• Tuberculosis and Respiratory Diseases
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• v.71 no.2
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• pp.106-113
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• 2011

Background: While asthma control is defined as the extent to which the various manifestations of asthma are reduced by treatment, current guidelines of asthma recommend assessment of asthma control without consideration of airway inflammation. Our aim was to investigate the relationships between fractional exhaled nitric oxide (FeNO), a reliable marker of airway inflammation, and levels of asthma control in patients treated with inhaled corticosteroids (ICS). Methods: We enrolled 71 adult patients with asthma who had been treated with ICS for more than four months. FeNO was measured and spirometry was performed at the time of enrollment. Asthma control was assessed (a) by the physician based on the Global Initiative for Asthma guidelines, (b) by the patients, and (c) by using the Asthma Control Test (ACT). Statistical analyses were done to analyze the relationships between (i) FeNO and (ii) measures of asthma control and clinical indices for asthma manifestations. Results: There was no significant difference in FeNO levels between the three groups according to levels of asthma control (controlled, partly controlled and uncontrolled) as determined by the physician (p=0.81), or by the patients (p=0.81). In addition, FeNO values were not significantly correlated with the ACT scores (r=0.031, p=0.807), while FeNO showed a correlation with peripheral blood eosinophil counts (p<0.001). Conclusion: These findings demonstrate that FeNO levels are not associated with measures of asthma control in patients treated with ICS. Information on airway inflammation from FeNO concentrations seems to be unrelated to levels of asthma control

• Tuberculosis and Respiratory Diseases
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• v.70 no.5
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• pp.416-422
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• 2011

Background: Inhaled corticosteroids (ICSs) are the most essential medication for asthma control. Many reports suggest that the usage of ICSs improves not only the control of asthma symptoms but also prevents exacerbation. We investigated whether increases in ICS prescriptions are associated with decreases in asthma exacerbation in the clinical practice setting. Methods: We retrospectively analyzed the database of adult asthma patients who had visited a tertiary referral hospital, the Asan Medical Center between January 2000 and December 2009. The number of emergency department (ED) visits, admissions, intensive care unit (ICU) care, deaths, and ICS prescriptions were analyzed to evaluate the time trend of asthma exacerbation as a function of the ICS prescription rate during the ten years. Results: The numbers of ED visits, admissions, and episodes of ICU care decreased during the ten years (p<0.001, p=0.033, p=0.001, respectively) while the number of ICS prescriptions increased (p<0.001). We found a correlation between the number of ICS prescriptions and the number of ED visits, admissions, or ICU care. For these outcomes, the correlation coefficients were r=-0.952, p<0.001; r=-0.673, p=0.033; r=-0.948, p<0.001, respectively. Conclusion: The number of ICS prescriptions increased during the past ten years while the number of asthma exacerbations decreased. Our results also showed a negative correlation between the ICS prescription rate and asthma exacerbation in the clinical practice setting. In other words, an increase in ICS prescription may be a major cause of a decrease in asthma exacerbations.

• Tuberculosis and Respiratory Diseases
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• v.83 no.3
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• pp.175-184
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• 2020

Quantitative sputum cytometry facilitates in assessing the nature of bronchitis associated with exacerbations of chronic obstructive pulmonary disease (COPD). This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, the vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (oral and inhaled), the limited efficacy of anti-interleukin 5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving the interleukin 13 and matrix metalloprotease pathways. The absence of eosinophils may facilitate in limiting the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. Additionally, sputum measurements may also provide insight into the mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while the low levels of immunoglobulins in sputum may also contribute to airway infections. The assessment of sputum at the time of exacerbations thus would facilitate in customizing treatment and treat current exacerbations and reduce future risk of exacerbations.

• Clinical and Experimental Pediatrics
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• v.55 no.9
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• pp.330-336
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• 2012

Purpose: Fractional exhaled nitric oxide (FeNO) and forced expiratory flow between 25% and 75% of vital capacity ($FEF_{25-75}$) are not included in routine monitoring of asthma control. We observed changes in FeNO level and $FEF_{25-75}$ after FeNO-based treatment with inhaled corticosteroid (ICS) in children with controlled asthma (CA). Methods: We recruited 148 children with asthma (age, 8 to 16 years) who had maintained asthma control and normal forced expiratory volume in the first second ($FEV_1$) without control medication for ${\geq}3$ months. Patients with FeNO levels >25 ppb were allocated to the ICS-treated (FeNO-based management) or untreated group (guideline-based management). Changes in spirometric values and FeNO levels from baseline were evaluated after 6 weeks. Results: Ninety-three patients had FeNO levels >25 ppb. These patients had lower $FEF_{25-75}$ % predicted values than those with FeNO levels ${\leq}25$ ppb (P<0.01). After 6 weeks, the geometric mean (GM) FeNO level in the ICS-treated group was 45% lower than the baseline value, and the mean percent increase in $FEF_{25-75}$ was 18.7% which was greater than that in other spirometric values. There was a negative correlation between percent changes in $FEF_{25-75}$ and FeNO (r=-0.368, P=0.001). In contrast, the GM FeNO and spirometric values were not significantly different from the baseline values in the untreated group. Conclusion: The anti-inflammatory treatment simultaneously improved the FeNO levels and $FEF_{25-75}$ in CA patients when their FeNO levels were >25 ppb.

