PURPOSE: Immunological mechanisms underlying asthma exacerbation have not been elucidated. The aim of this study was to assess the associations of various asthma exacerbation traits with selected serum microRNA (miRNA) expression and T-cell subpopulations. METHODS: Twenty-one asthmatics were studied during asthma exacerbation (exacerbation visit [EV] and the follow-up visit [FV] at 6 weeks). At both visits, spirometry was performed, fractional exhaled nitric oxide (FeNO) was measured, and nasopharyngeal and blood samples were collected. In nasopharyngeal samples, respiratory viruses were assayed by multiplex polymerase chain reaction (PCR), and bacterial cultures were performed. Serum miRNAs were assayed with real-time PCR. T-cell surface markers, eosinophil progenitors and intracellular cytokines were assessed by flow cytometry. RESULTS: Two-thirds of patients had moderate or severe exacerbation and the FV, overall improvement in asthma control was observed. The mean expression of serum miRNA-126a, miRNA-16 and miRNA-21 was significantly lower at the EV than at the FV. At EV, miRNA-29b correlated with FeNO (r = 0.44, P < 0.05), and 5 of 7 miRNA tested correlated with pulmonary function tests. The number of cluster of differentiation (CD)45+CD4+interleukin (IL)4+ cells was significantly higher at the EV than at the FV, and positive correlations of T-regulatory cells and eosinophil progenitors with asthma control was found. At the EV, serum miRNAs negatively correlated with the number of T cells expressing IL-4, IL-17, IL-22 and interferon gamma, while at the FV both positive and negative correlations with T-cell subsets were observed. No association of detected pathogen (viruses and bacteria) in nasopharyngeal fluid with clinical, functional and immunological parameters was found. CONCLUSIONS: Epigenetic dysregulation during asthma exacerbation could be related to respiratory function, airway inflammation and T-cell cytokine expression.
Asthma ; Cytokines ; Disease Progression ; Eosinophils ; Epigenomics ; Flow Cytometry ; Follow-Up Studies ; Humans ; Inflammation ; Interferons ; Interleukin-17 ; Interleukin-4 ; MicroRNAs ; Multiplex Polymerase Chain Reaction ; Nitric Oxide ; Real-Time Polymerase Chain Reaction ; Respiratory Function Tests ; Spirometry ; T-Lymphocyte Subsets ; T-Lymphocytes

BACKGROUND: The incidence of asthma exacerbation (AE) and the predictive value of spirometry and fractional exhaled nitric oxide (FeNO) in school children have not been evaluated.OBJECTIVE: We sought to evaluate the efficacy of spirometry measurement and FeNO monitoring for predicting AE in school children in the Cheongju area in Korea.METHODS: With parental agreement, we studied 170 students aged 7–12 years. Children were evaluated by an asthma specialist using baseline spirometry, skin prick test, seasonal FeNO measurement, and asthma control test. The study participants underwent a physical examination and their medical history was also evaluated by the specialist. They were assessed for asthma control status during regular doctor visits for 1 year.RESULTS: In total, 160 children (94.1%) completed follow-up and FeNO monitoring. Of which, 26 children (16.3%) had AE. AE was associated with male children and children with allergic rhinitis (p < 0.05). While, children with AE tended to have higher FeNO than those without AE, no significant difference was found. The maximum value of FeNO ≥35 ppb was associated with AE (p < 0.05). Children with AE had a significantly decreased baseline forced expiratory volume in 1 second/forced vital capacity (FEV₁/FVC), %predicted, forced expiratory flow at 25%–75% of FVC (FEF(25%–75%)). FEV₁/FVC < 80% was associated with AE in children regardless of inhalant allergen sensitization (all p < 0.05).CONCLUSION: Baseline spirometry had a predictive value of AE in school children. Sensitive spirometric parameters such as FEV₁/FVC and FEF(25%–75%) can be used as prognostic factors to predict future childhood AE. FeNO value ≥ 35 ppb during monitoring was associated with AE in school children.
Asthma ; Child ; Chungcheongbuk-do ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Incidence ; Korea ; Male ; Nitric Oxide ; Parents ; Physical Examination ; Rhinitis, Allergic ; Seasons ; Skin ; Specialization ; Spirometry ; Vital Capacity

