• Tuberculosis and Respiratory Diseases
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• v.49 no.1
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• pp.37-48
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• 2000

Backgrounds : The pathophysiology of chronic airflow obstruction, such as bronchial asthma, is characterized by mucus hypersecretion, goblet cell hyperplasia(GCH), smooth muscle hypertrophy, and inflammatory cells infiltration. In fatal asthma patients, one distinct findings is mucus hypersecretion due to GCH. However, the mechanisms of GCH in these hypersecretory diseases remain still unknown. In this study, a rat model was rapidly induced with GCH by instillation of $TiO_2$, intratracheally. We intend to confirm GCH and association of concomitant inflammatory cells infiltration and to observe the effect of potent antiinflammatory agent, that is dexamethasone, on GCH with inflammatory cells. Methods : Twenty-one 8-weeks-old male Sprague-Dawley rats were divided into three groups. Endotoxinfree water was instilled intratracheally in group 1(control) ; $TiO_2$, was instilled in the group 2 ; and dexamethasone was injected intraperitoneally to group 3 before $TiO_2$ instillation. After 120 hours, all rats were sacrificed, and trachea, bronchi, and lungs were resected respectively. These tissues were made as paraffin blocks and stained as PAS for goblet cells and Luna stain for eosinophils. We calculated the ratio of goblet cell to respiratory epithelium and number of infiltrated eosinophils from each tissue. Results : (1) Fraction of goblet cells was significantly increased in group 2 than in group 1 in the trachea and in the main bronchus. (10.19$\pm$11.33% vs 4.09$\pm$8.28%, p<0.01 and 34.09$\pm$23.91% vs 3.61$\pm$4.84%, p<0.01, respectively). (2) Eosinophils were significantly increased in the airway of group 2 than that of group 1. (5.43$\pm$3.84% vs 0.17$\pm$0.47 in trachea and 47.71$\pm$16.91 vs 2.71$\pm$1.96 in main bronchi). (3) There was a positive correlation between goblet cells and eosinophils(r=0.719, p=0.001). (4) There was significant difference in the decrease of goblet cells after dexamethasone injection between group 2 and group 3 (p<0.01). Also, infiltration of eosinophils was suppressed by dexamethasone. Conclusion : We made an animal model of $TiO_2$-induced goblet cell hyperplasia. GCH was observed mainly in the main bronchi with concomitant eosinophilic infiltration. Both goblet cell hyperplasia and eosinophilic infiltration were suppressed by dexamethasone. This animal model may serve as a useful tool in understanding of the mechanism of GCH in chronic airway diseases.

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.521-530
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• 1994

Background : The past studies on prediction formulas of pulmonary function parameters in healthy nonsmoking Korean adults have been performed in relatively small number of subjects and the reported results were restricted on a few parameters. Also there was no systematic investigation into the effect of smoking on pulmonary function parameters in smokers who have no respiratory symptoms. Therefore we attempted to establish prediction formulas of pulmonary function parameters and examined the effect of smoking on pulmonary function parameters. Methods We analyzed the result of parameters derived from the forced expiratory spirogram in 1,067 nonsmoking subjects from June in 1990 to December in 1991. They consisted of 306 males and 761 females and had neither respitatory symptoms nor history of respiratory disease. We derived prediction formulas by multiple linear regression method from their age, heights, and weights in each sex. To examine the effect of smoking on pulmonary function parameters, we classified 383 smoking men into three groups according to the past amount of smoking as follows : i.e. group of smokers who have smoked below 10 pack-years, 10-20 pack-years and above 20 pack-years. Regarding each group of past smoking as an independent dummy variable, we analyzed pulmonary function parameters including nonsmoking men as a baseline by multiple linear regression. We evaluated the smoking effect on pulmonary function parameters according to estimated p-value. Result : 1) Prediction formulas for pulmonary function parameters in each sex were derived. 2) The past smoking less than 10 pack-years does not give any effect on pulmonary function parameters. The past smoking of 10~20 pack-years showed significant negative correlation with $FEV_1$/FVC and FEF 25~75%, and the smoking above 20 pack years showed negative correlation with $FEV_1$ and $FEV_1$/FVC. Conclusion : We have got prediction formulas of pulmonary function parameters which is driven from forced expiratory spirogram in nonsmoking Korean adults by multiple linear regression from age, heights and weights of subjects. The past smoking more than 10 pack-years showed negative correlation with some pulmonary function parameters of airflow obstruction.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.103-110
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• 1994

