Prevalence of Uncontrolled Asthma despite Treatment with Medium- or High-Dose ICS/LABA Using Patient-Reported Outcomes in Japan: The KOCU (KnOwing the Controlled statUs of Asthma in Japan) Study.

INTRODUCTION: Evidence on the prevalence of uncontrolled asthma upon the standard of care in Japan is scarce and inconsistent. We report the prevalence of uncontrolled asthma using the Japanese Guidelines for Asthma (JGL) 2018 and Global Initiative for Asthma (GINA) 2019 classifications in patients who are currently receiving standard-of-care treatment in a real-life setting. METHODS: In this prospective, 12-week, noninterventional study, patients with asthma aged 20-75 years and continuously treated with medium- or high-dose inhaled corticosteroid (ICS)/LABA, with or without other controller(s), were assessed for their asthma control status. The demographics, clinical characteristics, treatment patterns, health care resource utilization, patient-reported outcomes (PROs), and adherence to prescribed treatments were assessed for patients classified as either controlled or uncontrolled. RESULTS: Of 454 patients, 53.7% and 36.3% of the patients reported their asthma as uncontrolled based on the JGL and GINA criteria, respectively. Uncontrolled asthma was even higher (JGL, 75.0%; GINA, 63.5%) within the subpopulation of 52 patients receiving long-acting muscarinic antagonists (LAMAs; i.e., ICS/LABA/LAMA subpopulation). Sensitivity analysis by propensity matching identified significant odds ratios of controlled versus uncontrolled asthma for several demographics and clinical characteristics: male; sensitization to animals, fungi, or birch; comorbidities including food allergy or diabetes; and history of exacerbation were associated with the risk of uncontrolled asthma. No significant changes in PROs were observed. CONCLUSION: The frequency of uncontrolled asthma in the study population was high, as per JGL and GINA guidelines, despite good adherence to ICS/LABA treatment and other prescribed treatments over 12 weeks.

Exploratory research on asthma exacerbation risk factors using the Japanese claims database and machine learning: a retrospective cohort study.

OBJECTIVE: Analytical studies of risk factor assessment using machine learning have recently been reported. We performed an exploratory detection study of asthma exacerbation-related factors using health insurance claims data and machine learning to explore risk factors that have high generalizability and can be easily obtained in daily practice. METHODS: A dataset of asthma patients during May 2014-April 2019 from the Japanese insurance claims database, MediScope® (DB) was used. Patient characteristics and disease information were extracted, and association with occurrence of asthma exacerbation was evaluated to comprehensively search for exacerbation risk factors. Asthma exacerbations were defined as the co-occurrence of emergency medical procedures, such as emergency transport and intravenous steroid injections, with asthma claims, which were recorded in the database. RESULTS: In total, 5,844 (13.7%) subjects had exacerbations in 42,685 eligible cases from the DB. Information on approximately 3,300 diseases was subjected to a machine learning, and 25 variables were extracted as variable importance and targeted for risk assessment. As a result, sex, days without exacerbation from cohort entry date at look-back period, Charlson Comorbidity Index, allergic rhinitis, chronic sinusitis, acute airway disease (upper airway), acute airway disease (lower airways), Chronic obstructive pulmonary disease/chronic bronchitis, gastroesophageal reflux disease, and hypertension were significantly associated with exacerbation. Dyslipidemia and periodontitis were detected as associated factors of reduced exacerbation risk. CONCLUSIONS: A comprehensive analysis of claims data using machine learning showed asthma exacerbation risk factors mostly consistent with those in previous studies. Further examination in other fields is warranted.Supplemental data for this article is available online at https://doi.org/10.1080/02770903.2021.1923740 .

Japanese guidelines for adult asthma 2020.

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting ß2-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled ß2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions to be considered in asthma therapy.

Asthma control and quality of life in a real-life setting: a cross-sectional study of adult asthma patients in Japan (ACQUIRE-2).

