2 at 0 h with LPS at 6 h (H2O2 + LPS), and control. We investigated mRNA expression (TNF-α, Fas, Fas ligand, Bax, Bcl-2, Caspase-7), protein expression (Fas, Bax, Bcl-2, Caspase-7) and apoptosis (Caspase-3 activity, TUNEL assay) at 0, 3, 6, 9, 12, and 24 h. RESULTS: In the H2O2 + LPS group, the Caspase-7, and Fas mRNA levels were significantly higher than the other groups at 9 h and 12 h, and Bax was higher at 12 h. The Bax/Bcl-2 protein expression ratio was significantly higher in the H2O2 + LPS group than that of the other groups at 12h and 24h. Apoptotic index was highest in the H2O2 + LPS group at 24 h. CONCLUSIONS: The sequence of stimulation may modify the cell response in rat AECs. The results suggest that previous oxidative stress and subsequent LPS-induced inflammation primarily influence apoptosis of L2 cells by up-regulation of cell signaling.

Ileal Perforation with Norovirus Gastroenteritis in a 3-Month-Old Infant.

Noroviruses have been recognized as the leading cause of epidemic and sporadic gastroenteritis since the advent of molecular diagnostic technique. They have been documented in 5-31% of pediatric patients hospitalized with gastroenteritis. Although norovirus gastroenteritis is typically mild and self-limited, it causes severe, but sometimes fatal, conditions in the vulnerable population such as immunocompromised patients, young children, and the elderly. Bowel perforation due to norovirus infection is rare. We report a case of small bowel perforation with norovirus gastroenteritis in the infant with Down syndrome during the hospitalization with pneumonia. Severe dehydration may cause bowel ischemia and could have triggered bowel perforation in this case. Physicians should be alert to the potential surgical complications followed by severe acute diarrhea, especially in high risk groups.

Hemagglutination inhibiting antibody persistence 1 year after influenza vaccination in Korean children and adolescents.

This study aimed to assess the 1-y immunogenicity of influenza vaccines and the association between immunogenicity at 1 m and further influenza infections in children aged 6 m to 18 y. Serum hemagglutination inhibition (HI) antibody titers and GMTs were determined for the recommended influenza strains 0, 1, 6, and 12 m post-vaccination. The serological evidence of influenza infections were defined as the increase of HI titer (HI ≥1:40 and 4-fold rise). The seroprotection rates for strains A(H1N1), A(H3N2), and B were 91.2%, 87.6%, and 87.6%, respectively, at 1 month (n = 174). These rates were 76.5%, 64.7%, and 54.6%, respectively, at 12 m. The seroprotection rates and GMTs for influenza A(H1N1) and A(H3N2) were higher at 12 m than at 0 m (p < 0.05) but not for B. There were 39 subjects (42 cases) of serological influenza infections. Subjects with seroprotection at 1 m post-vaccination had showed fewer serologic A(H1N1) (10.1 vs 54.5%) and A(H3N2) (7.2 vs 38.1%) infections than the ones with HI titer <1:40 during follow-up (P < 0.01). In conclusion, influenza vaccines used during the 2008-09 season induced adequate 1-y immunogenicity for A(H1N1) and A(H3N2). The immunogenicity at one month after vaccination influenced further serological influenza infections.

Clinical Practice Guideline of Acute Respiratory Distress Syndrome.

There is no well-stated practical guideline for mechanically ventilated patients with or without acute respiratory distress syndrome (ARDS). We generate strong (1) and weak (2) grade of recommendations based on high (A), moderate (B) and low (C) grade in the quality of evidence. In patients with ARDS, we recommend low tidal volume ventilation (1A) and prone position if it is not contraindicated (1B) to reduce their mortality. However, we did not support high-frequency oscillatory ventilation (1B) and inhaled nitric oxide (1A) as a standard treatment. We also suggest high positive end-expiratory pressure (2B), extracorporeal membrane oxygenation as a rescue therapy (2C), and neuromuscular blockage for 48 hours after starting mechanical ventilation (2B). The application of recruitment maneuver may reduce mortality (2B), however, the use of systemic steroids cannot reduce mortality (2B). In mechanically ventilated patients, we recommend light sedation (1B) and low tidal volume even without ARDS (1B) and suggest lung protective ventilation strategy during the operation to lower the incidence of lung complications including ARDS (2B). Early tracheostomy in mechanically ventilated patients can be performed only in limited patients (2A). In conclusion, of 12 recommendations, nine were in the management of ARDS, and three for mechanically ventilated patients.

The priming effect of previous natural pandemic H1N1 infection on the immunogenicity to subsequent 2010-2011 influenza vaccination in children: a prospective cohort study.

