Japanese Asthmatic Patients Research Articles

Validity study of the Japanese version of the Nijmegen Questionnaire for verifying dysfunctional breathing in Japanese asthma patients

Dysfunctional breathing (DB) is a clinical condition characterized by irregular breathing patterns presenting a sensation of dyspnea and a feeling of chest tightness. DB is a known comorbidity of asthma that is difficult to control, leading to poor quality of life, so early diagnosis and therapeutic intervention are essential to improve the clinical condition of asthma. The Nijmegen Questionnaire (NQ), developed to screen for DB and translated into various languages, is used worldwide. However, a Japanese NQ (JNQ) is unavailable, so DB has not been clinically verified in people with asthma in Japan. This study aimed to prepare a JNQ, verify its reliability and validity, and demonstrate its clinical benefits in asthma treatment. The JNQ was prepared by back-translating the NQ with the author's consent. The answers to self-administered questionnaires, including the JNQ, Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), and Patient Health Questionnaire 9 (PHQ-9), were obtained with the consent of 68 people with asthma (average age ± SD, 52.04± 12.43 years) who visited Nihon University Itabashi Hospital. The reliability of the JNQ was analyzed by the Cronbach alpha coefficient. Acomparative test was conducted for each questionnaire (ACT, ACQ, Mini-AQLQ, PHQ-9), considering a JNQ score of 23 as the cutoff value. Patients with a score of 23 or more were assigned to the DB group, whereas patients with a score of less than 23 were assigned to the non-DB group. We analyzed the correlation between the JNQ and each questionnaire. The JNQ showed sufficient reliability (Cronbach alpha= 0.875). Correlation analysis between the JNQ score and each questionnaire revealed negative correlations with the ACT score (r= 0.262) and Mini-AQLQ score (r= -0.453) and positive correlations with the ACQ score (r= 0.337) and PHQ-9 score (r= 0.539). All of these correlations were statistically significant. As a result of the comparative test, the DB and non-DB groups showed a significant difference in Mini-AQLQ (P= .023) and PHQ-9 (P= .003) scores. No significant difference was observed between ACT (P= .294) and ACQ (P= .177) scores. The JNQ validates DB in Japanese people with asthma and reflects the deterioration of asthma control, decreased quality of life, and depression. Using the JNQ, early diagnosis and therapeutic intervention (eg, breathing exercises and a psychosomatic approach) for DB in people with asthma may help suppress the severity of asthma in Japan.

Usefulness of Computed Tomography for Evaluating the Effects of Bronchial Thermoplasty in Japanese Patients with Severe Asthma.

Bronchial thermoplasty (BT) improves clinical outcomes and quality of life for patients with severe asthma and has shown sustained reductions in airway narrowing and air trapping in previous CT studies. However, there is a lack of a comprehensive analysis, including CT evaluation, of clinical outcomes in Japanese patients who have undergone BT for severe asthma. This study aimed to evaluate the impact of BT in Japanese asthma patients, with a focus on the CT metric "WA at Pi10" to assess airway disease. Twelve patients with severe persistent asthma who underwent BT were assessed using ACQ6, AQLQ, pulmonary function tests, FeNO measurement, blood sampling, and chest CT before BT and one year after the third procedure for the upper lobes. The median age of the patient was 62.0 years, 7/12 (58.3%) were male, 4/12 (33.3%) used regular oral corticosteroids, and 8/12 (66.7%) received biologics. Median FEV1% was 73.6%, and median peripheral eosinophil count was 163.8/μL. After one year of BT, ACQ6 scores improved from 2.4 to 0.8 points (p = 0.007), and AQLQ scores improved from 4.3 to 5.8 points (p < 0.001). Significant improvements were also observed in asthma exacerbations, unscheduled visits due to exacerbations, FeNO, and √WA at Pi10 (p < 0.05). The baseline mucus score on the CT findings was negatively correlated with FEV1 (r = -0.688, p = 0.013) and with the maximum mid-expiratory flow rate (r = -0.631, p = 0.028), and positively correlated with the peripheral blood eosinophil count (r = -0.719, p = 0.008). Changes in √WA at Pi10 after one year were positively correlated with changes in the mucus score (r = 0.742, p = 0.007). This study has limitations, including its single-arm observational design and the small sample size. However, BT led to a symptomatic improvement in patients with severe asthma. The validated "√WA at Pi10" metric on CT effectively evaluated the therapeutic response in Japanese asthma patients after BT.