• YAKHAK HOEJI
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• v.56 no.2
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• pp.126-135
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• 2012

Purpose: To develop therapeutic duplication criteria for the drugs used for respiratory diseases. Method: Therapeutic duplication was defined as "more than 2 drug ingredient-usage in which each has the same therapeutic effect and combination therapy does not confer additional therapeutic benefit". Respiratory system drugs approved in Korea were examined for the study. The WHO's Anatomical Therapeutic Chemical Classification System was used for grouping of the corresponding drug ingredients. The principles and recommendations on combination usage or multiple drug regimens were reviewed by using the clinical practice guidelines, textbooks, product labelings, and clinical articles. Clinical expert group consultation was performed and expert opinions were incorporated into the final criteria. Results: Nine hundred sixty two drug products with Korean Food and Drug Administration classification codes of 141, 149, 222, and 229 were evaluated, of which 87 active ingredients were composed. The drug ingredients were classified into 12 groups (antihistamines, oral nasal decongestants, leukotriene receptor antagonists, inhaled anticholinergics, inhaled corticosteroids, oral ${\beta}2$-agonists, long-acting ${\beta}2$-agonists, short-acting ${\beta}2$-agonists, xanthines, antiallergics, mucolytics and cough suppressants). The use of more than 2 drug ingredients including the same group was therapeutic duplication, and thus combination should be recommended not to be used. Conclusion: Twelve drug groups were identified as therapeutic duplication criteria. Combination therapy within each group should not be used otherwise therapeutic benefits outweigh potential risks.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.298-305
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• 2016

Background: This study is to investigate the prescription patterns and factors related to the number of medications treating chronic obstructive pulmonary disease (COPD) in patients under 65 years old according to GOLD guidelines. Methods: We retrospectively analyzed the medical records of patients aged 40-64 years with a diagnosis of COPD from January to March 2016. Patients were classified by combined assessment of COPD (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. We analyzed prescribed medications, treatment options and factors related to the numbers of COPD medications. Results: The total number of prescriptions were 251. About 35.5% of patients were classified as GOLD A, 34.2% as GOLD B, 17.1% as GOLD C and 13.2% as GOLD D. Inhaled bronchodilator was prescribed for 86.9% of patients and the most frequent COPD medication was long-acting muscarinic antagonist (LAMA) followed by inhaled corticosteroids/long acting beta agonist (ICS/LABA). The majority of low risk patients (GOLD A/B) were prescribed a monotherapy with LAMA or LABA. For high risk patients (GOLD C/D), combination treatment with ICS+LAMA+LABA was mostly prescribed. The 21.2% of patients in GOLD D received systemic corticosteroid. The average number of medications per prescription was 3.7, and this number increased with increasing COPD grade, COPD duration and lung function reduction ($FEV_1$, $FEV_1/FVC$). Conclusion: Generally high adherence to GOLD guideline recommendations was reported. Given the progressive nature of the disease, results suggest that closer attention to respiratory symptoms for early detection, diagnosis, and appropriate treatment of COPD is warranted.

• Tuberculosis and Respiratory Diseases
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• v.51 no.1
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• pp.25-34
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• 2001