BACKGROUND: The effect of previous natural pandemic H1N1 (H1N1 pdm09) influenza infection on the immunogenicity to subsequent inactivated influenza vaccination in children has not been well studied. We aimed to evaluate the effect of H1N1 pdm09 natural infection and vaccination on the immunogenicity to subsequent 2010-2011 seasonal inactivated influenza vaccination in children. METHODS: From October 2010 to May 2011, we conducted an open-label, multi-center study in children aged 6 months -18 years in Korea. We measured antibody titers with a hemagglutination-inhibition (HI) assay at baseline, 1 month, and 6 months after vaccination with trivalent split or subunit vaccines containing H1N1 pdm, A/H3N2, and B. The subjects were classified into 4 groups depending on the presence of laboratory-confirmed H1N1 pdm09 infection and/or vaccination in the 2009-2010 season; Group I: vaccination (-)/infection(-), Group II: vaccination (-)/infection(+), Group III: vaccination (+)/infection(-), Group IV: vaccination (+)/infection(+). RESULTS: Among the subjects in group I, 47 subjects who had a baseline titer >1:10 were considered to have an asymptomatic infection. They were included into the final group II (n = 80). We defined the new group II as the infection-primed (IP) group and group III as the vaccine-primed (VP) group. Seroconversion rate (57.5 % vs 35.9 %, p = 0.001), seroprotection rate at 6 months after vaccination (70.8 % vs 61.8 %, p = 0.032), and GMT at 1 month after vaccination (129.9 vs 66.5, p = 0.002) were significantly higher in the IP group than in the VP group. In the 9-18 year-old group, seroconversion rate and immunogenicity at 1 and 6 months were significantly higher in the IP group than in the VP group. However in the 1-7 year-old age group, there was no significant difference between the two groups. CONCLUSIONS: Previous H1N1 pdm09 infection appears to have positive effects on immunogenicity of subsequent inactivated influenza vaccines against H1N1 pdm09 in older children.

Fulminant hepatitis linked to dapsone hypersensitivity syndrome requiring urgent living donor liver transplantation: a case report.

Dapsone is a sulfone-type drug used widely for different infectious, immune, and hypersensitivity disorders as an antibacterial treatment alone or in combination for leprosy and sometimes for infected skin lesions. DHS is a severe idiosyncratic adverse reaction with multi-organ involvement. However, acute necrotic hepatitis requiring an emergent LT is rare. Herein, we report a case of 12-yr-old girl who suffered from fulminant hepatitis and multi-organ failure due to DHS for PPD. She was saved by emergent LDLT. A high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal but rare disease.

Comparison of immune response by virus infection and vaccination to 2009 pandemic influenza A/H1N1 in children.

We aimed to compare the immune response induced by natural infection with 2009 pandemic influenza A/H1N1 (pH1N1) virus and by monovalent pH1N1 vaccination in children and adolescents. This cross-sectional clinical study was conducted at 3 hospitals in Korea from February to May 2010. A total of 266 healthy subjects aged from 6 months to 18 yr were tested for the presence of the antibody against pH1N1 using hemagglutination inhibition (HI) test. Information about pH1N1 vaccination and laboratory-confirmed pH1N1 infection history was obtained. The overall rate of HI titers of ≥ 1:40 against pH1N1 was 38.7%, and the geometric mean titer (GMT) was 20.5. Immunogenicity of pH1N1 vaccination only was reflected by a 41.1% of seroprotection rate and a GMT of 22.5. Immunogenicity of natural infection only was reflected by a 61.0% of seroprotection rate and a GMT of 40.0. GMT was significantly higher in the subjects of natural infection group than in the subjects of pH1N1 vaccination group (P < 0.001). The immune responses induced by natural pH1N1 infection exceed those induced by pH1N1 vaccinations.

Comparison of immunogenicity and reactogenicity of split versus subunit influenza vaccine in Korean children aged 6-35 months.

BACKGROUND: Studies comparing the immunogenicity and reactogenicity of trivalent inactivated subunit (SU) and split (SPL) vaccines in children in Asia are limited. In 2008, we assessed the safety and immunogenicity of SU and SPL influenza vaccines in Korean children aged 6-35 months. METHODS: We studied 2 non-randomized cohorts of children who received either SU or SPL vaccine in an open-label non-stratified controlled trial at 6 hospitals in Korea. We measured antibody titers with a hemagglutination-inhibition assay at baseline and 30 days after the first or second flu shot. The primary goal was the determination of vaccine immunogenicity according to the European Union Committee of Human Medicinal Products licensing criteria. RESULTS: Out of a total of 106 participants aged 6-35 months, 47 received the SPL vaccine and 59 the SU vaccine. After vaccination, 41 (87.2%), 40 (85.1%), and 33 (70.2%) of the 47 subjects in the SPL group had titers ≥ 1:40 against H1N1, H3N2, and B, respectively. In the SU group, 42 (71.2%), 34 (57.6%), and 22 (37.3%) of 59 subjects had titers ≥ 1:40 against H1N1, H3N2, and B, respectively. The post-vaccination geometric mean titers of H1N1, H3N2, and B (SPL vs SU) were 119.1, 99.8, and 61.4 vs 75.4, 51.2, and 24.1, respectively. There were no serious vaccine-related adverse events. There were no differences between the SPL and SU vaccines with respect to adverse events. CONCLUSIONS: The immunogenicity of the SPL vaccine appears to be better than that of the SU vaccine in children aged 6-35 months in Korea.

