• Clinical and Experimental Pediatrics
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• v.51 no.8
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• pp.842-847
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• 2008

Purpose : Measurement of forced expiratory volume in 1 second ($FEV_1$) is usually difficult to obtain in children under six years of age because it requires active cooperation. This study evaluates the sensitivity of impulse oscillometry system (IOS) parameters for detecting airway obstruction in comparison with $FEV_1$. Methods : We studied 174 children who performed the lung function and methacholine challenge tests to diagnose asthma by IOS and spirometry. Children were divided into two subgroups according to their $PC_{20}$, which is a parameter for bronchial sensitivity. We compared IOS parameters with $FEV_1$ at the baseline, post-methacholine challenge, and evaluated their correlation. Results : At the baseline, reactance at 5 Hz (X5) and resistance at 5 Hz (R5) significantly differed between the $PC_{20}$ positive ($PC_{20}{\leq}16mg/mL$) group and $PC_{20}$ negative ($PC_{20}$ >16 mg/mL) group; however, $FEV_1$, $FEV_1$ % predicted, $FEV_1_-Zs$ (Z score) did not differ. $FEV_1$ is correlated with X5 (r=0.45, P<0.01) and R5 (r=-0.69, P<0.01). $FEV_1_-Zs$ is also correlated with X5_Zs (r=-0.26, P<0.01) and R5_Zs (r=-0.31, P<0.01). After the methacholine challenge test, dose-response slopes in $FEV_1$ and X5 significantly differed between the two subgroups (P<0.05). Conclusion : IOS parameters were more discriminative than $FEV_1$ for detecting decreased baseline lung function between two subgroups and have a good correlation with $FEV_1$.

• Tuberculosis and Respiratory Diseases
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• v.47 no.4
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• pp.517-524
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• 1999

Background : Airway inflammation and hyperresponsiveness are recognized as major characteristics of bronchial asthma. Airway inflammation has usually been assessed by invasive methods, e.g. BAL or bronchial biopsy, but recent studies proposed induced sputum as another reliable and non-invasive tool to investigate airway inflammation in asthmatic patients. Thus, the relationship between airway inflammation assessed by induced sputum and airway hyperresponsiveness was investigated in asthmatic patient. Method : Airway responsiveness was determined by the concentration that caused a 20% decrease in $FEV_1$($PC_{20}$) after inhaling incremental concentrations of methacholine. The numbers of inflammatory cells and the concentration of eosinophilic cationic protein(ECP) were assessed in induced sputum obtained by inhalation of hypertonic saline(3%). Result: We analyzed sputum induced in 15 stable asthmatic patients. The differential cell count(%) of macrophages, neutrophils, eosinophils and lymphocytes in induced sputum were $39.1{\pm}27.0%$, $29.6{\pm}21.0%$, $28.8{\pm}18.8%$, $1.3{\pm}3.1%$ respectively. The mean value of baseline FEV1(predicted) and ECP were $76.3{\pm}30.3%$ and $1,101{\pm}833{\mu}g/L$ respectively. The geometric mean value of $PC_{20}$ was 0.56 mg/mL. The relationships between the sputum eosinophil and ECP in induced sputum, and between sputum eosinophil and degree of airway responsiveness($PC_{20}$) were found to be significantly correlated (r=0.81, p<0.05 and r=-0.78, p<0.05, respectively). Sputum neutrophils and $PC_{20}$ were not correlated to each other (r=0.11, p=0.69) and a significant negative correlation was found between ECP and baseline $FEV_1$(predicted)(r=-0.62, p<0.05). Conclusion : The results of this study suggest that an induced sputum via a inhalation of hypertonic saline is useful to determine a patient's status of airway inflammation, and airway inflammation is one of the major causal factors in the development of bronchial hyperresponsiveness in asthmatic patients.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.486-494
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• 2000