Objective: The level of asthma control in adult asthma patients receiving treatment in clinical practice from allergy and/or respiratory specialists in Japan remains unclear. We conducted the ACQUIRE-2 study (NCT02640742) to evaluate level of asthma control, asthma symptoms, health-related quality of life (HR-QoL), and reliever medication use in this setting. Methods: This observational study was undertaken between December 2015 and June 2016 in 58 medical institutions across Japan. We enrolled outpatients aged ≥20 years diagnosed with asthma for ≥1 year who were being managed by specialists. Criteria to evaluate the level of asthma control were based on modified definitions of the Asthma Prevention and Management Guideline 2015, Japan (JGL 2015) and Global Initiative for Asthma (GINA) 2012. Asthma symptoms, HR-QoL, and reliever medication use were also evaluated. Results: Of 1250 enrolled patients, 1175 were analyzed, 62.9% of whom were women. Mean (± standard deviation) age and duration of asthma were 59.7 ± 14.5 years and 16.9 ± 14.0 years, respectively. Using JGL 2015-based criteria, 24.4%, 69.2%, and 6.5% of patients had well-controlled, insufficiently-controlled, and poorly-controlled asthma, respectively. Using GINA-based criteria, 35.1%, 49.8%, and 15.1% of patients had controlled, partly controlled, and uncontrolled asthma, respectively. Daytime and nighttime asthma symptoms were experienced by 51.5% and 44.9% of patients, respectively. The mean MiniAQLQ score was 5.8 ± 1.0 (7-point scale). Conclusions: Asthma was not well-controlled in the majority of patients in this study. To achieve better asthma control, improvements in symptom monitoring and management may be required.

Examination of the cut-off values for a questionnaire used to evaluate asthma control in Japanese asthma patients.

BACKGROUND: The Japan Asthma Control Survey (JACS) questionnaire, developed as a tool for measuring asthma control levels in Japanese asthma patients, was previously tested for its reliability and validity. However, many of the patients enrolled in the original validation study had mild asthma; thus a re-evaluation including severe cases was required to calculate more reliable cut-off values. METHODS: Pooled analysis of data from the original validation study and the subsequent medication guidance study including adult patients with severe asthma was conducted to calculate the JACS questionnaire cut-off values and to assess their sensitivity and specificity for identifying "well-controlled", "not well-controlled", and "poorly controlled" asthma as described in the Asthma Prevention and Management Guideline 2015 (JGL2015). The data were from 353 patients with mild to severe persistent asthma classified according to JGL2015. RESULTS: The JACS questionnaire cut-off values were 8.0 (sensitivity, 67.9%; specificity, 81.9%) for "well-controlled" and "not well-controlled" and 4.8 (sensitivity, 85.3%; specificity, 53.3%) for "not well-controlled" and "poorly controlled". CONCLUSIONS: JACS cut-off values can be expected to be more useful for evaluating asthma control status in clinical practice and clinical research, thus improving asthma treatment, in Japan. This analysis was the original validation study (UMIN000016589) and the subsequent medication guidance study (UMIN000024353).

Development of a questionnaire to evaluate asthma control in Japanese asthma patients.

BACKGROUND: The asthma control questionnaires used in Japan are Japanese translations of those developed outside Japan, and have some limitations; a questionnaire designed to optimally evaluate asthma control levels for Japanese may be necessary. The present study was conducted to validate the Japan Asthma Control Survey (JACS) questionnaire in Japanese asthma patients. METHODS: A total of 226 adult patients with mild to severe persistent asthma were enrolled and responded to the JACS questionnaire, asthma control questionnaire (ACQ), and Mini asthma quality of life questionnaire (Mini AQLQ) at Weeks 0 and 4. The reliability, validity, and sensitivity/responsiveness of the JACS questionnaire were evaluated. RESULTS: The intra-class correlation coefficients (ICCs) were within the range of 0.55-0.75 for all JACS scores, indicating moderate/substantial reproducibility. For internal consistency, Cronbach's alpha coefficients ranged from 0.76 to 0.92 in total and subscale scores, which were greater than the lower limit of internal consistency. As for factor validity, the cumulative contribution ratio of four main factors was 0.66. For criterion-related validity, the correlation coefficients between the JACS total score and ACQ5, ACQ6, and Mini AQLQ scores were -0.78, -0.78, and 0.77, respectively, showing a significant correlation (p < 0.0001). CONCLUSIONS: The JACS questionnaire was validated in terms of reliability and validity. It will be necessary to evaluate the therapeutic efficacy measured by the JACS questionnaire and calculate cutoff values for the asthma control status in a higher number of patients. CLINICAL TRIAL REGISTRATION: UMIN000016589.