A case of hypersensitivity to mosquito bites without peripheral natural killer cell lymphocytosis in a 6-year-old Korean boy.

Hypersensitivity to mosquito bites (HMB) is a rare disease characterized by intense skin reactions such as bulla and necrotic ulcerations at bite sites, accompanied by general symptoms such as high-grade fever and malaise occurred after mosquito bites. It has been suggested that HMB is associated with chronic Epstein-Barr virus (EBV) infection and natural killer (NK) cell leukemia/lymphoma. We describe here a Korean child who presented with 3-yr history of HMB without natural killer cell lymphocytosis. He has been ill for 6 yr with HMB. Close observation and examination for the development of lymphoproliferative status or hematologic malignant disorders is needed.

Evaluation of immunogenicity of the 2008-2009 seasonal influenza vaccines by microneutralization test.

PURPOSE: For evaluating the immunogenicity of an influenza vaccine, the microneutralization (MN) test has a higher sensitivity and specificity as compared to the hemagglutination inhibition (HI) test. However, the MN test is more time consuming and is difficult to standardize. We performed the MN test to determine its usefulness as an alternative or complementary test to the HI test for evaluating the immunogenicity of influenza vaccines. METHODS: We compared the MN test with the HI test using 50 paired samples taken from a previous clinical study (2008-2009) in Korean children under 18 years of age. RESULTS: The linear correlation coefficients of the 2 tests for H3N2, H1N1, and influenza B were 0.69, 0.70, and 0.66, respectively. We identified a high index of coincidence between the 2 tests. For an influenza vaccine, the postvaccination seroprotection rates and seroconversion rates determined by the MN test were 78.0% and 96.0%, 90% and 42.0%, and 42.0% and 48.0% for H3N2, H1N1, and influenza B, respectively. Geometric mean titer fold increases of H3N2, H1N1, and influenza B were 2.89, 5.04, and 4.29, respectively, and were 2.5-fold higher. We obtained good results in the evaluation of the immunogenicity of the 2008-2009 seasonal influenza vaccines. CONCLUSION: We found that the MN test was as effective as the HI test. Therefore, we suggest that the MN test can be used as an alternative or complementary test to the HI test for evaluating the immunogenicity of influenza vaccines.

Bronchial hyperresponsiveness in adolescents with long-term asthma remission: importance of a Family history of bronchial hyperresponsiveness.

BACKGROUND: The mechanisms responsible for bronchial hyperresponsiveness (BHR) in symptomatic asthma include genetic predisposition and airway inflammation, but the causes of BHR in adolescents with asthma remission are poorly understood. It has been shown that BHR in adolescents with asthma remission was not reduced by prolonged treatment with inhaled corticosteroids, in contrast to the BHR of symptomatic asthma. OBJECTIVE: The aim of this study was to investigate whether family history of BHR may contribute to the persistence of BHR in asthma remission during adolescence. METHODS: One hundred twenty-six adolescents with long-term asthma remission (neither symptoms nor any medication used during the previous 2 years) and their parents underwent a methacholine inhalation test. The provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)) and the bronchial responsiveness (BR) index were calculated for each individual. RESULTS: Sixty-nine adolescents (54.8%) were found to have persisting BHR (PC(20) < 18 mg/mL). The frequency of BHR and the BR index were significantly higher in parents (n = 138) of the BHR-persisting group (28.3% and 1.150 +/- 0.103, respectively [mean +/- 1 SD]) than in parents (n = 114) of BHR-nonpersisting group (16.7% [p = 0.030] and 1.124 +/- 0.088 [p = 0.029], respectively). Furthermore, adolescents (n = 56) with at least one BHR-positive parent were found to have a higher frequency of BHR (66.1% vs 45.7%, p = 0.023) and a higher BR index (1.244 +/- 0.090 vs 1.204 +/- 0.082, p = 0.011) than adolescents (n = 70) with non-BHR parents. CONCLUSION: Our results suggest that adolescents in asthma remission are more likely to have BHR when there is a family history of BHR. Further studies are needed to examine the possible involvement of genetic factors in the BHR of adolescents in asthma remission.