The prevalence of obstructive sleep apnea in Japanese asthma patients.

Obstructive sleep apnea (OSA) occurs more commonly in asthma patients than in the general population because these conditions share some comorbidities. In Japan, the prevalence of OSA in the general population is reported to be approximately 20%; however, few reports have described the prevalence of OSA in asthma patients. Furthermore, the characteristics of Japanese patients with OSA and asthma are not clear. Adult asthma patients were recruited from the outpatient departments of our institution between August 31, 2017, and March 31, 2019. In all included patients, the presence and severity of OSA were evaluated by the Epworth Sleepiness Scale (ESS) and a home sleep test (HST) using portable polysomnography (PSG). The rate of coexisting OSA in asthma patients and the characteristics of those patients according to the severity of OSA were investigated. Fifty-three patients were included. OSA was detected in 36 (67.9%) patients (mild, n = 15; moderate, n = 14; and severe, n = 7). Patients with OSA had significantly higher body mass index, Brinkman index, apnea-hypopnea index (AHI), and 3% oxygen desaturation index (ODI) values in comparison to those without OSA, while the percentage of the predicted value of forced vital capacity (%FVC) and lowest SpO2 levels were significantly lower. As the severity of OSA increased, age, brain natriuretic peptide level, AHI, and 3%ODI increased, and in contrast, FVC, %FVC, forced expiratory volume in one second (FEV1), percentage of the predicted value of FEV1 (%FEV1), Epworth Sleepiness Scale (ESS), 3%ODI, and lowest SpO2 levels decreased. In particular, the fact that the ESS value was inversely correlated with the severity of OSA in our patients was different from the general characteristics of OSA. Moreover, the AHI value was negatively correlated with FVC, %FVC, FEV1, and %FEV1. BMI was the only independent factor for the presence of OSA, and for asthma severity (FEV1, % of predicted), there was a weak correlation with smoking history. This is the first report to investigate the prevalence of OSA in Japanese asthma patients, using an HST. This study suggests that an HST should be performed in addition to the sleep interview for asthma patients with refractory disease, a low pulmonary function, advanced age, and high BMI because the more severe the OSA, the lower the ESS value may be.

The association between control level and self-reported treatment adherence across different treatment types in Japanese asthma patients.

Poor control of asthma symptoms is associated with a higher asthma disease burden, and asthma medication adherence is a known predictor for a better control status. This study sought to describe the current asthma control status, self-reported treatment adherence, and the association between them, as well as to describe how control level and better adherence impact the health outcomes of asthma patients. This study used cross-sectional data from the 2018 Japan National Health and Wellness Survey (NHWS). Asthma control status and adherence were assessed using the Asthma Control Test (ACT) and Morisky Medication Adherence Scale-8 (MMAS-8), respectively. Asthma treatment and patients' health outcomes, i.e. health-related quality of life (HRQoL) and work productivity, were self-reported. Asthma control and self-reported treatment adherence were analyzed descriptively, and the association was investigated by comparing mean ACT scores across adherence levels. Health outcomes were compared across control and adherence levels by multivariate analyses. A total of 816 patients had a physician diagnosis of asthma, with 67.0% reporting at least well controlled (ALWC). Of 505 asthma patients receiving prescription medication, half reported low adherence to medication use. Among asthma patients reporting high adherence, 35.6% were not well controlled (NWC). After adjusting for covariates, NWC asthma patients had significantly worse health outcomes than ALWC patients. One-third of asthma patients in Japan suffer from poorly controlled asthma. Results of the 2018 NHWS show that poor control status negatively affects patients' HRQoL and work productivity, suggesting an unmet need for better treatments to lessen the burden of asthma.

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

BackgroundThe 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. MethodsPooled 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. ResultsThe 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”. ConclusionsJACS 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

BackgroundThe 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. MethodsA 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. ResultsThe 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). ConclusionsThe 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 registrationUMIN000016589