Staphylococcus aureus enterotoxin sensitization involvement and its association with the CysLTR1 variant in different asthma phenotypes.

BACKGROUND: Sensitization to Staphylococcus aureus enterotoxin (SE) is a known risk factor for asthma susceptibility and severity. However, how SE sensitization is involved in asthma, particularly nonatopic asthma and/or late-onset asthma, remains uncertain. OBJECTIVE: To clarify the involvement of SE sensitization in nonatopic and/or late-onset asthma and its association with a polymorphism of the cysteinyl leukotriene receptor 1 gene (CysLTR1), which was examined because CysLT signaling is closely associated with late-onset eosinophilic asthma. METHODS: We assessed associations between sensitization to SE (A and/or B) and clinical indexes in 224 patients with asthma (mean age, 62.3 years; 171 women) from a cohort of the Kinki Hokuriku Airway Disease Conference, particularly those with nonatopic asthma (not sensitized to common aeroallergens) and/or late-onset asthma. Associations between SE sensitization and CysLTR1 polymorphism (rs2806489), a potential regulatory variant for atopic predisposition in women, were also assessed in a sex-stratified manner. RESULTS: A total of 105 patients (47%) with asthma were sensitized to SE. Among patients with nonatopic asthma (n = 67) or with late-onset asthma (n = 124), those sensitized to SE had significantly higher serum total IgE and periostin levels than those not sensitized. In nonatopic patients, a rapid decrease in forced expiratory volume in 1 second was associated with SE sensitization. In women with asthma, rs2806489 was associated with sensitization to SEB and age at asthma onset. CONCLUSION: SE sensitization contributes to TH2 inflammation in nonatopic and/or late-onset asthma. In women with asthma, the CysLTR1 variant might be associated with sensitization to SEB and age at asthma onset.

Comparison of early effects of budesonide/formoterol maintenance and reliever therapy with fluticasone furoate/vilanterol for asthma patients requiring step-up from inhaled corticosteroid monotherapy.

BACKGROUND: If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, addition of a long-acting ß2 agonist (LABA) is the preferred treatment. Currently, there are several combinations of ICS/LABA that are available, each of which has a different property. Here, we aimed to compare the early effects of budesonide/formoterol (BUD/FM; Symbicort(®)) for maintenance and reliever therapy (SMART) with a fixed dose of fluticasone furoate/vilanterol (FF/VI; Relvar(®)). METHODS: Inadequately controlled asthma patients (defined as having an Asthma Control Questionnaire, 5-item version [ACQ5] score≥1.5) with a fractional exhaled nitric oxide (FeNO) value > 35 ppb, who had been treated with a medium dose of ICS alone, were enrolled. Patients were randomized into two groups and treated with two inhalations twice-daily of BUD/FM 160/4.5 µg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation once-daily of FF/VI 100/25 µg plus as-needed procaterol (FF/VI group, n = 15) for 4 weeks. Outcomes including FeNO, impulse oscillometry (IOS) parameters and ACQ5 scores were measured at 0, 2 and 4 weeks. RESULTS: Both groups showed improvement in airway inflammation, pulmonary function and symptoms from baseline to 2 weeks. From 2 to 4 weeks, the SMART group exhibited continuous improvement in most measured parameters, whereas improvement in the FF/VI group seemed to reach a plateau transiently. Consequently, the SMART group showed significant improvement in the FeNO, IOS parameters (resonance frequency and integrated area of low frequency reactance) and ACQ5 score as compared with the FF/VI group at 4 weeks. CONCLUSION: As compared with the FF/VI group, the SMART group achieved a greater improvement in FeNO, small airway parameters regarding IOS and ACQ score, in patients with airway inflammation and uncontrolled symptoms treated with a medium dose of ICS alone. In this 4-week study, these two ICS/LABA combination therapies showed different treatment outcomes; they must be investigated further to clarify suitable patient characters and the long term efficacies for each combination.