BACKGROUND: A reliable objective tool using as a predictor of asthma control status could assist asthma management.OBJECTIVE: To find the parameters of forced oscillation technique (FOT) as predictors for the future loss of asthma symptom control.METHODS: Children with well-controlled asthma symptom, aged 6–12 years, were recruited for a 12-week prospective study. FOT and spirometer measures and their bronchodilator response were evaluated at baseline. The level of asthma symptom control was evaluated according to Global Initiative for Asthma.RESULTS: Among 68 recruited children, 41 children (60.3%) maintain their asthma control between 2 visits (group C-C), and 27 children (39.7%) lost their asthma control on the follow-up visit (group C-LC). Baseline FOT parameters, including the values of respiratory resistance at 5 Hz (R5), respiratory resistance at 20 Hz (R20), respiratory reactance at 5 Hz, area of reactance, %predicted of R5 and percentage of bronchodilator response (%∆) of R5 and R20 were significantly different between C-C and C-LC groups. In contrast, only %∆ of forced vital capacity, forced expiratory volume in 1 second (FEV₁), and FEF25%–75% (forced expiratory flow 25%–75%) were significantly different between groups. Multiple logistic regression analysis revealed that %predicted of R5, %∆R5, %predicted of FEV₁ and %∆FEV₁ were the predictive factors for predicting the future loss of asthma control. The following cutoff values demonstrated the best sensitivity and specificity for predicting loss of asthma control: %predicted of R5=91.28, %∆R5=21.2, %predicted of FEV₁=89.5, and %∆FEV₁=7.8. The combination of these parameters predicted the risk of loss of asthma control with area under the curve of 0.924, accuracy of 83.8%.CONCLUSION: Resistance FOT measures have an additive role to spirometric parameter in predicting future loss of asthma control.
Asthma ; Child ; Follow-Up Studies ; Forced Expiratory Volume ; Humans ; Logistic Models ; Prospective Studies ; Sensitivity and Specificity ; Spirometry ; Vital Capacity

BACKGROUND/AIMS: Many systems including the cardiovascular system (ischemic heart diseases, heart failure, and hypertension) may act as comorbidities that can be seen during the course of chronic obstructive pulmonary disease (COPD). Comorbidities affect the severity and prognosis of COPD negatively. Nearly 25% of patients with COPD die due to cardiovascular diseases. In this study, we aimed to evaluate the relationship between the blood pressure, inflammation, hypoxia, hypercapnia, and the severity of airway obstruction. METHODS: We included 75 COPD patients in the study with 45 control cases. We evaluated age, sex, body mass index, smoking history, C-reactive protein levels, 24-hour ambulatory blood pressure Holter monitoring, arterial blood gas, and respiratory function tests of the patient and the control groups. RESULTS: In COPD patients, the night time systolic, diastolic blood pressures and pulse per minute and the mean blood pressures readings were significantly elevated compared to the control group (p < 0.05). In the correlation analysis, night time systolic pressure was associated with all the parameters except forced expiratory volume in 1 second (FEV₁%). Diastolic blood pressure was associated with pH and HCO₃ levels. The mean night time, day time pulse pressures and 24-hour pulse per minute values were also associated with all the parameters except FEV₁%. CONCLUSIONS: In this study we found that parameters of systolic and diastolic blood pressures and pulse pressures were significantly elevated in COPD patients compared to the control groups. Blood pressure was associated blood gas parameters and inflammation parameters in COPD patients. This, in turn, may cause understanding of the pathophysiology of COPD and its complications.
Airway Obstruction ; Anoxia ; Blood Pressure* ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cardiovascular System ; Comorbidity ; Electrocardiography, Ambulatory ; Forced Expiratory Volume ; Heart Diseases ; Heart Failure ; Humans ; Hydrogen-Ion Concentration ; Hypercapnia ; Inflammation* ; Prognosis ; Pulmonary Disease, Chronic Obstructive* ; Reading ; Respiratory Function Tests ; Smoke ; Smoking ; Spirometry*