Phenotype of asthma related with high serum periostin levels

BackgroundAsthma is a heterogeneous disease composed of various phenotypes. Periostin, a molecule inducible with interleukin (IL)-4 or IL-13 in bronchial epithelial cells, is a biomarker of “TH2-high” asthma. The objective of this study is to examine whether the serum periostin concentrations are correlated with the severity, specific phenotype(s), or comorbidity of asthma. MethodsSerum concentrations of periostin were measured in 190 Japanese asthmatic patients and 11 healthy controls. The protocol was registered under UMIN 000002980 in the clinical trial registry. ResultsThe serum concentrations of periostin were significantly higher (P = 0.014) in asthmatics [70.0 (54.0–93.5) ng/ml] than in healthy subjects [57.0 (39.0–63.0) ng/ml], though we found no correlation between serum periostin concentrations and treatment steps required to control asthma. To characterize “high-periostin” phenotype(s), the patients with asthma were divided among tertiles based on the serum concentrations of periostin. The high-periostin group was older at onset of asthma (P = 0.04), had a higher prevalence of aspirin intolerance (P = 0.04) or concomitant nasal disorders (P = 0.03–0.001), higher peripheral eosinophil counts (P < 0.001), and lower pulmonary function (P = 0.02–0.07). The serum concentrations of periostin were particularly high in asthmatic patients complicated by chronic rhinosinusitis with nasal polyps and olfactory dysfunction. In contrast, neither atopic status, control status of asthma, nor quality of life were related with the “high-periostin” phenotype. ConclusionElevated periostin concentrations in serum were correlated with a specific phenotype of eosinophilic asthma, late-onset and often complicated by obstructive pulmonary dysfunction and nasal disorders.

Analysis of the Influenza A (H1N1) 2009 Pandemic Infection in Japanese Asthmatic Patients: Using a Questionnaire-Based Survey

Influenza infection is known to be an exacerbating factor in the control of asthma, therfore its prevention is critical in managing asthma. The aim of this study was to investigate the influenza A H1N1 2009 pandemic virus (H1N1 pdm09) infection in adult asthmatic patients. Data were obtained from a questionnaire-based survey of asthmatic patients conducted from September to October 2010 in Niigata Prefecture. Patient background, H1N1 pdm09 infection, vaccination status, and asthma exacerbation due to influenza infection were analyzed. In total, 2,555 cases were analyzed. The incidence of the infection was 6.7% (95% confidence interval [CI]: 5.7-7.6), and the rate of vaccination was 63.9% (95% CI: 62.1-65.8). The odds ratio (OR) for vaccination against the infection among adult patients and younger patients (≤ the median age) were 0.61 (95% CI: 0.45-0.84) and 0.62 (95% CI: 0.42-0.90), respectively. However, OR among the older patient (> median age) were 1.38 (95%CI: 0.66-2.89). The rate of infection-induced asthma exacerbation was 23.2% (95% CI: 18.6-29.6), and the OR for vaccination against the infection-induced asthma exacerbation was 1.42 (95% CI: 0.69-2.92). The effectiveness of the vaccination against the H1N1 pdm09 virus was confirmed during the first pandemic season, but it was limited. Further investigation on H1N1 pdm09 virus infection in asthmatics will be required.

Effect of Lifestyle on Asthma Control in Japanese Patients: Importance of Periodical Exercise and Raw Vegetable Diet

BackgroundThe avoidance of inhaled allergens or tobacco smoke has been known to have favorable effects on asthma control. However, it remains unclear whether other lifestyle-related factors are also related to asthma control. Therefore, a comprehensive study to examine the associations between various lifestyle factors and asthma control was conducted in Japanese asthmatic patients.MethodsThe study subjects included 437 stable asthmatic patients recruited from our outpatient clinic over a one-year period. A written, informed consent was obtained from each participant. Asthma control was assessed using the asthma control test (ACT), and a structured questionnaire was administered to obtain information regarding lifestyle factors, including tobacco smoking, alcohol drinking, physical exercise, and diet. Both bivariate and multivariate analyses were conducted.ResultsThe proportions of total control (ACT = 25), well controlled (ACT = 20-24), and poorly controlled (ACT < 20) were 27.5%, 48.1%, and 24.5%, respectively. The proportions of patients in the asthma treatment steps as measured by Global Initiative for Asthma 2007 in step 1, step 2, step 3, step 4, and step 5 were 5.5%, 17.4%, 7.6%, 60.2%, and 9.4%, respectively. Body mass index, direct tobacco smoking status and alcohol drinking were not associated with asthma control. On the other hand, younger age (< 65 years old), passive smoking, periodical exercise (> 3 metabolic equivalents-h/week), and raw vegetable intake (> 5 units/week) were significantly associated with good asthma control by bivariate analysis. Younger age, periodical exercise, and raw vegetable intake were significantly associated with good asthma control by multiple linear regression analysis.ConclusionsPeriodical exercise and raw vegetable intake are associated with good asthma control in Japanese patients.