Ethnic sensitivity assessment of fluticasone furoate/vilanterol in East Asian asthma patients from randomized double-blind multicentre Phase IIb/III trials.

BACKGROUND: Fluticasone furoate (FF)/vilanterol (VI) is a once daily (OD) inhaled corticosteroid/long-acting ß2-agonist combination asthma therapy approved in Japan and the EU. FF/VI efficacy and safety data from asthma studies including patients in East Asia were evaluated to assess ethnic sensitivity. METHODS: Randomized, double-blind, multicenter Phase IIb/III trials were assessed. Change from baseline relative to placebo or twice-daily fluticasone propionate 500 µg in trough FEV1 was compared between patients from Japan (N = 148) and Not-Japan (N = 3,066; three studies). Adverse events (AEs), laboratory results, and electrocardiograms were compared between patients from Japan + Korea (N = 188) and Not-Japan + Korea (N = 3,840; five studies). RESULTS: For trough FEV1, improvements from baseline (least-squares mean difference [95% confidence interval]) were reported for FF/VI 100/25 µg OD versus placebo at Week 12 (Japan: 0.323 L [0.104-0.542]; Not-Japan: 0.168 L [0.095-0.241]). Improvements from baseline (least-squares mean change [standard error]) were reported with FF/VI 200/25 µg OD at Week 24 (Japan: 0.355 L [0.1152]; Not-Japan: 0.396 L [0.0313]). A greater proportion of patients from Japan + Korea versus Not-Japan + Korea reported AEs in all treatment arms including placebo (FF/VI 100/25 µg: 79% versus 57%; FF/VI 200/25 µg: 64% versus 45%; placebo: 41% versus 23%). There were no notable differences in treatment-related or class-related AEs. No clinically significant changes in electrocardiogram assessments or statistically significant differences in 24 h urinary cortisol excretion were observed between the Japan + Korea and Not-Japan + Korea cohorts. CONCLUSIONS: Good efficacy and an acceptable safety profile were observed for FF/VI 100/25 µg and 200/25 µg OD in East Asian asthma patients; these globally recommended doses are appropriate for asthma patients in Japan. TRIAL REGISTRATION: Clinicaltrials.gov registration numbers: NCT01165138 , NCT01134042 , NCT01086384 , NCT00603278 , NCT00603382 .

Comparison of the effects of budesonide/formoterol maintenance and reliever therapy with fluticasone/salmeterol fixed-dose treatment on airway inflammation and small airway impairment in patients who need to step-up from inhaled corticosteroid monotherapy.

BACKGROUND: If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, adding a long-acting ß2 agonist (LABA) is the preferred treatment. We aimed to compare the effect of two widely available ICS/LABA combinations in these patients in real-life conditions: budesonide/formoterol (BUD/FM; Symbicort(®)) for maintenance and reliever therapy (SMART) and a fixed dose of fluticasone propionate/salmeterol (FP/SM). METHODS: Inadequately controlled asthma patients treated with a medium dose of ICS alone, with an Asthma Control Questionnaire (ACQ) score >0.75 and using a short-acting ß2-agonist (SABA) 2-6 occasions/week, were enrolled. Patients were randomized into two groups and treated with two inhalation twice-daily BUD/FM 160/4.5 µg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation twice-daily FP/SM 250/50 µg plus as-needed procaterol (FP/SM group, n = 15) for 8 weeks. RESULTS: Both groups showed significant improvement in airway inflammation, pulmonary functions and symptoms from baseline. The SMART group showed significant improvement in the fraction of nitric oxide, ACQ score, rescue medication use and small airway parameter R5-R20 measured by impulse oscillometry compared with the FP/SM group. CONCLUSION: For stepping up treatment from ICS alone to an ICS/LABA combination, SMART is preferable for controlling asthma symptoms by suppressing airway inflammation and improving small airway impairment compared with a fixed dose of FP/SM. It may be achieved by the property of BUD/FM itself and as-needed use, but the degree of each contribution must be investigated further.