Wheezing is one of the characteristic symptoms of asthma, but all preschool children with wheezing are not diagnosed with asthma. Preschool children are not cooperative enough to participate in spirometry and invasive tests. Thus, there is no conventional method to diagnose asthma in preschool children. We reviewed studies on non-invasive biomarkers for assessing asthma in preschool children. Specimens that can be easily obtained by non-invasive methods are blood, exhaled breath and urine. Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin (EDN) in blood are helpful in evaluating eosinophilic inflammation of the airways. Exhaled breath contains nitric oxide, volatile organic compounds, various cytokines and mediators as analytical components. Fraction of exhaled nitric oxide has been used to assess the degree of eosinophil inflammation and has been standardized in school-age children and adults, but not yet in preschool children. Exhaled breath condensate (EBC) pH and various cytokines/mediators that are detected in EBC seem to be promising biomarkers for assessing asthma, but need more standardization and validation. There are several biomarkers useful for assessing asthma, but none are ideal. Some biomarkers need standardized methods of obtaining samples from uncooperative preschool children for clinical use and require sufficient validation. Recently, another activated eosinophil marker, serum EDN, has shown promising results as a biomarker for recurrent wheezing and asthma in preschool children.
Adult ; Asthma* ; Biomarkers* ; Child ; Child, Preschool* ; Cytokines ; Eosinophil Cationic Protein ; Eosinophil-Derived Neurotoxin ; Eosinophils ; Humans ; Hydrogen-Ion Concentration ; Inflammation ; Methods ; Nitric Oxide ; Respiratory Sounds* ; Spirometry ; Volatile Organic Compounds

BACKGROUND: Vitamin D deficiency is associated with an increased risk of pulmonary tuberculosis (PTB) infection and the treatment outcome. The aim of this study was to examine the relationship between the serum 25-hydroxyvitamin D (25[OH]D) level and lung function in Korean adults according to whether or not there is a history of PTB. METHODS: The data for subjects aged 19 years or older from the Korea National Health and Nutrition Examination Survey 2008–2012 who underwent spirometry, chest radiography, and serum 25(OH)D level measurement were analyzed. RESULTS: Evidence of past PTB infection was found in 1,482 (9.6%) of 15,516 subjects. The serum 25(OH)D level was lower in the group with past PTB than in the non-PTB group (P=0.013). Respiratory dysfunction was more common in the past PTB group than in the non-PTB group (restrictive pattern, 14.0% vs. 9.6%; obstructive pattern, 29.6% vs. 8.2%; both P<0.001). After adjusting for age, sex, height, and season, the mean difference in forced expiratory volume in 1 second (FEV1) between the highest and lowest quartiles of 25(OH)D was 100.2 mL (standard error= 49.3 mL, P for trend=0.049) in the past PTB group and 34.7 mL (standard error=13.6 mL, P=0.009) in the non-PTB group. CONCLUSION: FEV1 tended to increase as the vitamin D quartile increased in both study groups. This relationship was more pronounced in subjects with a history of PTB. A higher serum 25(OH)D level might be beneficial in preserving lung function after PTB infection.
Adult ; Forced Expiratory Volume ; Humans ; Korea ; Lung ; Mass Chest X-Ray ; Nutrition Surveys ; Radiography ; Seasons ; Spirometry ; Thorax ; Treatment Outcome ; Tuberculosis ; Tuberculosis, Pulmonary ; Vitamin D ; Vitamin D Deficiency

Central hypoventilation syndrome is a rare and fatal condition resulting from various central nervous system disorders that is characterized by a failure of automatic breathing. We report a case of central hypoventilation syndrome following posterior circulation stroke whose pulmonary function was improved by respiratory rehabilitation. A 59-year-old woman with a history of hemorrhagic stroke of the bilateral cerebellum was hospitalized due to pneumonia. A portable ventilator was applied via tracheostomy, recurrent episodes of apnea and hypercapnia impeded weaning. A respiratory rehabilitation program including chest wall range of motion exercise, air stacking exercise, neuromuscular electrical stimulation (NMES) on abdominal muscles, upper extremity ergometer, locomotor training, high-frequency chest wall oscillator, mechanical insufflation, and exsufflation was employed, as spirometry showed a severe restrictive pattern. A spontaneous breathing trial was started, and a portable ventilator was applied for 8 hours, only during nighttime, to prevent sudden apneic event. After 4 weeks of treatment, follow-up spirometry showed much improved respiratory parameters. This case suggests that respiratory rehabilitation can improve pulmonary function parameters and quality of life in central hypoventilation syndrome.
Abdominal Muscles ; Apnea ; Central Nervous System Diseases ; Cerebellum ; Electric Stimulation ; Female ; Follow-Up Studies ; Humans ; Hypercapnia ; Hypoventilation ; Insufflation ; Middle Aged ; Pneumonia ; Quality of Life ; Range of Motion, Articular ; Rehabilitation ; Respiration ; Respiratory Center ; Spirometry ; Stroke ; Thoracic Wall ; Tracheostomy ; Upper Extremity ; Ventilators, Mechanical ; Weaning