Influence of Underweight on Asthma Control

Although the association between asthma control and body mass index (BMI) has been thoroughly investigated, most of this work has focused on the influence on asthma incidence or the effect of obesity on asthma control. To date, there have been no published studies on the influence of underweight on asthma control. The aim of this study was to investigate the influence of underweight, as defined by the Japan Society for the Study of Obesity (JASSO), on asthma control in Japanese asthmatic patients. Using data from questionnaire surveys administered by the Niigata Asthma Treatment Study Group, we compared asthma control, as measured by the Asthma Control Test (ACT), between a normal weight group (18.5kg/m2 =< BMI < 25kg/m2) and an underweight group (BMI < 18.5kg/m2). Of the asthmatic patients who completed the 2008 and 2010 surveys, 1464 and 1260 cases were classified as being in the normal weight group, and 174 and 155 cases were classified as being in the underweight group. The ACT score (median, [interquartile range]) in the underweight group in 2008 (22, [19-24]) and 2010 (23, [19-25]) was significantly lower than that in the normal group in 2008 (23, [20-25]) and in 2010 (24, [21-25]). This study is the first, large-scale investigation of the influence of underweight on asthma control, and we have confirmed an adverse influence in a clinical setting. A potential mechanism for this interaction was unknown. Further investigation will be required.

Comparison of high‐dose salmeterol/fluticasone and moderate‐dose salmeterol/fluticasone plus low‐dose mometasone in patients with severe persistent asthma

The effects of adding a second inhaled corticosteroid with a different particle size, compared with using an increased dose of a single inhaled corticosteroid, were assessed in patients with persistent asthma. This was an open-label study of Japanese asthma patients over 20 years of age. After a 1-month run-in period, 36 patients with inadequate control while using salmeterol/fluticasone propionate 50/250 µg (SFC50/250) bd, were randomized to receive SFC50/500 bd or SFC50/250 plus mometasone 100 µg bd (SFC50/250/MF100) for 2 months. Both treatments resulted in improvements in morning and evening PEF. There were no significant changes in FEV(1) , maximum mid-expiratory flow, maximum expiratory flow rate at 50%, maximum expiratory flow rate at 25% or exhaled NO (FENO) in the SFC50/500 group. On the other hand, there were significant improvements in FEV(1) % (+12.2%, P = 0.0142), %maximum mid-expiratory flow (+28.9%, P = 0.0181), %MEF50 (+32.4%, P = 0.0206) and %MEF25 (+30.3%, P = 0.0113) in the SFC50/250/MF100 group. The changes in FENO (-23.2% (P = 0.0157) in the SFC50/250/MF100 group and -14.5% (not significant) in the SFC50/500 group) did not differ significantly between the groups. In patients with severe persistent asthma, addition of low-dose mometasone to SFC50/250 improved spirometric parameters, FENO and PEF, while an increase in dose from SFC50/250 to SFC50/ 500 only improved PEF.

Influence of Obesity on Control in Asthmatic Japanese Patients Defined by the Japanese Definition of Obesity

BACKGROUND Despite the use of inhaled corticosteroid (ICS) becoming increasingly widespread, many problems related to asthma management still need to be addressed. One of them, obesity, has been reported to exert a harmful influence on asthma control. However, there have been few reports focusing not only on both obesity and its influence on Japanese asthma patients but also on the Japanese definition of obesity, as defined by the Japan Society for the Study of Obesity (JASSO). AIMS & METHODS The aim of this study was to confirm the influence of obesity, as defined by the JASSO, on asthma management in Japanese asthmatic patients. Using data from the Niigata Asthma Treatment Study Group 2008 questionnaire survey, differences between the "normal" group (18.5 kg/m(2) ≤ BMI <25 kg/m(2)) and the "obese" group (25 kg/m(2) ≤ BMI) were analyzed. RESULTS There was a significantly lower step 1 rate (19.4% v.s. 26.8%) and a higher proportion of patients using inhaled salmeterol (43.6% v.s. 35.8%) and leukotriene receptor antagonist (49.8% v.s. 40.8%) in the obese group relative to the normal group, although there were no significant differences in indicators of asthma control, including asthma control test scores. CONCLUSION This study investigated influences of JASSO-defined obesity on asthma severity and management in a clinical setting in Japan. It is possible that there are strong interactions between asthma and obesity, such as obesity causing decreased ICS therapy efficacy and leukotriene (LT)-related inflammation, although further investigation is necessary.