Increased periostin associates with greater airflow limitation in patients receiving inhaled corticosteroids.

BACKGROUND: Periostin, an extracellular matrix protein, contributes to subepithelial thickening in asthmatic airways, and its serum levels reflect airway eosinophilic inflammation. However, the relationship between periostin and the development of airflow limitation, a functional consequence of airway remodeling, remains unknown. OBJECTIVE: We aimed to determine the relationship between serum periostin levels and pulmonary function decline in asthmatic patients on inhaled corticosteroid (ICS) treatment. METHODS: Two hundred twenty-four asthmatic patients (average age, 62.3 years) treated with ICS for at least 4 years were enrolled. Annual changes in FEV1, from at least 1 year after the initiation of ICS treatment to the time of enrollment or later (average, 16.2 measurements over 8 years per individual), were assessed. At enrollment, clinical indices, biomarkers that included serum periostin, and periostin gene polymorphisms were examined. Associations between clinical indices or biomarkers and a decline in FEV1 of 30 mL or greater per year were analyzed. RESULTS: High serum periostin levels (≥ 95 ng/mL) at enrollment, the highest treatment step, higher ICS daily doses, a history of admission due to asthma exacerbation, comorbid or a history of sinusitis, and ex-smoking were associated with a decline in FEV1 of 30 mL or greater per year. Multivariate analysis showed that high serum periostin, the highest treatment step, and ex-smoking were independent risk factors for the decline. Polymorphisms of periostin gene were related to higher serum periostin levels (rs3829365) and a decline in FEV1 of 30 mL or greater per year (rs9603226). CONCLUSIONS: Serum periostin appears to be a useful biomarker for the development of airflow limitation in asthmatic patients on ICS.

A Retrospective Claims Database Study to Clarify Treatment Reality of Asthma Patients Before and After Referral to a Specialist.

Purpose: Japanese guidelines recommend that patients with uncontrolled asthma be referred by non-specialists to specialists (allergists and/or pulmonologists). This study investigated the reality of clinical practice in asthma patients referred to specialists in Japan. Patients and Methods: This was a retrospective, observational cohort study of asthma patients in a health insurance claim database (Cross Fact) referred from facilities with non-specialists to those with specialists from January 2016 to December 2018. The referred asthma patients were defined as patients with ≥4 inhaled corticosteroid (ICS)-containing prescriptions during a 1-year baseline period, with an asthma diagnosis, and who had visited a facility with specialists. Asthma exacerbation, maintenance treatment, laboratory tests, and medical procedures before and after referral were analyzed. Results: Data for 2135 patients were extracted, of which 420 with referral codes were analyzed. The proportion of patients with asthma exacerbations was 50.2% (95% confidence interval [CI]: 45.4-55.1%) before referral and 37.4% (95% CI: 32.7-42.2%) after, a significant decrease (P<0.001; McNemar test). The proportions of patients prescribed ICS alone, long-acting beta-agonists (LABA), and ICS/LABA were lower after referral than before, but the proportions of patients prescribed long-acting muscarinic antagonists (LAMA), ICS/LABA/LAMA, and biologics increased after referral. More asthma-related laboratory tests were performed after referral, and spirometry incidence increased from 16.4% before referral to 51.4% after referral. Conclusion: This study shows a decrease in asthma exacerbations, change in asthma treatments, and increase in laboratory tests after referral to a specialist, suggesting that referrals to specialists lead to better management of asthma.

Prevalence and causes of chronic cough in Japan.

