• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.296-301
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• 2011

This meta-analysis was performed to evaluate the difference of the therapeutic effi cacy and adverse effects of leukotriene receptor antagonist and theophylline added to inhaled corticosteroids in adult asthma. Databases were searched for studies published through Nov, 2010. Randomized-controlled trials containing inhaled corticosteroids plus leukotriene receptor antagonist and inhaled corticosteroids plus sustained-release theophylline for asthma therapy were selected. For each report, data were extracted to the outcomes analyzed: mean change in morning peak expiratory flow, mean change in evening peak expiratory flow, mean change in morning forced expiratory volume in 1 sec, mean change in daily short bete2-agonist use, asthma exacerbation and adverse effects. Four assessable trials including 182 asthmatic patients were identified. Inhaled corticosteroids plus leukotriene receptor antagonist was superior to inhaled corticosteroids plus theophylline therapy in improving morning peak expiratory flow in asthmatics (mean difference 19.08 [95% confidence interval 13.37-23.79] l/min, p<0.001) and morning forced expiratory volume in 1 sec in asthmatics (mean difference 0.09 [95% confidence interval 0.03-0.14] liter, p=0.001). In evening peak expiratory flow, daily short bete2-agonist use, asthma exacerbation and adverse effects, there was no significant difference between these two therapies (All p>0.05). Our meta-analysis showed that the combination of inhaled corticosteroids plus leukotriene receptor antagonist resulted in more improvement in both peak expiratory flow and forced expiratory volume in 1 sec in the morning than inhaled corticosteroids plus sustained-release theophylline in adult asthmatics. Further trials are necessary to evaluate the dominant effects of the former combination.

• Tuberculosis and Respiratory Diseases
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• v.86 no.3
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• pp.151-157
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• 2023

The introduction of inhaled corticosteroids (ICS) for the management of asthma has led to a decrease in acute exacerbation of asthma. However, there are concerns regarding the safety of long-term ICS use, particularly pneumonia. Growing evidence indicates that ICS use is associated with an increased risk of pneumonia in patients with chronic obstructive pulmonary disease, whereas the risk in patients with asthma remains unclear. This review discusses the effect of ICS on pneumonia among patients with asthma to update the existing literature. Asthma is associated with an increased risk of pneumonia. Several hypotheses have been proposed to explain this association, including that asthma impairs the clearance of bacteria owing to chronic inflammation. Therefore, controlling airway inflammation with ICS may prevent the occurrence of pneumonia in asthma. In addition, two meta-analyses investigating randomized control trials showed that ICS use was associated with a protective effect against pneumonia in asthma.

• Tuberculosis and Respiratory Diseases
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• v.81 no.1
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• pp.1-5
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• 2018

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as "severe" asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

• Clinical and Experimental Pediatrics
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• v.53 no.11
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• pp.951-956
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• 2010

Purpose: To compare the profiles of the bronchodilator response (BDR) among children with asthma and/or allergic rhinitis (AR) and to determine whether BDR in these children is reduced by treatment with inhaled and/or nasal corticosteroid. Methods: Sixty-eight children with asthma (mean age, 10.9 years), 45 children with comorbid asthma and AR (mean age, 10.5 years), and 44 children with AR alone (mean age, 10.2 years) were investigated. After a 2-week baseline period, all children were treated with inhaled fluticasone propionate (either 100 or $250{\mu}g$ b.i.d., tailored to asthma severity) or nasal fluticasone propionate (one spray b.i.d. in each nostril) or both, according to the condition. Before and 2 weeks after starting treatment, all children were evaluated with spirometry and bronchodilator testing. BDR was calculated as a percent change from the forced expiratory volume in 1 second ($FEV_1$) at baseline. Results: The mean BDR was 10.3% [95% confidence interval (CI) 8.3-12.4%] in children with asthma, 9.0% (95% CI 7.3-10.9%) in subjects with asthma and AR, and 5.0% (95% CI 4.1-5.9%) in children with AR alone ($P$<0.001). After treatment, the mean BDR was reduced to 5.2% (95% CI 4.2-6.3%) ($P$<0.001) in children with asthma and to 4.5% (95% CI 3.5-5.5%) ($P$<0.001) in children with asthma and AR. However, children with rhinitis showed no significant change in BDR after treatment, with the mean value being 4.7% (95% CI 3.7-5.8%) ($P$=0.597). Conclusion: The findings of this study imply that an elevated BDR in children with AR cannot be attributed to nasal inflammation alone and highlights the close relationship between the upper and lower airways.

• Tuberculosis and Respiratory Diseases
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• v.83 no.1
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• pp.42-50
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• 2020

Background: Fractional exhaled nitric oxide (FeNO) is regarded as a potential biomarker for identifying eosinophilic inflammation. We aimed to evaluate the clinical implication of FeNO and its influence on inhaled corticosteroids (ICS) prescription rate in Korean chronic obstructive pulmonary disease (COPD) patients. Methods: FeNO level and its association with clinical features were analyzed. Changes in the prescription rate of ICS before and after FeNO measurement were identified. Results: A total of 160 COPD patients were divided into increased (≥25 parts per billion [ppb], n=74) and normal (<25 ppb, n=86) FeNO groups according to the recommendations from the American Thoracic Society. Compared with the normal FeNO group, the adjusted odds ratio for having history of asthma without wheezing and with wheezing in the increased FeNO group were 2.96 (95% confidence interval [CI], 1.40-6.29) and 4.24 (95% CI, 1.37-13.08), respectively. Only 21 out of 74 patients (28.4%) with increased FeNO prescribed ICS-containing inhaler and 18 of 86 patients (20.9%) with normal FeNO were given ICS-containing inhaler. Previous exacerbation, asthma, and wheezing were the major factors to maintain ICS at normal FeNO level and not to initiate ICS at increased FeNO level. Conclusion: Increased FeNO was associated with the history of asthma irrespective of wheezing. However, FeNO seemed to play a subsidiary role in the use of ICS-containing inhalers in real-world clinics, which was determined with prior exacerbation and clinical features suggesting Th2 inflammation.