To find out the predictors of nocturnal arterial oxygen desaturation in patients with respiratory diseases, transcutaneous oxygen saturation($StcO_2$) monitoring studies using a pulse oximeter were performed during sleep in 20 patients. $StcO_2$ was decreased more than 4% from the baseline value in 18 patients(90%) and more than 10%("Desaturator") in 8(40%). Five of the seven patients(71.4%) with awake $PaO_2$<60mmHg and three of the thirteen patients(23.1%) with awake $PaO_2{\geq}60mmHg$ were "desaturators". The awake $PaO_2/FIO_2$ and $PaO_2/PAO_2$ could distinguish "desaturator" from "nondesaturator", and $PaO_2,\;SaO_2$ or $StcO_2$ could not. These results suggest that the nocturnal oxygen desaturation depends on the severity of the underlying disease rather than the baseline $PaO_2$. Anthropomorphic and lung function factors could not separate between "desaturator" and "non-desaturator", and about a quater of patients with a wake $PaO_2{\geq}60mmHg$ developed significant desaturation. Therefore, it is necessary to monitor the nocturnal arterial oxygen saturation in patients with respiratory diseases regardless of their severity of airflow obstruction or awake $PaO_2$.

• Tuberculosis and Respiratory Diseases
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• v.50 no.3
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• pp.320-333
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• 2001

Background : Peak expiratory flow (PEF) provides a simple, quantitative, and reproducible measure of the existence and severity of airflow obstructions. Peak flow meters are designed to monitor the condition asthma patients. There are many reports showing the normal predicted value of PEF in other countries. Studies on healthy Korean adults have been performed in a relatively small sample number and a lower limit for the normal value was not reported. Therefore, an attempt to provide normal predictive PEF value with a lower limit was made. Method : The PEF(Mini-Wright Peak Flow Meter) measurements and spirometry were done in 233 men and 631 women without history of respiratory disease. All subjects were non-smokers with no respiratory symptoms. The normal predictive value and its lower limit were developed by multiple regression analysis. The result was compared with regression equations in other reports. Results : The regression equation for the normal PEF predictive value(L/min) is $25.117+4.587{\times}$Age(year)-$0.064{\times}Age^2+2.931{\times}$Height(cm) in men($R^2=025$), and 146.942-$0.011{\times}Age^2+1.795{\times}$Height(cm)+$0.836{\times}$Weight(kg) in women($R^2=0.21$). The regression equation for the lower limit of this value (L/min) is $25.117+4.587{\times}$Age(year)-$0.064{\times}Age^2+1.936{\times}$Height(cm) in men, and $146.942-0.011{\times}Age^2+1.232{\times}$Height(cm)+$0.481{\times}$Weight(kg) in women. The residuals were normally distributed. The PEF in Korean males was sililar to those reported in British and Japanese subjects. The PEF in Korean females was similar to that in British subjects, but higher than the PEF in Japanese subjects. The lower limit of normal value was 71% of normal predictive PEF value in men and 76% in women. Conclusion : The normal predictive PEF value and its lower limit was measured from 233 male and 631 female asymptomatic, lifelong non-smoking participants. The normal predictive value was different from those of other studies on Korean subjects. Therefore, further studies are required.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.77-89
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• 1998

Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.

• Tuberculosis and Respiratory Diseases
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• v.44 no.3
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• pp.559-573
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• 1997

Background : Asthma causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough. These symptoms are usually associated with widespread but variable airflow limitation that is partly reversible either spontaneously or with treatment. The inflammation also causes an associated increase in airway responsiveness to a variety of stimuli. Method : Of the 403 adult bronchial asthma patients enrolled from March 1992 to March 1994 in Allergy Clinics of Severance Hospital in Yonsei University, this study reviewed the 97 cases to evaluate the treatment effects and to analyse prognostic factors. The patients were classified to five groups according to treatment responses ; group 1 (non control group) : patients who were not controlled during following up, group 2 (high step treatment group) : patients who were controlled longer than 3 months by step 3 or 4 treatment of "Global initiative for asthma, Global strategy for asthma management and prevention" (NHLBI/WHO) with PFR(%) larger than 80%, group 3 (short term control group) : patients who were controlled less than 1 year by step 1 or 2 treatment of NHLBI/WHO, group 4 (intermediate term control group) : patients who were controlled for more than 1 year but less than 2 years by step 1 or 2 treatment of NHLBI/WHO, group 5 (long term control group) : patients who were controlled for more than 2 years by step 1 or 2 treatment of NHLBI/WHO. Especially the patients who were controlled more than 1 year with negatively converted methacholine test and no eosinophil in sputum were classified to methacholine negative conversion group. We reviewed patients' history, atopy score, total IgE, specific IgE, methacholine PC20 and peripheral blood eosinophil count, pulmonary function test, steroid doses and aggrevation numbers after treatment. Results : On analysis of 98 patients, 20 cases(20.6%) were classified to group 1, 26 cases(26.8%) to group 2, 23 cases(23.7%) to group 3, 15 cases(15.5%) to group 4, and 13 cases(13.4%) to groups 5. There were no differences of sex, asthma type, family history, smoking history, allergic rhinitis and aspirin allergy among the groups. In long term control group, asthma onset age was younger, symptom duration was shorter, and initial pulmonary function was better. The long term control group required lower amounts of oral steroid. had less aggrevation during first 3months after starting treatment and shorter duration from enrollment to control Atopy, allergic skin test, sputum and blood eosinophil, total IgE, nonspecific bronchial responsiveness was not significantly different among the groups. Seven out of 28 patients who were controlled more than 1 years showed negatively converted methachloine test and no eosinophils in the sputum. The mean control duration was $20.3{\pm}9.7$ months and relapse did not occur. Conclusion : Patients who had asthma of onset age younger, shorter symptom duration, better PFT, lower treatment initial steps, lower amounts of steroid needs and less aggravation numbers after starting treatment were classified in the long term control groups compared to the others.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.379-388
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• 1994