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.
Allergens ; Animals ; Asthma ; Bronchial Provocation Tests ; Cats ; Child ; Cohort Studies ; Dogs ; Humans ; Infant ; Korea ; Medical Records ; Methacholine Chloride ; Odds Ratio ; Ownership ; Parturition ; Pets ; Prevalence ; Protective Factors ; Respiratory Sounds ; Risk Factors ; Skin ; Spirometry

PURPOSE: Assessing asthma control is important for proper management, and various indices for objective assessment of asthma control, such as fractional exhaled nitric oxide (FeNO) and asthma control test (ACT) score have been proposed. Recently, bronchodilator response (BDR) was reported as a marker of poor asthma control in adults. This study aimed to assess the usefulness of BDR as a biomarker for childhood asthma. METHODS: A total of 305 children diagnosed with asthma were included. Spirometry with bronchodilator test was done at the time of diagnosis and about 14 months after asthma treatment. All children were evaluated by childhood asthma control test (c-ACT) and FeNO after asthma treatment. The patients were divided into 2 groups according to BDR results: the positive and negative BDR groups. Various biomarkers for asthma control, such as c-ACT, FeNO and changes of forced expiratory volume in 1 second (FEV1), were compared between the 2 groups. RESULTS: Of the 305 patients, 143 (46.9%) were positive and 162 (53.1%) were negative for BDR. The BDR-positive group showed lower FEV1. In the BDR positive group, FEV1 was significantly increased after asthma treatment, especially in children with airflow limitation which was defined as below 80% of FEV1 or atopy. In atopic children, BDR showed a significant negative correlation with c-ACT and a positive correlation with FeNO. CONCLUSION: In asthmatic children with airflow limitation at the time of diagnosis, BDR can be a useful index for predicting improvement in lung function by asthma maintenance treatment. BDR could be a reliable marker for the assessment of asthma control in atopic children.
Adult ; Asthma ; Biomarkers ; Child ; Diagnosis ; Forced Expiratory Volume ; Humans ; Lung ; Nitric Oxide ; Spirometry

BACKGROUND: Long-term management of bronchial asthma based on the fractional exhaled nitric oxide (FeNO) value alone is not conclusive yet. Therefore, we combined FeNO testing and spirometry, a commonly used test in routine practice, to evaluate acute exacerbation and respiratory function in children with bronchial asthma. OBJECTIVE: We combined FeNO testing and spirometry, commonly used in routine practice, to evaluate acute exacerbations and respiratory function in children with bronchial asthma. METHODS: Subjects were school aged children 7 years and older with bronchial asthma who underwent FeNO testing in January 2015 to May 2016. We evaluated the changes in the frequency of acute exacerbations and respiratory function in the 30 subsequent months. Subjects were divided into 2 groups: those with initial FeNO levels ≥ 21 parts per billion (ppb) (high FeNO) and < 20 ppb (normal FeNO) groups. RESULTS: There were 48 children (33 boys) in the high FeNO group and 68 children (46 boys) in the normal FeNO group. Spirometry was conducted on 83 children (72%) prior to the initial FeNO test, revealing no difference in the ratio of detecting lung dysfunction between the 2 groups. The observation period was 25.8 ± 0.7 and 24.7 ± 0.6 months for the high and normal FeNO groups, respectively. The children in the high FeNO group with lung dysfunction in the initial FeNO test continued to exhibit lung dysfunction at the test at 30 months. In the normal FeNO group, even if lung dysfunction was observed at the initial FeNO, it improved within the 20-month point, and the improvement was maintained thereafter. CONCLUSION: Children with bronchial asthma with high FeNO levels and lung dysfunction are at a higher risk of prolonged lung dysfunction.
Asthma ; Child ; Humans ; Lung ; Nitric Oxide ; Spirometry