BACKGROUND: Chronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients' quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. METHODS: Patients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. RESULTS: A total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. CONCLUSIONS: We confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.

Real-world evaluation of asthma reliever therapy among continuous users of asthma maintenance medication in Japan: A retrospective cohort study using a claims database.

BACKGROUND: The decrease in mortality rate owing to asthma has slowed in recent years. A large proportion of patients with asthma remain uncontrolled in Japan. This study aimed to determine the prevalence of short-acting beta 2 agonists (SABA) overuse and its associated factors. METHODS: This large-scale retrospective cohort study analyzed continuously treated patients with asthma aged 15-74 years between January 2017 and December 2017 using a Japanese insurance claims database. Characteristics, disease information, and prescribed drugs were extracted from the database, and treatment steps were defined according to drug combinations based on the criteria of the Japanese asthma guidelines. SABA overuse was defined as ≥3 canisters per year. Factors associated with SABA overuse were estimated using multivariable logistic regression. RESULTS: Among 7,483 patients with mild-to-moderate asthma, 7,001 (93.6%) and 482 (6.4%) had low and high SABA use, respectively. Inhaled corticosteroids (ICS)/long-acting ß-agonists (LABA) were the main asthma control treatments. The proportions of patients who overused SABA were 347 (9.9%) and 1,201 (5.6%) in the ICS and ICS/LABA groups, respectively. The factors associated with SABA overuse were male sex, ICS monotherapy, higher treatment steps, no history of allergic rhinitis, no history of chronic sinusitis, and no asthma management. CONCLUSIONS: There is a relatively low prevalence of SABA overuse among asthmatic patients in Japan. ICS/LABA therapy, treatment steps, allergic rhinitis, chronic sinusitis, and asthma management are associated with a decreased risk of SABA overuse. Further studies are needed to investigate the association between SABA overuse and asthma exacerbation and mortality.

Impulse oscillometry; therapeutic impacts of transdermal long-acting Beta-2 agonist patch in elderly asthma with inhaled corticosteroid alone.

Growing interest had been focused on the involvement of the small airways in asthma, and impulse oscillometry (IOS) has been utilized as pulmonary functions for detecting large and small airways diseases separately. IOS can measure respiratory resistance and reactance at multiple frequencies, not available by spirometry or body plethysmography, is non-invasive techniques and convenient for elderly patients with a low dependency on cooperation during tidal breathing. IOS indices were well correlated with not only predicted FEV1 but also FEF25-75, residual volume/total lung capacity, delta N2 of a single nitrogen washout test which representing air trapping and inhomogeneous ventilation in the distal lung. These parameters and QOL scores were improved by additional transdermal long-acting beta-2 agonist patch even in well-controlled elderly asthma treating with inhaled corticosteroids alone. IOS may have a complementary role of spirometry in detecting subtle airways changes in general practice. However, systemic studies are required to investigate the clinical implication of each IOS index.

Association Between Patient Preference for Inhaler Medications and Asthma Outcomes.

Purpose: Asthma guidelines recommend considering the patient preference to optimize medication choices. Patient preference for inhaler medication may affect asthma outcomes, but evidence regarding this is lacking. This study investigated the associations between patient preference for inhaler medications and asthma outcomes. Patients and Methods: A multicenter questionnaire survey was conducted among 351 adult patients with asthma treated with regular inhaled corticosteroids. Agreement between patients' preferences and current medication was evaluated using two questions: matched preference was defined as patients answering that the current inhaler medication was the most preferred treatment and they were satisfied with it. Mismatched preference was defined as when patients reported that the current inhaler medication was not the most preferred treatment and/or they were not satisfied with it. We investigated the factors associated with patient preference for asthma inhaler medications. Results: In total, 269 (76.6%) patients were classified into the matched preference group and 82 (23.4%) patients into the mismatched preference group. Multivariate analyses showed that matched preference was independently associated with higher asthma control test scores (P<0.001), fewer exacerbations (P=0.009), less regular oral corticosteroid use (P=0.009), and better inhaler adherence (P=0.006) than the mismatched preference group. In subgroup analysis, younger age was associated with matched preference in patients using dry powder inhalers but not in those using pressurized metered dose inhalers. Conclusion: The use of preference-matched inhaler medication was associated with better asthma outcomes. Evaluation of patients' preference for inhaler medication might provide useful information for individualized treatment with asthma inhaler medications.