• Clinical and Experimental Pediatrics
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• v.58 no.12
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• pp.472-477
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• 2015

Purpose: Adherence to treatment with inhaled corticosteroids (ICS) is a critical determinant of asthma control. The objective of this study was to assess factors that determine adherence to ICS therapy in children with asthma. Methods: Fifty-eight children with asthma, aged 5 to 16 years, used ICS with or without a spacer for 3 months. Adherence rates as measured from questionnaires and canisters, asthma symptom scores, and inhalation technique scores were assessed every 30 days. The degree of supervision by caregivers was assessed at day 30. Results: Adherence rates measured using canisters were lower at day 60 than at day 30 (P=0.044) and did not change thereafter ($74.4%{\pm}17.4%$ at day 30, $66.5%{\pm}18.4%$ at day 60, and $67.4%{\pm}22.2%$ at day 90). Adherence rates at days 60 and 90 and during the total study period were significantly different when measured by using questionnaires versus canisters (P<0.001, P=0.022, and P =0.001, respectively). In the comparison of adherence rates repeatedly measured at days 30, 60, and 90 and adherence rates during the total study period among the 3 groups, adherence rates in the high-degree supervision group were significantly higher than those in the low-degree supervision group ($82.0{\pm}16.0$ vs. $66.1{\pm}14.5$, $75.4{\pm}14.4$ vs. $56.2{\pm}18.4$, $75.0{\pm}18.3$ vs. $55.0{\pm}19.7$ [P=0.027]; $77.9{\pm}12.2$ vs. $59.1{\pm}11.4$ [P=0.021]) after adjustment for sex and age. Conclusion: The level of caregiver supervision is an important factor affecting adherence to ICS therapy in children with asthma. Therefore, a high degree of supervision may be required to increase adherence to ICS therapy in children with asthma.

• Tuberculosis and Respiratory Diseases
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• v.83 no.3
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• pp.185-194
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• 2020

Blood eosinophil counts have emerged as a chronic obstructive pulmonary disease (COPD) biomarker that predict the effects of inhaled corticosteroids (ICS) in clinical practice. Post-hoc and prospective analysis of randomized control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to ICS. COPD patients with frequent exacerbations (2 or more moderate exacerbations/yr) or a history of hospitalization have a greater response to ICS. Ex-smokers also appear to have a greater ICS response. Blood eosinophil counts can be combined with clinical information such as exacerbation history and smoking status to enable a precision medicine approach to the use of ICS. Higher blood eosinophil counts are associated with increased eosinophilic lung inflammation, and other biological features that may contribute to the increased ICS response observed. Emerging data indicates that lower blood eosinophil counts are associated with an increased risk of bacterial infection, suggesting complex relationships between eosinophils, ICS response, and the airway microbiome.

• Tuberculosis and Respiratory Diseases
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• v.83 no.4
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• pp.257-267
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• 2020

Patients with chronic obstructive pulmonary disease receive a range of treatments including but not limited to inhaled bronchodilators, inhaled and systemic corticosteroids, supplemental oxygen, and pulmonary rehabilitation. Pulmonary rehabilitation is a multidisciplinary intervention that seeks to combine patient education, exercise, and lifestyle changes into a comprehensive program. Programs 6 to 8 weeks in length have been shown to improve health, reduce dyspnea, increase exercise capacity, improve psychological well-being, and reduce healthcare utilization and hospitalization. Although the use of pulmonary rehabilitation is widely supported by the literature, controversy still exists regarding what should be included in the programs. The goal of this review was to summarize the evidence for pulmonary rehabilitation and identify the areas that hold promise in improving its utilization and effectiveness.

• Tuberculosis and Respiratory Diseases
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• v.70 no.5
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• pp.384-389
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• 2011

The prevention of and the controlling of symptoms, reductions in the frequency of exacerbations, and disease severity are central to the pharmacologic therapy of chronic obstructive pulmonary disease (COPD). COPD patients are inclined to be older, have more comorbidities, and use polypharmacy as a result. Long-acting inhaled muscarinic antagonists (LAMAs) is a preferred treatment modality. However, the cardiovascular (CV) safety of anti-cholinergics, including LAMA, has been an issue. In contrast, the results of the UPLIFT trial and a pooled analysis of data from 30 trials of tiotropium illustrates the association of tiotropium with reductions in the risk of all cause mortality, CV mortality and CV events. And, the UPLIFT trial provides clues regarding the additive advantages of tiotropium in COPD patients who already are using long-acting inhaled ${\beta}_2$ agonists and inhaled corticosteroids. Following the contribution of tiotropium as a first LAMA, new LAMAs such as aclidinium and glycopyrrolate (NVA-237) seem to be emerging.

• Tuberculosis and Respiratory Diseases
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• v.85 no.1
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• pp.18-24
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• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.