Background : Inhaled glucocorticoids are the medical treatment of choice in asthma patients. Fluticasone propionate is one of the most effective inhaled corticosteroids and has been reported to have minimal effect on the hypothalamic-pituitary-adrenal axis at the recommended dose. However, reports of long-term trials characterizing their systemic safety with chronic use are rare. This study was designed to evaluate the long-term safety of inhaled fluticasone propionate to the hypothalamic-pituitary-adrenal axis. Method : This study was conducted on 21 patients to evaluate the adrenal response to rapid ACTH stimulation test after 6 months of treatment with fluticasone propionate from $200\;{\mu}g$ to $750\;{\mu}g$ daily. The serum cortisol levels was measured to assess its effect on the hypothalamic-pituitary-adrenal axis just prior to the injection, at 30 minutes and 60 minutes after an intramuscular injection of synthetic ACTH. Result : The mean dose of inhaled fluticasone propionate was $355\;{\mu}g$ per day(SD=$174\;{\mu}g$, range=$200\;{\mu}g$ to $750\;{\mu}g$). The mean serum cortisol levels of the patients was $11.0\;{\mu}g/d{\ell}$(SD=$6.4\;{\mu}g/d{\ell}$) prior to the injection, $20.0\;{\mu}g/d{\ell}$ (SD=$7.7\;{\mu}g/d{\ell}$) after 30 minutes, and $23.0\;{\mu}g/d{\ell}$(SD=$6.3\;{\mu}g/d{\ell}$) after 60 minutes. Sixteen patients of the 21 patients had a normal response(> $18\;{\mu}g/d{\ell}$), and 5 out of the 21 patients had serum cortisol levels below the normal range after the rapid ACTH stimulation test. Conclusion: Adrenal suppression occurred in 5 out of 21 patients with 6 months treatment with inhaled fluticasone propionate.

• Tuberculosis and Respiratory Diseases
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• v.77 no.4
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• pp.161-166
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• 2014

Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

• Tuberculosis and Respiratory Diseases
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• v.42 no.6
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• pp.888-899
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• 1995

Background: Topical inhaled steroids, budesonide(Bu) and beclomethasone dipropionate (BOP), are now established as effective drugs in the management of chronic asthma. These drugs have high topical anti-inflammatory effect with low systemic activity. This study was performed to determine the effects of two inhaled corticosteroids, Bu and BOP, on the adrenocortical supression in 44 patients with bronchial asthma or chronic obstructive pulmonary disease. Methods: The adrenocortical function was assessed by measurement of serum cortisol concentration at 8 o'clock in morning and free cortisol in 24-hour urine collection at interval in 44 patients. No steroid was administered during the pretreatment period of 10 days and the final 6 days of the study. Each subject inhaled BOP or Bu, in daily doses of 800 or 1,600 micrograms for 12 days. The dose was delivered by metered dose inhaler (MDI) or diskhaler or large spacing device attached to MDI. Results: The levels of serum cortisol and 24-hour urinary free cortisol were decreased during the treatment period in patients inhaled Bu delivered by MDI in daily doses of 800 and 1,600 micrograms. In contrast, serum cortisol level was decreased on 6 and 12th day of treatment period in patients with BDP diskhaler in daily doses of 800 micrograms. In daily doses of 1,600 micrograms, the serum cortisol and 24hour urine free cortisol levels were decreased on 6, 9 and 12th day of treatment period in patients with BDP disk haler. The serum cortisol and 24-hour urinary free cortisol levels were not significantly decreased during the treatment period in patients inhaled Bu delivered by large spacing device attached to a MDI. Conclusion: These results showed that 1) the endogenous cortisol secretion was suppressed after inhalation of BDP and Bu in daily doses of 800 and 1,600micrograms, 2) Bu with MDI suppressed the adrenocortical function more than BDP with diskhaler, in daily doses of 1600 micrograms. and 3)large spacing device attached to a MDI might decrease the risk of suppression in the hypothalamic -pituitary- adrenal axis.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.164-169
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• 2005

Background : The role of combination therapy of inhaled corticosteroid (ICS) plus long-acting ${\beta}_2-agonist$ (LABA) in asthma is well established, but nor much is known about this treatment in COPD. Recent studies have revealed that combining therapy is associated with fewer acute exacerbations in COPD, but in most of the studies, high-dose combination therapies have been employed. The current study assessed the effect of moderate or high-dose combination therapy of ICS plus LABA on the frequency of acute exacerbations in COPD. Methods : Between January 1, 2001 and August 31, 2004, 46 patients with COPD (moderate, severe, very severe) were enrolled who received either fluticasone/salmeterol (flu/sal) $250{\mu}g/50{\mu}g$ twice a day (group A) or flu/sal $500{\mu}g/50{\mu}g$ twice a day (group B) for more than a year. We divided them into two groups depending on the dosage of ICS plus LABA. Effect of drugs was compared based on the factors such as symptom aggravation, number of admission, and time to first exacerbation during a year after use. Results : Eleven of twenty-six patients in group A (42.3%) experienced acute exacerbation and eleven of twenty patients in group B (55%) experienced acute exacerbation during 1 year. Mean exacerbation rate of Group A was 0.96 and Group B was 1.05. Mean admission rate was 0.15 and 0.30, respectively. There was no statistically significant difference of aggravation rate, number of administration and time to first exacerbation between the two treatment groups. Conclusion : There was no significant difference between moderate and high dose combined inhaler therapy to reduce acute exacerbation in COPD patients (moderate, severe, very severe). Hence, the effective dose of combination therapy needs further study in patients with COPD.