Association between β‐adrenoceptor gene polymorphisms and relative response to β2‐agonists and anticholinergic drugs in Japanese asthmatic patients

Whether beta(2)-adrenoceptor gene (ADRB2) polymorphisms are associated with airway responsiveness to beta(2)-agonist medications remains controversial, partly due to factors that may confound pharmacogenetic associations, including age, cigarette smoking and airway remodelling. To overcome these problems, we performed an analysis using parameters that reflected the specific bronchodilator response to beta(2)-agonists. The increases in FEV(1) after inhalation of procaterol hydrochloride (Delta FEV(1) procaterol) or oxitropium bromide (Delta FEV(1) oxitropium), and after sequential inhalation of procaterol and oxitropium (total airway reversibility), were measured in 81 Japanese patients with moderate to severe asthma. Approximately 3 kb of the DNA sequence of the coding and 5'-flanking regions of ADRB2 were genotyped by direct sequencing and PCR-restriction fragment length polymorphism assay. The mean age of the participants was 54 years, and 38 (47%) were smokers. Although Delta FEV(1) procaterol and Delta FEV(1) oxitropium adjusted for predicted FEV(1) were not associated with ADRB2 polymorphisms, the ratio of Delta FEV(1) procaterol to total airway reversibility was significantly associated with the ADRB2 A46G genotype (P < 0.05). Patients who were homozygous for the A46 allele (arginine at amino acid 16) were more responsive than carriers of the G46 (glycine 16) allele (P = 0.008). Multivariate linear regression analysis showed that Delta FEV(1) procaterol was correlated with the number of A46 alleles (P = 0.014), and also with total airway reversibility (P < 0.001) and smoking index in current smokers (P = 0.009). The ADRB2 A46G polymorphism was associated with a relatively greater bronchodilator responsiveness to beta(2)-agonists even in elderly asthmatic patients and smokers.

Impact of pharmacokinetics and pharmacogenetics on the efficacy of pranlukast in Japanese asthmatics

Wide inter-individual variability in therapeutic effects limits the efficacy of leukotriene (LT) receptor antagonists in the treatment of asthma. We have reported that genetic variability in the expression of LTC(4) synthase is associated with responsiveness to pranlukast in Japanese asthmatic patients. However, the effects of pharmacokinetic variability are less well known. This was an analysis of the pharmacokinetics of pranlukast in a population of adult asthmatics, and its effect on clinical responses. Other factors that may be related to the therapeutic effects of pranlukast, including LTC(4) synthase gene polymorphisms, were also investigated. The population pharmacokinetics of pranlukast was analysed in a one-compartment model, using data collected in 50 Japanese adults with moderate to severe asthma, who were treated with pranlukast, 225 mg bd for 4 days. In 32 of these patients, in whom the clinical response to pranlukast (increase in FEV(1) after 4 weeks of treatment) was measured in a previous study, a combined pharmacokinetic and pharmacogenetic analysis was performed. Using the population pharmacokinetic model, the estimated the mean oral clearance (CL/F) of pranlukast was 16.4 L/h, and the inter-individual variability was 30.1%. Univariate and multivariate analyses showed that LTC(4) synthase polymorphisms, but not the CL/F of the drug, predicted an improvement in pulmonary function with pranlukast treatment (P < 0.05). There was marked inter-individual variability in the pharmacokinetics of pranlukast among adult asthmatics, but this had little impact on the clinical effectiveness of the drug.

Age- and Gender-specific Risk Factors Associated with Difficult-to-treat Asthma Phenotype among Japanese Asthmatic Patients

RATIONALE: Although the widespread use of anti-inflammatory drugs has resulted in good control of asthma for many patients, an important subgroup of patients remain symptomatic despite the high-dose treatment. The risk factors associated with difficult-to-treat asthma phenotype among Japanese adult asthmatic patients are yet unknown.