Background : The dominant innervation of airway smooth muscle is parasympathetic fibers which are carried in the vagus nerve. Activation of these cholinergic nerves releases acetylcholine which binds to $M_3$ muscarinic receptors on the smooth muscle causing bronchocontraction. Acetylcholine also feeds back onto neuronal $M_2$ muscarinic receptors located on the postganglionic cholinergic nerves. Stimulation of these receptors further inhibits acetylcholine release, so these $M_2$, muscarinic receptors act as autoreceptors. Loss of function of these $M_2$ receptors, as it occurs in animal models of hyperresponsiveness, leads to an increase in vagally mediated hyperresponsiveness. However, there are limited data pertaining to whether there are dysfunctions of these receptors in patients with asthma. The aim of this study is to determine whether there are dysfunction of $M_2$ muscarinic receptors in asthmatic patients and difference of function of these receptors according to severity of asthma. Method : We studied twenty-seven patients with asthma who were registered at Pulmonology Division of Korea University Hospital. They all met asthma criteria of ATS. Of these patients, eleven patients were categorized as having mild asthma, eight patients moderate asthma and eight patients severe asthma according to severity by NAEPP Expert Panel Report 2(1997). All subjects were free of recent upper respiratory tract infection within 2 weeks and showed positive methacholine challenge test ($PC_{20}$<16mg/ml). Methacholine provocation tests were performed twice on separate days allowing for an interval of one week. In the second test, pretreatment with the $M_2$ muscarinic receptor agonist pilocarpine($180{\mu}g$) through inhalation was performed be fore the routine procedures. Results : Eleven subjects with mild asthma and eight subjects with moderate asthma showed significant increase of $PC_{20}$ from 5.30$\pm$5.23mg/ml(mean$\pm$SD) to 20.82$\pm$22.56mg/ml(p=0.004) and from 2.79$\pm$1.51mg/ml to 4.67$\pm$3.53mg/ml(p=0.012) after pilocarpine inhalation, respectively. However, in the eight subjects with severe asthma significant increase of $PC_{20}$ from l.76$\pm$1.50mg/ml to 3.18$\pm$4.03mg/ml(p=0.161) after pilocarpine inhalation was not found. Conclusion : In subjects with mild and moderate asthma, function of $M_2$ muscarinic receptors was normal, but there was a dysfunction of these receptors in subjects with severe asthma. ηlese results suggest that function of $M_2$ muscarinic receptors is different according to severity of asthma.

• Tuberculosis and Respiratory Diseases
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• v.61 no.2
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• pp.137-142
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• 2006

Background: Recent studies have suggested an association between chronic cough and gastroesophageal reflux. Our study aimed to assess the utility of a proton-pump inhibitor in unexplained chronic cough patients. Methods: Patients with chronic cough of unknown etiology were evaluated using a chest x-ray, methacholine challenge test, and an empirical trial of postnasal drip therapy. After excluding other potential causes of the cough, forty patients were included in the study and treated for 8 weeks with a proton-pump inhibitor. Results: Eleven and three patients in the first and second 4 weeks were lost to follow-up, leaving twenty-six patients finally included in the study. Of these patients, two were unimproved, eight partially responded to the proton-pump inhibitor and sixteen responded completely after the 8 week treatment. Conclusion: We suggest that empirical treatment with a proton pump inhibitor in all patients with persistent cough, which is not secondary to asthma or postnasal drip syndrome, represents a practical and simple approach to this ailment.

• Tuberculosis and Respiratory Diseases
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• v.46 no.4
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• pp.555-563
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• 1999

Background: Chronic cough is a common symptom that requires the systematic diagnostic approach for proper evaluation. Postnasal drip syndrome(PNDS), bronchial asthma, gastroesophageal reflux disease(GERD), and chronic bronchitis are among the common causes. This study was conducted to evaluate the spectrum and the frequency of the causes of chronic cough. Methods: We prospectively evaluated 93 patients who had chronic cough despite normal chest radiographic finding. History and physical examination were done along with paranasal sinus radiograph, spirometry, bronchoprovocation test and 24-hours' ambulatory aesophageal pH monitoring as necessary. Results: Forty-nine(52%) of the 93 patients had PNDS, 15 patients(16%) bronchitis, 10 patients(11%) asthma, 4 patients (4%) GERD, 7 patients (8%) both PNDS and asthma, 4 patients (4%) undiagnosed condition and 4 patients(4%) were taking ACE inhibitor. Sixty-nine percent of the patients with PNDS improved after follow up, 73% patients with bronchitis, 80% patients with asthma, 50% patients with GERD, 100% patients with both PNDS and asthma, and 100% patients with ACE inhibitor. Conclusion: PNDS was the most common causes of chronic cough. Bronchitis was the second and asthma the third in frequency. The etiology of chronic cough can be determined easily by history and physical examination, successful therapy initiated in most patients. The response to specific therapy also was important in evaluation of chronic cough.

• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.556-564
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• 2007

Purpose : We hypothesized that the persisting bronchial hyperresponsiveness (BHR) of adolescents with asthma remission may be controlled mainly by genetic factors, and the BHR of symptomatic asthma by airway inflammation. ${\beta}_2$-adrenoceptor gene is considered to be a candidate gene in the development of BHR. Thus, ${\beta}_2$-adrenoceptor gene polymorphism may be associated with the BHR of adolescents with asthma remission, but not with the BHR of symptomatic asthma. To evaluate this hypothesis, ${\beta}_2$-adrenoceptor gene polymorphism at 2 sites (Arg16-Gly, Gln27-Glu) were examined. Methods : Two hundred two adolescents with BHR ($PC_{20}<18\;mg/mL$) and long term remission (neither asthma-related symptoms nor medication during the previous 2 years) of their asthma (remission group), 182 adolescents with symptomatic asthma (symptomatic group), and 200 healthy adolescents (control group) were studied. Asthma phenotypes were determined using methacholine bronchial provocation test and skin prick test. Genotypes of ${\beta}_2$-adrenoceptor polymorphism were evaluated by PCR-based methods. Results : Gly/Gly allele and Gly16-Gln27 haplotype were more prevalent in the remission group than in the control group (P=0.01, P=0.02), although there was no difference between the symptomatic group and the control group. In the remission group, there was significant difference in geometric mean of $PC_{20}$ among the 3 groups subdivided by the number of Gly16-Gln27 haplotype, showing that the Gly16-Gln27 haplotype was positively associated with BHR. However, no association was found between Gly16-Gln27 haplotype and BHR in the symptomatic group. Conclusion : This study demonstrates that ${\beta}_2$-adrenoceptor polymorphism at amino acid 16 and 27 was associated with BHR persisting in adolescents with asthma remission.

• Clinical and Experimental Pediatrics
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• v.51 no.2
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• pp.181-187
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• 2008

Purpose : Asthma is characterized by reversible airway obstruction and bronchial hyperresponsiveness result from airway inflammation. Fraction of nitric oxide in expired air (FeNO) has recently been investigated as a noninvasive measure of airway inflammation. FeNO has been reported to correlate with induced sputum eosinophilia and methacholine challenge test that it is represent severity of asthma. The purpose of this study was to analyze the relationship of FeNO with pulmonary function tests in patients with intermittent asthma. Methods : Eighty children included in this study were diagnosed as asthma from April through August, 2005 in Department of Pediatrics, College of Medicine, Kyunghee University. They aged from 4 to 15 years who were able to conduct spirometry and FeNO monitoring. They did not have upper respiratory tract infection and did not use an asthma controller which contain corticosteroids within 4 weeks. Pulmonary function test was done and FeNO was measured with online tidal breathing method using a chemiluminescence NO analyzer (CLD 88 sp, Eco Medics, Duernten, Switzerland). The correlations between pulmonary function test and FeNO were analyzed using Spearman correlation coefficient method. Results : The mean of FeNO of subject was 16.88 parts per billion (ppb). The mean of forced expiratory volume in 1 second ($FEV_1$) was $0.890{\pm}0.455L$ and forced vital capacity (FVC) was $1.071{\pm}0.630L$. The mean of predicted $FEV_1%$ ($FEV_1%pred$) was $98.39{\pm}34.27%$ and $FEV_1/FVC$ was $88.53{\pm}19.49$. FeNO was significantly correlate with $FEV_1$ (r=0.345, P<0.01) and FVC (r=0.244, P<0.05). FeNO did not correlate with $FEV_1%pred$ or $FEV_1/FVC$. Conclusion : The measurement of FeNO could be a useful marker in the management of childhood asthma and it is evolving to provide a complementary role alongside existing pulmonary function test. We propose that measuring technique and establishment of normal reference range are important area for future research.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.875-883
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• 2002