Arg16Gly ß2-adrenergic receptor gene polymorphism in Japanese patients with aspirin-exacerbated respiratory disease.

BACKGROUND: There has been no report that investigated ß(2)-adrenergic receptor (ADRB2) gene polymorphism in patients with aspirin-exacerbated respiratory disease (AERD). METHODS: DNA in the specimens in three groups of study subjects classified patients with AERD, patients with aspirin-tolerant asthma (ATA) and normal controls was extracted, and the target DNA sequence of the ADRB2 was amplified using a set of primers to generate an amplicon of 219 bp in length. Allelic discrimination assay for single nucleotide polymorphisms relating to the ADRB2 gene expression was carried out by using a previously described single nucleotide polymorphism detective system, sequence-specific thermal-elution chromatography. RESULTS: The frequency of the Gly variant allele in patients with AERD was significantly lower than that in patients with ATA (p = 0.007), and the odds ratio (OR) of AERD to ATA associated with wild-type ArgArg homozygote was 3.300. Frequencies of wild-type ArgArg homozygote are significantly higher than those of variant-type ArgGly/GlyGly genotype in patients with AERD compared with those with ATA (p < 0.001, OR = 3.153). In patients with AERD, frequencies of wild-type ArgArg homozygote in both female and male patients are significantly higher than those of variant-type ArgGly/GlyGly genotype in male patients compared with those with ATA (p < 0.001, OR = 5.128 and p = 0.007, OR = 4.367, respectively). Also, in patients with AERD, frequencies of wild-type ArgArg homozygote in female patients are significantly higher than those of variant-type ArgGly/GlyGly genotype in female patients compared with those with ATA (p = 0.002, OR = 2.825). CONCLUSIONS: We were the first to analyze Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD, and showed that Arg16Gly ADRB2 gene polymorphism in Japanese patients with AERD is different from that in the patients with ATA.

Comparison of budesonide/formoterol Turbuhaler with fluticasone/salmeterol Diskus for treatment effects on small airway impairment and airway inflammation in patients with asthma.

BACKGROUND: A course of combination therapy with an inhaled corticosteroid (ICS) and a long-acting ß(2) agonist (LABA) for asthma can improve lung function, asthma symptoms and reduce exacerbations. Because both medicinal substance and inhalation devices are associated with clinical efficacy, each ICS/LABA combination may have different features. This study aimed to compare the effects of two widely available formulations, budesonide/formoterol (BUD/FM) delivered by a Turbuhaler(®), and fluticasone/salmeterol (FP/SM) delivered by a Diskus(®), on small airway function and airway inflammation. METHODS: Asthmatic patients (n = 40) treated twice daily with FP/SM 250/50 µg with forced expiratory volume in 1 s values controlled above 80% of the predicted normal but with suspected persistent airway inflammation and small airway impairment were enrolled in the study. Patients were randomized into two groups, receiving either twice daily BUD/FM 320/9 µg or FP/SM 250/50 µg, and treatment efficacy was compared after 4 weeks. Outcomes included impulse oscillometry (IOS), fractional exhaled nitric oxide (FeNO), spirometry and Asthma Control Questionnaire (ACQ) scores. RESULTS: Patients in the BUD/FM group showed significant improvements in their IOS and spirometry parameters of small airway function, FeNO values and ACQ scores, compared with the FP/SM group. There were good correlations between IOS parameters, FeNO and ACQ score changes over the course of the treatment. CONCLUSIONS: BUD/FM twice daily significantly improved small airway impairment and airway inflammation in asthmatic patients, leading to a reduction in asthma symptoms and achievement of good asthma control. In addition, improvement of small airway function may improve airway inflammation and/or lead to better controlled asthma.