The Relationship between Exhaled Nitric Oxide Measured with an Off-line Method and Airway Reversible Obstruction in Japanese Adults with Asthma

Exhaled nitric oxide (eNO) is a useful marker of eosinophilic airway inflammation in asthma patients. There is no study to show the relationship between the eNO measured by using an off-line method and the degree of reversibility of airflow limitation in Japanese asthma patients. We sought to investigate the relationship between the eNO level measured by using an off-line method and the degree of reversibility of bronchial constriction in Japanese asthma patients. The study population comprised 97 asthma patients in our outpatient clinic with some patients in both groups who received inhaled corticosteroid treatment. We measured eNO levels, forced expiratory volume in one second (FEV1) before and after treatment, reversible airway obstruction (DeltaFEV1) after inhalation of bronchodilator, and other parameters. eNO was significantly correlated with peripheral blood eosinophil counts in asthma patients (in steroid-naïve asthma patients, r=0.544, p<0.0001; in asthma patients treated with inhaled corticosteroid, r=0.463, p=0.026), and subjects with severe eosinophilia in sputum showed high levels of eNO (mild eosinophilia versus severe, p=0.0152). Among patients with obstructive impairment, eNO levels were correlated with DeltaFEV1 regardless of whether patients received (r=0.527, p=0.0435) or did not receive (r=0.64, p = 0.0056) inhaled corticosteroid. In subjects with normal pulmonary function, there was no significant relationship between eNO and DeltaFEV1 with or without inhaled corticosteroid. In patients with obstructive impairment, eNO reflects the degree of reversible airflow limitation. In subjects with normal pulmonary function, eNO may facilitate the diagnosis and management of asthma, rather than indicate reversible bronchial obstruction. eNO measurement by off-line methods is applicable as a potential tool for the diagnosis of asthma and management of asthma patients.

Validation Study of a Disease-specific Module, the Asthma Health Questionnaire (AHQ) Using Japanese Adult Asthmatic Patients

An asthma-specific questionnaire, the Asthma Health Questionnaire (AHQ) was developed for Japanese asthmatic patients. A self-administered 37-item version (AHQ-37) consisting of 36 disease-specific items and a Face Scale was designed for socially active patients. Exploratory factor analysis, test-retest reliability, internal consistency, concurrent validity and longitudinal validity were evaluated. A total of 326 asthma patients (202 men; range of age from 18 to 65 years) answered the AHQ-37 twice. Each item of the AHQ-37 was well accepted by the patients with answering rates of 95 to 100%. Six subscales (Asthmatic Symptoms, Emotion, Daily Activity, Factors which Worsened Symptoms, Social Activity and Economics) were extracted by factor analysis. Psychometric testing showed high feasibility, good repeatability and good internal consistency. The Face Scale moderately correlated with all subscales except for Economics, indicating that the Face Scale alone could measure global quality of life (QOL) functioning of asthmatic patients. Concurrent validity with peak-flow values was insufficient (Spearman’s correlation coefficient = 0.05−0.27), showing that the peak flow alone could not estimate QOL. In longitudinal validity, however, changes in peak-flow values had an impact on the Asthmatic Symptoms, Daily Activity and Factors which Worsened Symptoms ( P = 0.000−0.419), indicating that changes in peak-flow were important to asthmatic patients’ QOL. The QOL of asthmatic patients must be evaluated by asthma-specific questionnaires, such as the AHQ-37.

Applicability of Hyland's Living with Asthma Questionnaire for Japanese asthmatic patients.

To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity. The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval. The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996). Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.

Inhibitory effects of azelastine hydrochloride in alcohol-induced asthma.

Alcohol-induced bronchoconstriction is due to high blood concentrations of acetaldehyde, a metabolic product of ethanol, which lead to the release of histamine from basophils and mast cells. We examined the inhibitory effects of azelastine hydrochloride, which inhibits histamine release and blocks H1 receptors, in alcohol-induced asthma. Subjects were 13 Japanese asthmatic patients. We measured the change in FEV1 after ingestion of 30 g of pure ethanol. Blood ethanol, acetaldehyde, histamine, leukotriene C4 (LTC4), and thromboxane B2 (TXB2) concentrations were also measured. Alcohol challenge test was repeated in responders after administration of azelastine for 1 week at 4 mg/day. Of 13 asthmatic patients, five (38.5%) tested positive during an ethanol challenge test, represented by a fall more than 20% in FEV1. The responders had a high blood ethanol, and showed a rise in blood acetaldehyde and histamine concentrations, but not in LTC4 or TXB2. After azelastine treatment, there was no significant fall in FEV1 among responders. Neither the rise in blood ethanol nor blood acetaldehyde levels were blunted by treatment with azelastine, but the rise in blood histamine was blunted by this treatment. Our results suggest that antihistamine agents may be effective against alcohol-induced asthma by both blocking H1 receptors and inhibiting histamine release.

The relationship between emotional and social problems and QOL in Japanese asthmatic patients

The relationship between emotional and social problems and QOL in Japanese asthmatic patients