Background : In sleep apnea syndrome, arterial oxygen saturation($SaO_2$) decreases at a variable rate and to a variable degree for a given apneic period from patient to patient, and various kinds of cardiac arrythmia are known to occur. Factors supposed to affect arterial oxygen desaturation during apnea are duration of apnea, lung voulume at which apnea occurs, and oxygen consumption rate of the subject. The lung serves as preferential oxygen source during apnea, and there have been many reports related with the influence of lung volume on $SaO_2$ during apnea, but there are few, if any, studies about the influence of oxygen consumption rate of an individual on $SaO_2$ during breath holding or about the profile of arterial oxygen resaturation after breathing resumed. Methods : To investigate the changes of $SaO_2$ and heart rate(HR) during breath holding(BH) and rebreathing(RB) and to evaluate the physiologic factors responsible for the changes, lung volume measurements, and arterial blood gas analyses were performed in 17 healthy subjects. Nasal airflow by thermistor, $SaO_2$ by pulse oxymeter and ECG tracing were recorded on Polygraph(TA 4000, Gould, U.S.A.) during voluntary BH & RB at total lung capacity(TLC), at functional residual capacity(FRC) and at residual volume(RV), respectively, for the study subjects. Each subject's basal metabolic rate(BMR) was assumed on Harris-Benedict equation. Results: The time needed for $SaO_2$ to drop 2% from the basal level during breath holding(T2%) were $70.1{\pm}14.2$ sec(mean${\pm}$standard deviation) at TLC, $44.0{\pm}11.6$ sec at FRC, and $33.2{\pm}11.1$ sec at RV(TLC vs. FRC, p<0.05; FRC vs. RV, p<0.05). On rebreathing after $SaO_2$ decreased 2%, further decrement in $SaO_2$ was observed and it was significantly greater at RV($4.3{\pm}2.1%$) than at TLC($1.4{\pm}1.0%$)(p<0.05) or at FRC($1.9{\pm}1.4%$)(p<0.05). The time required for $SaO_2$ to return to the basal level after RB(Tr) at TLC was not significantly different from those at FRC or at RV. T2% had no significant correlation either with lung volumes or with BMR respectively. On the other hand, T2% had significant correlation with TLC/BMR(r=0.693, p<0.01) and FRC/BMR (r=0.615, p<0.025) but not with RV/BMR(r=0.227, p>0.05). The differences between maximal and minimal HR(${\Delta}HR$) during the BH-RB manuever were $27.5{\pm}9.2/min$ at TLC, $26.4{\pm}14.0/min$ at RV, and $19.1{\pm}6.0/min$ at FRC which was significantly smaller than those at TLC(p<0.05) or at RV(p<0.05). The mean difference of 5 p-p intervals before and after RB were $0.8{\pm}0.10$ sec and $0.72{\pm}0.09$ sec at TLC(p<0.001), $0.82{\pm}0.11$ sec and $0.73{\pm}0.09$ sec at FRC(p<0.025), and $0.77{\pm}0.09$ sec and $0.72{\pm}0.09$ sec at RV(p<0.05). Conclusion Healthy subjects showed arterial desaturation of various rates and extent during breath holding at different lung volumes. When breath held at lung volume greater than FRC, the rate of arterial desaturation significantly correlated with lung volume/basal metabolic rate, but when breath held at RV, the rate of arterial desaturation did not correlate linearly with RV/BMR. Sinus arrythmias occurred during breath holding and rebreathing manuever irrespective of the size of the lung volume at which breath holding started, and the amount of change was smallest when breath held at FRC and the change in vagal tone induced by alteration in respiratory movement might be the major responsible factor for the sinus arrythmia.