Purpose : Airways eosinophilia and increased IgE, characteristic features of asthma, result from a predominant Th2 response. In this study, we investigated the effect of CpG oligodeoxynucleotides (ODNs) on the inhibition of airways eosinophilia in mice with established airway inflammation. We also investigated the immunological mechanisms involved. Methods : Groups of BALB/c mice were sensitized intradermally with ovalbumin(OVA). At week 10, airway inflammation was induced by intranasal challenge of the mice with OVA. At week 14, the mice were challenged intranasally again with OVA in the presence and without the presence of CpG ODNs. Mice with saline administration served as negative controls. Bronchoalveolar lavage fluids(BALF) were obtained and eosinophils were counted. Th1 and Th2 cytokines in the spleen cell cultures were measured by ELISA. Serum OVA-specific IgE and IgG2a antibodies were also measured by ELISA. Results : BALF eosinophils were significantly inhibited in the CpG ODNs-treated mice(P<0.01). IgE and IgG2a levels increased significantly in both CpG ODNs-treated and untreated groups as compared to the negative control group; there was, however, no significant difference between the two groups four days after intranasal administration of CpG ODNs. Cytokine analysis revealed decreased production of IL-4, IL-5, and IL-13 and increased production of IL-12 in the CpG ODNs-treated group as compared to the untreated group. Interestingly, $IFN-{\gamma}$ levels were not upregulated in the CpG ODNs-treated group. Conclusion : CpG ODNs vaccination is a potentially useful approach for reversing airways eosinophilia in mice with established airways inflammation.

• Tuberculosis and Respiratory Diseases
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• v.39 no.2
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• pp.159-166
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• 1992

Background:Sulfiting agents are widely used as preservatives and antioxidants in foods, beverages and drugs including bronchodilators. There have been reports of sulfite-related reactions such as anaphylaxis, urticaria, angioedema, abdominal discomfortness as well as bronchospasm. Several investigators reported that sulfite-sensitive asthmatic patients comprised from 3.9% to 8.2% of all asthmatic patients and its prevalence was higher in steroid-dependent group than in steroid-independent group. Subjects and Method:We performed oral provocation test with sodium bisulfite and aspirin in 17 asthmatic patients who have experienced aggravation of their symptoms after administration of drugs or foods. All of them were steroid dependent asthmatics. We observed clinical symptoms and steroid requirements from 1 to 18 months. Result:Ten of them showed severe bronchoconstriction after the ingestion of sodium bisulfite (50 to 200 mg) within 30 minutes. Concurrent aspirin intolerance was noted by oral provocation test in four cases (40%). Three of them showed positive responses on skin prick test with sulfite (10 or 100 mg/ml). Mean total eosinophil counts was $844/mm^3$ at asthmatic attack. And there was no significant responses on skin prick test and IgE-RAST to common inhalant allergens. After complete avoidance from sulfite containing foods and drugs as well as antiasthmatic medication for 1 to 18 months, nine of them (90%) could stop or reduce the steroid requirements. ConcIusion:It was suggested that severe steroid dependent and intrinsic type of asthmatic patients should be evaluated for sulfite-sensitivity.

• Tuberculosis and Respiratory Diseases
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• v.57 no.5
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• pp.425-433
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• 2004

Background : Induction of oral tolerance (OT) has been known to prevent allergic inflammation in acute asthma model within 4 weeks. However it is remained whether induction of OT may effectively prevent allergic inflammation in chronic asthma model over 4 weeks. We observed the effect of induction of OT on allergic inflammation and airway remodeling in chronic asthma model up to 8 weeks. Methods : 5-week-old female BALB/c mice divided into 4 groups-control group, asthma group, low dose OT group, and high dose OT group. To induce oral tolerance mice were fed ovalbumin (OVA) before sensitization with OVA and aluminum hydroxide-1 mg for 6 consecutive days in the low dose OT group and 25 mg once in the high dose OT group. Mice in the asthma group were fed phosphate buffered saline instead of OVA. After sensitization followed by repeated challenge with aerosolized 1% OVA during 6 weeks, enhanced pause (Penh), inflammatory cells, IL-13, and IFN-${\gamma}$ levels in bronchoalveolar lavage (BAL) fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum were measured. In addition the degree of goblet cell hyperplasia and peribronchial fibrosis were observed from lung tissues by PAS and Masson's trichrome stain. Results : Both OT groups showed a significant decrease in Penh, inflammatory cells, IL-13, and IFN-${\gamma}$ levels in BAL fluids as well as OVA-specific IgE, IgG1, and IgG2a levels in serum compared with the asthma group (P<0.05). In addition, the degree of goblet cell hyperplasia and peribronchial fibrosis were significantly attenuated in both OT groups compared with the asthma group (P<0.01). Conclusion : These results suggest that induction of OT may effectively prevent allergic inflammation as well as airway remodeling even in chronic asthma model up to 8 weeks.